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Sample records for pathological complete response

  1. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  2. Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

    International Nuclear Information System (INIS)

    Toxopeus, Eelke Lucie Anne; Nieboer, Daan; Shapiro, Joel; Biermann, Katharina; Gaast, Ate van der; Rij, Carolien M. van; Steyerberg, Ewout Willem; Lanschot, Joseph Jan Baptiste van; Wijnhoven, Bas Peter Louis

    2015-01-01

    Background: A pathologically complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in 30% of the patients with oesophageal cancer. The aim is to identify patient and tumour characteristics associated with a pCR and to develop a nomogram for the prediction of pCR. Patients and methods: Patients who underwent nCRT followed by surgery were identified and response to nCRT was assessed according to a modified Mandard classification in the resection specimen. A model was developed with age, gender, histology and location of the tumour, differentiation grade, alcohol use, smoking, percentage weight loss, Charlson Comorbidity Index (CCI), cT-stage and cN-stage as potential predictors for pCR. Probability of pCR was studied via logistic regression. Performance of the prediction nomogram was quantified using the concordance statistic (c-statistic) and corrected for optimism. Results: A total of 381 patients were included. After surgery, 27.6% of the tumours showed a pCR. Female sex, squamous cell histology, poor differentiation grade, and low cT-stage were predictive for a pCR with a c-statistic of 0.64 (corrected for optimism). Conclusion: A nomogram for the prediction of pathologically complete response after neoadjuvant chemoradiotherapy was developed, with a reasonable predictive power. This nomogram needs external validation before it can be used for individualised clinical decision-making

  3. Two cases of pathological complete response to neoadjuvant chemoradiation therapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Fujii-Nishimura, Yoko; Nishiyama, Ryo; Kitago, Minoru

    2015-01-01

    Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years. (author)

  4. Complete pathological response after neoadjuvant therapy in patients with rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    E.A. Sánchez-Pérez

    2017-10-01

    Full Text Available Background: Colorectal cancer is the fourth most common cancer and the second leading cause of death from cancer in the United States. Preoperative neoadjuvant therapy (chemotherapy and radiotherapy is the gold standard in the management of rectal cancer before surgical resection. The literature includes reports of absence of neoplastic cells after neoadjuvant therapy. There are no reports on complete pathological response to this type of therapy in Mexico. Objectives: Determine the percentage of patients with rectal adenocarcinoma with complete pathological response after neoadjuvant therapy. All patients were treated in a colorectal surgery department of a tertiary care hospital. Materials and methods: A total of 64 patients with rectal adenocarcinoma diagnosed by biopsy were treated from January 2010 to December 2015. Demographic data, tumour localisation, pathological report, TNM stage, neoadjuvant therapy, surgical procedure and postoperative pathological report were collected from patient records. Results: Mean patient age was 52.8 years (range of 26–73; 31 were women and 33 men. Twenty-seven patients (27 were stage II and 27 stage III. The preoperative biopsy results were classified as: well differentiated (10; moderately differentiated (48; and poorly differentiated/undifferentiated adenocarcinoma (6. Twenty patients received neoadjuvant therapy (31.2%. In these, 2 tumours were localised in the upper third of the rectum, 6 in the middle third, and 12 in the lower third. Six patients underwent abdominoperineal resection, 10 total mesorectal excision, and four posterior pelvic exenteration. Six patients undergoing neoadjuvant therapy had a complete pathological response. Conclusions: The percentage of patients with a complete pathological response is similar to that in other literature reports. More evidence is needed to define good prognosis factors in patients who might not require surgery after neoadjuvant therapy. Resumen

  5. Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

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    Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

    2013-01-01

    Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

  6. Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility.

    Science.gov (United States)

    van Soest, Johan; Meldolesi, Elisa; van Stiphout, Ruud; Gatta, Roberto; Damiani, Andrea; Valentini, Vincenzo; Lambin, Philippe; Dekker, Andre

    2017-09-01

    Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences). © 2017 American Association of Physicists in Medicine.

  7. Analysis of clinical factors for pathological complete response after preoperative neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Ayiguli Hare; Palida Apizi; Iskandar Abulimiti; Zhang Jinrong; Tian Hanhan

    2014-01-01

    Objective: To evaluate the clinical factors associated with pathological complete response (pCR) after preoperative neoadjuvant chemoradiotherapy for rectal cancer. Methods: A retrospective analysis was performed on the clinical data of 116 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy followed by radical surgery from January 2009 to December 2012. All patients received pelvic intensity-modulated radiotherapy (50 Gy/25 fractions) with concurrent fluorouracil based chemotherapy and then underwent radical surgery 4-8 weeks later. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Of the 116 patients, 20 (17.2%) achieved a pCR after neoadjuvant chemoradiotherapy. The univariate analysis showed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum carcinoembryonic antigen (CEA) level, T stage, N stage, distance from the anal verge, degree of tumor differentiation, and maximum tumor diameter were associated with pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. The multivariate analysis revealed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum CEA level,and T stage were predictive factors for pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. Conclusions: Non-circumferential tumor (percentage of circumference of the rectal tube invaded by the tumor <75 %), low CEA level, and early T stage before treatment may be associated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. (authors)

  8. MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

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    Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

    2017-06-01

    Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pathologic complete response in patients with neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Espinola M, Daniela; Espinola M, Daniela; Bellolio R, Felipe; Gellona V, Jose; Bustos C, Mariza; Zuniga D, Alvaro

    2013-01-01

    Background: The standard treatment of locally advanced rectal cancer (RC) of the middle and lower third of the rectum is neoadjuvant chemoradiotherapy (XRQT) follow by oncologic resection. After this treatment in 15-25% of the cases, the pathologist reports complete pathological response (pCR). Aim: To describe demographic, clinical and survival data of patients with pCR undergoing chemoradiotherapy and radical resection for RC. Material and Methods: Historic cohort study. In a prospectively maintained database between 2000 and 2010, we identified patients with RC, who underwent neoadjuvant chemoradiotherapy according to protocol, followed by radical resection. The preoperative staging was obtained by clinical examination, endoscopy, rectal ultrasound, CT scan of chest, abdomen and pelvis and pelvic MRI. Demographic data, tumor location, time between the end of XRTQ and surgery, postoperative staging (according AJCC) and survival, were collected. Results: 119 patients received preoperative XRTQ, 65% male, with a mean age of 58 years. The most frequent tumor site was the lower third (63%). Surgery was performed 8 weeks after the end of XRTQ. Of 119 patients with XRTQ, 15.1% had a pCR. Overall survival was 75%, and cancer-specific survival was 80.4% at 5 years in patients without pCR. For patients with pCR, the 5 year survival estimates for overall and cancer specific survival was 100%. We did not identify factors associated with pCR. Conclusions: In this study, pCR was comparable to other larger series reported elsewhere. No factors associated with pCR were identified

  10. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: A single center experience

    International Nuclear Information System (INIS)

    Choi, Eun Cheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results

  11. Prognosis of Esophageal Cancer Patients With Pathologic Complete Response After Preoperative Concurrent Chemoradiotherapy

    International Nuclear Information System (INIS)

    Park, Jae Won; Kim, Jong Hoon; Choi, Eun Kyung; Lee, Sang-wook; Yoon, Sang Min; Song, Si Yeol; Lee, Yu Sun; Kim, Sung Bae; Park, Seung il; Ahn, Seung Do

    2011-01-01

    Purpose: To define failure patterns and predictive factors in esophageal cancer patients who had a pathologic complete response (pCR) after preoperative concurrent chemoradiotherapy (PCRT). Methods and Materials: We performed a retrospective analysis of 61 esophageal cancer patients who were enrolled in prospective studies and showed pCR after PCRT. All of the patients had squamous cell carcinoma. Of the patients, 40 were treated with hyperfractionated radiotherapy (4,560 cGy in 28 fractions) with 5-fluorouracil (5-FU) and cisplatin (FP), and 21 patients received conventional fractionation radiotherapy with capecitabine and cisplatin (XP). Results: The median follow-up time was 45.2 months (range, 6.5-162.3 months). The 5-year overall survival (OS) and disease-free survival rates (DFS) were 60.2% and 80.4%, respectively. In univariate analysis, age and lymph node (LN) metastasis were poor prognostic factors for OS, and pretreatment weight loss (>2 kg) was a poor prognostic factor for DFS. In multivariate analysis, lymph node metastasis and pretreatment weight loss were independent prognostic factors for OS and DFS. Nine patients (15%) had disease recurrence. Of the nine patients, 5 patients had locoregional failure, 1 patients had distant metastasis, and 3 patients had distant and locoregional failure. In-field failure occurred in 5 patients; out-of-field failure occurred in 1 patient; both in-field and out-of-field failure occurred in 2 patients; and both marginal and out-of-field failure occurred in 1 patient. Conclusions: Even in pCR patients, the most common failure site was within the radiation field, which suggests that more efficient local treatment is needed. Tumor recurrence was more common in patients with older age and with pretreatment weight loss.

  12. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: A single center experience

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    Choi, Eun Cheol [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of); Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2016-06-15

    To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results.

  13. A nomogram for predicting pathological complete response in patients with human epidermal growth factor receptor 2 negative breast cancer

    International Nuclear Information System (INIS)

    Jin, Xi; Jiang, Yi-Zhou; Chen, Sheng; Yu, Ke-Da; Ma, Ding; Sun, Wei; Shao, Zhi-Min; Di, Gen-Hong

    2016-01-01

    The response to neoadjuvant chemotherapy has been proven to predict long-term clinical benefits for patients. Our research is to construct a nomogram to predict pathological complete response of human epidermal growth factor receptor 2 negative breast cancer patients. We enrolled 815 patients who received neoadjuvant chemotherapy from 2003 to 2015 and divided them into a training set and a validation set. Univariate logistic regression was performed to screen for predictors and construct the nomogram; multivariate logistic regression was performed to identify independent predictors. After performing the univariate logistic regression analysis in the training set, tumor size, hormone receptor status, regimens of neoadjuvant chemotherapy and cycles of neoadjuvant chemotherapy were the final predictors for the construction of the nomogram. The multivariate logistic regression analysis demonstrated that T4 status, hormone receptor status and receiving regimen of paclitaxel and carboplatin were independent predictors of pathological complete response. The area under the receiver operating characteristic curve of the training set and the validation set was 0.779 and 0.701, respectively. We constructed and validated a nomogram to predict pathological complete response in human epidermal growth factor receptor 2 negative breast cancer patients. We also identified tumor size, hormone receptor status and paclitaxel and carboplatin regimen as independent predictors of pathological complete response. The online version of this article (doi:10.1186/s12885-016-2652-z) contains supplementary material, which is available to authorized users

  14. Chemotherapy induced pathologic complete response in malignant pleural mesothelioma: a review and case report

    DEFF Research Database (Denmark)

    Bech, Cecilia; Sørensen, Jens Benn

    2010-01-01

    Malignant pleural mesothelioma is a rare aggressive disease with a poor prognosis and usually modest responses to chemotherapy. Complete responses (CRs) to chemotherapy are rare. Evaluation is usually based on radiology, and CR is therefore clinical CR (cCR) and whether this indicates absence...

  15. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-01-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  16. Clinical Outcome of Patients with Complete Pathological Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancers: The Indian Scenario

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    Snita Sinukumar

    2014-01-01

    Full Text Available Introduction. Neoadjuvant chemoradiotherapy and total mesorectal excision are considered the standard treatment for locally advanced rectal cancer. Various studies have reported pathological downstaging and a complete pathological response rate of 15%–27% following neoadjuvant chemoradiotherapy which has translated into improved survival. We endeavour to determine the clinical outcome of patients attaining a complete pathological tumor response following neoadjuvant chemoradiotherapy in the Indian setting where most of our patient population is younger and presents with aggressive tumor biology. Materials and Methods. Clinicopathological and treatment details were recorded for 64 patients achieving pathological complete response from 2010 to 2013. Disease-free survival (DFS, overall survival (OS, and locoregional and systemic recurrence rates were evaluated for these patients. Results. After a median follow-up of 30.5 months (range 11–59 months, the 3-year overall survival (OS was 94.6% and the 3-year disease-free survival (DFS was 88.5%. The locoregional and systemic recurrence rates were 4.7% and 3.1%, respectively. Conclusion. In the Indian subcontinent, despite younger patients with aggressive tumor biology, outcome in complete responders is good.

  17. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  18. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L.; Gonen, M.; Kuk, D.; Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L.; Saltz, L.; Schrag, D.; Goodman, K.; Shia, J.; Schwartz, L.H.

    2012-01-01

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K trans , k ep , v e , AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K trans (mean 0.5 min -1 vs. 0.2 min -1 , P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  19. Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

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    Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

    2014-01-17

    Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

  20. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

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    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Gonen, M.; Kuk, D. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States); Saltz, L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY (United States); Schrag, D. [Dana Farber Cancer Institute, Boston, MA (United States); Goodman, K. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Shia, J. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Schwartz, L.H. [Columbia University Medical Center/New York Presbyterian Hospital, Department of Radiology, New York, NY (United States)

    2012-04-15

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K{sup trans}, k{sub ep}, v{sub e}, AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P {<=} 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K{sup trans} (mean 0.5 min{sup -1} vs. 0.2 min{sup -1}, P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  1. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    International Nuclear Information System (INIS)

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-01-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  2. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    Directory of Open Access Journals (Sweden)

    I.P.C. Buzatto

    Full Text Available The purpose of this study was to retrospectively review the pathologic complete response (pCR rate from patients (n=86 with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012. Stage II patients achieved a higher response rate compared to stage III (P=0.03. The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively. Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03 and death (HR=0.21; P=0.02. In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

  3. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

    Science.gov (United States)

    Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

    2018-06-01

    To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

  4. 18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi

    2012-01-01

    The background of this study was to assess the usefulness of positron emission tomography combined with computed tomography using 18 F-fluorodeoxyglucose (FDG positron emission tomography (PET)/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. Tumors with pCR had significantly higher baseline SUV (9.3±3.7 SD) compared to those with non-pCR (7.2±3.8 SD) (p=0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR. (author)

  5. A deep learning classifier for prediction of pathological complete response to neoadjuvant chemotherapy from baseline breast DCE-MRI

    Science.gov (United States)

    Ravichandran, Kavya; Braman, Nathaniel; Janowczyk, Andrew; Madabhushi, Anant

    2018-02-01

    Neoadjuvant chemotherapy (NAC) is routinely used to treat breast tumors before surgery to reduce tumor size and improve outcome. However, no current clinical or imaging metrics can effectively predict before treatment which NAC recipients will achieve pathological complete response (pCR), the absence of residual invasive disease in the breast or lymph nodes following surgical resection. In this work, we developed and applied a convolu- tional neural network (CNN) to predict pCR from pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans on a per-voxel basis. In this study, DCE-MRI data for a total of 166 breast cancer pa- tients from the ISPY1 Clinical Trial were split into a training set of 133 patients and a testing set of 33 patients. A CNN consisting of 6 convolutional blocks was trained over 30 epochs. The pre-contrast and post-contrast DCE-MRI phases were considered in isolation and conjunction. A CNN utilizing a combination of both pre- and post-contrast images best distinguished responders, with an AUC of 0.77; 82% of the patients in the testing set were correctly classified based on their treatment response. Within the testing set, the CNN was able to produce probability heatmaps that visualized tumor regions that most strongly predicted therapeutic response. Multi- variate analysis with prognostic clinical variables (age, largest diameter, hormone receptor and HER2 status), revealed that the network was an independent predictor of response (p=0.05), and that the inclusion of HER2 status could further improve capability to predict response (AUC = 0.85, accuracy = 85%).

  6. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

    Science.gov (United States)

    Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

    2018-05-03

    BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

  7. High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer.

    Science.gov (United States)

    Makhoul, Issam; Griffin, Robert J; Siegel, Eric; Lee, Jeannette; Dhakal, Ishwori; Raj, Vinay; Jamshidi-Parsian, Azemat; Klimberg, Suzanne; Hutchins, Laura F; Kadlubar, Susan

    2016-06-01

    Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has been marked by the development of the monoclonal antibody bevacizumab, which targets VEGF in many solid tumors. As patients do not equally benefit from bevacizumab, it has become necessary to define the profile of patients who will benefit from the drug. We have conducted a prospective phase II study in 39 patients using bevacizumab in breast cancer in the neoadjuvant setting, and found improved pathologic complete response (pCR) when bevacizumab was added to chemotherapy in patients with hormone receptor negative and invasive ductal carcinoma. Blood samples were collected at baseline and serially while patients were on treatment. Circulating angiogenesis-related proteins angiopoietin (ANG)1, ANG2, basic fibroblast growth factor, IL-1a, matrix metalloproteinase 9, platelet derived growth factor - BB, platelet endothelial cell adhesion molecule -1, Tie2, VEGF, and vascular endothelial growth factor receptor 2 were measured at baseline and during treatment. This correlative study was conducted to identify specific serum angiogenic factor profiles that might be associated with pCR in the neoadjuvant setting in breast cancer patients receiving bevacizumab and chemotherapy. Elevated baseline serum Tie2 and basic fibroblast growth factor were associated with pCR in response to this combination. Changes in serum levels of these proteins were seen during treatment but were not significantly different between the pCR and non-pCR groups. Baseline-circulating Tie2 levels may help distinguish patients who will have pCR from those who will not and may form the basis for future development of antiangiogenic therapy in breast cancer. Larger studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT00203502.

  8. Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

    International Nuclear Information System (INIS)

    Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S.

    2011-01-01

    Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

  9. Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

    Directory of Open Access Journals (Sweden)

    Gabriella Macchia

    2017-06-01

    Results: Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585 or 2-drugs (N = 509 was administered. Overall, pCR was 22.3% (N = 468 patients. The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group, 23% (2nd group and 31.1% (3rd group (p 5040 cGy (p = 0.002 and longer interval (p 13 weeks from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

  10. [A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

    Science.gov (United States)

    Ichinohe, Daichi; Morohashi, Hajime; Umetsu, Satoko; Yoshida, Tatsuya; Wakasa, Yusuke; Odagiri, Tadashi; Kimura, Toshirou; Suto, Akiko; Saito, Takeshi; Yoshida, Eri; Akasaka, Harue; Jin, Hiroyuki; Miura, Takuya; Sakamoto, Yoshiyuki; Hakamada, Kenichi

    2016-11-01

    We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

  11. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent

  12. Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

    Science.gov (United States)

    Kawai, Kazushige; Ishihara, Soichiro; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

    2017-04-01

    Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. This was a retrospective comparative study. This study was conducted at a single referral hospital. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. Although endoscopic assessment after chemoradiotherapy correlated with pathological response

  13. T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

    Science.gov (United States)

    Kim, Sungwon; Han, Kyunghwa; Seo, Nieun; Kim, Hye Jin; Kim, Myeong-Jin; Koom, Woong Sub; Ahn, Joong Bae; Lim, Joon Seok

    2018-06-01

    To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm 3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

  14. Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

    Science.gov (United States)

    Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

    2016-07-01

    To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

  15. Pathological responses to terrorism.

    Science.gov (United States)

    Yehuda, Rachel; Bryant, Richard; Marmar, Charles; Zohar, Joseph

    2005-10-01

    Many important gains have been made in understanding PTSD and other responses to trauma as a result of neuroscience-based observations. Yet there are many gaps in our knowledge that currently impede our ability to predict those who will develop pathologic responses. Such knowledge is essential for developing appropriate strategies for mounting a mental health response in the aftermath of terrorism and for facilitating the recovery of individuals and society. This paper reviews clinical and biological studies that have led to an identification of pathologic responses following psychological trauma, including terrorism, and highlights areas of future-research. It is important to not only determine risk factors for the development of short- and long-term mental health responses to terrorism, but also apply these risk factors to the prediction of such responses on an individual level. It is also critical to consider the full spectrum of responses to terrorism, as well as the interplay between biological and psychological variables that contribute to these responses. Finally, it is essential to remove the barriers to collecting data in the aftermath of trauma by creating a culture of education in which the academic community can communicate to the public what is and is not known so that survivors of trauma and terrorism will understand the value of their participation in research to the generation of useful knowledge, and by maintaining the acquisition of knowledge as a priority for the government and those involved in the immediate delivery of services in the aftermath of large-scale disaster or trauma.

  16. [A case of transverse colon cancer with multiple liver metastases and hepatic pedicle lymph node involvement showing pathological complete response by XELOX plus bevacizumab].

    Science.gov (United States)

    Mukai, Toshiki; Akiyoshi, Takashi; Koga, Rintaro; Arita, Junichi; Saiura, Akio; Ikeda, Atsushi; Nagasue, Yasutomo; Oikawa, Yoshinori; Yamakawa, Keiko; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi; Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Yamamoto, Chiriko; Yamaguchi, Toshiharu

    2012-12-01

    A 70-year-old woman was referred to our hospital because of abdominal pain. Abdominal computed tomography(CT)and colonoscopy revealed transverse colon cancer with multiple liver metastases, with involvement of the hepatic pedicle and superior mesenteric artery lymph nodes. The patient received eight courses of XELOX plus bevacizumab, and CT showed a decrease in the size of the liver metastases and hepatic pedicle lymphadenopathy. Right hemicolectomy, partial hepatectomy, and hepatic pedicle lymph node resection were performed. Histopathological examination of the resected tissue revealed no residual cancer cells, suggesting a pathological complete response. The patient remains well 7 months after operation, without any signs of recurrence. Surgical resection should be considered for patients with initially unresectable colon cancer with liver metastases and hepatic pedicle lymph nodes involvement if systemic chemotherapy is effective.

  17. Pathologic features of suicidal complete decapitations.

    Science.gov (United States)

    Tsokos, M; Türk, E E; Uchigasaki, S; Püschel, K

    2004-01-28

    Despite high suicide rates all over the world, complete decapitation as a consequence of violent suicide methods is exceptionally rare and there is always a potential for confusion with homicide as well as with body dismemberment or mutilation. We analyzed the phenomenology and morphology of 10 cases (six male, four female; individual age 18-60 years) of suicidal complete decapitation that were subjected to medico-legal autopsies at the Institute of Legal Medicine, University of Hamburg, Germany, between 1995 and 2002. All decapitations occurred while the person was alive as proven by signs of vitality. Blood alcohol levels were positive in five cases and ranged between 28 and 202 mg/dl. The applied methods of suicide were running over by a train in eight cases and hanging in two cases. In suicidal hanging resulting in complete decapitation the wound margins were clear-cut with an adjacent sharply demarcated circumferential band-like abrasion zone showing a homogenous width, the latter determined by the thickness of the rope. In decapitations due to railway interference a broad spectrum of pathologic alterations such as the co-existence of irregular, ragged and sharp-edged wound margins, vascular and nervous pathways forming bridges in the depth of the wound and bruising could be observed. In such cases skin abrasion zones were generally not circumferential and showed a heterogenous width. Concerning hanging-related complete decapitations, our findings are well in line with those of other authors, namely that heavy body weight of the suicidal, fall from a great height and in some cases inelastic and/or thin rope material used for the noose are the determining factors decisive for complete decapitation.

  18. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Drisis, Stylianos; Stathopoulos, Konstantinos; Chao, Shih-Li; Lemort, Marc [Institute Jules Bordet, Radiology Department, Brussels (Belgium); Metens, Thierry [Erasme University Hospital, Radiology Department, Brussels (Belgium); Ignatiadis, Michael [Institute Jules Bordet, Oncology Department, Brussels (Belgium)

    2016-05-15

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  19. Prognostic role of acellular mucin pools in patients with rectal cancer after pathological complete response to preoperative chemoradiation: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Bhatti, A.B.H.

    2017-01-01

    The prognostic implication of acellular mucin pools (AMP) in rectal cancer is controversial. There is no Level-I evidence regarding their prognostic impact. This systematic review was performed to determine the impact of AMP on survival in patients with rectal cancer, who demonstrate pathological complete response (PCR) to preoperative chemoradiation (CRT). A systematic literature review was performed by searching MEDLINE and EMBASE database. For overall survival, the overall random effect model favored mucin negative tumors (HR=2, 95% CI=0.8-4.8) with heterogeneity (I-squared=0, p=0.6). However, the pooled analysis was not significant due to small sample. For disease-free survival, four studies showed HR >1; however, the pooled random effect model indicated little difference in risk (HR=1.06, 95% CI=0.4-2.4) with heterogeneity (I-squared=49.5%, p=0.07). No definite prognostic role of AMP in rectal cancer patients with PCR was found. These results, however, should be interpreted with caution. (author)

  20. [Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

    Science.gov (United States)

    He, Y J; Li, X T; Fan, Z Q; Li, Y L; Cao, K; Sun, Y S; Ouyang, T

    2018-01-23

    Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR =0.942 (95% CI : 0.918-0.967) and 0.961 (95% CI : 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95% CI : 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

  1. Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zschaeck, Sebastian [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Hofheinz, Frank [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). PET Center, Inst. of Radiopharmaceutical Cancer Research; Zoephel, Klaus; Kotzerke, Joerg [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Carl Gustav Carus, Dresden (Germany). Dept. of Nuclear Medicine; National Center for Tumor Diseases (NCT), Dresden (Germany); Buetof, Rebecca; Schmollack, Julia [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Jentsch, Christina [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Loeck, Steffen; Baumann, Michael; Krause, Mechthild [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Baretton, Gustavo [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Pathology; Weitz, Juergen [German Cancer Consortium (DKTK), Dresden (DE); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Visceral, Thoracic and Vascular Surgery

    2017-10-15

    Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis. This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV{sub max}, SUV{sub mean}) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis. Increased FDG uptake, measured in terms of SUV{sub mean} in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV{sub max} and SUV{sub mean} in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV{sub max} and SUV{sub mean} in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011). FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization. (orig.)

  2. Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Koolen, Bas B.; Pengel, Kenneth E.; Wesseling, Jelle; Vogel, Wouter V.; Valdes Olmos, Renato A.; Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T.; Vincent, Andrew D.; Gilhuijs, Kenneth G.A.; Rodenhuis, Sjoerd

    2014-01-01

    To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

  3. Sequential {sup 18}F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, Bas B. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Pengel, Kenneth E. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Wesseling, Jelle [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Vogel, Wouter V.; Valdes Olmos, Renato A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vincent, Andrew D. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, Sjoerd [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2014-01-15

    To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

  4. Comparison of diffusion-weighted MR imaging and FDG PET/CT to predict pathological complete response to neoadjuvant chemotherapy in patients with breast cancer

    International Nuclear Information System (INIS)

    Park, Sang Hee; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min; Im, Seock-Ah; Park, In Ae; Kang, Keon Wook; Han, Wonshik; Noh, Dong-Young

    2012-01-01

    To compare the use of diffusion-weighted MR imaging (DWI) and 18 F-FDG PET/CT to predict pathological complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy. Thirty-four women with 34 invasive breast cancers underwent DWI and PET/CT before and after chemotherapy and before surgery. The percentage changes in the apparent diffusion coefficient (ADC) and the standardised uptake value (SUV) were calculated, and the diagnostic performances for predicting pCR were evaluated using receiver operating characteristic (ROC) curve analysis. After surgery, 7/34 patients (20.6%) were found to have pCR. A z values for DWI, PET/CT and the combined use of DWI and PET/CT were 0.910, 0.873 and 0.944, respectively. The best cut-offs for differentiating pCR from non-pCR were a 54.9% increase in the ADC and a 63.9% decrease in the SUV. DWI showed 100% (7/7) sensitivity and 70.4% (19/27) specificity and PET/CT showed 100% sensitivity and 77.8% (21/27) specificity. When DWI and PET/CT were combined, there was a trend towards improved specificity compared with DWI. DWI and FDG PET/CT show similar diagnostic accuracy for predicting pCR to neoadjuvant chemotherapy in breast cancer patients. The combined use of DWI and FDG PET/CT has the potential to improve specificity in predicting pCR. (orig.)

  5. Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

    Science.gov (United States)

    Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

    2010-01-01

    Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

  6. Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI.

    Science.gov (United States)

    Braman, Nathaniel M; Etesami, Maryam; Prasanna, Prateek; Dubchuk, Christina; Gilmore, Hannah; Tiwari, Pallavi; Plecha, Donna; Madabhushi, Anant

    2017-05-18

    In this study, we evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on pretreatment breast cancer dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). A total of 117 patients who had received NAC were retrospectively analyzed. Within the intratumoral and peritumoral regions of T1-weighted contrast-enhanced MRI scans, a total of 99 radiomic textural features were computed at multiple phases. Feature selection was used to identify a set of top pCR-associated features from within a training set (n = 78), which were then used to train multiple machine learning classifiers to predict the likelihood of pCR for a given patient. Classifiers were then independently tested on 39 patients. Experiments were repeated separately among hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR + , HER2 - ) and triple-negative or HER2 + (TN/HER2 + ) tumors via threefold cross-validation to determine whether receptor status-specific analysis could improve classification performance. Among all patients, a combined intratumoral and peritumoral radiomic feature set yielded a maximum AUC of 0.78 ± 0.030 within the training set and 0.74 within the independent testing set using a diagonal linear discriminant analysis (DLDA) classifier. Receptor status-specific feature discovery and classification enabled improved prediction of pCR, yielding maximum AUCs of 0.83 ± 0.025 within the HR + , HER2 - group using DLDA and 0.93 ± 0.018 within the TN/HER2 + group using a naive Bayes classifier. In HR + , HER2 - breast cancers, non-pCR was characterized by elevated peritumoral heterogeneity during initial contrast enhancement. However, TN/HER2 + tumors were best characterized by a speckled enhancement pattern within the peritumoral region of nonresponders. Radiomic features were found to strongly predict pCR independent of

  7. The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

    Science.gov (United States)

    Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

    2017-06-01

    The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis.

    Science.gov (United States)

    Criscitiello, Carmen; Golshan, Mehra; Barry, William T; Viale, Giulia; Wong, Stephanie; Santangelo, Michele; Curigliano, Giuseppe

    2018-05-04

    We conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC). The primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant. Thirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5-76% across arms with an average BCT of 57% (95% CI 52-62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I 2  = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3-60% across studies. The average pCR across all study arms was 24% (95% CI 19-29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27). pCR does not increase BCT in patients receiving NST for EBC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design

    International Nuclear Information System (INIS)

    Lefevre, Jérémie H; Rousseau, Alexandra; Svrcek, Magali; Parc, Yann; Simon, Tabassome; Tiret, Emmanuel

    2013-01-01

    Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery. The current study is a multicenter randomized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors. At the end of the RCT, surgery is planified and randomization is performed after patient’s written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5 years after surgery. Participation in this trial does not change patient’s management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264. ClinicalTrial.gov: http://www.clinicaltrials.gov/NCT01648894

  10. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    . This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...... in individuals with exacerbated pathological gambling symptoms. These findings may have important implications for detecting behaviors underlying pathological gambling....

  11. Percentage of pathological complete response in patients with rectal cancer that received neoadjuvant therapy with chemotherapy and radiotherapy at the Servicio de Radioterapia from Hospital Mexico, in the period from January 2009 to December 2013

    International Nuclear Information System (INIS)

    Lopez Mena, Stephanie

    2015-01-01

    Percentage of pathologic complete response is determined in patients with rectal cancer, treated with neoadjuvant chemotherapy and radiotherapy, in the Servicio de Radioterapia from Hospital Mexico, in the period between January 2009 and December 2013. Tumor histology is determined. The distance of the tumor is identified with respect to the anal margin. The correlation between the TNM staging and the response received in this type of neoadjuvant therapy is described. Radiotherapy dose used in each case is described. Different schemes of chemotherapy used are characterized. The acute side effects most common are determined in the study population [es

  12. Tumor Volume Changes Assessed by Three-Dimensional Magnetic Resonance Volumetry in Rectal Cancer Patients After Preoperative Chemoradiation: The Impact of the Volume Reduction Ratio on the Prediction of Pathologic Complete Response

    International Nuclear Information System (INIS)

    Kang, Jeong Hyun; Kim, Young Chul; Kim, Hyunki; Kim, Young Wan; Hur, Hyuk; Kim, Jin Soo; Min, Byung Soh; Kim, Hogeun; Lim, Joon Seok; Seong, Jinsil; Keum, Ki Chang; Kim, Nam Kyu

    2010-01-01

    Purpose: The aim of this study was to determine the correlation between tumor volume changes assessed by three-dimensional (3D) magnetic resonance (MR) volumetry and the histopathologic tumor response in rectal cancer patients undergoing preoperative chemoradiation therapy (CRT). Methods and Materials: A total of 84 patients who underwent preoperative CRT followed by radical surgery were prospectively enrolled in the study. The post-treatment tumor volume and tumor volume reduction ratio (% decrease ratio), as shown by 3D MR volumetry, were compared with the histopathologic response, as shown by T and N downstaging and the tumor regression grade (TRG). Results: There were no significant differences in the post-treatment tumor volume and the volume reduction ratio shown by 3D MR volumetry with respect to T and N downstaging and the tumor regression grade. In a multivariate analysis, the tumor volume reduction ratio was not significantly associated with T and N downstaging. The volume reduction ratio (>75%, p = 0.01) and the pretreatment carcinoembryonic antigen level (≤3 ng/ml, p = 0.01), but not the post-treatment volume shown by 3D MR (≤ 5ml), were, however, significantly associated with an increased pathologic complete response rate. Conclusion: More than 75% of the tumor volume reduction ratios were significantly associated with a high pathologic complete response rate. Therefore, limited treatment options such as local excision or simple observation might be considered after preoperative CRT in this patient population.

  13. Predictive ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for pathological complete response and prognosis after neoadjuvant chemotherapy in triple-negative breast cancer patients

    Directory of Open Access Journals (Sweden)

    Sachiko Kiyoto

    2016-01-01

    Full Text Available Objective The mortality of patients with locally advanced triple-negative breast cancer (TNBC is high, and pathological complete response (pCR to neoadjuvant chemotherapy (NAC is associated with improved prognosis. This retrospective study was designed and powered to investigate the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT to predict pathological response to NAC and prognosis after NAC.Methods The data of 32 consecutive women with clinical stage II or III TNBC from January 2006 to December 2013 in our institution who underwent FDG-PET/CT at baseline and after NAC were retrospectively analyzed. The maximum standardized uptake value (SUVmax in the primary tumor at each examination and the change in SUVmax (ΔSUVmax between the two scans were measured. Correlations between PET parameters and pathological response, and correlations between PET parameters and disease-free survival (DFS were examined.Results At the completion of NAC, surgery showed pCR in 7 patients, while 25 had residual tumor, so-called non-pCR. Median follow-up was 39.0 months. Of the non-pCR patients, 9 relapsed at 3 years. Of all assessed clinical, biological, and PET parameters, N-stage, clinical stage, and ΔSUVmax were predictors of pathological response (p=0.0288, 0.0068, 0.0068; Fischer’s exact test. The cut-off value of ΔSUVmax to differentiate pCR evaluated by the receiver operating characteristic (ROC curve analysis was 81.3%. Three-year disease-free survival (DFS was lower in patients with non-pCR than in patients with pCR (p=0.328, log-rank test. The cut-off value of ΔSUVmax to differentiate 3-year DFS evaluated by the ROC analysis was 15.9%. In all cases, 3-year DFS was lower in patients with ΔSUVmax

  14. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  15. Evaluation of Clinical and Pathological Response after Two Cycles ...

    African Journals Online (AJOL)

    Results: The clinical response rate was 83%; 11 patients (11.2%) had a complete clinical remission (cCR); 71 had a partial remission (72.4%); 13 had stable disease (13.3%), and 3 had progressive disease (3.1%). Seven patients had complete pathological response. Conclusion: Neoadjuvant chemotherapy can achieve a ...

  16. Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: Effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival

    International Nuclear Information System (INIS)

    Wiltshire, Kirsty L.; Ward, Iain G.; Swallow, Carol; Oza, Amit M.; Cummings, Bernard; Pond, Gregory R.; Catton, Pamela; Kim, John; Ringash, Jolie; Wong, Chong S.; Wong, Rebecca; Siu, Lillian L.; Moore, Malcolm; Brierley, James

    2006-01-01

    Purpose: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). Methods and Materials: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m 2 /day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. Results: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). Conclusions: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy

  17. Impact of Race, Ethnicity and BMI on Achievement of Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer: A Pooled Analysis of Four Prospective Alliance Clinical Trials (A151426)

    Science.gov (United States)

    Warner, Erica T.; Ballman, Karla V.; Strand, Carrie; Boughey, Judy; Buzdar, Aman U.; Carey, Lisa A.; Sikov, William M.; Partridge, H.

    2016-01-01

    Purpose Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. Methods 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95% confidence intervals (CI) for the associations of race, ethnicity, and BMI with pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. Results 253 (14.1%) were black, 199 (11.1%) Hispanic, 520 (28.9%) overweight, and 743 (41.4%) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs. white: OR: 1.18, 95% CI: 0.85–1.62) nor ethnicity (Hispanic vs. non-Hispanic: OR: 1.30, 95% CI: 0.67–2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER−/HER2+ cancers. Conclusions There was no difference in breast pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. PMID:27449492

  18. Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Diocésio Alves Pinto de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Zucca-Matthes, Gustavo; Vieira, René Aloísio da Costa [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Andrade, Cristiane Thomaz de Aquino Exel de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Costa, Allini Mafra da [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Monteiro, Aurélio Julião de Castro [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Lago, Lissandra Dal [Institut Jules Bordet, Brussels (Belgium); Nunes, João Soares [Hospital de Câncer de Barretos, Barretos, SP (Brazil)

    2013-07-01

    To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/ cyclophosphamide regimen followed by paclitaxel. A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m{sup 2} and cyclophosphamide 600mg/m{sup 2} every 21 days; 4 cycles of paclitaxel 175mg/m{sup 2} every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose – duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. Neoadjuvant chemotherapy with doxorubicin/ cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

  19. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

    Science.gov (United States)

    Bonnefoi, H; Litière, S; Piccart, M; MacGrogan, G; Fumoleau, P; Brain, E; Petit, T; Rouanet, P; Jassem, J; Moldovan, C; Bodmer, A; Zaman, K; Cufer, T; Campone, M; Luporsi, E; Malmström, P; Werutsky, G; Bogaerts, J; Bergh, J; Cameron, D A

    2014-06-01

    Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P analysis. EORTC 10994/BIG 1-00 Trial registration number NCT00017095. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.

