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Sample records for hepatic colorectal metastases

  1. Hepatic resection for colorectal metastases - a national perspective.

    Heriot, A. G.; Reynolds, J.; Marks, C. G.; Karanjia, N.

    2004-01-01

    BACKGROUND: Many consultant surgeons are uncertain about peri-operative assessment and postoperative follow-up of patients for colorectal liver metastases, and indications for referral for hepatic resection. The aim of this study was to assess the views the consultant surgeons who manage these patients. METHODS: A postal questionnaire was sent to all consultant members of the Association of Coloproctology of Great Britain and Ireland and of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland. The questionnaire assessed current practice for preoperative assessment and follow-up of patients with colorectal malignancy and timing of and criteria for hepatic resection of metastases. Number of referrals/resections were also assessed. RESULTS: The response rate was 47%. Half of the consultants held joint clinics with an oncologist and 89% assessed the liver for secondaries prior to colorectal resection. Ultrasound was used by 75%. Whilst 99% would consider referring a patient with a solitary liver metastasis for resection, only 62% would consider resection for more than 3 unilobar metastases. The majority (83%) thought resections should be performed within the 6 months following colorectal resection. During follow-up, 52% requested blood CEA levels and 72% liver ultrasound. Half would consider chemotherapy prior to liver resection and 76% performed at least one hepatic resection per year with a median number of 2 resections each year. CONCLUSIONS: A substantial proportion of patients are assessed for colorectal liver metastases preoperatively and during follow-up though there is spectrum of frequency of assessment and modality for imaging. Virtually all patients with solitary hepatic metastases are considered for liver resection. Patients with more than one metastasis are likely to be not considered for resection. Many surgeons are carrying out less than 3 resections each year. PMID:15527578

  2. Sequential surgical resection of hepatic and pulmonary metastases from colorectal cancer

    Limmer, Stefan; Oevermann, Elisabeth; Killaitis, Claudia; Kujath, Peter; Hoffmann, Martin; Bruch, Hans-Peter

    2010-01-01

    Background Resection of isolated hepatic or pulmonary metastases from colorectal cancer is widely accepted and associated with a 5-year survival rate of 25?40%. The value of aggressive surgical management in patients with both hepatic and pulmonary metastases still remains a controversial area. Materials and methods A retrospective review of 1,497 patients with colorectal carcinoma (CRC) was analysed. Of 73 patients identified with resection of CRC and, at some point in time, both liver and l...

  3. Intraoperative ultrasonography in detection of hepatic metastases from colorectal cancer

    Rafaelsen, Søren Rafael; Kronborg, Ole; Fenger, Claus

    1995-01-01

    PURPOSE: This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. METHODS: Blind, prospective comparisons of diagnostic...... examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware...

  4. Transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization for the treatment of hepatic metastases from colorectal carcinoma

    Wang Xuan; Chen Xiaofei

    2009-01-01

    Objective: To evaluate the clinical efficacy of transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization in the treatment of hepatic metastases from colorectal carcinoma. Methods: Sixty-eight cases with hepatic metastases from colorectal carcinoma were equally and randomly divided into two groups. The patients in study group were treated with transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization, while the patients in control group were treated with conventional (normal temperature) transcatheter hepatic arterial chemotherapy lipiodol embolization. Results: The effective rate of study group and control group was 65%(22/34) and 32%(11/34) respectively, the difference between two groups was statistically significant (P<0.05). No significant difference in the postoperative changes of hepatic function tests was found between the two groups. The survival rate at 6,12,18 and 24 months after the treatment was 100%, 82%, 44% and 18% respectively in study group, while it was 91%, 47%, 15% and 6% respectively in control group. Conclusion: Transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization is an effective and safe treatment for the hepatic metastases from colorectal carcinoma and has no obvious damage to the hepatic function. (authors)

  5. Resection of Concomitant Hepatic and Extrahepatic Metastases from Colorectal Cancer - A Worthwhile Operation?

    Diaconescu, Andrei; Alexandrescu, Sorin; Ionel, Zenaida; Zlate, Cristian; Grigorie, Razvan; Brasoveanu, Vladislav; Hrehoret, Doina; Ciurea, Silviu; Botea, Florin; Tomescu, Dana; Droc, Gabriela; Croitoru, Adina; Herlea, Vlad; Boros, Mirela; Grasu, Mugur; Dumitru, Radu; Toma, Mihai; Ionescu, Mihnea; Vasilescu, Catalin; Popescu, Irinel

    2017-01-01

    Background: The benefit of hepatic resection in case of concomitant colorectal hepatic and extrahepatic metastases (CHEHMs) is still debatable. The purpose of this study is to assess the results of resection of hepatic and extrahepatic metastases in patients with CHEHMs in a high-volume center for both hepatobiliary and colorectal surgery and to identify prognostic factors that correlate with longer survival in these patients. It was performed a retrospective analysis of 678 consecutive patients with liver resection for colorectal cancer metastases operated in a single Centre between April 1996 and March 2016. Among these, 73 patients presented CHEHMs. Univariate analysis was performed to identify the risk factors for overall survival (OS) in these patients. Results: There were 20 CHMs located at the lymphatic node level, 20 at the peritoneal level, 12 at the ovary and lung level, 12 presenting as local relapses and 9 other sites. 53 curative resections (R0) were performed. The difference in overall survival between the CHEHMs group and the CHMs group is statistically significant for the entire groups (p 0.0001), as well as in patients who underwent R0 resection (p 0.0001). In CHEHMs group, the OS was statistically significant higher in patients who underwent R0 resection vs. those with R1/R2 resection (p=0.004). Three variables were identified as prognostic factors for poor OS following univariate analysis: 4 or more hepatic metastases, major hepatectomy and the performance of operation during first period of the study (1996 - 2004). There was a tendency toward better OS in patients with ovarian or pulmonary location of extrahepatic disease, although the difference was not statistically significant. In patients with concomitant hepatic and extrahepatic metastases, complete resection of metastatic burden significantly prolong survival. The patients with up to 4 liver metastases, resectable by minor hepatectomy benefit the most from this aggressive onco

  6. Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-04-14

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

  7. Role of MicroRNA in the Diagnosis and Therapy of Hepatic Metastases from Colorectal Cancer.

    Chorti, Angeliki; Bangeas, Petros; Papavramidis, Theodossis S; Tsoulfas, Georgios

    2018-05-24

    Colorectal cancer is one of the most common malignancies in both genders and liver metastasis appear in more than 50% of patients with colorectal cancer, worsening its morbidity and mortality rates. The existing methods for the diagnosis and prognosis of colorectal cancer seem to be insufficient to predict its aggressiveness, leading to poor outcomes for the patient. MicroRNAs are small non-coding RNAs, which interact with mRNAs in a post-transcriptional stage, and have been found to be involved in pathogenesis of cancer and its metastases. Their utility in diagnosis of colorectal liver metastasis gains ground through serum or tissue examination. Several miRNAs are related to colorectal cancer and its liver metastasis. Some of them have oncogenic and other tumor suppressive role in the development of colorectal liver metastasis, while many of them have been proved to be correlated with the overall survival and prognosis of patients with colorectal cancer. The aim of the present review is to give a detailed account of the different miRNAs that have been described as playing a role in hepatic metastases from colorectal cancer, emphasizing their diagnostic, prognostic and therapeutic implications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Can the National Health Service Cancer Plan timeline be applied to colorectal hepatic metastases?

    Jones, Claire

    2012-02-01

    INTRODUCTION: The National Health Service (NHS) Cancer Plan guidelines recommend a maximum 2-week wait from referral to first appointment, and 2 months from referral to treatment for primary cancers. However, there are currently no guidelines available for metastatic disease. In the UK, nearly half of all colorectal cancer patients develop hepatic metastases. Timely, surgical resection offers the potential for cure. The aim of this study was to audit current practice for colorectal liver metastases in a regional hepatobiliary unit, and compare this to the NHS Cancer Plan standards for primary disease. PATIENTS AND METHODS: A retrospective review of the unit\\'s database was performed for all hepatic metastases referrals from January 2006 to December 2008. The dates of referral, first appointment, investigations and initiation of treatment, along with patient\\'s age and sex, were recorded on Microsoft Excel and analysed. Time was expressed as mean +\\/- SD in days. RESULTS: A total of 102 patients with hepatic metastases were identified. Five were excluded due to incomplete data. The average time from referral to first appointment was 10.6 +\\/- 9.4 days and the average time from referral to treatment was 38.5 +\\/- 28.6 days. Seventy-five (72.7%) had surgical intervention, of whom 37 also had chemotherapy. CONCLUSIONS: The data compare favourably to the NHS Cancer Plan guidelines for primary malignancy, demonstrating that a regional hepatobiliary unit is capable of delivering a service for colorectal liver metastases that adheres to the NHS Cancer Plan. Therefore, the NHS Cancer Plan can be applied to this cohort.

  9. Management of isolated nonresectable liver metastases in colorectal cancer patients: a case-control study of isolated hepatic perfusion with melphalan versus systemic chemotherapy

    van Iersel, L. B. J.; Koopman, M.; van de Velde, C. J. H.; Mol, L.; van Persijn van Meerten, E. L.; Hartgrink, H. H.; Kuppen, P. J. K.; Vahrmeijer, A. L.; Nortier, J. W. R.; Tollenaar, R. A. E. M.; Punt, C.; Gelderblom, H.

    2010-01-01

    To compare the median overall survival of patients with isolated nonresectable liver metastases in comparable groups of patients treated with either isolated hepatic perfusion (IHP) with melphalan or systemic chemotherapy. Colorectal cancer patients with isolated liver metastases, who underwent IHP,

  10. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Fendler, Wolfgang Peter; Ilhan, Harun; Paprottka, Philipp M.; Jakobs, Tobias F.; Heinemann, Volker; Bartenstein, Peter; Haug, Alexander R.; Khalaf, Feras; Ezziddin, Samer; Hacker, Marcus

    2015-01-01

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  11. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Fendler, Wolfgang Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Paprottka, Philipp M. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Jakobs, Tobias F. [Hospital Barmherzige Brueder, Department of Diagnostic and Interventional Radiology, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter; Haug, Alexander R. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Khalaf, Feras [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Ezziddin, Samer [Saarland University Medical Center, Department of Nuclear Medicine, Homburg (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

    2015-09-15

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  12. The economic impact of 18FDG positron emission tomography in the surgical management of colorectal cancer with hepatic metastases.

    Zubeldia, Jose M; Bednarczyk, Edward M; Baker, John G; Nabi, Hani A

    2005-08-01

    (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is recognized as a powerful tool in the management of patients with recurrent and/or metastatic colorectal cancer. The aim of this was was to analyze costs from the payer's perspective, of adding FDG-PET to a computed tomography (CT) scan preoperatively in colorectal cancer patients with resectable hepatic metastases. CT with and without FDG-PET were compared among patients with colorectal cancer in staging for surgical resection of hepatic metastases. Outcomes included uncomplicated surgery, complicated surgery, or death. Extrahepatic disease occurrence rates and diagnostic accuracy of CT and FDG-PET were obtained from published sources. Complication rates and costs for CT, FDG-PET, and surgical procedures were obtained from Healthcare Finance Administration data. The average expected surgical cost per patient when FDG-PET was used to determine the presence of extrahepatic disease was 16,278 dollars compared to 21,547 dollars for conventional management-a net savings of 5,269 dollars. Integration of FDG-PET into the presurgical evaluation of patients with hepatic metastases could substantially reduce overall costs and patients' morbidity. This substantial net saving results from the unique ability of FDG-PET in excluding patients with extrahepatic disease, and avoiding unnecessary surgical expenses.

  13. Synchronous colorectal liver metastases

    A.E.M. van der Pool (Anne)

    2011-01-01

    textabstractColorectal cancer is one of the most common malignancies worldwide and ranks second in cancer-related deaths in many parts of the Western world. Once in the lymph or blood vessels, colorectal cancer can quickly spread and the liver is known to be a favourable site for metastases. The

  14. Potential of MR histogram analyses for prediction of response to chemotherapy in patients with colorectal hepatic metastases.

    Liang, He-Yue; Huang, Ya-Qin; Yang, Zhao-Xia; Ying-Ding; Zeng, Meng-Su; Rao, Sheng-Xiang

    2016-07-01

    To determine if magnetic resonance imaging (MRI) histogram analyses can help predict response to chemotherapy in patients with colorectal hepatic metastases by using response evaluation criteria in solid tumours (RECIST1.1) as the reference standard. Standard MRI including diffusion-weighted imaging (b=0, 500 s/mm(2)) was performed before chemotherapy in 53 patients with colorectal hepatic metastases. Histograms were performed for apparent diffusion coefficient (ADC) maps, arterial, and portal venous phase images; thereafter, mean, percentiles (1st, 10th, 50th, 90th, 99th), skewness, kurtosis, and variance were generated. Quantitative histogram parameters were compared between responders (partial and complete response, n=15) and non-responders (progressive and stable disease, n=38). Receiver operator characteristics (ROC) analyses were further analyzed for the significant parameters. The mean, 1st percentile, 10th percentile, 50th percentile, 90th percentile, 99th percentile of the ADC maps were significantly lower in responding group than that in non-responding group (p=0.000-0.002) with area under the ROC curve (AUCs) of 0.76-0.82. The histogram parameters of arterial and portal venous phase showed no significant difference (p>0.05) between the two groups. Histogram-derived parameters for ADC maps seem to be a promising tool for predicting response to chemotherapy in patients with colorectal hepatic metastases. • ADC histogram analyses can potentially predict chemotherapy response in colorectal liver metastases. • Lower histogram-derived parameters (mean, percentiles) for ADC tend to have good response. • MR enhancement histogram analyses are not reliable to predict response.

  15. Response of colo-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil

    Rotman, M.; Kuruvilla, A.M.; Choi, K.; Bhutiani, I.; Aziz, H.; Rosenthal, J.; Braverman, A.; Marti, J.; Brandys, M.

    1986-12-01

    Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.

  16. Significance of diagnosis of liver metastases from colorectal cancer by angio helical CT and intermittent hepatic arterial infusion chemotherapy after hepatic resection in terms of prognosis

    Hatsuse, Kazuo; Aoki, Hideki; Murayama, Michinori

    1997-01-01

    Seventy five cases had undergone hepatic resection for liver metastases from colorectal cancer from 1979 to 1994. Computed tomography during hepatic angiography (angio CT) was tried in 27 cases. At first, we compared detection ratios of angio CT for liver metastase to those of ultrasonography, conventional CT, and operative ultrasonography on these 27 cases. Next, the prognosis of seventy five cases was examined. They were divided into three groups; the HX group 29 cases with only hepatic resection; the HX+AP group of 19 cases with intermittent hepatic arterial infusion chemotherapy after hepatic resection; the angio CT group of 27 cases selected for hepatic resection by angio CT, followed by the same infusion chemotherapy as that given to the HX+AP group. Fifty metastases were diagnosed histopathologically in twenty seven cases that underwent hepatic resection after angio CT. Detection ratios for small metastases 1.0 cm or smaller in diameter were 8.3% with ultrasonography, 25% with CT, 75% with angio CT, and 50% with operative ultrasonography. Detection ratios of angio CT were superior to those of ultrasonography and CT. Recurrence rates of the remnant liver were significantly low and survival rates were significantly superior in the angio CT group compared to the other two groups (p<0.02). The prognosis with and without intermittent hepatic arterial infusion chemotherapy after hepatic resection were significantly different (p<0.03). The above data suggest that improvement of detection ratios for liver metastases by angio CT, and probably concomitant intermittent hepatic infusion chemotherapy contribute to decreased remnant liver recurrence and an increased survival rate. (author)

  17. Decision tree analysis to assess the cost-effectiveness of yttrium microspheres for treatment of hepatic metastases from colorectal cancer

    Kelley, B.B.; Walker, G.D.; Miles, K.A.

    2002-01-01

    Full text: The aim is to determine the cost-effectiveness of yttrium microsphere treatment of hepatic metastases from colorectal cancer, with and without FDG-PET for detection of extra-hepatic disease. A decision tree was created comparing two strategies for yttrium treatment with chemotherapy, one incorporating PET in addition to CT in the pre-treatment work-up, to a strategy of chemotherapy alone. The sensitivity and specificity of PET and CT were obtained from the Federal Government PET review. Imaging costs were obtained from the Medicare benefits schedule with an additional capital component added for PET (final cost $1200). The cost of yttrium treatment was determined by patient-tracking. Previously published reports indicated a mean gain in life-expectancy from treatment of 0.52 years. Patients with extra-hepatic metastases were assumed to receive no survival benefit. Cost effectiveness was expressed as incremental cost per life-year gained (ICER). Sensitivity analysis determined the effect of prior probability of extra-hepatic disease on cost-savings and cost-effectiveness. The cost of yttrium treatment including angiography, particle perfusion studies and bed-stays, was $10530. A baseline value for prior probability of extra-hepatic disease of 0.35 gave ICERs of $26,378 and $25,271 for the no-PET and PET strategies respectively. The PET strategy was less expensive if the prior probability of extra-hepatic metastases was greater than 0.16 and more cost-effective if above 0.28. Yttrium microsphere treatment is less cost-effective than other interventions for colon cancer but comparable to other accepted health interventions. Incorporating PET into the pre-treatment assessment is likely to save costs and improve cost-effectiveness. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  18. Intrabilary obstruction by colorectal metastases

    Traeger, Luke; Kiroff, George

    2018-01-01

    Abstract Intrabiliary colorectal metastases are rare. We present a case of an 84-year-old man who developed obstructive jaundice secondary to intrabiliary growth of colorectal metastases. The patient presented with three weeks of jaundice and significant weight loss in the preceding months. The patient’s background included metastatic colorectal carcinoma, with a previous right hemicolectomy and left hepatectomy for liver metastases. A MRCP showed an obstruction of the biliary tract transitio...

  19. Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy

    Lewandowski, Robert J.; Memon, Khairuddin; Hickey, Ryan; Gates, Vanessa L.; Atassi, Bassel; Vouche, Michael; Atassi, Rohi; Desai, Kush; Hohlastos, Elias; Sato, Kent; Habib, Ali [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Mulcahy, Mary F.; Kircher, Sheetal; Newman, Steven B.; Nimeiri, Halla; Benson, Al B. [Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States); Marshall, Karen; Williams, Melissa; Salzig, Krystina; Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

    2014-10-15

    The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC. (orig.)

  20. Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

    Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

    2009-07-08

    Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently

  1. Brain metastases from colorectal cancer

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  2. Response rates of hepatocellular carcinoma and hepatic colorectal cancer metastases to drug eluting bead regional liver therapy

    Glenn W. Stambo; Deborah Cragan

    2017-01-01

    Aim: The purpose of this study was to evaluate and compare how hepatocellular carcinoma (HCC) and colorectal metastases respond to LC Bead chemoembolization using doxorubicin and irinotecan. Methods: The authors report their experience with doxorubicin and irinotecan eluting beads to treat 13 patients with primary HCC and 25 patients with colorectal metastases over a 1-year period at a single community based oncology practice. Within the colorectal cancer group they compared irinotecan eluting beads to doxorubicin eluting beads. Results:Nine of the 11 (81.8%) doxorubicin treated HCC patients had either complete response or partial response. All of the HCC lesions showed reduction in size and tumor enhancement and 10/11 (91%) HCC patients were alive at 24 months post treatment. Fisher's exact test revealed that among the 22 with colorectal metastases for whom follow-up data were available, those 11 who were treated with doxorubicin were significantly more likely to demonstrate complete or partial response compared to the 11 in the irinotecan treated group (P < 0.001). Conclusion:Overall, HCC and colon metastasis patients clearly demonstrated the effectiveness of drug eluting beads with 91% of the HCC patients alive 24 months after treatment.

  3. Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients.

    Nordlinger, B; Quilichini, M A; Parc, R; Hannoun, L; Delva, E; Huguet, C

    1987-01-01

    This report analyses an experience with 80 liver resections for metastatic colorectal carcinoma. Primary colorectal cancers had all been resected. Liver metastases were solitary in 44 patients, multiple in 36 patients, unilobar in 76 patients, and bilobar in 4 patients. Tumor size was less than 5 cm in 33 patients, 5-10 cm in 30 patients, and larger than 10 cm in 17 patients. There were 43 synchronous and 37 metachronous liver metastases with a delay of 2-70 months. The surgical procedures included more major liver resections (55 patients) than wedge resections (25 patients). Portal triad occlusion was used in most cases, and complete vascular exclusion of the liver was performed for resection of the larger tumors. In-hospital mortality rate was 5%. Three- and 5-year survival rates were 40.5% and 24.9%, respectively. None of the analysed criteria: size and number of liver metastases, delay after diagnosis of the primary cancer, Duke's stage, could differentiate long survivors from patients who did not benefit much from liver surgery due to early recurrence. Recurrences were observed in 51 patients during the study, two thirds occurring during the first year after liver surgery. Eight patients had resection of "secondary" metastases after a first liver resection: two patients for extrahepatic recurrences and six patients for liver recurrences. Encouraging results raise the question of how far agressive surgery for liver metastases should go. PMID:3827361

  4. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era?

    Mocellin, Simone; Pilati, Pierluigi; Lise, Mario; Nitti, Donato

    2007-12-10

    The treatment of unresectable liver-confined metastatic disease from colorectal cancer (CRC) is a challenging issue. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomized controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT). To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves. HAI regimens were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT, fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU + leucovorin, or a miscellany of FU and best supportive care in three, one, four, and two studies, respectively. Pooling the data, tumor response rate was 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively; the meta-risk of death was not statistically different between the two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24). Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.

  5. Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

    Goldberg, J A; Bradnam, M S; Kerr, D J; McKillop, J H; Bessent, R G; McArdle, C S; Willmott, N; George, W D

    1987-12-01

    As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

  6. Treatment of colorectal liver metastases

    Ismaili Nabil

    2011-11-01

    Full Text Available Abstract Colorectal cancer (CRC is the third most common cancer in the word. Liver metastasis is the most common site of colorectal metastases. The prognosis of resectable colorectal liver metastases (CRLM was improved in the recent years with the consideration of chemotherapy and surgical resection as part of the multidisciplinary management of the disease; the current 5-year survival rates after resection of liver metastases are 25% to 40%. Resectable synchronous or metachronous liver metastases should be treated with perioperative chemotherapy based on three months of FOLFOX4 (5-fluorouracil [5FU], folinic acid [LV], and oxaliplatin chemotherapy before surgery and three months after surgery. In the case of primary surgery, pseudo-adjuvant chemotherapy for 6 months, based on 5FU/LV, FOLFOX4, XELOX (capecitabine and oxaliplatin or FOLFIRI (5FU/LV and irinotecan, should be indicated. In potentially resectable disease, primary chemotherapy based on more intensive regimens such as FOLFIRINOX (5FU/LV, irinotecan and oxaliplatin should be considered to enhance the chance of cure. The palliative chemotherapy based on FOLFIRI, or FOLFOX4/XELOX with or without targeted therapies, is the mainstay treatment of unresectable disease. This review would provide additional insight into the problem of optimal integration of chemotherapy and surgery in the management of CRLM.

  7. Resection Of Hepatal Metastases In Patients With Colorectal Carcinoma - Multidisciplinary Approach

    Hlavata, Z.

    2007-01-01

    Recent developments in the treatment of colorectal cancer have focused on the role of chemotherapy as systemic treatment in an attempt to prolong survival and improve treatment outcomes for patients. Despite the use of systemic chemotherapy, however, the median survival of patients with metastatic disease has been reported 33 months in maximum. It is important to underline the role of surgery not only by the elimination of the primary tumor, but also of metastasis in the liver. Using correct combination of surgery and chemotherapy for the treatment of metastatic disease, substantial prolongation in the survival can be achieved. Communication between oncologist, surgeon and radiologist as the multidisciplinary approach is crucial for correct management of patients with metastatic liver disease with respect to their maximal benefit. (author)

  8. Outcomes of Therasphere Radioembolization for Colorectal Metastases.

    Abbott, Andrea M; Kim, Richard; Hoffe, Sarah E; Arslan, Bulent; Biebel, Ben; Choi, Junsung; El-Haddad, Ghassan; Kis, Bela; Sweeney, Jennifer; Meredith, Kenneth L; Almhanna, Khaldoun; Strosberg, Jonathan; Shibata, David; Fulp, William J; Shridhar, Ravi

    2015-09-01

    The liver is the most common site for colorectal cancer (CRC) metastases. Radioembolization with yttrium-90 (Y90) represents an alternative approach in the management of unresectable hepatic colorectal metastases. The objective of this study was to evaluate outcomes after treatment with Y90. A retrospective review of patients undergoing Y90 glass microsphere treatment for metastatic CRC from 2009 to 2013 was conducted. Multivariable analysis (MVA) of factors related to overall survival (OS) was performed using the Cox proportional hazard and OS estimates were calculated using the Kaplan-Meier method. We identified 68 patients. Median and 2-year OS were 11.6 months and 34%. For patients with ≤ 25% hepatic burden of disease (HBD) and 1 chemotherapy regimen, 2-year OS was 63%. Median and 2-year OS for patients with ≤ 25% versus > 25% HBD were 19.6 months and 42% versus 3.4 months and 0% (P 25% HBD, ≥ 3 lines of chemotherapy, and higher CEA were independently prognostic for increased mortality, and resected status of the primary tumor was associated with decreased mortality. The presence of extrahepatic metastases was not prognostic. Toxicities were mild and only 5 patients experienced Grade 3/4 biochemical toxicity. Yttrium-90 was associated with acceptable OS with minimal morbidity in this series. Minimal exposure to chemotherapy and low HBD were found to be associated with better OS, however, even patients with chemotherapy-refractory disease received a benefit from treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

    Hernández-Socorro, Carmen Rosa; Saavedra, Pedro; Ramírez Felipe, José; Bohn Sarmiento, Uriel; Ruiz-Santana, Sergio

    2017-04-21

    The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  10. Randomized phase II study of 5-fluorouracil hepatic arterial infusion with or without antineoplastons as an adjuvant therapy after hepatectomy for liver metastases from colorectal cancer.

    Yutaka Ogata

    Full Text Available Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10, phenylacetylglutamine plus phenylacetylisoglutamine (A10-I, and phenylacetylglutamine plus phenylacetate (AS2-1. This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver.Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1 plus HAI (AN arm or HAI alone (control arm based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS; secondary endpoints were relapse-free survival (RFS, status and extent of recurrence, salvage surgery (rate and toxicity.Overall survival was not statistically improved (p=0.105 in the AN arm (n=32. RFS was not significant (p=0.343. Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33 with a median survival time 67 months (95%CI 43-not calculated versus 39 months (95%CI 28-47 (p=0.037 and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No

  11. Phase II study on stereotactic body radiotherapy of colorectal metastases

    Høyer, Morten; Roed, Henrik; Traberg Hansen, Anders

    2006-01-01

    Surgical resection provides long term survival in approximately 30% of patients with colorectal carcinoma (CRC) liver metastases. However, only a limited number of patients with CRC-metastases are amendable for surgery. We have tested the effect of stereotactic body radiotherapy (SBRT) in the tre......Surgical resection provides long term survival in approximately 30% of patients with colorectal carcinoma (CRC) liver metastases. However, only a limited number of patients with CRC-metastases are amendable for surgery. We have tested the effect of stereotactic body radiotherapy (SBRT......) in the treatment of inoperable patients with CRC-metastases. Sixty-four patients with a total number of 141 CRC-metastases in the liver (n = 44), lung (n = 12), lymph nodes (n = 3), suprarenal gland (n = 1) or two organs (n = 4) were treated with SBRT with a central dose of 15 Gy x 3 within 5-8 days. Median follow...... due to hepatic failure, one patient was operated for a colonic perforation and two patients were conservatively treated for duodenal ulcerations. Beside these, only moderate toxicities such as nausea, diarrhoea and skin reactions were observed. SBRT in patients with inoperable CRC-metastases resulted...

  12. Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy

    Alexander, HR.; Libutti, S. K.; Barlett, D. L.; Pingpank, J. F.; Kranda, Karel; Helsabeck, C.; Beresnev, T.

    2002-01-01

    Roč. 95, č. 4 (2002), s. 730-736 ISSN 0008-543X R&D Projects: GA AV ČR KSK4055109 Keywords : colorectal carcinoma * liver metastases * regional chemotherapy Subject RIV: FD - Oncology ; Hematology Impact factor: 1.000, year: 2002

  13. Cytogenetic findings in metastases from colorectal cancer

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

  14. LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

    Schimanski Carl

    2012-04-01

    Full Text Available Abstract Background 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2 and 12-week (year 3 intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS time between groups. Secondary endpoints are overall survival (OS time, safety, tolerability, RFS/OS in MUC-1 positive

  15. Specific extracellular matrix remodeling signature of colon hepatic metastases.

    Maguy Del Rio

    Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

  16. Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228).

    Lévi, Francis; Karaboué, Abdoulaye; Saffroy, Raphaël; Desterke, Christophe; Boige, Valerie; Smith, Denis; Hebbar, Mohamed; Innominato, Pasquale; Taieb, Julien; Carvalho, Carlos; Guimbaud, Rosine; Focan, Christian; Bouchahda, Mohamed; Adam, René; Ducreux, Michel; Milano, Gérard; Lemoine, Antoinette

    2017-09-26

    The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes. Single-nucleotide polymorphisms passing stringent Hardy-Weinberg equilibrium test were tested for their association with outcomes in 52 patients (male/female, 36/16; WHO PS, 0-1). VKORC1 SNPs (rs9923231 and rs9934438) were associated with early and objective responses, and survival. For rs9923231, T/T achieved more early responses than C/T (50% vs 5%, P=0.029) and greatest 4-year survival (46% vs 0%, P=0.006). N-acetyltransferase-2 (rs1041983 and rs1801280) were associated with up to seven-fold more macroscopically complete hepatectomies. Progression-free survival was largest in ABCB1 rs1045642 T/T (P=0.026) and rs2032582 T/T (P=0.035). Associations were found between toxicities and gene variants (P<0.05), including neutropenia with ABCB1 (rs1045642) and SLC0B3 (rs4149117 and rs7311358); and diarrhoea with CYP2C9 (rs1057910), CYP2C19 (rs3758581), UGT1A6 (rs4124874) and SLC22A1 (rs72552763). VKORC1, NAT2 and ABCB1 variants predicted for HAI efficacy. Pharmacogenetics could guide the personalisation of liver-targeted medico-surgical therapies.

  17. Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

    Akinwande, Olaguoke K., E-mail: gokeakin@gmail.com [University of Louisville Hospital, Department of Interventional Radiology (United States); Philips, Prejesh, E-mail: prejesh.philips@louisville.edu [University of Louisville, Division of Surgical Oncology, Department of Surgery (United States); Duras, Petr, E-mail: durasp@seznam.cz [Fakultní nemocnice Plzeň (Czech Republic); Pluntke, Stefan, E-mail: stefan.pluntke@t-online.de [Onkologe bei Kliniken Essen-Mitte (Germany); Scoggins, Charles, E-mail: charles.scoggins@louisville.edu; Martin, Robert C. G., E-mail: Robert.Martin@louisville.edu [University of Louisville, Division of Surgical Oncology, Department of Surgery (United States)

    2015-04-15

    PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02) in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity.

  18. Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

    Akinwande, Olaguoke K.; Philips, Prejesh; Duras, Petr; Pluntke, Stefan; Scoggins, Charles; Martin, Robert C. G.

    2015-01-01

    PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02) in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity

  19. Colorectal liver metastases: factors affecting outcome after surgery

    Snoeren, N.

    2013-01-01

    Colorectal cancer is the second leading cause of cancer related death in Europe. The overall survival rate of patients with colorectal cancer is greatly affected by the presence of liver metastases, which occurs in about 50% of patients. Radical resection of colorectal liver metastases means a

  20. Ultrasound imaging of flow patterns in liver metastases from colorectal cancer

    Rafaelsen, Søren Rafael; Solvig, Jan

    2004-01-01

    BACKGROUND: The ability of colour Doppler, power Doppler and echo-enhanced Doppler imaging to detect the blood flow in liver metastases from colorectal cancer was investigated. An evaluation was then made to determine whether the flow pattern could be used as an indication of disease elsewhere....... METHODS: Forty-two patients with hepatic metastases from colorectal cancer were examined, 8 of whom had local recurrence of their colorectal cancer. Seventy-seven liver metastases were evaluated with colour Doppler and power Doppler, and the presence or absence of a Doppler signal in the halo or centre...... was noted. Forty-three of these metastases were further examined after contrast media echo-enhancement. RESULTS: Signals from the peripheral halo were detected by colour Doppler imaging in 34% of the metastases, and in 77% by power Doppler (P power Doppler...

  1. Detection of colorectal hepatic metastases using MnDPDP MR imaging and diffusion-weighted imaging (DWI) alone and in combination

    Koh, D.M.; Brown, G.; Riddell, A.M.; Scurr, E.; Allen, S.D.; Husband, J.E.; Collins, D.J.; Souza, N.M. de; Leach, M.O.; Chau, I.; Cunningham, D.

    2008-01-01

    To compare the diagnostic accuracy of MnDPDP MR imaging and diffusion-weighted imaging (DWI), alone and in combination, for detecting colorectal liver metastases in patients with suspected metastatic disease. Thirty-three consecutive patients with suspected colorectal liver metastases underwent MR imaging. Three image sets (MnDPDP, DWI and combined MnDPDP and DWI) were reviewed independently by two observers. Lesions were scored on a five-point scale for malignancy and the areas (Az) under the receiver operating characteristic curves were calculated for each observer and image set. The sensitivity and specificity for lesion detection were calculated for each image set and compared. There were 83 metastases, 49 cysts and 1 haemangioma. Using the combined set resulted in the highest diagnostic accuracy for both observers (Az = 0.94 and 0.96), with improved averaged sensitivity of lesion detection compared with the DWI set (p = 0.01), and a trend towards improved sensitivity compared with the MnDPDP set (p = 0.06). There was no difference in the averaged specificity using any of the three image sets (p > 0.5). Combination of MnDPDP MR imaging and DWI resulted in the highest diagnostic accuracy and can increase sensitivity without loss in specificity. (orig.)

  2. Influence of Transfusions on Perioperative and Long-Term Outcome in Patients Following Hepatic Resection for Colorectal Metastases

    Kooby, David A.; Stockman, Jennifer; Ben-Porat, Leah; Gonen, Mithat; Jarnagin, William R.; Dematteo, Ronald P.; Tuorto, Scott; Wuest, David; Blumgart, Leslie H.; Fong, Yuman

    2003-01-01

    Objective To determine if transfusion affected perioperative and long-term outcome in patients undergoing liver resection for metastatic colorectal cancer. Summary Background Data Blood transfusion produces host immunosuppression and has been postulated to result in adverse outcome for patients undergoing surgical resection of malignancies. Methods Blood transfusion records and clinical outcomes for 1,351 patients undergoing liver resection at a tertiary cancer referral center were analyzed. Results Blood transfusion was associated with adverse outcome after liver resection. The greatest effect was in the perioperative course, where transfusion was an independent predictor of operative mortality, complications, major complications, and length of hospital stay. This effect was dose-related. Patients receiving one or two units or more than two units had an operative mortality of 2.5% and 11.1%, respectively, compared to 1.2% for patients not requiring transfusions. Transfusion was also associated with adverse long-term survival by univariate analysis, but this factor was not significant on multivariate analysis. Even patients receiving only one or two units had a more adverse outcome. Conclusions Perioperative blood transfusion is a risk factor for poor outcome after liver resection. Blood conservation methods should be used to avoid transfusion, especially in patents currently requiring limited amounts of transfused blood products. PMID:12796583

  3. Scrotal metastases from colorectal carcinoma: a case report.

    McWeeney, Doireann M

    2012-01-31

    ABSTRACT: A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier\\'s gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin.

  4. [Management of synchronous colorectal liver metastases].

    Dupré, Aurélien; Gagnière, Johan; Chen, Yao; Rivoire, Michel

    2013-04-01

    At time of diagnosis, 10 to 25% of patients with colorectal cancer present synchronous liver metastases. The treatment of such patients remains controversial without any evidence based organization. Therapeutic sequences are discussed including chemotherapy, colorectal surgery, liver resection and even radio-chemotherapy for some rectal cancers. In case of resectable liver metastases, preoperative chemotherapy offers the advantage of earlier treatment of micro-metastases as well as evaluation of tumor responsiveness, which can help shape future therapy. In this setting, different surgical strategies can be chosen (classical staged procedures with colorectal surgery followed by liver surgery, simultaneous resections or liver first approach) depending on the importance of the primary and metastatic tumors. The literature remains limited, but the results of these strategies seem identical in term of postoperative morbidity and long-term survival. Staged procedures are preferred in case of major liver resection. Location of the primary tumor on the low or mid rectum will necessitate preoperative long course chemoradiotherapy and a more complex multidisciplinary organization. For patients with extensive liver metastases, non-resectability must be assessed by experienced surgeon and radiologist before treatment and during chemotherapy. In this group of patients, improved chemotherapy regimen associated with targeted therapies and new surgical strategies (portal vein embolization, ablation, staged hepatectomies…) have improved resection rate (15 to 30-40%) and long-term survival. Treatment organization for the primary tumor remains controversial. Resection of the primary to manage symptoms such as obstruction, perforation or bleeding is advocated. For patients with asymptomatic primary a non-surgical approach permits to begin rapidly chemotherapy and obtain a better control of the disease. On the other hand, initial resection of the primary may avoid complications and

  5. Roentgen therapy of hepatic metastases

    Phillips, R.; Karnofsky, D.A.; Hamilton, L.D.; Nickson, J.J.

    1984-01-01

    The results of treatment of hepatic metastases secondary to carcinoma of the breast, bronchus and gastrointestinal tract, are reported in 36 patients; asymptomatic improvement was obtained in 26 patients. The symptomatic relief of pain, anorexia, nausea, vomiting, weakness, fatigue, sweating and abdominal distention was accompanied by reduction in the size of the enlarged liver, by gain in body weight, and by improvement in liver function as measured by determination of the serum bilirubin, alkaline phosphatase, cholesterols and proteins, and by the bromsulphalein retention test, the prothrombin time, the cephalin flocculation test and the thymol turbidity. The method of treatment was supervoltage roentgen therapy alone in 22 cases; in 14 cases a single intravenous dose of nitrogen mustard (0.4 mg. per kilogram body weight) was given immediately before the first roentgen treatment. The whole liver, however large, was irradiated through opposed anterior and posterior fields, and the tumor dose ranged from 2,000 to 3,750 roentgens. The over-all time of treatment was eight days in 24 cases, fifteen days in 6 cases, and twenty-two days in 6 cases

  6. [Percutaneous radiofrequency ablation of hepatic metastases. Preliminary experience].

    De Baere, T; Elias, D; Ducreux, M; Dromain, C; Kuach, V; Gamal El Din, M; Sobotka, A; Lasser, P; Roche, A

    1999-11-01

    To evaluate the efficiency of percutaneous radiofrequency ablation in the treatment of liver metastases. Eighteen patients with 31 liver metastases, mainly from colorectal cancer, 10 - 35 mm in diameter (m = 23), underwent 26 courses of percutaneous radiofrequency ablation. Fifteen patients had previously undergone hepatectomy, and 3 patients had contra-indications to surgery. Imaging guidance was ultrasound in 21 patients, CT in 4 (tumors not seen with ultrasound), and both in 1. A generator working at 450 KHz with a maximum output power of 150 W was used to treat each lesion for 18 - 20 min. Treatment was monitored with real time ultrasound. Among the 12 patients followed more than 3 months, only one of the 24 treated lesions recurred after a mean follow up of 259 ¿ 109 days. Liver disease was controlled in 8 of the 12 patients after 90 - 509 days (m = 306). Among these 8 patients, 3 were tumor free after 559, 378 and 90 days, respectively; 2 died tumor free of non-tumoral disease (pulmonary embolism, digestive bleeding); 3 developed lung metastases treated with chemotherapy (n = 2) or surgery (n = 1). Three of the 12 patients had widespread hepatic tumor occurrence, and one patient died of these metastases. Six patients experienced mild skin burns, but no major complication was observed. Radiofrequency ablation of hepatic metastases appears safe and promising in this preliminary experience. Further investigation is needed.

  7. Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes.

    Boas, F Edward; Bodei, Lisa; Sofocleous, Constantinos T

    2017-09-01

    Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using 90 Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types of 90 Y microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of 90 Y microspheres selectively to treat a tumor

  8. Unresectable liver metastases in colorectal cancer: review of current strategies.

    Sueur, Benjamin; Pellerin, Olivier; Voron, Thibault; Pointet, Anne L; Taieb, Julien; Pernot, Simon

    2016-12-01

    The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.

  9. The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy

    Robertson, John M; Lawrence, Theodore S; Walker, Suzette; Kessler, Marc L; Andrews, James C; Ensminger, William D

    1995-05-15

    Purpose: Whole-liver radiation, with or without chemotherapy, has been of modest benefit in the treatment of unresectable hepatic metastases from colorectal cancer. A Phase I/II study combining escalating doses of conformally planned radiation therapy (RT) with intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd) was performed. Methods and Materials: Twenty-two patients with unresectable hepatic metastases from colorectal cancer, 14 of whom had progressed after previous chemotherapy (2 with prior IAH FdUrd), were treated with concurrent IAH FdUrd (0.2 mg/kg/day) and conformal hepatic radiation therapy (1.5-1.65 Gy/fraction twice a day). The total dose of radiation given to the tumor (48-72.6 Gy) depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for response, toxicity, hepatobiliary relapse, and survival. Median potential follow-up was 42 months. Results: Eleven of 22 patients demonstrated an objective response, with the remainder showing stable disease. Actuarial freedom from hepatic progression was 25% at 1 year. The most common acute toxicity was mild to moderate nausea and transient liver function test abnormalities. There were three patients with gastrointestinal bleeding (none requiring surgical intervention) after the completion of treatment. Overall median survival was 20 months. The presence of extrahepatic disease was associated with decreased survival (p < 0.01). Conclusions: Combined conformal radiation therapy and IAH FdUrd can produce an objective response in 50% of patients with hepatic metastases from colorectal cancer. However, response was not durable, and hepatic progression was frequent. Improvements in hepatic tumor control for patients with metastatic colorectal cancer may require higher doses of conformal radiation and/or improved radiosensitization. In an effort to increase radiosensitization, we have recently initiated a clinical trial combining IAH bromodeoxyuridine, a thymidine analog

  10. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  11. The prognostic significance of lymphatics in colorectal liver metastases.

    Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

    2014-01-01

    Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  12. The Prognostic Significance of Lymphatics in Colorectal Liver Metastases

    Vijayaragavan Muralidharan

    2014-01-01

    Full Text Available Background. Colorectal Cancer (CRC is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%–60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM and surrounding host tissue. Lymphatic vessel density (LVD was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P=0.01, P>0.01, and P=0.05, resp.. Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P=0.05. Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

  13. Evaluation of a gadolinium-based nanoparticle (AGuIX) for contrast-enhanced MRI of the liver in a rat model of hepatic colorectal cancer metastases at 9.4 tesla

    Fries, P.; Morr, D.; Mueller, A.; Massmann, A.; Seidel, R.; Schneider, G.; Buecker, A. [Saarland University Medical Center, Homburg (Germany). Clinic of Diagnostic and Interventional Radiology; Lux, F.; Tillement, O. [Universite Claude Bernard, Lyon (France). Laboratoire de Physico-Chimie des Materiaux Luminescents; Schaefer, T. [Saarland University Medical Center, Homburg (Germany). Dept. of General, Visceral and Pediatric Surgery; Menger, M.D. [Saarland University Medical Center, Homburg (Germany). Inst. for Clinical and Experimental Surgery

    2015-12-15

    The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE=45/2.5 ms, alpha = 45 , TA=1: 23 min, FOV=5.12 x 5.12 cm{sup 2}, matrix = 256 x 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 ± 0.7; AGuIX: 28.2 ± 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 ± 1.2; AGuIX: 29.6 ± 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 ± 0.7; AGuIX: 15.4 ± 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 ± 0.3; AGuIX: 14.0 ± 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 ± 0.2; AGuIX: -7.5 ± 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 ± 0.7; AGuIX: 14.9 ± 2.8, p=0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors.

  14. Evaluation of a gadolinium-based nanoparticle (AGuIX) for contrast-enhanced MRI of the liver in a rat model of hepatic colorectal cancer metastases at 9.4 tesla

    Fries, P.; Morr, D.; Mueller, A.; Massmann, A.; Seidel, R.; Schneider, G.; Buecker, A.; Lux, F.; Tillement, O.; Schaefer, T.; Menger, M.D.

    2015-01-01

    The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE=45/2.5 ms, alpha = 45 , TA=1: 23 min, FOV=5.12 x 5.12 cm 2 , matrix = 256 x 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 ± 0.7; AGuIX: 28.2 ± 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 ± 1.2; AGuIX: 29.6 ± 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 ± 0.7; AGuIX: 15.4 ± 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 ± 0.3; AGuIX: 14.0 ± 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 ± 0.2; AGuIX: -7.5 ± 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 ± 0.7; AGuIX: 14.9 ± 2.8, p=0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors.

  15. Gd-EOB-DTPA-Enhanced MRI for Detection of Liver Metastases from Colorectal Cancer: A Surgeon’s Perspective!

    Kelly J. Lafaro

    2013-01-01

    Full Text Available Colorectal cancer affects over one million people worldwide annually, with the liver being the most common site of metastatic spread. Adequate resection of hepatic metastases is the only chance for a cure in a subset of patients, and five-year survival increases to 35% with complete resection. Traditionally, computed tomographic imaging (CT was utilized for staging and to evaluate metastases in the liver. Recently, the introduction of hepatobiliary contrast-enhanced magnetic resonance imaging (MRI agents including gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Eovist in the United States, Primovist in Europe, or Gd-EOB-DTPA has proved to be a sensitive method for detection of hepatic metastases. Accurate detection of liver metastases is critical for staging of colorectal cancer as well as preoperative planning.

  16. Minimally invasive surgery using the open magnetic resonance imaging system combined with video-assisted thoracoscopic surgery for synchronous hepatic and pulmonary metastases from colorectal cancer: report of four cases.

    Sonoda, Hiromichi; Shimizu, Tomoharu; Takebayashi, Katsushi; Ohta, Hiroyuki; Murakami, Koichiro; Shiomi, Hisanori; Naka, Shigeyuki; Hanaoka, Jun; Tani, Tohru

    2015-05-01

    Simultaneous resection of hepatic and pulmonary metastases (HPM) from colorectal cancer (CRC) has been reported to be effective, but it is also considered invasive. We report the preliminary results of performing minimally invasive surgery using the open magnetic resonance (MR) imaging system to resect synchronous HPM from CRC in four patients. All four patients were referred for thoracoscopy-assisted interventional MR-guided microwave coagulation therapy (T-IVMR-MCT) combined with video-assisted thoracoscopic surgery (VATS). The median diameters of the HPM were 18.2 and 23.2 mm, respectively. The median duration of VATS and T-IVMR-MCT was 82.5 and 139 min, respectively. All patients were discharged without any major postoperative complications. One patient was still free of disease at 24 months and the others died of disease progression 13, 36, and 47 months without evidence of recurrence in the treated area. Thus, simultaneous VATS + T-IVMR-MCT appears to be an effective option as a minimally invasive treatment for synchronous HPM from CRC.

  17. From scratch: developing a hepatic resection service for metastatic colorectal cancer.

    Wylie, Neil; Hider, Phillip; Armstrong, Delwyn; Rajkomar, Kheman; Srinivasa, Sanket; Rodgers, Michael; Brown, Anna; Koea, Jonathan

    2018-05-01

    Waitemata District Health Board has New Zealand's largest catchment and busiest colorectal unit. The upper gastrointestinal unit was established in 2005, in part to provide a hepatic resection service for patients with colorectal carcinoma metastatic to the liver. The aim of this investigation was to report on quality indicators for the hepatic resection of colorectal carcinoma in the development of a regional resection service. Prospectively collected data on patients undergoing hepatic resection for colorectal carcinoma between 2005 and 2014 was reviewed and correlated with costing data and national hepatic resection rates. A total of 123 patients underwent 138 hepatic resections for metastatic colorectal cancer with a median hospital stay of 8 days (range 4-37 days), a zero 30-day mortality and a median cost of NZ$21 374 for minor hepatectomy and NZ$43 133 for major hepatectomy. Actuarial 5-year disease-free survival was 44%, with 28 patients alive and disease free at 5 years post-resection. Median overall survival was not reached. Review of national hepatic resection rates indicate that Waitemata District Health Board performs one sixth of all hepatic resections in New Zealand and that this treatment modality may be underutilized in the management of patients with metastatic colorectal cancer. A regional hepatic resection centre for colorectal metastases can be established in areas of population need and can provide a high-quality, cost-effective service. © 2016 Royal Australasian College of Surgeons.

  18. Radio-frequency ablation of colorectal liver metastases in 167 patients

    Gillams, A.R.; Lees, W.R.

    2004-01-01

    The objective of this paper is to report our results from a prospective study of 167 patients with colorectal liver metastases treated with radio-frequency ablation (RFA). Three hundred fifty-four treatments were performed in 167 patients, 99 males, mean age 57 years (34-87). The mean number of metastases was 4.1 (1-27). The mean maximum diameter was 3.9 cm (1-12). Fifty-one (31%) had stable/treated extra-hepatic disease. Treatments were performed under general anaesthesia using US and CT guidance and single or cluster water-cooled electrodes (Valleylab, Boulder, CO). All patients had been rejected for or had refused surgical resection. Eighty percent received chemotherapy. Survival data were stratified by tumour burden at the time of first RFA. The mean number of RFA treatments was 2.1 (1-7). During a mean follow-up of 17 months (0-89), 72 developed new liver metastases and 71 developed progressive extra-hepatic disease. There were 14/354 (4%) major local complications and 22/354 (6%) minor local complications. For patients with ≤5 metastases, maximum diameter ≤5 cm and no extra-hepatic disease, the 5-year survival from the time of diagnosis was 30% and from the time of first thermal ablation was 26%. Given that the 5-year survival for operable patients is a median of 32%, our 5-year survival of 30% is promising. (orig.)

  19. Mismatch repair status and synchronous metastases in colorectal cancer

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...

  20. Pulmonary nodules and metastases in colorectal cancer

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...

  1. Boron biodistribution study in colorectal liver metastases patients in Argentina

    Cardoso, J.; Nievas, S.; Pereira, M.; Schwint, A.; Trivillin, V.; Pozzi, E.; Heber, E.; Monti Hughes, A.; Sanchez, P.; Bumaschny, E.; Itoiz, M.; Liberman, S.

    2009-01-01

    Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver≤ 15 Gy-Eq and tumor≥40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6±1)x10 9 n cm -2 s -1 ), ex-situ treatment of liver metastases at RA-3 would be feasible.

  2. Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases

    Mekenkamp, L. J. M.; Koopman, M.; Teerenstra, S.; van Krieken, J. H. J. M.; Mol, L.; Nagtegaal, I. D.; Punt, C. J. A.

    2010-01-01

    Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. We retrospectively investigated patient demographics, primary tumour characteristics and overall

  3. Pulmonary nodules and metastases in colorectal cancer

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...... detected in 7.5% of the patients and in 37% of these cases the metastatic spread was confined to the lungs. The prevalence of SPCM increased with the implementation of thoracic CT in CRC staging. SPCM impaired survival significantly and was associated with increasing age and rectal cancer. Resection...

  4. Histopathological findings in colorectal liver metastases after electrochemotherapy.

    Gorana Gasljevic

    Full Text Available Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8-10 weeks in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8-10 weeks after electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by electrochemotherapy is provided. These findings are important because electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy.

  5. Radiofrequency Ablation for Treating Liver Metastases from a Non-Colorectal Origin

    Yun, Bo La; Lee, Jeong Min; Baek, Ji Hyun; Kim, Se Hyung; Lee, Jae Young; Han, Joon Koo; Choi, Byung Ihn

    2011-01-01

    We wanted to assess the safety and efficacy of performing radiofrequency ablation (RFA) in patients with non-colorectal liver metastases. In this retrospective study, 25 patients with 40 hepatic metastases (M:F = 17:8; mean age, 57 years; tumor size, 0.5-5.0 cm) from a non-colorectal origin (stomach, biliary, breast, pancreas, kidney and skin) were treated with RFA. The RFA procedures were performed using either an internally cooled electrode or a clustered electrode under ultrasound or CT guidance. Contrast-enhanced CT scans were obtained immediately after RFA and follow-up CT scans were performed within three months after ablation and subsequently at least every six months. The intrahepatic disease-free interval was estimated and the overall survival from the time of the initial RFA was analyzed using the Kaplan-Meier method. No intraprocedural deaths occurred, but four major complications developed, including abscesses (n = 3) and pneumothorax (n 1). Technical effectiveness was determined on the initial follow-up images. During the follow-up period (range, 5.9-68.6 months; median time, 18.8 months) for 37 tumors in 22 patients where technical effectiveness was achieved, 12 lesions (32%, 12 of 37) showed local tumor progression and new intrahepatic metastases occurred in 13 patients (59%, 13 of 22). The median intrahepatic disease-free interval was 10.1 months. The 1-year, 3-year and 5-year overall survival rates after RFA were 86%, 39% and 19%, respectively RFA showed intermediate therapeutic effectiveness for the treatment of non-colorectal origin liver metastases.

  6. Radiofrequency Ablation for Treating Liver Metastases from a Non-Colorectal Origin

    Yun, Bo La; Lee, Jeong Min; Baek, Ji Hyun; Kim, Se Hyung; Lee, Jae Young; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of)

    2011-10-15

    We wanted to assess the safety and efficacy of performing radiofrequency ablation (RFA) in patients with non-colorectal liver metastases. In this retrospective study, 25 patients with 40 hepatic metastases (M:F = 17:8; mean age, 57 years; tumor size, 0.5-5.0 cm) from a non-colorectal origin (stomach, biliary, breast, pancreas, kidney and skin) were treated with RFA. The RFA procedures were performed using either an internally cooled electrode or a clustered electrode under ultrasound or CT guidance. Contrast-enhanced CT scans were obtained immediately after RFA and follow-up CT scans were performed within three months after ablation and subsequently at least every six months. The intrahepatic disease-free interval was estimated and the overall survival from the time of the initial RFA was analyzed using the Kaplan-Meier method. No intraprocedural deaths occurred, but four major complications developed, including abscesses (n = 3) and pneumothorax (n 1). Technical effectiveness was determined on the initial follow-up images. During the follow-up period (range, 5.9-68.6 months; median time, 18.8 months) for 37 tumors in 22 patients where technical effectiveness was achieved, 12 lesions (32%, 12 of 37) showed local tumor progression and new intrahepatic metastases occurred in 13 patients (59%, 13 of 22). The median intrahepatic disease-free interval was 10.1 months. The 1-year, 3-year and 5-year overall survival rates after RFA were 86%, 39% and 19%, respectively RFA showed intermediate therapeutic effectiveness for the treatment of non-colorectal origin liver metastases.

  7. Image guidance improves localization of sonographically occult colorectal liver metastases

    Leung, Universe; Simpson, Amber L.; Adams, Lauryn B.; Jarnagin, William R.; Miga, Michael I.; Kingham, T. Peter

    2015-03-01

    Assessing the therapeutic benefit of surgical navigation systems is a challenging problem in image-guided surgery. The exact clinical indications for patients that may benefit from these systems is not always clear, particularly for abdominal surgery where image-guidance systems have failed to take hold in the same way as orthopedic and neurosurgical applications. We report interim analysis of a prospective clinical trial for localizing small colorectal liver metastases using the Explorer system (Path Finder Technologies, Nashville, TN). Colorectal liver metastases are small lesions that can be difficult to identify with conventional intraoperative ultrasound due to echogeneity changes in the liver as a result of chemotherapy and other preoperative treatments. Interim analysis with eighteen patients shows that 9 of 15 (60%) of these occult lesions could be detected with image guidance. Image guidance changed intraoperative management in 3 (17%) cases. These results suggest that image guidance is a promising tool for localization of small occult liver metastases and that the indications for image-guided surgery are expanding.

  8. Maximum Diameter and Number of Tumors as a New Prognostic Indicator of Colorectal Liver Metastases.

    Yoshimoto, Toshiaki; Morine, Yuji; Imura, Satoru; Ikemoto, Tetsuya; Iwahashi, Syuichi; Saito, Y U; Yamada, Sinichiro; Ishikawa, Daichi; Teraoku, Hiroki; Yoshikawa, Masato; Higashijima, Jun; Takasu, Chie; Shimada, Mitsuo

    2017-01-01

    Surgical resection is currently considered the only potentially curative option as a treatment strategy of colorectal liver metastases (CRLM). However, the criteria for selection of resectable CRLM are not clear. The aim of this study was to confirm a new prognostic indicator of CRLM after hepatic resection. One hundred thirty nine patients who underwent initial surgical resection from 1994 to 2015 were investigated retrospectively. Prognostic factors of overall survival including the product of maximum diameter and number of metastases (MDN) were analyzed. Primary tumor differentiation, vessel invasion, lymph node (LN) metastasis, non-optimally resectable metastases, H score, grade of liver metastases, resection with non-curative intent and MDN were found to be prognostic factors of overall survival (OS). In multivariate analyses of clinicopathological features associated with OS, MDN and non-curative intent were independent prognostic factors. Patients with MDN ≥30 had shown significantly poorer prognosis than patients with MDN <30 in OS and relapse-free survival (RFS). MDN ≥30 is an independent prognostic factor of survival in patients with CRLM and optimal surgical criterion of hepatectomy for CRLM. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Microvascular Architecture of Hepatic Metastases in a Mouse Model

    Darshini Kuruppu

    1997-01-01

    Full Text Available Development of effective treatment for hepatic metastases can be initiated by a better understanding of tumour vasculature and blood supply. This study was designed to characterise the microvascular architecture of hepatic metastases and observe the source of contributory blood supply from the host. Metastases were induced in mice by an intrasplenic injection of colon carcinoma cells (106 cells/ml. Vascularization of tumours was studied over a three week period by scanning electron microscopy of microvascular corrosion casts. Metastatic liver involvement was observed initially within a week post induction, as areas approximately 100 μm in diameter not perfused by the casting resin. On histology these spaces corresponded to tumour cell aggregates. The following weeks highlighted the angiogenesis phase of these tumours as they received a vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of metastases was maintained throughout tumour growth. At the tumour periphery most sinusoids were compressed to form a sheath demarcating the tumour from the hepatic vasculature. No direct supply from the hepatic artery or the portal vein was observed. Dilated vessels termed vascular lakes dominated the complex microvascular architecture of the tumours, most tapering as they traversed towards the periphery. Four vascular branching patterns could be identified as true loops, bifurcations and trifurcations, spirals and capillary networks. The most significant observation in this study was the direct sinusoidal supply of metastases, together with the vascular lakes and the peripheral sinusoidal sheaths of the tumour microculature.

  10. Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

    Lorenz, Kerstin; Brauckhoff, Michael; Behrmann, Curd; Sekulla, Carsten; Ukkat, Jörg; Brauckhoff, Katrin; Gimm, Oliver; Dralle, Henning

    2005-12-01

    Hepatic metastases from medullary thyroid carcinoma (MTC) may impair quality of life by hypercalcitonemia-associated diarrhea and pain. In this prospective study, the effect of selective arterial chemoembolization (SACE) was evaluated. Eleven patients with hepatic metastases from MTC received 1 to 9 courses of SACE using epirubicine. Symptomatic, biochemical, and morphologic responses on SACE were recorded. Symptomatic response was observed in all symptomatic patients. However, biochemical and radiologic response occurred only in 6 patients. Liver function was not affected by SACE. One patient with unexpected concurrent pheochromocytoma metastases died after the first course. Development of side effects in the course was observed in 8 patients but were only World Health Organization grade 1. Patients' satisfaction with SACE was excellent. Long-term follow-up found 7 patients alive (1-72 months). Three patients died with tumor 6, 12, and 24 months after SACE, respectively. SACE provided good symptom palliation for the majority of patients with hepatic metastases from MTC. However, transient remission or stabilization of hepatic metastases resulted in only 60%. Further studies using a randomized protocol are required.

  11. Findings of the radioisotope color scan of the hepatic metastases

    Choi, M. S.; Yoo, H. S.; Park, C. Y.; Choi, B. S.

    1975-01-01

    Recently, the space occupying lesions in the liver were well established and recognized by radioisotope color scan. In addition, the lesions were easily localized in the supine and the right lateral projections. The findings of hepatoma, abscess and cyst were seen as filling defects which were similar to the findings of the hepatic metastases. In this study, we analysis of 70 cases of the hepatic metastases, 80 cases of the hepatoma and 100 cases of the liver abscess which were obtained by radiogold color scan and confirmed by a needle biopsy or laparotomy. Summary of analysis as follows: 1. Primary site in 70 cases of hepatic metastases. Stomach 30 cases (42.8%) Biliary Tract 10 cases (12.3%) Colon 8 cases (11.4%) Lung 6 cases (8.5%) Ovary 6 cases (8.5%) Pancreas 3 case (4.3%) Thyroid 2 cases (3.5%) Breast 2 cases (3.5%) Kidney, Cervix, Esophagus 1 case. 2. Hepatomegaly were seen in 22 cases (32%) of the hepatic metastases and relatively small in percentage compare with the hepatoma and abscess. 3. Single space occupying lesion were demonstrated in 26 cases (35.7%) of the hepatic metastases, 55 cases (70.2%) of the hepatoma and 72 cases (72%) of the abscess. Two space occupying lesion were in the scan in 10 cases (12.3%) of the hepatic metastases, 8 cases (9.5%) of the hepatoma and 10 cases (10%) of the abscess. Multiple space occupying lesions were scan in 15 cases (21.4%) of the hepatic metastases, 14 cases (17.5%) of the hepatoma and 13 cases (13%) of the abscess. Compare with the hepatoma and abscess, the hepatic metastases tend to more than one space occupying lesions. 4. The appearance and location of the metastatic lesions showed somewhat significant. In 26 of 30 cases (81.6%) of the stomach carcinoma revealed the lesions mostly located in the porta hepatis and right lower lobe of the liver. Multiple and discrete metastatic lesions were usually from the colon carcinoma.

  12. Findings of the radioisotope color scan of the hepatic metastases

    Choi, M S; Yoo, H S; Park, C Y; Choi, B S [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1975-06-15

    Recently, the space occupying lesions in the liver were well established and recognized by radioisotope color scan. In addition, the lesions were easily localized in the supine and the right lateral projections. The findings of hepatoma, abscess and cyst were seen as filling defects which were similar to the findings of the hepatic metastases. In this study, we analysis of 70 cases of the hepatic metastases, 80 cases of the hepatoma and 100 cases of the liver abscess which were obtained by radiogold color scan and confirmed by a needle biopsy or laparotomy. Summary of analysis as follows: 1. Primary site in 70 cases of hepatic metastases. Stomach 30 cases (42.8%) Biliary Tract 10 cases (12.3%) Colon 8 cases (11.4%) Lung 6 cases (8.5%) Ovary 6 cases (8.5%) Pancreas 3 case (4.3%) Thyroid 2 cases (3.5%) Breast 2 cases (3.5%) Kidney, Cervix, Esophagus 1 case. 2. Hepatomegaly were seen in 22 cases (32%) of the hepatic metastases and relatively small in percentage compare with the hepatoma and abscess. 3. Single space occupying lesion were demonstrated in 26 cases (35.7%) of the hepatic metastases, 55 cases (70.2%) of the hepatoma and 72 cases (72%) of the abscess. Two space occupying lesion were in the scan in 10 cases (12.3%) of the hepatic metastases, 8 cases (9.5%) of the hepatoma and 10 cases (10%) of the abscess. Multiple space occupying lesions were scan in 15 cases (21.4%) of the hepatic metastases, 14 cases (17.5%) of the hepatoma and 13 cases (13%) of the abscess. Compare with the hepatoma and abscess, the hepatic metastases tend to more than one space occupying lesions. 4. The appearance and location of the metastatic lesions showed somewhat significant. In 26 of 30 cases (81.6%) of the stomach carcinoma revealed the lesions mostly located in the porta hepatis and right lower lobe of the liver. Multiple and discrete metastatic lesions were usually from the colon carcinoma.

  13. Selective internal radiation therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma

    Welsh, James S.; Kennedy, Andrew S.; Thomadsen, Bruce

    2006-01-01

    Introduction: Selective internal radiation therapy (SIRT) is a relatively new commercially available microbrachytherapy technique for treatment of malignant hepatic lesions using 9 Y embedded in resin microspheres, which are infused directly into the hepatic arterial circulation. It is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, such as hepatocellular carcinoma and neuroendocrine malignancies. Materials/Methods: A modest number of clinical trials, preclinical animal studies, and dosimetric studies have been reported. Here we review several of the more important results. Results: High doses of beta radiation can be selectively delivered to tumors, resulting in impressive local control and survival rates. Ex vivo analyses have shown that microspheres preferentially cluster around the periphery of tumor nodules with a high tumor:normal tissue ratio of up to 200:1. Toxicity is usually mild, featuring fatigue, anorexia, nausea, abdominal discomfort, and slight elevations of liver function tests. Conclusions: Selective internal radiation therapy represents an effective means of controlling liver metastases from colorectal adenocarcinoma. Clinical trials have demonstrated improved local control of disease and survival with relatively low toxicity. Investigations of SIRT for other hepatic malignancies and in combination with newer chemotherapy agents and targeted biologic therapies are under way or in planning. A well-integrated team involving interventional radiology, nuclear medicine, medical oncology, surgical oncology, medical physics, and radiation oncology is essential for a successful program. Careful selection of patients through the combined expertise of the team can maximize therapeutic efficacy and reduce the potential for adverse effects

  14. Computed tomography in brain metastases of colorectal cancer

    Kuratsu, Jun-ichi; Matsukado, Yasuhiko; Sueyoshi, Nobuyuki [Kumamoto Univ. (Japan). School of Medicine; Nonaka, Nobuhito; Sano, Yoshinori; Itoyama, Yoichi; Miura, Giichi

    1984-10-01

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery.

  15. Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

    Méndez Romero, Alejandra; Keskin-Cambay, Fatma; van Os, Rob M.; Nuyttens, Joost J.; Heijmen, Ben J. M.; Ijzermans, Jan N. M.; Verhoef, Cornelis

    2017-01-01

    To investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity. A cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between

  16. Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden.

    Norén, A; Sandström, P; Gunnarsdottir, K; Ardnor, B; Isaksson, B; Lindell, G; Rizell, M

    2018-04-01

    Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p 70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient's chances of being offered liver surgery.

  17. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

    Nielsen, Kåre; Rolff, Hans C; Eefsen, Rikke L

    2014-01-01

    Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217....... Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases.Modern Pathology advance online publication, 23 May 2014; doi:10.1038/modpathol.2014.4....

  18. Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases

    Eefsen, Rikke Løvendahl; Van den Eynden, Gert G; Høyer-Hansen, Gunilla

    2012-01-01

    The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern......-type plasminogen activator receptor (P = 0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P = 0.0007) and replacement growth pattern (P = 0.021). Although a minor fraction of the patients harboured metastases with different growth...

  19. Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

    Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M.J.

    2010-01-01

    A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe (P=0.009) from independent T test.

  20. Computer-based decision making in medicine : A model for surgery of colorectal liver metastases

    Langenhoff, B S; Krabbe, P F M; Ruers, T J M

    2007-01-01

    AIMS: Seeking the best available treatment for patients with colorectal liver metastases may be complex due to the interpretation of many variables. In this study conjoint analysis is used to develop a decision model to help clinicians selecting patients eligible for surgery of liver metastases.

  1. Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver.

    de Leede, Eleonora M; Burgmans, Mark C; Martini, Christian H; Tijl, Fred G J; van Erkel, Arian R; Vuyk, Jaap; Kapiteijn, Ellen; Verhoef, Cornelis; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

    2016-07-31

    Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

  2. The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

    Thalheimer, Andreas; Waaga-Gasser, Ana M; Otto, Christoph; Bueter, Marco; Illert, Bertram; Gattenlohner, Stefan; Gasser, Martin; Meyer, Detlef; Fein, Martin; Germer, Christoph T

    2009-01-01

    The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. We injected immunoincompetent nude mice intraportally with different numbers (1 × 10 5 , 1 × 10 6 and 5 × 10 6 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Only the injection of 1 × 10 6 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 10 6 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD

  3. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

  4. NM23 protein expression in colorectal carcinoma using TMA (tissue microarray: association with metastases and survival

    Levindo Alves de Oliveira

    2010-12-01

    Full Text Available CONTEXT: NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma. OBJECTIVE: To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. METHODS: One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001. NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57, vascular invasion (P = 0.85, lymphatic invasion (P = 0.41, perineural infiltration (P = 0.46, staging (P = 0.19, lymph node metastases (P = 0.08, or liver metastases (P = 0.59. Disease-free survival showed significant association (P = 0.01 with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13. CONCLUSIONS: NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma

  5. Early PET/CT after radiofrequency ablation in colorectal cancer liver metastases: is it useful?

    LIU Zhao-yu; CHANG Zhi-hui; LU Zai-ming; GUO Qi-yong

    2010-01-01

    Background Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by an inflammatory response in the ablation margin, making the identification of local tumor progression (LTP) difficult. The aim of this study was to evaluate the efficacy of early 18F-FDG PET/CT scanning to monitor the effectiveness of RFA in colorectal liver metastases.Methods Twelve patients with 20 metastases were treated with RFA for colorectal liver metastases. They underwent PET/CT within 2 weeks before RFA and within 24 hours after RFA (so termed "early PET/CT"). PET/CT was repeated at 1, 3, and 6 months, and then every 6 months after ablation. The standard of reference was based on available clinical and radiological follow-up data.Results Early PET/CT revealed total photopenia in 16 RFA-treated metastases, which were found to be without residual tumor on the final PET/CT scan. Three RFA-treated metastases with focal uptake were identified as local tumor progression, which necessitated further treatment. One RFA-treated metastasis with rim-shaped uptake was regarded as inflammation. The results of the early PET/CT scanning were consistent with the findings of the final follow-up. Conclusions PET/CT performed within 24 hours after RFA can effectively detect whether residual tumor exists for colorectal cancer liver metastases. The results can guide further treatment, and may improve the efficacy of RFA.

  6. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

  7. Preoperative detection of colorectal liver metastases in fatty liver: MDCT or MRI?

    Kulemann, Vanessa; Schima, Wolfgang; Tamandl, Dietmar; Kaczirek, Klaus; Gruenberger, Thomas; Wrba, Friedrich; Weber, Michael; Ba-Ssalamah, Ahmed

    2011-01-01

    Objective: To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods: Twenty preoperative tri-phasic MDCT (4-64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1-60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results: Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference (p 1 cm. Conclusion: For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.

  8. Short-Term Outcomes of Simultaneous Laparoscopic Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Liver Metastases

    Inoue, Akira; Uemura, Mamoru; Yamamoto, Hirofumi; Hiraki, Masayuki; Naito, Atsushi; Ogino, Takayuki; Nonaka, Ryoji; Nishimura, Junichi; Wada, Hiroshi; Hata, Taishi; Takemasa, Ichiro; Eguchi, Hidetoshi; Mizushima, Tsunekazu; Nagano, Hiroaki; Doki, Yuichiro

    2014-01-01

    Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer an...

  9. Hepatic artery infusion (HAI) for hepatic metastases in combination with hepatic resection and hepatic radiation

    Merrick, H.W.; Dobelbower, R.R.; Ringleint, J.F.; Skeel, R.T.

    1986-01-01

    Renewed interest in hepatic artery infusion has been stimulated by the development of a totally implantable pump which eliminates many of the problems encountered by the external pumps and catheters. As the potential benefit of hepatic artery infusion would be greater if either all gross disease were removed by prior resection, or alternatively, if non-resectable disease were irradiated in conjunction with hepatic artery infusion, the authors initiated a phase I-II trial to evaluate combined modality therapy

  10. Transcatheter arterial chemoembolization of colorectal liver metastases using degradable starch microspheres (Spherex registered). Own investigations and review to the literature

    Wasser, K.; Landwehr, P.