    Science.gov (United States)

    Pierga, J-Y; Bidard, F-C; Autret, A; Petit, T; Andre, F; Dalenc, F; Levy, C; Ferrero, J-M; Romieu, G; Bonneterre, J; Lerebours, F; Bachelot, T; Kerbrat, P; Campone, M; Eymard, J-C; Mouret-Reynier, M-A; Gligorov, J; Hardy-Bessard, A-C; Lortholary, A; Soulie, P; Boher, J-M; Proudhon, C; Charafe-Jaufret, E; Lemonnier, J; Bertucci, F; Viens, P

    2017-01-01

    We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials. © The Author 2016

  1. Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

    Science.gov (United States)

    Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

    2017-08-01

    The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation

  2. Prognostic value of pathological response to chemo radiotherapy of locally advanced low rectal cancer

    International Nuclear Information System (INIS)

    Bannura C, Guillermo; Vargas N, Claudio; Barrera E, Alejandro; Melo L, Carlos; Illanes F, Felipe

    2013-01-01

    Background: Preoperative chemo radiotherapy improves the prognosis of locally advanced low rectal cancer and induces a pathological response in the tumor, which may have prognostic value. Aim: To assess the results of rectal cancer treatment according to the degree of pathological response of the tumor after chemo radiotherapy. Patients and Methods: All patients with a locally advanced rectal cancer located within 11 cm of the rectal margin, subjected to preoperative chemo radiotherapy followed by surgical treatment in a period of 13 years, were included. Pathological response was classified as complete, intermediate and poor. The tumor was staged according to TNM 2002 classification. Survival was analyzed with Kaplan Meier curves and Cox regression. Results: Patients were followed for a mean of 50 months (range 18-156). Exclusive and global local relapse was observed in 3 and 9.6% of patients, respectively. Pathological response was complete in 13 patients (none died), intermediate in 23 (three died) and poor in 68 (22 died). Global five years survival was 74%. There was a concordance of 0.64 between survival and pathological response. The concordance between survival and TNM classification was 0.69. Conclusions: The pathological response of the tumor to chemo radiotherapy has a good concordance with prognosis, although it is not superior to the final pathological status

  3. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

    LENUS (Irish Health Repository)

    Toomey, Sinead

    2017-07-27

    The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K\\/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.

  4. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  5. Pathological response for neoadjuvant chemotherapy in locally ...

    African Journals Online (AJOL)

    Background: Breast cancer is the leading cancer in Sudanese females. Objectives: This study was done to evaluate the clinical response to neoadjuvant chemotherapy for patients treated at National Cancer Institute (NCI) and to compare it with the published literature. Methods: This is a retrospective study conducted in ...

  6. Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

    Science.gov (United States)

    Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

    2015-06-01

    Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  7. [The clinical and pathological research of complete mesocolic excision on the treatment of right colon cancer].

    Science.gov (United States)

    Yang, Yingchi; Wang, Jin; Jin, Lan; Zhao, Xiaomu; Wu, Guocong; Wang, Kangli; Zhang, Zhongtao

    2016-01-01

    To verify the clinical safety of complete mesocolic excision (CME) and manufacture pathological large slices. A prospective analysis clinical data of 85 right colon cancer in patients by the same group of surgeons at the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2012 to December 2013 which were divided into two groups: CME group (n=39) and traditional radical operation group (n=46) by surgical approach. CME group and control group were compared the differences of clinic and pathologic variables, precise tissues morphometry, lymph nodes harvest, mesocolic area and so on. By comparison to operation time, blood loss, postoperative complications, flatus restoring time, drainage removal time and length of stay, the security of CME was analyzed. Statistical methods included independent sample t-test, Wilcoxon rank sum test and χ(2) test. In order to manufacture pathological large slices, the CME operation specimens were fixed. The large slices were stained by routine HE staining to detection of circumferential resection margin. Mean number of total lymph nodes was increased obviously in CME group (26.8±1.9 vs. 23.2±3.4, t=4.261, P=0.000). Mean number of lymph nodes of stage Ⅰ, Ⅱ were different between two groups (25.8±3.6 vs. 18.2±4.5, 26.8±7.7 vs. 24.9±6.2, t=8.776, 2.802, P=0.000). The positive lymph nodes of CME group was higher than control group (4(7) vs. 1.5(2), P=0.032), above all with statistically significant difference. Comparing CME group with the control group, there were the larger area of mesentery ((15 555±1 263) mm(2) vs. (12 493±1 002) mm(2,) t=12.456, P=0.000), the greater distance between the tumor and the high vascular tie ((116±22) mm vs. (82±11) mm, t=9.295, P=0.000), the greater distance between the normal bowel and the high vascular tie ((92±17) mm vs. (74±10) mm, t=8.132, P=0.000) of CME, with statistically significant difference. There were no statistically significant

  8. Limited accuracy of DCE-MRI in identification of pathological complete responders after chemoradiotherapy treatment for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, Marc J. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Tong, Tong [Fudan University Medical Center, Department of Radiology, Shanghai (China); Weiser, Martin [Memorial Sloan Kettering Cancer Center, Department of Surgery, Divison of Colorectal Surgery, New York, NY (United States); Zheng, Junting; Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Zakian, Kristen L. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States)

    2017-04-15

    To examine whether post-chemoradiotherapy (CRT) DCE-MRI can identify rectal cancer patients with pathologic complete response (pCR). From a rectal cancer surgery database 2007-2014, 61 consecutive patients that met the following inclusion criteria were selected for analysis: (1) stage II/III primary rectal adenocarcinoma; (2) received CRT; (3) underwent surgery (4); underwent rectal DCE-MRI on a 1.5-T MRI scanner. Two experienced radiologists, in consensus, drew regions of interest (ROI) on the sagittal DCE-MRI image in the tumour bed. These were exported from ImageJ to in-house Matlab code for modelling using the Tofts model. K{sup trans}, K{sub ep} and v{sub e} values were compared to pathological response. Of the 61 initial patients, 37 had data considered adequate for fitting to obtain perfusion parameters. Among the 13 men and 24 women, median age 53 years, there were 8 pCR (22 %). K{sup trans} could not distinguish patients with pCR. For patients with 90 % or greater response, mean K{sup trans} and K{sub ep} values were statistically significant (p = 0.032 and 0.027, respectively). Using a cutoff value of K{sup trans} = 0.25 min{sup -1}, the AUC was 0.71. K{sup trans} could be used to identify patients with 90 % or more response to chemoradiotherapy for rectal cancer with an AUC of 0.7. (orig.)

  9. Pathological Imitative Behavior and Response Preparation in Schizophrenia.

    Science.gov (United States)

    Dankinas, Denisas; Melynyte, Sigita; Siurkute, Aldona; Dapsys, Kastytis

    2017-08-01

    Pathological imitative behavior (ehopraxia) is occasionally observed in schizophrenia patients. However, only a severe form of echopraxia can be detected with the help of a direct observation. Therefore, our goal was to study a latent form of pathological imitative behavior in this disorder, which is indicated by an increase of imitative tendencies. In our study, 14 schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in an imitative task they had to copy a hand action seen on a screen; (b) in a counter-imitative task they had to make a different movement (which involves an inhibition of prepotent imitative tendency that is impaired in case of pathological imitative behavior). Imitative tendencies were assessed by an interference score - a difference between counter-imitative and imitative response parameters. We also studied a response preparation in both groups by employing precueing probabilistic information. Our results revealed that schizophrenia patients were able to employ probabilistic information to prepare properly not only the imitative, but also the counter-imitative responses, the same as the healthy subjects did. Nevertheless, we detected increased prepotent imitative tendencies in schizophrenia patients, what indicates the latent pathological imitative behavior in case of this disorder. The obtained results suggest that in the case of schizophrenia problems with pathological imitative behavior more likely occurred in executive rather than in the preparatory stage of response. Our findings can help to detect a latent echopraxia in schizophrenia patients that cannot be revealed by direct observation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Using pathology-specific laboratory profiles in Clinical Pathology to reduce inappropriate test requesting: two completed audit cycles

    Science.gov (United States)

    2012-01-01

    Background Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Methods Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs’ request forms. Results Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p < 0.001); 2) the provisional diagnosis on the request forms was 52.8% in the trial district and 42% in the control district (P < 0.001); 3) the decrease of the number of tests on each request form was much more marked in the trial district (8.73 vs. 10.77; p < 0.001). Conclusions The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the

  11. ER, PgR, Ki67, p27Kip1, and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab

    International Nuclear Information System (INIS)

    Kurozumi, Sasagu; Inoue, Kenichi; Takei, Hiroyuki; Matsumoto, Hiroshi; Kurosumi, Masafumi; Horiguchi, Jun; Takeyoshi, Izumi; Oyama, Tetsunari

    2015-01-01

    Neoadjuvant chemotherapy (NAC) with taxanes followed by fluorouracil, epirubicin, and cyclophosphamide (FEC), and concurrent trastuzumab is a potent regimen for HER2 over-expressing breast cancer. A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear. In the present study, we determined whether pCR was related to histological grade (HG) and several biological factors including p27 Kip1 . We also assessed the prognosis of the pCR and non-pCR groups, and expected differences between those positive and negative for lymph node metastasis after chemotherapy. A total of 129 Japanese women with HER2-positive invasive breast cancer received either paclitaxel or docetaxel followed by FEC, with the concomitant administration of trastuzumab. The statuses of HG, ER, PgR, Ki67, and p27 Kip1 were evaluated to determine their relationship with pCR. Relapse-free survival (RFS) and overall survival (OS) were also analyzed for their relationship with pCR and pathological nodal involvement. pCR was obtained in 84 out of 129 patients and the pCR rate was 65.1 %. The pCR rates related to 5 factors were as follows: HG (grade 3, 70.0 % vs. grades 1–2, 36.8 %), ER (negative, 78.6 % vs. positive, 40.0 %), PgR (negative, 75.3 % vs. positive, 38.9 %), Ki67 (high, 72.0 % vs. low, 47.2 %), and p27 Kip1 (low, 71.0 % vs. high, 50.0 %). RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018). Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002). High-HG, low-ER, low-PgR, high-Ki67, and low-p27 Kip1 were identified as predictive factors of pCR in NAC with trastuzumab, while pCR and negative nodes were predictive of better survivals. The online version of this article (doi:10.1186/s12885-015-1641-y) contains supplementary material, which is available to authorized users

  12. Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Dhanya Vasudevan

    2015-01-01

    Full Text Available Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT in the setting of locally advanced breast cancer (LABC can render inoperable tumor (T4, N2/N3 resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma (n=48 were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier’s system which graded the responses into pathological complete response (pCR, pathological partial response (pPR, and pathological no response (pNR. Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2–5 cms and Bloom Richardson’s grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response.

  13. Correlates of motivation to change in pathological gamblers completing cognitive-behavioral group therapy.

    Science.gov (United States)

    Gómez-Peña, Mónica; Penelo, Eva; Granero, Roser; Fernández-Aranda, Fernando; Alvarez-Moya, Eva; Santamaría, Juan José; Moragas, Laura; Neus Aymamí, Maria; Gunnard, Katarina; Menchón, José M; Jimenez-Murcia, Susana

    2012-07-01

    The present study analyzes the association between the motivation to change and the cognitive-behavioral group intervention, in terms of dropouts and relapses, in a sample of male pathological gamblers. The specific objectives were as follows: (a) to estimate the predictive value of baseline University of Rhode Island Change Assessment scale (URICA) scores (i.e., at the start of the study) as regards the risk of relapse and dropout during treatment and (b) to assess the incremental predictive ability of URICA scores, as regards the mean change produced in the clinical status of patients between the start and finish of treatment. The relationship between the URICA and the response to treatment was analyzed by means of a pre-post design applied to a sample of 191 patients who were consecutively receiving cognitive-behavioral group therapy. The statistical analysis included logistic regression models and hierarchical multiple linear regression models. The discriminative ability of the models including the four URICA scores regarding the likelihood of relapse and dropout was acceptable (area under the receiver operating haracteristic curve: .73 and .71, respectively). No significant predictive ability was found as regards the differences between baseline and posttreatment scores (changes in R(2) below 5% in the multiple regression models). The availability of useful measures of motivation to change would enable treatment outcomes to be optimized through the application of specific therapeutic interventions. © 2012 Wiley Periodicals, Inc.

  14. Preoperative external beam radiotherapy and reduced dose brachytherapy for carcinoma of the cervix: survival and pathological response

    International Nuclear Information System (INIS)

    Jacinto, Alexandre A; Maia, Maria AC; Fogaroli, Ricardo C; Castilho, Marcus S; Novaes, Paulo ERS; Novick, Pablo R; Viani, Gustavo A; Salvajoli, João V; Ferrigno, Robson; Pellizzon, Antonio Cássio A; Lima, Stella SS

    2007-01-01

    To evaluate the pathologic response of cervical carcinoma to external beam radiotherapy (EBRT) and high dose rate brachytherapy (HDRB) and outcome. Between 1992 and 2001, 67 patients with cervical carcinoma were submitted to preoperative radiotherapy. Sixty-five patients were stage IIb. Preoperative treatment included 45 Gy EBRT and 12 Gy HDRB. Patients were submitted to surgery after a mean time of 82 days. Lymphadenectomy was performed in 81% of patients. Eleven patients with residual cervix residual disease on pathological specimen were submitted to 2 additional insertions of HDRB. median follow up was 72 months. Five-year cause specific survival was 75%, overall survival 65%, local control 95%. Complete pelvic pathological response was seen in 40%. Surgery performed later than 80 days was associated with pathological response. Pelvic nodal involvement was found in 12%. Complete pelvic pathological response and negative lymphnodes were associated with better outcome (p = .03 and p = .005). Late grade 3 and 4 urinary and intestinal adverse effects were seen in 12 and 2% of patients. Time allowed between RT and surgery correlated with pathological response. Pelvic pathological response was associated with improved outcome. Postoperative additional HDRB did not improve therapeutic results. Treatment was well tolerated

  15. Attaining pathological complete regression for breast conservation – A pilot experience in a developing country

    Directory of Open Access Journals (Sweden)

    E.A. Sule

    2016-08-01

    Conclusion: Extended chemotherapy sessions alongside re-excisions were successful in achieving much enhanced rates of pathologically complete remissions at 100% in this yet early report, thus improving breast conservation rates even for T3 and T4 tumours. Our study reports higher PCR rates.

  16. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Seyda Gunduz

    2012-07-01

    Full Text Available Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein.

  17. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

    Directory of Open Access Journals (Sweden)

    Steven J. Brookes

    2017-09-01

    Full Text Available During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  18. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Dixon, Michael J; Kirkham, Jennifer

    2017-01-01

    During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other "professional" secretory cells, ameloblasts employ the unfolded protein response (UPR) to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum)/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI) and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  19. Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

    Directory of Open Access Journals (Sweden)

    Hanson Jesse E

    2010-08-01

    Full Text Available Abstract Background Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1 Strength of long-term potentiation (LTP, 2 Strength of long-term depression (LTD, 3 Relative inhibition levels (Inhibition, and 4 Excitatory connectivity levels (Connectivity. Results To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties. Conclusions Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.

  20. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  1. Living with Smartphones: Does Completion Device Affect Survey Responses?

    Science.gov (United States)

    Lambert, Amber D.; Miller, Angie L.

    2015-01-01

    With the growing reliance on tablets and smartphones for internet access, understanding the effects of completion device on online survey responses becomes increasing important. This study uses data from the Strategic National Arts Alumni Project, a multi-institution online alumni survey designed to obtain knowledge of arts education, to explore…

  2. Improving Completion Rates in Adult Education through Social Responsibility

    Science.gov (United States)

    Wahlgren, Bjarne; Mariager-Anderson, Kristina

    2017-01-01

    Dropout is a serious problem within education. This article reports on an intervention project, titled "New Roles for the Teacher--Increased Completion Rates Through Social Responsibility," which sought to reduce nonattendance and drop-out rates in the Danish adult educational system by improving teachers' competences. This goal was…

  3. Complete and Partial Organizing for Corporate Social Responsibility

    NARCIS (Netherlands)

    Rasche, A.; de Bakker, F.G.A.; Moon, J.

    2013-01-01

    This paper investigates different modes of organizing for corporate social responsibility (CSR). Based on insights from organization theory, we theorize two ways to organize for CSR. "Complete" organization for CSR happens within businesses and depends on the availability of certain organizational

  4. Complete and Partial Organizing for Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Rasche, Andreas; de Bakker, Frank; Moon, Jeremy

    2013-01-01

    This paper investigates different modes of organizing for corporate social responsibility (CSR). Based on insights from organization theory, we theorize two ways to organize for CSR. 'Complete' organization for CSR happens within businesses and depends on the availability of certain organizationa...

  5. Weak simulated extratropical responses to complete tropical deforestation

    Science.gov (United States)

    Findell, K.L.; Knutson, T.R.; Milly, P.C.D.

    2006-01-01

    The Geophysical Fluid Dynamics Laboratory atmosphere-land model version 2 (AM2/LM2) coupled to a 50-m-thick slab ocean model has been used to investigate remote responses to tropical deforestation. Magnitudes and significance of differences between a control run and a deforested run are assessed through comparisons of 50-yr time series, accounting for autocorrelation and field significance. Complete conversion of the broadleaf evergreen forests of South America, central Africa, and the islands of Oceania to grasslands leads to highly significant local responses. In addition, a broad but mild warming is seen throughout the tropical troposphere (deforested run and the control run are similar in magnitude and area to the differences between nonoverlapping segments of the control run. These simulations suggest that extratropical responses to complete tropical deforestation are unlikely to be distinguishable from natural climate variability.

  6. Non-pathological complete paternal uniparental isodisomy of chromosome 2 revealed in a maternity testing case.

    Science.gov (United States)

    Chen, Man; Jiang, Jian; Li, Chen; Ren, He; Chen, Wei; Liu, Zhiyong; Cheng, Feng; Zhao, Jing; Chen, Tong; Chen, Chuguang; Yan, Jiangwei

    2018-05-25

    We present a duo paternity test case to assess the biological relationship between a woman and her female child. After analyzing 57 autosomal and 19 X-chromosomal short tandem repeat loci, mother-daughter exclusions were discovered at four loci, which were all located on chromosome 2. Further testing of whole-genome single nucleotide polymorphisms confirmed that the daughter had complete uniparental disomy (UPD) of chromosome 2. This study presents a cautionary case demonstrating that hasty decisions of parentage exclusion should not be made when genetic markers on the same chromosome do not conform to Mendel's laws due to UPD.

  7. Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma

    International Nuclear Information System (INIS)

    Roberge, David; Skamene, Tanya; Nahal, Ayoub; Turcotte, Robert E.; Powell, Tom; Freeman, Carolyn

    2010-01-01

    Purpose: To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas. Materials/methods: Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case. Results: Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction ≥ 50%) was highly predictive of a good pathological response (p < 0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses. Conclusions: Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response.

  8. Fatal inanition in reindeer (Rangifer tarandus tarandus: Pathological findings in completely emaciated carcasses

    Directory of Open Access Journals (Sweden)

    Mørk Torill

    2007-09-01

    Full Text Available Abstract Background In a project to determine the causes of winter mortality in reindeer in Finnmark County, northern Norway, the most frequent diagnosis turned out to be complete emaciation, despite several of the reindeer having been given silage for up to 4 weeks before they died. The present paper describes autopsy results and other findings in these animals. Methods Autopsies were made of 32 reindeer carcasses, and 28 of these were diagnosed as completely emaciated based on lack of visible fat and serous atrophy of subepicardial and bone marrow fat. Other investigations of the carcasses included histology, bacteriology, parasitology (counting of macro parasites and faecal egg counting, analysis of vitamin E and selenium in liver, chemical and botanical analysis of rumen content, analysis of lipid content in femur bone marrow and estimation of muscle atrophy by use of a muscle index. Results Main findings were: Low carcass weight, severe muscle atrophy, hemosiderosis in liver and spleen, subcutaneous oedema (18% and effusions to body cavities (18%. Two types of lipofuscin granula were identified in the liver: One type occurred in liver endothelial cells of all carcasses, while the other type occurred in hepatocytes, and prevailed in adult animals. Abomasal haemorrhages, consistent with previously described stress lesions, was present in 68% of the carcasses. Diarrhoea occurred in 2 cases, and loose faecal consistency was associated with silage feeding. Rumen content was low in crude protein. Grass dominated rumen content in silage-fed carcasses, while reindeer on natural pastures had mainly woody plants, mosses and litter in rumen. Stem dominated the grass fraction in rumens with high grass content, indicating ruminal indigestion as a cause of emaciation in silage fed animals. Some cases had heavy infestation of parasites such as warble fly larvae (Hypoderma tarandi, throat bot larvae (Cephenemyiae trompe and lung nematodes. Conclusion Lack

  9. Improving completion rates in adult education through social responsibility

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne; Mariager-Anderson, Kristina

    2017-01-01

    Dropout is a serious problem within education. This article reports on an intervention project, titled “New Roles for the Teacher—Increased Completion Rates Through Social Responsibility,” which sought to reduce nonattendance and dropout rates in the Danish adult educational system by improving...... of reducing drop-out rates. As a consequence, the teachers acted more consistently and purposefully to prevent dropout, and a positive effect of the intervention on drop-out rates was documented....

  10. Complete super-sample lensing covariance in the response approach

    Science.gov (United States)

    Barreira, Alexandre; Krause, Elisabeth; Schmidt, Fabian

    2018-06-01

    We derive the complete super-sample covariance (SSC) of the matter and weak lensing convergence power spectra using the power spectrum response formalism to accurately describe the coupling of super- to sub-survey modes. The SSC term is completely characterized by the survey window function, the nonlinear matter power spectrum and the full first-order nonlinear power spectrum response function, which describes the response to super-survey density and tidal field perturbations. Generalized separate universe simulations can efficiently measure these responses in the nonlinear regime of structure formation, which is necessary for lensing applications. We derive the lensing SSC formulae for two cases: one under the Limber and flat-sky approximations, and a more general one that goes beyond the Limber approximation in the super-survey mode and is valid for curved sky applications. Quantitatively, we find that for sky fractions fsky ≈ 0.3 and a single source redshift at zS=1, the use of the flat-sky and Limber approximation underestimates the total SSC contribution by ≈ 10%. The contribution from super-survey tidal fields to the lensing SSC, which has not been included in cosmological analyses so far, is shown to represent about 5% of the total lensing covariance on multipoles l1,l2 gtrsim 300. The SSC is the dominant off-diagonal contribution to the total lensing covariance, making it appropriate to include these tidal terms and beyond flat-sky/Limber corrections in cosmic shear analyses.

  11. Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

    Science.gov (United States)

    Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

    2017-01-01

    The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

  12. The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation

    NARCIS (Netherlands)

    Levels, Maria J.; Van Tok, Melissa N.; Cantaert, Tineke; Canete, Juan D.; Kroese, Frans G. M.; Germar, Kristine; Spits, Hergen; Baeten, Dominique L. P.; Yeremenko, Nataliya G.

    Objective. The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA). Methods. Candidate molecules were identified by gene

  13. Lymphocytic Colitis: Pathologic predictors of response to therapy.

    Science.gov (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

    2018-02-13

    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  14. The impact of borderline personality pathology on mothers' responses to infant distress.

    Science.gov (United States)

    Kiel, Elizabeth J; Gratz, Kim L; Moore, Sarah Anne; Latzman, Robert D; Tull, Matthew T

    2011-12-01

    This study sought to extend extant research on the association between borderline personality (BP) pathology and at-risk parenting by examining the dynamic nature of parenting in response to infant distress in mothers with and without clinically relevant levels of BP pathology. Findings revealed that mothers with clinically relevant levels of BP pathology were less likely than those without BP pathology to display positive affect in response to infant distress. There were no differences in the overall likelihood of insensitive parenting behaviors as a function of BP pathology, either in general or in response to infant distress. However, consistent with literature emphasizing the transactional nature of parent-child relationships, findings revealed that the likelihood of insensitive parenting behaviors among mothers with clinically relevant levels of BP pathology changed over time, increasing significantly as infant distress persisted for longer durations (a pattern not present for mothers without BP pathology). Moreover, maternal responses to infant distress were found to influence infant distress, with the likelihood of infant distress decreasing after maternal positive affect and increasing after maternal insensitive behaviors. The implications of findings for understanding the mechanisms of risk for children of mothers with BP pathology, as well as the transactional nature of mother-infant relationships in general, are discussed.

  15. [Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

    Science.gov (United States)

    Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

    2015-01-01

    To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  16. Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

    Science.gov (United States)

    Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

    2016-11-01

    Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

  17. Gambling pathology is associated with dampened cortisol response among men and women.

    Science.gov (United States)

    Paris, J J; Franco, C; Sodano, R; Frye, C A; Wulfert, E

    2010-02-09

    Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect. Published by Elsevier Inc.

  18. Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

    Science.gov (United States)

    Manole, Andreea; Jaunmuktane, Zane; Hargreaves, Iain; Ludtmann, Marthe H R; Salpietro, Vincenzo; Bello, Oscar D; Pope, Simon; Pandraud, Amelie; Horga, Alejandro; Scalco, Renata S; Li, Abi; Ashokkumar, Balasubramaniem; Lourenço, Charles M; Heales, Simon; Horvath, Rita; Chinnery, Patrick F; Toro, Camilo; Singleton, Andrew B; Jacques, Thomas S; Abramov, Andrey Y; Muntoni, Francesco; Hanna, Michael G; Reilly, Mary M; Revesz, Tamas; Kullmann, Dimitri M; Jepson, James E C; Houlden, Henry

    2017-11-01

    Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in

  19. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-01-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  20. Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

    International Nuclear Information System (INIS)

    Mannina, Edward Michael; Cardenes, Higinia Rosa; Lasley, Foster D.; Goodman, Benjamin; Zook, Jennifer; Althouse, Sandra; Cox, John Alvin; Saxena, Romil; Tector, Joseph; Maluccio, Mary

    2017-01-01

    Purpose: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). Methods and Materials: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. Results: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non–statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (−25 IU/mL vs −162 IU/mL). Conclusions: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.

  1. Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Mannina, Edward Michael, E-mail: emmannina@gmail.com [Department of Radiation Oncology, Slidell Memorial Hospital Regional Cancer Center, Slidell, Louisiana (United States); Cardenes, Higinia Rosa [Department of Radiation Oncology, Schneck Medical Center, Seymour, Indiana (United States); Lasley, Foster D. [Department of Radiation Oncology, Mercy Hospital, Oklahoma City, Oklahoma (United States); Goodman, Benjamin [Department of Radiation Oncology, St. Francis Healthcare, Cape Girardeau, Missouri (United States); Zook, Jennifer [Department of Radiation Oncology, Community Hospital Anderson, Anderson, Indiana (United States); Althouse, Sandra [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); Cox, John Alvin [Department of Radiation Oncology, Columbus Regional, Columbus, Indiana (United States); Saxena, Romil [Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Tector, Joseph [Department of Surgery, University of Alabama-Birmingham, Birmingham, Alabama (United States); Maluccio, Mary [Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States)

    2017-04-01

    Purpose: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). Methods and Materials: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. Results: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survival are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non–statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (−25 IU/mL vs −162 IU/mL). Conclusions: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.

  2. Evaluation of treatment response for breast cancer: are we entering the era of "biological complete remission"?

    Institute of Scientific and Technical Information of China (English)

    Li Bian; Tao Wang; Yi Liu; Hui-Qiang Zhang; Jin-Jie Song; Shao-Hua Zhang; Shi-Kai Wu; San-Tai Song; Ze-Fei Jiang

    2012-01-01

    Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circulating tumor cell (CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile,we attempted to assess the concept of "biological complete remission" (bCR) in this regard.A 56-year-old patient with breast cancer (T2N1M1,stage Ⅳ left breast cancer,with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab.Then,she underwent CTC detection and PET/CT for efficacy evaluation.CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer.The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological (pathological) complete remission.The integrated application of the concepts including bCR,imageological CR,and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.

  3. HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer

    International Nuclear Information System (INIS)

    Urushibara, Masayasu; Kageyama, Yukio; Akashi, Takumi; Otsuka, Yukihiro; Takizawa, Touichiro; Koike, Morio; Kihara, Kazunori

    2007-01-01

    Heat shock proteins (HSPs) play crucial roles in cellular responses to stressful conditions. Expression of HSPs in invasive or high-risk superficial bladder cancer was investigated to identify whether HSPs predict pathological response to neoadjuvant chemoradiotherapy (CRT). Immunohistochemistry was used to assess expression levels of HSP27, HSP60, HSP70, HSP90 and p53 in 54 patients with invasive or high-risk superficial bladder cancer, prior to low-dose neoadjuvant CRT, followed by radical or partial cystectomy. Patients were classified into two groups (good or poor responders) depending on pathological response to CRT, which was defined as the proportion of morphological therapeutic changes in surgical specimens. Good responders showed morphological therapeutic changes in two-thirds or more of tumor tissues. In contrast, poor responders showed changes in less than two-thirds of tumor tissues. Using a multivariate analysis, positive HSP60 expression prior to CRT was found to be marginally associated with good pathological response to CRT (P=0.0564). None of clinicopathological factors was associated with HSP60 expression level. In the good pathological responders, the 5-year cause-specific survival was 88%, which was significantly better than survival in the poor responders (51%) (P=0.0373). Positive HSP60 expression prior to CRT may predict good pathological response to low-dose neoadjuvant CRT in invasive or high-risk superficial bladder cancer. (author)

  4. Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission. Results of a multivariate analysis

    International Nuclear Information System (INIS)

    Matuschek, C.; Boelke, E.; Roth, S.L.

    2012-01-01

    An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. Patients and methods: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 x 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or - in case of breast conservation - a 10-Gy interstitial boost with 192 Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. Results: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p 2 months) increases the probability of pCR after NRT-CHX. (orig.)

  5. Low HER2/neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Formenti, Silvia C.; Spicer, Darcy; Skinner, Kristin; Cohen, Deidre; Groshen, Susan; Bettini, Anna; Naritoku, Wesley; Press, Michael; Salonga, Dennis; Tsao-Wei, Denice; Danenberg, Kathy; Danenberg, Peter

    2002-01-01

    Purpose: The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response. Methods and Materials: Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m 2 twice a week for a total of 8 weeks, and radiation delivered Weeks 2-6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of ≤10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, β-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR). Results: A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p=0.009 and p=0.006, respectively). Conversely, p53 protein

  6. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  7. Anaphase onset before complete DNA replication with intact checkpoint responses

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; De Piccoli, Giacomo; Cordon-Preciado, Violeta

    2007-01-01

    Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most...

  8. Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

    2010-01-01

    Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

  9. Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

    Science.gov (United States)

    Maniaci, G; Goudriaan, A E; Cannizzaro, C; van Holst, R J

    2018-03-01

    Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

  10. Barium enema and CT volumetry for predicting pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

    Science.gov (United States)

    Murono, Koji; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2014-06-01

    Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. This study was conducted at a single tertiary care institution in Japan. This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. The study is limited by its retrospective nature. Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

  11. Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation

    International Nuclear Information System (INIS)

    Arthur, Douglas W.; Schmidt-Ullrich, Rupert K.; Friedman, Richard B.; Wazer, David E.; Kachnic, Lisa A.; Amir, Cyrus; Bear, Harry D.; Hackney, Mary Helen; Smith, Thomas J.; Lawrence, Walter

    1999-01-01

    Purpose: Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. Methods and Materials: Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. Results: Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for

  12. Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists

    Directory of Open Access Journals (Sweden)

    Evren UZUN

    2018-05-01

    Full Text Available Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs and cell-free circulating nucleic acids, effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

  13. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    Science.gov (United States)

    Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

    2014-01-01

    To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  14. EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology

    DEFF Research Database (Denmark)

    Riber-Hansen, Rikke; Hastrup, N; Clemmensen, O.

    2010-01-01

    EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology......EORTC recommended protocol for melanoma sentinel lymph node sectioning misclassifies up to 50% of the patients compared with complete step sectioning. Danish Society for Pathological Anatomy and Clinical Cytology...

  15. Locally advanced rectal cancer: post-chemoradiotherapy ADC histogram analysis for predicting a complete response.

    Science.gov (United States)

    Cho, Seung Hyun; Kim, Gab Chul; Jang, Yun-Jin; Ryeom, Hunkyu; Kim, Hye Jung; Shin, Kyung-Min; Park, Jun Seok; Choi, Gyu-Seog; Kim, See Hyung

    2015-09-01

    The value of diffusion-weighted imaging (DWI) for reliable differentiation between pathologic complete response (pCR) and residual tumor is still unclear. Recently, a few studies reported that histogram analysis can be helpful to monitor the therapeutic response in various cancer research. To investigate whether post-chemoradiotherapy (CRT) apparent diffusion coefficient (ADC) histogram analysis can be helpful to predict a pCR in locally advanced rectal cancer (LARC). Fifty patients who underwent preoperative CRT followed by surgery were enrolled in this retrospective study, non-pCR (n = 41) and pCR (n = 9), respectively. ADC histogram analysis encompassing the whole tumor was performed on two post-CRT ADC600 and ADC1000 (b factors 0, 600 vs. 0, 1000 s/mm(2)) maps. Mean, minimum, maximum, SD, mode, 10th, 25th, 50th, 75th, 90th percentile ADCs, skewness, and kurtosis were derived. Diagnostic performance for predicting pCR was evaluated and compared. On both maps, 10th and 25th ADCs showed better diagnostic performance than that using mean ADC. Tenth percentile ADCs revealed the best diagnostic performance on both ADC600 (AZ 0.841, sensitivity 100%, specificity 70.7%) and ADC1000 (AZ 0.821, sensitivity 77.8%, specificity 87.8%) maps. In comparison between 10th percentile and mean ADC, the specificity was significantly improved on both ADC600 (70.7% vs. 53.7%; P = 0.031) and ADC1000 (87.8% vs. 73.2%; P = 0.039) maps. Post-CRT ADC histogram analysis is helpful for predicting pCR in LARC, especially, in improving the specificity, compared with mean ADC. © The Foundation Acta Radiologica 2014.

  16. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

    OpenAIRE

    Chen, Victor E.; Gillespie, Erin F.; Zakeri, Kaveh; Murphy, James D.; Yashar, Catheryn M.; Lu, Sharon; Einck, John P.

    2017-01-01

    Purpose: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. Methods and materials: This was an institutional review board–approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservat...

  17. The special features of response on the disease and victim behavior in women with thyroid pathologies

    Directory of Open Access Journals (Sweden)

    Олена Вікторівна Варібрус

    2015-12-01

    Full Text Available Thyroid pathologies are characterized with an expressed somatic distress and transformations of psychic sphere. Elimination of hormonal imbalance as pathogenetic mechanism levels the clinic symptomatology to a great extent. That is why the problem of inclination to treatment in endocrinological patients becomes particularly topical.The aim of research was the study of the special features of response on treatment and manifestations of victim behavior connected with chronic somatic pathology in women with the different types of thyroid pathologies.Contingent and methods of research. There were used the clinical methodology of diagnostics of the type of an attitude to disease (TAD and the Andronnikova modified questionnaire of inclination to victim behavior.Results. Most of all interrogated patients with thyroid pathologies had intrapsychic (49,6 % against 32,0 % and combined maladjustment (18,6 % against 8,0 %, the lesser part of them had adaptive types of response on disease comparing with healthy women (9,7 % against 40,0 %. The intragroup differences were expressed in prevalence of types with intrapsychic maladjustment in women with hypothyroidism (57,4 % against 42,4 %, and interpsychic and combined at hyperthyroidism (27,1 % against 16,7 % and 22,0 % against 14,8 %. The main types of response on disease in persons with thyroid pathologies were anxious and sensitive (10,6 %, anxious (8,8 %, sensitive (8,8 % and anosognosic (8,8 %, in healthy women – ergopathic (16,0 %, anosognosic (14,0 %, energopathic and sensitive (12,0 % and harmonic types (10,0 %.An intensity of the victim behavior was higher in patients with thyroid pathologies, in women with hyperthyroidism took place aggressive, self-destructive and hypersocial ones, in patients with hypothyroidism – dependent and uncritical types of victimhood that indicated the presence of somatogenic victimhood as a factor of psychological and psychosocial maladjustment.Conclusions. The

  18. Correlation between Tumor-Infiltrating Lymphocytes and Pathological Response in Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy in H. Adam Malik General Hospital

    Directory of Open Access Journals (Sweden)

    Kamal Basri Siregar

    2017-08-01

    Full Text Available Background: Tumor-infiltrating lymphocytes (TILs are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value, particularly in triple-negative and human epidermal growth factor receptor-2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy, and there is a strong correlation with pathologically complete response. In this study, we analyzed whether changes in TILs take place after neoadjuvant therapy and if they correlate with pathological response to treatment. Patients and Methods: We retrospectively analyzed the specimen slides from the Department of Anatomic Pathology of H. Adam Malik General Hospital during 2011–2015. We identified 51 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. Each case was also defined as high- or low-TIL breast cancer adopting previously validated cutoffs. Results: The mean age of the 51 patients was 49.22 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 49 (96% patients, and there were 2 (4% patients with lobular carcinoma. The histopathological grading for high TILs was grade 1 in 5 patients, grade 2 in 15 patients, and grade 3 in 3 patients. High TILs that had a pathologically complete response were found in 47.8% of patients, and low TILs were found in 28.8%. There was no significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.157. Conclusions: This research has not been able to demonstrate a significant correlation between TILs and

  19. Breast conserving surgery following primary irradiation in 3-7 cm breast cancer: pathologic response and outcome

    International Nuclear Information System (INIS)

    Saint-Gaudens, Anne Bareille; Vilcoq, Jacques R.; Campana, Francois; Gautier, Chantal; Asselain, Bernard; Rocherfordiere, Anne de la; Clough, Krishna B.; Fourquet, Alain

    1997-01-01

    Purpose: To retrospectively evaluate histologic response and outcome of patients treated by primary irradiation followed by conservative surgery. Materials and Methods: Between 1981 and 1993, 1742 patients (pts.) with large 3-7 cm invasive breast cancer were treated by primary breast and nodes irradiation in our institution. Of these, 311 pts. (18%) further underwent a wide excision of the residual tumor. Median age was 55 years (yrs.) (29 - 79 yrs.). Median breast tumor size was 40 mm (35 - 70mm). 149 pts. (48%) were premenopausal. 142 pts (46%) had clinically palpable axillary nodes. Diagnosis of invasive breast cancer was performed in all patients by drill biopsy. Following diagnosis, all 311 patients were treated by external irradiation to the breast and regional nodes. Median dose to the breast was 55 Gy (50 - 64 Gy) over 5.5 weeks. Following this irradiation, all patients underwent a wide surgical excision with (140 pts; 45%) or without (171 pts; 55%) axillary node dissection. In addition, 70 pts (22.5%) received adjuvant chemotherapy and 70 pts. received hormone therapy after local treatment. All patients were then regularly followed. Results: Median residual breast tumor size after completion of irradiation was 20 mm (0 - 50mm). On pathologic examination, 34 (11%) tumors had no residual malignant cells (complete response), 137 tumors (44%) had residual fibrosis with clusters of viable cells (partial response), and 138 tumors (45%) had residual viable malignant cells (no response). Median follow up was 106 months (10 - 188 months). Actuarial 9-year overall survival rate was 69 % ± 6%. The 9-year metastasis-free interval was 58 % ± 6%. The 9-year breast recurrence rate was 22 % ± 5 %. The 9-year breast preservation rate was 84% ± 5%. Pathologic response was not predictive of outcome, either distant or local. Conclusion: This retrospective study showed that in patients with tumors too large to be treated by upfront breast-conserving surgery, primary breast

  20. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

    Science.gov (United States)

    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  1. Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload

    NARCIS (Netherlands)

    Koitabashi, Norimichi; Danner, Thomas; Zaiman, Ari L.; Pinto, Yigal M.; Rowell, Janelle; Mankowski, Joseph; Zhang, Dou; Nakamura, Taishi; Takimoto, Eiki; Kass, David A.