    2005-01-01

    Since two decades transarterial chemoembolization (TACE) of liver metastases has been investigated in numerous studies. However, no standardized therapeutic procedure exists so far. The present study retrospectively investigated survival, response and side effects after TACE of liver metastases in 21 patients with colorectal cancer and results are compared with previous literature. A total of 68 TACE procedures were performed. A suspension of degradable starch microspheres (DSM, Spherex registered ) and Mitomycin C was applied selectively into hepatic arteries via a transfemoral approach. DSM effect a temporary arterial occlusion. Follow-up studies were performed by contrast enhanced spiral computed tomography (CT). The median survival was 13.8 months. Therapeutic response (according to WHO) was observed only in three patients. The progression free interval was 5.8 months. Patients developed a postembolization-syndrome (abdominal pain, fever, nausea) and increased transaminases in 27-43% of all interventions. A gastric ulcer occurred after four, cholecystitis after two TACE. As already shown in most previous studies, regardless of the used agents, also this investigation underlines the moderate therapeutic effect of TACE on colorectal liver metastases. So far, no significant survival benefit has been shown in the literature and the response rates are rather limited. In general, complications of TACE seem to be rare, but should not to be underestimated. Compared to TACE with long or permanent arterial occlusion, postembolization syndrome seems to be less pronounced using DSM. As TACE is rather a palliative therapeutic approach, DSM therefore might be more suited. Further studies on TACE of liver metastases should focus on to the patients' quality of life. (orig.) [de

  11. [Strategy of liver resection during chemotherapy for otherwise unresectable colorectal metastases].

    Tanaka, Kuniya; Kumamoto, Takafumi; Takeda, Kazuhisa; Nojiri, Kazunori; Endo, Itaru

    2013-07-01

    With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Surgery in isolation may be approaching technical limits, but now is likely to help more patients because of success of complementary strategies, particularly newer chemotherapy and targeted therapy. Leaving behind disappearing metastases after chemotherapy, margin-positive resection, staged liver resection, and liver-first reversed management permit potentially curative surgery for patients previously unable to survive resection. Further, survival benefit from maximum debulking surgery, like ovarian cancer, for colorectal liver metastases is uncertain at present, but likely. Individualized multidisciplinary treatment planning using such strategies is essential.

  12. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  13. Preoperative evaluation of colorectal liver metastases: comparison between gadoxetic acid-enhanced 3.0-T MRI and contrast-enhanced MDCT with histopathological correlation

    Scharitzer, M.; Ba-Ssalamah, A.; Ringl, H.; Koelblinger, C.; Weber, M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Gruenberger, T. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Schima, W. [Department of Radiology, KH Goettlicher Heiland, KH der Barmherzigen Schwestern and St Josef-Krankenhaus, Vienna (Austria)

    2013-08-15

    The aim of this prospective study was to compare the diagnostic performance of 64-row MDCT and gadoxetic-acid-enhanced MRI at 3.0 T in patients with colorectal liver metastases in correlation with histopathological findings. Lesions detected at MDCT and MRI were interpreted by three blinded readers and compared with histopathological workup as the term of reference. Two subgroups of lesions were additionally evaluated: (1) metastases smaller than 10 mm and (2) lesions in patients with and without steatosis of the liver, assessed histopathologically. Surgery and histopathological workup revealed 81 colorectal liver metastases in 35 patients and diffuse metastatic involvement in 3 patients. In a lesion-by-lesion analysis, significant sensitivity differences could only be found for reader 1 (P = 0.035) and reader 3 (P = 0.003). For segment-based evaluation, MRI was more sensitive only for reader 3 (P = 0.012). The number of false-positive results ranged from 3 to 12 for MDCT and 8 to 11 for MRI evaluation. In the group of small lesions, the sensitivity differed significantly between both methods (P = 0.003). In patients with hepatic steatosis, MRI showed a trend toward better performance than MDCT, but without statistical performance. The 3.0-T MRI with liver-specific contrast agents is the preferred investigation in the preoperative setting, especially for the assessment of small colorectal liver metastases. (orig.)

  14. Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

    Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Choi, Junsung [Moffitt Cancer Center, Department of Interventional Radiology (United States); Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States); Werner, Philip; Chaudhry, Tariq A. [Moffitt Cancer Center, Department of Anesthesia (United States); Zager, Jonathan S., E-mail: Jonathan.Zager@Moffitt.org [Moffitt Cancer Center, Department of Cutaneous and Sarcoma Oncology (United States)

    2012-12-15

    Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

  15. Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

    Deneve, Jeremiah L.; Choi, Junsung; Gonzalez, Ricardo J.; Conley, Anthony P.; Stewart, Steven; Han, Dale; Werner, Philip; Chaudhry, Tariq A.; Zager, Jonathan S.

    2012-01-01

    Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significant improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.

  16. Stereotactic body radiation therapy for liver metastases from colorectal cancer: analysis of safety, feasibility, and early outcomes

    Marie-Adele Sorel Kress

    2012-02-01

    Full Text Available Introduction: Colorectal cancer (CRC is the 3rd leading cause of cancer-related death in the U.S. Many patients with CRC develop hepatic metastases as the sole site of metastases. Historical treatment options were limited to resection or conventional radiation therapy. Stereotactic body radiation therapy (SBRT has emerged as a rational treatment approach. This study reviews our experience with SBRT for patients with liver metastases from CRC.Material and Methods: Fourteen histologically confirmed hepatic CRC metastases in 11 consecutive patients were identified between November, 2004 and June, 2009 at Georgetown University. All patients underwent CT-based treatment planning; a few also had MRI or PET/CT. All patients had fiducial markers placed under CT guidance and were treated using the CyberKnife system. Treatment response and toxicities were examined; survival and local control were evaluated.Results: Most patients were treated to a single hepatic lesion (n=8, with a few treated to 2 lesions (n=3. Median treatment volume was 99.7 cm3, and lesions were treated to a median BED10 of 49.7 Gy (range: 28 – 100.8 Gy. Median follow-up was 21 months; median survival was 16.1 months, with 2-year actuarial survival of 25.7%. One-year local control was 72%. Among patients with post-treatment imaging, 8 had stable disease (80% and 2 had progressive disease (20% at first follow-up. The most common grade 1-2 acute toxicities included nausea and alterations in liver function tests; there was one grade 3 toxicity (elevated bilirubin, and no grade 4-5 toxicities.Discussion: SBRT is safe and feasible for the treatment of limited hepatic metastases from CRC. Our results compare favorably with outcomes from previous studies of SBRT. Further studies are needed to better define patient eligibility, study the role of combined modality treatment, optimize treatment parameters, and characterize quality of life after treatment.

  17. R1 Resection by Necessity for Colorectal Liver Metastases Is It Still a Contraindication to Surgery?

    de Haas, Robbert J.; Wicherts, Dennis A.; Flores, Eduardo; Azoulay, Daniel; Castaing, Denis; Adam, Rene

    2008-01-01

    Objective: To compare long-term outcome of R0 (negative margins) and R1 (positive margins) liver resections for colorectal liver metastases (CLM) treated by an aggressive approach combining chemotherapy and repeat surgery. Summary Background Data: Complete macroscopic resection with negative margins

  18. Initial experiences of simultaneous laparoscopic resection of colorectal cancer and liver metastases

    Hoekstra, L. T.; Busch, O. R. C.; Bemelman, W. A.; van Gulik, T. M.; Tanis, P. J.

    2012-01-01

    Introduction. Simultaneous resection of primary colorectal carcinoma (CRC) and synchronous liver metastases (SLMs) is subject of debate with respect to morbidity in comparison to staged resection. The aim of this study was to evaluate our initial experience with this approach. Methods. Five patients

  19. Staged or simultaneous resection of synchronous liver metastases from colorectal cancer - a systematic review

    Hillingso, J.G.; Wille-Jørgensen, Peer

    2009-01-01

    A systematic review of the literature was undertaken to estimate the differences in length of hospital stay, morbidity, mortality and long-term survival between staged and simultaneous resection of synchronous liver metastases from colorectal cancer to determine the level of evidence for recommen......A systematic review of the literature was undertaken to estimate the differences in length of hospital stay, morbidity, mortality and long-term survival between staged and simultaneous resection of synchronous liver metastases from colorectal cancer to determine the level of evidence...... with grade C recommendations. Synchronous resections can be undertaken in selected patients, provided that surgeons specialized in colorectal and hepatobiliary surgery are available Udgivelsesdato: 2009/1...

  20. Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

    Gillams, Alice, E-mail: alliesorting@gmail.com [The London Clinic, Radiology Department (United Kingdom); Khan, Zahid [Countess of Chester Hospital (United Kingdom); Osborn, Peter [Queen Alexandra Hospital (United Kingdom); Lees, William [University College London Medical School (United Kingdom)

    2013-06-15

    Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, and factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.

  1. Biokinetics of indium-111 labeled platelets after cryotherapy of hepatic metastases

    Alexander, C.; Kirsch, C.-M.; Pistorius, G.; Feifel, G.

    2002-01-01

    Full text: The present investigation was performed to evaluate mean platelet live-span and the proportion of platelet disposal in different organs in patients after hepatic cryotherapy. Seven patients with advanced colorectal cancer and liver metastases were included. Directly before the surgical procedure a blood specimen was drawn and an in vitro labeling of patients platelets with 18 MBq Indium-111 oxime was performed. Reinjection was done intraoperatively just before cryotherapy. Blood specimen were drawn at 1, 2, 3, 24 und 48 h p.i.. Whole-body scintigraphy was acquired on day two alter operation. The evaluation comprised the calculation of mean platelet live-span and of organ activities as percentage of whole-body activity. The local disposal of platelets at the site of cryotherapy ranged from 0 to 35.2 percent, the mean value was 16,2 ± 12,2 percent (mean ± SD). The mean half-time of time-activity curve gave 0.6 to 2.4 days (mean ± SD: 1.6 ± 0.6 d; normal value: 3.5-6 d), the mean platelet life-span was between 2.1 and 5.2 days corresponding to a mean value of 3.4 ± 1.0 days (normal value: 7-11 d). The evaluation of SPECT slices of large liver metastases demonstrated that platelet disposal takes place at the border zone of the metastases just around the necrotic center. We conclude that the enhanced local platelet trapping is a major cause for cryothermia-induced systemic thrombocytopenia. (author)

  2. Laparoscopic versus open 1-stage resection of synchronous liver metastases and primary colorectal cancer.

    Gorgun, Emre; Yazici, Pinar; Onder, Akin; Benlice, Cigdem; Yigitbas, Hakan; Kahramangil, Bora; Tasci, Yunus; Aksoy, Erol; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Berber, Eren

    2017-08-01

    The aim of this study is to compare the perioperative and oncologic outcomes of open and laparoscopic approaches for concomitant resection of synchronous colorectal cancer and liver metastases. Between 2006 and 2015, all patients undergoing combined resection of primary colorectal cancer and liver metastases were included in the study (n=43). Laparoscopic and open groups were compared regarding clinical, perioperative and oncologic outcomes. There were 29 patients in the open group and 14 patients in the laparoscopic group. The groups were similar regarding demographics, comorbidities, histopathological characteristics of the primary tumor and liver metastases. Postoperative complication rate (44.8% vs . 7.1%, P=0.016) was higher, and hospital stay (10 vs . 6.4 days, P=0.001) longer in the open compared to the laparoscopic group. Overall survival (OS) was comparable between the groups (P=0.10); whereas, disease-free survival (DFS) was longer in laparoscopic group (P=0.02). According to the results, in patients, whose primary colorectal cancer and metastatic liver disease was amenable to a minimally invasive resection, a concomitant laparoscopic approach resulted in less morbidity without compromising oncologic outcomes. This suggests that a laparoscopic approach may be considered in appropriate patients by surgeons with experience in both advanced laparoscopic liver and colorectal techniques.

  3. Short-Term Outcomes of Simultaneous Laparoscopic Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Liver Metastases

    Inoue, Akira; Uemura, Mamoru; Yamamoto, Hirofumi; Hiraki, Masayuki; Naito, Atsushi; Ogino, Takayuki; Nonaka, Ryoji; Nishimura, Junichi; Wada, Hiroshi; Hata, Taishi; Takemasa, Ichiro; Eguchi, Hidetoshi; Mizushima, Tsunekazu; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki

    2014-01-01

    Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases with curative intent at our institute. The median operative time was 452 minutes, and the median estimated blood loss was 245 mL. Median times to discharge from the hospital and adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative resection margins were achieved in all cases, with no postoperative mortality or major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases appears feasible with low morbidity and favorable outcomes. PMID:25058762

  4. Open versus laparoscopic liver resection for colorectal liver metastases (the Oslo-CoMet Study): study protocol for a randomized controlled trial.

    Fretland, Åsmund Avdem; Kazaryan, Airazat M; Bjørnbeth, Bjørn Atle; Flatmark, Kjersti; Andersen, Marit Helen; Tønnessen, Tor Inge; Bjørnelv, Gudrun Maria Waaler; Fagerland, Morten Wang; Kristiansen, Ronny; Øyri, Karl; Edwin, Bjørn

    2015-03-04

    Laparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial. The Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed. After 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases. The trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

  5. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    Roth, Eira S; Fetzer, David T; Barron, Bruce J; Joseph, Usha A; Gayed, Isis W; Wan, David Q

    2009-01-01

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18 F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  6. Contemporary surgical management of synchronous colorectal liver metastases [version 1; referees: 2 approved

    Danielle Collins

    2017-04-01

    Full Text Available Historically, the 5-year survival rates for patients with stage 4 (metastatic colorectal cancer were extremely poor (5%; however, with advances in systemic chemotherapy combined with an ability to push the boundaries of surgical resection, survival rates in the range of 25–40% can be achieved. This multimodal approach of combining neo-adjuvant strategies with surgical resection has raised a number of questions regarding the optimal management and timing of surgery. For the purpose of this review, we will focus on the treatment of stage 4 colorectal cancer with synchronous liver metastases.

  7. Microwave Ablation and Immune Activation in the Treatment of Recurrent Colorectal Lung Metastases: A Case Report

    Magnus Bäcklund

    2017-04-01

    Full Text Available We present a patient with colorectal metastases confined to the lungs and treated with multiple resections until this was not an option anymore, followed by stereotactic body radiation therapy until this option was drained. Then, the patient was successfully treated with multiple microwave ablations combined with immunological activation targeting the programmed cell death 1 receptor (PD-1, possibly instigating a powerful abscopal effect. Techniques, doses, and radiological findings are presented.

  8. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  9. PTEN expression is consistent in colorectal cancer primaries and metastases and associates with patient survival

    Atreya, Chloe E; Sangale, Zaina; Xu, Nafei; Matli, Mary R; Tikishvili, Eliso; Welbourn, William; Stone, Steven; Shokat, Kevan M; Warren, Robert S

    2013-01-01

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates the phosphoinositide-3-kinase (PI3K) signaling pathway. In colorectal cancer (CRC), observed frequencies of loss of PTEN expression, concordant expression in primary tumors and metastases, and the association of PTEN status with outcome vary markedly by detection method. We determined the degree to which PTEN expression is consistent in 70 matched human CRC primaries and liver metastases using a validated immunohistochemistry assay. We found loss of PTEN expression in 12.3% of assessable CRC primaries and 10.3% of assessable liver metastases. PTEN expression (positive or negative) was concordant in 98% of matched colorectal primaries and liver metastases. Next we related PTEN status to mutations in RAS and PI3K pathway genes (KRAS, NRAS, BRAF, and PIK3CA) and to overall survival (OS). PTEN expression was not significantly associated with the presence or absence of mutations in RAS or PI3K pathway genes. The median OS of patients whose tumors did not express PTEN was 9 months, compared to 49 months for patients whose tumors did express PTEN (HR = 6.25, 95% confidence intervals (CI) (1.98, 15.42), P = 0.0017). The association of absent PTEN expression with increased risk of death remained significant in multivariate analysis (HR = 6.31, 95% CI (2.03, 17.93), P = 0.0023). In summary, PTEN expression was consistent in matched CRC primaries and in liver metastases. Therefore, future investigations of PTEN in metastatic CRC can use primary tumor tissue. In patients with liver-only metastases, loss of PTEN expression predicted poor OS. We observed concordant PTEN expression in 98% of colorectal cancer (CRC) primary and liver metastasis pairs using a validated immunohistochemistry assay. Consistent PTEN expression at both disease sites is significant because tumor tissue is usually available from CRC primaries but not metastases. Loss of PTEN expression associated with poor survival of

  10. Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

    Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

    2010-01-01

    Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade

  11. Immunohistochemistry - Microarray Analysis of Patients with Peritoneal Metastases of Appendiceal or Colorectal Origin

    Danielle E Green

    2015-01-01

    Full Text Available BackgroundThe value of immunohistochemistry (IHC-microarray analysis of pathological specimens in the management of patients is controversial although preliminary data suggests potential benefit. We describe the characteristics of patients undergoing a commercially available IHC-microarray method in patients with peritoneal metastases (PM and the feasibility of this technique in this population.MethodsWe retrospectively analyzed consecutive patients with pathologically confirmed PM from appendiceal or colorectal primary who underwent Caris Molecular IntelligenceTM testing. IHC, microarray, FISH and mutational analysis were included and stratified by PCI score, histology and treatment characteristics. Statistical analysis was performed using non-parametric tests.ResultsOur study included 5 patients with appendiceal and 11 with colorectal PM. The median age of patients was 51 (IQR 39-65 years, with 11(68% female. The median PCI score of the patients was 17(IQR 10-25. Hyperthermic intra-peritoneal chemoperfusion (HIPEC was performed in 4 (80% patients with appendiceal primary tumors and 4 (36% with colorectal primary. KRAS mutations were encountered in 40% of appendiceal vs. 30% colorectal tumors, while BRAF mutations were seen in 40% of colorectal PM and none of the patients with appendiceal PM (p=0.06. IHC biomarker expression was not significantly different between the two primaries. Sufficient tumor for microarray analysis was found in 44% (n=7 patients, which was not associated with previous use of chemotherapy (p>0.20 for 5-FU/LV, Irinotecan and Oxaliplatin.ConclusionsIn a small sample of patients with peritoneal metastases, the feasibility and results of IHC-microarray staining based on a commercially available test is reported. The apparent high incidence of the BRAF mutation in patients with PM may potentially offer opportunities for novel therapeutics and suggest that IHC-microarray is a method that can be used in this population.

  12. The detectability of hepatic metastases in candidates of radiofrequency ablation: comparison for helical CT scanning and late-phase pulse-inversion harmonic imaging

    Lee, Kang Won; Yoon, Kwon Ha; Kim, Eun A; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [School of Medicine, Wonkwang Univ., Iksan (Korea, Republic of)

    2002-02-01

    To compare dual-phase helical CT and pulse inversion harmonic US using microbubble contrast agents in the detection of hepatic metastases prior to radiofrequency (RF) ablation. Twenty-one patients in whom hepatic metastases from colorectal cancer had been diagnosed by dual-phase CT scanning and who were considered to be candidates for RF ablation underwent pulse-inversion barmonic US examination. Images were obtained 5 minutes after the bolus injection of microbubble contrast agent SH U 508 A (4.0 g, 300 mg/mL). The number of metastatic tumors revealed by CT and US was determined, and the findings were statistically analysed. The influence of the results of US examination on treatment planning was also evaluated. In 21 patients, 48 metastaic lesions were detected by helical CT, and 56 lesions by US. These eight additional lesions revealed by US occurred in six patients (29%), and their diameter was 3-13 (mean, 7.2) mm. In three of these patients, RF ablation could not be performed ,while in the other three, the additional lesions were ablated. Pulse-inversion harmonic US imaging using microbubble contrast agents may depict small hepatic metastatic tumors that were not apparent at CT. US-therefore appears to be useful in the planning of treatment prior to the RF ablation of hepatic metastases.

  13. Percutaneous stereotactic radiofrequency ablation of colorectal liver metastases

    Bale, Reto; Widmann, Gerlig; Schullian, Peter; Haidu, Marion; Pall, Georg; Klaus, Alexander; Weiss, Helmut; Biebl, Matthias; Margreiter, Raimund

    2012-01-01

    To evaluate the outcome of patients with colorectal liver metastasis (CRLM) treated with stereotactic radiofrequency ablation (SRFA). Following IRB approval, a retrospective evaluation of 98 SRFA treatment sessions of 189 CRLMs in 63 consecutive patients was performed. Local recurrence rate (LR), overall survival (OS) and disease-free survival (DFS) were analysed. LR was identified in 16% of the tumours (31/189), with no significant differences (P = 0.635) when comparing tumour sizes 5 cm (17.4%). The median OS from SRFA treatment was 33.2 months after a mean follow-up of 25 months (range 2-66); the corresponding 1-, 3- and 5- year survival rates were 87%, 44% and 27%. The median OS was significantly different when comparing unresectable and resectable patients (27 vs. 58 months, P = 0.002) with OS rates of 92%, 66% and 48% at 1, 3 and 5 years in resectable patients. Tumour size did not affect OS and DFS. Due to the favourable outcome, SRFA challenges resection as first-line local treatment of patients with CRLM. As long as randomised studies are pending, we recommend entering an individual decision-making process with every patient. (orig.)

  14. Contrast-enhanced ultrasound vs multidetector-computed tomography for detecting liver metastases in colorectal cancer: a prospective, blinded, patient-by-patient analysis

    Rafaelsen, S R; Jakobsen, A

    2011-01-01

    This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer.......This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer....

  15. Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury.

    Jiao, Shu-Fan; Sun, Kai; Chen, Xiao-Jing; Zhao, Xue; Cai, Ning; Liu, Yan-Jun; Xu, Long-Mei; Kong, Xian-Ming; Wei, Li-Xin

    2014-01-08

    Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection. Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors. These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

  16. Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

    Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh

    2014-01-01

    To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

  17. Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

    Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

  18. Percutaneous radiofrequency ablation (RFA) or robotic radiosurgery (RRS) for salvage treatment of colorectal liver metastases

    Stintzing, Sebastian; Hendrich, Saskia; Heinemann, Volker [Dept. of Medical Oncology and Comprehensive Cancer Center, Klinikum Grosshadern, LMU, Munich (Germany)], E-mail: sebastian.stintzing@med.uni-muenchen.de; Grothe, Alexander; Trumm, Christoph G. [Dept. of Clinical Radiology, Univ. Hospital Grosshadern, LMU Munich, Munich (Germany); Hoffmann, Ralf-Thorsten [Dept. and Policlinics of Diagnostic Radiology, Universitaetsklinikum Carl Gustav Carus Dresden (Germany); Rentsch, Markus [Dept. of Surgery, Univ. Hospital Grosshadern, LMU Munich, Munich (Germany); Fuerweger, Christoph; Muacevic, Alexander [European Cyberknife Center Munich, Munich (Germany)

    2013-06-15

    Background. Stereotactic radiation therapy is an evolving modality to treat otherwise unresectable liver metastases. In this analysis, two local therapies: 1) single session robotic radiosurgery (RRS) and 2) percutaneous radiofrequency ablation (RFA) were compared in a total of 60 heavily pretreated colorectal cancer patients. Methods. Thirty patients with a total of 35 colorectal liver metastases not qualifying for surgery that were treated in curative intent with RRS were prospectively followed. To compare efficacy of both treatment modalities, patients treated with RFA during the same period of time were matched according to number and size of the treated lesions. Local tumor control, local disease free survival (DFS), and freedom from distant recurrence (FFDR) were analyzed for effi cacy. Treatment-related side effects were recorded for comparison. Results. The median diameter of the treated lesions was 33 mm (7-53 mm). Baseline characteristics did not differ significantly between the groups. One- and two-year local control rates showed no signifi cant difference but favored RRS (85% vs. 65% and 80% vs. 61%, respectively). A signifi cantly longer local DFS of patients treated with RRS compared to RFA (34.4 months vs. 6.0 months; p 0.001) was found. Both, median FFDR (11.4 months for RRS vs. 7.1 months for RFA p=0.25) and the recurrence rate (67% for RRS and 63% for RFA, p>0.99) were comparable. Conclusion. Single session RRS is a safe and effective method to treat colorectal liver metastases. In this analysis, a trend towards longer DFS was seen in patients treated with RRS when compared to RFA.

  19. Percutaneous radiofrequency ablation (RFA) or robotic radiosurgery (RRS) for salvage treatment of colorectal liver metastases

    Stintzing, Sebastian; Hendrich, Saskia; Heinemann, Volker; Grothe, Alexander; Trumm, Christoph G.; Hoffmann, Ralf-Thorsten; Rentsch, Markus; Fuerweger, Christoph; Muacevic, Alexander

    2013-01-01

    Background. Stereotactic radiation therapy is an evolving modality to treat otherwise unresectable liver metastases. In this analysis, two local therapies: 1) single session robotic radiosurgery (RRS) and 2) percutaneous radiofrequency ablation (RFA) were compared in a total of 60 heavily pretreated colorectal cancer patients. Methods. Thirty patients with a total of 35 colorectal liver metastases not qualifying for surgery that were treated in curative intent with RRS were prospectively followed. To compare efficacy of both treatment modalities, patients treated with RFA during the same period of time were matched according to number and size of the treated lesions. Local tumor control, local disease free survival (DFS), and freedom from distant recurrence (FFDR) were analyzed for effi cacy. Treatment-related side effects were recorded for comparison. Results. The median diameter of the treated lesions was 33 mm (7-53 mm). Baseline characteristics did not differ significantly between the groups. One- and two-year local control rates showed no signifi cant difference but favored RRS (85% vs. 65% and 80% vs. 61%, respectively). A signifi cantly longer local DFS of patients treated with RRS compared to RFA (34.4 months vs. 6.0 months; p 0.001) was found. Both, median FFDR (11.4 months for RRS vs. 7.1 months for RFA p=0.25) and the recurrence rate (67% for RRS and 63% for RFA, p>0.99) were comparable. Conclusion. Single session RRS is a safe and effective method to treat colorectal liver metastases. In this analysis, a trend towards longer DFS was seen in patients treated with RRS when compared to RFA

  20. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  1. Fluid–fluid level in hepatic metastases: A characteristic sign of metastases of neuroendocrine origin

    Sommer, Wieland H.; Zech, Christoph J.; Bamberg, Fabian; Auernhammer, Christoph J.; Helck, Andreas; Paprottka, Philipp M.; Notohamiprodjo, Mike; Reiser, Maximilian F.; Herrmann, Karin A.

    2012-01-01

    Objectives: The aim of this study is to determine MRI characteristics which indicate liver metastases of neuroendocrine tumors (NET) rather than metastases of other origin (non-NET). Methods: Sixty-nine patients with histopathologically proven liver metastases from NET and 69 patients with known liver metastases of other origin underwent MRI of the liver using a 1.5 T MR-scanner. Two board certified radiologists assessed presence of fluid–fluid-levels, number and distribution pattern, signal intensity (SI) characteristics, lesion homogeneity, presence of central necrosis and intratumoral hemorrhage in T2w and T1w non-contrast imaging. A multivariate logistic regression analysis was performed to determine the independent association of image findings and occurrence of NET. Results: Fluid–fluid-levels were identified in 19/69 of patients with NET-metastases, and in none of the patients in the control group (p < 0.0001). Hyperintense SI in T1w imaging, markedly hyperintense SI in T2w imaging, a disseminated distribution pattern and intratumoral hemorrhage were indicative of NET metastases (p < 0.05). After statistical adjustment for all significant MRI findings, fluid–fluid-levels (OR: 17.6, 95% CI: 1.9–166.5), strongly hyperintense SI in T2w (OR: 4.7, 95% CI: 1.8–12.7) and a disseminated distribution pattern (OR: 2.9, 95% CI: 1.1–7.4) were independent predictors for NET metastases. Conclusions: The presence of fluid–fluid-levels is highly indicative of NET liver metastases and can be used as an independent predictor to distinguish them from metastases of other origin

  2. Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

    Grimm, Martin; Thalheimer, Andreas; Gasser, Martin; Bueter, Marco; Strehl, Johanna; Wang, Johann; Nichiporuk, Ekaterina; Meyer, Detlef; Germer, Christoph T; Waaga-Gasser, Ana M

    2010-01-01

    The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-β and TNF-α were increased during tumor growth whereas IFN-γ showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the

  3. Definition and scope of the surgical treatment in patients with pulmonary metastases from colorectal cancer

    B. B. Ahmedov

    2016-01-01

    Full Text Available Surgical treatment of metastatic colorectal cancer in lungs is a relatively new trend of modern oncology. In this connection, still there are no clearly formulated criteria for patient selection for this type of intervention, approaches to repeated resections and scope of the surgical operation in case of multiple lesions. Established key prognostic factors include lesion of intrathoracic lymph nodes, timing of the development of metastatic disease, baseline level of carcinoembryonic antigen, number of foci and the volume of metastatic lesion, stage of the disease. Options for surgical access include lateral thoracotomy, sternotomy, thoracoscopy and thoracoscopy combined with additional minithoracotomy.If a patient has a single peripheral metastatic lesions, physician should prefer thoracoscopic operations. One of their advantages include minimum development of adhesions and possibility of subsequent re-thoracoscopy. Resection of pulmonary metastases from colorectal cancer (R0 resection rate allows to achieve persistent healing of the tumor process in a significant number of patients.

  4. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    Pua, Uei

    2013-01-01

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192–198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960–966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  5. Safety margin in irradiation of colorectal liver metastases: assessment of the control dose of micrometastases

    Seidensticker Max

    2010-03-01

    Full Text Available Abstract Backround Micrometastases of colorectal liver metastases are present in up to 50% of lesions. In this study we sought to determine the threshold dose for local control of occult micrometastases in patients undergoing CT (computed tomography-guided brachytherapy of colorectal liver metastases. Materials and methods Nineteen patients demonstrated 34 local tumor recurrences originating from micrometastases after CT-guided brachytherapy of 27 colorectal liver metastases. We considered a local tumor recurrence as originating from a micrometastasis if tumor regrowth occurred adjacent to a formerly irradiated lesion and the distance of the 3D isocenter of the new lesion was ≤ 23.5 mm from the previous tumor margin. Follow-up MRI was fused with the planning-CT and dosimetry data. Two reviewers independently indicated the dose exposure at the isocenter of the micrometastases. Statistical analysis included an analysis of variance (ANOVA using backward selection. 95% tolerance intervals with coverage of 87.5 and 75% of the data of the normal distribution were calculated. Results The median distance of the micrometastases to the margin of the originating colorectal metastases was 8.75 mm (1-21 mm. Dose exposure at the isocenter was 12.25 Gy (7-19.8 in median. We stratified according to the distance from the isocenter to the initial tumor margin: ≤ 9 mm, > 9-15 mm and > 15 mm. The median dose in the according isocenters was 13.18, 11.6 and 11.85 Gy. The threshold dose failing to prevent micrometastasis growth was sigificantly higher in a subgroup of lesions with ≤ 9 mm distance as compared to > 15 mm (13.18 vs 11.85 Gy. Adjuvant chemotherapy correlated with greater distance of micrometastasis growth to the tumor but not with the threshold dose. Conclusion To prevent loss of local tumor control by continuous growth of micrometastases a threshold dose of 15,4 Gy (single fraction should be delivered at a distance of 21 mm to the gross tumor

  6. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

    2013-06-15

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  7. Dual phase helical CT versus portal venous phase CT for the detection of colorectal liver metastases: Correlation with intra-operative sonography, surgical and pathological findings

    Scott, D. John; Guthrie, J. Ashley; Arnold, Paul; Ward, Janice; Atchley, Julian; Wilson, Daniel; Robinson, Philip J.

    2001-01-01

    AIM: To assess whether dual phase helical computed tomography (DPCT) of the liver improves the detection of colorectal liver metastases compared with portal venous phase (PVP) imaging alone. MATERIALS AND METHODS: DPCT was performed in 33 consecutive patients before laparotomy for resection of colorectal liver metastases. CT comprised 8-mm slice collimation with a pitch of 1 to 1.25; imaging was commenced 20-25 and 65-70 s after the start of injection of 150 ml of contrast medium at 5 ml/s to coincide with hepatic arterial phase (HAP) and PVP contrast enhancement, respectively. Four blinded observers independently reviewed the HAP, PVP and DPCT images recording the site and size of all lesions. Alternative-free response receiver operating characteristic (AFROC) methodology was used to analyse the results, which were correlated with surgery, intra-operative ultrasound and histology. RESULTS: The mean observer sensitivities for malignant lesion detection were 75.3% for DPCT, 69.7% for PVP imaging and 66.7% for HAP imaging alone. There was a statistically significant improvement in malignant lesion detection using DPCT when compared with PVP imaging alone (P < 0.05). The mean areas under the AFROC curves were 0.84 for DPCT and 0.82 for PVP (P < 0.03) imaging alone. CONCLUSION: The detection of colorectal liver metastases was marginally better with DPCT than with PVP imaging alone, but the discovery of additional lesions did not affect the management of any of the patients in this study. Scott, D.J. et al. (2001)

  8. Gastric and Colorectal Metastases of Lobural Breast Carcinoma: A Case Report

    David Buka

    2016-04-01

    Full Text Available Background: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. Case Report: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. Conclusions: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

  9. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma

    Jereb Sara

    2016-06-01

    Full Text Available Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment.

  10. Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation

    Gillams, A.R.; Lees, W.R.

    2009-01-01

    There is little published long-term survival data for patients with colorectal liver metastases treated with radiofrequency ablation (RFA). We present a multivariate analysis of 5-year survival in 309 patients (198 male, aged 64 (24-92)) treated at 617 sessions. Our standard protocol used internally cooled electrodes introduced percutaneously under combined US and CT guidance/monitoring. The number and size of liver metastases, the presence and location of extrahepatic disease, primary resection, clinical, chemotherapy and follow-up data were recorded. Data analysis was performed using SPSS v.10. On multivariate analysis, significant survival factors were the presence of extrahepatic disease (p < 0.001) and liver tumour volume (p = 0.001). For 123 patients with five or less metastases of 5 cm or less maximum diameter and no extrahepatic disease median survival was 46 and 36 months from liver metastasis diagnosis and ablation, respectively; corresponding 3- and 5-year survival rates were 63%, 34% and 49%, 24%. Sixty-nine patients had three or less tumours of below 3.5 cm in diameter and their 5-year survival from ablation was 33%. There were 23/617(3.7%) local complications requiring intervention. Five-year survival of 24-33% post ablation in selected patients is superior to any published chemotherapy data and approaches the results of liver resection. (orig.)

  11. Na,K-ATPase isozymes in colorectal cancer and liver metastases

    Marc eBaker Bechmann

    2016-01-01

    Full Text Available The goal of this study was to define Na,K-ATPase α and β subunit isoform expression and isozyme composition in colorectal cancer cells and liver metastases. The α1, α3 and β1 isoforms were the most highly expressed in tumor cells and metastases; in the plasma membrane of non-neoplastic cells and mainly in a cytoplasmic location in tumor cells. α1β1 and α3β1 isozymes found in tumor and metastatic cells exhibit the highest and lowest Na+ affinity respectively and the highest K+ affinity. Mesenchymal cell isozymes possess an intermediate Na+ affinity and a low K+ affinity. In cancer, these ions are likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis, especially a high intra-nuclear K+ concentration. A major and striking finding of this study was that in liver, metastasized CRC cells express the α3β1 isozyme. Thus, the α3β1 isozyme could potentially serve as a novel exploratory biomarker of CRC metastatic cells in liver.

  12. BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

    Torres, Orlando Jorge Martins; Marques, Márcio Carmona; Santos, Fabio Nasser; Farias, Igor Correia de; Coutinho, Anelisa Kruschewsky; Oliveira, Cássio Virgílio Cavalcante de; Kalil, Antonio Nocchi; Mello, Celso Abdon Lopes de; Kruger, Jaime Arthur Pirola; Fernandes, Gustavo Dos Santos; Quireze, Claudemiro; Murad, André M; Silva, Milton José de Barros E; Zurstrassen, Charles Edouard; Freitas, Helano Carioca; Cruz, Marcelo Rocha; Weschenfelder, Rui; Linhares, Marcelo Moura; Castro, Leonaldson Dos Santos; Vollmer, Charles; Dixon, Elijah; Ribeiro, Héber Salvador de Castro; Coimbra, Felipe José Fernandez

    2016-01-01

    In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

  13. Sinusoidal obstructive syndrome diagnosed with superparamagnetic iron oxide-enhanced magnetic resonance imaging in patients with chemotherapy-treated colorectal liver metastases.

    Ward, Janice; Guthrie, James A; Sheridan, Maria B; Boyes, Sheila; Smith, Jonathan T; Wilson, Daniel; Wyatt, Judy I; Treanor, Darren; Robinson, Philip J

    2008-09-10

    To assess the predictive value of superparamagnetic iron oxide (SPIO) -enhanced T2-weighted gradient echo (GRE) imaging to determine the presence and severity of sinusoidal obstructive syndrome (SOS). Sixty hepatic resection patients with colorectal metastases treated with chemotherapy underwent unenhanced magnetic resonance imaging (MRI) followed by T2-weighted GRE sequences obtained after SPIO. The images were reviewed in consensus by two experienced observers who determined the presence and severity of linear and reticular hyperintensities, indicating SOS-type liver injury, using a 4-point ordinal scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% CIs for the detection of SOS were calculated. Twenty-four of 60 patients had moderate to severe SOS on MRI. MRI achieved a sensitivity of 87% (95% CI, 66% to 97%), specificity of 89% (95% CI, 75% to 97%), PPV of 83% (95% CI, 63% to 95%), and NPV of 92% (95% CI, 77% to 98%). SOS was never found at surgery or histology in patients whose background liver parenchyma was normal on SPIO-enhanced MRI. SOS is present in a significant proportion of patients with treated colorectal metastases and is effectively detected on SPIO-enhanced T2-weighted GRE images.

  14. Initial Experiences of Simultaneous Laparoscopic Resection of Colorectal Cancer and Liver Metastases

    L. T. Hoekstra

    2012-01-01

    Full Text Available Introduction. Simultaneous resection of primary colorectal carcinoma (CRC and synchronous liver metastases (SLMs is subject of debate with respect to morbidity in comparison to staged resection. The aim of this study was to evaluate our initial experience with this approach. Methods. Five patients with primary CRC and a clinical diagnosis of SLM underwent combined laparoscopic colorectal and liver surgery. Patient and tumor characteristics, operative variables, and postoperative outcomes were evaluated retrospectively. Results. The primary tumor was located in the colon in two patients and in the rectum in three patients. The SLM was solitary in four patients and multiple in the remaining patient. Surgical approach was total laparoscopic (2 patients or hand-assisted laparoscopic (3 patients. The midline umbilical or transverse suprapubic incision created for the hand port and/or extraction of the specimen varied between 5 and 10 cm. Median operation time was 303 (range 151–384 minutes with a total blood loss of 700 (range 200–850 mL. Postoperative hospital stay was 5, 5, 9, 14, and 30 days. An R0 resection was achieved in all patients. Conclusions. From this initial single-center experience, simultaneous laparoscopic colorectal and liver resection appears to be feasible in selected patients with CRC and SLM, with satisfying short-term results.

  15. Anatomical versus nonanatomical resection of colorectal liver metastases: Is there a difference in surgical and oncological outcome?

    Z.S. Lalmahomed (Zarina); N. Ayez (Ninos); A.E.M. van der Pool (Anne); J. Verheij (Joanne); J.N.M. IJzermans (Jan); C. Verhoef (Kees)

    2011-01-01

    textabstractBackground: The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy to save as much liver volume as possible pivotal. In this study, we determined the difference in

  16. What to choose as radical local treatment for lung metastases from colo-rectal cancer: surgery or radiofrequency ablation?

    Schlijper, R.C.; Grutters, J.P.C.; Houben, R.; Dingemans, A.M.; Wildberger, J.E.; Raemdonck, D. Van; Cutsem, E. van; Haustermans, K.; Lammering, G.; Lambin, P.; Ruysscher, D. de

    2014-01-01

    BACKGROUND: Long-term survival can be obtained with local treatment of lung metastases from colorectal cancer. However, it is unclear as to what the optimal local therapy is: surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT). METHODS: A systematic review included 27 studies

  17. Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases Data From the Oslo-CoMet Trial: Erratum.

    2016-03-01

    In the article ''Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases Data From the Oslo-CoMet Trial'', which appeared in Volume 94, Issue 42 of Medicine, the University of Oslo was not credited as the affiliation for several authors. The article has since been corrected online.

  18. Comparison between local ablative therapy and chemotherapy for non-resectable colorectal liver metastases: a prospective study

    Ruers, Theo J. M.; Joosten, Joris J.; Wiering, Bastiaan; Langenhoff, Barbara S.; Dekker, Heleen M.; Wobbes, Theo; Oyen, Wim J. G.; Krabbe, Paul F. M.; Punt, Cornelis J. A.

    2007-01-01

    There is a growing interest for the use of local ablative techniques in patients with non-resectable colorectal liver metastases. Evidence on the efficacy over systemic chemotherapy is, however, extremely weak. In this prospective study we aim to assess the additional benefits of local tumour

  19. Comparison between local ablative therapy and chemotherapy for non-resectable colorectal liver metastases: a prospective study.

    Ruers, T.J.M.; Joosten, J.J.; Wiering, B.; Langenhoff, B.S.; Dekker, H.M.; Wobbes, Th.; Oyen, W.J.G.; Krabbe, P.F.M.; Punt, C.J.A.

    2007-01-01

    BACKGROUND: There is a growing interest for the use of local ablative techniques in patients with non-resectable colorectal liver metastases. Evidence on the efficacy over systemic chemotherapy is, however, extremely weak. In this prospective study we aim to assess the additional benefits of local

  20. Tissue inhibitor of matrix metalloproteinase-1 expression in colorectal cancer liver metastases is associated with vascular structures

    Illemann, Martin; Eefsen, Rikke Helene Løvendahl; Bird, Nigel Charles

    2016-01-01

    several proteases, involved in the degradation of extracellular matrix components, are up-regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is a strong prognostic marker in plasma from colorectal cancer patients...

  1. Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms

    Song, Yan [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014 (China); Lv, Liyang [Department of Health, Jinan Military Area Command, Jinan 250022 (China); Du, Juan; Yue, Longtao [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014 (China); Cao, Lili, E-mail: cllly22@163.com [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014 (China)

    2013-09-20

    Highlights: •We clarified NDRG1 subcellular location in colorectal cancer. •We found the changes of NDRG1 distribution during colorectal cancer progression. •We clarified the correlation between NDRG1 distribution and lymph node metastasis. •It is possible that NDRG1 subcellular localization may determine its function. •Maybe NDRG1 is valuable early diagnostic markers for metastasis. -- Abstract: In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P < 0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.

  2. Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms

    Song, Yan; Lv, Liyang; Du, Juan; Yue, Longtao; Cao, Lili

    2013-01-01

    Highlights: •We clarified NDRG1 subcellular location in colorectal cancer. •We found the changes of NDRG1 distribution during colorectal cancer progression. •We clarified the correlation between NDRG1 distribution and lymph node metastasis. •It is possible that NDRG1 subcellular localization may determine its function. •Maybe NDRG1 is valuable early diagnostic markers for metastasis. -- Abstract: In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P < 0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis

  3. Simultaneous resection for colorectal cancer with synchronous liver metastases is a safe procedure: Outcomes at a single center in Turkey.

    Dulundu, Ender; Attaallah, Wafi; Tilki, Metin; Yegen, Cumhur; Coskun, Safak; Coskun, Mumin; Erdim, Aylin; Tanrikulu, Eda; Yardimci, Samet; Gunal, Omer

    2017-05-23

    The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.

  4. Low Accuracy of Computed Tomography and Positron Emission Tomography to Detect Lung and Lymph Node Metastases of Colorectal Cancer.

    Guerrera, Francesco; Renaud, Stéphane; Schaeffer, Mickaël; Nigra, Victor; Solidoro, Paolo; Santelmo, Nicola; Filosso, Pier Luigi; Falcoz, Pierre-Emmanuel; Ruffini, Enrico; Oliaro, Alberto; Massard, Gilbert

    2017-10-01

    Minimally invasive surgery, stereotactic radiotherapy, and radiofrequency ablation are commonly proposed in the case of pulmonary colorectal-metastasis as alternatives to conventional open surgery. Preoperative imaging assessment by computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (FDG-PET) are critical to guide oncologic radical treatment. Our aim was to investigate the accuracy of CT and FDG-PET for the evaluation of the number of pulmonary colorectal metastases and thoracic lymph nodal involvement (LNI). Patients who underwent lung surgical resection for pulmonary colorectal metastases from 2004 to 2014 were analyzed. Concordance between histology, CT scan, and FDG-PET findings were assessed. Data of 521 patients were analyzed. Of those, FDG-PET was performed in 435 (83.5%). A moderate agreement between both CT scan (kappa index: 0.42) and FDG-PET (kappa index: 0.42) findings and the histologically proven number of metastases was observed. The number of histologically proven metastases was correctly discriminated in 61.7% of cases with CT scan and in 61.8% of cases with FDG-PET. Multiple metastases were discovered in 20.9% of clinical single metastasis cases with CT scan, and in 24.4% of those cases with FDG-PET. One hundred fifty patients (29.1%) presented with pathologic LNI. A poor agreement was observed between LNI and CT scan findings (kappa index: 0.02), and a weak agreement was observed concerning LNI and FDG-PET findings (kappa index: 0.39). Computed tomography and FDG-PET have limitations if the objective is to detect all malignant nodules and to discriminate the LNI in cases of pulmonary metastases of colorectal cancer. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial.

    Ruers, Theo; Van Coevorden, Frits; Punt, Cornelis J A; Pierie, Jean-Pierre E N; Borel-Rinkes, Inne; Ledermann, Jonathan A; Poston, Graeme; Bechstein, Wolf; Lentz, Marie-Ange; Mauer, Murielle; Folprecht, Gunnar; Van Cutsem, Eric; Ducreux, Michel; Nordlinger, Bernard

    2017-09-01

    Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases. © The Author 2017. Published by Oxford University Press.

  6. GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity.

    Magee, Michael S; Kraft, Crystal L; Abraham, Tara S; Baybutt, Trevor R; Marszalowicz, Glen P; Li, Peng; Waldman, Scott A; Snook, Adam E

    2016-01-01

    Adoptive T-cell therapy (ACT) is an emerging paradigm in which T cells are genetically modified to target cancer-associated antigens and eradicate tumors. However, challenges treating epithelial cancers with ACT reflect antigen targets that are not tumor-specific, permitting immune damage to normal tissues, and preclinical testing in artificial xenogeneic models, preventing prediction of toxicities in patients. In that context, mucosa-restricted antigens expressed by cancers exploit anatomical compartmentalization which shields mucosae from systemic antitumor immunity. This shielding may be amplified with ACT platforms employing antibody-based chimeric antigen receptors (CARs), which mediate MHC-independent recog-nition of antigens. GUCY2C is a cancer mucosa antigen expressed on the luminal surfaces of the intestinal mucosa in mice and humans, and universally overexpressed by colorectal tumors, suggesting its unique utility as an ACT target. T cells expressing CARs directed by a GUCY2C-specific antibody fragment recognized GUCY2C, quantified by expression of activation markers and cytokines. Further, GUCY2C CAR-T cells lysed GUCY2C-expressing, but not GUCY2C-deficient, mouse colorectal cancer cells. Moreover, GUCY2C CAR-T cells reduced tumor number and morbidity and improved survival in mice harboring GUCY2C-expressing colorectal cancer metastases. GUCY2C-directed T cell efficacy reflected CAR affinity and surface expression and was achieved without immune-mediated damage to normal tissues in syngeneic mice. These observations highlight the potential for therapeutic translation of GUCY2C-directed CAR-T cells to treat metastatic tumors, without collateral autoimmunity, in patients with metastatic colorectal cancer.

  7. Which patients will benefit from percutaneous radiofrequency ablation of colorectal liver metastases? Critically appraised topic.

    McGrane, Siobhan

    2012-02-03

    In clinical radiology, there are numerous examples of new techniques that were initially enthusiastically promoted and then subsequently abandoned when early promise was not realized in routine patient care. Appropriateness of new or established interventional radiology techniques to specific clinical conditions must be determined from clinical experience, from communication with experts in the field and\\/or careful review of available medical literature, and on an individual patient basis by means of review of clinical notes and diagnostic imaging studies. For patients with liver neoplasms, regional techniques such as radiofrequency ablation (RFA) have been developed and are now the subject of ongoing research. This article describes the utilization of Evidence-Based Practice (EBP) techniques as a means of deciding the appropriateness of percutaneous RFA in treating colorectal liver metastases (CLM).

  8. Colorectal Liver Metastases: Does the Future of Precision Medicine Lie in Genetic Testing?

    Barbon, Carlotta; Margonis, Georgios Antonios; Andreatos, Nikolaos; Rezaee, Neda; Sasaki, Kazunari; Buettner, Stefan; Damaskos, Christos; Pawlik, Timothy M; He, Jin; Wolfgang, Christopher L; Weiss, Matthew J

    2018-04-11

    Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.

  9. Application of computed tomography virtual noncontrast spectral imaging in evaluation of hepatic metastases: a preliminary study.

    Tian, Shi-Feng; Liu, Ai-Lian; Liu, Jing-Hong; Sun, Mei-Yu; Wang, He-Qing; Liu, Yi-Jun

    2015-03-05

    The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography (CT) virtual noncontrast (VNC) spectral imaging in a retrospective analysis. Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast (TNC) and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial, portal venous, and equilibrium phases. The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial (VNCa), venous (VNCv), and equilibrium (VNCe) phase by the material decomposition process using water and iodine as a base material pair. The image quality and the contrast-to-noise ratio (CNR) of metastasis of the four groups were compared with ANOVA analysis. The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chi-square test. There were no significant differences in image quality among TNC, VNCa and VNCv images (P > 0.05). The quality of VNCe images was significantly worse than that of other three groups (P 0.05). The metastasis detection rate of the four nonenhanced groups with no statistically significant difference (P > 0.05). The quality of VNCa and VNCv images is identical to that of TNC images, and the metastasis detection rate in VNC images is similar to that in TNC images. VNC images obtained from arterial phase show metastases more clearly. Thus, VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.

  10. Application of Computed Tomography Virtual Noncontrast Spectral Imaging in Evaluation of Hepatic Metastases: A Preliminary Study

    Shi-Feng Tian

    2015-01-01

    Full Text Available Objective: The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography (CT virtual noncontrast (VNC spectral imaging in a retrospective analysis. Methods: Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast (TNC and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial, portal venous, and equilibrium phases. The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial (VNCa, venous (VNCv, and equilibrium (VNCe phase by the material decomposition process using water and iodine as a base material pair. The image quality and the contrast-to-noise ratio (CNR of metastasis of the four groups were compared with ANOVA analysis. The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chi-square test. Results: There were no significant differences in image quality among TNC, VNCa and VNCv images (P > 0.05. The quality of VNCe images was significantly worse than that of other three groups (P 0.05. The metastasis detection rate of the four nonenhanced groups with no statistically significant difference (P > 0.05. Conclusions: The quality of VNCa and VNCv images is identical to that of TNC images, and the metastasis detection rate in VNC images is similar to that in TNC images. VNC images obtained from arterial phase show metastases more clearly. Thus, VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.

  11. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial.

    Fretland, Åsmund Avdem; Dagenborg, Vegar Johansen; Bjørnelv, Gudrun Maria Waaler; Kazaryan, Airazat M; Kristiansen, Ronny; Fagerland, Morten Wang; Hausken, John; Tønnessen, Tor Inge; Abildgaard, Andreas; Barkhatov, Leonid; Yaqub, Sheraz; Røsok, Bård I; Bjørnbeth, Bjørn Atle; Andersen, Marit Helen; Flatmark, Kjersti; Aas, Eline; Edwin, Bjørn

    2018-02-01

    To perform the first randomized controlled trial to compare laparoscopic and open liver resection. Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking. Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins. The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001). In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued

  12. Colorectal liver metastases: contrast agent diffusion coefficient for quantification of contrast enhancement heterogeneity at MR imaging.

    Jia, Guang; O'Dell, Craig; Heverhagen, Johannes T; Yang, Xiangyu; Liang, Jiachao; Jacko, Richard V; Sammet, Steffen; Pellas, Theodore; Cole, Patricia; Knopp, Michael V

    2008-09-01

    To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases. This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material-enhanced MR imaging was performed by using a saturation-recovery fast gradient-echo sequence. A simplified contrast agent diffusion model was proposed, and a contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of the CDC measurement was evaluated by using the Bland-Altman plot and a linear regression model. The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73 mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot showed good agreement, with a mean difference in measurement pairs of 0.017 mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95% confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence interval: -0.08, 0.09). The CDC enables a quantitative description of contrast enhancement heterogeneity in lesions. Given the high reproducibility of the CDC metric, CDC appears promising for further qualification as an imaging biomarker of change measurement in response assessment. http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1. RSNA, 2008

  13. Carbon ion radiotherapy for oligo-recurrent lung metastases from colorectal cancer: a feasibility study

    Takahashi, Wataru; Nakajima, Mio; Yamamoto, Naoyoshi; Yamada, Shigeru; Yamashita, Hideomi; Nakagawa, Keiichi; Tsuji, Hiroshi; Kamada, Tadashi

    2014-01-01

    The purpose of this study was to evaluate the efficacy and feasibility of carbon ion radiotherapy (CIRT) for oligo-recurrent lung tumors from colorectal cancer (CRC). From May 1997 to October 2012, 34 consecutive patients with oligo-recurrent pulmonary metastases from CRC were treated with CIRT. The patients were not surgical candidates for medical reasons or patient refusal. Using a respiratory-gated technique, carbon ion therapy was delivered with curative intent using 4 coplanar beam angles. A median dose of 60 GyE (range, 44–64.8 GyE) was delivered to the planning target volume (PTV), with a median daily dose of 15 GyE (range, 3.6–44 GyE). Treatment outcome was analyzed in terms of local control rate (LCR), survival rate, and treatment-related complications. In total, 34 patients with 44 oligo-recurrent pulmonary lesions were treated with CIRT. Median follow-up period was 23.7 months. The 2- and 3-year actuarial LCRs of the treated patients were 85.4% ± 6.2% and 85.4% ± 6.2%, respectively. Overall survival was 65.1% ± 9.5% at 2 years, and 50.1% ± 10.5% at 3 years. Although survival rates were relatively worse in the subsets of patients aged < 63 years or with early metastasis (< 36 months after resection of primary site), these factors were not significantly correlated with overall survival (P = 0.13 and 0.19, respectively). All treatment-related complications were self-limited, without any grade 3–5 toxicity. CIRT is one of the most effective nonsurgical treatments for colorectal lung metastases, which are relatively resistant to stereotactic body radiotherapy. CIRT is considered to be the least invasive approach even in patients who have undergone repeated prior thoracic metastasectomies

  14. Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

    Fahmueller, Yvonne Nadine; Nagel, Dorothea; Hoffmann, Ralf-Thorsten; Tatsch, Klaus; Jakobs, Tobias; Stieber, Petra; Holdenrieder, Stefan

    2012-01-01

    Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy

  15. Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients

    Gu, Xiao-Dong; Cai, Yan-Tao; Zhou, Yi-Ming; Li, Zhen-Yang; Xiang, Jian-Bin; Chen, Zong-You

    2015-01-01

    The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. The overall 1- and 2-year survival rates were 27.7 and 9.9 %. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P = 0.02 and P = 0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P = 0.11). Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis

  16. Microinvasion of liver metastases from colorectal cancer: predictive factors and application for determining clinical target volume

    Qian, Yang; Zeng, Zhao-Chong; Ji, Yuan; Xiao, Yin-Ping

    2015-01-01

    This study evaluates the microscopic characteristics of liver metastases from colorectal cancer (LMCRC) invasion and provides a reference for expansion from gross tumor volume (GTV) to clinical targeting volume (CTV). Data from 129 LMCRC patients treated by surgical resection at our hospital between January 2008 and September 2009 were collected for study. Tissue sections used for pathology and clinical data were reviewed. Patient information used for the study included gender, age, original tumor site, number of tumors, tumor size, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199), synchronous or metachronous liver metastases, and whether patients received chemotherapy. The distance of liver microinvasion from the tumor boundary was measured microscopically by two senior pathologists. Of 129 patients evaluated, 81 (62.8 %) presented microinvasion distances from the tumor boundary ranging between 1.0 − 7.0 mm. A GTV-to-CTV expansion of 5, 6.7, or 7.0 mm was required to provide a 95, 99, or 100 % probability, respectively, of obtaining clear resection margins by microscopic observation. The extent of invasion was not related to gender, age, synchronous or metachronous liver metastases, tumor size, CA199 level, or chemotherapy. The extent of invasion was related to original tumor site, CEA level, and number of tumors. A scoring system was established based on the latter three positive predictors. Using this system, an invasion distance less than 3 mm was measured in 93.4 % of patients with a score of ≤1 point, but in only 85.7 % of patients with a score of ≤2 points. The extent of tumor invasion in our LMCRC patient cohort correlated with original tumor site, CEA level, and number of tumors. These positive predictors may potentially be used as a scoring system for determining GTV-to-CTV expansion

  17. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  18. T cells but not NK cells are associated with a favourable outcome for resected colorectal liver metastases

    Pugh, Siân A; Harrison, Rebecca J; Primrose, John N; Khakoo, Salim I

    2014-01-01

    The adaptive immune response to colorectal cancer is important for survival. Less is understood about the role of innate lymphocytes, such as Natural Killer (NK) cells, which are abundant in human liver. Samples of fresh liver (n = 21) and tumour (n = 11) tissue were obtained from patients undergoing surgical resection of colorectal liver metastases. Flow cytometry was used to analyse the presence and phenotype of NK cells, as compared to T cells, in the tumour and liver tissue. Results were correlated with survival. NK cells were poorly recruited to the tumours (distant liver tissue 38.3%, peritumoural liver 34.2%, tumour 12.9%, p = 0.0068). Intrahepatic and intratumoural NK cells were KIR (killer immunoglobulin-like receptor) lo NKG2A hi whereas circulating NK cells were KIR hi NKG2A lo . By contrast T cells represented 65.7% of the tumour infiltrating lymphocytes. Overall survival was 43% at 5 years, with the 5-year survival for individuals with a T cell rich infiltrate being 60% (95% CI 17-93%) and for those with a low T cell infiltrate being 0% (95% CI 0-48%). Conversely individuals with higher levels of NK cells in the tumour had an inferior outcome, although there were insufficient numbers to reach significance (median survivals: NK Hi 1.63 years vs NK Lo 3.92 years). T cells, but not NK cells, are preferentially recruited to colorectal liver metastases. NK cells within colorectal metastases have an intrahepatic and potentially tolerogenic, rather than a peripheral, phenotype. Similar to primary tumours, the magnitude of the T cell infiltrate in colorectal metastases is positively associated with survival

  19. Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial)

    Olofsson, Roger; Ny, Lars; Eilard, Malin Sternby

    2014-01-01

    for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting...... of the longest surviving patients in Sweden during the same time period (26 versus 12 months). METHODS/DESIGN: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver....... The planned sample size is 78 patients throughout five years. DISCUSSION: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall...

  20. Hepatic Metastases of Granulosa Cell Tumour of the Ovary

    José I. Rodríguez García

    1996-01-01

    Full Text Available A case of metastatic granulosa cell tumour of the ovary is reported. Investigations revealed a secondary tumour in segment VI and VII of the liver. Right hepatic resection was performed. Microscopic findings revealed a tumour with histological features identical to that removed eleven years before.

  1. A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX vs CAPOX alone as adjuvant treatment

    Schouten Sander B

    2010-10-01

    Full Text Available Abstract Background About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX. Methods/design The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall

  2. Biofunctionalized Hybrid Magnetic Gold Nanoparticles as Catalysts for Photothermal Ablation of Colorectal Liver Metastases.

    White, Sarah B; Kim, Dong-Hyun; Guo, Yang; Li, Weiguo; Yang, Yihe; Chen, Jeane; Gogineni, Venkateswara R; Larson, Andrew C

    2017-12-01

    Purpose To demonstrate that anti-MG1 conjugated hybrid magnetic gold nanoparticles (HNPs) act as a catalyst during photothermal ablation (PTA) of colorectal liver metastases, and thus increase ablation zones. Materials and Methods All experiments were performed with approval of the institutional animal care and use committee. Therapeutic and diagnostic multifunctional HNPs conjugated with anti-MG1 monoclonal antibodies were synthesized, and the coupling efficiency was determined. Livers of 19 Wistar rats were implanted with 5 × 10 6 rat colorectal liver metastasis cell line cells. The rats were divided into three groups according to injection: anti-MG1-coupled HNPs (n = 6), HNPs only (n = 6), and cells only (control group, n = 7). Voxel-wise R2 and R2* magnetic resonance (MR) imaging measurements were obtained before, immediately after, and 24 hours after injection. PTA was then performed with a fiber-coupled near-infrared (808 nm) diode laser with laser power of 0.56 W/cm 2 for 3 minutes, while temperature changes were measured. Tumors were assessed for necrosis with hematoxylin-eosin staining. Organs were analyzed with inductively coupled plasma mass spectrometry to assess biodistribution. Therapeutic efficacy and tumor necrosis area were compared by using a one-way analysis of variance with post hoc analysis for statistically significant differences. Results The coupling efficiency was 22 μg/mg (55%). Significant differences were found between preinfusion and 24-hour postinfusion measurements of both T2 (repeated measures analysis of variance, P = .025) and T2* (P the anti-MG1 HNP and HNP-only groups (P = .034). Mean temperature ± standard deviation with PTA in the anti-MG1-coated HNP, HNP, and control groups was 50.2°C ± 7.8, 51°C ± 4.4, and 39.5°C ± 2.0, respectively. Inductively coupled plasma mass spectrometry revealed significant tumor targeting and splenic sequestration. Mean percentages of tumor necrosis in the anti-MG1-coated HNP, HNP, and

  3. The impact of PET/CT on the management of hepatic and extra hepatic metastases from gastrointestinal cancers

    Polat, Erdal, E-mail: erdal066@yahoo.com [Kartal Kosuyolu High Specialty Training and Research Hospital, Department of Gastrointestinal Surgery, Istanbul (Turkey); Bostanci, Erdal Birol [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Aksoy, Erol [Turkiye Yuksek Ihtisas Teaching and Research Hospital, Department of Gastroenterological Surgery, Ankara (Turkey); Karaman, Kerem [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Poyraz, Nilufer Yildirim [Ataturk Teaching and Research Hospital, Department of Nuclear Medicine, Ankara (Turkey); Duman, Ugur [Sevket Yilmaz Training and Research Hospital, Department of General Surgery, Bursa (Turkey); Gencturk, Zeynep Biyikli [Ankara University, Faculty of Medicine, Department of Biostatistics, Ankara (Turkey); Yol, Sinan [Medeniyet University, Faculty of Medicine, Department of General surgery, Istanbul (Turkey)

    2015-06-15

    Highlights: • CT is more sensitive than PET/CT in detecting hepatic metastases. • PET/CT is more specific in detecting hepatic metastases. • CT and PET/CT have equal sensitivity in detecting extra hepatic metastases. • PET/CT is more specific in detecting extra hepatic metastases. • PET/CT has an impact of about 40% on changing the management strategies. - Abstract: Purpose: To investigate the efficacy of positron emission tomography/computed tomography (PET/CT) in detection and management of hepatic and extrahepatic metastases from gastrointestinal cancers. Materials and methods: Between February 2008 and July 2010, patients histopathologically diagnosed with gastrointestinal cancer and showing suspected metastasis on CT screening were subsequently evaluated with PET/CT. All patients were subgrouped according to histopathological origin and localization of the primary tumor. Localization of gastrointestinal cancers was further specified as lower gastrointestinal system (GIS), upper GIS, or hepato-pancreato-biliary (HPB). Both accuracy and impact of CT and PET/CT on patient management were retrospectively evaluated. Results: One hundred and thirteen patients diagnosed histopathologically with gastrointestinal cancers were retrospectively evaluated. Seventy-nine patients had adenocarcinoma and 34 patients other gastrointestinal tumors. Forty-one patients were in the upper GIS group, 30 patients in the HPB group, and 42 patients in the lower GIS group. Evaluation the diagnostic performance of PET/CT for suspected metastasis according to histopathological origin of the tumor, revealed that the sensitivity of PET/CT – although statistically not different – was higher in adenocarcinomas than in non-adenocarcinomas (90% (95% CI, 0.78–0.96) vs. 71.4% (95% CI, 0.45–0.88), P = 0.86). The specificity was not significantly different (85.7% (95% CI, 0.70–0.93) vs. 85% (95% CI, 0.63–0.94), P = 1.00). In the overall patient group; CT was significantly more

  4. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma

    Jereb, Sara; Trotovsek, Blaz; Skrbinc, Breda

    2016-01-01

    Abstract Background Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment. Case report Twenty-two-year old male was treated for immature teratoma linked to undescended right testicle after birth. On regular follow-up examination...

  5. Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

    Mogensen, Marie Benzon; Hansen, Martin Lundsgaard; Henriksen, Birthe Merete

    2017-01-01

    Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective...... study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured....... Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy...

  6. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma.

    Jereb, Sara; Trotovsek, Blaz; Skrbinc, Breda

    2016-06-01

    Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment. Twenty-two-year old male was treated for immature teratoma linked to undescended right testicle after birth. On regular follow-up examinations no signs of disease relapse or long-term consequences were observed. He was presented with incidental finding of mature cystic teratoma after elective surgery for what appeared to be left-sided inguinal hernia. The tumour was most likely a metastasis of childhood teratoma. Origin within remaining left testicle was not found. Upon further imaging diagnostics, several intrahepatic lesions were revealed. Based on radiologic appearance they were suspicious to be metastases. The patient underwent two ultrasound guided fine-needle aspiration biopsies. Cytologic diagnosis was inconclusive. Histology of laparoscopically obtained tissue disclosed presence of normal splenic tissue and led to diagnosis of hepatic splenosis. Though hepatic splenosis is rare, it needs to be included in differential diagnosis of nodular hepatic lesions. Accurate interpretation of those lesions is crucial for appropriate management of the patient. If diagnosis eludes after cytologic diagnostics alone, laparoscopic excision of nodular lesion is warranted before considering more extensive liver resection.

  7. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab

    Eefsen, Rikke Løvendahl; Engelholm, Lars Henning; Willemoe, Gro L.

    2016-01-01

    with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy......The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing...... treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell...

  8. Differential impact of obesity and diabetes mellitus on survival after liver resection for colorectal cancer metastases.

    Amptoulach, Sousana; Gross, Gillis; Kalaitzakis, Evangelos

    2015-12-01

    Data on the potential effect of obesity and diabetes mellitus on survival after liver resection due to colorectal cancer (CRC) metastases are very limited. Patients undergoing liver resection for CRC metastases in a European institution in 2004-2011 were retrospectively enrolled. Relevant data, such as body mass index, extent of resection, chemotherapy, and perioperative outcome, were collected from medical records. The relation of obesity and diabetes mellitus with overall and disease-free survival was assessed using adjusted Cox models. Thirty of 207 patients (14.4%) included in the study were obese (BMI ≥30 kg/m(2)) and 25 (12%) had diabetes mellitus. Major hepatectomy was performed in 46%. Although both obese patients and those with diabetes had higher American Society of Anesthesiologist scores (P diabetes was significantly related to primary tumor characteristics, liver metastasis features, extent or radicality of resection, extrahepatic disease at hepatectomy, preoperative or postoperative oncologic therapy, or perioperative outcome (P > 0.05 for all). Patients were followed up for a median of 39 mo posthepatectomy (interquartile range, 13-56 mo). After adjustment for confounders, obesity was an independent predictor of improved (hazard ratio, 0.305, 95% confidence interval, 0.103-0.902) and diabetes of worse overall survival (hazard ratio, 3.298, 95% confidence interval, 1.306-8.330). Obese patients with diabetes had also worse disease-free survival compared with the rest of the cohort (P diabetes mellitus has a negative impact on prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Determinants of long-term outcome in patients undergoing simultaneous resection of synchronous colorectal liver metastases.

    Qi Lin

    Full Text Available BACKGROUND: It remains unclear which patients can benefit from simultaneous resection of synchronous colorectal liver metastases (SCRLMs. This study aimed to examine the prognostic value of patient- and tumor-related factors in predicting long-term outcomes of patients undergoing simultaneous resection of SCRLMs and to help patients select a suitable therapeutic regimen and proper surveillance. METHODS: Clinicopathological and outcome data of 154 consecutive SCRLM patients who underwent simultaneous resection between July 2003 and July 2013 were collected from our prospectively established SCRLM data and analyzed with univariate and multivariate methods, and the prognostic index (PI was formulated based on the regression coefficients (β of the Cox model. The patients were classified into high- and low-risk groups according to the PI value; the cut-off point was the third quartile. RESULTS: The 5-year overall survival rate was 46%, and the 5-year disease-free survival rate was 35%. Five factors were found to be independent predictors of poor overall survival (OS by multivariate analysis: positive lymph node status, vascular invasion, BRAF mutation, the distribution of bilobar liver metastases (LMs and non-R0 resection of LMs. Compared to low PI (≤5.978, high PI (>5.978 was highly predictive of shorter OS. Three factors were found to be independent predictors of poor disease-free survival (DFS by multivariate analysis: tumor deposits, BRAF mutation and bilobar LM distribution. We also determined the PI for DFS. Compared to low PI (≤2.945, high PI (>2.945 was highly predictive of shorter DFS. CONCLUSIONS: Simultaneous resection of SCRLM may lead to various long-term outcomes. Patients with low PI have longer OS and DFS, while those with high PI have shorter OS and DFS. Thus, patients with high PI may receive more aggressive treatment and intensive surveillance, This model needs further validation.

  10. Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

    Turtoi, Andrei; Blomme, Arnaud; Debois, Delphine; Somja, Joan; Delvaux, David; Patsos, Georgios; Di Valentin, Emmanuel; Peulen, Olivier; Mutijima, Eugène Nzaramba; De Pauw, Edwin; Delvenne, Philippe; Detry, Olivier; Castronovo, Vincent

    2014-03-01

    Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. © 2014 by the American Association for the Study of Liver Diseases.

  11. IFNα gene/cell therapy curbs colorectal cancer colonization of the liver by acting on the hepatic microenvironment.

    Catarinella, Mario; Monestiroli, Andrea; Escobar, Giulia; Fiocchi, Amleto; Tran, Ngoc Lan; Aiolfi, Roberto; Marra, Paolo; Esposito, Antonio; Cipriani, Federica; Aldrighetti, Luca; Iannacone, Matteo; Naldini, Luigi; Guidotti, Luca G; Sitia, Giovanni

    2016-02-01

    Colorectal cancer (CRC) metastatic dissemination to the liver is one of the most life-threatening malignancies in humans and represents the leading cause of CRC-related mortality. Herein, we adopted a gene transfer strategy into mouse hematopoietic stem/progenitor cells to generate immune-competent mice in which TEMs-a subset of Tie2(+) monocytes/macrophages found at peritumoral sites-express interferon-alpha (IFNα), a pleiotropic cytokine with anti-tumor effects. Utilizing this strategy in mouse models of CRC liver metastasis, we show that TEMs accumulate in the proximity of hepatic metastatic areas and that TEM-mediated delivery of IFNα inhibits tumor growth when administered prior to metastasis challenge as well as on established hepatic lesions, improving overall survival. Further analyses unveiled that local delivery of IFNα does not inhibit homing but limits the early phases of hepatic CRC cell expansion by acting on the radio-resistant hepatic microenvironment. TEM-mediated IFNα expression was not associated with systemic side effects, hematopoietic toxicity, or inability to respond to a virus challenge. Along with the notion that TEMs were detected in the proximity of CRC metastases in human livers, these results raise the possibility to employ similar gene/cell therapies as tumor site-specific drug-delivery strategies in patients with CRC. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Radiofrequency Ablation of Colorectal Liver Metastases: Small Size Favorably Predicts Technique Effectiveness and Survival

    Veltri, Andrea; Sacchetto, Paola; Tosetti, Irene; Pagano, Eva; Fava, Cesare; Gandini, Giovanni

    2008-01-01

    The objective of this study was to analyze long-term results of radiofrequency thermal ablation (RFA) for colorectal metastases (MTS), in order to evaluate predictors for adverse events, technique effectiveness, and survival. One hundred ninety-nine nonresectable MTS (0.5-8 cm; mean, 2.9 cm) in 122 patients underwent a total of 166 RFA sessions, percutaneously or during surgery. The technique was 'simple' or 'combined' with vascular occlusion. The mean follow-up time was 24.2 months. Complications, technique effectiveness, and survival rates were statistically analyzed. Adverse events occurred in 8.1% of lesions (major complication rate: 1.1%), 7.1% with simple and 16.7% with combined technique (p = 0.15). Early complete response was obtained in 151 lesions (81.2%), but 49 lesions (26.3%) recurred locally after a mean of 10.4 months. Sustained complete ablation was achieved in 66.7% of lesions ≤3 cm versus 33.3% of lesions >3 cm (p 3 cm (p = 0.006). We conclude that 'simple' RFA is safe and successful for MTS ≤3 cm, contributing to prolong survival when patients can be completely treated.