    2011-01-01

    The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted

  2. Pathological gambling and age: differences in personality, psychopathology, and response to treatment variables.

    Science.gov (United States)

    González-Ibáñez, A; Mora, M; Gutiérrez-Maldonado, J; Ariza, A; Lourido-Ferreira, M R

    2005-02-01

    The aim of this study was to ascertain the possible differences in personality, psychopathology, and response to treatment in pathological gambling according to age. The sample, comprising 67 participants, was divided into three groups: 32.6% with ages ranging between 17 and 26 years, 31.3% between 27 and 43 years, and 35.8% over 44 years of age. The participants were administered the following tests, Minnesota Multiphasic Personality Inventory [MMPI; Hathaway, S.R. & McKinley, J.C. (1943, 1961). Cuestionario de personalidad MMPI. Madrid Seccion de Estudios de TEA ed. 1970, 1975], sensation-seeking questionnaire [SSS; Zuckerman, M. (1979). Sensation seeking; beyond the optimal level of arousal. Hillsdale, NJ: Lawrence Erlbaum Associates], and the Symptom Check List Revised [SCL-90-R; Derogatis, L.R. (1977). Symptom check list-90 revised. Administration scoring and procedures manual. Baltimore]. All underwent a group treatment programme that was carried out in the Pathological Gambling Unit at Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Teaching hospital, Barcelona, Spain. The findings show differences depending on age in the participants' personality and in psychopathology and in their response to treatment.

  3. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

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    Franklin, J.M., E-mail: jamiemfranklin@hotmail.com [Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M.; Gleeson, F.V. [Churchill Hospital, Headington, Oxford (United Kingdom)

    2012-06-15

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having {>=}80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  4. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

    International Nuclear Information System (INIS)

    Franklin, J.M.; Anderson, E.M.; Gleeson, F.V.

    2012-01-01

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  5. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome

    Science.gov (United States)

    Teachey, David T.; Greiner, Robert; Seif, Alix; Attiyeh, Edward; Bleesing, Jack; Choi, John; Manno, Catherine; Rappaport, Eric; Schwabe, Dirk; Sheen, Cecilia; Sullivan, Kathleen E.; Zhuang, Hongming; Wechsler, Daniel S.; Grupp, Stephan A.

    2010-01-01

    Summary We hypothesized that sirolimus, an mTOR inhibitor, may be effective in patients with autoimmune lymphoproliferative syndrome (ALPS) and treated patients who were intolerant to or failed other therapies. Four patients were treated for autoimmune cytopenias; all had a rapid complete or near complete response. Two patients were treated for autoimmune arthritis and colitis, demonstrating marked improvement. Three patients had complete resolution of lymphadenopathy and splenomegaly and all patients had a reduction in double negative T cells, a population hallmark of the disease. Based on these significant responses, we recommend that sirolimus be considered as second-line therapy for patients with steroid-refractory disease. PMID:19208097

  6. Metal concentrations and pathological responses of wild native fish exposed to sewage discharge in a Mediterranean river

    Energy Technology Data Exchange (ETDEWEB)

    Maceda-Veiga, Alberto, E-mail: albertomaceda@gmail.com [Department of Animal Biology (Vertebrates) and Biodiversity Research Institute (IRBio), University of Barcelona, E-08028 Barcelona (Spain); Monroy, Mario; Navarro, Elisenda [Department of Animal Biology (Vertebrates) and Biodiversity Research Institute (IRBio), University of Barcelona, E-08028 Barcelona (Spain); Viscor, Ginés [Department of Animal Physiology (Faculty of Biology), University of Barcelona, E-08028 Barcelona (Spain); Sostoa, Adolfo de [Department of Animal Biology (Vertebrates) and Biodiversity Research Institute (IRBio), University of Barcelona, E-08028 Barcelona (Spain)

    2013-04-01

    The requirements of the Water Framework Directive suggest the need for further research to test and develop sensitive tools that will allow freshwater managers to detect impacts on fish communities. Diagnostic refinement often encompasses the use of lethal diagnostic tools that are incompatible with the conservation of native ichthyofauna. Here we determine the metal concentration and the pathological response of Squalius laietanus exposed to sewage discharges in the Ripoll river (north-eastern Spain), and compare these findings with our previous studies on Barbus meridionalis using lethal and non-lethal diagnostic tools. Metals concentrations (Zn, Cu, Pb, Hg, Fe, Cd and Ni) were determined in liver and muscle. A complete blood cell profile (haematocrit, haemoglobin, differential leukocyte count, erythrocytic nuclear abnormalities, erythrocytes in division and the development stage of erythrocytes) was used as a non-lethal diagnostic tool to determine early warning signs of disease in these two fish species. As the reference range for these haematological variables is lacking, liver histology, calculation of body condition (CF) and organosomatic indices (HSI and GSI) were employed to support the findings of the blood analyses. Compared to our previous results on B. meridionalis, S. laietanus appeared to have fewer pathological responses than B. meridionalis under the environmental conditions measured and the fish size range examined in this study. Both species showed a similar bioaccumulation pattern, but B. meridionalis stored high Hg and Cu concentrations in muscle and liver, respectively. Hg, Cu and Pb concentrations in fish tissues exceeded the thresholds of European and Spanish legislation. Our findings pinpoint the potential suitability of the blood variables determined in the health diagnoses of these species. Further research will be necessary to establish the natural variability of these and other haematological variables to convert haematology into a

  7. Metal concentrations and pathological responses of wild native fish exposed to sewage discharge in a Mediterranean river

    International Nuclear Information System (INIS)

    Maceda-Veiga, Alberto; Monroy, Mario; Navarro, Elisenda; Viscor, Ginés; Sostoa, Adolfo de

    2013-01-01

    The requirements of the Water Framework Directive suggest the need for further research to test and develop sensitive tools that will allow freshwater managers to detect impacts on fish communities. Diagnostic refinement often encompasses the use of lethal diagnostic tools that are incompatible with the conservation of native ichthyofauna. Here we determine the metal concentration and the pathological response of Squalius laietanus exposed to sewage discharges in the Ripoll river (north-eastern Spain), and compare these findings with our previous studies on Barbus meridionalis using lethal and non-lethal diagnostic tools. Metals concentrations (Zn, Cu, Pb, Hg, Fe, Cd and Ni) were determined in liver and muscle. A complete blood cell profile (haematocrit, haemoglobin, differential leukocyte count, erythrocytic nuclear abnormalities, erythrocytes in division and the development stage of erythrocytes) was used as a non-lethal diagnostic tool to determine early warning signs of disease in these two fish species. As the reference range for these haematological variables is lacking, liver histology, calculation of body condition (CF) and organosomatic indices (HSI and GSI) were employed to support the findings of the blood analyses. Compared to our previous results on B. meridionalis, S. laietanus appeared to have fewer pathological responses than B. meridionalis under the environmental conditions measured and the fish size range examined in this study. Both species showed a similar bioaccumulation pattern, but B. meridionalis stored high Hg and Cu concentrations in muscle and liver, respectively. Hg, Cu and Pb concentrations in fish tissues exceeded the thresholds of European and Spanish legislation. Our findings pinpoint the potential suitability of the blood variables determined in the health diagnoses of these species. Further research will be necessary to establish the natural variability of these and other haematological variables to convert haematology into a

  8. Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

    2014-12-09

    Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

  9. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  10. [Responsible gambling: is it an alternative for prevention and treatment of pathological gambling?].

    Science.gov (United States)

    Echeburua, Enrique; de Corral, Paz

    2008-01-01

    This paper deals with the new development of controlled gambling embedded in a harm-reduction context as a viable solution both for primary prevention at school and for treatment of some kinds of problematic gamblers. Pathological gambling significantly improves with psychological therapies, such as stimulus control and in vivo exposure with response prevention or cognitive interventions. In some cases psychopharmacological therapy may complement the benefits of treatment for pathological gambling when patients have comorbid depression or high impulsivity. However, in this mental disorder the goal of treatment (total abstinence or controlled gambling) is currently a controversial issue. Controlled gambling may be a therapeutic option for young gamblers or patients without severe dependence. Furthermore, controlled gambling may be a relevant issue for health education in schools, with a view to teaching teenagers how to cope with actual and virtual exposure to gambling. Likewise, the gambling industry and governments are involved in harm minimization initiatives. Thus, it is necessary to coordinate a program of research that includes the industry, science, and public representatives, based on cooperative research that will permit the introduction of controlled gambling within a global strategic framework. We discuss the relevance of this review for clinical practice and for future research, as well as the unsolved problems in this field.

  11. Pathological and immunological responses associated with differential survival of Chinook salmon following Renibacterium salmoninarum challenge

    Science.gov (United States)

    Metzger, David C.; Elliott, Diane G.; Wargo, Andrew; Park, Linda K.; Purcell, Maureen K.

    2010-01-01

    Chinook salmon Oncorhynchus tshawytscha are highly susceptible to Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD). Previously we demonstrated that introduced Chinook salmon from Lake Michigan, Wisconsin (WI), USA, have higher survival following R. salmoninarum challenge relative to the progenitor stock from Green River, Washington, USA. In the present study, we investigated the pathological and immunological responses that are associated with differential survival in the 2 Chinook salmon stocks following intra-peritoneal R. salmoninarum challenge of 2 different cohort years (2003 and 2005). Histological evaluation revealed delayed appearance of severe granulomatous lesions in the kidney and lower overall prevalence of membranous glomerulopathy in the higher surviving WI stock. The higher survival WI stock had a lower bacterial load at 28 d post-infection, as measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). However, at all other time points, bacterial load levels were similar despite higher mortality in the more susceptible Green River stock, suggesting the possibility that the stocks may differ in their tolerance to infection by the bacterium. Interferon-γ, inducible nitric oxide synthase (iNOS), Mx-1, and transferrin gene expression were up-regulated in both stocks following challenge. A trend of higher iNOS gene expression at later time points (≥28 d post-infection) was observed in the lower surviving Green River stock, suggesting the possibility that higher iNOS expression may contribute to greater pathology in that stock.

  12. Using Flow Characteristics in Three-Dimensional Power Doppler Ultrasound Imaging to Predict Complete Responses in Patients Undergoing Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Shia, Wei-Chung; Huang, Yu-Len; Wu, Hwa-Koon; Chen, Dar-Ren

    2017-05-01

    Strategies are needed for the identification of a poor response to treatment and determination of appropriate chemotherapy strategies for patients in the early stages of neoadjuvant chemotherapy for breast cancer. We hypothesize that power Doppler ultrasound imaging can provide useful information on predicting response to neoadjuvant chemotherapy. The solid directional flow of vessels in breast tumors was used as a marker of pathologic complete responses (pCR) in patients undergoing neoadjuvant chemotherapy. Thirty-one breast cancer patients who received neoadjuvant chemotherapy and had tumors of 2 to 5 cm were recruited. Three-dimensional power Doppler ultrasound with high-definition flow imaging technology was used to acquire the indices of tumor blood flow/volume, and the chemotherapy response prediction was established, followed by support vector machine classification. The accuracy of pCR prediction before the first chemotherapy treatment was 83.87% (area under the ROC curve [AUC] = 0.6957). After the second chemotherapy treatment, the accuracy of was 87.9% (AUC = 0.756). Trend analysis showed that good and poor responders exhibited different trends in vascular flow during chemotherapy. This preliminary study demonstrates the feasibility of using the vascular flow in breast tumors to predict chemotherapeutic efficacy. © 2017 by the American Institute of Ultrasound in Medicine.

  13. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  14. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    International Nuclear Information System (INIS)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

    2011-01-01

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

  15. Gut pathology and responses to the microsporidium Nosema ceranae in the honey bee Apis mellifera.

    Science.gov (United States)

    Dussaubat, Claudia; Brunet, Jean-Luc; Higes, Mariano; Colbourne, John K; Lopez, Jacqueline; Choi, Jeong-Hyeon; Martín-Hernández, Raquel; Botías, Cristina; Cousin, Marianne; McDonnell, Cynthia; Bonnet, Marc; Belzunces, Luc P; Moritz, Robin F A; Le Conte, Yves; Alaux, Cédric

    2012-01-01

    The microsporidium Nosema ceranae is a newly prevalent parasite of the European honey bee (Apis mellifera). Although this parasite is presently spreading across the world into its novel host, the mechanisms by it which affects the bees and how bees respond are not well understood. We therefore performed an extensive characterization of the parasite effects at the molecular level by using genetic and biochemical tools. The transcriptome modifications at the midgut level were characterized seven days post-infection with tiling microarrays. Then we tested the bee midgut response to infection by measuring activity of antioxidant and detoxification enzymes (superoxide dismutases, glutathione peroxidases, glutathione reductase, and glutathione-S-transferase). At the gene-expression level, the bee midgut responded to N. ceranae infection by an increase in oxidative stress concurrent with the generation of antioxidant enzymes, defense and protective response specifically observed in the gut of mammals and insects. However, at the enzymatic level, the protective response was not confirmed, with only glutathione-S-transferase exhibiting a higher activity in infected bees. The oxidative stress was associated with a higher transcription of sugar transporter in the gut. Finally, a dramatic effect of the microsporidia infection was the inhibition of genes involved in the homeostasis and renewal of intestinal tissues (Wnt signaling pathway), a phenomenon that was confirmed at the histological level. This tissue degeneration and prevention of gut epithelium renewal may explain early bee death. In conclusion, our integrated approach not only gives new insights into the pathological effects of N. ceranae and the bee gut response, but also demonstrate that the honey bee gut is an interesting model system for studying host defense responses.

  16. Gut pathology and responses to the microsporidium Nosema ceranae in the honey bee Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Claudia Dussaubat

    Full Text Available The microsporidium Nosema ceranae is a newly prevalent parasite of the European honey bee (Apis mellifera. Although this parasite is presently spreading across the world into its novel host, the mechanisms by it which affects the bees and how bees respond are not well understood. We therefore performed an extensive characterization of the parasite effects at the molecular level by using genetic and biochemical tools. The transcriptome modifications at the midgut level were characterized seven days post-infection with tiling microarrays. Then we tested the bee midgut response to infection by measuring activity of antioxidant and detoxification enzymes (superoxide dismutases, glutathione peroxidases, glutathione reductase, and glutathione-S-transferase. At the gene-expression level, the bee midgut responded to N. ceranae infection by an increase in oxidative stress concurrent with the generation of antioxidant enzymes, defense and protective response specifically observed in the gut of mammals and insects. However, at the enzymatic level, the protective response was not confirmed, with only glutathione-S-transferase exhibiting a higher activity in infected bees. The oxidative stress was associated with a higher transcription of sugar transporter in the gut. Finally, a dramatic effect of the microsporidia infection was the inhibition of genes involved in the homeostasis and renewal of intestinal tissues (Wnt signaling pathway, a phenomenon that was confirmed at the histological level. This tissue degeneration and prevention of gut epithelium renewal may explain early bee death. In conclusion, our integrated approach not only gives new insights into the pathological effects of N. ceranae and the bee gut response, but also demonstrate that the honey bee gut is an interesting model system for studying host defense responses.

  17. Relationship between the temporal changes in positron-emission-tomography-imaging-based textural features and pathologic response and survival in esophageal cancer patients

    Directory of Open Access Journals (Sweden)

    Stephen ShingFan Yip

    2016-03-01

    Full Text Available Purpose: Although change in SUV measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Methods: Fifty-four esophageal cancer patients received PET/CT scans before and after chemo-radiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two co-occurrence matrix (Entropy and Homogeneity, two run-length-matrix (High-gray-run-emphasis and Short-run-high-gray-run-emphasis, and two size-zone-matrix (High-gray-zone-emphasis and Short-zone-high-gray-emphasis textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC and Kaplan-Meier statistics respectively. Results: All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC=0.79, p=1.7x10^-4 and partial (AUC=0.71, p=0.01 responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run length and size zone matrix textures (AUC=0.71‒0.76, p≤0.02. Homogeneity, SUVmax and SUVmean failed to differentiate between any of the responders (AUC=0.50‒0.57, p≥0.46. However, none of the measures were found to significantly distinguish between complete and partial responders with AUC0.25. Conclusions: For the patients studied, temporal change in Entropy and all Run length matrix were better correlated with pathological response and survival than the SUV

  18. Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

    Science.gov (United States)

    Yip, Stephen S F; Coroller, Thibaud P; Sanford, Nina N; Mamon, Harvey; Aerts, Hugo J W L; Berbeco, Ross I

    2016-01-01

    Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC textures significantly discriminated patients with good and poor survival (log-rank p textures and survival were poorly related

  19. Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: A randomized Phase II study

    International Nuclear Information System (INIS)

    Duenas-Gonzalez, Alfonso; Cetina-Perez, Lucely; Lopez-Graniel, Carlos; Gonzalez-Enciso, Aaron; Gomez-Gonzalez, Ernesto; Rivera-Rubi, Lesbia; Montalvo-Esquivel, Gonzalo; Munoz-Gonzalez, David; Robles-Flores, Juan; Vazquez-Govea, Elisa; Garza, Jaime de la; Mohar, Alejandro

    2005-01-01

    Purpose: To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2, IIA, and IIB cervical carcinoma in a preoperative setting. The main endpoints were the pathologic response rate and toxicity. Methods and materials: A total of 83 patients were randomized to either C or GC. Treatment consisted of six doses of cisplatin at 40 mg/m 2 every week for Arm 1 (C) and six doses of gemcitabine at 125 mg/m 2 plus cisplatin at 40 mg/m 2 every week for or Arm 2 (GC) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks. After chemoradiotherapy, patients underwent radical hysterectomy. Results: All 83 patients were studied for toxicity and 80 for response. The complete pathologic response rate in the C arm and GC arm was 55% (95% confidence interval, 35.5-73%) and 77.5% (95% confidence interval, 57-90%; p = 0.0201). Among those with a partial response, 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients, respectively, with these characteristics in the CG arm. The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm. The CG combination produced greater GI and hematologic toxicity. Conclusion: The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer

  20. Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer.

    Directory of Open Access Journals (Sweden)

    Sheng Chen

    Full Text Available BACKGROUND: To evaluate the relationship between body mass index (BMI and response to neoadjuvant chemotherapy (NCT for breast cancer among Chinese women. PATIENTS AND METHODS: A total of 307 eligible patients were assigned to receive four cycles of paclitaxel and carboplatin before standard surgery for breast cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were categorized as obese, overweight, normal weight, or underweight based on BMI according to World Health Organization (WHO criteria. Pathological complete response (pCR was defined as no invasive cancer in the breast or axillary tissue. A logistic regression and the Chi-squared test were used for detecting the predictors of pCR and determining the relationship between BMI category and pCR rate in the subgroup analysis with respect to other variables. RESULTS: Categorical BMI, estrogen receptor (ER, and progesterone receptor (PR status were independent predictors of pCR according to the multivariate analysis. Patients with BMI≥25 were less likely to achieve a pCR to NCT compared with patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis. In the subgroup analysis, the predictive value of BMI for pCR to NCT was significantly shown in post-menopausal patients (p = 0.004 and hormonal receptor status-negative patients (p = 0.038. The incidence of treatment-induced toxicity was similar among the different BMI categories. CONCLUSION: Higher BMI was associated with worse pCR to NCT. Further approaches to investigating the mechanism of this influence of BMI on treatment response and a more appropriate schedule for calculating NCT dose for high-BMI-patients should be considered.

  1. A prospective study of shoulder pain in primary care: Prevalence of imaged pathology and response to guided diagnostic blocks

    Directory of Open Access Journals (Sweden)

    McNair Peter J

    2011-05-01

    Full Text Available Abstract Background The prevalence of imaged pathology in primary care has received little attention and the relevance of identified pathology to symptoms remains unclear. This paper reports the prevalence of imaged pathology and the association between pathology and response to diagnostic blocks into the subacromial bursa (SAB, acromioclavicular joint (ACJ and glenohumeral joint (GHJ. Methods Consecutive patients with shoulder pain recruited from primary care underwent standardised x-ray, diagnostic ultrasound scan and diagnostic injections of local anaesthetic into the SAB and ACJ. Subjects who reported less than 80% reduction in pain following either of these injections were referred for a magnetic resonance arthrogram (MRA and GHJ diagnostic block. Differences in proportions of positive and negative imaging findings in the anaesthetic response groups were assessed using Fishers test and odds ratios were calculated a for positive anaesthetic response (PAR to diagnostic blocks. Results In the 208 subjects recruited, the rotator cuff and SAB displayed the highest prevalence of pathology on both ultrasound (50% and 31% respectively and MRA (65% and 76% respectively. The prevalence of PAR following SAB injection was 34% and ACJ injection 14%. Of the 59% reporting a negative anaesthetic response (NAR for both of these injections, 16% demonstrated a PAR to GHJ injection. A full thickness tear of supraspinatus on ultrasound was associated with PAR to SAB injection (OR 5.02; p p p p ≤ 0.05. Conclusions Rotator cuff and SAB pathology were the most common findings on ultrasound and MRA. Evidence of a full thickness supraspinatus tear was associated with symptoms arising from the subacromial region, and a biceps tendon sheath effusion and an intact rotator cuff were associated with an intra-articular GHJ pain source. When combined with clinical information, these results may help guide diagnostic decision making in primary care.

  2. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

    Directory of Open Access Journals (Sweden)

    Irma Estela Sommerfelt

    2014-07-01

    Full Text Available Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi. Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  3. Follicular helper T cells poise immune responses to the development of autoimmune pathology.

    Science.gov (United States)

    Gómez-Martín, Diana; Díaz-Zamudio, Mariana; Romo-Tena, Jorge; Ibarra-Sánchez, María J; Alcocer-Varela, Jorge

    2011-04-01

    Follicular helper T cells (T(FH)) have been implicated as a lineage that provides sufficient help to B cells in order to become professional antibody producers. This T helper subset is characterized by a distinctive cell-surface phenotype (CD4(+)CD57(+)CXCR5(+)) and cytokine profile (IL-21, IL-6, and IL-27) as well as transcriptional program (BCL-6, ICOS, and PD-1). Evidence supports the concept that T(FH) subset development, as well as for other lineages, is dependent on microenvironment cues that modulate a particular transcriptional program, susceptible to plasticity. Recently, it has been shown that BCL-6 and IL-21 act as master regulators for the development and function of T(FH) cells. Moreover, costimulation via ICOS, as well as signaling proteins such as SAP constitute required elements of the regulatory network that modulates T(FH) functions. T(FH) dysregulation has been implicated in the development of autoimmune pathology, such as SLE. Indeed, the Sanroque mice associated to the mutation of Roquin, a ubiquitin ligase, essential for the regulation of ICOS and germinal center responses, constitutes a model that shares features with human SLE. Recently, the expansion of "circulating T(FH) cells" (CD4(+)CXCR5(+)ICOS(high)PD1(high)) has been described for a subset of SLE patients that share T(FH) dependent features of disease with Sanroque mice, such as glomerulonephritis and cytopenias. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer

    NARCIS (Netherlands)

    Loo, Claudette E; Rigter, Lisanne S; Pengel, Kenneth E; Wesseling, Jelle; Rodenhuis, Sjoerd; Peeters, Marie-Jeanne T F D Vrancken; Sikorska, Karolina; Gilhuijs, Kenneth G A

    2016-01-01

    BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We

  5. A conclusive scalable model for the complete actuation response for IPMC transducers

    International Nuclear Information System (INIS)

    McDaid, A J; Aw, K C; Haemmerle, E; Xie, S Q

    2010-01-01

    This paper proposes a conclusive scalable model for the complete actuation response for ionic polymer metal composites (IPMC). This single model is proven to be able to accurately predict the free displacement/velocity and force actuation at varying displacements, with up to 3 V inputs. An accurate dynamic relationship between the force and displacement has been established which can be used to predict the complete actuation response of the IPMC transducer. The model is accurate at large displacements and can also predict the response when interacting with external mechanical systems and loads. This model equips engineers with a useful design tool which enables simple mechanical design, simulation and optimization when integrating IPMC actuators into an application. The response of the IPMC is modelled in three stages: (i) a nonlinear equivalent electrical circuit to predict the current drawn, (ii) an electromechanical coupling term and (iii) a segmented mechanical beam model which includes an electrically induced torque for the polymer. Model parameters are obtained using the dynamic time response and results are presented demonstrating the correspondence between the model and experimental results over a large operating range. This newly developed model is a large step forward, aiding in the progression of IPMCs towards wide acceptance as replacements to traditional actuators

  6. Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

    Directory of Open Access Journals (Sweden)

    Orchard Jo

    2007-02-01

    Full Text Available Abstract Background Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of £5 for the completion of postal questionnaires. Methods We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of £5 to patients for the completion and return of questionnaires. The first 105 patients did not receive the £5 incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results The response rate following reminders for the historical controls was 78.1% (82 of 105 compared with 88.0% (389 of 442 for those patients who received the £5 payment (diff = 9.9%, 95% CI 2.3% to 19.1%. Direct payments significantly increased the odds of response (adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009 with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial – the extra cost per additional respondent was almost £50. Conclusion The direct payment of £5 significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study.

  7. Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

    Science.gov (United States)

    Brealey, Stephen D; Atwell, Christine; Bryan, Stirling; Coulton, Simon; Cox, Helen; Cross, Ben; Fylan, Fiona; Garratt, Andrew; Gilbert, Fiona J; Gillan, Maureen GC; Hendry, Maggie; Hood, Kerenza; Houston, Helen; King, David; Morton, Veronica; Orchard, Jo; Robling, Michael; Russell, Ian T; Torgerson, David; Wadsworth, Valerie; Wilkinson, Clare

    2007-01-01

    Background Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of £5 for the completion of postal questionnaires. Methods We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of £5 to patients for the completion and return of questionnaires. The first 105 patients did not receive the £5 incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results The response rate following reminders for the historical controls was 78.1% (82 of 105) compared with 88.0% (389 of 442) for those patients who received the £5 payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response (adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial – the extra cost per additional respondent was almost £50. Conclusion The direct payment of £5 significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study. PMID:17326837

  8. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  9. Intraperitoneal cisplatin versus no further treatment : 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy

    NARCIS (Netherlands)

    Piccart, MJ; Floquet, A; Scarfone, G; Willemse, PHB; Emerich, J; Vergote, [No Value; Giurgea, L; Coens, C; Awada, A; Vermorken, JB

    2003-01-01

    First-line intravenous chemotherapy (CT) following debulking surgery is associated with prolonged survival, in particular in patients who achieve a pathological complete remission (pCR) at second-look surgery but in whom a high rate of relapses still occurs. Between 1988 and 1997, 153 patients in

  10. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Taylor, G.N.; Stevens, W.

    1986-01-01

    In the completed 226 Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226 Ra and 239 Pu, 42 of 116 animals injected with 226 Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs

  11. The effectiveness of a monetary incentive offer on survey response rates and response completeness in a longitudinal study.

    Science.gov (United States)

    Yu, Shengchao; Alper, Howard E; Nguyen, Angela-Maithy; Brackbill, Robert M; Turner, Lennon; Walker, Deborah J; Maslow, Carey B; Zweig, Kimberly C

    2017-04-26

    Achieving adequate response rates is an ongoing challenge for longitudinal studies. The World Trade Center Health Registry is a longitudinal health study that periodically surveys a cohort of ~71,000 people exposed to the 9/11 terrorist attacks in New York City. Since Wave 1, the Registry has conducted three follow-up surveys (Waves 2-4) every 3-4 years and utilized various strategies to increase survey participation. A promised monetary incentive was offered for the first time to survey non-respondents in the recent Wave 4 survey, conducted 13-14 years after 9/11. We evaluated the effectiveness of a monetary incentive in improving the response rate five months after survey launch, and assessed whether or not response completeness was compromised due to incentive use. The study compared the likelihood of returning a survey for those who received an incentive offer to those who did not, using logistic regression models. Among those who returned surveys, we also examined whether those receiving an incentive notification had higher rate of response completeness than those who did not, using negative binomial regression models and logistic regression models. We found that a $10 monetary incentive offer was effective in increasing Wave 4 response rates. Specifically, the $10 incentive offer was useful in encouraging initially reluctant participants to respond to the survey. The likelihood of returning a survey increased by 30% for those who received an incentive offer (AOR = 1.3, 95% CI: 1.1, 1.4), and the incentive increased the number of returned surveys by 18%. Moreover, our results did not reveal any significant differences on response completeness between those who received an incentive offer and those who did not. In the face of the growing challenge of maintaining a high response rate for the World Trade Center Health Registry follow-up surveys, this study showed the value of offering a monetary incentive as an additional refusal conversion strategy. Our

  12. Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

    LENUS (Irish Health Repository)

    Mulsow, J

    2012-02-01

    Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

  13. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

    Science.gov (United States)

    Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

    2016-11-01

    To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test

    NARCIS (Netherlands)

    Maniaci, G.; Goudriaan, A. E.; Cannizzaro, C.; van Holst, R. J.

    2017-01-01

    Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST)

  15. 77 FR 31858 - Draft Guidance for Industry on Pathologic Complete Response in Neoadjuvant Treatment of High-Risk...

    Science.gov (United States)

    2012-05-30

    ... of the drug. This draft guidance is intended to assist applicants in designing trials to support...., Bldg. 51, Rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that... Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Tatiana...

  16. Accepting "total and complete responsibility": new age neo-feminist violence against women.

    Science.gov (United States)

    Sethna, C

    1992-02-01

    Barry Konikov, a hypnotherapist, of Potentials Unlimited Inc., a Michigan-based company which produces approximately 160 Subliminal Persuasion/Self Hypnosis tapes, promises his listeners miracles. The tapes on premenstrual syndrome, abortion, and sexual abuse were analyzed. The self-hypnosis message by Konikov is dangerous for women, because his antifeminism, misogyny, and patriarchism are couched insidiously within New Age neofeminism. Under therapeutic guidance the woman listener can direct her own transformation to complete mental, physical, and spiritual well-being, and her new and improved self is so empowered as to accept total and complete responsibility to overcome the hurt about menstruation, abortion, or sexual abuse. Growth therapies such as Gestalt, guided fantasies, and bioenergetics undermine women with false promises of power. If women are so powerful, then it is their fault if they got raped, or battered, or if they have not received love, money, and inner peace. While seemingly empowering women to develop a strong sense of personal agency, Konikov ignores the patriarchal structures which intersect his women listeners' experience of menstrual discomfort, abortion, and sexual abuse. Konikov's New Age, neofeminist stance contains 4 stages of healing: responsibility, absolution, forgiveness, and resolution. Accepting responsibility for the wound next leads to absolution, and particularly absolution for men. As an example of absolution, Konikov's woman client-ex-plantation slave accepted her past-life relationship to her husband, absolved him of guild, and decided upon a divorce. The issue of absolution widens into forgiveness in the healing process, whereby Konikov wants women to hypnotize themselves therapy should be to help a woman see how her own power as an individual is inextricably bound to the collective power of women as a group. There is no doubt that the New Age neofeminist stance taken by Konikov on the tapes leaves women profoundly

  17. Culturally and linguistically diverse students in speech-language pathology courses: A platform for culturally responsive services.

    Science.gov (United States)

    Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

    2017-06-01

    Increasing the proportion of culturally and linguistically diverse (CALD) students and providing intercultural learning opportunities for all students are two strategies identified to facilitate greater access to culturally responsive speech-language pathology services. To enact these strategies, more information is needed about student diversity. This study collected descriptive information about CALD speech-language pathology students in Australia. Cultural and linguistic background information was collected through surveying 854 domestic and international speech-language pathology students from three Australian universities. Students were categorised according to defined or perceived CALD status, international student status, speaking English as an Additional Language (EAL), or speaking a Language Other than English at Home (LOTEH). Overall, 32.1% of students were either defined or perceived CALD. A total of 14.9% spoke EAL and 25.7% identified speaking a LOTEH. CALD students were more likely to speak EAL or a LOTEH than non-CALD students, were prominently from Southern and South-Eastern Asian backgrounds and spoke related languages. Many students reported direct or indirect connections with their cultural heritage and/or contributed linguistic diversity. These students may represent broader acculturative experiences in communities. The sociocultural knowledge and experience of these students may provide intercultural learning opportunities for all students and promote culturally responsive practices.

  18. Response of EBR-II to a complete loss of primary forced flow during power operation

    International Nuclear Information System (INIS)

    Singer, R.M.; Gillette, J.L.; Mohr, D.; Tokar, J.V.; Sullivan, J.E.; Dean, E.M.

    1980-01-01

    Detailed measurements of the thermal, hydraulic, and neutronic response of EBR-II to a complete loss of primary forced flow followed by a PPS-activated scram are presented. The experimental results clearly indicate a smooth transition to natural convective flow with a quite modest incore temperature transient. The accompanying calculations using the NATDEMO code agree quite well with the measured temperatures and flow rates throughout the primary system. The only region of the plant where a significant discrepancy between the measurements and calculations occurred was in the IHX. The reasons for this result could not be definitively determined, but it is speculated that the one-dimensional assumptions used in the modeling may not be valid in the IHX during buoyancy driver flows

  19. Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

    Directory of Open Access Journals (Sweden)

    Alfredo Addeo

    2013-05-01

    Full Text Available Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, as second-line treatment after progression with dacarbazine, for (wild-type BRAF metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

  20. Increased cortisol awakening response after completing the summer treatment program in children with ADHD.

    Science.gov (United States)

    Okabe, Rumiko; Okamura, Hisayoshi; Egami, Chiyomi; Tada, Yasuhiro; Anai, Chizuru; Mukasa, Akiko; Iemura, Akiko; Nagamitsu, Shinichiro; Furusho, Junichi; Matsuishi, Toyojiro; Yamashita, Yushiro

    2017-08-01

    Little is known about the cortisol awakening response (CAR) in children with attention deficit hyperactivity disorder (ADHD). Here, we examined the CAR in children with ADHD and their mothers before, immediately after, and 4months after an intensive summer treatment program (STP). Participants were 37 children aged 7-12years who completed the STP in 2009 and 2010, and their mothers. Daily saliva samples for cortisol measurement were collected twice daily at awakening and 30min afterwards at pre-STP, post-STP, and during a follow-up measurement period. ADHD symptom scores were evaluated by parents, and participants completed the Kid-KINDL R QOL questionnaire. CAR was low in children with ADHD before the STP, and increased to the control range 4months after STP. Maternal CAR also tended to increase after STP. Changes in the CAR in children tended to correlate with an improved ADHD inattention scores (p=0.091), physical health (p=0.070), and school life subscales scores in the Kid-KINDL R (p=0.079). We demonstrated that STP improved the behavior and QOL of children with ADHD. Our results indicate that STP could lead to improvements in HPA axis function, as reflected by increased CAR after STP. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  1. Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

    Science.gov (United States)

    Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

    2012-04-01

    To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ

  2. Prognostic impact of {sup 18}F-FDG PET/CT staging and of pathological response to neoadjuvant chemotherapy in triple-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, D.; Merlet, P. [Saint-Louis Hospital, Department of Nuclear Medicine, Paris Cedex 10 (France); University of Paris VII, B2T Doctoral School, Institut Universitaire d' Hematologie, Paris (France); Giacchetti, S.; Hamy, A.S.; Espie, M. [Saint-Louis Hospital, Breast Diseases Unit, Department of Medical Oncology, Paris (France); Delord, M. [Institut Universitaire d' Hematologie, Department of Biostatistics and Bioinformatics, Paris (France); Roquancourt, A. de [Saint-Louis Hospital, Department of Pathology, Paris (France); Hindie, E. [University of Bordeaux, Department of Nuclear Medicine, Haut-Leveque Hospital, CHU Bordeaux, Bordeaux (France)

    2014-11-29

    Mortality is high in patients with locally advanced triple-negative breast cancer (TNBC), especially in those with residual tumour after neoadjuvant chemotherapy (NAC). The aim of this study was to determine if pretreatment {sup 18}F-FDG PET/CT staging and pathological findings after NAC could together allow stratification of patients into prognostic groups. Initial staging with {sup 18}F-FDG PET/CT was performed prospectively in 85 consecutive patients with stage II/III TNBC. Correlations between PET findings and disease-specific survival (DSS) were examined. In patients without distant metastases on PET staging, the impact of pathological response to NAC on DSS was examined. Patterns of recurrence were also analysed. {sup 18}F-DG PET/CT revealed distant metastases in 11 of 85 patients (12.9 %). Among 74 M0 patients, 23 (31.1 %) showed a pathological complete response (pCR) at surgery, while 51 had residual invasive disease (no pCR). DSS differed considerably among the three groups of patients (log-rank P <.001): among patients with occult metastases on baseline PET/CT, 2-year DSS was 18.2 %, and among patients without initial metastases on PET/CT, 5-year DSS was 61.3 % in patients without pCR after NAC and 95.2 % in those with pCR. Of the 51 patients who did not achieve pCR, 21 relapsed (17 developed distant metastases). The sites of distant recurrence were: lung/pleura (nine patients), brain (eight patients), liver (six patients), distant lymph nodes (six patients) and bone (five patients). In patients with clinical stage II/III TNBC, {sup 18}F-FDG PET/CT findings at initial staging and pathological response at the end of NAC allow three groups of patients with quite different prognoses to be defined. Extraskeletal recurrences predominated. Specific follow-up strategies in patients with TNBC who do not achieve pCR deserve investigation. (orig.)

  3. System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

    Energy Technology Data Exchange (ETDEWEB)

    Snyder-Talkington, Brandi N. [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Dymacek, Julian [Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506-6070 (United States); Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States); Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R. [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Pacurari, Maricica [Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States); Denvir, James [Department of Biochemistry and Microbiology, Marshall University, Huntington, WV 25755 (United States); Castranova, Vincent [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Qian, Yong, E-mail: yaq2@cdc.gov [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Guo, Nancy L., E-mail: lguo@hsc.wvu.edu [Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States)

    2013-10-15

    The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung

  4. System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

    International Nuclear Information System (INIS)

    Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

    2013-01-01

    The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung

  5. Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.

    Science.gov (United States)

    Oliveira, Mafalda; Braga, Sofia; Passos-Coelho, José Luís; Fonseca, Ricardo; Oliveira, João

    2011-06-01

    Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

  6. Developing Responsibility for Completing and Handing in Daily Homework Assignments for Students in Grades Three, Four, and Five.

    Science.gov (United States)

    Shepard, Joan M.

    This practicum was designed to increase responsibility for completing and handing in homework among students in grades three, four, and five in a mid-Atlantic school district. Of a total of 128 students in these grades, 28 were identified to learn strategies to aid in completing homework. Nine solution strategies were employed: (1) provide…

  7. SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Nie, K; Yue, N; Jabbour, S; Kim, S [Rutgers-Cancer Institute of New Jersey, Rutgers-Robert Wood Johnson Medical, New Brunswick, NJ (United States); Shi, L; Mao, T; Qian, L; Hu, X; Sun, X; Niu, T [Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang (China)

    2016-06-15

    Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of blood flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in the good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value

  8. Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer.

    Science.gov (United States)

    Datta, Jashodeep; Berk, Erik; Xu, Shuwen; Fitzpatrick, Elizabeth; Rosemblit, Cinthia; Lowenfeld, Lea; Goodman, Noah; Lewis, David A; Zhang, Paul J; Fisher, Carla; Roses, Robert E; DeMichele, Angela; Czerniecki, Brian J

    2015-05-23

    A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p vs. 22.4 SFC/10(6), p non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-γ(+) (i.e., Th1) - not CD4(+)GATA-3(+)IFN-γ(+) (i.e., Th2

  9. Pathological Responses of White Leghorn Breeder Hens Kept on Ochratoxin A Contaminated Feed

    Directory of Open Access Journals (Sweden)

    Zahoor-ul-Hassan, M. Zargham Khan*, Ahrar Khan and Ijaz Javed1

    2010-04-01

    Full Text Available Mycotoxins are among the most important environmental contaminants. In the present study, ochratoxin A (OTA was produced by propagation of Aspergillus ochraceus and fed to breeder hens. For this purpose, 84 breeder hens were divided into seven groups (A-G. Group A served as control, while groups B, C, D, E, F and G were fed OTA at 0.1, 0.5, 1.0, 3.0, 5.0 and 10.0 mg/Kg feed, respectively for 3 weeks. Clinical signs, feed intake, feed conversion ratio and egg mass production were recorded on daily basis, while body weight was recorded on weekly basis. Lesions on visceral organs and serum biochemical parameters were determined. Significant decrease in feed intake, body weight and egg mass production was found in the OTA treated groups compared to control (P<0.05. Among different groups, diarrhea, unthriftiness, water intake and depression increased with increase in dietary OTA levels. Enlargement and hemorrhages on liver and kidney were more severe in birds fed higher dietary OTA levels. Serum ALT, urea, creatinine and total protein levels were significantly higher in OTA treated groups. It was concluded that production performance, pathological alterations and serum biochemical changes determined became more severe with increase in dietary levels of OTA.

  10. Prevalence of bronchopulmonary pathology in the participants of Chernobyl Nuclear Power Plant accident response

    International Nuclear Information System (INIS)

    Antonov, N.S.; Yakushin, S.P.; Stulova, O.Yu.; Zajtseva, O.Yu.; Stroev, E.A.

    1998-01-01

    Epidemiologic examination of the participants of the Chernobyl accident response is performed. Fact of acute effect of the Chernobyl aerosol inhalation on respiratory organs is found. Prevalence of bronchopulmonary diseases in participants of accident response is almost 2 times higher than that in reference group. Further program of investigations includes the hospital stage and the preventive measures at prehospital stage under ambulatory conditions. Assessments of the efficiency of performed treatment - prophylactic measures and their economic benefit are made [ru

  11. The complete genome sequence of Trueperella pyogenes UFV1 reveals a processing system involved in the quorumsensing signal response

    DEFF Research Database (Denmark)

    Duarte, Vinicius da Silva; Treu, Laura; Campanaro, Stefano

    2017-01-01

    We present here the complete genome sequence of Trueperella pyogenes UFV1. The 2.3-Mbp genome contains an extremely interesting AI-2 transporter and processing system related to the quorum-sensing signal response. This specific feature is described in this species for the first time and might be ...... be responsible for a new pathogenic behavior.......We present here the complete genome sequence of Trueperella pyogenes UFV1. The 2.3-Mbp genome contains an extremely interesting AI-2 transporter and processing system related to the quorum-sensing signal response. This specific feature is described in this species for the first time and might...

  12. Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

    Science.gov (United States)

    Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

    2017-08-01

    We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers

  13. Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers

    Directory of Open Access Journals (Sweden)

    Andrew S. Kayser

    2017-01-01

    Full Text Available Failures of self-regulation in problem and pathological gambling (PPG are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT, reduced delay discounting, a measure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC, a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general.

  14. Predictive value of PET-CT for pathological response in stages II and III breast cancer patients following neoadjuvant chemotherapy with docetaxel.

    Science.gov (United States)

    García García-Esquinas, Marta A; Arrazola García, Juan; García-Sáenz, José A; Furió-Bacete, V; Fuentes Ferrer, Manuel E; Ortega Candil, Aída; Cabrera Martín, María N; Carreras Delgado, José L

    2014-01-01

    To prospectively study the value of PET-CT with fluorine-18 fluorodeoxyglucose (FDG) to predict neoadjuvant chemotherapy (NAC) response of locoregional disease of stages II and III breast cancer patients. A written informed consent and approval were obtained from the Ethics Committee. PET-CT accuracy in the prediction of pathologic complete response (pCR) after NAC was studied in primary tumors and lymph node metastasis in 43 women (mean age: 50 years: range: 27-71 years) with histologically proven breast cancer between December 2009 and January 2011. PET-CT was performed at baseline and after NAC. SUV(max) percentage changes (ΔSUV(max)) were compared with pathology findings at surgery. Receiver-operator characteristic (ROC) analysis was used to discriminate between locoregional pCR and non-pCR. In patients not achieving pCR, it was investigated if ΔSUV(max) could accurately identify the residual cancer burden (RCB) classes: RCB-I (minimal residual disease (MRD)), RCB-II (moderate RD), and RCB-III (extensive RD). pCR was obtained in 11 patients (25.6%). Residual disease was found in 32 patients (74.4%): 16 (37.2%) RCB-I, 15 (35.6%) RCB-II and 2 (4.7%) RCB-III. Sensitivity, specificity, and accuracy to predict pCR were 90.9%, 90.6%, and 90.7%, respectively. Specificity was 94.1% in the identification of a subset of patients who had either pCR or MRD. Accuracy of ΔSUV(max) in the locoregional disease of stages II and III breast cancer patients after NAC is high for the identification of pCR cases. Its specificity is potentially sufficient to identify a subgroup of patients who could be managed with conservative surgery. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  15. Autonomic and Emotional Responses of Graduate Student Clinicians in Speech-Language Pathology to Stuttered Speech

    Science.gov (United States)

    Guntupalli, Vijaya K.; Nanjundeswaran, Chayadevie; Dayalu, Vikram N.; Kalinowski, Joseph

    2012-01-01

    Background: Fluent speakers and people who stutter manifest alterations in autonomic and emotional responses as they view stuttered relative to fluent speech samples. These reactions are indicative of an aroused autonomic state and are hypothesized to be triggered by the abrupt breakdown in fluency exemplified in stuttered speech. Furthermore,…

  16. Endobronchial valves in severe emphysematous patients: CT evaluation of lung fissures completeness, treatment radiological response and quantitative emphysema analysis

    Energy Technology Data Exchange (ETDEWEB)

    Koenigkam-Santos, Marcel, E-mail: marcelk46@yahoo.com.br, E-mail: marcelk46@usp.b [Universidade de Sao Paulo (HCFMRP/USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas da Faculdade de Medicina; Paula, Wagner Diniz de [University of Brasilia (UnB), DF (Brazil). Brasilia University Hospital; Gompelmann, Daniela [University of Heidelberg (Germany). Department of Pneumology and Respiratory Medicine of the Chest Clinic (Thoraxklinik); Kauczor, Hans-Ulrich [University of Heidelberg (Germany). Department of Diagnostic and Interventional Radiology; Heussel, Claus Peter; Puderbach, Michael [University of Heidelberg (Germany). Department of Diagnostic and Interventional Radiology with Nuclear Medicine of the Chest Clinic (Thoraxklinik)

    2013-01-15

    Objective: To evaluate lung fissures completeness, post-treatment radiological response and quantitative CT analysis (QCTA) in a population of severe emphysematous patients submitted to endobronchial valves (EBV) implantation. Materials and Methods: Multi-detectors CT exams of 29 patients were studied, using thin-section low dose protocol without contrast. Two radiologists retrospectively reviewed all images in consensus; fissures completeness was estimated in 5% increments and post-EBV radiological response (target lobe atelectasis/volume loss) was evaluated. QCTA was performed in pre and post-treatment scans using a fully automated software. Results: CT response was present in 16/29 patients. In the negative CT response group, all 13 patients presented incomplete fissures, and mean oblique fissures completeness was 72.8%, against 88.3% in the other group. QCTA most significant results showed a reduced post-treatment total lung volume (LV) (mean 542 ml), reduced EBV-submitted LV (700 ml) and reduced emphysema volume (331.4 ml) in the positive response group, which also showed improved functional tests. Conclusion: EBV benefit is most likely in patients who have complete interlobar fissures and develop lobar atelectasis. In patients with no radiological response we observed a higher prevalence of incomplete fissures and a greater degree of incompleteness. The fully automated QCTA detected the post-treatment alterations, especially in the treated lung analysis. (author)

  17. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Glenn Wagner

    2011-01-01

    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  18. Predicting pathologic tumor response to chemoradiotherapy with histogram distances characterizing longitudinal changes in 18F-FDG uptake patterns

    Science.gov (United States)

    Tan, Shan; Zhang, Hao; Zhang, Yongxue; Chen, Wengen; D’Souza, Warren D.; Lu, Wei

    2013-01-01

    Purpose: A family of fluorine-18 (18F)-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) features based on histogram distances is proposed for predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT). These features describe the longitudinal change of FDG uptake distribution within a tumor. Methods: Twenty patients with esophageal cancer treated with CRT plus surgery were included in this study. All patients underwent PET/CT scans before (pre-) and after (post-) CRT. The two scans were first rigidly registered, and the original tumor sites were then manually delineated on the pre-PET/CT by an experienced nuclear medicine physician. Two histograms representing the FDG uptake distribution were extracted from the pre- and the registered post-PET images, respectively, both within the delineated tumor. Distances between the two histograms quantify longitudinal changes in FDG uptake distribution resulting from CRT, and thus are potential predictors of tumor response. A total of 19 histogram distances were examined and compared to both traditional PET response measures and Haralick texture features. Receiver operating characteristic analyses and Mann-Whitney U test were performed to assess their predictive ability. Results: Among all tested histogram distances, seven bin-to-bin and seven crossbin distances outperformed traditional PET response measures using maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC = 0.80). The seven bin-to-bin distances were: L2 distance (AUC = 0.84), χ2 distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC = 0.83), squared Euclidean distance (AUC = 0.83), L1 distance (AUC = 0.82), and Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov distance (AUC = 0.88), quadratic form distance

  19. TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

    International Nuclear Information System (INIS)

    Zhang, H; Chen, W; Kligerman, S; D’Souza, W; Suntharalingam, M; Lu, W; Tan, S; Kim, G

    2014-01-01

    Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had 18 F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including

  20. Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: Interim results

    International Nuclear Information System (INIS)

    Bernstein, David M.; Rogers, Rick; Sepulveda, Rosalina; Kunzendorf, Peter; Bellmann, Bernd; Ernst, Heinrich; Phillips, James I.

    2014-01-01

    Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (> 20 μm) cleared quickly with T 1/2 estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T 1/2 > 1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation. - Highlights: • We evaluated brake dust w/wo added chrysotile in comparison to crocidolite asbestos. • Persistence, translocation, pathological response in the lung and pleural cavity. • Chrysotile cleared rapidly from the lung while the crocidolite asbestos persisted. • No significant pathology observed at any time point in the brake-dust groups. • Crocidolite produced pathological response - Wagner 4 interstitial fibrosis by 32d

  1. Latin American radio pathology net, training program for the medical response in cases of accidents

    International Nuclear Information System (INIS)

    Perez, M. R.; Valverde, N.; Sanhueza, S.; Di Tramo, J. L.; Gisone, P.; Cardenas, J.

    2003-01-01

    In Latin America exists a wide application of the nuclear techniques in different fields. These tendencies, to the increasing use of nuclear techniques, should carry out the invigoration of the infrastructures and the development of the authorities in radiation protection charge of the regulate and control the sources and practical, associated to ionizing radiation, guided to guarantee their safe use and in consequence to minimize the derived risks of the same ones. In spite of the efforts before mentioned a potential possibility of occurrence of accidental radiological events linked to human errors and violation's of the principles of the radiation protection exists. Reason that they advise to have response capacities to confront and to mitigate the consequences in situations of radiological accidents, including in the same ones the medical assistance of the accident victims. However, the radiological accidents happened in the international environment in the last decades, they have demonstrated inability paradoxically to confront with effectiveness these fortuitous events. Being characterized additionally by the insufficient training of the medical professionals to interpret and to act in consequence before the prejudicial effects to the health of the ionizing radiation. In our geographical context this situation is even more complicated, if we consider the happened radiological accidents of span that put in risk the life and the health of people involved in the same ones, for examples: Argentina (1968, 1963), Brazil (1985, 1987, 1995), Costa Rica (1996). El Salvador (1989), Mexico (1962, 1983, 1984) and Peru (1984, 1999). These reasons justify the development of an action program with the purpose of the consolidate and to integrate the capacity of response of our countries as regards radiological emergencies. Regrettably in Latin American subsist inequalities the development radiation protection programs, that propitiate the possibility of accidental situations

  2. Computational Pathology

    Science.gov (United States)

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  3. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

    2014-09-01

    The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

  4. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2012-05-01

    Full Text Available Brendon J Coventry, Martin L AshdownDiscipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, AustraliaAbstract: Over 50 years of cancer therapy history reveals complete clinical responses (CRs from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained?Over some 20 years, realization that (1 chronic inflammation is intricately associated with cancer, and (2 the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of "final common pathways" of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This "missing" aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer

  5. Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans

    DEFF Research Database (Denmark)

    Kjaer, M; Perko, G; Secher, N H

    1994-01-01

    Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and co...

  6. Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Hee Jin Lee

    Full Text Available Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB, residual disease in breast and nodes (RDBN, tumor response ratio, Sataloff's classification, and Miller-Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan-Meier curves.Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.

  7. Applications for approval to market a new drug; complete response letter; amendments to unapproved applications. Final rule.

    Science.gov (United States)

    2008-07-10

    The Food and Drug Administration (FDA) is amending its regulations on new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for approval to market new drugs and generic drugs (drugs for which approval is sought in an ANDA). The final rule discontinues FDA's use of approvable letters and not approvable letters when taking action on marketing applications. Instead, we will send applicants a complete response letter to indicate that the review cycle for an application is complete and that the application is not ready for approval. We are also revising the regulations on extending the review cycle due to the submission of an amendment to an unapproved application and starting a new review cycle after the resubmission of an application following receipt of a complete response letter. In addition, we are adding to the regulations on biologics license applications (BLAs) provisions on the issuance of complete response letters to BLA applicants. We are taking these actions to implement the user fee performance goals referenced in the Prescription Drug User Fee Amendments of 2002 (PDUFA III) that address procedures and establish target timeframes for reviewing human drug applications.

  8. DNA damage response is hijacked by human papillomaviruses to complete their life cycle

    OpenAIRE

    Hong, Shi-yuan

    2017-01-01

    The DNA damage response (DDR) is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses (HPVs) are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identifi...

  9. Diabetic Driving Studies-Part 3: A Comparison of Mean Brake Response Time Between Neuropathic Diabetic Drivers With and Without Foot Pathology.

    Science.gov (United States)

    Sansosti, Laura E; Spiess, Kerianne E; Meyr, Andrew J

    We have previously demonstrated an abnormally delayed mean brake response time and an increased frequency of abnormally delayed brake responses in a group of neuropathic diabetic drivers compared with a control group of drivers with neither diabetes nor lower extremity neuropathy. The objective of the present case-control study was to compare the mean brake response time between neuropathic diabetic drivers with and without specific diabetic foot pathology. The braking performances of the participants were evaluated using a computerized driving simulator with specific measurement of the mean brake response time and the frequency of abnormally delayed brake responses. We analyzed a control group of 20 active drivers with type 2 diabetes, lower extremity neuropathy, and no history of diabetic foot pathology and an experimental group of 20 active drivers with type 2 diabetes, lower extremity neuropathy, and a history of diabetic foot pathology (ulceration, amputation, and/or Charcot neuroarthropathy) from an urban U.S. podiatric medical clinic. Neuropathic diabetic drivers without a history of specific foot pathology demonstrated an 11.11% slower mean brake response time (0.790 ± 0.223 versus 0.711 ± 0.135 second; p time slower than a suggested threshold of 0.70 second. The results of the present investigation provide evidence that diabetic patients across a spectrum of lower extremity sensorimotor neuropathy and foot pathology demonstrate abnormal automobile brake responses and might be at risk of impaired driving function. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders

    Directory of Open Access Journals (Sweden)

    Loftis Jennifer M

    2007-01-01

    Full Text Available Abstract Background Individuals with substance use disorders (SUDs are at increased risk for hepatitis C viral infection (HCV, and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20 of the Veterans Healthcare Administration (VHA between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN or combination therapy (IFN and ribavirin who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group and patients without a history of SUD (SUD- Group. Results Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%, and if they had genotypes 1 and 4 (39.5% vs. 39.9%. Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8% and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%. Conclusion Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

  11. Promoting change through political consciousness: a South African speech-language pathology response to the World Report on Disability.

    Science.gov (United States)

    Kathard, Harsha; Pillay, Mershen

    2013-02-01

    In the context of the World Report on Disability, Wylie, McAllister, Davidson, and Marshall (2013) question how speech-language pathologists (SLPs) change practices to benefit under-served people with communication disability. This commentary provides a South African response premised on Political Consciousness. In South Africa, a grossly unequal society, the under-served population is not only those with communication disability but also include those who are at a communication disadvantage due to disabling conditions. As a consequence of the combined effects of a severe shortage of SLPs as well as maldistribution in service provision, the under-served are mainly poor Black South Africans who are the majority population. Political Consciousness allows one to examine how selected forces at the macro-level, meso-level, and micro-level may enable or limit services to the under-served majority. At a macro-level, this study appraises policies and actions advancing and impeding service delivery. At the meso-level it is argued that hegemonic professional knowledge is limiting and an equity-driven population-based approach is advocated. At a micro-level, the Relationship of Labouring Affinities is offered as a conceptual tool for critical engagement. In conclusion, it is suggested that the speech-language pathology profession must collectively become political actors at all levels to effect change.

  12. Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

    Science.gov (United States)

    Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

    2015-09-01

    Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

  13. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

    Directory of Open Access Journals (Sweden)

    Xu Chaoyang

    2009-07-01

    Full Text Available Abstract Background Preoperative chemotherapy (PCT has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide, VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide and EFC (epirubicin+5-fluorouracil+cyclophosphamide were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p p Conclusion ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

  14. Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

    Science.gov (United States)

    Ottaiano, Alessandro; Napolitano, Maria; Capozzi, Monica; Tafuto, Salvatore; Avallone, Antonio; Scala, Stefania

    2017-11-16

    Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer (NK) cells (35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

  15. Sustained Complete Response after Maintenance Therapy with Topotecan and Erlotinib for Recurrent Cervical Cancer with Distant Metastases

    Directory of Open Access Journals (Sweden)

    Donato Callegaro-Filho

    2014-01-01

    Full Text Available Introduction: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR inhibitors may have a role in this setting. Case Description: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. Conclusion: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance.

  16. Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

    Science.gov (United States)

    Lou, Emil; Schomaker, Matthew; Wilson, Jon D; Ahrens, Mary; Dolan, Michelle; Nelson, Andrew C

    2016-08-12

    Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma.

  17. Acute neuromuscular and performance responses to Nordic hamstring exercises completed before or after football training.

    Science.gov (United States)

    Lovell, Ric; Siegler, Jason C; Knox, Michael; Brennan, Scott; Marshall, Paul W M

    2016-12-01

    The optimal scheduling of Nordic Hamstring exercises (NHEs) relative to football training sessions is unknown. We examined the acute neuromuscular and performance responses to NHE undertaken either before (BT) or after (AT) simulated football training. Twelve amateur players performed six sets of five repetitions of the NHE either before or after 60 min of standardised football-specific exercise (SAFT 60 ). Surface electromyography signals (EMG) of the hamstring muscles were recorded during both the NHE, and maximum eccentric actions of the knee flexors (0.52 rad · s -1 ) performed before and after the NHE programme, and at 15 min intervals during SAFT 60 . Ten-metre sprint times were recorded on three occasions during each 15 min SAFT 60 segment. Greater eccentric hamstring fatigue following the NHE programme was observed in BT versus AT (19.8 %; very likely small effect), which was particularly apparent in the latter range of knee flexion (0-15°; 39.6%; likely moderate effect), and synonymous with hamstring EMG declines (likely small-likely moderate effects). Performing NHE BT attenuated sprint performance declines (2.0-3.2%; likely small effects), but decreased eccentric hamstring peak torque (-14.1 to -18.9%; likely small effects) during football-specific exercise. Performing NHE prior to football training reduces eccentric hamstring strength and may exacerbate hamstring injury risk.

  18. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

  19. The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated. The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought. The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent “functional paradox” has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature. This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described “bimodal” effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future

  20. 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

    Energy Technology Data Exchange (ETDEWEB)

    Seith, Ferdinand; Schmidt, Holger; Pfannenberg, Christina; Gueckel, Brigitte; Schwenzer, Nina [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Forschner, Andrea; Garbe, Claus [Eberhard Karls University, Department of Dermatology, Tuebingen (Germany); Nikolaou, Konstantin [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); La Fougere, Christian [German Cancer Consortium (DKTK), Heidelberg (Germany); Eberhard Karls University, Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

    2018-01-15

    The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t{sub 0}, base-line), two weeks (t{sub 1}, study examination) and three months after treatment initiation (t{sub 2}, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t{sub 1} turned out to have complete response at t{sub 2}. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t{sub 2}, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t{sub 1}. OS in patients with PMD at t{sub 2} varied between 148 and 814 days. SMD at both t{sub 1} and t{sub 2} was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future. (orig.)

  1. Evaluation of the deposition, translocation and pathological response of brake dust with and without added chrysotile in comparison to crocidolite asbestos following short-term inhalation: interim results.

    Science.gov (United States)

    Bernstein, David M; Rogers, Rick; Sepulveda, Rosalina; Kunzendorf, Peter; Bellmann, Bernd; Ernst, Heinrich; Phillips, James I

    2014-04-01

    Chrysotile has been frequently used in the past in manufacturing brakes and continues to be used in brakes in many countries. This study was designed to provide an understanding of the biokinetics and potential toxicology following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6 h/day for 5 days to either brake dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake dust or crocidolite asbestos. No significant pathological response was observed at any time point in either the brake dust or chrysotile/brake dust exposure groups. The long chrysotile fibers (>20 μm) cleared quickly with T(½) estimated as 30 and 33 days, respectively in the brake dust and the chrysotile/brake dust exposure groups. In contrast, the long crocidolite fibers had a T(½)>1000 days and initiated a rapid inflammatory response in the lung following exposure resulting in a 5-fold increase in fibrotic response within 91 days. These results provide support that brake dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung following short term inhalation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. {sup 18}F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer: review of the literature and recommendations for use in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, David [Saint-Louis Hospital, Department of Nuclear Medicine, Paris Cedex 10 (France); INSERM/CNRS UMR944/7212, University Paris-Diderot, PRES Paris Cite, Paris (France); Mankoff, David [University of Pennsylvania Perelman School of Medicine, Department of Radiology, Philadelphia (United States); Espie, Marc [INSERM/CNRS UMR944/7212, University Paris-Diderot, PRES Paris Cite, Paris (France); Saint-Louis Hospital, Department of Medical Oncology, Breast Diseases Centre, Paris (France); Hindie, Elif [University of Bordeaux, Department of Nuclear Medicine, Haut-Leveque Hospital, Bordeaux (France)

    2016-05-15

    Early assessment of response to neoadjuvant chemotherapy (NAC) might be helpful in avoiding the toxicity of ineffective chemotherapy and allowing refinement of treatment. We conducted a review of the literature regarding the applicability of {sup 18}F-FDG PET/CT to the prediction of an early pathological response in different subgroups of breast cancer. Clinical research in this field has intensified in the last few years. Early studies by various groups have shown the potential of {sup 18}F-FDG PET/CT in the early assessment of response to NAC. However, interim PET/CT in breast cancer has not yet gained wide acceptance compared to its use in other settings such as lymphomas. This is in part due to a lack of consensus that early evaluation of response can be used to direct change in therapy in the neoadjuvant breast cancer setting, and only limited data showing that response-adaptive therapy leads to improved outcomes. However, one major element that has hampered the use of {sup 18}F-FDG PET/CT in directing neoadjuvant therapy is its evaluation in populations with mixed subtypes of breast cancer. However, major improvements have occurred in recent years. Pilot studies have highlighted the need for considering breast cancer subtype and the type of treatment, and have offered criteria for the use of PET/CT for the early prediction of response in specific settings. {sup 18}F-FDG PET/CT has considerable potential for the early prediction of pathological complete response to NAC in aggressive subtypes such as triple-negative or HER2-positive breast cancers. The results of a multicentre trial that used early metabolic response on {sup 18}F-FDG PET/CT as a means to select poor responders to adapt neoadjuvant treatment have recently been published. Other trials are ongoing or being planned. (orig.)

  3. [Complete hormonal and metabolic response after iodine-131 metaiodobenzylguanidine treatment in a patient diagnosed of malignant pheochromocytoma].

    Science.gov (United States)

    García Alonso, M P; Balsa Bretón, M A; Paniagua Correa, C; Castillejos Rodríguez, L; Rodríguez Pelayo, E; Mendoza Paulini, A; Ortega Valle, A; Penín González, J

    2013-01-01

    Radiolabeled metaiodobenzylguanidine is an analogue of norepinephrine used to localize tumors that express the neurohormone transporters, specifically those derived from the neural crest having a neuroendocrine origin. It is also used to treat non-surgical metastases derived from them. A review of the literature revealed symptomatic improvements associated to a decrease in hormone levels in a significant percentage of patients after (131)I-MIBG treatment. However, complete tumor remission has been described only in very few cases and hardly ever when bone metastases exist. We present a case of a patient diagnosed of malignant pheochromocytoma who achieved complete hormonal and metabolic response after (131)I-MIBG treatment (600 mCi) in spite of the presence of bone metastases. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  4. High levels of virus replication and an intense inflammatory response contribute to the severe pathology in lymphoid tissues caused by Newcastle disease virus genotype VIId.

    Science.gov (United States)

    Hu, Zenglei; Hu, Jiao; Hu, Shunlin; Song, Qingqing; Ding, Pingyun; Zhu, Jie; Liu, Xiaowen; Wang, Xiaoquan; Liu, Xiufan

    2015-03-01

    Some strains of Newcastle disease virus (NDV) genotype VIId cause more-severe tissue damage in lymphoid organs compared to other virulent strains. In this study, we aim to define the mechanism of this distinct pathological manifestation of genotype VII viruses. Pathology, virus replication, and the innate immune response in lymphoid tissues of chickens infected with two genotype VIId NDV strains (JS5/05 and JS3/05), genotype IX NDV F48E8 and genotype IV NDV Herts/33, were compared. Histopathologic examination showed that JS5/05 and JS3/05 produced more-severe lesions in the spleen and thymus, but these four virulent strains caused comparable mild lesions in the bursa. In addition, JS3/05 and JS5/05 replicated at significantly higher levels in the lymphatic organs than F48E8 and Herts/33. A microarray assay performed on the spleens of chickens infected with JS5/05 or Herts/33 revealed that JS5/05 elicited a more potent inflammatory response by increasing the number and expression levels of activated genes. Moreover, cytokine gene expression profiling showed that JS5/05 and JS3/05 induced a stronger cytokine response in lymphoid tissues compared to F48E8 and Herts/33. Taken together, our results indicate that the severe pathology in immune organs caused by genotype VIId NDV strains is associated with high levels of virus replication and an intense inflammatory response.

  5. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

    Science.gov (United States)

    Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

    2017-01-02

    There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

  6. The use of virtual microscopy and a wiki in pathology education: Tracking student use, involvement, and response.

    Science.gov (United States)

    Leifer, Zev

    2015-01-01

    The pathology laboratory course at the New York College of Podiatric Medicine involves the use of Virtual Microscopy. The students can scan the whole slide, section by section, and zoom in or out. Using the advantages of digital pathology, the students can, in addition, access the slide collections from other medical schools and put up normal histology (control) slides side-by-side with the pathology. They can cut and paste and preserve the region of interest that they find. They can edit and annotate their slides. A wiki was created (http://pathlab2014.wikifoundry.com)for the Class of 2014. The students saved, edited and uploaded their slides. In the wiki format, other students could comment, further edit, and even delete the slides. The students studied Basic Mechanisms and System Pathology. During this time, they saved, edited, shared, and uploaded their slides to the wiki. These were available in one full presentation and were also grouped into 16 albums. They were available to all. Student access was followed by Google analytics. At the end of the course, a questionnaire was distributed, assessing their impression of the wiki format and soliciting strengths and weaknesses. The use of a wiki has a number of important advantages in pathology education. It trains the students in the more sophisticated skills that they will use as professional pathologists or as clinicians: (1) Telepathology-it enables them to share slides and discuss observations. (2) Archiving and retrieval - It models the challenge faced by hospitals, diagnostic labs and physicians in maintaining a collection of slides in a form that is easily accessible. (3) Image analysis-familiarity with the wiki format allows them to jump easily to capturing and storing images found in the literature or in a pathologist's report. Experience with the use of a wiki in pathology education has been quite satisfactory from both the faculty and the student's point of view.

  7. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

    Directory of Open Access Journals (Sweden)

    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  8. Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Tiffany A. Pompa

    2017-01-01

    Full Text Available Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC, the National Comprehensive Cancer Network (NCCN suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles, intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

  9. Comment and response document for the UMTRA Project vitro processing site completion report Salt Lake City, Utah. Revision 1

    International Nuclear Information System (INIS)

    1995-03-01

    This Comment and Response Document is a series of UMTRA document review forms regarding the UMTRA Project Vitro Processing Site Completion Report for Salt Lake City, Utah in March, 1995. The completion report provides evidence that the final Salt Lake City, Utah, processing site property conditions are in accordance with the approved design and that all U.S. Environmental Protection Agency (EPA) standards have been satisfied. Included as appendices to support the stated conclusions are the record drawings; a summary of grid test results; contract specifications and construction drawings, the EPA standards (40 CFR Part 192); the audit, inspection, and surveillance summary; the permit information; and project photographs. The principal objective of the remedial action at Salt Lake City is to remove the tailings from the processing site, render the site free of contamination to EPA standards, and restore the site to the final design grade elevations. Each section is evaluated in detail to check all aspects of above report, especially the inclusion of adequate verification data. Each review form contains a section entitled State of Utah Response and Action, which is an explanation or correction of DOE criticisms of the report

  10. [A case of a geriatric patient with stage IV anal canal cancer showing complete response to chemoradiation therapy].

    Science.gov (United States)

    Kuroda, Masatoshi; Hirai, Ryuji; Ikeda, Eiji; Tsuji, Hisashi; Takagi, Shoji; Yamano, Toshihisa; Yoshitomi, Seiji

    2012-11-01

    We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

  11. New developments in digital pathology: from telepathology to virtual pathology laboratory.

    Science.gov (United States)

    Kayser, Klaus; Kayser, Gian; Radziszowski, Dominik; Oehmann, Alexander

    2004-01-01

    To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under

  12. Pathological gambling and criminality.

    Science.gov (United States)

    Folino, Jorge Oscar; Abait, Patricia Estela

    2009-09-01

    To review research results on the relationship between pathological gambling and criminality, published in 2007 and 2008, in English and in Spanish. An important association between pathological gambling and criminality was confirmed in populations of anonymous gamblers, helpline callers and substance abusers. Helplines provide a timely service to gamblers who have not reached the maximum stages in the development of a pathological gambling pattern. Pathological gambling is associated with violence in couples and dysfunctional families. Inversely, violence is also an antecedent promoting vulnerability toward pathological gambling. Impulsiveness shows diverse relationships with pathological gambling and violence as well. A pathological gambler's involvement in crime is exceptionally considered without responsibility by justice, but it may be an indicator of the disorder severity and the need for special therapeutic tactics. While reviewing the present study, research work was published that contributed to a better understanding of the association between pathological gambling and criminality and went further into their complex relationship and the formulation of explanatory models related to impulsiveness.

  13. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J; Gong, G; Cui, Y; Li, R [Stanford University, Palo Alto, CA (United States)

    2016-06-15

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  14. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    International Nuclear Information System (INIS)

    Wu, J; Gong, G; Cui, Y; Li, R

    2016-01-01

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  15. MRI evaluation of residual breast cancer after neoadjuvant chemotherapy: influence of patient, tumor and chemotherapy characteristics on the correlation with pathological response.

    Science.gov (United States)

    Diguisto, Caroline; Ouldamer, Lobna; Arbion, Flavie; Vildé, Anne; Body, Gilles

    2015-01-01

    The aim of this study was to evaluate the correlation between the residual tumor measured on magnetic resonance imaging and pathological results and to assess whether this correlation varies according to patient, tumor or chemotherapy characteristics. The study population included women treated for breast cancer with indication of neoadjuvant chemotherapy in our tertiary breast cancer Unit between January 2008 and December 2011. Factors related to patients, tumor and chemotherapy were studied. Pearson's correlation coefficient between the size of the tumor on MRI and pathological response was calculated for the entire population. It was also calculated according to patient, tumor and chemotherapy characteristics. During the study period, 107 consecutive women were included. The size of residual tumor on the MRI significantly correlated with the size on pathological result with a Pearson correlation coefficient of 0.52 (pcorrelation was stronger for women aged 50 years and older (r=0.64, pcorrelation was stronger for those with triple-negative tumors (r=0.69, p=0.002) but weaker for those with tumors with a ductal carcinoma in situ component (r =0.18, p=0.42). The size of breast cancer obtained by MRI is significantly correlated to the pathological size of the tumor. This correlation was stronger among women aged 50 years and more, among post-menopausal women, and among women who had triple-negative tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial

    International Nuclear Information System (INIS)

    Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; Laroche, Guy de; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

    2015-01-01

    Background: During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Material and methods: Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine + oxaliplatin + 50 Gy vs Cap 45: capecitabine + 45 Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. Results: The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p = 0.025); tumors <4 cm in diameter (14%; p = 0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p = 0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 “watch and wait”. A complete response was associated with more ypT0 (73%; p < 0.001); ypNO (92%); R0 circumferential margin (100%). Conclusion: These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers

  17. Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial.

    Science.gov (United States)

    Gérard, Jean-Pierre; Chamorey, Emmanuel; Gourgou-Bourgade, Sophie; Benezery, Karène; de Laroche, Guy; Mahé, Marc-André; Boige, Valérie; Juzyna, Béata

    2015-05-01

    During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    Directory of Open Access Journals (Sweden)

    Hiroki Hashida

    2017-01-01

    Full Text Available It has been reported that many patients with lung metastasis of colorectal cancer (CRC underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI plus bevacizumab (BV therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped.

  19. Complete Electric Dipole Response in 120Sn and 208Pb and Implications for Neutron Skin and Symmetry Energy

    Directory of Open Access Journals (Sweden)

    von Neumann-Cosel Peter

    2015-01-01

    Full Text Available Polarized proton scattering at energies of a few 100 MeV and extreme forward angles including 0° has been established as a new tool to extract the complete E1 response in nuclei up to excitation energies of about 20 MeV. A case study of 208Pb demonstrates excellent agreement with other electromagnetic probes. From the information on the B(E1 strength one can derive the electric dipole dipole polarizability, which is strongly correlated to the neutron skin and to parameters of the symmetry energy. Recently, we have extracted the polarizability of 120Sn with a comparable precision. The combination of both results further constrains the symmetry energy parameters and presents a challenge for mean-field models, since the relativistic and many Skyrme parameterizations cannot reproduce both experimental results simultaneously.

  20. Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

    Science.gov (United States)

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A; Janssen, Paulus M L; Martin, Paul T

    2015-10-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses

    OpenAIRE

    Ramezanifard, Rouhallah; Kabiri, Mahboubeh; Hanaee Ahvaz, Hana

    2017-01-01

    Regarding the inadequate healing capability of cartilage tissue, cell-based therapy is making the future of cartilage repair and regeneration. Mesenchymal stem cells (MSC) have shown great promise in cartilage regeneration. However, a yet-unresolved issue is the emergence of hypertrophic and pathologic markers during in vitro MSC chondrogenesis. Articular chondrocytes (AC) can suppress the undesired hypertrophy when co-cultured with MSC. On the other hand, platelet rich plasma (PRP), is consi...

  2. The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE

    Directory of Open Access Journals (Sweden)

    Jung Hee Kim

    2017-03-01

    Full Text Available Background/Aims We investigated the outcomes of early-stage hepatocellular carcinoma (HCC patients who showed a complete response (CR to initial transarterial chemoembolization (TACE, with a focus on the role of scheduled TACE repetition. Methods A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria on one month follow-up computed tomography (CT were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT. Results During a median follow-up period of 4.6 years (range: 0.4-8.8 years, mortality was observed in 71 patients (39.9%. The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025. When stratified using Barcelona clinic liver cancer (BCLC stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients. Conclusions Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients.

  3. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality.