  13. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

    Hawkes Eliza A

    2012-08-01

    Full Text Available Abstract Background Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC. Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy. Methods Patients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities. Results Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS and those who underwent surgery alone (S respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens. Conclusions Peri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.

  14. Peritoneal metastases of colorectal origin - cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect.

    Jastrzębski, Tomasz; Bębenek, Marek

    2017-12-30

    The incidence of peritoneal carcinomatosis of colorectal cancer amounts to 5%-15% for synchronous metastases and as much as 40% in cases of local recurrence. Best results are obtained for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment offers much better outcomes, leading to 5-year survival rates of as much as 30%-50%. The procedures require significant experience in abdominal surgery, are time-consuming (mean duration of the procedure ranging from 6 to 8 hours) and are burdened by complications that are due not only to the procedure itself but also to the intraperitoneal administration of the cytostatic drug at elevated temperature (41.5 °C). After the procedure, patients are required to be admitted to intensive care units due to potential complications associated with the extent and duration of the procedure as well as chemotherapy administered in hyperthermia. Postoperative management of these patients requires appropriate experience of the entire medical and nursing team. Cytoreductive surgeries combined with HIPEC as highly specialized medical procedures should be assessed for their potential long-term benefits and their costs should be appropriately calculated with consideration to realistic reimbursement rates. Realistic valuation and reimbursement covering the overall average cost of the procedure is recommended by the National Consultant in Surgical Oncology as well as the ESMO consensus guidelines.

  15. Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

    Nikol Snoeren

    Full Text Available BACKGROUND AND OBJECTIVES: This study was designed to identify and validate gene signatures that can predict disease free survival (DFS in patients undergoing a radical resection for their colorectal liver metastases (CRLM. METHODS: Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France and the University Medical Center Utrecht (The Netherlands. Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort. RESULT: No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort. CONCLUSIONS: No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.

  16. Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma.

    Ito, Katsuki; Hibi, Kenji; Ando, Hideyuki; Hidemura, Kazuhiko; Yamazaki, Taiji; Akiyama, Seiji; Nakao, Akimasa

    2002-02-01

    Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p Clearance (k) showed a significant difference between the groups (p time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.

  17. Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer.

    Jarzabek, Monika A; Proctor, William R; Vogt, Jennifer; Desai, Rupal; Dicker, Patrick; Cain, Gary; Raja, Rajiv; Brodbeck, Jens; Stevens, Dale; van der Stok, Eric P; Martens, John W M; Verhoef, Cornelis; Hegde, Priti S; Byrne, Annette T; Tarrant, Jacqueline M

    2018-01-01

    Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively. Putative mechanistic biomarkers of bevacizumab (bev)-mediated protection against oxaliplatin-induced SD were also investigated. RNA was extracted from whole liver sections or centrilobular regions by laser-capture microdissection (LCM) obtained from NHP administered anti-DLL4 fragment antigen-binding (F(ab')2 or patients with CRLM receiving oxaliplatin-based chemotherapy with or without bev. mRNA expression was quantified using high-throughput real-time quantitative PCR. Significance analysis was used to identify genes with differential expression patterns (false discovery rate (FDR) < 0.05). Eleven (CCL2, CCND1, EFNB2, ERG, ICAM1, IL16, LFNG, NOTCH1, NOTCH4, PRDX1, and TGFB1) and six (CDH5, EFNB2, HES1, IL16, MIK67, HES1 and VWF) candidate genes were differentially expressed in the liver of anti-DLL4- and oxaliplatin-induced SD, respectively. Addition of bev to oxaliplatin-based chemotherapy resulted in differential changes in hepatic CDH5, HEY1, IL16, JAG1, MMP9, NOTCH4 and TIMP1 expression. This work implicates NOTCH and IL16 pathways in the pathogenesis of drug-induced SD and further explains the hepato-protective effect of bev in oxaliplatin-induced SD observed in CRLM patients.

  18. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer

    Reissfelder, Christoph; Büchler, Markus W; Beckhove, Philipp; Huber, Peter E; Weitz, Jürgen; Timke, Carmen; Schmitz-Winnenthal, Hubertus; Rahbari, Nuh N; Koch, Moritz; Klug, Felix; Roeder, Falk; Edler, Lutz; Debus, Jürgen

    2011-01-01

    Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases. This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome. This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01191632

  19. Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

    Amouyal, G; Pernot, S; Déan, C; Cholley, B; Scotté, F; Sapoval, M; Pellerin, O

    2017-11-01

    The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18 FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18 FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS

  20. Prognostic factors for survival in patients with colorectal liver metastases: experience of a single brazilian cancer center

    Héber Salvador de Castro Ribeiro

    2012-12-01

    Full Text Available CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients

  1. Radioimmunodetection of metastases of colorectal carcinoma by external scintigraphy after administration of 131I-antibody to carcinoembryonic antigen

    Jones, B.E.; Begent, R.H.J.; Jewkes, R.F.; Vernon, P.; Searle, F.; Keep, P.A.; Green, A.J.; Bagshawe, K.D.

    1982-01-01

    Patients suspected of having metastases of colorectal carcinoma but without palpable tumour deposits were given an intravenous injection of affinity purified goat antibody to carcinoembryonic antigen (CEA) which had been labelled with 131 I by the chloramine T method. 24 Hours later images of antibody distribution were obtained with a large field gamma camera. Computer substraction of background radioactivity was performed using the image obtained after injection of sup(99m)Technetium labelled albumen and free sup(99m)TcO 4 . 23 Scans were carried out in 16 patients and 22 scan images showed residual uptake in specific areas which were considered positive for tumour. Evidence of metastasis was found at these sites in 10 patients, at surgery in 6, by computerised tomography in 3 and by ultrasound in 1. Probable false positive results were obtained in 3 scans. Metastases are still suspected in 4 patients although localisation has not been confirmed. Radioimmunodetection appears to have potential as a method for detecting metastases of colorectal carcinoma. (Author)

  2. Multidisciplinary Approach to Hepatic Metastases of Intracranial Hemangiopericytoma: A Case Report and Review of the Literature

    Dimitrios K. Manatakis

    2015-01-01

    Full Text Available Hemangiopericytoma is a rare primary tumor originating from Zimmerman’s pericytes, with significant metastatic potential. Hepatic metastatic disease requires an aggressive approach by a multidisciplinary team of dedicated oncology specialists, to prolong survival in selected patients. We report on a patient with recurrent hepatic metastases of grade II intracranial hemangiopericytoma 5 years after initial treatment, managed by a stepwise combination of liver resection, radiofrequency ablation, and transarterial embolization. Although metastatic disease implies hematogenous dissemination, long-term survival after liver resection has been reported and major hepatectomies are justified in patients with adequate local control. Liver resections combined with transarterial embolization are highly recommended, due to hypervascularity of the tumor.

  3. Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes—A 10-year Experience at a Single Center

    Shady, Waleed; Petre, Elena N.; Gonen, Mithat; Erinjeri, Joseph P.; Brown, Karen T.; Covey, Anne M.; Alago, William; Durack, Jeremy C.; Maybody, Majid; Brody, Lynn A.; Siegelbaum, Robert H.; D’Angelica, Michael I.; Jarnagin, William R.; Solomon, Stephen B.; Kemeny, Nancy E.

    2016-01-01

    Purpose To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. Materials and Methods This study consisted of a HIPAA-compliant institutional review board–approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material–enhanced CT was used to assess technique effectiveness 4–8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2–4 months. Overall survival (OS) and local tumor progression–free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. Results Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. Conclusion Tumor size of less than 3 cm and ablation margins greater than 5 mm

  4. Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases

    Passot, Guillaume; Chun, Yun Shin; Kopetz, Scott E; Zorzi, Daria; Brudvik, Kristoffer Watten; Kim, Bradford J; Conrad, Claudius; Aloia, Thomas A; Vauthey, Jean-Nicolas

    2016-01-01

    Background In patients with bilateral colorectal liver metastases (CLM) not resectable in one operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy. Study Design The study included all 109 patients for whom two-stage hepatectomy for CLM was planned during 2003-2014. RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis. Results Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after first stage were disease progression (n=12), insufficient liver growth (n=5), and complications after first stage or portal vein embolization (n=3). More than six cycles of preoperative chemotherapy were associated with failure to proceed to second stage (p=0.009). Rates of major complications (26% vs. 6%; p<0.001) and 90-day mortality (7% vs. 0%; p=0.006) were higher after second stage. The cumulative rate of major complications was 15% (n=29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than one lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs. 6%; p<0.001) and 5-year overall survival rates (49% vs. 0%; p<0.001) were better after two-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p=0.044), more than five CLM (p=0.043), need for chemotherapy after first stage (p=0.046), and RAS mutation (p<0.001). Conclusions RAS mutation independently predicts the oncologic efficacy of two-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy. PMID:26968325

  5. Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience.

    Ntourakis, Dimitrios; Memeo, Ricardo; Soler, Luc; Marescaux, Jacques; Mutter, Didier; Pessaux, Patrick

    2016-02-01

    Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.

  6. Regional differences in prostaglandin E2 metabolism in human colorectal cancer liver metastases

    Young, Alastair L; Chalmers, Claire R; Hawcroft, Gillian; Perry, Sarah L; Treanor, Darren; Toogood, Giles J; Jones, Pamela F; Hull, Mark A

    2013-01-01

    Prostaglandin (PG) E 2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE 2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE 2 content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE 2 in human CRC cells in vitro. Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE 2 levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β. PGE 2 levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE 2 . Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo. There is significant intra-tumoral heterogeneity in PGE 2 content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE 2 metabolism should be targeted for novel treatment of advanced CRC

  7. Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

    Valdimarsson, Valentinus T; Syk, Ingvar; Lindell, Gert; Norén, Agneta; Isaksson, Bengt; Sandström, Per; Rizell, Magnus; Ardnor, Bjarne; Sturesson, Christian

    2018-05-01

    Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  8. Seeding after ultrasound-guided percutaneous biopsy of liver metastases in patients with colorectal or breast cancer

    Chen, Inna; Lorentzen, Torben; Linnemann, Dorte

    2016-01-01

    BACKGROUND: Neoplasm seeding is a serious complication after liver metastases biopsy. Reported incidences vary between 10% and 19% for colorectal cancer (CRC) and are unknown for breast cancer (BC). The aim of this retrospective study was to determine the frequency of tumor seeding after ultrasound...... retrospectively reviewed. The endpoint was the development of abdominal wall recurrence following liver biopsy. RESULTS: Of total 2981 biopsies we identified 278 patients with CRC and 155 patients with BC biopsy-verified liver metastases. During the median follow-up of 25 months after biopsy (range 3-253 months......), no seeding was recorded in patients with BC. Within the median follow-up of 34 months (3-111 months), seeding was registered in 17/278 (6%) of patients with CRC; three patients of 278 (1%) had undoubtedly biopsy-related seeding, which became apparent six, nine, and 26 months after biopsy, respectively...

  9. Elevated C-reactive protein and hypoalbuminemia measured before resection of colorectal liver metastases predict postoperative survival.

    Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

    2010-01-01

    Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases > or =3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright 2010 S. Karger AG, Basel.

  10. Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy

    Binkley, Michael S. [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Trakul, Nicholas [Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Jacobs, Lisa Rose; Eyben, Rie von; Le, Quynh-Thu; Maxim, Peter G.; Loo, Billy W. [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Shultz, David Benjamin, E-mail: DavidS4@Stanford.edu [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes. Methods and Materials: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses. Results: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED{sub 10}) of <100 Gy versus BED{sub 10} of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed. Conclusions: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  11. Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors

    Denecke, Timm [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Baur, Alexander D.J., E-mail: alexander.baur@charite.de [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Ihm, Claudia; Steffen, Ingo G. [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Tischer, Elisabeth [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Arsenic, Ruza [Institut für Pathologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin (Germany); Pascher, Andreas [Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Wiedenmann, Bertram; Pavel, Marianne [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany)

    2013-10-01

    Purpose: There are different therapeutic options in non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) with unresectable hepatic metastases including systemic chemotherapy and novel molecular targeted therapies. Treatment with somatostatin analogs (SSA) as antiproliferative agents is optional. At initial diagnosis watchful waiting until tumor progression is a well-established approach. Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression in order to select patients that might benefit from an earlier initiation of medical treatment. Patients and methods: In 44 patients we correlated tumor grade, chromogranin A (CgA) levels, treatment with SSA and imaging features of hepatic metastases on contrast-enhanced multiphase CT and MR imaging with time to tumor progression (TTP) according to RECIST 1.0. Results: In the total patient cohort none of the tested imaging features was found to be a statistically significant prognostic factor for TTP. Since treatment with SSA was associated with an increased TTP we also analyzed a subgroup of 30 patients not treated with SSA. In this subgroup of patients hypoenhancement of hepatic metastases during early contrast phases was found to be a negative prognostic factor for early tumor progression within 12 months (p = 0.039). The other evaluated parameters including hepatic tumor load, number of metastases, and presence of regressive morphological changes did not reveal significant results. Conclusion: Hypovascularization of liver metastases from G1 and G2 pNET reflected by hypoenhancement during the early contrast phases seems to be associated with early tumor progression. In patients with hypoenhancing metastases repeated biopsy for reassessment of grading of these metastases, and early initiation of therapy should be considered.

  12. Comparison of gadolinium-EOB-DTPA-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases.

    Shimada, Kotaro; Isoda, Hiroyoshi; Hirokawa, Yuusuke; Arizono, Shigeki; Shibata, Toshiya; Togashi, Kaori

    2010-11-01

    To compare the accuracy of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI with that of diffusion-weighted MRI (DWI) in the detection of small hepatic metastases (2 cm or smaller). Forty-five patients underwent abdominal MRI at 3 T, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), heavily T2WI (HASTE), DWI with a b-value of 500 s/mm(2) and contrast-enhanced MRI with Gd-EOB-DTPA. Two groups were assigned and compared: group A (T1WI, T2WI, HASTE and contrast-enhanced study with Gd-EOB-DTPA), and group B (T1WI, T2WI, HASTE and DWI). Two observers independently interpreted the images obtained in a random order. For all hepatic metastases, the diagnostic performance using each imaging set was evaluated by receiver-operating characteristic (ROC) curve analysis. A total of 51 hepatic metastases were confirmed. The area under the ROC curve (Az) of group A was larger than that of group B, and the difference in the mean Az values between the two image sets was statistically significant, whereas, there were three metastases that lay near thin vessels or among multiple cysts and were better visualised in group B than in group A. Gd-EOB-DTPA-enhanced MRI showed higher accuracy in the detection of small metastases than DWI.

  13. A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

    Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol [Donga Univ. School of Medicine, Busan (Korea, Republic of); Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk [Busan National University College of Medicine, Busan (Korea, Republic of)

    2008-06-15

    injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The 12x10{sup 6} DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The DCVac/IR immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

  14. A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

    Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol; Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk

    2008-01-01

    , of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The 12x10 6 DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The DCVac/IR immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials

  15. Transaxillary intra-arterial treatment of hepatic metastases with cytostatics and embolization: its control by isotope studies

    Voorthuisen, A.E. van; Herben, M.G.; Pauwels, E.K.J.

    1980-01-01

    Intra-arterial treatment of hepatic metastases has indicated that this is a rewarding procedure and that embolization of the liver has in a few cases resulted in a high remission rate lasting up to one or two years. The distribution of a cytostatic agent can be accurately controlled by isotope studies. (C.F.)

  16. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    Pua, Uei [Dept. of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore (Singapore)

    2013-08-15

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  17. Rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases following combined loco-regional therapy

    Pua, Uei

    2013-01-01

    This manuscript describes an unusual case of rapid intra-hepatic dissemination of hepatocellular carcinoma with pulmonary metastases occurring 1 month after combined chemoembolization and radiofrequency ablation. Inferior vena cava and portal vein invasion tumor thrombus was also detected, possibly accounting for the mechanism of disease dissemination route of disease.

  18. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  19. Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

    Méndez Romero, Alejandra; Verheij, Joanne; Dwarkasing, Roy S.; Seppenwoolde, Yvette; Redekop, William K.; Zondervan, Pieter E.; Nowak, Peter J.C.M.; Ijzermans, Jan N.M.; Levendag, Peter C.; Heijmen, Ben J.M.; Verhoef, Cornelis

    2012-01-01

    Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r s = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r s = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r s = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r s = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed

  20. Localization of hepatic metastases by radiolabelled anti-carcino-embryonic antigen antibody and meta-iodobenzylguanidine in a patient with medullary thyroid carcinoma

    Liewendahl, K.; Vaelimaeki, M.; Taavitsainen, M.

    1993-01-01

    Sonography, computed tomography and magnetic resonance imaging examinations did not detect recurrence or metastases of medullary thyroid carcinoma (MTC) in a patient with a rapidly rising serum calcitonin concentration after total thyroidectomy. Scintigraphy with technetium-99m labelled anti-carcinoembryonic antigen antibody, 99m Tc-colloid and iodine-131 metaiodobenzylguanidine indicated liver metastases. The three scintigrams were to some extent discrepant but from the combined information the diagnosis of hepatic metastases could be established; it was subsequently verified by sonography and aspiration biopsy. This case demonstrates the usefulness of applying nuclear medicine imaging methods for the localization of hepatic MTC metastases. (orig.)

  1. The Results of the Combine Treatment of Patients with Liver Bilobar Metastases from Colorectal Cancer Using Radiofrequency Ablation.

    Kaganov, Oleg Igorevich; Kozlov, Sergei Vasilevich; Orlov, Andrei Evgenyevich; Blinov, Nikita Vyacheslavovich

    2018-06-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. The mortality from CRC remains very high. The main cause of such a high mortality is a disseminate process with the appearance of distant metastases. In this regard, the treatment of metastatic lesions is recognized as an important trend in modern oncology. The program of study included 176 patients with colorectal cancer after primary tumor removal with the malignant progression-multiple (more than 4) bilobar liver metastases. The research was organized in Samara Regional Oncology Centre from 2001 to 2014. By the treatment method, patients were divided into two groups. Main group got the combined (chemotherapy + radiofrequency ablation (RFA)) treatment ( n  = 98). In control group, only chemotherapy was applied ( n  = 78). One-, two-, and three-year OS were 73.5, 25.1, and 7.2% in the main group and 39.6, 6.3, and 2.1% in the control group. The RFA application allowed us to reach the index of 4-year survival 1.8% in the main group, while we received only 2.1 of 3-year survival in the control group. The OS median reached 18 months in the main group and 11 months in the control group. So, the OS curves in two comparing groups were significantly different according to statistics (log-rank test 3.77, р  = 0.000). The application of RFA in combination with chemotherapy in the treatment of bilobar metastasis colorectal cancer allows to improve the performance of disease-free survival and overall survival significantly, compared with the group of patients who received only chemotherapy.

  2. Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

    Mark I James

    Full Text Available Tumor initiating cells (TIC are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent

  3. Bleeding from ruptured hepatic metastases as a cause of syncope in an octogenarian: a case report

    Rizeq Mazen M

    2010-06-01

    Full Text Available Abstract Introduction Acute hemoperitoneum as a result of hemorrhage from liver metastases is an uncommon but serious condition. The use of appropriate imaging is important in the diagnosis and can have a profound impact on subsequent management. This case is important because the presentation was of recurrent syncopal episodes with an unusual underlying cause. This case highlights the need to consider this diagnosis in the differential in patients presenting with collapse in the acute setting. Case presentation We present the case of an 85-year-old Caucasian man who was admitted following a collapse episode and was found to be persistently hypotensive despite aggressive resuscitation. An acute intra-peritoneal bleed originating from hepatic metastases from an unknown primary was identified promptly with computed tomography imaging and was subsequently managed conservatively. Conclusions This case aims to convey key teaching points: (A the need to consider intra-abdominal hemorrhage in the differential diagnosis when assessing patients with collapse; and (B the use of appropriate imaging such as computed tomography can facilitate a prompt diagnosis and appropriate management steps can then be taken accordingly.

  4. Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil.

    Laarhoven, H.W.M. van; Klomp, D.W.J.; Rijpkema, M.J.P.; Kamm, Y.J.L.; Wagener, D.J.T.; Barentsz, J.O.; Punt, C.J.A.; Heerschap, A.

    2007-01-01

    Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of

  5. Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil

    van Laarhoven, H. W. M.; Klomp, D. W. J.; Rijpkema, M.; Kamm, Y. L. M.; Wagener, D. J. Th; Barentsz, J. O.; Punt, C. J. A.; Heerschap, A.

    2007-01-01

    Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of

  6. Contrast-enhanced ultrasound compared with computed tomography, magnetic resonance imaging, and positron emission tomography for diagnosing liver metastases in people with newly diagnosed colorectal cancer

    Lund, Martin; Bjerre, Thomas Abramovitz; Grønbæk, Henning

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To compare the accuracy of CEUS, CECT, MRI, and 18F-FDG PET-CT for diagnosing liver metastases in people with newly-diagnosed colorectal cancer. Potential sources of heterogeneity We will investigate...

  7. Increase in Volume of Ablation Zones during Follow-up Is Highly Suggestive of Ablation Site Recurrence in Colorectal Liver Metastases Treated with Radiofrequency Ablation

    Kele, Petra G.; de Jong, Koert P.; van der Jagt, Eric J.

    Purpose: To test the hypothesis that volume changes of ablation zones (AZs) on successive computed tomography (CT) scans could predict ablation site recurrences (ASRs) in patients with colorectal liver metastases treated by radiofrequency (RF) ablation. Materials and Methods: RF ablation was

  8. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect. © 2015 UICC.

  9. Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

    Muruzabal Francisco J

    2008-10-01

    Full Text Available Abstract Background The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of Results Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

  10. Role of external radiotherapy when taking into care hepatic metastases; Place de la radiotherapie externe dans la prise en charge des metastases hepatiques

    Dietmann, A.S.; Taste-Geroge, H.; Peiffert, D. [Centre Alexis-Vautrin, 54 - Nancy (France)

    2010-10-15

    After having indicated the various origins of hepatic metastases, the authors outline that surgery and local treatment are applicable for 20 per cent of patients. But some of these local treatments may have contra-indications or may entail complications. Radiotherapy techniques used to have possible severe late effects on the liver, but new external radiotherapy apparatus, like the Cyberknife, can now be used. With its ballistic technique and its tracking system, it allows healthy tissues to be protected. It is also well tolerated by the patients. A comparative study with other local treatment techniques (radio-frequency, alcoolization, chemoembolisation) is still to be done. Short communication

  11. Tumor deposit is a poor prognostic indicator in patients who underwent simultaneous resection for synchronous colorectal liver metastases

    Lin Q

    2015-01-01

    Full Text Available Qi Lin,# Ye Wei,# Li Ren,# Yunshi Zhong,# Chunzhi Qin, Peng Zheng, Pingping Xu, Dexiang Zhu, Meiling Ji, Jianmin XuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China#These authors contributed equally to this workBackground: Tumor deposits are one of the important influencing factors among the different editions of Tumor, Node, Metastasis classification. Incidence and prognosis of tumor deposits in stage I, II, and III colorectal cancer patients has been explored. The aim of this study was to determine the prognostic value of tumor deposits in stage IV colorectal cancer patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLM.Methods: Clinicopathological and outcome data of 146 consecutive SCRLM patients who underwent simultaneous R0 resection between July 2003 and July 2013 were collected from our prospectively established SCRLM database. The prognostic value of tumor deposits was evaluated by Kaplan–Meier and Cox regression analysis.Results: Tumor deposits were detected in 41.8% (61/146 of these SCRLM patients. Tumor deposits were significantly correlated with lymph node metastasis and nerve invasion of the primary tumors (P=0.002, P=0.041; respectively. The Kaplan–Meier survival analysis revealed that the overall survival (OS and disease-free survival (DFS of SCRLM patients with tumor deposits were significantly poorer than those with no tumor deposits (P=0.039, P=0.001; respectively. And with multivariate analysis, we found that positive tumor deposits were significantly associated with shorter DFS independent of lymph node status (P=0.002. Subgroup analysis found that of the 57 SCRLM patients with negative lymph node status, the OS and DFS of patients with positive tumor deposits were significantly shorter than those with negative tumor deposits (P=0.002 and P=0.031, respectively. Of the 89 patients with positive lymph node status, the OS of

  12. Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans

    Kobaek-Larsen, M; Thorup, I; Diederichsen, Axel Cosmus Pyndt

    2000-01-01

    BACKGROUND AND PURPOSE: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC...

  13. Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats

    Mayer-Kuckuk, Philipp; Bertino, Joseph R.; Banerjee, Debabrata [Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); The Cancer Institute of New Jersey, Robert Wood Johnson Medical School/UMDNJ, 195 Little Albany Street, NJ 08903, New Brunswick (United States); Doubrovin, Mikhail; Blasberg, Ronald; Tjuvajev, Juri Gelovani [Department of Neurooncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gusani, Niraj J.; Fong, Yuman [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gade, Terence; Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Balatoni, Julius; Finn, Ronald [Radiochemistry/Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Akhurst, Tim; Larson, Steven [Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2003-09-01

    Radionuclide imaging has been demonstrated to be feasible to monitor transgene expression in vivo. We hypothesized that a potential application of this technique is to non-invasively detect in deep tissue, such as cancer cells metastatic to the liver, a specific molecular response following systemic drug treatment. Utilizing human colon adenocarcinoma cells derived from a patient's liver lesion we first developed a nude rat xenograft model for colorectal cancer metastatic to the liver. Expression of a dihydrofolate reductase-herpes simplex virus 1 thymidine kinase fusion (DHFR-HSV1 TK) transgene in the hepatic tumors was monitored in individual animals using the tracer [{sup 124}I]2'-fluoro-2'-deoxy-5-iodouracil-{beta}-d-arabinofuranoside (FIAU) and a small animal micro positron emission tomograph (microPET), while groups of rats were imaged using the tracer [{sup 131}I]FIAU and a clinical gamma camera. Growth of the human metastatic colorectal cancer cells in the rat liver was detected using magnetic resonance imaging and confirmed by surgical inspection. Single as well as multiple lesions of different sizes and sites were observed in the liver of the animals. Next, using a subset of rats bearing hepatic tumors, which were retrovirally bulk transduced to express the DHFR-HSV1 TK transgene, we imaged the fusion protein expression in the hepatic tumor of living rats using the tracer [{sup 124}I]FIAU and a microPET. The observed deep tissue signals were highly specific for the tumors expressing the DHFR-HSV1 TK fusion protein compared with parental untransduced tumors and other tissues as determined by gamma counting of tissue samples. A subsequent study used the tracer [{sup 131}I]FIAU and a gamma camera to monitor two groups of transduced hepatic tumor-bearing rats. Prior to imaging, one group was treated with trimetrexate to exploit DHFR-mediated upregulation of the fusion gene product. Imaging in the living animal as well as subsequent gamma

  14. Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

    Kim, Hayeon, E-mail: kimh2@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Gill, Beant; Beriwal, Sushil; Huq, M. Saiful [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Roberts, Mark S. [Department of Health Policy and Management, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania (United States); Smith, Kenneth J. [Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (United States)

    2016-07-15

    Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

  15. Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

    Kim, Hayeon; Gill, Beant; Beriwal, Sushil; Huq, M. Saiful; Roberts, Mark S.; Smith, Kenneth J.

    2016-01-01

    Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

  16. Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: Results of the RTOG dose escalating protocol

    Russell, A.H.; Clyde, C.; Wasserman, T.H.; Turner, S.S.; Rotman, M.

    1993-01-01

    This study was prepared to address two objectives: (a) to determine whether progressively higher total doses of hepatic irradiation can prolong survival in a selected population of patients with liver metastases and (b) to refine existing concepts of liver tolerance for fractionated external radiation. One hundred seventy-three analyzable patients with computed tomography measurable liver metastases from primary cancers of the gastrointestinal tract were entered on a dose escalating protocol of twice daily hepatic irradiation employing fractions of 1.5 Gy separated by 4 hr or longer. Sequential groups of patients received 27 Gy, 30 Gy, and 33 Gy to the entire liver and were monitored for acute and late toxicities, survival, and cause of death. Dose escalation was implemented following survival of 10 patients at each dose level for a period of 6 months or longer without clinical or biochemical evidence of radiation hepatitis. The use of progressively larger total doses of radiation did not prolong median survival or decrease the frequency with which liver metastases were the cause of death. None of 122 patients entered at the 27 Gy and 30 Gy dose levels revealed clinical or biochemical evidence of radiation induced liver injury. Five of 51 patients entered at the 33 Gy level revealed clinical or biochemical evidence of late liver injury with an actuarial risk of severe (Grade 3) radiation hepatitis of 10.0% at 6 months, resulting in closure of the study to patient entry. The study design could not credibly establish a safe dose for hepatic irradiation, however, it did succeed in determining that 33 Gy in fractions of 1.5 Gy is unsafe, carrying a substantial risk of delayed radiation injury. The absence of apparent late liver injury at the 27 Gy and 30 Gy dose levels suggests that a prior clinical trial of adjuvant hepatic irradiation in patients with resected colon cancer may have employed an insufficient radiation dose (21 Gy) to fully test the question

  17. The influence of blood supply pattern of hepatic metastases on the short-term effect of TACE

    Li Guowen; Liang Zhaoyu; Yu Xiaoping; Gu Shanzhi; Zhang Tiegang; He Qing; Xiong Zhengping; Huang Manping

    2010-01-01

    Objective: To discuss the influence of blood supply pattern of hepatic metastases on the short-term effect of transcatheter arterial chemoembolization (TACE). Methods: A total of 58 cases of liver metastases who had been treated with TACE were selected, the clinical data and short-term effects were retrospectively analyzed. Results: Based on the DSA findings, 58 cases of liver metastases were divided into the hypervascular pattern (n=14), the isovascular pattern (n=12) and the hypovascular pattern group (n=32). After TACE the clinical effective rate (CR + PR) of hypervascular, isovascular and hypo vascular pattern group was 92.9% (13 /14), 83.3% (10/12) and 9.4% (3/32) respectively, with a significant difference existing between hyper vascular and hypo vascular group as well as between iso vascular and hypo vascular group (P 0.05). The survival rate at half and one year after Tace treatment for all cases was 67.2% and 42.3%, respectively. The survival rate at half and one year for hyper vascular, iso vascular and hypo vascular group was 100% and 78.6%, 100% and 58.3%, 40.6% and 7.6%, respectively. A significant difference in the survival rate existed between hypervascular and hypovascular group as well as between isovascular and hypovascular group (P 0.05). Conclusion: TACE shows much better effectiveness for the hypervascular hepatic metastases, and it is very useful for making an appropriate therapeutic plan to distinguish the blood supply pattern of hepatic metastases. (authors)

  18. Preoperative lymphocyte-to-monocyte ratio represents a superior predictor compared with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for colorectal liver-only metastases survival

    Peng JH

    2017-07-01

    Full Text Available Jianhong Peng,1,* Hui Li,2,* Qingjian Ou,1,* Junzhong Lin,1 Xiaojun Wu,1 Zhenhai Lu,1 Yunfei Yuan,1 Desen Wan,1 Yujing Fang,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR in patients with colorectal liver-only metastases (CLOM undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS and overall survival (OS related to the LMR, NLR, and PLR were analyzed using both Kaplan–Meier and multivariate Cox regression methods. Elevated LMR (≥2.82 and lower NLR (<4.63 were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17. Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32–0.844; P=0.008 and OS (hazard ratio, 0.426; 95% CI, 0.254–0.716; P=0.001. In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non

  19. Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases

    Larsen, Nicolai Balle; Heiberg Engel, Peter Johan; Rasmussen, Merete

    2009-01-01

    in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined....... Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly...... hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant...

  20. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    Miles, K.A.; Keith, C.J.; Griffiths, M.R.; Fuentes, M.; Bunce, I.

    2002-01-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  1. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    Miles, K A [Southernex Imaging Group, QLD (Australia); Queensland University of Technology, QLD (Australia); Keith, C J [Southernex Imaging Group, QLD (Australia); Wesley Research Institute, QLD (Australia); Griffiths, M R [Queensland University of Technology, QLD (Australia); Fuentes, M [Southernex Imaging Group, QLD (Australia); Bunce, I [Wesley Research Institute, QLD (Australia)

    2002-07-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc.

  2. Challenging the dogma of colorectal peritoneal metastases as an untreatable condition: Results of a population-based study.

    Razenberg, Lieke G E M; Lemmens, Valery E P P; Verwaal, Victor J; Punt, Cornelis J A; Tanis, Pieter J; Creemers, Geert-Jan; de Hingh, Ignace H J T

    2016-09-01

    To determine the impact of the implementation of novel systemic regimens and locoregional treatment modalities on survival at population level in colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs). All consecutive CRC patients with synchronous PM (<3 months) between 1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer Registry. Trends in treatment and overall survival were assessed in four time periods. Multivariable regression analysis was used to analyse the impact of systemic and locoregional treatment modalities on survival. A total of 37,036 patients were diagnosed with primary CRC between 1995 and 2014. Synchronous PM was diagnosed in 1,661 patients, of whom 55% had also metastases at other sites (n = 917) and 77% received anticancer therapy (n = 1,273). Treatment with systemic therapy increased from 23% in 1995-1999 to 56% in 2010-2014 (p < 0.0001). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was applied since 2005 and increased from 10% in 2005-2009 to 23% in 2010-2014. Surgery for lymphatic or haematogenous metastases increased from 2% to 10% in these periods. Median overall survival of the complete cohort improved from 6.0 months in 1995-2000 to 12.5 months in 2010-2014 (p < 0.0001), with a doubling of survival for both PM alone and PM with other involved sites. The influence of year of diagnosis on survival (hazard ratio, 2010-2014 versus 1995-1999; 0.5, 95% confidence interval: 0.43-0.62; p < 0.0001) disappeared after including systemic therapy and locoregional treatment modalities in subsequent multivariable models. CRC patients presenting with PM are increasingly offered a multidisciplinary treatment approach, resulting in an increased overall survival for the entire cohort. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Neoadjuvant TACE before laser induced thermotherapy (LITT) in the treatment of non-colorectal non-breast cancer liver metastases: Feasibility and survival rates

    Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Kreutzträger, Martin; Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Diagnostic and Interventional Radiology, Cairo University, Cairo (Egypt); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

    2014-10-15

    Purpose: To evaluate safety, feasibility and overall survival rates for transarterial chemoembolization (TACE) alone or combined with MR-guided laser-induced-thermotherapy (LITT) in liver metastases of non-colorectal and non-breast cancer origin. Methods and materials: Included were patients with unresectable non-colorectal non-breast cancer liver metastases with progression under systemic chemotherapy. Excluded were patients with Karnofsky score ≤70, respiratory, renal and cardiovascular failure, and general TACE contraindications. TACE using Mitomycin alone, Mitomycin–Gemcitabine or Mitomycin–Gemcitabine–Cisplatin was performed to all patients. After TACE 146 metastases were ablated with MR-guided LITT. To be eligible for LITT metastases should be <5 cm in size and ≤5 in number. Tumor response was evaluated using MRI according to RECIST. Survival was evaluated using Kaplan–Meier analysis. Results: A total of 110 patients (mean age 59.2 years) with 371 metastases received TACE (mean 5.4 sessions/patient, n = 110) with 76 (69%) receiving LITT (mean 1.6 session/patient) afterwards. TACE resulted in a mean decrease of mean maximum diameter of 52% ± 26.6 and volume change of −68.5% ± 22.9 in the 25 patients (23%) with partial response. Stable disease (n = 59, 54%). Progressive disease (n = 26, 23%). The RECIST outcome after LITT showed complete response (n = 13, 17%), partial response (n = 1, 1%), stable situation (n = 41, 54%) and progressive disease (n = 21, 28%). The mean time to progression (TTP) was 8.6 months. Median survival of all patients was 21.1 months. Conclusion: TACE with different protocols alone and in combination with LITT is a feasible palliative treatment option resulting in a median survival of 21.1 months for unresectable liver metastases of non-colorectal and non-breast cancer origin.