    Science.gov (United States)

    Martínez-López, Joaquín; Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F; Lahuerta, Juan José

    2015-08-13

    Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. © 2015 by The American Society of Hematology.

  4. Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy

    International Nuclear Information System (INIS)

    Maffione, Anna Margherita; Ferretti, Alice; Grassetto, Gaia; Chondrogiannis, Sotirios; Marzola, Maria Cristina; Rampin, Lucia; Bondesan, Claudia; Rubello, Domenico; Bellan, Elena; Gava, Marcello; Capirci, Carlo; Colletti, Patrick M.

    2013-01-01

    The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p 3 , 23.4 cm 3 , 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG. (orig.)

  5. Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.

    Science.gov (United States)

    Subramaniam, Renuka; Herndon, Caroline N; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Bavananthasivam, Jegarubee; Potter, Kathleen A; Knowles, Donald P; Foreyt, William J; Srikumaran, Subramaniam

    2011-12-15

    The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M. haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of functional phagocytes in the lung. We hypothesized that enhanced lung pathology is due to defective clearance of M. haemolytica from the lungs of BHS. To test this hypothesis, M. haemolytica (1 × 10(7) colony forming units [cfu]) were inoculated intra-tracheally into three groups each of BHS and DS, which were euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF) collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a significantly higher number of M. haemolytica than that from DS. More importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still had significant numbers. As expected, the BHS did exhibit more extensive lung lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from BHS had significantly lower titers of antibodies to Lkt and surface antigens of M. haemolytica, than that of DS. These findings suggest that the enhanced pathology in BHS lungs is due to defective clearance of M. haemolytica from the lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. [Pathological gambling].

    Science.gov (United States)

    Dembinsky, Yael; Iancu, Iulian; Dannon, Pinhas

    2007-10-01

    Gambling behaviour is well-known for many centuries and is growing in popularity and frequency. Its etiology is multi-factorial and in this paper we review new developments in the field of pathological gambling, both regarding etiology and treatment progress. The aim of this review is to increase the physicians' awareness towards this entity.

  7. Balanced nuclear and cytoplasmic activities of EDS1 are required for a complete plant innate immune response.

    Directory of Open Access Journals (Sweden)

    Ana V García

    2010-07-01

    Full Text Available An important layer of plant innate immunity to host-adapted pathogens is conferred by intracellular nucleotide-binding/oligomerization domain-leucine rich repeat (NB-LRR receptors recognizing specific microbial effectors. Signaling from activated receptors of the TIR (Toll/Interleukin-1 Receptor-NB-LRR class converges on the nucleo-cytoplasmic immune regulator EDS1 (Enhanced Disease Susceptibility1. In this report we show that a receptor-stimulated increase in accumulation of nuclear EDS1 precedes or coincides with the EDS1-dependent induction and repression of defense-related genes. EDS1 is capable of nuclear transport receptor-mediated shuttling between the cytoplasm and nucleus. By enhancing EDS1 export from inside nuclei (through attachment of an additional nuclear export sequence (NES or conditionally releasing EDS1 to the nucleus (by fusion to a glucocorticoid receptor (GR in transgenic Arabidopsis we establish that the EDS1 nuclear pool is essential for resistance to biotrophic and hemi-biotrophic pathogens and for transcriptional reprogramming. Evidence points to post-transcriptional processes regulating receptor-triggered accumulation of EDS1 in nuclei. Changes in nuclear EDS1 levels become equilibrated with the cytoplasmic EDS1 pool and cytoplasmic EDS1 is needed for complete resistance and restriction of host cell death at infection sites. We propose that coordinated nuclear and cytoplasmic activities of EDS1 enable the plant to mount an appropriately balanced immune response to pathogen attack.

  8. Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment

    Directory of Open Access Journals (Sweden)

    Koichi Suyama

    2013-10-01

    Full Text Available The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.

  9. Response of loblolly pine to complete woody and herbaceous control: projected yields and economic outcomes - the COMProject

    Science.gov (United States)

    James H. Miller; R.L. Busby; B.R. Zutter; S.M. Zedaker; M.B. Edwards; R.A. Newbold

    1995-01-01

    Abstract.Age-8 and -9 data from the 13 study plantations of the Competition Omission Monitoring Project (COMP) were used to project yields and derive economic outcomes for loblolly pine (Pinus taeda L.). COMP treatments were chop-burn, complete woody plant control, complete herbaceous plant control for 4 years, and complete woody...

  10. Complete pathological response in patients treated with Neoadyuvancia in rectal cancer at Hospital San Juan de Dios from January 2008 to December 2010

    International Nuclear Information System (INIS)

    Laurito Torres, Paula

    2014-01-01

    The cure rate of patients treated with chemotherapy under the condition of locally advanced rectal adenocarcinoma is characterized in the Hospital San Juan de Dios between January 2008 and December 2010. Factors related to this treatment are described. Clinical records of 36 patients who received neoadjuvant treatment are studied. The data are collected, on staging studies; treatment toxicity; preservation of anal sphincter; downstaging; equipment and doses of radiotherapy; surgical resectability; complications of treatment; chemotherapy regimens; survival and free period of recurrence. The curative index of the patients investigated is similar to the publications of international studies. Some particularities of the treatment can be improved to obtain better results [es

  11. [Dual pathology].

    Science.gov (United States)

    Rougier, A

    2008-05-01

    Dual pathology is defined as the association of two potentially epileptogenic lesions, hippocampal (sclerosis, neuronal loss) and extrahippocampal (temporal or extratemporal). Epileptic activity may be generated by either lesion and the relative importance of every lesion's epileptogenicity conditions the surgical strategy adopted. Most frequently associated with hippocampal sclerosis are cortical dysplasias. The common physiopathology of the two lesions is not clearly established. Extrahippocampal lesions may be undetectable on MRI (microdysgenesis, for example) and ictal discharge patterns may vary among dual pathology patients. The surgical strategy depends on the location of the extrahippocampal lesion and its relative role in seizure generation; however, reported surgical results suggest that simultaneous resection of mesial temporal structures along with the extrahippocampal lesion should be performed.

  12. Microglial pathology

    OpenAIRE

    Streit, Wolfgang J; Xue, Qing-Shan; Tischer, Jasmin; Bechmann, Ingo

    2014-01-01

    This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer’s disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial ...

  13. SU-F-R-47: Quantitative Shape Relationship Analysis of PTV Modification for Critical Anatomy Sparing and Its Impact On Pathologic Response for Neoadjuvant Stereotactic Radiotherapy for Pancreatic Cancer

    International Nuclear Information System (INIS)

    Cheng, Z; Rosati, L; Chen, L; Robertson, S; Moore, J; Peng, L; Mian, O; Narang, A; Hacker-Prietz, A; Herman, J; McNutt, T

    2016-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) may be used to increase surgery candidacy in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. However, the planning target volume (PTV) may need to be limited to avoid toxicity when the gross tumor volume (GTV) is anatomically involved with surrounding critical structures. Our study aims to characterize the coverage of GTV and investigate the association between modified PTV and pathologic (pCR) or near pathologic (npCR) complete response rates determined from the surgical specimen. Methods: Patients treated with neoadjuvant pancreas SBRT followed by surgery from 2010–2015 were selected from Oncospace. Overlap volume histogram (OVH) analysis was performed to determine the extent of compromise of the PTV from both the GTV and a standard target (GTV+3mm). Subsequently, normalized overlap volume (%) was calculated for: (1) GTV-PTV, and (2) GTV+3mm expansion-PTV. A logistic regression model was used to identify the association between the overlap ratios and ≥ npCR(pCR/npCR) stratified by active breathing control (ABC) versus free-breathing status. Results: Eighty-one (BRPC: n=42, LAPC: n=39) patients were available for analysis. Nearly 40% (31/81) had ≥npCR and 75% (61/81) were able to complete ABC. Mean coverage of the GTV-PTV was 92.6% (range, 59.9%–100%, SD = 8.68) and coverage of the GTV+3mm expansion-PTV was 85. 2% (range, 59.9% −100.0%, SD= 8.67). Among the patients with ABC, every 10% increase in GTV coverage doubled the odds to have ≥npCR (OR = 1.82, p=0.06). Coverage of GTV+3mm expansion was not associated with ≥npCR regardless of ABC status. Conclusion: Preferential sparing of critical anatomy over GTV-PTV coverage with ABC management suggests worse ≥npCR rates for neoadjuvant SBRT in BRPC and LAPC. Limiting the GTV and GTV+3mm expansion in free-breathing patients was not associated with pathologic response perhaps due to larger GTV definitions as a result of motion

  14. SU-F-R-47: Quantitative Shape Relationship Analysis of PTV Modification for Critical Anatomy Sparing and Its Impact On Pathologic Response for Neoadjuvant Stereotactic Radiotherapy for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Z; Rosati, L; Chen, L; Robertson, S; Moore, J; Peng, L; Mian, O; Narang, A; Hacker-Prietz, A; Herman, J; McNutt, T [Johns Hopkins University, Baltimore, MD (United States)

    2016-06-15

    Purpose: Stereotactic body radiation therapy (SBRT) may be used to increase surgery candidacy in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer. However, the planning target volume (PTV) may need to be limited to avoid toxicity when the gross tumor volume (GTV) is anatomically involved with surrounding critical structures. Our study aims to characterize the coverage of GTV and investigate the association between modified PTV and pathologic (pCR) or near pathologic (npCR) complete response rates determined from the surgical specimen. Methods: Patients treated with neoadjuvant pancreas SBRT followed by surgery from 2010–2015 were selected from Oncospace. Overlap volume histogram (OVH) analysis was performed to determine the extent of compromise of the PTV from both the GTV and a standard target (GTV+3mm). Subsequently, normalized overlap volume (%) was calculated for: (1) GTV-PTV, and (2) GTV+3mm expansion-PTV. A logistic regression model was used to identify the association between the overlap ratios and ≥ npCR(pCR/npCR) stratified by active breathing control (ABC) versus free-breathing status. Results: Eighty-one (BRPC: n=42, LAPC: n=39) patients were available for analysis. Nearly 40% (31/81) had ≥npCR and 75% (61/81) were able to complete ABC. Mean coverage of the GTV-PTV was 92.6% (range, 59.9%–100%, SD = 8.68) and coverage of the GTV+3mm expansion-PTV was 85. 2% (range, 59.9% −100.0%, SD= 8.67). Among the patients with ABC, every 10% increase in GTV coverage doubled the odds to have ≥npCR (OR = 1.82, p=0.06). Coverage of GTV+3mm expansion was not associated with ≥npCR regardless of ABC status. Conclusion: Preferential sparing of critical anatomy over GTV-PTV coverage with ABC management suggests worse ≥npCR rates for neoadjuvant SBRT in BRPC and LAPC. Limiting the GTV and GTV+3mm expansion in free-breathing patients was not associated with pathologic response perhaps due to larger GTV definitions as a result of motion

  15. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

    Science.gov (United States)

    Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

    2015-10-01

    To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

  16. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  17. Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice.

    Science.gov (United States)

    Omorogbe, Osarume; Ajayi, Abayomi M; Ben-Azu, Benneth; Oghwere, Ejiroghene E; Adebesin, Adaeze; Aderibigbe, Adegbuyi O; Okubena, Olajuwon; Umukoro, Solomon

    2018-02-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn ® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn ® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. The Prospect of Using Complete Feed in Goat Production: A Review on its Utility and Physical Form and Animal Responses

    Directory of Open Access Journals (Sweden)

    Simon P Ginting

    2009-06-01

    Full Text Available Complete feed is a strategic feeding system that has been widely adopted by the dairy cattle industry, but it has been rarely practised in goat enterprises. The prospect of using complete feed for goat production could be considered from two aspects, namely 1 its relevancy to the goat metabolic requirement, and 2 its potential as an effective means for maximal utilization of crop residues and agro-industrial byproducts as alternative feeds. Metabolically, the higher energy requirement and the lower gut capacity of goats due to its relatively smaller body size make this animal more adapted to feedstuffs with denser nutrient contents as typified by the complete feed. As complete feed is characteristically dry, it has potential to cause hypovolemia and induce later a lower feed consumption when fed to goats. But, this event occurs only during the initial meal and the condition returns to the normal state thereafter. Total saliva secretion tend to decrease by consuming dry feed which can cause parakeratosis, laminitis or acidosis. However, these metabolic disorder could be prevented by formulating complete feed with optimal roughage/concentrate ratio. Review from literatures showed that, when used in complete feed, the inclusion rate of several low palatability crop residues or agro-industrial ranged from 15 to 60%. The roughage/concentrate ratio was in the range of 0.25 to 3.0. Some physical characteristics are important for effective complete feed such as the particle size of roughage, the content of physically effective fibre and the form of the complete feed. Complete feed processed into pellet generally resulted in better performances. The ME and CP content of complete feed used ranged from 1800 to 2800 kcal/kg DM and from 15 to 20%, respectively. The rate of feed intake by goats receiving complete feed ranged from 2.0 to 4.9% BW, the ADG ranged from 40 to 145 g, FCR ranged from 5.2 to 13.0 and DM digestibility ranged from 62 to 81%. These

  19. Microglial pathology.

    Science.gov (United States)

    Streit, Wolfgang J; Xue, Qing-Shan; Tischer, Jasmin; Bechmann, Ingo

    2014-09-26

    This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer's disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial pathology and its significance during aging and in the pathogenesis of Alzheimer dementia (AD). The identification of dystrophic (senescent) microglia has created an ostensible conflict with prior work claiming a role for activated microglia and neuroinflammation during normal aging and in AD, and this has raised a basic question: does the brain's immune system become hyperactive (inflamed) or does it become weakened (senescent) in elderly and demented people, and what is the impact on neuronal function and cognition? Here we strive to reconcile these seemingly contradictory notions by arguing that both low-grade neuroinflammation and microglial senescence are the result of aging-associated free radical injury. Both processes are damaging for microglia as they synergistically exhaust this essential cell population to the point where the brain's immune system is effete and unable to support neuronal function.

  20. Assessment of gill pathological responses in the tropical fish yellowfin seabream of Persian Gulf under mercury exposure

    Directory of Open Access Journals (Sweden)

    Leila Hassaninezhad

    2014-01-01

    Full Text Available Gill histomorphological alterations were used to assess the effects of chronic exposure to HgCl2 on the yellowfin seabream, Acanthopagrus latus. In this regard, 90 A. latus were exposed to sublethal concentrations of HgCl2 (10, 20, 35 and 50 μg/L for 3 weeks. Treated fish were erratic and showed respiratory distress. The most common morphological abnormalities included: filaments disorganization, increase of mucus secretion, debris and blood plaques on the filaments, losing or shortening of some filaments. The most frequent histopathological changes detected in the gills included extensive lifting of the lamellar epithelium and edema of lamellae with enlarged sub-epithelial spaces, exfoliated epithelium of lamellae, telangiectasia, hypertrophy and hyperplasia of the epithelial cell resulted in partial fusion of the secondary lamellae and a reduction of the water space, club shaping of gill lamellae, blood congestion. Some more severe alternations found in the gill of fish exposed to higher levels of HgCl2 (35 and 50 μg/L included lamellar aneurysm and hemorrhages with rupture of the lamellar epithelium. According to the results of the present study, mercuric chloride could cause major histomorphological changes in the gill of A. latus, decreasing its gas exchange capability. Two mercury concentrations (10 and 20 μg/L used in the present study were in agreement with the concentration of mercury in the water of different parts of Mahshahr creeks (the north of Persian Gulf (3.66 to 15 μg/L. Therefore, based on the results the presence of pathological alteration in A. latus inhibited in the natural environment (Mahshahr creeks seems to be logical.

  1. Radiation dose reduction for patients with extranodal NK/T-cell lymphoma with complete response after initial induction chemotherapy

    Directory of Open Access Journals (Sweden)

    Wang L

    2016-09-01

    Full Text Available Liang Wang,1,2,* Xi-wen Bi,1,3,* Zhong-jun Xia,1,2 Hui-qiang Huang,1,3 Wen-qi Jiang,1,3 Yu-jing Zhang1,4 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Hematologic Oncology, 3Department of Medical Oncology, 4Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Previous studies have found that radiotherapy (RT dose less than 50 Gy resulted in inferior outcomes for early stage extranodal NK/T-cell lymphoma (ENKTL. Nowadays, induction chemotherapy (CT followed by RT consolidation is often used. For patients who get complete response (CR after CT, whether RT dose can be safely reduced or not remains unknown. This retrospective study compared the survival outcomes between patients who received higher dose (>50 Gy and lower dose (≤50 Gy RT after CR was attained by CT. One hundred and forty four patients of early stage ENKTL got CR after induction CT and received RT consolidation. Thirty-one patients received lower dose RT (median 46 Gy, range, 36–50 Gy, and 113 patients received higher dose RT (median 56 Gy, range, 52–66 Gy. In univariate survival analysis, age >60, local tumor invasion, and non-asparaginase-based CT were associated with inferior progression-free survival (PFS and overall survival (OS. However, there were no differences in PFS and OS between patients treated with higher and lower dose RT, which was confirmed in the multivariate survival analysis. Furthermore, reduced dose RT did not affect local control rate. Most common RT-related side effects were grade 1/2 mucositis and dermatitis, and the incidence rate of grade 3 mucositis or dermatitis was lower in patients treated with reduced dose RT (9.7% vs 15.0% for mucositis, and 6.5% vs 17.7% for dermatitis. In conclusion, this study found that RT dose could be safely reduced without

  2. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

    Science.gov (United States)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. [Pathologic gambling].

    Science.gov (United States)

    Nespor, K

    1996-01-31

    The author presents a review on pathological gambling. Similarly as in other addictive diseases, early therapeutic intervention is important. The latter may include: 1: Evaluation of the problem 2. Recommendation that the subject should avoid places where the gambling is pursued. He should not have larger financial sums on him. 3. Recommendations pertaining to lifestyle and prevention of excessive stress. 4. Handling of printed material (the author mentions the text issued to his patients). In the paper therapeutic procedures are described, incl. the author's experience such as the foundation of the group of Gamblers anonymous. Prevention is also considered. It is important that gambling should be less readily available and the demand for it should be smaller.

  4. Next-Generation Pathology.

    Science.gov (United States)

    Caie, Peter D; Harrison, David J

    2016-01-01

    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  5. Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other’s body parts

    Science.gov (United States)

    Fossataro, C.; Gindri, P.; Mezzanato, T.; Pia, L.; Garbarini, F.

    2016-01-01

    Do conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person’s hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients’ intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients’ affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body. PMID:27292285

  6. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Kim, Jin C.; Ha, Ye J.; Roh, Seon A.; Cho, Dong H.; Choi, Eun Y.; Kim, Tae W.; Kim, Jong H.; Kang, Tae W.; Kim, Seon Y.; Kim, Yong S.

    2013-01-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts

  7. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Ye J. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Chan W. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Park, Jong L.; Kim, Seon Y. [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun K. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

  8. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    International Nuclear Information System (INIS)

    Ha, Ye J.; Kim, Chan W.; Roh, Seon A.; Cho, Dong H.; Park, Jong L.; Kim, Seon Y.; Kim, Jong H.; Choi, Eun K.; Kim, Yong S.; Kim, Jin C.

    2015-01-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types

  9. SU-C-207B-06: Comparison of Registration Methods for Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Riyahi, S; Choi, W; Bhooshan, N; Tan, S; Zhang, H; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States)

    2016-06-15

    Purpose: To compare linear and deformable registration methods for evaluation of tumor response to Chemoradiation therapy (CRT) in patients with esophageal cancer. Methods: Linear and multi-resolution BSpline deformable registration were performed on Pre-Post-CRT CT/PET images of 20 patients with esophageal cancer. For both registration methods, we registered CT using Mean Square Error (MSE) metric, however to register PET we used transformation obtained using Mutual Information (MI) from the same CT due to being multi-modality. Similarity of Warped-CT/PET was quantitatively evaluated using Normalized Mutual Information and plausibility of DF was assessed using inverse consistency Error. To evaluate tumor response four groups of tumor features were examined: (1) Conventional PET/CT e.g. SUV, diameter (2) Clinical parameters e.g. TNM stage, histology (3)spatial-temporal PET features that describe intensity, texture and geometry of tumor (4)all features combined. Dominant features were identified using 10-fold cross-validation and Support Vector Machine (SVM) was deployed for tumor response prediction while the accuracy was evaluated by ROC Area Under Curve (AUC). Results: Average and standard deviation of Normalized mutual information for deformable registration using MSE was 0.2±0.054 and for linear registration was 0.1±0.026, showing higher NMI for deformable registration. Likewise for MI metric, deformable registration had 0.13±0.035 comparing to linear counterpart with 0.12±0.037. Inverse consistency error for deformable registration for MSE metric was 4.65±2.49 and for linear was 1.32±2.3 showing smaller value for linear registration. The same conclusion was obtained for MI in terms of inverse consistency error. AUC for both linear and deformable registration was 1 showing no absolute difference in terms of response evaluation. Conclusion: Deformable registration showed better NMI comparing to linear registration, however inverse consistency of

  10. Pathogenesis and pathology of shoulder ulcerations in sows with special reference to peripheral nerves and behavioural responses to palpation

    DEFF Research Database (Denmark)

    Dahl-Pedersen, Kirstin; Bonde, Marianne Kjær; Herskin, Mette S.

    2013-01-01

    Shoulder ulcerations are common in breeding sows in production systems but the consequences for the animals in terms of pain or discomfort are not well-described. This study presents data from a histopathological examination of shoulders of sows, specially focusing on the peripheral nerves...... the lesions have healed. This is further supported by the behavioural finding that rubbing behaviour in response to palpation was increased on the day of sample collection of the shoulders in sows with traumatic neuromas but without shoulder ulcers (P=0.053). Further studies are needed for final confirmation...

  11. Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Choi, Noah C.; Fischman, Alan J.; Niemierko, Andrzej; Ryu, Jin-Sook; Lynch, Thomas; Wain, John; Wright, Cameron; Fidias, Panos; Mathisen, Douglas

    2002-01-01

    MRglc was measured in each separately. The tumor histologic types included squamous cell carcinoma (n=9), adenocarcinoma (n=13), large cell carcinoma (n=6), and poorly differentiated carcinoma (n=2). The extent of the primary and nodal disease was as follows: Stage IIB (T3N0M0), Pancoast tumor (n=2); Stage IIIA, T2-T3N2M0 (n=18); Stage IIIB: T1-T3N3M0 (n=5) and T4N0M0 (n=2); a second lesion, T1 (n=1); and localized stump recurrence (n=2). A pathologically complete response was obtained in 14 (47%) of the 30 lesions. The remaining 16 lesions had residual cancer. The mean baseline value of the maximal MRglc was 0.333 ± 0.087 μmol/min/g (n=16), and it was reduced to 0.0957 ± 0.059 μmol/min/g 2 weeks after chemoradiotherapy (p=0.011). The correlation between residual MRglc and pTCP was made using an increment value of 0.02 μmol/min/g between the maximal and minimal values of MRglc. A pathologically complete response was obtained in 6 of 6 patients with residual MRglc of ≤0.050 μmol/min/g, 3 of 4 with ≤0.070, 4 of 7 with ≤0.090, 0 of 4 with ≤0.110, 1 of 3 with ≤0.130, and 0 of 6 with ≥0.130 μmol/min/g. The fitted logistic model showed that residual MRglc corresponding to pTCP 50% and pTCP ≥95% was 0.076 and ≤0.040 μmol/min/g, respectively. Conclusion: The correlation between the gradient of residual MRglc after chemoradiotherapy and pTCP is an inverse dose-response relationship. Residual MRglc of 0.076 and ≤0.040 μmol/min/g, representing pTCP 50% and pTCP ≥95%, respectively, may be useful surrogate markers for the tumor response to radiotherapy or chemoradiotherapy in lung cancer

  12. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...

  13. Oligoclonal CD8+ T-cell expansion in patients with chronic hepatitis C is associated with liver pathology and poor response to interferon-alpha therapy.

    Science.gov (United States)

    Manfras, Burkhard J; Weidenbach, Hans; Beckh, Karl-Heinz; Kern, Peter; Möller, Peter; Adler, Guido; Mertens, Thomas; Boehm, Bernhard O

    2004-05-01

    The role of CD8(+) T lymphocytes in chronic hepatitis C virus (HCV) infection and in liver injury with subsequent development of fibrosis and cirrhosis is poorly understood. To address this question, we performed a follow-up study including 27 chronically HCV-infected individuals. We determined clonality and phenotypes of circulating CD8(+) T cells employing TCRBV spectratyping. Antigen specificity was tested by rMHC-peptide tetramer staining and stimulation with recombinant HCV antigens. In addition, T-cell clonality and phenotypes were followed during the variable clinical response of interferon- (IFN) alpha treatment. We could demonstrate that CD8(+) T-cell expansions were significantly associated with liver fibrosis and cirrhosis. Likewise, increased oligoclonality of circulating CD8(+) T cells in chronic HCV infection was identified as an indicator for poor clinical response to IFN-alpha therapy. Moreover, we also found that IFN-alpha therapy enhanced the differentiation of CD8(+) T cells towards a late differentiation phenotype (CD28(-) CD57(+)). In cases of virus elimination the disappearance of expanded terminally differentiated CD8(+) cells was observed. Thus, this study identifies an association of clonal expansions of circulating CD8(+) T cells with liver pathology and provides a possible explanation for the fact that response to IFN-alpha therapy diminishes with the duration of infection.

  14. Effects of Handling and Crowding on the Stress Response and Viability of Chinook Salmon Parr and Smolts, 1984 Completion Report.

    Energy Technology Data Exchange (ETDEWEB)

    Congleton, James L.

    1985-02-01

    Transportation of migrating chinook salmon smolts from Snake River dams to the Columbia River estuary has not reversed a downward trend in Idaho stocks of this species that first became apparent in the late 1960s. Poor survival of transported smolts may be a consequence of physiological responses to stressful events during collection and transportation. This study was undertaken to evaluate the intensity of stress responses in transported smolts, to determine if stress responses decrease the viability of transported smolts, and to investigate ways of avoiding or mitigating stressful events during transportation. 34 refs., 58 figs., 13 tabs.

  15. [Eosinophilic esophagitis, a pathology on the rise].

    Science.gov (United States)

    Miranda García, M; Gutiérrez Teira, B

    2013-10-01

    The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesofágico, gastroenteritis eosinofílica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinofílico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  16. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

    Science.gov (United States)

    Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

    2013-11-01

    We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival

  17. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal 18F-FDG PET Features, Clinical Parameters, and Demographics

    International Nuclear Information System (INIS)

    Zhang, Hao; Tan, Shan; Chen, Wengen; Kligerman, Seth; Kim, Grace; D'Souza, Warren D.; Suntharalingam, Mohan; Lu, Wei

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV] max , tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than

  18. The value of {sup 18}F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Rossum, Peter S.N. van [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States); University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Fried, David V.; Zhang, Lifei; Court, Laurence E. [The University of Texas MD Anderson Cancer Center, Department of Radiation Physics, Houston, TX (United States); Hofstetter, Wayne L. [The University of Texas MD Anderson Cancer Center, Department of Thoracic and Cardiovascular Surgery, Houston, TX (United States); Ho, Linus [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Meijer, Gert J. [University Medical Center Utrecht, Department of Radiation Oncology, Utrecht (Netherlands); Carter, Brett W. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lin, Steven H. [The University of Texas MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX (United States)

    2017-01-15

    The purpose of our study was to determine the value of {sup 18}F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, {sup 18}F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV{sub max}, SUV{sub mean}, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). {sup 18}F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early {sup 18}F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  19. The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Rossum, Peter S.N. van; Fried, David V.; Zhang, Lifei; Court, Laurence E.; Hofstetter, Wayne L.; Ho, Linus; Meijer, Gert J.; Carter, Brett W.; Lin, Steven H.

    2017-01-01

    The purpose of our study was to determine the value of 18 F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18 F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV max , SUV mean , metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). 18 F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18 F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders. (orig.)

  20. Pathologic Response, When Increased by Longer Interval, Is a Marker but Not the Cause of Good Prognosis in Rectal Cancer: 17-year Follow-up of the Lyon R90-01 Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Cotte, Eddy, E-mail: eddy.cotte@chu-lyon.fr [Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite (France); Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins (France); Passot, Guillaume [Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite (France); Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins (France); Decullier, Evelyne; Maurice, Christelle [Hospices Civils de Lyon, Pôle IMER, Lyon (France); Glehen, Olivier; François, Yves [Department of Digestive Surgery, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite (France); Lyon 1 University, EMR 3738, Lyon-Sud/Charles Mérieux Medical University, Oullins (France); Lorchel, Fabrice; Chapet, Olivier [Department of Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite (France); Gerard, Jean-Pierre [Department of Radiotherapy, Centre Antoine-Lacassagne, University Nice-Sophia, Nice (France)

    2016-03-01

    Purpose: The Lyon R90-01 randomized trial investigated whether the interval between preoperative radiation therapy and surgery influenced rectal cancer outcome. Long-term results are reported here after a median follow-up of 17 years. Methods and Materials: Between February 1991 and December 1995, 210 patients from 29 French centers were randomly assigned (ratio of 1:1) to groups that waited either 2 weeks (short interval [SI]) or 6 to 8 weeks (long interval [LI]) between neoadjuvant radiation therapy and surgery. The primary endpoint was sphincter-preserving surgery. Results: LI group showed a better pathologic response (complete response or few residual cells) after radiation therapy than the SI group (26% vs 10.3%, P=.015). A better pathologic response was associated in multivariate analysis with significant improvement of overall survival (pT: P=.0293 and pN: P=.0048) but it was irrespective of the interval duration. The median follow-up was 17.2 years. The 5-, 10-, 15-, and 17-year overall survival rates were, respectively, 66.8%, 48.7%, 40.0%, and 34.0% for the SI group and, respectively, 67.1%, 53.5%, 41.9%, and 34.0% for the LI group. There were no significant differences between groups in terms of survival (P=.7656) or local recurrence rates (SI: 14.4% vs LI: 12.1%, respectively; P=.6202). Of 24 local disease recurrences, 20 (83%) occurred during the first 2 postoperative years, and all but one (96%) occurred during the first 5 postoperative years. The rate of second new malignancies was 9.4% (19 patients). Conclusions: The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the sterilization rate has no impact on survival. Radiation therapy did not postpone local recurrence, because the rate of local relapse after 5 years was low. Radiation-induced cancers after radiation therapy were unusual and should not influence

  1. Complete electric dipole response in 120Sn and 208Pb and implications for neutron skin and symmetry energy

    International Nuclear Information System (INIS)

    Von Neumann-Cosel, Peter

    2015-01-01

    Polarized proton scattering at energies of a few 100 MeV and very forward angles including 0° has been established as a new tool to extract the complete E1 strength distribution in nuclei for excitation energies between about 5 and 20 MeV. A case study of 208 Pb demonstrates excellent agreement with other electromagnetic probes. From the information on the B(E1) strength one can derive the electric dipole dipole polarizability, which is strongly correlated to the neutron skin and to parameters of the symmetry energy. Recently, we have extracted the polarizability of 120 Sn with a comparable precision. The combination of both results further constrains the symmetry energy parameters and presents a challenge for mean-field models, since relativistic and many Skyrme parameterizations cannot reproduce both experimental results simultaneously. (paper)

  2. Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

    Science.gov (United States)

    Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

    2013-06-01

    Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at presponse rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  3. Sequential Therapy with Nivolumab Followed by Ipilimumab Induces Complete Response in Metastatic Melanoma of the Lung but with Severe Hepatotoxicities

    Directory of Open Access Journals (Sweden)

    Sadanori Furudate

    2016-10-01

    Full Text Available Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30–40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks, but with severe liver dysfunction.

  4. Enhancement of immune response induced by DNA vaccine cocktail expressing complete LACK and TSA genes against Leishmania major.

    Science.gov (United States)

    Ghaffarifar, Fatemeh; Jorjani, Ogholniaz; Sharifi, Zohreh; Dalimi, Abdolhossein; Hassan, Zuhair M; Tabatabaie, Fatemeh; Khoshzaban, Fariba; Hezarjaribi, Hajar Ziaei

    2013-04-01

    Leishmaniasis is an important disease in humans. Leishmania homologue of receptor for Activated C Kinase (LACK) and thiol specific antioxidant (TSA) as immuno-dominant antigens of Leishmania major are considered the most promising molecules for a DNA vaccine. We constructed a DNA cocktail, containing plasmids encoding LACK and TSA genes of Leishmania major and evaluated the immune response and survival rate in BALB/c mice. IgG and Interferon gamma values were noticeably increased in the immunized group with DNA cocktail vaccine, which were significantly higher than those in the single-gene vaccinated and control groups (p 0.05). The immunized mice with the cocktail DNA vaccine presented a considerable reduction in diameter of lesion compared to other groups and a significant difference was observed (p < 0.05) in this regard. The survival time of the immunized mice with the cocktail DNA vaccine was significantly higher than that in the other groups (p < 0.05) after their being challenged with Leishmania major. The findings of this study indicated that the cocktail DNA vaccine increased the cellular response and survival rate and induced protection against infection with Leishmania in the mice. © 2012 The Authors © 2012 APMIS.

  5. A complete Holocene record of trematode-bivalve infection and implications for the response of parasitism to climate change.

    Science.gov (United States)

    Huntley, John Warren; Fürsich, Franz T; Alberti, Matthias; Hethke, Manja; Liu, Chunlian

    2014-12-23

    Increasing global temperature and sea-level rise have led to concern about expansions in the distribution and prevalence of complex-lifecycle parasites (CLPs). Indeed, numerous environmental variables can influence the infectivity and reproductive output of many pathogens. Digenean trematodes are CLPs with intermediate invertebrate and definitive vertebrate hosts. Global warming and sea level rise may affect these hosts to varying degrees, and the effect of increasing temperature on parasite prevalence has proven to be nonlinear and difficult to predict. Projecting the response of parasites to anthropogenic climate change is vital for human health, and a longer term perspective (10(4) y) offered by the subfossil record is necessary to complement the experimental and historical approaches of shorter temporal duration (10(-1) to 10(3) y). We demonstrate, using a high-resolution 9,600-y record of trematode parasite traces in bivalve hosts from the Holocene Pearl River Delta, that prevalence was significantly higher during the earliest stages of sea level rise, significantly lower during the maximum transgression, and statistically indistinguishable in the other stages of sea-level rise and delta progradation. This stratigraphic paleobiological pattern represents the only long-term high-resolution record of pathogen response to global change, is consistent with fossil and recent data from other marine basins, and is instructive regarding the future of disease. We predict an increase in trematode prevalence concurrent with anthropogenic warming and marine transgression, with negative implications for estuarine macrobenthos, marine fisheries, and human health.

  6. Curriculum Guidelines for Pathology and Oral Pathology.

    Science.gov (United States)

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  7. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report

    Directory of Open Access Journals (Sweden)

    Lincer Robert

    2010-10-01

    Full Text Available Abstract Background Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. Case presentation A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2 on day 1 and 8 every 21 days as well as daily erlotinib (100 mg. After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. Conclusion This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

  8. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report

    International Nuclear Information System (INIS)

    Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

    2010-01-01

    Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status

  9. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report.

    Science.gov (United States)

    Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

    2010-10-20

    Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

  10. Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Zhang, Qiang [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Nguyen-Tan, Phuc Felix [Centre Hospitalier de l' Universite de Montreal-Notre Dame, Montréal, Québec (Canada); Rosenthal, David I. [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Soulieres, Denis [Centre Hospitalier de l' Universite de Montreal-Notre Dame, Montréal, Québec (Canada); Fortin, André [L Hotel-Dieu de Quebec, Québec City, Québec (Canada); Silverman, Craig L. [The James Brown Cancer Center–University of Louisville, Louisville, Kentucky (United States); Daly, Megan E. [University of California Davis Medical Center, Sacramento, California (United States); Ridge, John A. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Hammond, J. Alexander [London Regional Cancer Program, London, Ontario (Canada); Le, Quynh-Thu [Stanford University Medical Center, Stanford, California (United States)

    2016-10-01

    Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.

  11. Science to Practice: Killing Dormant Cells-Is Targeting Autophagy the Key to Complete Tumor Response in Transarterial Chemoembolization?

    Science.gov (United States)

    Savic, Lynn Jeanette; Chapiro, Julius; Geschwind, Jean-François

    2017-06-01

    In this issue of Radiology, Gade et al ( 1 ) describe a unique mechanism of hepatocellular carcinoma (HCC) cells for surviving ischemia induced by transarterial embolization (TAE)/transarterial chemoembolization (TACE) in a state of cell cycle arrest-a function that may serve as a defensive shield against conventional chemotherapeutic agents. This finding adds to our knowledge and establishes a previously poorly understood mechanism of chemoresistance in HCC. As the Achilles heel in terms of this process, a concurrent upregulation of autophagic flux as an adaptive response to TAE-like ischemia was found by the authors. This is a targetable mechanism that can potentially be exploited for combined therapeutic approaches of embolotherapy and autophagy inhibition in HCC.

  12. Changes in alcohol policies and practices in bars and restaurants after completion of manager-focused responsible service training.

    Science.gov (United States)

    Lenk, Kathleen M; Erickson, Darin J; Nelson, Toben F; Horvath, Keith J; Nederhoff, Dawn M; Hunt, Shanda L; Ecklund, Alexandra M; Toomey, Traci L

    2018-03-01

    Irresponsible and illegal serving practices at bars and restaurants, such as sales to obviously intoxicated patrons, can lead to various public health harms. Training managers of bars and restaurants in the development and promotion of responsible alcohol policies may help prevent risky and illegal alcohol serving practices. We implemented a training program for managers of bars/restaurants designed to establish and promote responsible beverage service policies/practices. The program included online and in-person components. Bars/restaurants were randomised to intervention (n = 171) and control (n = 163) groups. To assess changes in policies/practices, we surveyed managers prior to and at 1 and 6 months post-training. Logistic regression models assessed changes in policies/practices across time points. The proportion in the intervention group that had written alcohol policies increased from 62% to 95% by 6 months post-training while the control group increased from 65% to 79% (P managers in the intervention group reported they had communicated to their staff how to cut off intoxicated patrons, a significant increase from baseline (37%) and from the change observed in the control group (43%-56%). Prevalence of other policies/practices also increased post-training but differences between intervention and control groups were not statistically significant. Our training program appears to have led to implementation of some policies/practices. Additional studies are needed to determine how training can be combined with other strategies to further improve establishment policies and ultimately reduce alcohol-related harms. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  13. Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript

    Directory of Open Access Journals (Sweden)

    Marianna Greco

    2013-01-01

    Full Text Available Chronic myeloid leukemia (CML with the rare fusion gene e19a2, encoding a p230 protein, has been described in patients with typical or rather aggressive clinical course. Although tyrosine kinase inhibitors (TKIs induce a substantial cytogenetic and molecular response in all phases of CML, a minority of p230 positive patients have been treated with TKIs. We report two cases of CML patients carrying the p230 transcript, who achieved fast and deep complete molecular response (CMR after frontline treatment with nilotinib. Our results suggest the use of nilotinib as frontline agent for the treatment of this CML variant.

  14. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

    2008-02-01

    This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

  15. Metabolic response 4 years after gastric bypass in a complete cohort with type 2 diabetes mellitus.

    Science.gov (United States)

    Carranza-Leon, B Gisella; Puzziferri, Nancy; Adams-Huet, Beverley; Jabbour, Ibrahim; Lingvay, Ildiko

    2018-03-01

    To evaluate the long-term remission rates of type 2 diabetes mellitus and associated comorbidities after gastric bypass surgery in a complete cohort, in a real-life clinic setting. A retrospective study of all consecutive patients with type 2 diabetes mellitus who underwent gastric bypass at a Veterans Affairs Medical Center from 2003 to 2010. The main outcome was remission of type 2 diabetes mellitus defined as HbA1c diabetic medication usage. Secondary outcomes were remission of hypertension and hyperlipidemia, weight loss, and long-term complications four years post-gastric bypass. Eighty-four patients with type 2 diabetes mellitus underwent gastric bypass. Four-year follow-up data were available for 92% (77/84) of patients. The patients (73% male; mean age 54 years) had a mean body mass index of 49 kg/m 2  ± 8.3. Hypertension and hyperlipidemia prevalence were 92% and 85%, respectively. The mean total body weight decrease over four years was 35 kg ± 21. Remission of type 2 diabetes mellitus occurred in 15% at 6 months and 49% four years after surgery. Diabetes remission was more likely (OR 3.2; 95% confidence interval 1.2-9.7) in patients not using insulin at baseline. Remission rates were 12% (9/74) for hypertension and 16% (11/68) for hyperlipidemia. Long-term surgical complications included reoperation (11%), incisional hernia (10%) and anastomotic ulcer (10%). Forty-four percent of patients had one or more nutritional complications. The metabolic effects of gastric bypass are significant and durable for at least four years, even in a predominantly male cohort and real-life clinical setting. Published by Elsevier B.V.

  16. Tumor infiltrating BRAFV600E-specific CD4 T cells correlated with complete clinical response in melanoma. | Office of Cancer Genomics

    Science.gov (United States)

    T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL).

  17. A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Matsuno Yoritaka

    2012-07-01

    Full Text Available Abstract Background Complete remission from advanced-stage synchronous double primary (SDP esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP. Case presentation The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment. Conclusion These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

  18. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N. A. T.; Smit, V. T. H. B. M.; Kessels, L.; van Bochove, A.; van Laarhoven, H. W.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van Leeuwen-Stok, A. E.; van der Hoeven, J. J. M.; van de Velde, C. J. H.; Nortier, J. W. R.; Kroep, J. R.

    2016-01-01

    Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the

  19. Regulator of G protein signaling 6 is a critical mediator of both reward-related behavioral and pathological responses to alcohol.

    Science.gov (United States)

    Stewart, Adele; Maity, Biswanath; Anderegg, Simon P; Allamargot, Chantal; Yang, Jianqi; Fisher, Rory A

    2015-02-17

    Alcohol is the most commonly abused drug worldwide, and chronic alcohol consumption is a major etiological factor in the development of multiple pathological sequelae, including alcoholic cardiomyopathy and hepatic cirrhosis. Here, we identify regulator of G protein signaling 6 (RGS6) as a critical regulator of both alcohol-seeking behaviors and the associated cardiac and hepatic morbidities through two mechanistically divergent signaling actions. RGS6(-/-) mice consume less alcohol when given free access and are less susceptible to alcohol-induced reward and withdrawal. Antagonism of GABA(B) receptors or dopamine D2 receptors partially reversed the reduction in alcohol consumption in RGS6(-/-) animals. Strikingly, dopamine transporter inhibition completely restored alcohol seeking in mice lacking RGS6. RGS6 deficiency was associated with alterations in the expression of genes controlling dopamine (DA) homeostasis and a reduction in DA levels in the striatum. Taken together, these data implicate RGS6 as an essential regulator of DA bioavailability. RGS6 deficiency also provided dramatic protection against cardiac hypertrophy and fibrosis, hepatic steatosis, and gastrointestinal barrier dysfunction and endotoxemia when mice were forced to consume alcohol. Although RGS proteins canonically function as G-protein regulators, RGS6-dependent, alcohol-mediated toxicity in the heart, liver, and gastrointestinal tract involves the ability of RGS6 to promote reactive oxygen species-dependent apoptosis, an action independent of its G-protein regulatory capacity. We propose that inhibition of RGS6 might represent a viable means to reduce alcohol cravings and withdrawal in human patients, while simultaneously protecting the heart and liver from further damage upon relapse.

  20. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

    Science.gov (United States)

    Wyluda, Edward J; Cheng, Jihua; Schell, Todd D; Haley, Jeremy S; Mallon, Carol; Neves, Rogerio I; Robertson, Gavin; Sivik, Jeffrey; Mackley, Heath; Talamo, Giampaolo; Drabick, Joseph J

    2015-01-01

    We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on

  1. Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses

    International Nuclear Information System (INIS)

    Gzyl, Jaroslaw; Bolesta, Elizabeth; Wierzbicki, Andrew; Kmieciak, Dariusz; Naito, Toshio; Honda, Mitsuo; Komuro, Katsutoshi; Kaneko, Yutaro; Kozbor, Danuta

    2004-01-01

    Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140 89.6 -derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (ΔV1/V2) region elicited increased levels of cross-reactive CD8 + T cell responses. Mice immunized with the mV2/mV3 or ΔV1/V2/mV3 gp140 89.6 plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and ΔV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein

  2. [Pathological gambling: risk factors].

    Science.gov (United States)

    Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

    2011-09-01

    In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

  3. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B

    2011-01-01

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  4. Cue-induced craving in pathological buying: empirical evidence and clinical implications.

    Science.gov (United States)

    Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

    2014-01-01

    Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

  5. Assessment of abdominal muscle function in individuals with motor-complete spinal cord injury above T6 in response to transcranial magnetic stimulation.

    Science.gov (United States)

    Bjerkefors, Anna; Squair, Jordan W; Chua, Romeo; Lam, Tania; Chen, Zhen; Carpenter, Mark G

    2015-02-01

    To use transcranial magnetic stimulation and electromyography to assess the potential for preserved function in the abdominal muscles in individuals classified with motor-complete spinal cord injury above T6. Five individuals with spinal cord injury (C5-T3) and 5 able-bodied individuals. Transcranial magnetic stimulation was delivered over the abdominal region of primary motor cortex during resting and sub-maximal (or attempted) contractions. Surface electromyography was used to record motor-evoked potentials as well as maximal voluntary (or attempted) contractions in the abdominal muscles and the diaphragm. Responses to transcranial magnetic stimulation in the abdominal muscles occurred in all spinal cord injury subjects. Latencies of muscle response onsets were similar in both groups; however, peak-to-peak amplitudes were smaller in the spinal cord injury group. During maximal voluntary (or attempted) contractions all spinal cord injury subjects were able to elicit electromyography activity above resting levels in more than one abdominal muscle across tasks. Individuals with motor-complete spinal cord injury above T6 were able to activate abdominal muscles in response to transcranial magnetic stimulation and during maximal voluntary (or attempted) contractions. The activation was induced directly through corticospinal pathways, and not indirectly by stretch reflex activations of the diaphragm. Transcranial magnetic stimulation and electromyography measurements provide a useful method to assess motor preservation of abdominal muscles in persons with spinal cord injury.

  6. Evaluation of the fate and pathological response in the lung and pleura of brake dust alone and in combination with added chrysotile compared to crocidolite asbestos following short-term inhalation exposure.

    Science.gov (United States)

    Bernstein, D M; Rogers, R A; Sepulveda, R; Kunzendorf, P; Bellmann, B; Ernst, H; Creutzenberg, O; Phillips, J I

    2015-02-15

    This study was designed to provide an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake dust following short term exposure in rats. The deposition, translocation and pathological response of brake-dust derived from brake pads manufactured with chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos. Rats were exposed by inhalation 6h/day for 5 days to either brake-dust obtained by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile and the brake-dust or crocidolite asbestos. The chrysotile fibers were relatively biosoluble whereas the crocidolite asbestos fibers persisted through the life-time of the animal. This was reflected in the lung and the pleura where no significant pathological response was observed at any time point in the brake dust or chrysotile/brake dust exposure groups through 365 days post exposure. In contrast, crocidolite asbestos produced a rapid inflammatory response in the lung parenchyma and the pleura, inducing a significant increase in fibrotic response in both of these compartments. Crocidolite fibers were observed embedded in the diaphragm with activated mesothelial cells immediately after cessation of exposure. While no chrysotile fibers were found in the mediastinal lymph nodes, crocidolite fibers of up to 35 μm were observed. These results provide support that brake-dust derived from chrysotile containing brake drums would not initiate a pathological response in the lung or the pleural cavity following short term inhalation. Copyright © 2014. Published by Elsevier Inc.

  7. {sup 18}F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Crippa, Flavio; Padovano, Barbara; Alessi, Alessandra; Bombardieri, Emilio; Pascali, Claudio; Bogni, Anna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Nuclear Medicine Unit; Agresti, Roberto; Maugeri, Ilaria; Rampa, Mario; Martelli, Gabriele [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Breast Surgery Unit; Sandri, Marco [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Molecular Targeting Unit; Mariani, Gabriella; Bianchi, Giulia; De Braud, Filippo [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Medical Oncology Unit; Carcangiu, Maria Luisa [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Pathology Unit; Trecate, Giovanna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Radiology-RMI Unit

    2015-05-01

    We evaluated whether {sup 18}F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. At baseline, median of maximum standardized uptake values (SUV{sub max}) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUV{sub max} and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUV{sub max}in the primary tumour (∇SUVT{sub max}(t{sub 1})) and axillary nodes (∇SUVN{sub max}(t{sub 1})) after the first NCT cycle showed that the power of ∇SUVT{sub max}(t{sub 1}) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∇SUVN{sub max}(t{sub 1}) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVT{sub max}(t{sub 1}) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVT{sub max}(t{sub 1}) and ΔSUVN{sub max}(t{sub 1}) parameters is proposed. The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population

  8. Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

    Science.gov (United States)

    Livraghi, Tito; Ceriani, R; Palmisano, A; Pedicini, V; Pich, M G; Tommasini, M A; Torzilli, G

    2011-02-01

    Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

  9. Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.

    Science.gov (United States)

    Amoroso, Loredana; Erminio, Giovanni; Makin, Guy; Pearson, Andrew D J; Brock, Penelope; Valteau-Couanet, Dominique; Castel, Victoria; Pasquet, Marlène; Laureys, Genevieve; Thomas, Caroline; Luksch, Roberto; Ladenstein, Ruth; Haupt, Riccardo; Garaventa, Alberto

    2018-01-01

    Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([ 123 I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m 2 /day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m 2 , and doxorubicin, 45 mg/m 2 . Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

  10. BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy.

    Science.gov (United States)

    Henríquez-Hernández, Luis Alberto; Lloret, Marta; Pinar, Beatriz; Bordón, Elisa; Rey, Agustín; Lubrano, Amina; Lara, Pedro Carlos

    2011-09-01

    To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect. Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (PMVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

    Science.gov (United States)

    Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

    2016-01-01

    The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  12. Pathology Assistant (C - Gamechanger Of Pathology Diagnostic

    Directory of Open Access Journals (Sweden)

    Asel Kudaybergenova

    2016-06-01

    When the competition ended, we received many favor- able reviews and we decided to start another project a little bit similar to the competition. Every month we show three interesting and difficult to diagnose cases provided by the leading Russian pathologists. The participants can look through the clinical data and digitized histological slides, and then discuss what they see among their professional society. There are 400  specialists  from  post  USSR countries.  Moreover, we get a few proposal of partnership to start a similar project in EU. And the last product in line is Pathology Assistant. It is a game changer. Pathology Assistant is a Digital Pathology©technology driven application for pathology diagnostics, tool to innovate pathology diagnostics in more simple, proven by analytical algo- rithm, automatically delivering anticipated support way. The service provides vast and structured database of validated cases, intuitive interface, fast and convenient system of analytical search. Pathology Assistant will streamline and simplify pathologist’s way to the right decision. Pathologists from Memorial Sloan Catering and biggest EU labs are working on preparing the con- tent for the project.  

  13. Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial

    International Nuclear Information System (INIS)

    Gregor, A.; Cull, A.; Stephens, R.J.; Girling, D.J.; Machin, D.; Kirkpatrick, J.A.; Yarnold, J.R.; Macbeth, F.R.; Stout, R.

    1997-01-01

    Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment of 6 months and 1 year, butt no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI. (author)

  14. Communication skills in diagnostic pathology.

    Science.gov (United States)

    Lehr, Hans-Anton; Bosman, Fred T

    2016-01-01

    Communication is an essential element of good medical practice also in pathology. In contrast to technical or diagnostic skills, communication skills are not easy to define, teach, or assess. Rules almost do not exist. In this paper, which has a rather personal character and cannot be taken as a set of guidelines, important aspects of communication in pathology are explored. This includes what should be communicated to the pathologist on the pathology request form, communication between pathologists during internal (interpathologist) consultation, communication around frozen section diagnoses, modalities of communication of a final diagnosis, with whom and how critical and unexpected findings should be communicated, (in-)adequate routes of communication for pathology diagnoses, who will (or might) receive pathology reports, and what should be communicated and how in case of an error or a technical problem. An earlier more formal description of what the responsibilities are of a pathologist as communicator and as collaborator in a medical team is added in separate tables. The intention of the paper is to stimulate reflection and discussion rather than to formulate strict rules.

  15. A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

    Directory of Open Access Journals (Sweden)

    Geoffrey Shouse

    2018-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

  16. High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy

    Directory of Open Access Journals (Sweden)

    Lorenzo Falchi

    2016-11-01

    Full Text Available Abstract Options for patients with relapsed or refractory (R/R classical Hodgkin lymphoma (cHL after brentuximab vedotin (Bv and autologous stem cell transplantation (ASCT are limited. Immune checkpoint inhibitors (ICI are active in this population but rarely induce complete response (CR. Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8 or nivolumab (n = 2. Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78% achieved CR, one partial response, and one reduction of tumor burden. All five patients who had received 5-azacitidine prior to ICI achieved CR, while only two of four who did not receive prior 5-azacitidine achieved CR. At a median follow-up of 9.9 months [0.5–14.3], eight patients are alive and five are still receiving treatment. We documented an unprecedented CR rate after ICI in patients with R/R cHL. We hypothesize that hypomethylating agents might have an immune priming effect and enhance the efficacy of ICI.

  17. Fifteen different {sup 18}F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Maffione, Anna Margherita [Santa Maria della Misericordia Hospital, Nuclear Medicine Department, PET Unit, Rovigo (Italy); Santa Maria della Misericordia Hospital, SOC Medicina Nucleare, Rovigo (Italy); Ferretti, Alice [Santa Maria della Misericordia Hospital, Nuclear Medicine Department, PET Unit, Rovigo (Italy); Santa Maria della Misericordia Hospital, Medical Physics Department, Rovigo (Italy); Grassetto, Gaia; Chondrogiannis, Sotirios; Marzola, Maria Cristina; Rampin, Lucia; Bondesan, Claudia; Rubello, Domenico [Santa Maria della Misericordia Hospital, Nuclear Medicine Department, PET Unit, Rovigo (Italy); Bellan, Elena; Gava, Marcello [Santa Maria della Misericordia Hospital, Medical Physics Department, Rovigo (Italy); Capirci, Carlo [Santa Maria della Misericordia Hospital, Radiotherapy Department, Rovigo (Italy); Colletti, Patrick M. [University of Southern California, Department of Radiology, Los Angeles, CA (United States)

    2013-06-15

    The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). SUVmax MTV and TLG after CRT, RI, {Delta}MTV% and {Delta}TLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm{sup 3}, 23.4 cm{sup 3}, 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG. (orig.)

  18. Rotator cuff pathology

    International Nuclear Information System (INIS)

    Pigeau, I.; Doursounian, L.; Maigne, J.Y.; Guinet, C.; Meary, E.; Buy, J.N.; Touzard, R.C.; Vadrot, D.; Laval-Jeantet, M.

    1989-01-01

    Fifteen volunteers and 73 patients with suspected rotator cuff lesions were examined at 0.5 T with T2 * -weighted gradient-echo (GE) MR imaging (700/33/30 degrees) (oblique coronal and sagittal 3 mm thick, surface coil). Results were compared with those of arthrography (all cases), T1-weighted GE imaging (400/20/90 degrees) (35 cases), surgery (28 cases), and T2-weighted spin-echo (SE) images (2,000/60-120) (17 cases). GE images demonstrated all tears (complete, 32, partial, 12) and was superior to arthrography in determining site and size and in displaying muscles (critical point in surgical planning). In 20 cases without tears on arthrography, GE imaging demonstrated five cases of tendinitis, five cases of bursitis, and six probable intratendinous or superficial partial tears. T2 * -weighted GE imaging was superior to T2-weighted SE and T1-weighted GE imaging, with higher fluid contrast and a low fat signal. Therefore, it might replace arthrography in the diagnosis and surgical approach to this pathology

  19. Eating pathology among Black and White smokers.

    Science.gov (United States)

    Sánchez-Johnsen, Lisa A P; Fitzgibbon, Marian L; Ahluwalia, Jasjit S; Spring, Bonnie J

    2005-02-01

    Among White smokers, many females use smoking as a weight control strategy. Little is known about the relationship between eating pathology and smoking among Black females, and whether smokers who enroll in treatment differ in eating pathology from smokers who decline treatment. We examined eating pathology among Black and White smokers who enrolled in a smoking cessation treatment and those who declined treatment. Participants were 100 Black and 100 White female smokers (ages 18-65) who completed three measures of eating pathology. After controlling for BMI, Whites reported greater levels of overall eating pathology than Blacks [F(1,195)=4.1; pWhite than Black smokers. However, once females seek smoking cessation treatment, these ethnic differences are not apparent.

  20. Pathology in Greece.

    Science.gov (United States)

    Sakellariou, S; Patsouris, E

    2015-11-01

    Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

  1. Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

    Science.gov (United States)

    Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

    2013-08-01

    Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

  2. On the Measure and Mismeasure of Narcissism: A Response to "Measures of Narcissism and Their Relations to DSM-5 Pathological Traits: A Critical Reappraisal".

    Science.gov (United States)

    Wright, Aidan G C

    2016-02-01

    Narcissism continues to suffer from a lack of consensual definition. Variability in the definition is reflected in the growing multitude of measures with oftentimes diverging nomological nets. Although the themes of narcissistic grandiosity and vulnerability appear to have achieved reasonable agreement on their central importance, the lower order structure of each is not well understood and debates remain about how (and whether) they can be integrated into a coherent whole. However, it is clear that a narrow focus on higher order grandiosity without consideration of concomitant vulnerability neglects clinically important features of narcissism. Occasioned by the potential for a new personality disorder model in the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition, several colleagues and I demonstrated that pathological narcissism, as measured by the Pathological Narcissism Inventory, could not be adequately summarized by the lower order traits of Grandiosity and Attention Seeking, and argued that this should be reflected in the diagnostic manual in some form. Miller, Lynam, and Campbell then subjected these same data to critical reanalysis and interpretation. I respond here to several points raised by Miller and colleagues. In so doing, I highlight areas of agreement, disagreement, and suggest directions for future research. © The Author(s) 2015.

  3. Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Hu Wei-xu

    2016-01-01

    Full Text Available This study aims to determine whether the combined blockade of IL-1β and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1 the AR model group treated with intranasal saline; (2 the 0.1% nonspecific IgY treatment group; (3 the 0.1% anti-TNF-α IgY treatment group; (4 the 0.1% anti-IL-1β IgY treatment group; (5 the 0.1% combined anti-IL-1β and TNF-α IgY treatment group; and (6 the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright’s staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P<0.05, and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P<0.05 in the combined 0.1% anti-IL-1β- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1β and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

  4. Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.

    Science.gov (United States)

    Wei-Xu, Hu; Wen-Yun, Zhou; Xi-Ling, Zhu; Zhu, Wen; Li-Hua, Wu; Xiao-Mu, Wu; Hui-Ping, Wei; Wen-Ding, Wang; Dan, He; Qin, Xiang; Guo-Zhu, Hu

    2016-01-01

    This study aims to determine whether the combined blockade of IL-1β and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1β IgY treatment group; (5) the 0.1% combined anti-IL-1β and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P guinea pigs. The data suggest that topical blockade of IL-1β and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.

  5. Two cases of cervical disc disease with intramedullary pathological changes, which are responsible for their neurological syndromes, on delayed CT myelography

    International Nuclear Information System (INIS)

    Isu, Toyohiko; Iwasaki, Yoshinobu; Abe, Hiroshi; Tashiro, Kunio; Murai, Hiroshi; Miyasaka, Kazuo

    1987-01-01

    We report two cases of cervical disc disease with myelopathy classified as of motor system syndrome type showing small contrast accumulation within the spinal cord on delayed CT myelography. In our two cases, high density spots on delayed CT myelography were bilaterally localized within the spinal cord, and believed represent pathological changes of the spinal cord, such as collection of microcavities or cystic necrosis. In case 1, the high density areas seemed to be localized in the anterior horn and corticospinal tract, and in case 2, they seemed to be localized in the corticospinal tract. The patient in case 1 produced signs and symptoms resembling motor neurone disease and lesion could not be differentiated from the latter. Delayed CT myelography showed that the cause of the upper limb amyotrophy was attributed to an anterior horn disorder and that of pyramidal tract sign to a corticospinal tract disorder. Therefore, we could differentiate the lesion from motor neurone disease on delayed CT myelography in case 1. In conclusion, we emphasize that delayed CT myelography can demonstrate the intramedullary pathological changes in the cervical disc disease and is useful in distinguishing between cervical disc disease simulating motor neurone disease and the latter. (author)

  6. Maximizing the Benefit-Cost Ratio of Anthracyclines in Metastatic Breast Cancer: Case Report of a Patient with a Complete Response to High-Dose Doxorubicin

    Directory of Open Access Journals (Sweden)

    Kevin Shee

    2016-12-01

    Full Text Available Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2– mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit.

  7. Mechanism of propylene oxidation over bismuth molybdate revealed by transient response method--1. An intermediate in the complete oxidation of C/sub 3/H/sub 6/

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, M.; Futaya, R.

    1979-01-01

    An intermediate in the complete oxidation of C/sub 3/H/sub 6/ and its nature were deduced from transient response studies of a flow reactor system with a 1:1 bismuth-molybdenum catalyst at temperatures below ordinary operating temperatures. The formation of a stable surface intermediate with a non-allylic structure resembling that of propylene on every site of the catalyst surface occurred at 310/sup 0/C in the presence of propylene/oxygen or acrolein/oxygen; under oxidative conditions at 310/sup 0/C about eight times more intermediate formed directly from propylene than from adsorbed acrolein. The intermediate reacted with weakly adsorbed oxygen from the gas phase, but not with lattice oxygen, to decompose into CO/sub 2/; in temperature programed desorption studies (2.3/sup 0/C/min) it desorbed as CO/sub 2/ into a stream of helium above 220/sup 0/C (peak at 420/sup 0/C), apparently by reaction with oxygen diffused from the bulk to the surface.

  8. Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

    Science.gov (United States)

    Arteche-López, A; Kreutzman, A; Alegre, A; Sanz Martín, P; Aguado, B; González-Pardo, M; Espiño, M; Villar, L M; García Belmonte, D; de la Cámara, R; Muñoz-Calleja, C

    2017-06-01

    The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 + T-cells was lower in patients, whereas an increment in the percentage of CD4 + and CD8 + effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

  9. Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

    Science.gov (United States)

    Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

    2018-01-01

    No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

  10. Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

    Directory of Open Access Journals (Sweden)

    Fumito Kuranishi

    2018-01-01

    Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

  11. The accuracy of {sup 18}F-FDG PET/CT in predicting the pathological response to neoadjuvant chemotherapy in patients with breast cancer. A meta-analysis and systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Fangfang; Shen, Guohua; Diao, Wei; Jia, Zhiyun [West China Hospital of Sichuan University, Department of Nuclear Medicine, Chengdu, Sichuan (China); Deng, Yunfu [West China Hospital of Sichuan University, Department of Oncology, Chengdu (China)

    2017-11-15

    The aim of this meta-analysis was to evaluate the accuracy of {sup 18}F-FDG PET/CT in predicting the pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. PubMed, Embase, the Cochrane Library (Central), and the Web of Science (SCI-Expanded) were systematically searched to identify pertinent studies. The methodologic quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2. The Spearman correlation coefficient was used to explore the existence of a threshold effect. Heterogeneity was assessed by the likelihood ratio I {sup 2} index. The pooled values calculated with a mixed-effects model for the sensitivity, specificity and diagnostic odds ratio with 95% confidence intervals were 81.9% (76.0-86.6%), 79.3% (72.1-85.1%) and 17.35 (10.98-27.42), respectively. {sup 18}F-FDG PET/CT has a moderate accuracy in predicting the pathological response during the early process of NAC in breast cancer patients. To increase the role of {sup 18}F-FDG PET/CT in monitoring the therapy response, future prospective studies are needed to explore how chemotherapy regimens and different subtypes affect the levels of glucose metabolism. (orig.)

  12. Complete Histological Resolution of Collagenous Sprue

    Directory of Open Access Journals (Sweden)

    Hugh J Freeman

    2004-01-01

    Full Text Available A 65-year-old woman developed a watery diarrhea syndrome with collagenous colitis. Later, weight loss and hypoalbuminemia were documented. This prompted small bowel biopsies that showed pathological changes of collagenous sprue. An apparent treatment response to a gluten-free diet and prednisone resulted in reduced diarrhea, weight gain and normalization of serum albumin. Later repeated biopsies from multiple small and large bowel sites over a period of over three years, however, showed reversion to normal small intestinal mucosa but persistent collagenous colitis. These results indicate that collagenous inflammatory disease may be a far more extensive process in the gastrointestinal tract than is currently appreciated. Moreover, collagenous colitis may be a clinical signal that occult small intestinal disease is present. Finally, collagenous sprue may, in some instances, be a completely reversible small intestinal disorder.

  13. Patterns of Response After Preoperative Treatment in Gastric Cancer

    International Nuclear Information System (INIS)

    Diaz-Gonzalez, Juan A.; Rodriguez, Javier; Hernandez-Lizoain, Jose L.; Ciervide, Raquel; Gaztanaga, Miren; San Miguel, Inigo; Arbea, Leire; Aristu, J. Javier; Chopitea, Ana; Martinez-Regueira, Fernando; Valenti, Victor; Garcia-Foncillas, Jesus; Martinez-Monge, Rafael; Sola, Jesus J.

    2011-01-01

    Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

  14. Radiographic pathology for technologists

    International Nuclear Information System (INIS)

    Mace, J.D.; Kowalczyk, N.

    1988-01-01

    This book explains the fundamentals of disease mechanisms and relates this to the practice of radiologic science. Each chapter begins with a discussion of normal anatomy and physiology, then covers pathology and demonstrates how the pathology appears on film. Imaging modalities such as computed tomography, MRI, and ultrasound are also discussed. Clinical case studies are included

  15. Pathology annual. Part 2

    International Nuclear Information System (INIS)

    Rosen, P.P.

    1987-01-01

    This book contains 11 selections. Some of the titles are: Applications of in situ DNA hybridization technology to diagnostic surgical pathology; Neoplasms associated with immune deficiencies; Chronic gastritis: The pathologists's role; Necrosis in lymph nodes; Pathologic changes of osteochondrodysplasia in infancy: A review; and Immunoglobulin light chain nephropathies

  16. Impaired decisional impulsivity in pathological videogamers.

    Directory of Open Access Journals (Sweden)

    Michael A Irvine

    Full Text Available Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice, and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task. We used stringent diagnostic criteria highlighting functional impairment.In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management.

  17. Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

    Science.gov (United States)

    Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

    2017-11-01

    To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

  18. Simple measurements on diffusion-weighted MR imaging for assessment of complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Pei-Qiang; Wu, Yao-Pan; Xie, Chuan-Miao; Wu, Pei-Hong [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Imaging and Interventional Radiology, Guangzhou (China); An, Xin [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Oncology, Guangzhou (China); Qiu, Xue; Kong, Ling-Heng; Liu, Guo-Chen; Pan, Zhi-Zhong; Ding, Pei-Rong [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Colorectal Surgery, Guangzhou (China)

    2014-11-15

    To determine diagnostic performance of simple measurements on diffusion-weighted MR imaging (DWI) for assessment of complete tumour response (CR) after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by signal intensity (SI) and apparent diffusion coefficient (ADC) measurements. Sixty-five patients with LARC who underwent neoadjuvant CRT and subsequent surgery were included. Patients underwent pre-CRT and post-CRT 3.0 T MRI. Regions of interest of the highest brightness SI were included in the tumour volume on post-CRT DWI to calculate the SI{sub lesion}, rSI, ADC{sub lesion} and rADC; diagnostic performance was compared by using the receiver operating characteristic (ROC) curves. In order to validate the accuracy and reproducibility of the current strategy, the same procedure was reproduced in 80 patients with LARC at 1.5 T MRI. Areas under the ROC curve for identification of a CR, based on SI{sub lesion}, rSI, ADC{sub lesion}, and rADC, respectively, were 0.86, 0.94, 0.66, and 0.71 at 3.0 T MRI, and 0.92, 0.91, 0.64, and 0.61 at 1.5 T MRI. Post-CRT DWI SI{sub lesion} and rSI provided high diagnostic performance in assessing CR and were significantly more accurate than ADC{sub lesion}, and rADC at 3.0 T MRI and 1.5 T MRI. (orig.)

  19. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    International Nuclear Information System (INIS)

    Habr-Gama, Angelita; Gama-Rodrigues, Joaquim; São Julião, Guilherme P.; Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B.; Perez, Rodrigo O.

    2014-01-01

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation

  20. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    Energy Technology Data Exchange (ETDEWEB)

    Habr-Gama, Angelita, E-mail: gamange@uol.com.br [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); Gama-Rodrigues, Joaquim [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); São Julião, Guilherme P. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Colorectal Surgery Division, University of São Paulo School of Medicine, São Paulo (Brazil); Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Perez, Rodrigo O. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Ludwig Institute for Cancer Research, São Paulo Branch (Brazil)

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  1. Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumors

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Nielsen, Jens N; Lindebjerg, Jan

    2007-01-01

    ) followed by total mesorectal excision eight weeks after treatment. Pathologic response was evaluated according to the tumor regression grade system. RESULTS: Thirty percent (18/60) of patients presented with complete pathologic response. Patients with thymidylate synthase genotype 2/2 had a significantly...

  2. Your Pathology Report

    Science.gov (United States)

    ... Pathology Tests Breast Cancer News February 20, 2013 Star-gazing software helps fight breast cancer See More ... Phone: (855) 807-6386 email Facebook Twitter Instagram YouTube Contact Us Privacy Policy Site Credits Terms of ...

  3. Stem Cell Pathology.

    Science.gov (United States)

    Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

    2018-01-24

    Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

  4. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging.

    Science.gov (United States)

    Curvo-Semedo, Luís; Lambregts, Doenja M J; Maas, Monique; Thywissen, Thomas; Mehsen, Rana T; Lammering, Guido; Beets, Geerard L; Caseiro-Alves, Filipe; Beets-Tan, Regina G H

    2011-09-01

    To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry. A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry. Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements. Post-CRT DW MR

  5. Pathology of pulmonary aspergillomas

    OpenAIRE

    Shah Rajeev; Vaideeswar Pradeep; Pandit Shobhana

    2008-01-01

    Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patien...

  6. Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

    Science.gov (United States)

    Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

    2017-03-01

    - Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

  7. Radiological, pathological and DNA remission in recurrent metastatic nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Chan Anthony TC

    2006-10-01

    Full Text Available Abstract Background Circulating plasma Epstein Barr Virus DNA (EBV-DNA is a sensitive and specific marker of nasopharyngeal carcinoma (NPC. The mainstay of treatment of metastatic NPC is systemic chemotherapy and resection for solitary metastasis. Despite high response rate to chemotherapy, complete remission is uncommonly seen. Case Presentation We report a case of recurrent metastatic NPC in a 43-year-old man, who achieved complete remission three times with chemotherapy and surgery. Serial plasma EBV-DNA levels were measured during the course of disease. The patient had three episodes of recurrences of NPC manifested as distant metastasis. Both time, rise in the plasma EBV-DNA level preceded detection of recurrences by imaging. Following systemic chemotherapy, he achieved complete remission each time, of which was confirmed by 18-flourodeoxyglucose positron emission tomography and hepatectomy pathology. The plasma EBV-DNA level dropped to zero copy/ml at the time of each remission. Conclusion This case highlights the high chemosensitivity of NPC by illustrating a rare occurrence of complete response of metastatic NPC to chemotherapy. This case also underscores the usefulness of EBV-DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response.

  8. [Adolescent pathological gambling].

    Science.gov (United States)

    Petit, A; Karila, L; Lejoyeux, M

    2015-05-01

    Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Pathologic conditions in pregnancy

    International Nuclear Information System (INIS)

    Beomonte Zobel, B.; Tella, S.; Innacoli, M.; D'Archivio, C.; Cardone, G.; Masciocchi, C.; Gallucci, M.; Passariello, R.; Cappa, F.

    1991-01-01

    Soma authors suggested that MR imaging could rapresent an effective diagnostic alternative in the study of pathologic conditions of mother and fetus during pregnancy. To verify the actual role of MR imaging, we examined 20 patients in the 2nd and 3rd trimester of gestation, after a preliminary US examination. Fifteen patients presented fetal or placental pathologies; in 4 patients the onset of the pathologic condition occurred during pregnancy; in 1 case of US diagnosis of fetal ascites, MR findings were nornal and the newborn was healty. As for placental pathologies, our series included a case of placental cyst, two hematomas between placenta and uterine wall, and two cases of partial placenta previa. As for fetal malformation, we evaluated a case of omphalocele, one of Prune-Belly syndrome, a case of femoral asimmetry, one of thanatophoric dwarfism, a case of thoracopagus twins with cardiovascular abnormalities, two fetal hydrocephali, and three cases of pyelo-ureteral stenosis. As for maternal pathologies during pregnancy, we observed a case of subserous uterine fibromyoma, one of of right hydronephrosis, one of protrusion of lumbar invertebral disk, and a large ovarian cyst. In our experience, MR imaging exhibited high sensitivity and a large field of view, which were both useful in the investigation of the different conditions occurring during pregnancy. In the evaluation of fetal and placental abnormalities, especially during the 3rd trimester, the diagnostic yieldof MR imaging suggested it as a complementary technique to US for the evaluation of fetal malformation and of intrauterine growth retardation

  10. Completion of treatment planning

    International Nuclear Information System (INIS)

    Lief, Eugene

    2008-01-01

    The outline of the lecture included the following topics: entering prescription; plan printout; print and transfer DDR; segment BEV; export to R and V; physician approval; and second check. Considerable attention, analysis and discussion. The summary is as follows: Treatment planning completion is a very responsible process which requires maximum attention; Should be independently checked by the planner, physicist, radiation oncologist and a therapist; Should not be done in a last minute rush; Proper communication between team members; Properly set procedure should prevent propagation of an error by one individual to the treatment: the error should be caught by somebody else. (P.A.)

  11. Audit in forensic pathology.

    Science.gov (United States)

    Burke, M P; Opeskin, K

    2000-09-01

    Autopsy numbers in Australian hospitals have declined markedly during the past decade despite evidence of a relatively static rate of demonstrable clinical misdiagnosis during this time. The reason for this decrease in autopsy numbers is multifactorial and may include a general lack of clinical and pathologic interest in the autopsy with a possible decline in autopsy standard, a lack of clinicopathologic correlation after autopsies, and an increased emphasis on surgical biopsy reporting within hospital pathology departments. Although forensic autopsies are currently maintaining their numbers, it is incumbent on forensic pathologists to demonstrate the wealth of important information a carefully performed postmortem examination can reveal. To this end, the Pathology Division of the Victorian Institute of Forensic Medicine has instituted a program of minimum standards in varied types of coroner cases and commenced a system of internal and external audit. The minimum standard for a routine, sudden, presumed natural death is presented and the audit system is discussed.

  12. Interleukin-21 receptor deficiency increases the initial toll-like receptor 2 response but protects against joint pathology by reducing Th1 and Th17 cells during streptococcal cell wall arthritis.

    Science.gov (United States)

    Marijnissen, Renoud J; Roeleveld, Debbie M; Young, Deborah; Nickerson-Nutter, Cheryl; Abdollahi-Roodsaz, Shahla; Garcia de Aquino, Sabrina; van de Loo, Fons A J; van Spriel, Annemiek B; Boots, Annemieke M H; van den Berg, Wim B; Koenders, Marije I

    2014-04-01

    The cytokine interleukin-21 (IL-21) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL-21 in experimental arthritis in relation to Th17 cells. Antigen-induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL-21 receptor-deficient (IL-21R(-/-) ) and wild-type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers. During AIA and chronic SCW arthritis, IL-21R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen-specific T cell responses. Levels of IL-17 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL-17+ interferon-γ (IFNγ)-positive T cells were reduced in IL-21R(-/-) mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL-6 expression. Interestingly, IL-21R(-/-) mice were significantly less capable of up-regulating suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 messenger RNA. IL-21 stimulation also affected the Toll-like receptor 2 (TLR-2)/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL-21 signaling might contribute to the increased local activation during SCW arthritis. In contrast to the proinflammatory role of IL-21 in adaptive immunity, which drives IL-17+IFN+ cells and joint pathology during chronic experimental arthritis, IL-21 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS-1 and SOCS-3. If this dual role of IL-21 in various immune processes is present in human disease, it could make IL-21 a difficult therapeutic target in rheumatoid arthritis. Copyright © 2014 by the American

  13. A case report of locally advanced triple negative breast cancer showing pathological complete response to weekly paclitaxel with bevacizumab treatment following disease progression during anthracycline-based neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Hideo Shigematsu

    2017-01-01

    Conclusions: Although the addition of bevacizumab to standard adjuvant chemotherapy is not recommended in unselected triple negative breast cancer, the potent effect on tumor shrinkage should be considered in the treatment of locally advanced triple negative breast cancer showing disease progression during standard NAC.