  4. Individual data meta-analysis for the study of survival after pulmonary metastasectomy in colorectal cancer patients: A history of resected liver metastases worsens the prognosis.

    Zabaleta, Jon; Iida, Tomohiko; Falcoz, Pierre E; Salah, Samer; Jarabo, José R; Correa, Arlene M; Zampino, Maria G; Matsui, Takashi; Cho, Sukki; Ardissone, Francesco; Watanabe, Kazuhiro; Gonzalez, Michel; Gervaz, Pascal; Emparanza, Jose I; Abraira, Víctor

    2018-03-21

    To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014. Exclusion criteria were that the paper was a review, concerned surgical techniques themselves (without follow-up), and included patients treated non-surgically. Using Stata 14, we performed aggregate data and individual data meta-analysis using random-effect and Cox multilevel models respectively. We collected data on 3501 patients from 17 studies. The overall median survival was 43 months. In aggregate data meta-analysis, the hazard ratio for patients with previous liver metastases was 1.19 (95% CI 0.90-1.47), with low heterogeneity (I 2 4.3%). In individual data meta-analysis, the hazard ratio for these patients was 1.37 (95% CI 1.14-1.64; p analysis identified the following factors significantly affecting survival: tumour-infiltrated pulmonary lymph nodes (p analysis protocol in PROSPERO (CRD42015017838). Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. Preliminary results of 'liver-first' reverse management for advanced and aggressive synchronous colorectal liver metastases: a propensity-matched analysis.

    Tanaka, Kuniya; Murakami, Takashi; Matsuo, Kenichi; Hiroshima, Yukihiko; Endo, Itaru; Ichikawa, Yasushi; Taguri, Masataka; Koda, Keiji

    2015-01-01

    Although a 'liver-first' approach recently has been advocated in treating synchronous colorectal metastases, little is known about how results compare with those of the classical approach among patients with similar grades of liver metastases. Propensity-score matching was used to select study subjects. Oncologic outcomes were compared between 10 consecutive patients with unresectable advanced and aggressive synchronous colorectal liver metastases treated with the reverse strategy and 30 comparable classically treated patients. Numbers of recurrence sites and recurrent tumors irrespective of recurrence sites were greater in the reverse group then the classic group (p = 0.003 and p = 0.015, respectively). Rates of freedom from recurrence in the remaining liver and of freedom from disease also were poorer in the reverse group than in the classical group (p = 0.009 and p = 0.043, respectively). Among patients treated with 2-stage hepatectomy, frequency of microvascular invasion surrounding macroscopic metastases at second resection was higher in the reverse group than in the classical group (p = 0.011). Reverse approaches may be feasible in treating synchronous liver metastases, but that strategy should be limited to patients with less liver tumor burden. © 2015 S. Karger AG, Basel.

  6. Gadoxetic acid-enhanced 3.0 T MRI for the evaluation of hepatic metastasis from colorectal cancer: Metastasis is not always seen as a “defect” on the hepatobiliary phase

    Kim, Aram, E-mail: arkim.rad@gmail.com [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Lee, Chang Hee, E-mail: chlee86@hanmail.net [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Kim, Baek Hui, E-mail: maelstrom@naver.com [Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Lee, Jongmee, E-mail: leejongmee@hanmail.net [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Choi, Jae Woong, E-mail: cooljay@korea.ac.kr [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Park, Yang Shin, E-mail: pys797979@naver.com [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Kim, Kyeong Ah, E-mail: kahkim@korea.ac.kr [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of); Park, Cheol Min, E-mail: chlee86@gmail.com [Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703 (Korea, Republic of)

    2012-12-15

    Purpose: To determine specific imaging features of hepatic metastasis from colorectal cancer, focusing on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI. Materials and methods: Over a 2-year period, 79 hepatic metastatic lesions were identified from 32 patients (22 men and 10 women) who proven colorectal cancer and underwent gadoxetic acid-enhanced 3.0 T MRI. Hepatic metastases were proven pathologically in 16 patients: by surgical liver resection (n = 14) and by US-guided biopsy (n = 2). The remaining 16 patients were considered to have hepatic metastasis based on imaging studies and clinical information. Two radiologists evaluated the imaging features of each MRI sequence, including high resolution T2WI, dynamic contrast enhancement study with hepatobiliary phase, and diffusion weighted image. We also compared SI of the lesions on T2WI and HBP. Results: T2WI showed homogeneous high SI (n = 25; 31.7%), target appearance (n = 3; 3.8%), reversed target appearance (n = 2; 2.6%), and heterogeneously high SI (n = 49; 62%). On HBP, homogeneous defect were seen in 22 lesions (27.9%), target appearance in five lesions (6.4%), reversed target appearance in two lesions (2.5%), and heterogeneous defect in 50 lesions (63.3%); including reticular (70%), partially globular (26%), and diffuse GGO-like (4%) patterns. According to the imaging features on HBP, the homogeneous defect and heterogeneous defect groups had a mean ADC value of 0.99 × 10{sup −3} and 1.07 × 10{sup −3} mm{sup 2}/s, respectively, without statistically significant difference. Conclusion: Hepatic metastasis from colorectal cancer usually showed as a heterogeneous defect on HBP and a heterogeneous high SI on T2WI. The generally accepted “true defect” was not a common finding in hepatic metastasis from colorectal cancer.

  7. Gadoxetic acid-enhanced 3.0 T MRI for the evaluation of hepatic metastasis from colorectal cancer: Metastasis is not always seen as a “defect” on the hepatobiliary phase

    Kim, Aram; Lee, Chang Hee; Kim, Baek Hui; Lee, Jongmee; Choi, Jae Woong; Park, Yang Shin; Kim, Kyeong Ah; Park, Cheol Min

    2012-01-01

    Purpose: To determine specific imaging features of hepatic metastasis from colorectal cancer, focusing on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI. Materials and methods: Over a 2-year period, 79 hepatic metastatic lesions were identified from 32 patients (22 men and 10 women) who proven colorectal cancer and underwent gadoxetic acid-enhanced 3.0 T MRI. Hepatic metastases were proven pathologically in 16 patients: by surgical liver resection (n = 14) and by US-guided biopsy (n = 2). The remaining 16 patients were considered to have hepatic metastasis based on imaging studies and clinical information. Two radiologists evaluated the imaging features of each MRI sequence, including high resolution T2WI, dynamic contrast enhancement study with hepatobiliary phase, and diffusion weighted image. We also compared SI of the lesions on T2WI and HBP. Results: T2WI showed homogeneous high SI (n = 25; 31.7%), target appearance (n = 3; 3.8%), reversed target appearance (n = 2; 2.6%), and heterogeneously high SI (n = 49; 62%). On HBP, homogeneous defect were seen in 22 lesions (27.9%), target appearance in five lesions (6.4%), reversed target appearance in two lesions (2.5%), and heterogeneous defect in 50 lesions (63.3%); including reticular (70%), partially globular (26%), and diffuse GGO-like (4%) patterns. According to the imaging features on HBP, the homogeneous defect and heterogeneous defect groups had a mean ADC value of 0.99 × 10 −3 and 1.07 × 10 −3 mm 2 /s, respectively, without statistically significant difference. Conclusion: Hepatic metastasis from colorectal cancer usually showed as a heterogeneous defect on HBP and a heterogeneous high SI on T2WI. The generally accepted “true defect” was not a common finding in hepatic metastasis from colorectal cancer.

  8. Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

    Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

    2018-04-11

    Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  9. Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency.

    Sugimoto, Maki; Yasuda, Hideki; Koda, Keiji; Yamazaki, Masato; Tezuka, Tohru; Takenoue, Tomohiro; Kosugi, Chihiro; Higuchi, Ryota; Yamamoto, Shiho; Watayo, Yoshihisa; Yagawa, Yohsuke; Suzuki, Masato

    2007-09-01

    Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.

  10. [Effect of PMU hepatic arterial chemotherapy for liver metastases of gastric cancer. Hokuriku Cisplatin Round-table Conference].

    Sakuma, H; Matsuki, N; Katayama, K; Hirosawa, H; Tomita, F; Takano, N; Tanaka, T; Sawa, T; Ueno, K; Uogishi, M

    1989-08-01

    We performed PMU hepatic arterial chemotherapy (a combination therapy consisting of intra-hepatic arterial infusion of CDDP and MMC, oral administration of UFT) in 20 patients with gastric cancer and liver metastases. In this method, 1-6 courses of one infusion of CDDP at 70-100 mg/body and MMC of 10 mg/body into the proper hepatic artery were administered at intervals of 3-4 weeks. UFT of 300-400 mg/day was orally administered with the infusion. The primary response for hepatic metastatic lesions was observed in one case of CR, 14 cases of PR, 4 cases of NC, and one case of PD. The efficacy for CR and PR was high at 75%. The median disease-free interval was 56 weeks in responders. The 50% survival period was 11.1 months; one-year survival rate, 42.1%; two-year survival rate, 12.3%; the longest survival period was 108 weeks. Mild and transient side effects were recognized in 17 cases (85%): gastrointestinal symptoms, sense of general malaise, fever, leukocytopenia, and elevated BUN. Thus, the results indicated that this combination chemotherapy was effective for liver metastases of gastric cancer.

  11. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases. Methods: A total of 126 patients were included. Analyses were performed...

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

    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.

  13. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  14. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de; Koch, Silvia A., E-mail: silvia.koch@web.de [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Lotz, Gösta, E-mail: goesta.lotz@kgu.de [University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany); Willinek, Winfried, E-mail: w.willinek@bk-trier.de [Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany); Engelke, Christoph, E-mail: engelke@ekweende.de [Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany); Brüning, Roland, E-mail: r.bruening@asklepios.com; Zeile, Martin, E-mail: m.zeile@asklepios.com [Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany); Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de [Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany); Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de [Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  15. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    Vogl, Thomas J.; Koch, Silvia A.; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-01-01

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  16. Disappearing or residual tiny (≤5 mm) colorectal liver metastases after chemotherapy on gadoxetic acid-enhanced liver MRI and diffusion-weighted imaging: Is local treatment required?

    Kim, Seung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Cheonan Hospital, Department of Radiology, Soonchunhyang University College of Medicine, Cheonan-si, Chungcheongnam-do (Korea, Republic of); Song, Kyoung Doo; Kim, Young Kon [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Hee Cheol; Huh, Jung Wook [Sungkyunkwan University School of Medicine, Department of Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Park, Young Suk; Park, Joon Oh; Kim, Seung Tae [Sungkyunkwan University School of Medicine, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-07-15

    To evaluate the clinical course of disappearing colorectal liver metastases (DLM) or residual tiny (≤5 mm) colorectal liver metastases (RTCLM) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in patients who had colorectal liver metastases (CLM) and received chemotherapy. Among 137 patients who received chemotherapy for CLM and underwent gadoxetic acid-enhanced MRI and DWI between 2010 and 2012, 43 patients with 168 DLMs and 48 RTCLMs were included. The cumulative in situ recurrence rate of DLM and progression rate of RTCLM and their predictive factors were evaluated. A total of 150 DLMs and 26 RTCLMs were followed up without additional treatment. At 1 and 2 years, respectively, the cumulative in situ recurrence rates for DLM were 10.9 % and 15.7 % and the cumulative progression rates for RTCLM were 27.2 % and 33.2 %. The in situ recurrence rate at 2 years was 4.9 % for the DLM group that did not show reticular hypointensity of liver parenchyma on hepatobiliary phase. DLM on gadoxetic acid-enhanced liver MRI and DWI indicates a high possibility of clinical complete response, especially in patients without chemotherapy-induced sinusoidal obstruction syndrome. Thirty-three percent of RTCLMs showed progression at 2 years. (orig.)

  17. Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab

    Scartozzi Mario

    2012-04-01

    Full Text Available Abstract Background Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment. Methods We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab. Results Seventy-two patients with histologically proven metastatic colorectal cancer, treated with Irinotecan and Cetuximab based chemotherapy, were eligible for our analysis. In metastases pAKT correlated with RR (9% vs. 58%, p = 0.004, PFS (2.3 months vs.9.2 months p  Discussion pAKT and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAKT and pMAPK metastases expression targeting these factors may be crucial.

  18. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.

    Lewandowski, Robert J; Thurston, Kenneth G; Goin, James E; Wong, Ching-Yee O; Gates, Vanessa L; Van Buskirk, Mark; Geschwind, Jean-Francois H; Salem, Riad

    2005-12-01

    The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

  19. Intermittent clamping of the hepatic pedicle in simultaneous ultrasonography-guided liver resection and colorectal resection with intestinal anastomosis: is it safe?

    De Raffele, Emilio; Mirarchi, Mariateresa; Vaccari, Samuele; Cuicchi, Dajana; Lecce, Ferdinando; Dalla Via, Barbara; Cola, Bruno

    2014-12-01

    In patients with colorectal cancer (CRC) and synchronous colorectal liver metastases (CRLM) potentially candidates to combined liver (LR) and colorectal resection (CRR), the extent of LR and the need of hepatic pedicle clamping (HPC) in selected cases are considered risk factors for the outcome of the intestinal anastomosis. This study aimed to determine whether intermittent HPC is predictive of anastomotic leakage (AL) and has an adverse effect on the clinical outcome in patients undergoing combined restorative CRR and LR. One hundred six LR have been performed for CRLM in our unit from July 2005. Patients who received CRR with anastomosis and simultaneous intraoperative ultrasonography (IOUS)-guided LR/ablation for resectable CRLM were included in this study. CRR was performed first. Intermittent HPC was decided at the discretion of the liver surgeon. The perioperative outcome was evaluated according to occurrence of AL and overall postoperative morbidity and mortality. Thirty-eight patients underwent simultaneous IOUS-guided LR/ablation and CRR with intestinal anastomosis; 19 underwent intermittent HPC (group ICHPY) while 19 did not (group ICHPN); the mean ± SD (range) duration of clamping in group ICHPY was 58.6 ± 32.2 (10.0-125.0) min. Postoperative results were similar between groups. One asymptomatic AL occurred in group ICHPY (5.2 %). Major postoperative complications were none in group ICHPY and one (5.2 %) in group ICHPN, respectively. One patient in group ICHPY died postoperatively (5.2 %). This study suggests that intermittent HPC during LR is not predictive of AL and has no adverse effect on the overall clinical outcome in patients undergoing combined restorative colorectal surgery and hepatectomy for advanced CRC.

  20. Tumor lysis syndrome following endoscopic radiofrequency interstitial thermal ablation of colorectal liver metastases.

    Barry, B D

    2012-02-03

    Radiofrequency interstitial thermal ablation (RITA) provides a palliative option for patients suffering from metastatic liver disease. This procedure can be performed using a laparoscopic approach with laparoscopic ultrasound used to position the RITA probe. We describe a case of laparoscopic RITA performed for colorectal liver metastasis that was complicated by tumor lysis syndrome (TLS) following treatment. We consider RITA to be a safe procedure, as supported by the literature, but where intracorporal tumor lysis is the treatment goal we believe that the systemic release of tumor products can overwhelm the excretory capacity; therefore, TLS is an inevitable consequence in some patients.

  1. The value of gadoxetic acid-enhanced MRI for differentiation between hepatic microabscesses and metastases in patients with periampullary cancer

    Choi, Seo-Youn [Soonchunhyang University College of Medicine, Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of); Kim, Young Kon; Cha, Dong Ik; Jeong, Woo Kyoung; Lee, Won Jae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Min, Ji Hye [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Chungnam National University Hospital, Chungnam National University College of Medicine, Department of Radiology, Daejeon (Korea, Republic of)

    2017-10-15

    We aimed to identify features that differentiate hepatic microabscess from hepatic metastasis on gadoxetic acid-enhanced MRI in patients with periampullary cancer. We included 72 patients (31 patients with 83 hepatic microabscesses and 41 patients with 71 hepatic metastases) who had a history of periampullary cancer and underwent gadoxetic acid-enhanced MRI. Image analysis was performed for margin, signal intensity, rim enhancement, perilesional hyperaemia, pattern on DWI and dynamic phases, and size discrepancy between sequences by consensus of two observers. Multivariate analysis revealed that the following significant parameters favour microabscess: a history of bile duct cancer, perilesional hyperaemia, persistent arterial rim enhancement through the transitional phase (TP), and size discrepancy between T1WI and T2WI and between T1WI and hepatobiliary phase image (HBPI). The diagnostic accuracy for microabscess was highest (90.9%) when showing a size discrepancy ≥30% between T1WI and HBPI or persistent arterial rim enhancement through the TP. When the lesion was positive for both these variables, specificity reached 100%. The combination of a size discrepancy between T1WI and HBPI and persistent arterial rim enhancement through the TP represents a reliable MRI feature for distinguishing between hepatic microabscess and metastasis in patients with periampullary cancer. (orig.)

  2. Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases: Data From the Oslo-CoMet Trial.

    Fretland, Asmund Avdem; Sokolov, Andrey; Postriganova, Nadya; Kazaryan, Airazat M; Pischke, Soren E; Nilsson, Per H; Rognes, Ingrid Nygren; Bjornbeth, Bjorn Atle; Fagerland, Morten Wang; Mollnes, Tom Eirik; Edwin, Bjorn

    2015-10-01

    Laparoscopic and open liver resection have not been compared in randomized trials. The aim of the current study was to compare the inflammatory response after laparoscopic and open resection of colorectal liver metastases (CLM) in a randomized controlled trial.This was a predefined exploratory substudy within the Oslo CoMet-study. Forty-five patients with CLM were randomized to laparoscopic (n = 23) or open (n = 22) resection. Ethylenediaminetetraacetic acid-plasma samples were collected preoperatively and at defined time points during and after surgery and snap frozen at -80 C. A total of 25 markers were examined using luminex and enzyme-linked immunosorbent assay techniques: high-mobility box group 1(HMGB-1), cell-free DNA (cfDNA), cytokines, and terminal C5b-9 complement complex complement activation.Eight inflammatory markers increased significantly from baseline: HMGB-1, cfDNA, interleukin (IL)-6, C-reactive protein, macrophage inflammatory protein -1β, monocyte chemotactic protein -1, IL-10, and terminal C5b-9 complement complex. Peak levels were reached at the end of or shortly after surgery. Five markers, HMGB-1, cfDNA, IL-6, C-reactive protein, and macrophage inflammatory protein -1β, showed significantly higher levels in the open surgery group compared with the laparoscopic surgery group.Laparoscopic resection of CLM reduced the inflammatory response compared with open resection. The lower level of HMGB-1 is interesting because of the known association with oncogenesis.

  3. Gadoxetic acid-enhanced MRI and diffusion-weighted imaging for the detection of colorectal liver metastases after neoadjuvant chemotherapy

    Yu, Mi Hye; Lee, Jeong Min; Han, Joon Koo; Choi, Byung-Ihn; Hur, Bo Yun; Kim, Tae-You; Jeong, Seung-Yong; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    To investigate the diagnostic performance of gadoxetic acid-enhanced MRI including diffusion-weighted imaging (DWI) for the detection of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NAC). Our study population comprised 77 patients with 140 CRLMs who underwent gadoxetic acid-enhanced MRI within 1 month prior to surgery: group A (without NAC, n = 38) and group B (with NAC, n = 39). Two radiologists independently assessed all MR images and graded their diagnostic confidence for CRLM on a 5-point scale. Diagnostic accuracy, sensitivity and positive predictive values (PPV) were calculated and compared between the two groups. Diagnostic accuracy of gadoxetic acid-enhanced MRI in group B was slightly lower than in group A, but a statistically significant difference was not observed (observer 1: A z , 0.926 in group A, 0.905 in group B; observer 2: A z , 0.944 in group A, 0.885 in group B; p > 0.05). Sensitivity and PPV of group B were comparable to those of group A (observer 1: sensitivity = 93.5 % vs. 93.6 %, PPV = 95.1 % vs. 86.9 %; observer 2: sensitivity = 96.8 % vs. 91.0 %; PPV = 90.0 % vs. 89.7 %; all p > 0.05). Gadoxetic acid-enhanced MRI including DWI provided good diagnostic performance with high sensitivity (>90 %) for the detection of CRLMs, regardless of the influence of NAC. (orig.)

  4. A multi-institutional analysis of 429 patients undergoing major hepatectomy for colorectal cancer liver metastases: The impact of concomitant bile duct resection on survival.

    Postlewait, Lauren M; Squires, Malcolm H; Kooby, David A; Weber, Sharon M; Scoggins, Charles R; Cardona, Kenneth; Cho, Clifford S; Martin, Robert C G; Winslow, Emily R; Maithel, Shishir K

    2015-10-01

    Data are lacking on long-term outcomes of patients undergoing major hepatectomy requiring bile duct resection (BDR) for the treatment of colorectal cancer liver metastases. Patients who underwent major hepatectomy (≥3 segments) for metastatic colorectal cancer from 2000-2010 at three US academic institutions were included. The primary outcome was disease-specific survival (DSS). Of 429 patients, nine (2.1%) underwent BDR, which was associated with pre-operative portal vein embolization (25.0% vs. 4.3%; P = 0.049). There were no significant differences in age, ASA class, margin status, number of lesions, tumor size, cirrhosis, perineural invasion, or lymphovascular invasion. BDR was independently associated with increased postoperative major complications (OR: 6.22; 95%CI:1.44-26.97; P = 0.015). There were no differences in length of stay, reoperation, readmission, or 30-day mortality. Patients who underwent BDR had markedly decreased DSS (9.3 vs. 39.9 mo; P = 0.002). When accounting for differences between the two groups, the need for BDR was independently associated with reduced DSS (HR: 3.06; 95%CI:1.12-8.34; P = 0.029). Major hepatectomy with concomitant bile duct resection is seldom performed in patients undergoing resection of colorectal cancer liver metastases and is associated with higher major morbidity and reduced disease-specific survival compared to major hepatectomy alone. Stringent selection criteria should be applied when patients may need bile duct resection during hepatectomy for colorectal cancer liver metastases. © 2015 Wiley Periodicals, Inc.

  5. A survival analysis of the liver-first reversed management of advanced simultaneous colorectal liver metastases: a LiverMetSurvey-based study.

    Andres, Axel; Toso, Christian; Adam, Rene; Barroso, Eduardo; Hubert, Catherine; Capussotti, Lorenzo; Gerstel, Eric; Roth, Arnaud; Majno, Pietro E; Mentha, Gilles

    2012-11-01

    Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches. The study was based on the LiverMetSurvey (January 1, 2000 to December 31, 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin-based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM, P = 0.231) and Fong scores of 3 or more (79% vs 87%, P = 0.164). Rectal cancer, neoadjuvant rectal radiotherapy, and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001), whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease-free survival were similar in the RM and CM groups (48% vs 46% at 5 years, P = 0.965 and 30% vs 26%, P = 0.992). Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.

  6. Assessment of Local Control after Laser-Induced Thermotherapy of Liver Metastases from Colorectal Cancer: Contribution of FDG-PET in Patients with Clinical Suspicion of Progressive Disease

    Denecke, T.; Steffen, I.; Hildebrandt, B.; Ruehl, R.; Streitparth, F.; Lehmk uhl, L.; Langrehr, J.; Ricke, J.; Amthauer, H.; Lopez Haenninen, E.

    2007-01-01

    Background: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Purpose: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. Material and Methods: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semi quantitatively (maximal standard uptake value [SUVmax], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. Results: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUVmax (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). Conclusion: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with LITT

  7. Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil.

    van Laarhoven, H W M; Klomp, D W J; Rijpkema, M; Kamm, Y L M; Wagener, D J Th; Barentsz, J O; Punt, C J A; Heerschap, A

    2007-04-01

    Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor. c 2006 John Wiley & Sons, Ltd.

  8. Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere®) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases

    Lo, Yuan-Hao; Tsai, Ming-Tsun; Kuo, Chen-Yu; Liu, Wen-Sheng; Lee, Rheun-Chuan; Yeh, Yi-Chen; Li, Chung-Pin; Chen, Jinn-Yang; Chao, Yee

    2012-01-01

    The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere ® ) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere ® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication

  9. Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG)

    Huiskens, Joost; Gulik, Thomas M van; Lienden, Krijn P van; Engelbrecht, Marc RW; Meijer, Gerrit A; Grieken, Nicole CT van; Schriek, Jonne; Keijser, Astrid; Mol, Linda; Molenaar, I Quintus; Verhoef, Cornelis; Jong, Koert P de; Dejong, Kees HC; Kazemier, Geert; Ruers, Theo M; Wilt, Johanus HW de; Tinteren, Harm van; Punt, Cornelis JA

    2015-01-01

    Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results. CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel. CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases. CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563, June 10, 2014

  10. High preoperative serum CA19-9 level is predictive of poor prognosis for patients with colorectal liver oligometastases undergoing hepatic resection.

    Lu, Zhenhai; Peng, Jianhong; Wang, Zhiqiang; Pan, Zhizhong; Yuan, Yunfei; Wan, Desen; Li, Binkui

    2016-11-01

    Oligometastasis is defined as a transitional state between localized and widespread systemic metastatic cancers. In colorectal cancer, the prognostic factors and prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for patients with colorectal liver oligometastases (CLOM) undergoing hepatic resection have not been well explored. Therefore, the present study included 141 patients with CLOM (≤5 liver metastases) who underwent R0 resection from 2005 to 2012. The association of clinicopathological factors including preoperative CA19-9 and CEA levels with overall survival (OS) was analyzed with univariate and multivariate analyses. Kaplan-Meier analysis showed that patients with high CA19-9 levels tended to have poorer OS than those with low levels (median OS 21.5 vs. 64.0 months, P = 0.002). Preoperative CEA levels were not significantly associated with OS (P > 0.05). Univariate and multivariate analyses demonstrated that larger tumor size of liver metastases (HR 1.911; 95 % CI 1.172-3.114; P = 0.009), bilobar distribution (HR 1.776; 95 % CI 1.097-2.873; P = 0.019), and higher preoperative CA19-9 levels (HR 1.954; 95 % CI 1.177-3.242; P = 0.010) were independent predictors of poor OS for patients with CLOM. Our study identified tumor size, distribution, and preoperative CA19-9 levels as independent prognostic factors for OS of patients with CLOM. In particular, measurement of preoperative CA19-9 levels offers an easy tool that could help identify high-risk patients and aid in improving the management of patients with CLOM.

  11. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration.

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-04-24

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration*

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-01-01

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors. PMID:25739439

  13. The prognostic value of 18F-FDG PET/CT prior to liver transplantation for nonresectable colorectal liver metastases

    Grut, Harald; Revheim, Mona Elisabeth; Dueland, Svein; Line, Paal Dag

    2018-01-01

    The main objective of this study was to evaluate the prognostic value of volumetric and metabolic information derivied from F-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) in combination with computed tomography (CT) prior to liver transplantation (LT) in patients with nonresectable colorectal liver metastases (CLM). Due to scarcity of liver grafts, prognostic information enabling selection of candidates who will gain the highest survival after LT is of vital importance. 18 F-FDG PET/CT was a part of the preoperative study protocol. Patients without evidence of extrahepatic malignant disease on 18 F-FDG PET/CT who also fulfilled all the other inclusion criteria underwent LT. The preoperative 18 F-FDG PET/CT examinations of all patients included in the SECA (secondary cancer) study were retrospectively assessed. Maximum, mean and peak standardized uptake values (SUV max , SUV mean and SUV peak ), tumor to background (T/B) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured and calculated for all liver metastases. Total MTV and TLG were calculated for each patient. Cut-off values were determined for each of these parameters by using receiver operating characteristic (ROC) analysis dividing the patients into two groups. One, three and five-year overall survival (OS) and disease free survival (DFS) for patients over and under the cut-off value were compared by using the Kaplan-Meier method and log rank test. Twenty-three patients underwent LT in the SECA study. Total MTV and TLG under the cut-off values were significantly correlated to improved OS at three and five years (p = 0.027 and 0.026) and DFS (p = 0.01). One, three and five-year OS and DFS were not significantly related to SUV max , SUV mean , SUV peak or T/B-ratio. Total MTV and TLG from 18 F FDG PET/CT prior to LT for nonresectable CLM were significantly correlated to improved three and five-year OS and DFS and can potentially improve the patient selection

  14. FLT-PET for early response evaluation of colorectal cancer patients with liver metastases: a prospective study.

    Mogensen, Marie Benzon; Loft, Annika; Aznar, Marianne; Axelsen, Thomas; Vainer, Ben; Osterlind, Kell; Kjaer, Andreas

    2017-12-01

    Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study was to evaluate whether FLT-PET can be used for the early evaluation of treatment response in colorectal cancer patients (CRC) with liver metastases. Patients with metastatic CRC having at least one measurable (>1 cm) liver metastasis receiving first-line chemotherapy were included. A FLT-PET/CT scan was performed at baseline and after the first treatment. The maximum and mean standardised uptake values (SUV max , SUV mean ) were measured. After three cycles of chemotherapy, treatment response was assessed by CT scan based on RECIST 1.1. Thirty-nine consecutive patients were included of which 27 were evaluable. Dropout was mainly due to disease complications. Nineteen patients (70%) had a partial response, seven (26%) had stable disease and one (4%) had progressive disease. A total of 23 patients (85%) had a decrease in FLT uptake following the first treatment. The patient with progressive disease had the highest increase in FLT uptake in SUV max . There was no correlation between the response according to RECIST and the early changes in FLT uptake measured as SUV max (p = 0.24). No correlation was found between early changes in FLT uptake after the first cycle of treatment and the response evaluated from subsequent CT scans. It seems unlikely that FLT-PET can be used on its own for the early response evaluation of metastatic CRC.

  15. Transcatheter Arterial Chemoembolization (TACE) of Colorectal Cancer Liver Metastases by Irinotecan-Eluting Microspheres in a Salvage Patient Population

    Huppert, Peter, E-mail: huppert@klinikum-darmstadt.de [Klinikum Darmstadt GmbH, Department of Diagnostic and Interventional Radiology (Germany); Wenzel, Thorsten [Klinikum Darmstadt GmbH, Department of Medical Oncology (Germany); Wietholtz, Hubertus [Klinikum Darmstadt GmbH, Department of Gastroenterology (Germany)

    2013-05-14

    PurposeThis prospective study evaluated the effectiveness and safety of TACE using irinotecan loaded superabsorbent polymer (SAP) microspheres for treatment of colorectal cancer liver metastases (CCLM) in a salvage setting of patients.MethodsA total of 71 TACE procedures were performed in 29 patients with liver only or liver-dominant CCLM. In all patients, systemic chemotherapy before TACE had failed. Two hundred milligrams of irinotecan were loaded into 50–100 mg of SAP microspheres (HepaSphere™ Microspheres) considering tumor size and vascularization. TACE was performed selectively with respect to tumor distribution. Response was evaluated following RECIST and EASL criteria, respectively. Median follow-up after last TACE was 8 (range 1–54) months. All patients had died at time of analysis.ResultsAll TACE procedures were performed successfully; 35–400 mg (mean 168.3 mg) of irinotecan loaded in 13–100 mg (mean 48.3 mg) SAP microspheres were injected during individual sessions. No major complications occurred. Three, 6, and 12 months after first TACE complete and partial response was present in 72, 32 %, 0 of patients by EASL criteria and stable disease was seen in 86, 48, and 8 % with no complete and no partial response by RECIST criteria. Median overall survival after first TACE was 8 months, and median time to progression was 5 months. Median overall survival was longer in patients with limited (<25 %) compared with extensive (>50 %) intrahepatic disease (21 vs. 5 months, p < 0.005).ConclusionsTACE using irinotecan loaded SAP microspheres is safe and effective in terms of tumor necrosis. Survival benefit in a salvage setting seems to be limited in patients with advanced intrahepatic tumor load.

  16. Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

    Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

    2016-12-01

    Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. Phase II/III Study of Radiofrequency Ablation Combined with Cytokine-Induced Killer Cells Treating Colorectal Liver Metastases

    Xiaodong Li

    2016-11-01

    Full Text Available Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA and cytokine-induced killer (CIK cells transfusion for patients with colorectal liver metastases (CRLMs. Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30 and Group B (RFA plus CIK, n = 30, and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336. The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187. Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010. After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001 and in 7 patients comparing with that post-RFA (P = 0.028. Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

  18. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy.

  19. Clinical study of combined use of tomudex (raltitrexed) and xeloda (capecitabine) as first-line treatment for patients with metastasizing colorectal cancer.

    Vakhabova, J V; Semenov, N N; Dobrova, N V; Lichinitser, M R

    2008-02-01

    We studied the efficiency of combined chemotherapy with tomudex and xeloda preparations in patients with metastasizing colorectal cancer. The treatment (240 courses) was effective in 75% patients. Time median before progression was 6.3 months, mean durations of partial remission and stabilization were 7.8 months, total survival 15.5 months, total survival after effective treatment was 18.2 months. The most prevalent manifestations of III-IV degree toxicity were neutropenia, diarrhea, and asthenia. Other symptoms of toxicity (increased transaminase level, bilirubin, nausea, vomiting) were observed in less than 3% courses. Thus, treatment with tomudex and xeloda are effective and safe for outpatient chemotherapy.

  20. Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

    Martins, Sandra Fernandes; Amorim, Ricardo; Viana-Pereira, Marta; Pinheiro, Céline; Costa, Ricardo Filipe Alves; Silva, Patrícia; Couto, Carla; Alves, Sara; Fernandes, Sara; Vilaça, Sónia; Falcão, Joaquim; Marques, Herlander; Pardal, Fernando; Rodrigues, Mesquita; Preto, Ana; Reis, Rui Manuel; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-01-01

    Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC

  1. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

    Ketao Jin

    Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

  2. Ultrasonic diagnosis of hepatic metastases in patients with stomach cancer and colon cancer

    Kye, Jong Sik; Lim, Jae Hoon; Ko, Young Tae; Ahn, Chi Yul

    1987-01-01

    To assess the value of hepatic ultrasound in cancer patients, a prospective evaluation was performed by comparing the preoperative ultrasound report and surgeon's diagnosis at the time of operation in 86 patients with stomach cancer and 26 patients with colon cancer. In a total of 112 patients considered to have a metastasis free liver on ultrasound scanning 10 patients were turned out to have had hepatic metastasis at the time of laparotomy. Among these, 4 patients had miliary metastasis, 4 patients had nodular metastasis at the dome of the right hepatic lobe, and 2 patients had surface metastasis or direct invasion from the primary tumor. These observations suggest that false negative preoperative hepatic ultrasound scanning is 9% had this is considered due to small size of the metastatic lesions, and lesions roundabout the dome of the right hepatic lobe or surface metastasis. Thus one should keep in mind the possibility of miliary metastasis in cancer patient was has coarse hepatic echotexture. In addition, the hepatic dome as well as hepatic surfaces should be searched carefully as the lesions in these areas tend to be easily neglected by ultrasound

  3. IMAGING DIAGNOSIS-ECTOPIC SPLEEN MIMICKING HEPATIC TUMOR WITH INTRA-ABDOMINAL METASTASES INVESTIGATED VIA TRIPLE-PHASE HELICAL COMPUTED TOMOGRAPHY IN A DOG.

    Kutara, Kenji; Konno, Toshiaki; Kondo, Hirotaka; Aoki, Kotoyo; Yamazoe, Hinako; Matsunaga, Satoru

    2017-05-01

    A 10-year-old castrated male miniature dachshund was presented with an abdominal mass. The dog had a history of splenectomy. Triple-phase helical computed tomography was utilized, revealing a hepatic mass and multiple intra-abdominal solid masses. In triple-phase helical computed tomography the images, hepatic mass and two of four intra-abdominal masses were heterogenous in all phases. Therefore, we diagnosed a malignant hepatic tumor and presumed intra-abdominal metastases. The masses were surgically removed and were histologically composed of normal spleen tissues, findings which were consistent with ectopic spleen. © 2016 American College of Veterinary Radiology.