  14. Disrupted sensory gating in pathological gambling.

    Science.gov (United States)

    Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

    2003-08-15

    Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

  15. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

    Science.gov (United States)

    Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

    2013-01-01

    An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may

  16. Dual Pathology of Mandible.

    Science.gov (United States)

    Rajurkar, Suday G; Deshpande, Mohan D; Kazi, Noaman; Jadhav, Dhanashree; Ranadive, Pallavi; Ingole, Snehal

    2017-01-01

    Aneurysmal Bone cyst (ABC)is a rare benign lesion of the bone which is infrequent in craniofacial region (12%). Rapid growth pattern causing bone expansion and facial asymmetry is a characteristic feature of ABC. Giant cell lesion is another distinct pathological entity. Here we present to you a rare case of dual pathology in an 11 year old female patient who presented with a large expansile lesion in the left hemimandible. All radiographic investigations were suggestive of ABC, aspiration of the lesion resulted in blood aspirate. However only after a histologic examination the dual nature of the lesion was revealed.

  17. Hip joint pathology

    DEFF Research Database (Denmark)

    Tijssen, M; van Cingel, R E H; de Visser, E

    2017-01-01

    The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18......-65 years) were included if they were referred to a physical therapist to gather pre-operative data and were then diagnosed during arthroscopy. Results of pre-operative patient history and physical tests were collected and compared to arthroscopy. Data of 77 active patients (mean age: 37 years) were...

  18. Otosclerosis: Temporal Bone Pathology.

    Science.gov (United States)

    Quesnel, Alicia M; Ishai, Reuven; McKenna, Michael J

    2018-04-01

    Otosclerosis is pathologically characterized by abnormal bony remodeling, which includes bone resorption, new bone deposition, and vascular proliferation in the temporal bone. Sensorineural hearing loss in otosclerosis is associated with extension of otosclerosis to the cochlear endosteum and deposition of collagen throughout the spiral ligament. Persistent or recurrent conductive hearing loss after stapedectomy has been associated with incomplete footplate fenestration, poor incus-prosthesis connection, and incus resorption in temporal bone specimens. Human temporal bone pathology has helped to define the role of computed tomography imaging for otosclerosis, confirming that computed tomography is highly sensitive for diagnosis, yet limited in assessing cochlear endosteal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. PLANT PATHOLOGY: a discipline at a crossroads.

    Science.gov (United States)

    Weinhold, A R

    1996-01-01

    The Department of Plant Pathology at the University of California at Berkeley was destroyed as a consequence of a contentious reorganization. The circumstances that led to the reorganization provide some insight into the challenges facing the discipline of plant pathology. The underlying basis for plant pathology as a science is to address problems of plant disease. This requires a balance between disciplinary and problem-solving research and a continuum from achieving fundamental advances in knowledge to the development and implementation of problem-solving approaches. Changes in colleges and universities have placed extreme stress on this essential structure. The dilemma that must be addressed is how to reestablish the problem-solving continuum where it has been broken and strengthen it where it has been weakened. Plants are essential for life, and they will always be affected by disease. The understanding and management of these diseases is the responsibility and the challenge of plant pathology today and in the future.

  20. Multislice ct in gut related pathologies

    International Nuclear Information System (INIS)

    Nadeem, A.; Shaukat, A.; Ahmad, M.W.; Amin, Y.

    2007-01-01

    The objective of this study is to evaluate the effectiveness of Multislice CT in Gut related pathologies. 50 consecutive patients, referred from surgical and medical departments, with gut pathology suspicion were scanned in this respect on Toshiba MSCT 4 slice Aquilion. Patients were. 100 ml iodinated non ionic IV contrast was given. Preferably water was used as oral contrast and oral iodinated contrast was used only in selective cases. As a result, 33 patients showed positive response and 17 were normal; 23 were females and 10 were males. We found following pathologies Acute Appendicitis 10, Diverticulitis 02, Inflammatory Bowel Disease 03, Small Bowel Obstruction 04, Malignant Gut masses 08, Omental Implants 05, Perforation (Duodenal) 01. It is thus concluded that MDCT has a definite role in gut pathologies especially when the ultrasound is negative. (author)

  1. Early Alzheimer's and Parkinson's disease pathology in urban children: Friend versus Foe responses--it is time to face the evidence.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael

    2013-01-01

    Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

  2. Food insecurity and eating disorder pathology.

    Science.gov (United States)

    Becker, Carolyn Black; Middlemass, Keesha; Taylor, Brigitte; Johnson, Clara; Gomez, Francesca

    2017-09-01

    The primary aim of this study was to investigate eating disorder (ED) pathology in those living with food insecurity. A secondary aim was to investigate whether any-reason dietary restraint, weight self-stigma, and worry increased as level of food insecurity increased. Participants (N = 503) seeking food from food pantries completed questionnaires assessing level of food insecurity, demographics, ED pathology, dietary restraint, weight self-stigma, and worry. Consistent with hypotheses, participants with the highest level of food insecurity (i.e., adults who reported having hungry children in their household) also endorsed significantly higher levels of binge eating, overall ED pathology, any-reason dietary restraint, weight self-stigma, and worry compared to participants with lower levels of food insecurity. Contrary to hypotheses, compensatory behaviors also increased as level of food insecurity worsened. Overall, 17% of those in the child hunger food insecurity group reported clinically significant ED pathology. This is the first study to assess the full spectrum of ED pathology in a low-income, marginalized population with food insecurity. Given that food insecurity is a global concern, results from this study suggest that greater attention to the association between ED pathology and food insecurity is warranted by researchers around the world. © 2017 Wiley Periodicals, Inc.

  3. Routine digital pathology workflow: The Catania experience

    Directory of Open Access Journals (Sweden)

    Filippo Fraggetta

    2017-01-01

    Full Text Available Introduction: Successful implementation of whole slide imaging (WSI for routine clinical practice has been accomplished in only a few pathology laboratories worldwide. We report the transition to an effective and complete digital surgical pathology workflow in the pathology laboratory at Cannizzaro Hospital in Catania, Italy. Methods: All (100% permanent histopathology glass slides were digitized at ×20 using Aperio AT2 scanners. Compatible stain and scanning slide racks were employed to streamline operations. eSlide Manager software was bidirectionally interfaced with the anatomic pathology laboratory information system. Virtual slide trays connected to the two-dimensional (2D barcode tracking system allowed pathologists to confirm that they were correctly assigned slides and that all tissues on these glass slides were scanned. Results: Over 115,000 glass slides were digitized with a scan fail rate of around 1%. Drying glass slides before scanning minimized them sticking to scanner racks. Implementation required introduction of a 2D barcode tracking system and modification of histology workflow processes. Conclusion: Our experience indicates that effective adoption of WSI for primary diagnostic use was more dependent on optimizing preimaging variables and integration with the laboratory information system than on information technology infrastructure and ensuring pathologist buy-in. Implementation of digital pathology for routine practice not only leveraged the benefits of digital imaging but also creates an opportunity for establishing standardization of workflow processes in the pathology laboratory.

  4. Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Shelley; Lerski, Richard [Ninewells Hospital and Medical School, Department of Medical Physics, Dundee (United Kingdom); Purdie, Colin [Ninewells Hospital and Medical School, Department of Pathology, Dundee (United Kingdom); Michie, Caroline [Ninewells Hospital and Medical School, Department of Oncology, Dundee (United Kingdom); Evans, Andrew; Vinnicombe, Sarah [University of Dundee, Division of Imaging and Technology, Ninewells Hospital and Medical School, Dundee (United Kingdom); Johnston, Marilyn [Ninewells Hospital and Medical School, Department of Clinical Radiology, Dundee (United Kingdom); Thompson, Alastair M. [University of Texas MD Anderson Cancer Centre, Department of Breast Surgical Oncology, Houston, TX (United States)

    2017-11-15

    To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. (orig.)

  5. Clinico-pathology, hematology and biochemistry responses in buffaloes towards Pasteurella multocida type B: 2 immunogen lypopolysaccharide via oral and intravenous routes of infection.

    Science.gov (United States)

    Chung, Eric Lim Teik; Abdullah, Faez Firdaus Jesse; Ibrahim, Hayder Hamzah; Marza, Ali Dhiaa; Zamri-Saad, Mohd; Haron, Abdul Wahid; Lila, Mohd Azmi Mohd; Norsidin, Mohd Jefri

    2016-02-01

    Haemorrhagic septicaemia is a disease caused by Pasteurella multocida serotype B: 2 and E: 2. The organism causes acute, highly fatal septicaemic disease with high morbidity and mortality in cattle and more susceptible in buffaloes. Lipopolysaccharide can be found on the outer cell wall of the organism. Lipopolysaccharide is released during multiplication which leads to inflammatory reaction. It represents the endotoxin of P. multocida type B: 2 and responsible for toxicity in haemorrhagic septicaemia which plays an important role in the pathogenesis of the disease. Therefore, the aim of this study was to investigate the clinical signs, blood parameters, gross post mortem lesions and histopathology changes caused by P. multocida type B:2 immunogen lipopolysaccharide infections initiated through intravenous and oral routes of infection. 9 buffalo heifers were divided equally into 3 treatment groups. Group 1 was inoculated orally with 10 ml of phosphate buffer saline (PBS); Group 2 and 3 were inoculated with 10 ml of lipopolysaccharide broth intravenously and orally respectively. For the clinical signs, there were significant differences (p hematology and biochemistry findings, there were significant differences (p 0.05) in the MCHC, leukocytes, band neutrophils, basophils, thrombocytes, plasma protein, icterus index, total protein, globulin and A:G ratio between intravenous and oral group. For Group 2 buffaloes, there were gross lesions in the lung, trachea, heart, liver, spleen, and kidney. In contrast, lesions were only observed in the lung, trachea and liver of Group 3 buffaloes. There were significant differences (p 0.05) in edema lesion between groups. In conclusion, this study is a proof that oral route infection of P. multocida type B:2 immunogen lipopolysaccharide can be used to stimulate host cell responses where oral vaccine through feed could be developed in the near future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  7. TC pathological Neck

    International Nuclear Information System (INIS)

    Garcia Fontes, M.

    2012-01-01

    This presentation is about different imaging techniques such as ultrasound, CT, RNM, PET-CT. These techniques permit to detect head and neck tumors, breast and digestive pathologies as well as congenital diseases and glandular tumor in the thyroid, parathyroid, muscles, lymphatic, nerves and vessels

  8. Pathological fractures in children

    Science.gov (United States)

    De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

    2012-01-01

    Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

  9. Forms of pathologization

    DEFF Research Database (Denmark)

    Brinkmann, Svend

    disorder, and similar figures are found for many other mental disorders. These figures are striking, but are hard to interpret. This presentation argues in favour of the pathologization thesis, which claims that it cannot be argued in a straightforward manner that we are simply more ill and disordered than...

  10. Endothelial Ca+-activated K+ channels in normal and impaired EDHF-dilator responses--relevance to cardiovascular pathologies and drug discovery.

    Science.gov (United States)

    Grgic, Ivica; Kaistha, Brajesh P; Hoyer, Joachim; Köhler, Ralf

    2009-06-01

    The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels (K(Ca)) has been suggested to play a critical role in initializing EDHF-dilator responses in conduit and resistance-sized arteries of many species including humans. Endothelial K(Ca) currents are mediated by the two K(Ca) subtypes, intermediate-conductance K(Ca) (KCa3.1) (also known as, a.k.a. IK(Ca)) and small-conductance K(Ca) type 3 (KCa2.3) (a.k.a. SK(Ca)). In this review, we summarize current knowledge about endothelial KCa3.1 and KCa2.3 channels, their molecular and pharmacological properties and their specific roles in endothelial function and, particularly, in the EDHF-dilator response. In addition we focus on recent experimental evidences derived from KCa3.1- and/or KCa2.3-deficient mice that exhibit severe defects in EDHF signalling and elevated blood pressures, thus highlighting the importance of the KCa3.1/KCa2.3-EDHF-dilator system for blood pressure control. Moreover, we outline differential and overlapping roles of KCa3.1 and KCa2.3 for EDHF signalling as well as for nitric oxide synthesis and discuss recent evidence for a heterogeneous (sub) cellular distribution of KCa3.1 (at endothelial projections towards the smooth muscle) and KCa2.3 (at inter-endothelial borders and caveolae), which may explain their distinct roles for endothelial function. Finally, we summarize the interrelations of altered KCa3.1/KCa2.3 and EDHF system impairments with cardiovascular disease states such as hypertension, diabetes, dyslipidemia and atherosclerosis and discuss the therapeutic potential of KCa3.1/KCa2.3 openers as novel types of blood pressure-lowering drugs.

  11. The effectiveness of annotated (vs. non-annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies.

    Science.gov (United States)

    Marsch, Amanda F; Espiritu, Baltazar; Groth, John; Hutchens, Kelli A

    2014-06-01

    With today's technology, paraffin-embedded, hematoxylin & eosin-stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images. The objective of this study was to compare the effectiveness of annotated digital pathology slides versus non-annotated digital pathology slides as a teaching tool during dermatology and pathology residencies. A study group composed of 31 dermatology and pathology residents was asked to complete an online pre-quiz consisting of 20 multiple choice style questions, each associated with a static digital pathology image. After completion, participants were given access to an online tutorial composed of digitally annotated pathology slides and subsequently asked to complete a post-quiz. A control group of 12 residents completed a non-annotated version of the tutorial. Nearly all participants in the study group improved their quiz score, with an average improvement of 17%, versus only 3% (P = 0.005) in the control group. These results support the notion that annotated digital pathology slides are superior to non-annotated slides for the purpose of resident education. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Pathology informatics fellowship training: Focus on molecular pathology

    Directory of Open Access Journals (Sweden)

    Diana Mandelker

    2014-01-01

    Full Text Available Background: Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Methods and Results: Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program′s core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. Conclusions: The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  13. Pathology informatics fellowship training: Focus on molecular pathology.

    Science.gov (United States)

    Mandelker, Diana; Lee, Roy E; Platt, Mia Y; Riedlinger, Gregory; Quinn, Andrew; Rao, Luigi K F; Klepeis, Veronica E; Mahowald, Michael; Lane, William J; Beckwith, Bruce A; Baron, Jason M; McClintock, David S; Kuo, Frank C; Lebo, Matthew S; Gilbertson, John R

    2014-01-01

    Pathology informatics is both emerging as a distinct subspecialty and simultaneously becoming deeply integrated within the breadth of pathology practice. As specialists, pathology informaticians need a broad skill set, including aptitude with information fundamentals, information systems, workflow and process, and governance and management. Currently, many of those seeking training in pathology informatics additionally choose training in a second subspecialty. Combining pathology informatics training with molecular pathology is a natural extension, as molecular pathology is a subspecialty with high potential for application of modern biomedical informatics techniques. Pathology informatics and molecular pathology fellows and faculty evaluated the current fellowship program's core curriculum topics and subtopics for relevance to molecular pathology. By focusing on the overlap between the two disciplines, a structured curriculum consisting of didactics, operational rotations, and research projects was developed for those fellows interested in both pathology informatics and molecular pathology. The scope of molecular diagnostics is expanding dramatically as technology advances and our understanding of disease extends to the genetic level. Here, we highlight many of the informatics challenges facing molecular pathology today, and outline specific informatics principles necessary for the training of future molecular pathologists.

  14. Completely continuous and weakly completely continuous abstract ...

    Indian Academy of Sciences (India)

    An algebra A is called right completely continuous (right weakly completely continuous) ... Moreover, some applications of these results in group algebras are .... A linear subspace S(G) of L1(G) is said to be a Segal algebra, if it satisfies the.

  15. Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response

    Directory of Open Access Journals (Sweden)

    Liise-anne Pirofski

    2017-12-01

    Full Text Available Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017, https://doi.org/10.1128/mBio.01415-17 that reports that CD4+ T cells mediate tissue damage in experimental murine cryptococcosis. This finding has fundamental implications for our understanding of the pathogenesis of cryptococcal disease; it helps explain why immunotherapy has been largely unsuccessful in treatment and provides insight into the paradoxical observation that HIV-associated cryptococcosis may have a better prognosis than cryptococcosis in those with no known immune impairment. The demonstration that host-mediated damage can drive cryptococcal disease provides proof of concept that the parabola put forth in the damage-response framework has the flexibility to depict complex and changing outcomes of host-microbe interaction.

  16. Muscular pathology: echographic and NMR imaging aspects

    International Nuclear Information System (INIS)

    Pascal-Suisse, P.; Beaurain, P.; Mougniot, C.

    1995-01-01

    A comparison of echographic techniques and NMR imaging has been done for the diagnosis of muscular trauma and tumor pathologies. In traumatic pathology, the echographic analysis allows to determine the complete assessment of recent muscular injuries. NMR imaging can be used in granuloma or fibrous callosity appreciation and for the analysis of deep injury (muscles and muscles-tendon junctions) and of muscular aponeurosis. Echography must be used together with color coding Doppler technique in the diagnosis of tumor pathology and for the study of slow fluxes. The recently available energy Doppler technique seems to be powerful in the study of vascularization of small expansive formations, but their extension to adjacent bone or tissue can only be appreciated using NMR imaging. (J.S.)

  17. Male breast pathology

    International Nuclear Information System (INIS)

    Puebla, C.; Sainz, J.M.; Pujala, M.; Villavieja, J.L.

    1998-01-01

    To review the specific radiological signs of male breast pathology observed in our center over the past five years, as well as the pertinent medical literature. A retrospective study was carried out of the 47 mammographic studies performed in 41 men. Oblique mediolateral and craniocaudal views were employed. The distribution of different types of male breast pathology among our patients was as follows: gynecomastia was detected in 30 cases (73.1%), pseudogynectomastia in 4 (9.7%), carcinoma in 3(7.3%), abscess in 2 (4.9%), lipoma in 1 (2.5%) and epidermoid cyst in the remaining patient (2.5%). The results obtained agree with those reported in the literature reviewed. The most significant findings were the low incidence of carcinoma and the high rate of gynecomastia. (Author) 26 refs

  18. Pathology of pulmonary aspergillomas.

    Science.gov (United States)

    Shah, Rajeev; Vaideeswar, Pradeep; Pandit, Shobhana P

    2008-01-01

    Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis (14.6%). Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis). Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.

  19. Pathology of pulmonary aspergillomas

    Directory of Open Access Journals (Sweden)

    Shah Rajeev

    2008-07-01

    Full Text Available Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%. Forty aspergillomas were complex, occurring in cavitatory lesions (82.9% or in bronchiectasis (14.6%. Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis. Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.

  20. Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

    Science.gov (United States)

    Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

    2015-11-01

    Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Contrasting population-level responses to Pleistocene climatic oscillations in an alpine bat revealed by complete mitochondrial genomes and evolutionary history inference

    DEFF Research Database (Denmark)

    Alberdi, Antton; Gilbert, M. Thomas P; Razgour, Orly

    2015-01-01

    Aim: We used an integrative approach to reconstruct the evolutionary history of the alpine long-eared bat, Plecotus macrobullaris, to test whether the variable effects of Pleistocene climatic oscillations across geographical regions led to contrasting population-level demographic histories within...... a single species. Location: The Western Palaearctic. Methods: We sequenced the complete mitochondrial genomes of 57 individuals from across the distribution of the species. The analysis integrated ecological niche modelling (ENM), approximate Bayesian computation (ABC), measures of genetic diversity...... and Bayesian phylogenetic methods. Results: We identified two deep lineages: a western lineage, restricted to the Pyrenees and the Alps, and an eastern lineage, which expanded across the mountain ranges east of the Dinarides (Croatia). ENM projections of past conditions predicted that climatic suitability...

  2. The long Tramp from Cellular Pathology to Molecular Pathology

    Directory of Open Access Journals (Sweden)

    Hans Guski

    2017-05-01

    Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

  3. Pathology in Undergraduate Training Program

    Directory of Open Access Journals (Sweden)

    Shiva Raj K.C.

    2018-04-01

    Full Text Available Pathology is a study of disease which deals with etiology, pathogenesis and morphological features and the associated clinical features. Pathology acts as a bridge that fills the gap between basic sciences and clinical medicine. With proper understanding of pathological processes, one can understand the disease process. In Nepal, since the beginning of medical school teaching, Pathology as a basic science discipline and is a component of the preclinical medical school curriculum.Pathology teaching in 19th century was vague, disorganized and very little, though precious. The lectures used to be conducted by surgeons. At Barts, surgeon Sir James Paget had taught surgical pathology. The real revolution in pathology teaching began in the early 1900s when, spurred on by increasing understanding of disease mechanisms, pathology began to be accepted as a specialty in its own right.During the early and mid of 20th century, pathology teaching was a part of clinical teaching with daily, autopsy demonstration. By the late 1980s, significant change had taken place. In many medical schools, debate started regarding relevance of vigorous preclinical teaching. Then system-based approach was incorporated and traditional preclinical course had been abandoned. With this pathology teaching also began to change with pathologists being involved in teaching histology, often alongside pathology to highlight its clinical relevance. In medical schools the pathology teaching time was cut. Autopsy demonstrations, which had been so popular with generations of medical students, were becoming irregular and less well attended.Though teaching of pathology in blocks to ‘avoid fragmentation’ has disappeared in western countries; it is still practice in Nepal. In western countries there was traditional practice of teaching general pathology in the first two years and systemic pathology in the clinical years. Now pathology teaching is integrated throughout the course. A

  4. Pathological Gambling among Italian Nursing Students.

    Science.gov (United States)

    Cicolini, Giancarlo; Della Pelle, Carlo; Simonetti, Valentina; Comparcini, Dania; Sepede, Gianna; Cipollone, Francesco

    2018-04-01

    To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students. Multicenter cross-sectional study. From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool. Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT scores were associated with higher SOGS scores. Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions. Nursing faculties should be aware of the prevalence of Gambling among students. Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A patologia da forma hépato-esplênica da esquistossomose mansoni em sua forma avançada (estudo de 232 necrópsias completas The pathology of the hepatosplenic form of schistosomiasis mansoni in its advanced form (study of 232 complete necropsies

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1983-09-01

    entendida em toda a sua extensão.This study includes an evaluation of pathological findings on 232 complete necropsies performed on subjects with advanced hepatic schistosomiasis in Salvador, Bahia, Brazil. The constant and characteristic feature was peri-portal hepatic fibrosis with destructive and obstructive vascular lesions of the intrahepatic branches of the portal vein. Usually the lesions were accomapained by signs of portal hypertension (splenomegaly and esophageal varices representing hepatosplenic schistosomiasis, but in 12 cases such signs were absent (advanced hepatic schistosomiasis. Some individuals progressed from a compensated to a decompensated form of hepatic schistosomiasis by showing progressive evidences of hepatic cell failure. In such cases the liver usually presented more intense septal fibrosis and changes of chronic active hepatitis, but not a transformation toward a diffuse cirrhosis. Spelonomegaly resulted from chronic passive congestion and cellular proliferation, specially of the phagocytic mononuclear system. Occasionally the enlarged spleen developed a peculiar nodular type of lymphoma. Intestinal involvement was less than expected. Only rarely some more prominent changes, such as peri-colonic and retroperitoneal fibrosis due to massive deposition of eggs, pseudo-neoplastic formations and polyps appeard. A frequent complication was cor pulmonale due to schistosomal pulmonary arteritis, which appeard in 44 cases (18,9%. Associated renal disease was found in 15% of the cases, usually represented by chronic diffuse glomerulonephritis, wich is presumed to represent a immune-complex manifestation of schistosomiasis. Concommitant infections were frequently observed, and some of them, such as salmonellosis and viral hepatitits, tended to run a rather prolonged course. Thus, advanced schistosomiasis appeard as a pathological process that damages mainly the liver, but that reaches various organs through a varied and complex pathogenesis, the

  6. Recent advances on glass-forming systems driven far from equilibrium. Special issue marking the completion of the Research Unit FOR 1394 `Nonlinear response to probe vitrification'

    Science.gov (United States)

    Fuchs, Matthias

    2017-08-01

    The nature of the glass transition is one of the frontier questions in Statistical Physics and Materials Science. Highly cooperative structural processes develop in glass-forming melts exhibiting relaxational dynamics which is spread out over many decades in time. While considerable progress has been made in recent decades towards understanding dynamical slowing-down in quiescent systems, the interplay of glassy dynamics with external fields reveals a wealth of novel phenomena yet to be explored. This special issue focuses on recent results obtained by the Research Unit FOR 1394 `Nonlinear response to probe vitrification' which was funded by the German Science Foundation (DFG). In the projects of the research unit, strong external fields were used in order to gain insights into the complex structural and transport phenomena at the glass transition under far-from-equilibrium conditions. This aimed inter alia to test theories of the glass transition developed for quiescent systems by pushing them beyond their original regime. Combining experimental, simulational, and theoretical efforts, the eight projects within the FOR 1394 measured and determined aspects of the nonlinear response of supercooled metallic, polymeric, and silica melts, of colloidal dispersions, and of ionic liquids. Applied fields included electric and mechanic fields, and forced active probing (`micro-rheology'), where a single probe is forced through the glass-forming host. Nonlinear stress-strain and force-velocity relations as well as nonlinear dielectric susceptibilities and conductivities were observed. While the physical manipulation of melts and glasses is interesting in its own right, especially technologically, the investigations performed by the FOR 1394 suggest to use the response to strong homogeneous and inhomogeneous fields as technique to explore on the microscopic level the cooperative mechanisms in dense melts of strongly interacting constituents. Questions considered concern the

  7. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P

    2000-01-01

    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  8. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, M. A.; Thom, M.; Ellison, D. W.; Wilkins, P.; Barnes, D.; Thompson, P. D.; Brown, P.

    2000-01-01

    OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  9. DE LEGE FERENDA PROPOSAL FOR THE COMPLETION OF THE LEGAL FRAMEWORK REGARDING THE TEXTILE PRODUCTS, IN THE CONTEXT OF A SOCIAL RESPONSIBLE MANAGEMENT

    Directory of Open Access Journals (Sweden)

    MUREȘAN (POȚINCU Laura

    2016-05-01

    Full Text Available In the case of this economic operator, manufacturing or trading textile products, the corporate social responsibility is a social must, and it consists of a set of objectives which must be implemented by the management of the economic operator in all departments. In order to understand the implications of a social responsibile management in the textile products domain, it is required to analise the juridical framework. Interesting is the choice in this area of the production and the marketing of textile products, to only adopt/use one regulation, not a directive or a legislative package consisting in a directive and a regulation. As a result of legal analysis performed, we support the maintenance of the use, as a legal instrument, of the European regulation type normative document, but we suggest the extension of the provisions of the European normative act and its transformation into a particular complex normative act, beyond the scope of the aspects concerning the labelling.

  10. Residency choices by graduating medical students: why not pathology?

    Science.gov (United States)

    Hung, Tawny; Jarvis-Selinger, Sandra; Ford, Jason C

    2011-06-01

    Pathology is an unpopular residency choice for medical students worldwide. In some countries, this has contributed to a crisis in pathologist human resources that has affected the quality of clinical laboratories. Several previous studies have used information from junior medical students and from residents to suggest ways of improving pathology recruitment. There are, however, no published studies of pathology residency choice that focus on the senior medical students who must be recruited. This study uses focus groups of senior medical students to explore both general and pathology-specific influences on residency choice. Several general influences are identified, including students' expectations for their future clinical practices, their own clinical rotation experiences, influences from other people including mentors, and their choice to reject certain fields. Several specific antipathology influences are also revealed, including negative stereotypes about pathologists, a perceived incompatibility of personality between most medical students (extroverted) and pathologists (introverted), and perceptions of pathologists as being in some ways nonmedical. The most important antipathology influence was that, from the students' perspective, pathology was utterly invisible in clinical practice. Most students did not consider and then reject a pathology residency: instead, pathology was completely ignored. Given the importance of clerkship electives in influencing medical student career choice, promoting clerkship experiences in pathology may improve recruitment. However, departments of pathology must first make pathology visible to students and teach them how pathologists contribute to clinical care. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction

    Directory of Open Access Journals (Sweden)

    Anna Paeschke

    2016-05-01

    Full Text Available Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ [type I, cT3cN+cM1 (hep, CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution.

  12. Pathology Gross Photography: The Beginning of Digital Pathology.

    Science.gov (United States)

    Rampy, B Alan; Glassy, Eric F

    2015-06-01

    The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Pathological gambling: An overview

    Directory of Open Access Journals (Sweden)

    Shalini Singh

    2017-01-01

    Full Text Available Gambling activities are popular as a form of recreation and have been a source of income for many people worldwide. Although gambling has been common across continents and time, and a subset of individuals experience problems with gambling. This review attempts to provide an overview of problem gambling for clinicians who are likely to encounter such patients in their practice. The review discusses the relevance, nosology, and epidemiology of gambling. We also discuss the associated comorbidities and principles of management of pathological gambling.

  14. [Apoptosis and pathological process].

    Science.gov (United States)

    Rami, Mukhammed Salim Iusef

    2007-01-01

    Apoptosis (programmed cell death) occurs normally for maitenance of tissue homeostasis and play an important role in morphogenesis, embriogenesis and tissue growth. On the other hand, apoptosis may be involved in different pathological processes such as malignancy, infectious diseases and autoimmune disorders. Apoptosis is regulated by various mediators. Caspases, death receptors, mitochondria, Bcl-2 protoncogenes and tumor supressor genes are considered to be the most important of them. Advance in apoptosis regulation research suggests enormouse facilities for therapy of wide range of human illnesses.

  15. Marketing the pathology practice.

    Science.gov (United States)

    Berkowitz, E N

    1995-07-01

    Effective marketing of the pathology practice is essential in the face of an increasingly competitive market. Successful marketing begins with a market-driven planning process. As opposed to the traditional planning process used in health care organizations, a market-driven approach is externally driven. Implementing a market-driven plan also requires recognition of the definition of the service. Each market to which pathologists direct their service defines the service differently. Recognition of these different service definitions and creation of a product to meet these needs could lead to competitive advantages in the marketplace.

  16. [Prevalence of pathological gambling in Lebanese students].

    Science.gov (United States)

    Etel, C; Tabchi, S; Bou Khalil, R; Hlais, S; Richa, S

    2013-02-01

    Pathological gambling is a behavioral dependency on hazard games that is classified, in the DSM-IV, among impulse control disorders. According to many studies, the international prevalence of pathological ranges between 2 and 6%. This disorder is often accompanied by a considerable impact on patients' life as well as on the life of people surrounding them. Adolescents and young adults are considered to be a population at risk to develop this kind of behavioral dependency. The problem of pathological gambling is one of the major problems from which the Lebanese population of university students in Lebanese society suffers. The prevalence of pathological gambling in the Lebanese population of university students is lacking from the contemporary medical literature. In our study, five of the biggest private universities in Lebanon (Notre-Dame University of Louaizé [NDU], Lebanese American University [LAU], American University of Beirut [AUB], Saint-Joseph University [USJ] and Holy Spirit University of Kaslik [USEK]) were surveyed. Each questionnaire was based essentially on the South Oaks Gambling Screen (SOGS). Four hundred and seventy-seven questionnaires were completed in these universities. Among the 477 students that completed the questionnaire, 5.87% appeared to be suffering from pathological gambling; 25.15% of responding students presented some problems related to gambling while the rest of them, corresponding to 68.92%, had no problems related to gambling. This is the first study of its kind conducted in the Lebanon. Its interest lies in that it offers an important evaluation of the prevalence of pathological gambling in the Lebanese population of university students. According to this study, the prevalence of pathological gambling in Lebanese university students is high. Prevention programs and sensitization strategies are needed in order to prevent the occurrence of this disorder in the Lebanese young. More studies are needed in this domain in order to

  17. Pathology of the vestibulocochlear nerve

    Energy Technology Data Exchange (ETDEWEB)

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

    2010-05-15

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  18. Pathology of the vestibulocochlear nerve

    International Nuclear Information System (INIS)

    De Foer, Bert; Kenis, Christoph; Van Melkebeke, Deborah; Vercruysse, Jean-Philippe; Somers, Thomas; Pouillon, Marc; Offeciers, Erwin; Casselman, Jan W.

    2010-01-01

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  19. Anesthesia and Tau Pathology

    Science.gov (United States)

    Whittington, Robert A.; Bretteville, Alexis; Dickler, Maya F.; Planel, Emmanuel

    2013-01-01

    Alzheimer’s disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. Recent reports suggest that general anesthetics may be such a factor and may contribute to the development and exacerbation of this neurodegenerative disorder. Intra-neuronal neurofibrillary tangles (NFT), composed of hyperphosphorylated and aggregated tau protein are one of the main neuropathological hallmarks of AD. Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration. PMID:23535147

  20. Evaluation of Complete Blood Count Indices (NLR, PLR, MPV/PLT, and PLCRi) in Healthy Dogs, Dogs With Periodontitis, and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response.

    Science.gov (United States)

    Rejec, Ana; Butinar, Janos; Gawor, Jerzy; Petelin, Milan

    2017-12-01

    The aim of the study was to retrospectively assess complete blood count (CBC) indices of dogs with periodontitis (PD; n = 73) and dogs with oropharyngeal tumors (OT; n = 92) in comparison to CBC indices of healthy dogs (HD; n = 71). Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet ratio, and platelet large cell ratio index (PLCRi) were evaluated as biomarkers of systemic inflammatory response provoked by PD and OT. Results of multivariable polytomous logistic regression analysis indicated no significant associations between CBC indices and PD. Both NLR and PLCRi were significantly higher in dogs with OT when compared to HD and dogs with PD and could, therefore, indicate a tumor-associated systemic inflammatory response. Additional studies of CBC indices, along with other biomarkers of systemic inflammatory response, are recommended to validate them as reliable indicators of clinical disease activity.

  1. Coronarography in pathologic morphology

    International Nuclear Information System (INIS)

    Rozenberg, V.D.; Nepomnyashchikh, L.M.; Borodin, Yu.I.

    1987-01-01

    Of many years experience of the authors and data in world literature on post mortal coronarography during the most important general pathological processes in heart have been generalized in the monograph. Problems of radioanatomy of coronary artery were considered and data on use of postmortal coronarography in terms of correlation together with selective in-life coronarography are given. Much place takes the description of main coronarography semiotics of obstructive atherosclerosis injuries of the heart coronal system, compensation and decompensation processes of broken coronary circulation. Results of coronarography investigations in geronitogenesis as well as in sudden death are presented. Electrocardiographic-coronarographic and pathomorphologic parallels, clinical-anatomical diagnostical symptomocomplex - syndrom of menocoronary ''robbing'' are elucidated in detail. Technology of different techniques of postmortal coronarography in order to investigate macro-, microhemocirculation heart bed are described in detail as well as techniques of coronarogramm analysis which permits to use the monograph as a manual

  2. Fetal Programming and Cardiovascular Pathology

    Science.gov (United States)

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  3. Fetal programming and cardiovascular pathology.

    Science.gov (United States)

    Alexander, Barbara T; Dasinger, John Henry; Intapad, Suttira

    2015-04-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption, or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes, and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology, and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress, and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. © 2015 American Physiological Society.

  4. Treatment of pathological gambling - integrative systemic model.

    Science.gov (United States)

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  5. Toxicologic Pathology: The Basic Building Block of Risk Assessment

    Science.gov (United States)

    Human health risk assessment is a critical factor in many risk management decisions. Evaluation of human health risk requires research the provides information that appropriately characterizes potential hazards from exposure. Pathology endpoints are the central response around ...

  6. The untapped potential of digital pathology in prostate cancer ...

    African Journals Online (AJOL)

    Xavier Farré

    2018-02-07

    Feb 7, 2018 ... prostate cancer diagnosis and medical education ... Discussion: Digital pathology platforms could offer new solutions to the diagnostic and ... Peer review under responsibility of Pan African Urological Surgeons' Association.

  7. Integrated Pathology Informatics Enables High-Quality Personalized and Precision Medicine: Digital Pathology and Beyond.

    Science.gov (United States)

    Volynskaya, Zoya; Chow, Hung; Evans, Andrew; Wolff, Alan; Lagmay-Traya, Cecilia; Asa, Sylvia L

    2018-03-01

    - The critical role of pathology in diagnosis, prognosis, and prediction demands high-quality subspecialty diagnostics that integrates information from multiple laboratories. - To identify key requirements and to establish a systematic approach to providing high-quality pathology in a health care system that is responsible for services across a large geographic area. - This report focuses on the development of a multisite pathology informatics platform to support high-quality surgical pathology and hematopathology using a sophisticated laboratory information system and whole slide imaging for histology and immunohistochemistry, integrated with ancillary tools, including electron microscopy, flow cytometry, cytogenetics, and molecular diagnostics. - These tools enable patients in numerous geographic locations access to a model of subspecialty pathology that allows reporting of every specimen by the right pathologist at the right time. The use of whole slide imaging for multidisciplinary case conferences enables better communication among members of patient care teams. The system encourages data collection using a discrete data synoptic reporting module, has implemented documentation of quality assurance activities, and allows workload measurement, providing examples of additional benefits that can be gained by this electronic approach to pathology. - This approach builds the foundation for accurate big data collection and high-quality personalized and precision medicine.

  8. Social cost of pathological gambling.

    Science.gov (United States)

    Ladouceur, R; Boisvert, J M; Pépin, M; Loranger, M; Sylvain, C

    1994-12-01

    Pathological gambling creates enormous problems for the afflicted individuals, their families, employers, and society, and has numerous disastrous financial consequences. The present study evaluates the financial burdens of pathological gambling by questioning pathological gamblers in treatment in Gamblers Anonymous (n=60; 56 males, 4 females; mean age = 40 years old) about personal debts, loss of productivity at work, illegal activities, medical costs and the presence of other dependencies. Results show that important debts, loss of productivity at work and legal problems are associated with pathological gambling. Discussion is formulated in terms of the social cost of adopting a liberal attitude toward the legalization of various gambling activities.

  9. Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

    Directory of Open Access Journals (Sweden)

    Masaaki Tsuji

    2017-01-01

    Full Text Available Myeloid blast crisis of chronic myeloid leukemia (CML-MBC is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML. We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

  10. Digital pathology access and usage in the UK: results from a national survey on behalf of the National Cancer Research Institute's CM-Path initiative.