  4. Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

    Rahbari, Nuh N; Reissfelder, Christoph; Schulze-Bergkamen, Henning; Jäger, Dirk; Büchler, Markus W; Weitz, Jürgen; Koch, Moritz

    2014-03-11

    Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy. A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients' risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models. A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69-0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23-0.69), whereas it was of no benefit in patients with a MSKCC-CRS ≤ 2 (HR 0.90; 95% CI 0.57-1.43). The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

  5. TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases

    Ham, Boram; Wang, Ni; D'Costa, Zarina

    2015-01-01

    Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked. In this st......Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked...... chemotherapy-naïve colon cancer patients confirmed the presence of CD33(+)HLA-DR(-)TNFR2(+) myeloid cells in the periphery of hepatic metastases. Overall, our findings implicate TNFR2 in supporting MDSC-mediated immune suppression and metastasis in the liver, suggesting the use of TNFR2 inhibitors...

  6. Eradication of Human Hepatic and Pulmonary Melanoma Metastases in SCID Mice by Antibody--Interleukin 2 Fusion Proteins

    Becker, Jurgen C.; Pancook, James D.; Gillies, Stephen D.; Mendelsohn, John; Reisfeld, Ralph A.

    1996-04-01

    Antibody--cytokine fusion proteins combine the unique targeting ability of antibodies with the multifunctional activity of cytokines. Here, we demonstrate the therapeutic efficacy of such constructs for the treatment of hepatic and pulmonary metastases of different melanoma cell lines. Two antibody--interleukin 2 (IL-2) fusion proteins, ch225-IL2 and ch14.18-IL2, constructed by fusion of a synthetic sequence coding for human IL-2 to the carboxyl end of the Cγ 1 gene of the corresponding antibodies, were tested for their therapeutic efficacy against xenografted human melanoma in vivo. Tumorspecific fusion proteins completely inhibited the growth of hepatic and pulmonary metastases in C.B-17 scid/scid mice previously reconstituted with human lymphokine-activated killer cells, whereas treatment with combinations of the corresponding antibodies plus recombinant IL-2 only reduced the tumor load. Even when treatment with fusion proteins was delayed up to 8 days after inoculation of tumor cells, it still resulted in complete eradication of micrometastases that were established at that time point. Selection of tumor cell lines expressing or lacking the targeted antigen of the administered fusion protein proved the specificity of the observed antitumor effect. Biodistribution analysis demonstrated that the tumorspecific fusion protein accumulated not only in subcutaneous tumors but also in lungs and livers affected with micrometastases. Survival times of animals treated with the fusion protein were more than doubled as compared to those treated with the combination of the corresponding antibody plus IL-2. Our data demonstrate that an immunotherapeutic approach using cytokines targeted by antibodies to tumor sites has potent effects against disseminated human melanoma.

  7. [Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report].

    Okamura, Shu; Mikami, Koji; Murata, Kohei; Nushijima, Yoichirou; Okada, Kazuyuki; Yanagisawa, Tetsu; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2015-11-01

    Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer.

  8. {sup 18}F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases

    Samim, M. [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands); Prevoo, W.; Wit-van der Veen, B.J. de; Stokkel, M.P.M. [Antoni van Leeuwenhoek Hospital, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Kuhlmann, K.F.; Ruers, T. [Antoni van Leeuwenhoek Hospital, Department Surgical Oncology, Amsterdam (Netherlands); Hillegersberg, R. van [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); Bosch, M.A.A.J. van den; Verkooijen, H.M.; Lam, M.G.E.H. [University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands)

    2017-07-15

    Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation {sup 18}F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline {sup 18}F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SUL{sub peak}, SUL{sub mean}, SUL{sub max}, partial volume corrected SUL{sub mean} (cSUL{sub mean}), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SUL{sub peak}, SUL{sub max}, SUL{sub mean}, and cSUL{sub mean} are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. We found no association between the metabolic parameters on pre-ablation {sup 18}F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly

  9. Phase I Hepatic Immunotherapy for Metastases study of intra-arterial chimeric antigen receptor modified T cell therapy for CEA+ liver metastases

    Katz, Steven C.; Burga, Rachel A.; McCormack, Elise; Wang, Li Juan; Mooring, Wesley; Point, Gary; Khare, Pranay D.; Thorn, Mitchell; Ma, Qiangzhong; Stainken, Brian F.; Assanah, Earle O.; Davies, Robin; Espat, N. Joseph; Junghans, Richard P.

    2015-01-01

    Purpose Chimeric antigen receptor modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases (LM), a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAI). Experimental Design We conducted a phase I trial to test HAI of CAR-T in patients with CEA+ LM. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (108, 109, and 1010 cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (1010 cells X 3) along with systemic IL2 support. Results Four patients had more than 10 LM and patients received a mean of 2.5 lines of conventional systemic therapy prior to enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range 19–48%) from baseline. Biopsies demonstrated an increase in LM necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases. Conclusions We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pre-treated population with large tumor burdens. Further clinical testing of CAR-T HAIs for LM is warranted. PMID:25850950

  10. CDX2 expression is concordant between primary colorectal cancer lesions and corresponding liver metastases independent of chemotherapy: a single-center retrospective study in Japan.

    Shigematsu, Yasuyuki; Inamura, Kentaro; Mise, Yoshihiro; Saiura, Akio; Rehnberg, Emil; Yamamoto, Noriko; Ishikawa, Yuichi; Takahashi, Shunji; Kanda, Hiroaki

    2018-03-30

    Loss of caudal-type homeobox transcription factor 2 (CDX2) expression in colorectal cancers (CRCs) has recently been proposed as a promising predictive biomarker for not only prognosis but also response to chemotherapy. However, the relationship between alterations in CDX2 expression during cancer progression and response to chemotherapy remains unclear. We herein aimed to determine the concordance of CDX2 expression between primary CRCs and corresponding liver metastases, in association with chemotherapy. Primary CRCs exhibited heterogeneous CDX2 expression. Seven of the 144 CRCs in the cohort (4.9%, 95% confidential interval, 2.0%-9.8%) were CDX2-negative. The concordance rate of the CDX2 expression status in patients who did not receive chemotherapy was 100% ( P = 0.041), whereas the concordance rate among patients who received chemotherapy only after primary resection was 96.3% ( P = 0.005). Moreover, the concordance rate in patients who received chemotherapy before both primary resection and liver metastasectomy was 100% ( P < 0.001). CDX2 expression status was highly concordant between primary CRCs and corresponding liver metastases, independent of chemotherapy, suggesting that the CDX2 expression status in CRCs was not affected by metastasis or chemotherapy. A total of 144 consecutive patients with CRC who were treated at a single center in Japan between 2006 and 2014 were included. Formalin-fixed paraffin-embedded whole sections of surgically resected primary CRCs and corresponding liver metastases were assessed for CDX2 expression by immunohistochemistry.

  11. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

    2013-01-01

    Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

  12. Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer.

    Heijmen, Linda; de Geus-Oei, Lioe-Fee; de Wilt, Johannes H W; Visvikis, Dimitris; Hatt, Mathieu; Visser, Eric P; Bussink, Johan; Punt, Cornelis J A; Oyen, Wim J G; van Laarhoven, Hanneke W M

    2012-12-01

    Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before (18)F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of (18)F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two (18)F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV(max), SUV(mean), volume and TLG. Tumours were delineated using an adaptive threshold method (PET(SBR)) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV(max) and SUV(mean) were ∼39 and ∼31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET(SBR), from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV(mean). Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with (18)F-FDG PET parameters. In conclusion, repeatability of SUV(mean) and SUV(max) was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when (18)F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively

  13. Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer

    Heijmen, Linda; Geus-Oei, Lioe-Fee de; Visser, Eric P.; Oyen, Wim J.G.; Wilt, Johannes H.W. de; Visvikis, Dimitris; Hatt, Mathieu; Bussink, Johan; Punt, Cornelis J.A.; Laarhoven, Hanneke W.M. van

    2012-01-01

    Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before 18 F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of 18 F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two 18 F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV max , SUV mean , volume and TLG. Tumours were delineated using an adaptive threshold method (PET SBR ) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV max and SUV mean were ∝39 and ∝31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET SBR , from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV mean . Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with 18 F-FDG PET parameters. In conclusion, repeatability of SUV mean and SUV max was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when 18 F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively use PET for

  14. Stromal expression of heat-shock protein 27 is associated with worse clinical outcome in patients with colorectal cancer lung metastases.

    Thomas Schweiger

    Full Text Available Pulmonary metastases are common in patients with primary colorectal cancer (CRC. Heat-shock protein 27 (Hsp27 is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs are also thought to play a role as prognostic and predictive markers in various malignancies including CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. Therefore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases.FFPE tissue samples from 51 pulmonary metastases (PMs and 33 paired primary tumors were evaluated for alpha-SMA, CD31, Hsp27 and vimentin expression by immunohistochemistry and correlated with clinicopathological variables. 25 liver metastases served as control group. Moreover, serum samples (n=10 before and after pulmonary metastasectomy were assessed for circulating phospho-Hsp27 and total Hsp27 by ELISA.Stromal expression of Hsp27 was observed in all PM and showed strong correlation with alpha-SMA (P<0.001 and vimentin (P<0.001. Strong stromal Hsp27 was associated with higher microvessel density in primary CRC and PM. Moreover, high stromal Hsp27 and αSMA expression were associated with decreased recurrence-free survival after pulmonary metastasectomy (P=0.018 and P=0.008, respectively and overall survival (P=0.031 and P=0.017, respectively. Serum levels of phospho- and total Hsp27 dropped after metastasectomy to levels comparable to healthy controls.Herein we describe for the first time that Hsp27 is highly expressed in tumor stroma of CRC. Stromal α-SMA and Hsp27 expressions correlate with the clinical outcome after pulmonary metastasectomy. Moreover, serum Hsp27 might pose a future marker for metastatic disease in CRC.

  15. Smoking is a risk factor for pulmonary metastasis in colorectal cancer.

    Yahagi, M; Tsuruta, M; Hasegawa, H; Okabayashi, K; Toyoda, N; Iwama, N; Morita, S; Kitagawa, Y

    2017-09-01

    The hepatic microenvironment, which may include chronic inflammation and fibrosis, is considered to contribute to the pathogenesis of liver metastases of colorectal cancer. A similar mechanism is anticipated for pulmonary metastases, although no reports are available. Smoking causes pulmonary inflammation and fibrosis. Thus, we hypothesized that smokers would be especially affected by pulmonary metastases of colorectal cancer. In this study, we attempted to clarify the impact of smoking on pulmonary metastasis of colorectal cancer. Between September 2005 and December 2010 we reviewed 567 patients with pathological Stage I, II or III colorectal cancer, whose clinicopathological background included a preoperative smoking history, pack-year history from medical records. Univariate and multivariate analyses using the Cox proportional hazard model were performed to determine the independent prognostic factors for pulmonary metastasis-free survival. Pulmonary metastases occurred in 39 (6.9%) patients. The smoking histories revealed 355 never smokers, 119 former smokers and 93 current smokers among the subjects. Multivariate analysis revealed that being a current smoker (hazard ratio = 2.72, 95% CI 1.18-6.25; P = 0.02) was an independent risk factor for pulmonary metastases. Smoking may be a risk factor for pulmonary metastasis of colorectal cancer. Cessation of smoking should be recommended to prevent pulmonary metastasis, although further basic and clinical studies are required. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  16. Successful Control of Liver Metastases From Pancreatic Solid-Pseudopapillary Neoplasm (SPN) Using Hepatic Arterial Embolization

    Violari, Elena G., E-mail: eviolari@live.com; Brody, Lynn A.; Covey, Anne M.; Erinjeri, Joseph P.; Getrajdman, George I.; Sofocleous, Constantinos T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States); Reidy, Diane L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology Service (United States); Jarnagin, William R. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Service (United States); Brown, Karen T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States)

    2015-04-15

    No systemic agents that are known to be effective for the treatment of solid-pseudopapillary neoplasm (SPN) are available. We report the prolonged and sustained control of metastatic pancreatic SPN to the liver using hepatic arterial embolization (HAE), where a total of 13 HAE sessions were performed over a 6-year period.

  17. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors

    Roche, Alain; Girish, Baragur V.; de Baere, Thierry; Baudin, Eric; Schlumberger, Martin; Boige, Valerie; Ducreux, Michel; Elias, Dominique; Lasser, Philippe

    2003-01-01

    Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment. (orig.)

  18. Loss of Cdx2 expression in primary tumors and lymph node metastases is specific for mismatch repair-deficiency in colorectal cancer

    Heather eDawson

    2013-10-01

    Full Text Available Background: Approximately 20% of all colorectal cancers are hypothesized to arise from the serrated pathway characterized by mutation in BRAF, high-level CpG Island Methylator Phenotype (CIMP and microsatellite instability/mismatch repair (MMR-deficiency. MMR-deficient cancers show frequent losses of Cdx2, a homeodomain transcription factor. Here, we determine the predictive value of Cdx2 expression for MMR-deficiency and investigate changes in expression between primary cancers and matched lymph node metastases. Methods: Immunohistochemistry for Cdx2, Mlh1, Msh2, Msh6, and Pms2 was performed on whole tissue sections from 201 patients with primary colorectal cancer and 59 cases of matched lymph node metastases. Receiver operating characteristic (ROC curve analysis and Area under the Curve (AUC were investigated; association of Cdx2 with clinicopathological features and patient survival was carried out.Results Loss of Cdx2 expression was associated with higher tumor grade (p=0.0002, advanced pT (p=0.0166, and perineural invasion (p=0.0228. Cdx2 loss was an unfavorable prognostic factor in univariate (p=0.0145 and multivariate (p=0.0427; HR (95%CI: 0.58 (0.34-0.98 analysis. The accuracy (AUC for discriminating MMR-proficient and –deficient cancers was 87% (OR (95%CI:0.96 (0.95-0.98; p<0.0001. Specificity and negative predictive value for MMR-deficiency was 99.1% and 96.3%. 174 patients had MMR-proficient cancers, of which 60 (34.5% showed Cdx2 loss. Cdx2 loss in metastases was related to MMR-deficiency (p<0.0001. There was no difference in expression between primary tumors and matched metastases.Conclusion: Loss of Cdx2 is a sensitive and specific predictor of MMR-deficiency, but is not limited to these tumors, suggesting that events upstream of the development of MSI may impact Cdx2 expression.

  19. [Effects of intra-arterial infusion of 3-bromopyruvate on metastases and survival benefit of hepatic VX2 tumor in rabbits].

    Jiang, Xiong-ying; Zhang, Xiao-ping; Huang, Jin-hua; Luo, Rong-guang; Miao, Bi-jian; Wang, Yan

    2013-10-22

    To evaluate the metastasis and survival of an intra-arterial infusion of 3-bromopyruvate (3-BrPA) on hepatic VX2 tumor in rabbits. VX2 tumor was implanted in left lateral lobe of liver of 18 white New Zealand rabbits. The animals were randomized into 3 groups (n = 6 each) and underwent an intra-arterial infusion of phosphate-buffered saline or 3-BrPA via hepatic artery at 14 days post-implantation. At 28 days post-implantation, 3 rabbits in each group were sacrificed. The abdomen of these rabbits was opened and inspected for metastases. Then the survival of the remaining rabbits was observed. At 28 days post-implantation, in PBS group, there were intrahepatic metastasis and abdominal cavity dissemination (n = 3), renal metastases (n = 2) and lung metastases (n = 2); in early 3-BrPA infusion group, intrahepatic metastasis (n = 2), abdominal cavity dissemination (n = 1) and lung metastases (n = 1); in late 3-BrPA infusion group, intrahepatic metastasis (n = 1) and lung metastases (n = 1). The survival of the remaining animals was observed. Rabbits in early 3-BrPA infusion group survived significantly longer than those in PBS group [(27 ± 5) vs (17 ± 3) days, P = 0.041]; rabbits in late 3-BrPA infusion group [(42 ± 6) days] survived significantly longer than those in early 3-BrPA infusion group (P = 0.007). An intra-arterial infusion of 3-BrPA could reduce metastasis and prolong survival in rabbits with hepatic VX2 tumor. The earlier the infusion, the better the outcome.

  20. An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

    Maeva Andriantsoa

    Full Text Available In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP levels are frequently normal in cases of metastatic neuroendocrine tumor (NET.We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female, with a median age of 60 years (range: 28 to 84 years. The primary tumors were located in the duodenum/pancreas (n = 29, small bowel (n = 17 or colon/rectum (n = 3; 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients.Serum AP levels were elevated (≥ upper limit of normal (ULN in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010 and AP level (p = 0.017.Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

  1. An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

    Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

    2017-01-01

    In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

  2. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

    2017-01-01

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p  50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  3. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

    2017-01-15

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  4. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004).

    Ruers, T; Punt, C; Van Coevorden, F; Pierie, J P E N; Borel-Rinkes, I; Ledermann, J A; Poston, G; Bechstein, W; Lentz, M A; Mauer, M; Van Cutsem, E; Lutz, M P; Nordlinger, B

    2012-10-01

    This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2-73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1-70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42-0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7-22.1) and 9.9 months (95% CI 9.3-13.7), respectively. This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain.

  5. The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases.

    Cohen, Stacey A; Yu, Ming; Baker, Kelsey; Redman, Mary; Wu, Chen; Heinzerling, Tai J; Wirtz, Ralph M; Charalambous, Elpida; Pentheroudakis, George; Kotoula, Vassiliki; Kalogeras, Konstantine T; Fountzilas, George; Grady, William M

    2017-01-01

    The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs. We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers ( CACNA1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 ) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and P  CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive). CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.

  6. Tumor and liver drug uptake following hepatic artery and portal vein infusion

    Sigurdson, E.R.; Ridge, J.A.; Kemeny, N.; Daly, J.M.

    1987-01-01

    Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13 N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3 H-FUdR (1 microCi/kg) and /sup 99m/Tc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3 H and /sup 99m/Tc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery

  7. Assessment of the residual tumour of colorectal liver metastases after chemotherapy: diffusion-weighted MR magnetic resonance imaging in the peripheral and entire tumour

    Wagner, Mathilde; Doblas, Sabrina; Giraudeau, Celine [Paris Diderot University, INSERM, UMR 1149, Clichy (France); Ronot, Maxime; Van Beers, Bernard; Vilgrain, Valerie [Paris Diderot University, INSERM, UMR 1149, Clichy (France); Radiology Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France); Belghiti, Jacques [Hepatobiliary Surgery Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France); Paradis, Valerie [Pathology Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France)

    2016-01-15

    To evaluate the value of diffusion-weighted imaging (DWI) in detecting residual tumours (RTs) in colorectal liver metastases (CLMs) following chemotherapy, with a focus on tumour periphery. From January 2009-January 2012, 57 patients who underwent liver resection for CLMs with preoperative MRI (<3 months) including DWI were retrospectively included. CLMs were classified into three response groups on pathology: (1) major histological (MHR, RTs ≤ 10 %), (2) partial histological (PHR, RT = 10-49 %), and (3) no histological (NHR, RT ≥ 50 %). On DWI, regions of interest (ROIs) were drawn around the entire tumour and tumour periphery. Apparent diffusion (ADC) and pure diffusion (D) coefficients were calculated using a monoexponential fit, and compared using Kruskal-Wallis test on a lesion-per-lesion analysis. 111 CLMs were included. Fourteen (12.5 %), 42 (38 %) and 55 (49.5 %) CLMs presented a MHR, PHR and NHR, respectively. ADC and D of the peripheral ROIs were significantly higher in the MHR group (P = 0.013/P = 0.013). ADC and D from the entire tumour were not significantly different among the groups (P = 0.220/P = 0.103). In CLM treated with chemotherapy, ADC and D values from the entire tumour are not related to the degree of RT, while peripheral zone diffusion parameters could help identify metastases with MHR. (orig.)

  8. Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung Metastases in Patients With Metastatic Colorectal Cancer Treated With Regorafenib.

    Vanwynsberghe, Hannes; Verbeke, Xander; Coolen, Johan; Van Cutsem, Eric

    2017-12-01

    The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared. Data of progressive-free survival and overall survival were collected from the CORRECT and CONSIGN trials. A significant difference in progressive-free survival was seen in 3 groups: response or stable disease in size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and response in corrected density (6.14 vs. 3.08 months). No difference was seen for response in size versus stable disease or progressive disease in size. For overall survival, a difference was observed in the same 3 groups: response or stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04 months), and response in corrected density (9.09 vs. 7.16 months). No difference was seen for response in size versus stable disease or progressive disease in size. Density reduction in lung metastases might be a good predictive parameter to predict outcome for regorafenib. Early tumor progression might be a negative predictive factor. If further validated, density reduction and early tumor progression might be useful to ameliorate the cost-benefit of regorafenib. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Changes in CT morphology can be an independent response marker for patients receiving regorafenib for colorectal liver metastases: retrospective pilot study.

    Ozaki, Yukinori; Shindoh, Junichi; Gonoi, Wataru; Nishioka, Yujiro; Kondoh, Chihiro; Tanabe, Yuko; Matoba, Shuichiro; Kuroyanagi, Hiroya; Hashimoto, Masaji; Takano, Toshimi

    2018-02-05

    Regorafenib is a multi-kinase inhibitor, which was shown to be effective for patients with metastatic colorectal cancer refractory to standard therapies. However, its patterns of response has not yet been fully understood. Clinical records of 10 patients who received regorafenib for evaluable colorectal liver metastases were reviewed. Response to chemotherapy was evaluated with the RECIST and morphologic response criteria, and its clinical relevance was analyzed. All patients received multiple lines of fluorouracil-based chemotherapy before regorafenib. The median follow-up duration after introduction of regorafenib was 4.9 months (range, 2 to 12.5 months). Median number of chemotherapy cycles was 2 (range, 1 to 15). In size-based response evaluation, 4 patients presented SD and 6 patients showed PD according to the RECIST. In non-size-based response evaluation, 3 patients were classified as optimal morphologic response and 7 patients were categorized as suboptimal morphologic response. Patients who presented optimal morphologic response showed significantly longer progression-free survival compared with those presented suboptimal response (median, 4.9 months vs. 0.7 months; P = 0.028), while size-based response evaluation could not well stratify patient prognosis. Non-size-based CT morphologic response could be a potential alternative response marker for patients treated with regorafenib.

  10. Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1

    Kathrin Rupertus

    2012-01-01

    Full Text Available Background. Mobilization of c-Kit+ hematopoietic cells (HCs contributes to tumor vascularization. Whereas survival and proliferation of HCs are regulated by binding of the stem cell factor to its receptor c-Kit, migration of HCs is directed by stromal cell-derived factor (SDF-1. Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy. Methods. BALB/c mice (=16 were pretreated with an anti-c-Kit antibody followed by implantation of CT26.WT-GFP colorectal cancer cells into dorsal skinfold chambers. Animals (=8 additionally received a neutralizing anti-SDF-1 antibody. Animals (=8 treated with a control antibody served as controls. Investigations were performed using intravital fluorescence microscopy, immunohistochemistry, flow cytometry and western blot analysis. Results. Blockade of c-Kit significantly enhanced tumor cell engraftment compared to controls due to stimulation of tumor cell proliferation and invasion without markedly affecting tumor vascularization. C-Kit blockade significantly increased VEGF and CXCR4 expression within the growing tumors. Neutralization of SDF-1 completely antagonized this anti-c-Kit-associated tumor growth by suppression of tumor neovascularization, inhibition of tumor cell proliferation and reduction of muscular infiltration. Conclusion. Our study indicates that bone marrow suppression via anti-c-Kit pretreatment enhances tumor cell engraftment of colorectal metastases due to interaction with the SDF-1/CXCR4 pathway which is involved in HC-mediated tumor angiogenesis.

  11. Reproducibility of functional volume and activity concentration in {sup 18}F-FDG PET/CT of liver metastases in colorectal cancer

    Heijmen, Linda [Radboud University Medical Centre, Department of Medical Oncology 452, PO Box 9101, Nijmegen (Netherlands); Geus-Oei, Lioe-Fee de; Visser, Eric P.; Oyen, Wim J.G. [Radboud University Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Wilt, Johannes H.W. de [Radboud University Medical Centre, Department of Surgery, Nijmegen (Netherlands); Visvikis, Dimitris; Hatt, Mathieu [LaTIM, INSERM U1101, Brest (France); Bussink, Johan [Radboud University Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Punt, Cornelis J.A. [University of Amsterdam, Department of Medical Oncology, Academic Medical Centre, Amsterdam (Netherlands); Laarhoven, Hanneke W.M. van [Radboud University Medical Centre, Department of Medical Oncology 452, PO Box 9101, Nijmegen (Netherlands); University of Amsterdam, Department of Medical Oncology, Academic Medical Centre, Amsterdam (Netherlands)

    2012-12-15

    Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before {sup 18}F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of {sup 18}F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two {sup 18}F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV{sub max}, SUV{sub mean}, volume and TLG. Tumours were delineated using an adaptive threshold method (PET{sub SBR}) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV{sub max} and SUV{sub mean} were {proportional_to}39 and {proportional_to}31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET{sub SBR}, from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV{sub mean}. Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with {sup 18}F-FDG PET parameters. In conclusion, repeatability of SUV{sub mean} and SUV{sub max} was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when {sup 18}F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements

  12. Concurrent chemoradiation of metastases with capecitabine and oxaliplatin and 3D-CRT in patients with oligometastatic colorectal cancer: results of a phase I study

    Dellas Kathrin

    2012-06-01

    Full Text Available Abstract Background Local control appears to be an important treatment aim in patients with limited metastases (oligometastases of colorectal cancer (CRC. Those patients show a favourable prognosis, if - in addition to the local effective treatment - an occurrence of new metastases may also be postponed by effective systemic therapy. The purpose of this dose escalation phase I study was to establish the efficacy of local radiotherapy (RT of oligometastatic CRC with a concurrent standard chemotherapy regimen. Methods Patients with first-, second- or third-line therapy of oligometastatic CRC (1–3 metastases or local recurrence plus max. 2 metastases received capecitabine (825 mg/m2/d BID d 1–14; 22–35 and oxaliplatin (50 mg/m2 d 1, 8, 22, 29. 3D-conformal RT of all metastatic lesions was delivered in 2.0 Gy up to 36 Gy to 50 Gy (3 dose levels. Primary endpoint was the maximal tolerable dose (MTD of RT defined as the level at which two or more of six patients experienced dose-limiting toxicity (DLT. Results Between 09/2004 and 08/2007, 9 patients (7 male, 2 female, 50–74 years were enrolled, 6 patients treated at dose level 1 (36 Gy, 3 patients at dose level 2 (44 Gy. 1 patient from the first cohort experienced DLT (oxaliplatin-related hypersensitivity reaction. No radiation-induced DLT occurred. 6/9 patients achieved objective response (partial remission. One year after initiation, all patients were alive, 6 patients survived (16 to 54 months patients died of tumor progression (14 to 23 months. The phase II part of the trial had to be closed due to recruitment failure. Conclusions Local 3D-CRT to metastatic lesions in addition to standard chemotherapy was feasible, DLT was not documented. 3/9 patients survived for a period of 3.5 to 4.4 years (time at the last evaluation. Radiotherapy of metastatic lesions should be incorporated into subsequent trials.

  13. Comparative Analysis between Simultaneous Resection and Staged Resection for Synchronous Colorectal Liver Metastases - A Single Center Experience on 300 Consecutive Patients.

    Alexandrescu, Sorin; Diaconescu, Andrei; Ionel, Zenaida; Zlate, Cristian; Grigorie, Răzvan; Hrehoreţ, Doina; Braşoveanu, Vladislav; Dima, Simona; Botea, Florin; Ionescu, Mihnea; Tomescu, Dana; Droc, Gabriela; Fota, Ruxandra; Croitoru, Adina; Gramaticu, Iulia; Buica, Florina; Iacob, Razvan; Gheorghe, Cristian; Herlea, Vlad; Grasu, Mugur; Dumitru, Radu; Boroş, Mirela; Popescu, Irinel

    2017-01-01

    Introduction: In synchronous colorectal liver metastases (SCLMs), simultaneous resection (SR) of the primary tumor and liver metastases has not gained wide acceptance. Most authors prefer staged resections (SgR), especially in patients presenting rectal cancer or requiring major hepatectomy. Methods: Morbidity, mortality, survival rates and length of hospital stay were compared between the two groups of patients (SR vs. SgR). A subgroup analysis was performed for patients with similar characteristics (e.g. rectal tumor, major hepatectomy, bilobar metastases, metastatic lymph nodes, preoperative chemotherapy). Results: Between 1995 and 2016, SR was performed in 234 patients, while 66 patients underwent SgR. Comparative morbidity (41% vs. 31.8%, respectively, p = 0.1997), mortality (3.8% vs. 3%, respectively, p = 1) and overall survival rates (85.8%, 51.3% and 30% vs. 87%, 49.6% and 22.5%, at 1-, 3- and 5-years, respectively, p = 0.386) were similar between the SR and SgR group. Mean hospital stay was significantly shorter in patients undergoing SR than SgR (15.11 ‚+- 8.60 vs. 19.42 ‚+- 7.36 days, respectively, p 0.0001). The characteristics of SR and SgR groups were similar, except the following parameters: rectal tumor (34.1% vs. 19.7%, respectively, p = 0.0245), metastatic lymph nodes (68.1% vs. 86.3%, respectively, p = 0.0383), bilobar liver metastases (22.6% vs. 37.8%, respectively, p = 0.0169), major hepatectomies (13.2% vs. 30.3%, respectively, p= 0.0025) and neo-adjuvant chemotherapy (13.2% vs. 77.2%, respectively, p 0.0001). A comparative analysis of morbidity, mortality and survival rates between SR and SgR was performed for subgroups of patients presenting these parameters. In each of these subgroups, SR was associated with similar morbidity, mortality and survival rates compared with SgR (p value 0.05). In patients with SCLMs, SR provides similar short-term and long-term outcomes as SgR, with a shorter hospital stay. Therefore, in most patients with

  14. Correlation of elvated tumor markers and hepatic and nodal metastases on CT in postgastrectomy patients for gastric cancer

    Lee, Hwa Jin; Park, Won Kyu; Seong, Ki Ho; Cho, Hyun Chul; Chang, Jae Chun; Park, Bok Hwan; Song, Sun Kyo

    1997-01-01

    The evaluation of tumor recurrence or metastasis in postgastrectomy cancer patients usually depends on a serum tumor marker test or radiologic study, but in both cases, accuracy is difficult to determine. The purpose of this study was to evaluate the relationship between abdominal CT and serum tumor markers. In 337cases involving 226 patients who had undergone curative surgery for gastric cancer, we compared serum tumor markers and CT for the evaluation of metastasis. Amoong these 337 cases, CEA level was measured in 317, CA 19-9 level in 166,and both of these in 146. The cutoff level for serum carcinoembryonic antigen (CEA) and CA19-9 were 10ng/ml and 33U/ml, respectively. CEA level was elevated in 59 of 317 cases(18.6%) and that of CA 19-9 in 58 of 166(34.9%). Slightly higher overall senstivity and specificity was observed for CEA than for CA19-9 (72.9% vs 67.2%, 83.3% vs 70.4%, respectively). Among the total of 337 cases, liver or lymph node metastases were detected in 91 cases (27.0%) on CT. Negative predictive value was significantly higher in CEA than in CA19-9 (93.1% vs 80%, respectively)(p<0.01), but positive predictive value was lower (50% vs 54.9%, respectively). On CT scan, there was a significant relationship between serum tumor marker level and hepatic and nodal metastasis ; specificity and positivity of serum tumor markers were both higher than senstivity and negativity. Follow-up CT less useful when tumor markers levels are not elevated, but when these are elevated in postgastrectomy cancer patients, meticulous radiologic evaluation is necessary for the early detection of residual or recurrent tumors

  15. Análise de fatores clínicos e histopatológicos em metástases hepáticas de adenocarcinoma colorretal Analysis of clinical and histopathological factors in adenocarcinoma colorectal cancer liver metastases

    Jefferson Cláudio Murad

    2007-12-01

    nodes dissection and involvement, neoplasia-free margin resection. Patients were evaluated clinically, undergoing laboratory exams analysis and imaging studies for disease follow-up. Exclusion criteria were non-histological proof of liver metastasis and evidence of disease in sites other than colon and liver, at the time of surgical treatment and liver metastasis. RESULTS: Casuistic group consisted of 24 female and 25 male patients. Mean and standard deviation for age was 55,9 + 11,9 years, median of 56 years. Surgical procedures included 15 right hepatectomy and 11 left hepatectomy; 13 right and left segmentectomy; 9 nodulectomy and 1 biopsy. Additionally, 2 alcoholization, 4 chemoembolization, 1 thermoablative therapy, 1 selective portal vein block with later right hepatectomy and thermoablative thereapy on segments III and IV were performed. Liver weighted 555,71 + 261,96 g, median of 600g. Median of lymph nodes resection was 2. The mean lesion size consisted in 4,45 + 2,8. Resection margin greater than 10 mm was observed in 32 cases. Serum CEA value before surgical procedure was 68,13 + 105,65 ng/ml, median of 22,2 ng/ml. Death occurred in 22 cases (44,89%. Predominant histological diagnoses was moderate differentiated tubular adenocarcinoma in 65,96%, 17,02% poorly and 17,02% well differentiated. Factors such as undifferentiated histological type, less inflammatory peritumor infiltration, greater desmoplastic reaction and the absence of capsule around the tumor seem to reflect worse prognosis, although none of the factors being statistic significantly isolated. Significant association was noticed between CEA serum level under 7 ng/mg and synchronic hepatic metastases. CONCLUSION: Radical surgical resection for colorectal cancer liver metastases with a resection margin greater than 10 mm promotes better survival rates; elevated serum CEA levels were related to recurrence after hepatic resection for metastatic colorectal cancer and worse clinical outcome

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

    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. Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial.

    Liu, Zhihua; Li, Chao; Huang, Meijin; Tong, Chao; Zhang, Xingwei; Wang, Lei; Peng, Hui; Lan, Ping; Zhang, Peng; Huang, Nanqi; Peng, Junsheng; Wu, Xiaojian; Luo, Yanxing; Qin, Huanlong; Kang, Liang; Wang, Jianping

    2015-03-20

    Colorectal liver metastases (CLM) occur frequently and postoperative intestinal infection is a common complication. Our previous study showed that probiotics could decrease the rate of infectious complications after colectomy for colorectal cancer. To determine the effects of the perioperative administration of probiotics on serum zonulin levels which is a marker of intestinal permeability and the subsequent impact on postoperative infectious complications in patients with CLM. 150 patients with CLM were randomly divided into control group (n = 68) and probiotics group (n = 66). Probiotics and placebo were given orally for 6 days preoperatively and 10 days postoperatively to control group and probiotics group respectively. We used the local resection for metastatic tumor ,while for large tumor, the segmental hepatectomy. Postoperative outcome were recorded. Furthermore, complications in patients with normal intestinal barrier function and the relation with serum zonulin were analyzed to evaluate the impact on the liver barrier dysfunction. The incidence of infectious complications in the probiotics group was lower than control group. Analysis of CLM patients with normal postoperative intestinal barrier function paralleled with the serum zonulin level. And probiotics could also reduce the concentration of serum zonulin (P = 0.004) and plasma endotoxin (P zonulin level, the rate of postoperative septicemia and maintain the liver barrier in patients undergoing CLM surgery. we propose a new model about the regulation of probiotics to liver barrier via clinical regulatory pathway. We recommend the preoperative oral intake of probiotics combined with postoperative continued probiotics treatment in patients who undergo CLM surgery. ChiCTR-TRC- 12002841 . 2012/12/21.