    Science.gov (United States)

    Williams, Bethany Jill; Lee, Jessica; Oien, Karin A; Treanor, Darren

    2018-05-01

    To canvass the UK pathology community to ascertain current levels of digital pathology usage in clinical and academic histopathology departments, and prevalent attitudes to digital pathology. A 15-item survey was circulated to National Health Service and academic pathology departments across the UK using the SurveyMonkey online survey tool. Responses were sought at a departmental or institutional level. Where possible, departmental heads were approached and asked to complete the survey, or forward it to the most relevant individual in their department. Data were collected over a 6-month period from February to July 2017. 41 institutes from across the UK responded to the survey. 60% (23/39) of institutions had access to a digital pathology scanner, and 60% (24/40) had access to a digital pathology workstation. The most popular applications of digital pathology in current use were undergraduate and postgraduate teaching, research and quality assurance. Investigating the deployment of digital pathology in their department was identified as a high or highest priority by 58.5% of institutions, with improvements in efficiency, turnaround times, reporting times and collaboration in their institution anticipated by the respondents. Access to funding for initial hardware, software and staff outlay, pathologist training and guidance from the Royal College of Pathologists were identified as factors that could enable respondent institutions to increase their digital pathology usage. Interest in digital pathology adoption in the UK is high, with usage likely to increase in the coming years. In light of this, pathologists are seeking more guidance on safe usage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Digital pathology access and usage in the UK: results from a national survey on behalf of the National Cancer Research Institute’s CM-Path initiative

    Science.gov (United States)

    Williams, Bethany Jill; Lee, Jessica; Oien, Karin A; Treanor, Darren

    2018-01-01

    Aim To canvass the UK pathology community to ascertain current levels of digital pathology usage in clinical and academic histopathology departments, and prevalent attitudes to digital pathology. Methods A 15-item survey was circulated to National Health Service and academic pathology departments across the UK using the SurveyMonkey online survey tool. Responses were sought at a departmental or institutional level. Where possible, departmental heads were approached and asked to complete the survey, or forward it to the most relevant individual in their department. Data were collected over a 6-month period from February to July 2017. Results 41 institutes from across the UK responded to the survey. 60% (23/39) of institutions had access to a digital pathology scanner, and 60% (24/40) had access to a digital pathology workstation. The most popular applications of digital pathology in current use were undergraduate and postgraduate teaching, research and quality assurance. Investigating the deployment of digital pathology in their department was identified as a high or highest priority by 58.5% of institutions, with improvements in efficiency, turnaround times, reporting times and collaboration in their institution anticipated by the respondents. Access to funding for initial hardware, software and staff outlay, pathologist training and guidance from the Royal College of Pathologists were identified as factors that could enable respondent institutions to increase their digital pathology usage. Conclusion Interest in digital pathology adoption in the UK is high, with usage likely to increase in the coming years. In light of this, pathologists are seeking more guidance on safe usage. PMID:29317516

  12. Core components of a comprehensive quality assurance program in anatomic pathology.

    Science.gov (United States)

    Nakhleh, Raouf E

    2009-11-01

    In this article the core components of a comprehensive quality assurance and improvement plan are outlined. Quality anatomic pathology work comes with focus on accurate, timely, and complete reports. A commitment to continuous quality improvement and a systems approach with a persistent effort helps to achieve this end. Departments should have a quality assurance and improvement plan that includes a risk assessment of real and potential problems facing the laboratory. The plan should also list the individuals responsible for carrying out the program with adequate resources, a defined timetable, and annual assessment for progress and future directions. Quality assurance monitors should address regulatory requirements and be organized by laboratory division (surgical pathology, cytology, etc) as well as 5 segments (preanalytic, analytic, postanalytic phases of the test cycle, turn-around-time, and customer satisfaction). Quality assurance data can also be used to evaluate individual pathologists using multiple parameters with peer group comparison.

  13. Forest pathology in Hawaii

    Science.gov (United States)

    Gardner, D.E.

    2003-01-01

    Native Hawaiian forests are characterised by a high degree of endemism, including pathogens as well as their hosts. With the exceptions of koa (Acacia koa Gray), possibly maile (Alyxia oliviformis Gaud.), and, in the past, sandalwood (Santalum spp.), forest species are of little commercial value. On the other hand, these forests are immensely important from a cultural, ecological, and evolutionary standpoint. Forest disease research was lacking during the mid-twentieth century, but increased markedly with the recognition of ohia (Metrosideros polymorpha Gaud.) decline in the 1970s. Because many pathogens are themselves endemic, or are assumed to be, having evolved with their hosts, research emphasis in natural areas is on understanding host-parasite interactions and evolutionary influences, rather than disease control. Aside from management of native forests, attempts at establishing a commercial forest industry have included importation of several species of pine, Araucaria, and Eucalyptus as timber crops, and of numerous ornamentals. Diseases of these species have been introduced with their hosts. The attacking of native species by introduced pathogens is problematic - for example, Armillaria mellea (Vahl ex Fr.) Que??l. on koa and mamane (Sophora chrysophylla (Salisb.) Seem.). Much work remains to be done in both native and commercial aspects of Hawaiian forest pathology.

  14. Aligning Organizational Pathologies and Organizational Resilience Indicators

    Directory of Open Access Journals (Sweden)

    Manuel Morales Allende

    2017-07-01

    Full Text Available Developing resilient individuals, organizations and communities is a hot topic in the research agenda in Management, Ecology, Psychology or Engineering. Despite the number of works that focus on resilience is increasing, there is not completely agreed definition of resilience, neither an entirely formal and accepted framework. The cause may be the spread of research among different fields. In this paper, we focus on the study of organizational resilience with the aim of improving the level of resilience in organizations. We review the relation between viable and resilient organizations and their common properties. Based on these common properties, we defend the application of the Viable System Model (VSM to design resilient organizations. We also identify the organizational pathologies defined applying the VSM through resilience indicators. We conclude that an organization with any organizational pathology is not likely to be resilient because it does not fulfill the requirements of viable organizations.

  15. Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy

    International Nuclear Information System (INIS)

    Wilson, Lynn D.; Licata, Anita L.; Braverman, Irwin M.; Edelson, Richard L.; Heald, Peter W.; Feldman, Andrea M.; Kacinski, Barry M.

    1995-01-01

    Purpose: To evaluate the impact of systemic adjuvant therapies on relapse-free (RFS) and overall survival (OS) of cutaneous T-cell lymphoma (CTCL) patients treated with total skin electron beam therapy (TSEBT). Methods and Materials: Between 1974 and 1990, TSEBT (36 Gy at 1 Gy/day; 9 weeks; 6 MeV electrons) was administered with curative intent to a total of 163 CTCL (mycosis fungoides) patients using six fields supplemented by orthovoltage boosts (120 kvp, 1 Gy x 20) to the perineum, soles of feet, and apical scalp (120 kvp, 2 Gy x 3). In this group, all patients who achieved a clinical complete response or a good partial response were offered one of two competing regimens of either adjuvant doxorubicin/cyclophosphamide or adjuvant extracorporeal photochemotherapy (ECP). Results: When the results for the group who achieved a complete response (CR) to TSEBT were analyzed, OS for T1 and T2 patients was excellent (85-90% at 5-10 years) and not improved by either adjuvant regimen. However, T3 and T4 patients who received either adjuvant doxorubicin/cyclophosphamide (75% at 3 years) or adjuvant ECP (100% at 3 years) had better overall survival than those who received neither adjuvant regimen (∼ 50% at 5 years). The difference between the OS curves for those who received ECP vs. those who received no adjuvant therapy approached statistical significance (p < 0.06), while a significant survival benefit from the addition of chemotherapy for TSEBT complete responders was not observed. Neither adjuvant therapy provided benefit with respect to relapse free survival after TSEBT. Conclusions: These results suggest that an adjuvant nontoxic regimen of extracorporeal photochemotherapy may prolong survival in advanced stage CTCL patients who have achieved a complete remission after TSEBT. The combination of doxorubicin/cyclophosphamide had no significant impact on overall survival in those patients who achieved CR to TSEBT, and neither adjuvant therapy had an impact on relapse

  16. Latino College Completion: Hawaii

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  17. Latino College Completion: Pennsylvania

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  18. FROM PHYSIOLOGICAL TO PATHOLOGICAL METEOSENSITIVITY

    Directory of Open Access Journals (Sweden)

    M. I. Yabluchanskiy

    2013-12-01

    Full Text Available This paper is dedicated to the problem of physiological and pathological meteosensitivity (meteodependency or meteopathy.We introduce and discuss the definition for individual meteodependency, define factors, mechanisms, clinical signs, diagnosis, and approaches to prophylaxy and treatment of individual pathological meteosensitivity.

  19. NMR imaging of osteoarticular pathology

    International Nuclear Information System (INIS)

    Frocrain, L.; Duvauferrier, R.; Gagey, N.

    1987-01-01

    NMR imaging is assuming an increasingly important role in the diagnosis of osteo-articular disorders. Semiological descriptions of the mean pathological disorders of the locomotor system are presented. Some investigation strategies are proposed to compare NMR imaging with other imaging techniques in various pathological states [fr

  20. Completeness, supervenience and ontology

    International Nuclear Information System (INIS)

    Maudlin, Tim W E

    2007-01-01

    In 1935, Einstein, Podolsky and Rosen raised the issue of the completeness of the quantum description of a physical system. What they had in mind is whether or not the quantum description is informationally complete, in that all physical features of a system can be recovered from it. In a collapse theory such as the theory of Ghirardi, Rimini and Weber, the quantum wavefunction is informationally complete, and this has often been taken to suggest that according to that theory the wavefunction is all there is. If we distinguish the ontological completeness of a description from its informational completeness, we can see that the best interpretations of the GRW theory must postulate more physical ontology than just the wavefunction

  1. Completeness, supervenience and ontology

    Energy Technology Data Exchange (ETDEWEB)

    Maudlin, Tim W E [Department of Philosophy, Rutgers University, 26 Nichol Avenue, New Brunswick, NJ 08901-1411 (United States)

    2007-03-23

    In 1935, Einstein, Podolsky and Rosen raised the issue of the completeness of the quantum description of a physical system. What they had in mind is whether or not the quantum description is informationally complete, in that all physical features of a system can be recovered from it. In a collapse theory such as the theory of Ghirardi, Rimini and Weber, the quantum wavefunction is informationally complete, and this has often been taken to suggest that according to that theory the wavefunction is all there is. If we distinguish the ontological completeness of a description from its informational completeness, we can see that the best interpretations of the GRW theory must postulate more physical ontology than just the wavefunction.

  2. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  3. Culturally diverse attitudes and beliefs of students majoring in speech-language pathology.

    Science.gov (United States)

    Franca, Maria Claudia; Smith, Linda McCabe; Nichols, Jane Luanne; Balan, Dianna Santos

    Academic education in speech-language pathology should prepare students to provide professional services that mirror current knowledge, skills, and scope of practice in a pluralistic society. This study seeks to examine the impact of speech-language pathology (SLP) students prior multicultural experiences and previous formal education on attitudes and beliefs toward language diversity. A survey to investigate SLP students attitudes toward language diversity was applied. After the research study and instructions to complete the consent form questionnaire was presented by a research assistant, an announcement was given by a graduate student who speaks English as a second language with an accent. The participants then completed a questionnaire containing questions related to attitudes about the presentation of the announcement in particular and toward language diversity in general. Responses suggested a relationship between self-reported cultural bias and ability to concentrate on speech with an accent, and the extent of interaction with individuals from a cultural and linguistic diverse (CLD) background. Additional outcomes revealed that cultural bias may be predicted by factors related to amount of CLD exposure. Results of this study indicated critical areas that need to be considered when developing curricula in speech-language pathology programs. The results will be useful in determining procedures applicable in larger investigations, and encourage future research on attitudes and beliefs toward aspects of cultural diversity.

  4. Personal and Social Disease Pathology

    Directory of Open Access Journals (Sweden)

    Giuseppe TRIBUZIO

    2015-06-01

    Full Text Available With the Ottawa Charter definition of the concept health is integrated and expanded, aiming at enhancing not only the "state" of health, but the "process" that leads to it, taking into account health That is considered a resource through which, the individual becomes an active player in the community. Therefore it considers very important the community aspect and the social existence of the person, it must be that within an active protagonist. Each person, therefore, should feel responsible for their own condition and must be fire "exercise opinions more control over health and over their own their environments, and to make choices conducive to health." To achieve this it is essential to enable people to learn throughout life, to prepare themselves for all of its stages and to be fire cope with injuries and chronic diseases. This should be made possible at school, at home, in the workplace and in all community settings. The purpose of the “Ottawa Charter” are really ambitious if one takes into account that not all western industrialized countries, starting from the USA, put into practice social policies that can raise standards of health, requiring structural reforms of the welfare state. The disease is the tip of the iceberg of a social pathology, which causes discomfort and influence individual, not finding answers in the institutions, become chronic changing for the worse the quality of life.

  5. Experimental radiation pathology and oncology

    International Nuclear Information System (INIS)

    Finkel, M.P.

    1975-01-01

    The program goal is to provide basic data for evaluating the hazard to man from radioactive materials deposited within the body. The original objective, to obtain dose-response information and to provide data from several species for extrapolating animal data to man, is receiving less attention at present as effort is being put into determining how radiation causes bone cancer and whether viruses play a role. The program began with the very early radiotoxicologic investigations of materials important in the development of the atomic bomb and the necessity to establish maximum permissible levels of exposure to these materials. With the demonstration that bone cancer is the most sensitive indicator of damage from transuranic elements and some of the fission products, bone pathology became the focus of attention. When it became evident that questions of human hazard cannot be answered unequivocally on the basis of dose-response relationships, different approaches were considered, and one based on knowledge of mechanisms of cancer induction seemed most likely to be successful. The detection of viruses in both radiation-induced and spontaneous bone cancer of mice, and the present evidence for a similar virus in bone cancer of man, support the hypothesis that radiation causes cancer by activating endogenous neoplastic information, which can also be expressed as oncornavirus. Present emphases therefore concern understanding the biological, biochemical, and physical attributes of the five murine oncornaviruses that have now been isolated in the course of the program; demonstrating the existence of a comparable human oncornavirus; and discovering how radiation and virus interact in the induction of bone cancer

  6. The Pathology Laboratory Act 2007 explained.

    Science.gov (United States)

    Looi, Lai-Meng

    2008-06-01

    laboratory practices are left to be specified by the Director-General of Health, providing for a formal recognition process and room for revision as pathology practices evolve. Encompassed in the responsibilities of the licensee is the requirement that samples are received and results issued through, and management vested in, a registered medical or dental practitioner. This effectively prohibits "walk-ins" to the laboratory and indiscriminate public screening. The requirement for a person-in-charge in accordance with class and speciality of laboratory ensures that the laboratory is under the charge of the pathology profession. Examined carefully, the requirements of the Act are similar to laboratory accreditation, but are backed by legislation. Many of these details will be spelt out in the Regulations, and these in turn are likely to fall back on National professional guidelines, as accreditation does. Although not at first obvious, enforcement of the Act is based on self-regulation by pathology laboratory professionals. Sincere professional input is thus required to embrace its philosophy, ensure rational and transparent enforcement of legislation, and develop National guidelines for good pathology practices upon which enforcement may be based.

  7. Guideline on the requirements of external quality assessment programs in molecular pathology

    NARCIS (Netherlands)

    van Krieken, J Han; Normanno, Nicola; Blackhall, Fiona; Boone, Elke; Botti, Gerardo; Carneiro, Fatima; Celik, Ilhan; Ciardiello, Fortunato; Cree, Ian A; Deans, Zandra C; Edsjö, Anders; Groenen, Patricia J T A; Kamarainen, Outi; Kreipe, Hans H; Ligtenberg, Marjolijn J L; Marchetti, Antonio; Murray, Samuel; Opdam, Frank J M; Patterson, Scott D; Patton, Simon; Pinto, Carmine; Rouleau, Etienne; Schuuring, Ed; Sterck, Silke; Taron, Miquel; Tejpar, Sabine; Timens, Wim; Thunnissen, Erik; van de Ven, Peter M; Siebers, Albert G; Dequeker, Elisabeth

    Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality

  8. The Role of Personality Pathology in Depression Treatment Outcome with Psychotherapy and Pharmacotherapy

    Science.gov (United States)

    Levenson, Jessica C.; Wallace, Meredith L.; Fournier, Jay C.; Rucci, Paola; Frank, Ellen

    2012-01-01

    Background: Depressed patients with comorbid personality pathology may fare worse in treatment for depression than those without this additional pathology, and comorbid personality pathology may be associated with superior response in one form of treatment relative to another, though recent findings have been mixed. We aimed to evaluate the effect…

  9. Panning artifacts in digital pathology images

    Science.gov (United States)

    Avanaki, Ali R. N.; Lanciault, Christian; Espig, Kathryn S.; Xthona, Albert; Kimpe, Tom R. L.

    2017-03-01

    In making a pathologic diagnosis, a pathologist uses cognitive processes: perception, attention, memory, and search (Pena and Andrade-Filho, 2009). Typically, this involves focus while panning from one region of a slide to another, using either a microscope in a traditional workflow or software program and display in a digital pathology workflow (DICOM Standard Committee, 2010). We theorize that during panning operation, the pathologist receives information important to diagnosis efficiency and/or correctness. As compared to an optical microscope, panning in a digital pathology image involves some visual artifacts due to the following: (i) the frame rate is finite; (ii) time varying visual signals are reconstructed using imperfect zero-order hold. Specifically, after pixel's digital drive is changed, it takes time for a pixel to emit the expected amount of light. Previous work suggests that 49% of navigation is conducted in low-power/overview with digital pathology (Molin et al., 2015), but the influence of display factors has not been measured. We conducted a reader study to establish a relationship between display frame rate, panel response time, and threshold panning speed (above which the artifacts become noticeable). Our results suggest visual tasks that involve tissue structure are more impacted by the simulated panning artifacts than those that only involve color (e.g., staining intensity estimation), and that the panning artifacts versus normalized panning speed has a peak behavior which is surprising and may change for a diagnostic task. This is work in progress and our final findings should be considered in designing future digital pathology systems.

  10. Complete Ureteral Avulsion

    Directory of Open Access Journals (Sweden)

    V. Gupta

    2005-01-01

    Full Text Available Complete avulsion of the ureter is one of the most serious complications of ureteroscopy. It requires open or laparoscopic intervention for repair. This case report emphasizes its management and presents recommendations for prevention in current urological practice.

  11. Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

    Science.gov (United States)

    Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas

    2017-06-01

    Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery. Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation. Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%). CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.

  12. MRI analysis of the rotator cuff pathology a new classification

    International Nuclear Information System (INIS)

    Tavernier, T.; Lapra, C.; Bochu, M.; Walch, G.; Noel, E.

    1995-01-01

    The different classifications use for the rotator cuff pathology seem to be incomplete. We propose a new classification with many advantages: (1) Differentiate the tendinopathy between less serious (grade 2A) and serious (grade 2B). (2) Recognize the intra-tendinous cleavage of the infra-spinatus associated with complete tear of the supra-spinatus. (3) Differentiate partial and complete tears of the supra-spinatus. We established this classification after a retrospective study of 42 patients operated on for a rotator cuff pathology. Every case had had a preoperative MRI. This classification is simple, especially for the associated intra tendinous cleavage. (authors). 24 refs., 9 figs., 2 tabs

  13. Utilization management in anatomic pathology.

    Science.gov (United States)

    Lewandrowski, Kent; Black-Schaffer, Steven

    2014-01-01

    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management. © 2013.

  14. Brain venous pathologies: MRI findings

    International Nuclear Information System (INIS)

    Salvatico, Rosana; Gonzalez, Alejandro; Yanez, Paulina; Romero, Carlos; Trejo, Mariano; Lambre, Hector

    2006-01-01

    Purpose: To describe MRI findings of the different brain venous pathologies. Material and Methods: Between January 2002 and March 2004, 18 patients were studied 10 males and 8 females between 6 and 63 years old; with different brain venous pathologies. In all cases brain MRI were performed including morphological sequences with and without gadolinium injection and angiographic venous sequences. Results: 10 venous occlusions were found, 6 venous angiomas, and 2 presented varices secondary to arteriovenous dural fistula. Conclusion: Brain venous pathologies can appear in many different clinical contexts, with different prognosis and treatment. In all the cases brain MRI was the best imaging study to disclose typical morphologic abnormalities. (author) [es

  15. [Comparative pathology of the microcirculatory bed].

    Science.gov (United States)

    Strukov, A I; Vorob'eva, A A

    1976-11-01

    This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

  16. Plant pathology: a story about biology.

    Science.gov (United States)

    Gordon, Thomas R; Leveau, Johan H J

    2010-01-01

    Disease is a universal feature of life for multicellular organisms, and the study of disease has contributed to the establishment of key concepts in the biological sciences. This implies strong connections between plant pathology and basic biology, something that could perhaps be made more apparent to undergraduate students interested in the life sciences. To that end, we present an instructional narrative that begins with a simple question: Why are there diseases? Responses and follow-up questions can facilitate exploration of such topics as the evolution of parasitism, plant adaptations to parasitism, impacts of parasites on native plant communities, and ways in which human intervention can foster the emergence of aggressive plant pathogens. This approach may help to attract students who would not have found their way to plant pathology through traditional pathways. Packaging the narrative as a game may render it more interesting and accessible, particularly to a younger audience.

  17. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints...... in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US...... pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis....

  18. Perinatal pathology: practice suggestions for limited-resource settings.

    Science.gov (United States)

    Roberts, Drucilla J

    2013-06-01

    The practice of perinatal pathology in much of the world suffers, as do all subspecialties of anatomic pathology, from inadequate resources (equipment, consumables, and both professional and technical personnel), from lack of education (not only of the pathologist but also of the clinicians responsible for sending the specimens, and the technicians processing the specimens), and from lack of appropriate government sector support. Perinatal pathology has significant public health-related utility and should be championing its service by providing maternal and fetal/infant mortality and morbidity data to governmental health ministries. It is with this pathologic data that informed decisions can be made on health-related courses of action and allocation of resources. These perinatal pathology data are needed to develop appropriate public health initiatives, specifically toward achieving the Millennium Developmental Goals as the best way to effectively decrease infant and maternal deaths and to determine causes of perinatal mortality and morbidity. The following overview will focus on the utility of perinatal pathology specifically as related to its public health function and will suggest methods to improve its service in resource-poor settings. This article is offered not as a critique of the current practice that most pathologists find themselves working in globally, but to provide suggestions for improving perinatal pathology services, which could be implemented with the limited available resources and manpower most pathology departments currently have. In addition, we offer suggestions for graded improvements ("ramping up") over time.

  19. Web-based pathology practice examination usage

    Directory of Open Access Journals (Sweden)

    Edward C Klatt

    2014-01-01

    Full Text Available Context: General and subject specific practice examinations for students in health sciences studying pathology were placed onto a free public internet web site entitled web path and were accessed four clicks from the home web site menu. Subjects and Methods: Multiple choice questions were coded into. html files with JavaScript functions for web browser viewing in a timed format. A Perl programming language script with common gateway interface for web page forms scored examinations and placed results into a log file on an internet computer server. The four general review examinations of 30 questions each could be completed in up to 30 min. The 17 subject specific examinations of 10 questions each with accompanying images could be completed in up to 15 min each. The results of scores and user educational field of study from log files were compiled from June 2006 to January 2014. Results: The four general review examinations had 31,639 accesses with completion of all questions, for a completion rate of 54% and average score of 75%. A score of 100% was achieved by 7% of users, ≥90% by 21%, and ≥50% score by 95% of users. In top to bottom web page menu order, review examination usage was 44%, 24%, 17%, and 15% of all accessions. The 17 subject specific examinations had 103,028 completions, with completion rate 73% and average score 74%. Scoring at 100% was 20% overall, ≥90% by 37%, and ≥50% score by 90% of users. The first three menu items on the web page accounted for 12.6%, 10.0%, and 8.2% of all completions, and the bottom three accounted for no more than 2.2% each. Conclusions: Completion rates were higher for shorter 10 questions subject examinations. Users identifying themselves as MD/DO scored higher than other users, averaging 75%. Usage was higher for examinations at the top of the web page menu. Scores achieved suggest that a cohort of serious users fully completing the examinations had sufficient preparation to use them to support

  20. A recurrent ovarian cancer patient with a history of nine prior chemotherapy regimens who was safely treated with weekly paclitaxel plus bevacizumab and achieved a complete response: a case report

    Directory of Open Access Journals (Sweden)

    Takatori E

    2015-08-01

    Full Text Available Eriko Takatori,1 Tadahiro Shoji,1 Takayuki Nagasawa,1 Satoshi Takeuchi,1 Akira Hosoyachi,2 Toru Sugiyama1 1Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan; 2Department of Obstetrics and Gynecology, Iwate Prefectural Miyako Hospital, Miyako, Japan Abstract: Herein, we describe our experience with a recurrent ovarian cancer patient who was treated safely with bevacizumab and who achieved a complete response despite receiving nine prior chemotherapy regimens. The patient was a 54-year-old woman with stage IIIC recurrent ovarian serous adenocarcinoma (grade 3. Computed tomography (CT revealed that no evidence of ascites, multiple intraperitoneal dissemination, or intrapelvic lymph node metastases was present. The absence of bowel obstruction and disseminated lesions involving the intestinal tract was confirmed by CT. Performance status was 0, and a blood test also indicated preservation of major organ function. In our hospital, weekly paclitaxel plus bevacizumab therapy (paclitaxel at 80 mg/m2 on days 1, 8, and 15; bevacizumab at 15/mg/kg on day 1 and every 21 days thereafter was started. Eight cycles were administered, with no signs of gastrointestinal perforation, and the antitumor effect was evaluated as a complete response. The observed adverse events included grade 1 hyponatremia and grade 1 hypochloremia, and there was one grade 1 sensory peripheral neuropathy. These adverse events neither delayed treatment nor necessitated any dosage reductions. This case suggests that bevacizumab can be safely administered even to patients with recurrent ovarian cancer who have received three or more prior chemotherapy regimens if there are neither symptoms of bowel obstruction nor lesions suggestive of intestinal invasion on diagnostic imaging. Keywords: recurrent ovarian cancer, gastrointestinal perforation 

  1. BILATERAL PATHOLOGICAL HIP DISLOCATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yuriy E. Garkavenko

    2017-03-01

    Full Text Available Introduction. Pathological dislocation of the hip is one of the most severe complications of acute hematogenous osteomyelitis. The program of treatment for children with pathological hip dislocation is complex, but it has been sufficiently developed and implemented very successfully. At the same time, the available literature provides no cases of treating children with bilateral pathological hip dislocations after hematogenous osteomyelitis. There is no information on the incidence of such cases or in regards to remote functional results. Materials and methods. The results of the treatment of 18 children with bilateral pathological dislocation of the hip after hematogenous osteomyelitis are presented, which constituted 23.1% of the total number of patients (78 who underwent surgery in 2000–2016 for the diagnosis of pathological hip dislocation. Both hip joints were surgically operated on in 12 patients, while one hip joint was operated on in 6 patients. To assess the anatomical and functional state of hip joints, the clinical and roentgenological diagnostic techniques were used. Results and discussion. To stabilize and restore the function of the hip joints, 18 children underwent 30 surgical interventions: simple open hip reduction (19 and open hip reduction with hip arthroplasty with one (6 or two (5 demineralized osteochondral allogeneic grafts. The decision regarding the possibility of performing surgical intervention on the second hip joint was made only after a child's check-up examination was complete and after positive information about the anatomical and functional state of the operated hip joint was obtained. According to these criteria, 14 (77.8% children underwent surgical treatment of the second hip joint 1–1.5 years after the course of conservative measures to restore the range of motion in the previously operated hip joint. Over a period of 1–12 years, 17 patients were examined, 10 of which underwent an operation on both

  2. The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Mak, Daisy; Joon, Daryl Lim; Chao, Michael; Wada, Morikatsu; Joon, Michael Lim; See, Andrew; Feigen, Malcolm; Jenkins, Patricia; Mercuri, Angelina; McNamara, Joanne; Poon, Aurora; Khoo, Vincent

    2010-01-01

    Purpose: To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. Methods and materials: Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed. Results: Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease. Conclusions: PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.

  3. Systems pathology: a critical review.

    Science.gov (United States)

    Costa, Jose

    2012-02-01

    The technological advances of the last twenty years together with the dramatic increase in computational power have injected new life into systems-level thinking in Medicine. This review emphasizes the close relationship of Systems Pathology to Systems Biology and delineates the differences between Systems Pathology and Clinical Systems Pathology. It also suggests an algorithm to support the application of systems-level thinking to clinical research, proposes applying systems-level thinking to the health care systems and forecasts an acceleration of preventive medicine as a result of the coupling of personal genomics with systems pathology. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Oral Pathology in Forensic Investigation.

    Science.gov (United States)

    Shamim, Thorakkal

    2018-01-01

    Forensic odontology is the subdiscipline of dentistry which analyses dental evidence in the interest of justice. Oral pathology is the subdiscipline of dentistry that deals with the pathology affecting the oral and maxillofacial regions. This subdiscipline is utilized for identification through oral and maxillofacial pathologies with associated syndromes, enamel rod patterns, sex determination using exfoliative cytology, identification from occlusal morphology of teeth, and deoxyribonucleic acid profiling from teeth. This subdiscipline is also utilized for age estimation studies which include Gustafson's method, incremental lines of Retzius, perikymata, natal line formation in teeth, neonatal line, racemization of collagen in dentin, cemental incremental lines, thickness of the cementum, and translucency of dentin. Even though the expertise of an oral pathologist is not taken in forensic investigations, this paper aims to discuss the role of oral pathology in forensic investigation.

  5. Pathology and risk assessment

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Programs for providing basic data for use in evaluating the hazard to man from exposure to radiation and other energy-related pollutants are reviewed. A computer program was developed that takes the existing mortality and fertility data on a given population and applies dose-response coefficients and estimated increments of exposure to chemical or radioactive effluents and derives the excess deaths by age and sex for 5-year intervals. The program was used in an analysis of the health effects of airborne coal combustion effluents. Preliminary results are reported from a study of the influence of products of fossil fuel combustion on the spontaneous activity patterns and daily metabolic cycles of mice as a factor of age, environment, and genetic constitution. Preliminary results are reported from studies on the early and late effects of polycyclic hydrocarbons on the immune competence of mice. Studies to determine the risk to human populations from radionuclides released to the environment from nuclear energy facilities use relative toxicity and dose response data from laboratory animals of different body size and life span and comparisons of the effects of internal exposure with those of external exposure to fission neutrons or gamma sources

  6. Stroop performance in pathological gamblers.

    Science.gov (United States)

    Kertzman, Semion; Lowengrub, Katherine; Aizer, Anat; Nahum, Zeev Ben; Kotler, Moshe; Dannon, Pinhas N

    2006-05-30

    Pathological gambling is a relatively prevalent psychiatric disorder that typically leads to severe family, social, legal, and occupational problems and is associated with a high rate of suicide attempts. Understanding the neurobiological basis of pathological gambling is a current focus of research, and emerging data have demonstrated that pathological gamblers may have impaired decision-making because of an inability to inhibit irrelevant information. In this study, we examined pathological gamblers by using the Stroop Color-Word Test, a neurocognitive task used to assess interference control. The "reverse" variant of the Stroop Color-Word Test was administered to a cohort of medication-free pathological gamblers (n=62) and a cohort of age-matched controls (n=83). In the reverse variant of the Stroop task, subjects are asked to read the meaning of the word rather than name the ink color. The reverse Stroop task was chosen because it highly discriminates ability to inhibit interference in a population of psychiatric patients. In our study, performance on the reverse Stroop task in the pathological gamblers was significantly slower and less accurate than in the healthy subjects. A new finding in our study was that for pathological gamblers, the average reaction time in the neutral condition (where the color names are displayed in black letters) was slower than the average reaction time in the incongruent condition (where the meaning of the color name and the color of the printed letters are different). This controlled study extends previous findings by showing that performance on the Stroop task is impaired in a sample of medication-free pathological gamblers.

  7. Profile of the pathological gambler.

    Science.gov (United States)

    Custer, R L

    1984-12-01

    Pathological (compulsive) gambling is a serious emotional and social problem that has existed for centuries but has only recently been recognized as a distinct diagnostic entity that can be effectively treated. The development and progression of pathological gambling are outlined. The progression of the disorder through three identifiable phases leads to predictable complications. The treatment of the gambler within the framework of Gamblers Anonymous and/or by mental health professionals is described.

  8. Late radiation pathology of mammals

    Energy Technology Data Exchange (ETDEWEB)

    Alexandrov, S N

    1982-01-01

    The comprehensive monograph on delayed radiation effects in mammals including man comprises 3 main chapters dealing with non-neoplastic as well as neoplastic manifestations of late radiation pathology, with the prophylaxis of delayed radiation effects, and with the therapy of radiation injuries. Alterations induced by whole-body irradiation and delayed radiation effects caused by partial body irradiation are described in detail. The developmental mechanisms and pathogenesis of non-neoplastic pathological changes and of radiation-induced neoplasms are elaborated.

  9. Interpersonal perception of pathological narcissism: a social relations analysis.

    Science.gov (United States)

    Lukowitsky, Mark R; Pincus, Aaron L

    2013-01-01

    Impairments in self and interpersonal functioning are core features of personality pathology. Clinical theory and research indicate that compromised self-awareness and distorted interpersonal perceptions are particularly prominent in individuals exhibiting pathological narcissism and Narcissistic Personality Disorder. Therefore we conducted a study to gain a better understanding of interpersonal perception of pathological narcissism. A large sample (N=437) of moderately acquainted individuals assigned to 1 of 93 small mixed-sex groups completed self- and informant ratings on the Pathological Narcissism Inventory (PNI) in a round-robin design. The social relations model (SRM) was used to partition the variance in dyadic ratings to investigate several hypotheses about interpersonal perception of pathological narcissism. SRM analyses demonstrated evidence of assimilation (the tendency to perceive and rate others similarly) and consensus (the extent to which multiple observers form similar impressions of another person) in interpersonal perception of pathological narcissism. Results also indicated modest self-other agreement and assumed similarity (the tendency for people to perceive others as similar to themselves) for PNI higher order factors and subscale ratings. Finally, results suggested that individuals high in pathological narcissism had some awareness of how peers would rate them (metaperception) but believed that others would rate them similarly to how they rated themselves.

  10. Standards to support information systems integration in anatomic pathology.

    Science.gov (United States)

    Daniel, Christel; García Rojo, Marcial; Bourquard, Karima; Henin, Dominique; Schrader, Thomas; Della Mea, Vincenzo; Gilbertson, John; Beckwith, Bruce A

    2009-11-01

    Integrating anatomic pathology information- text and images-into electronic health care records is a key challenge for enhancing clinical information exchange between anatomic pathologists and clinicians. The aim of the Integrating the Healthcare Enterprise (IHE) international initiative is precisely to ensure interoperability of clinical information systems by using existing widespread industry standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level Seven (HL7). To define standard-based informatics transactions to integrate anatomic pathology information to the Healthcare Enterprise. We used the methodology of the IHE initiative. Working groups from IHE, HL7, and DICOM, with special interest in anatomic pathology, defined consensual technical solutions to provide end-users with improved access to consistent information across multiple information systems. The IHE anatomic pathology technical framework describes a first integration profile, "Anatomic Pathology Workflow," dedicated to the diagnostic process including basic image acquisition and reporting solutions. This integration profile relies on 10 transactions based on HL7 or DICOM standards. A common specimen model was defined to consistently identify and describe specimens in both HL7 and DICOM transactions. The IHE anatomic pathology working group has defined standard-based informatics transactions to support the basic diagnostic workflow in anatomic pathology laboratories. In further stages, the technical framework will be completed to manage whole-slide images and semantically rich structured reports in the diagnostic workflow and to integrate systems used for patient care and those used for research activities (such as tissue bank databases or tissue microarrayers).

  11. Frozen section pathology for decision making in parotid surgery.

    Science.gov (United States)

    Olsen, Kerry D; Moore, Eric J; Lewis, Jean E

    2013-12-01

    For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required. To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making. Retrospective review of patients undergoing parotidectomy at a tertiary care center. Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section. Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors. Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient was overtreated (lymphoma initially deemed carcinoma). Frozen section pathology for parotid lesions has high accuracy and utility in intraoperative decision making, facilitating timely complete procedures.

  12. Completeness of Lyapunov Abstraction

    DEFF Research Database (Denmark)

    Wisniewski, Rafal; Sloth, Christoffer

    2013-01-01

    the vector field, which allows the generation of a complete abstraction. To compute the functions that define the subdivision of the state space in an algorithm, we formulate a sum of squares optimization problem. This optimization problem finds the best subdivisioning functions, with respect to the ability......This paper addresses the generation of complete abstractions of polynomial dynamical systems by timed automata. For the proposed abstraction, the state space is divided into cells by sublevel sets of functions. We identify a relation between these functions and their directional derivatives along...

  13. Construction completion report

    International Nuclear Information System (INIS)

    1990-01-01

    This Construction Completion Report documents the major construction projects at the Waste Isolation Pilot Plant (WIPP) site and related information on contracts, schedules, and other areas which affected construction. This report is not intended to be an exhaustive detailed analysis of construction, but is a general overview and summary of the WIPP construction. 10 refs., 29 figs

  14. Complete Rerouting Protection

    DEFF Research Database (Denmark)

    Stidsen, Thomas K.; Kjærulff, Peter

    2005-01-01

    In this paper we present a new protection method: Complete Rerouting. This is the most capacity e cient protection method for circuit switched networks and it is, to the best of our knowledge, the first time it has been described. We implement a column generation algorithm and test the performance...

  15. Complete French Teach Yourself

    CERN Document Server

    Graham, Gaelle

    2010-01-01

    The best-selling complete course for a fun and effective way to learn French. This ISBN is for the paperback book. The corresponding audio support (ISBN: 9781444100068) is also available. The book and audio support can also be purchased as a pack (ISBN: 9781444100051).

  16. Completeness of Lyapunov Abstraction

    Directory of Open Access Journals (Sweden)

    Rafael Wisniewski

    2013-08-01

    Full Text Available In this work, we continue our study on discrete abstractions of dynamical systems. To this end, we use a family of partitioning functions to generate an abstraction. The intersection of sub-level sets of the partitioning functions defines cells, which are regarded as discrete objects. The union of cells makes up the state space of the dynamical systems. Our construction gives rise to a combinatorial object - a timed automaton. We examine sound and complete abstractions. An abstraction is said to be sound when the flow of the time automata covers the f