  18. Prognostic Significance of Pre-operative FDG-PET in Colorectal Cancer Patients with Hepatic Metastasis

    Lee, Hyo Sang; Lee, Won Woo; Kim, Duck Woo; Kang, Sung Bum; Lee, Kyoung Ho; Lee, Keun Wook; Kim, Jee Hyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul (Korea, Republic of)

    2009-10-15

    The purpose of this study was to assess the prognostic value of preoperative FDG-PET in colorectal cancer (CRC) patients with hepatic metastasis (HM). 24 CRC patients (M:F=14:10; age, 63{+-}10 yrs) with HM who had undergone preoperative FDG PET were included. Cure-intent surgery was performed in all the patients and HMs were controlled using resection (n=13), radio-frequency ablation (RFA) (n=7), and resection plus RFA (n=4). Potential prognostic markers tested were maxSUV of primary tumor, maxSUV of HM, maxSUV ratio of HM over primary tumor (M/P ratio), histologic grade, CEA level, venous/lymphatic/nerve invasion, T stage, N stage, no. of HM, no. of lymph node metastasis, and treatment modality of HM. 14 CRC patients developed a recurrence with a median follow-up duration of 244 days, whereas 10 patients did not develop recurrence with a median follow-up duration of 504 days. M/P ratios but other potential prognostic markers were significantly higher in the recurrent patients (0.72{+-}0.14) than recurrence-free patients (0.54{+-}0.23) (p=0.038). M/P ratio only was found to predict recurrence by Cox multivariate analysis (hazard ratio 37.7, 95% confidence interval 2.01-706.1, p=0.016). The 11 patients with lower M/P ratio of <0.61 had significantly better disease-free survival rate than the 13 patients with higher M/P ratio ({>=}0.61) (p=0.026). maxSUV ratio of HM over primary tumor (M/P ratio) may be useful for prognosis prediction of CRC patients with HM. Higher FDG uptake of HM than that of primary tumor may indicate a more advanced status in stage IV CRC.

  19. Complex Liver Resections for Colorectal Metastases: Are They Safe in the Low-Volume, Resource-Poor Caribbean Setting?

    Shamir O. Cawich

    2015-01-01

    Full Text Available Introduction. Although many authorities suggest that major liver resections should only be carried out in high-volume specialized centres, many patients in the Caribbean do not have access to these health care systems. Presentation of a Case. A 50-year-old woman with a solitary colorectal metastasis invading the inferior vena cava underwent an extended left hepatectomy with caval resection and reconstruction. Several technical maneuvers were utilized that were suited to the resource-poor environment. Conclusion. We suggest that good outcomes can still be attained in the resource-poor, low-volume centres once dedicated and appropriately trained teams are available.

  20. Radiofrequency Ablation Combined with Hepatic Arterial Chemoembolization Using Degradable Starch Microsphere Mixed with Mitomycin C for the Treatment of Liver Metastasis from Colorectal Cancer: A Prospective Multicenter Study

    Yamakado, Koichiro; Inaba, Yasutaka; Sato, Yozo; Yasumoto, Taku; Hayashi, Sadao; Yamanaka, Takashi; Nobata, Koji; Takaki, Haruyuki; Nakatsuka, Atsuhiro

    2017-01-01

    PurposeThis phase II prospective study investigates possible benefits of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization using degradable starch microsphere (DSM) mixed with mitomycin C (MMC) in non-surgical candidates with colorectal liver metastases.Materials and MethodsThis study, approved by the respective institutional review board, included non-surgical candidates with 3 or fewer liver tumors of 3 cm or smaller, or a single lesion 5 cm or smaller. Percutaneous RFA was performed immediately after chemoembolization using DSM-MMC. Primary and secondary endpoints were the local tumor control rate, safety, and 2-year recurrence-free and overall survival rates.ResultsThis study examined 25 patients (22 males, 3 females) with 38 tumors of mean maximum diameter of 2.2 ± 0.9 cm (standard deviation) (range 1.0–4.2 cm). Their mean age was 70.2 ± 8.2 years (range 55–82 years). Local tumor progression developed in 3 tumors (7.9%, 3/38) of 3 patients (12%, 3/25) during the mean follow-up of 34.9 ± 9.2 months (range 18.3–50.1 months). The 2-year local tumor control rates were 92.0% [95% confidence interval (CI), 81.4–100%] on a patient basis and 94.6% (95% CI, 87.3–100%) on a tumor basis. The respective 2-year overall and recurrence-free survival rates were 88.0% (95% CI, 75.3–98.5%) and 63.3% (95% CI, 44.2–82.5%), with median survival time of 48.4 months. Fever was the only adverse event requiring treatments in 2 patients (8%).ConclusionsThis combination therapy is safe, exhibiting strong anticancer effects on colorectal liver metastasis, which might contribute to patient survival.

  1. Radiofrequency Ablation Combined with Hepatic Arterial Chemoembolization Using Degradable Starch Microsphere Mixed with Mitomycin C for the Treatment of Liver Metastasis from Colorectal Cancer: A Prospective Multicenter Study

    Yamakado, Koichiro, E-mail: yamakado47@gmail.com [Hyogo College of Medicine, Department of Radiology (Japan); Inaba, Yasutaka; Sato, Yozo [Aichi Cancer Center, Department of Radiology (Japan); Yasumoto, Taku [Toyonaka Municipal Hospital, Department of Radiology (Japan); Hayashi, Sadao [Kagoshima University, Department of Radiology (Japan); Yamanaka, Takashi [Mie University, Department of Radiology (Japan); Nobata, Koji [Kouseiren Takaoka Hospital, Department of Radiology (Japan); Takaki, Haruyuki [Hyogo College of Medicine, Department of Radiology (Japan); Nakatsuka, Atsuhiro [Mie University, Department of Radiology (Japan)

    2017-04-15

    PurposeThis phase II prospective study investigates possible benefits of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization using degradable starch microsphere (DSM) mixed with mitomycin C (MMC) in non-surgical candidates with colorectal liver metastases.Materials and MethodsThis study, approved by the respective institutional review board, included non-surgical candidates with 3 or fewer liver tumors of 3 cm or smaller, or a single lesion 5 cm or smaller. Percutaneous RFA was performed immediately after chemoembolization using DSM-MMC. Primary and secondary endpoints were the local tumor control rate, safety, and 2-year recurrence-free and overall survival rates.ResultsThis study examined 25 patients (22 males, 3 females) with 38 tumors of mean maximum diameter of 2.2 ± 0.9 cm (standard deviation) (range 1.0–4.2 cm). Their mean age was 70.2 ± 8.2 years (range 55–82 years). Local tumor progression developed in 3 tumors (7.9%, 3/38) of 3 patients (12%, 3/25) during the mean follow-up of 34.9 ± 9.2 months (range 18.3–50.1 months). The 2-year local tumor control rates were 92.0% [95% confidence interval (CI), 81.4–100%] on a patient basis and 94.6% (95% CI, 87.3–100%) on a tumor basis. The respective 2-year overall and recurrence-free survival rates were 88.0% (95% CI, 75.3–98.5%) and 63.3% (95% CI, 44.2–82.5%), with median survival time of 48.4 months. Fever was the only adverse event requiring treatments in 2 patients (8%).ConclusionsThis combination therapy is safe, exhibiting strong anticancer effects on colorectal liver metastasis, which might contribute to patient survival.

  2. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores.

    Lewin, Joel W; O'Rourke, Nicholas A; Chiow, Adrian K H; Bryant, Richard; Martin, Ian; Nathanson, Leslie K; Cavallucci, David J

    2016-02-01

    This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  3. Sinusoidal obstruction syndrome (SOS) related to chemotherapy for colorectal liver metastases: factors predictive of severe SOS lesions and protective effect of bevacizumab.

    Hubert, Catherine; Sempoux, Christine; Humblet, Yves; van den Eynde, Marc; Zech, Francis; Leclercq, Isabelle; Gigot, Jean-François

    2013-11-01

    The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS. A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3). Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions. The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS. © 2013 International Hepato-Pancreato-Biliary Association.

  4. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  5. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

    2015-01-01

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  6. Diffusion-weighted and T2-weighted MR imaging for colorectal liver metastases detection in a rat model at 7 T: a comparative study using histological examination as reference

    Wagner, Mathilde; Ronot, Maxime; Vilgrain, Valerie; Beers, Bernard E. van [University Paris Diderot, Sorbonne Paris Cite, INSERM UMR 773, University Hospitals Paris Nord Val de Seine, Beaujon, Assistance Publique- Hopitaux de Paris, Laboratory of Physiological and Molecular Imaging of the Abdomen (IPMA) and Department of Radiology, Clichy Cedex (France); Maggiori, Leon; Panis, Yves [University Paris Diderot, Sorbonne Paris Cite, INSERM UMR 773, University Hospitals Paris Nord Val de Seine, Beaujon, Assistance Publique-Hopitaux de Paris, Department of Colorectal Surgery, Clichy (France); Paradis, Valerie [University Paris Diderot, Sorbonne Paris Cite, INSERM UMR 773, University Hospitals Paris Nord Val de Seine, Beaujon, Assistance Publique-Hopitaux de Paris, Department of Pathology, Clichy (France)

    2013-08-15

    To compare diffusion-weighted (DW) and T2-weighted MR imaging in detecting colorectal liver metastases in a rat model, using histological examination as a reference method. Eighteen rats had four liver injections of colon cancer cells. MR examinations at 7 T included FSE-T2-weighted imaging and SE-DW MR imaging (b = 0, 20 and 150 s/mm{sup 2}) and were analysed by two independent readers. Histological examination was performed on 0.4-mm slices. McNemar's test was used to compare the sensitivities and the Wilcoxon matched pairs test to compare the average number of false-positives per rat. One hundred and sixty-six liver metastases were identified on histological examination. The sensitivity in detecting liver metastases was significantly higher on DW MR than on T2-weighted images (99/166 (60 %) (reader 1) and 92/166 (55 %) (reader 2) versus 77/166 (46 %), P {<=} 0.001), without an increase in false-positives per rat (P = 0.773/P = 0.850). After stratification according to metastasis diameter, DW MR imaging had a significantly higher sensitivity than T2-weighted imaging only for metastases with a diameter (0.6-1.2 mm) similar to that of the spatial resolution of MR imaging in the current study. This MR study with histological correlations shows the higher sensitivity of DW relative to T2-weighted imaging at 7 T for detecting liver metastases, especially small ones. (orig.)

  7. Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer

    Vlems, F. A.; Diepstra, J. H. S.; Punt, C. J. A.; Ligtenberg, M. J. L.; Cornelissen, I. M. H. A.; van Krieken, J. H. J. M.; Wobbes, T.; van Muijen, G. N. P.; Ruers, T. J. M.

    2003-01-01

    In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated

  8. Morbidity and mortality in a large series of surgical patients with pulmonary metastases of colorectal carcinoma: a prospective multicentre Spanish study (GECMP-CCR-SEPAR).

    Rodríguez-Fuster, Alberto; Belda-Sanchis, José; Aguiló, Rafael; Embun, Raul; Mojal, Sergio; Call, Sergi; Molins, Laureano; Rivas de Andrés, Juan José

    2014-04-01

    Little information is available on postoperative morbidity and mortality after pulmonary metastasectomy. We describe the postoperative morbidity and mortality in a large multicentre series of patients after a first surgical procedure for pulmonary metastases of colorectal carcinoma (CRC) and identify the pre- and intraoperative variables influencing the clinical outcome. A prospective, observational and multicentre study was conducted. Data were collected from March 2008 to February 2010. Patients were grouped into Groups A and B according to the presence or absence of postoperative complications. Variables in both groups were compared by univariate and multivariate analyses. P-values of <0.05 were considered statistically significant. A total of 532 patients (64.5% males) from 32 hospitals were included. The mean (SD) ages of both study groups were similar [68 (10) vs 67 (10) years, P = NS). A total of 1050 lung resections were performed (90% segmentectomies or wedge, n = 946 and 10% lobectomies or greater, n = 104). Group A included 83 (15.6%) patients who developed a total of 100 complications. These included persistent air leaks in 18, atelectasis in 13, pneumonia in 13, paralytic ileum in 12, arrhythmia in 9, acute respiratory distress syndrome in 4 and miscellanea in 31. Reoperation was performed in 5 (0.9%) patients due to persistent air leaks in 4 and lung ischaemia in 1. The mortality rate was 0.4% (n = 2). Causes of death were sepsis in 1 patient and ventricular fibrillation in 1. In the multivariate analysis, lobectomy or greater lung resection [odds ration (OR) 1.9, 95% confidence interval (95% CI) 1.04-3.3, P = 0.03], respiratory co-morbidity (OR 2.3, 95% CI 1.1-4.6, P = 0.01) and cardiovascular co-morbidity (OR 2, 95% CI 1-3.8, P = 0.02) were independent risk factors for postoperative morbidity. Video-assisted surgery vs thoracotomy showed a protective effect (OR 0.3, 95% CI 0.1-0.8, P = 0.01). The first episode of lung surgery for pulmonary

  9. The prognostic value of {sup 18}F-FDG PET/CT prior to liver transplantation for nonresectable colorectal liver metastases

    Grut, Harald; Revheim, Mona Elisabeth [Oslo University Hospital, Division of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway); Dueland, Svein [Oslo University Hospital, Division of Oncology, Oslo (Norway); Line, Paal Dag [University of Oslo, Institute of Clinical Medicine, Oslo (Norway); Oslo University Hospital, Department of Transplantation Medicine, Oslo (Norway)

    2018-02-15

    The main objective of this study was to evaluate the prognostic value of volumetric and metabolic information derivied from F-18 fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) in combination with computed tomography (CT) prior to liver transplantation (LT) in patients with nonresectable colorectal liver metastases (CLM). Due to scarcity of liver grafts, prognostic information enabling selection of candidates who will gain the highest survival after LT is of vital importance. {sup 18}F-FDG PET/CT was a part of the preoperative study protocol. Patients without evidence of extrahepatic malignant disease on {sup 18}F-FDG PET/CT who also fulfilled all the other inclusion criteria underwent LT. The preoperative {sup 18}F-FDG PET/CT examinations of all patients included in the SECA (secondary cancer) study were retrospectively assessed. Maximum, mean and peak standardized uptake values (SUV{sub max}, SUV{sub mean} and SUV{sub peak}), tumor to background (T/B) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured and calculated for all liver metastases. Total MTV and TLG were calculated for each patient. Cut-off values were determined for each of these parameters by using receiver operating characteristic (ROC) analysis dividing the patients into two groups. One, three and five-year overall survival (OS) and disease free survival (DFS) for patients over and under the cut-off value were compared by using the Kaplan-Meier method and log rank test. Twenty-three patients underwent LT in the SECA study. Total MTV and TLG under the cut-off values were significantly correlated to improved OS at three and five years (p = 0.027 and 0.026) and DFS (p = 0.01). One, three and five-year OS and DFS were not significantly related to SUV{sub max}, SUV{sub mean}, SUV{sub peak} or T/B-ratio. Total MTV and TLG from {sup 18}F FDG PET/CT prior to LT for nonresectable CLM were significantly correlated to improved three and five-year OS and DFS

  10. Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

    Isbert, Christoph; Ritz, Jörg-Peter; Roggan, André; Schuppan, Detlef; Ajubi, Navid; Buhr, Heinz Johannes; Hohenberger, Werner; Germer, Christoph-Thomas

    2007-01-01

    Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT. (c) 2006 Wiley-Liss, Inc.

  11. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

    Youns, Mаhmoud; Abdel Halim Hegazy, Wael

    2017-01-01

    Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

  12. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

    Mаhmoud Youns

    Full Text Available Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2, colorectal (Caco-2 and pancreatic (Suit-2 cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

  13. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

    Youns, Mаhmoud; Abdel Halim Hegazy, Wael

    2017-01-01

    Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes. PMID:28052097

  14. Detection of hepatic metastases by superparamagnetic iron oxide-enhanced MR imaging: prospective comparison between 1.5-T and 3.0-T images in the same patients

    Sofue, Keitaro; Miyake, Mototaka; Sakurada, Aine; Arai, Yasuaki; Tsurusaki, Masakatsu; Sugimura, Kazuro

    2010-01-01

    To prospectively compare the diagnostic performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging at 3.0 T and 1.5 T for detection of hepatic metastases. A total of 28 patients (18 men, 10 women; mean age, 61 years) with 80 hepatic metastases were prospectively examined by SPIO-enhanced MR imaging at 3.0 T and 1.5 T. T1-weighted gradient-recalled-echo (GRE) images, T2*-weighted GRE images and T2-weighted fast spin-echo (SE) images were acquired. The tumour-to-liver contrast-to-noise ratio (CNR) of the lesions was calculated. Three observers independently reviewed each image. Image artefacts and overall image quality were analysed, sensitivity and positive predictive value for the detection of hepatic metastases were calculated, and diagnostic accuracy using the receiver-operating characteristics (ROC) method was evaluated. The tumour-to-liver CNRs were significantly higher at 3.0 T. Chemical shift and motion artefact were more severe, and overall image quality was worse on T2-weighted fast SE images at 3.0 T. Overall image quality of the two systems was similar on T1-weighted GRE images and T2*-weighted GRE images. Sensitivity and area under the ROC curve for the 3.0-T image sets were significantly higher. SPIO-enhanced MR imaging at 3.0 T provided better diagnostic performance for detection of hepatic metastases than 1.5 T. (orig.)

  15. Matched-Pair Comparison of Radioembolization Plus Best Supportive Care Versus Best Supportive Care Alone for Chemotherapy Refractory Liver-Dominant Colorectal Metastases

    Seidensticker, Ricarda; Denecke, Timm; Kraus, Patrick; Seidensticker, Max; Mohnike, Konrad; Fahlke, Jörg; Kettner, Erika; Hildebrandt, Bert; Dudeck, Oliver; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2012-01-01

    Purpose: This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC). Methods: This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan–Meier analysis. Results: Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60–100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P < 0.001) with a hazard ratio of 0.3 (95% confidence interval, 0.16–0.55; P < 0.001) in a multivariate Cox proportional hazard model. Treatment-related adverse events following radioembolization included: grade 1–2 fatigue (n = 20, 69%), grade 1 abdominal pain/nausea (n = 14, 48.3%), and grade 2 gastrointestinal ulceration (n = 3, 10.3%). Three cases of grade 3 radiation-induced liver disease were symptomatically managed. Conclusions: Radioembolization offers a promising addition to BSC in treatment-refractory patients for whom there are limited options. Survival was prolonged and adverse events were generally mild-to-moderate in nature and manageable.

  16. Matched-Pair Comparison of Radioembolization Plus Best Supportive Care Versus Best Supportive Care Alone for Chemotherapy Refractory Liver-Dominant Colorectal Metastases

    Seidensticker, Ricarda, E-mail: ricarda.seidensticker@med.ovgu.de [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany); Denecke, Timm [Universitaetsmedizin Berlin (Germany); Kraus, Patrick; Seidensticker, Max; Mohnike, Konrad [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany); Fahlke, Joerg [Universitaetsklinikum Magdeburg, Klinik fuer Allgemein-, Viszeral- und Gefaesschirurgie (Germany); Kettner, Erika [Klinik fuer Haematologie/Onkologie, Klinikum Magdeburg (Germany); Hildebrandt, Bert [Universitaetsmedizin Berlin (Germany); Dudeck, Oliver; Pech, Maciej; Amthauer, Holger; Ricke, Jens [Universitaetsklinikum Magdeburg, Klinik fuer Radiologie and Nuklearmedizin (Germany)

    2012-10-15

    Purpose: This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC). Methods: This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan-Meier analysis. Results: Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60-100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P < 0.001) with a hazard ratio of 0.3 (95% confidence interval, 0.16-0.55; P < 0.001) in a multivariate Cox proportional hazard model. Treatment-related adverse events following radioembolization included: grade 1-2 fatigue (n = 20, 69%), grade 1 abdominal pain/nausea (n = 14, 48.3%), and grade 2 gastrointestinal ulceration (n = 3, 10.3%). Three cases of grade 3 radiation-induced liver disease were symptomatically managed. Conclusions: Radioembolization offers a promising addition to BSC in treatment-refractory patients for whom there are limited options. Survival was prolonged and adverse events were generally mild-to-moderate in nature and manageable.

  17. Blocking hepatic metastases of colon cancer cells using an shRNA against Rac1 delivered by activatable cell-penetrating peptide.

    Bao, Ying; Guo, Huihui; Lu, Yongliang; Feng, Wenming; Sun, Xinrong; Tang, Chengwu; Wang, Xiang; Shen, Mo

    2016-11-22

    Hepatic metastasis is one of the critical progressions of colon cancer. Blocking this process is key to prolonging survival time in cancer patients. Studies on activatable cell-penetrating peptides (dtACPPs) have demonstrated their potential as gene carriers. It showed high tumor cell-targeting specificity and transfection efficiency and low cytotoxicity in the in vitro settings of drug delivery. However, using this system to silence target genes to inhibit metastasis in colorectal cancer cells has not been widely reported and requires further investigation. In this study, we observed that expression of Rac1, a key molecule for cytoskeletal reorganization, was higher in hepatic metastatic tumor tissue compared with prime colon cancer tissue and that patients with high Rac1-expressing colon cancer showed shorter survival time. Base on these findings, we created dtACPP-PEG-DGL (dtACPPD)/shRac1 nanoparticles and demonstrated that they downregulated Rac1 expression in colon cancer cells. Moreover, we observed inhibitory effects on migration, invasion and adhesion in HCT116 colorectal cancer cells in vitro, and our results showed that Rac1 regulated colon cancer cell matrix adhesion through the regulation of cytofilament dynamics. Moreover, mechanically, repression of Rac1 inhibiting cells migration and invasion by enhancing cell to cell adhesion and reducing cell to extracellular matrix adhesion. Furthermore, when atCDPPD/shRac1 nanoparticles were administered intravenously to a HCT116 xenograft model, significant tumor metastasis to the liver was inhibited. Our results suggest that atCDPP/shRac1 nanoparticles may enable the blockade of hepatic metastasis in colon cancer.

  18. Follow-up of hepatic and peritoneal metastases of gastrointestinal tumors (GIST) under Imatinib therapy requires different criteria of radiological evaluation (size is not everything!!!)

    Mabille, Mylene; Vanel, Daniel; Albiter, Marcela; Le Cesne, Axel; Bonvalot, Sylvie; Le Pechoux, Cecile; Terrier, Philippe; Shapeero, Lorraine G.; Dromain, Clarisse

    2009-01-01

    Purpose: To define computed tomography (CT) criteria for evaluating the response of patients with gastrointestinal stromal tumors (GIST) who are receiving Imatinib (tyrosine-kinase inhibitor therapy). Materials and methods: This prospective CT study evaluated 107 consecutive patients with advanced metastatic GIST treated with Imatinib. Results: Seventy patients had total or partial cystic-like transformation of hepatic and/or peritoneal metastases. These pseudocysts remained unchanged in size or stable in size on successive CT examinations (stable disease according to RECIST criteria). Forty-six patients developed metastases, 17 patients showed increasing parietal thickness and 29 patients with peripheral enhancing nodules. These CT changes represented local recurrence consistent with GIST resistance to Imatinib treatment. WHO or RECIST criteria did not provide a reliable evaluation of disease evolution or recurrence. Development of new enhancement of lesions (parietal thickness or nodule) was the only reliable criterion. Conclusion: The development of peripheral thickening or enhancing nodules within cystic-like metastatic lesions, even without any change in size, represented progressive GIST under Imatinib, growing in a short time and should alert the clinician for the possible need for a change in therapy

  19. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2010-01-01

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis. PMID:20383296

  20. Respiratory gated PET/CT of the liver: A novel method and its impact on the detection of colorectal liver metastases

    Schulz, Anselm; Godt, Johannes Clemens; Dormagen, Johann Baptist; Holtedahl, Jon Erik; Bogsrud, Trond Velde; Labori, Knut Jørgen; Kløw, Nils-Einar; Bach-Gansmo, Tore

    2015-01-01

    Highlights: • Combined PET/CT and respiratory gated PET/CT improved sensitivity significantly. • Respiratory gated PET/CT had greatest impact on detection of small CRLM <10 mm. • Our results were comparable to earlier reported more complex and expensive methods. • The method used is inexpensive and requires only limited additional imaging time. - Abstract: Purpose: To evaluate the diagnostic performance of a new method for respiratory gated positron emission tomography (rgPET/CT) for colorectal liver metastases (CRLM), secondly, to assess its additional value to standard PET/CT (PET/CT). Materials and methods: Forty-three patients scheduled for resection of suspected CRLM were prospectively included from September 2011 to January 2013. None of the patients had previously undergone treatment for their CRLM. All patients underwent PET/CT and rgPET/CT in the same session. For rgPET/CT an in-house developed electronic circuit was used which displayed a color-coded countdown for the patient. The patients held their breath according to the countdown and only the data from the inspiration breath-hold period was used for image reconstruction. Two independent and blinded readers evaluated both PET/CT and rgPET/CT separately. The reference standard was histopathological confirmation for 73 out of 131 CRLM and follow-up otherwise. Results: Reference standard identified 131 CRLM in 39/43 patients. Nine patients accounted for 25 mucinous CRLM. The overall per-lesion sensitivity for detection of CRLM was for PET/CT 60.0%, for rgPET/CT 63.1%, and for standard + rgPET/CT 67.7%, respectively. Standard + rgPET/CT was overall significantly more sensitive for CRLM compared to PET/CT (p = 0.002) and rgPET/CT (p = 0.031). The overall positive predictive value (PPV) for detection of CRLM was for PET/CT 97.5%, for rgPET/CT 95.3%, and for standard + rgPET/CT 93.6%, respectively. Conclusion: Combination of PET/CT and rgPET/CT improved the sensitivity significantly for CRLM. However

  1. Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials.

    Cremolini, Chiara; Milione, Massimo; Marmorino, Federica; Morano, Federica; Zucchelli, Gemma; Mennitto, Alessia; Prisciandaro, Michele; Lonardi, Sara; Pellegrinelli, Alessio; Rossini, Daniele; Bergamo, Francesca; Aprile, Giuseppe; Urbani, Lucio; Morelli, Luca; Schirripa, Marta; Cardellino, Giovanni Gerardo; Fassan, Matteo; Fontanini, Gabriella; de Braud, Filippo; Mazzaferro, Vincenzo; Falcone, Alfredo; Pietrantonio, Filippo

    2018-04-01

    Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than

  2. Respiratory gated PET/CT of the liver: A novel method and its impact on the detection of colorectal liver metastases

    Schulz, Anselm, E-mail: anselm.schulz@gmail.com [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway); Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318 Oslo (Norway); Godt, Johannes Clemens, E-mail: UXGODJ@ous-hf.no [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway); Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318 Oslo (Norway); Dormagen, Johann Baptist, E-mail: UXJORM@ous-hf.no [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway); Holtedahl, Jon Erik, E-mail: JONHOL@ous-hf.no [The Intervention Centre, Oslo University Hospital, Postboks 4950 Nydalen, 0424 Oslo (Norway); Bogsrud, Trond Velde, E-mail: tvbog@aol.com [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway); Department of Nuclear Medicine and PET-Center, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C (Denmark); Labori, Knut Jørgen, E-mail: uxknab@ous-hf.no [Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Postboks 4950 Nydalen, 0424 Oslo (Norway); Kløw, Nils-Einar, E-mail: NILKLO@ous-hf.no [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway); Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, 0318 Oslo (Norway); Bach-Gansmo, Tore, E-mail: bat@ous-hf.no [Department of Radiology and Nuclear Medicine, Oslo University Hospital, Postboks Pb 4956 Nydalen, 0424 Oslo (Norway)

    2015-08-15

    Highlights: • Combined PET/CT and respiratory gated PET/CT improved sensitivity significantly. • Respiratory gated PET/CT had greatest impact on detection of small CRLM <10 mm. • Our results were comparable to earlier reported more complex and expensive methods. • The method used is inexpensive and requires only limited additional imaging time. - Abstract: Purpose: To evaluate the diagnostic performance of a new method for respiratory gated positron emission tomography (rgPET/CT) for colorectal liver metastases (CRLM), secondly, to assess its additional value to standard PET/CT (PET/CT). Materials and methods: Forty-three patients scheduled for resection of suspected CRLM were prospectively included from September 2011 to January 2013. None of the patients had previously undergone treatment for their CRLM. All patients underwent PET/CT and rgPET/CT in the same session. For rgPET/CT an in-house developed electronic circuit was used which displayed a color-coded countdown for the patient. The patients held their breath according to the countdown and only the data from the inspiration breath-hold period was used for image reconstruction. Two independent and blinded readers evaluated both PET/CT and rgPET/CT separately. The reference standard was histopathological confirmation for 73 out of 131 CRLM and follow-up otherwise. Results: Reference standard identified 131 CRLM in 39/43 patients. Nine patients accounted for 25 mucinous CRLM. The overall per-lesion sensitivity for detection of CRLM was for PET/CT 60.0%, for rgPET/CT 63.1%, and for standard + rgPET/CT 67.7%, respectively. Standard + rgPET/CT was overall significantly more sensitive for CRLM compared to PET/CT (p = 0.002) and rgPET/CT (p = 0.031). The overall positive predictive value (PPV) for detection of CRLM was for PET/CT 97.5%, for rgPET/CT 95.3%, and for standard + rgPET/CT 93.6%, respectively. Conclusion: Combination of PET/CT and rgPET/CT improved the sensitivity significantly for CRLM. However

  3. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefratory liver metastases from colerectal cancer

    Yu, Jeong Il; Park, Hee Chul; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

    2016-03-15

    A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

  4. A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

    Lim, L; Gibbs, P; Yip, D; Shapiro, JD; Dowling, R; Smith, D; Little, A; Bailey, W; Liechtenstein, M

    2005-01-01

    To prospectively evaluate the efficacy and safety of selective internal radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0–2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36 – 77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2–18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond

  5. Hepatitis

    ... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

  6. [Oligometastasized colorectal cancer-modern treatment strategies].

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  7. CT texture features of liver parenchyma for predicting development of metastatic disease and overall survival in patients with colorectal cancer.

    Lee, Scott J; Zea, Ryan; Kim, David H; Lubner, Meghan G; Deming, Dustin A; Pickhardt, Perry J

    2018-04-01

    To determine if identifiable hepatic textural features are present at abdominal CT in patients with colorectal cancer (CRC) prior to the development of CT-detectable hepatic metastases. Four filtration-histogram texture features (standard deviation, skewness, entropy and kurtosis) were extracted from the liver parenchyma on portal venous phase CT images at staging and post-treatment surveillance. Surveillance scans corresponded to the last scan prior to the development of CT-detectable CRC liver metastases in 29 patients (median time interval, 6 months), and these were compared with interval-matched surveillance scans in 60 CRC patients who did not develop liver metastases. Predictive models of liver metastasis-free survival and overall survival were built using regularised Cox proportional hazards regression. Texture features did not significantly differ between cases and controls. For Cox models using all features as predictors, all coefficients were shrunk to zero, suggesting no association between any CT texture features and outcomes. Prognostic indices derived from entropy features at surveillance CT incorrectly classified patients into risk groups for future liver metastases (p < 0.001). On surveillance CT scans immediately prior to the development of CRC liver metastases, we found no evidence suggesting that changes in identifiable hepatic texture features were predictive of their development. • No correlation between liver texture features and metastasis-free survival was observed. • Liver texture features incorrectly classified patients into risk groups for liver metastases. • Standardised texture analysis workflows need to be developed to improve research reproducibility.

  8. Hepatic entropy and uniformity: additional parameters that can potentially increase the effectiveness of contrast enhancement during abdominal CT

    Ganeshan, B.; Miles, K.A.; Young, R.C.D.; Chatwin, C.R.

    2007-01-01

    Aim: To determine how hepatic entropy and uniformity of computed tomography (CT) images of the liver change after the administration of contrast material and to assess whether these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion. Materials and methods: Hepatic attenuation, entropy, uniformity, and perfusion were measured using multi-phase CT following resection of colorectal cancer. Based on conventional CT and fluorodeoxyglucose positron emission tomography, 12 patients were classified as having no evidence of malignancy, eight with extra-hepatic tumours only, and eight with metastatic liver disease. Results: Hepatic attenuation and entropy increased after CM administration whereas uniformity decreased. Unlike hepatic attenuation, entropy and uniformity changed maximally in the arterial phase. No significant differences in hepatic perfusion or attenuation were found between patient groups, whereas arterial-phase entropy was lower (p = 0.034) and arterial-phase uniformity was higher (p = 0.034) in apparently disease-free areas of liver in patients with hepatic metastases compared with those with no metastases. Conclusion: Temporal changes in hepatic entropy and uniformity differ from those for hepatic attenuation. By reflecting the distribution of hepatic enhancement, these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion

  9. Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection

    2007-01-01

    We report a 55-year-old male who developed advanced hepatic metastasis and peritoneal carcinomatosis after resection of remnant gastric cancer resection 3 mo ago. The patient only received epidermal growth factor (EGF) receptor antibody (Cetuximab) plus recombinant human endostatin (Endostar).Anti-tumor activity was assessed by 18F-fluorodeoxyglucose (18F-FDG)positron emission tomography/computer tomography (PET/CT) at baseline and then every 4 wk. The case illustrates that 18FDG-PET/CT could make an early prediction of the response to Cetuximab plus Endostar in such clinical situations. 18FDG-PET/CT is a useful molecular imaging modality to evaluate the biological response advanced hepatic metastasis and peritoneal carcinomatosis to Cetuximab plus Endostar in patients after remnant gastric cancer resection.

  10. [A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

    Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

    2008-11-01

    We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

  11. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study.

    Benson, Al B; Geschwind, Jean-Francois; Mulcahy, Mary F; Rilling, William; Siskin, Gary; Wiseman, Greg; Cunningham, James; Houghton, Bonny; Ross, Mason; Memon, Khairuddin; Andrews, James; Fleming, Chad J; Herman, Joseph; Nimeiri, Halla; Lewandowski, Robert J; Salem, Riad

    2013-10-01

    To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Tissue detection of natural killer cells in colorectal adenocarcinoma

    Patsouris Efstratios S

    2004-09-01

    Full Text Available Abstract Background Natural killer (NK cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. Methods Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57. The number of immunopositive cells (% was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. Results NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031. Conclusions Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages.

  13. Investigating intra-tumor heterogeneity and expression gradients of miR-21, miR-92a and miR-200c and their potential of predicting lymph node metastases in early colorectal cancer

    Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg

    2016-01-01

    Introduction miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels...... in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC. Material and methods Two parallel studies on archived formalin-fixed paraffin......-embedded (FFPE) CRC tissue. Intra-tumor and inter-patient variances were analyzed in 9 early metastatic CRCs by measuring expression levels by qRT-PCR on isolated tissue samples from luminal, central and invasive border zones. Associations between miRNA expression levels and early metastasizing tumors...

  14. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004)

    Ruers, T.; Punt, C.; Van Coevorden, F.; Pierie, J. P. E. N.; Borel-Rinkes, I.; Ledermann, J. A.; Poston, G.; Bechstein, W.; Lentz, M. A.; Mauer, M.; Van Cutsem, E.; Lutz, M. P.; Nordlinger, B.

    2012-01-01

    Background This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. Methods This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. Results The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2–73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1–70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42–0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7–22.1) and 9.9 months (95% CI 9.3–13.7), respectively. Conclusions This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain. PMID:22431703

  15. Selective hepatic arterial infusion of In-111-DTPA-Phe{sup 1}-octreotide in neuroendocrine liver metastases

    Limouris, Georgios S.; Kontogeorgakos, Dimitrios; Lyra, Maria; Dimitriou, Panagiotis; Stavraka, Anastasia [Athens Medical School, Divisions of Nuclear Medicine, Radiology I Department, Athens (Greece); Aretaieion University Hospital, Athens (Greece); Chatziioannou, Achilles; Mourikis, Dimitrios; Gouliamos, Athanassios; Vlahos, Lambros [Athens Medical School, Divisions of Angiography, Radiology I Department, Athens (Greece); Aretaieion University Hospital, Athens (Greece)

    2008-10-15

    The aim of this study is to evaluate the effectiveness of {sup 111}In-DTPA-Phe{sup 1}-octreotide infusions after selective catheterization of the hepatic artery in inoperable metastasised liver, sst{sub 2} receptor-positive neuroendocrine tumours due to the effect of {sup 111}In Auger electron emission, minimising in parallel the toxicity of non-target tissue. The average dose per session administered monthly to each patient (17 cases in total) was 6.3{+-}2.3 GBq. Repetitions did not exceed 12-fold, except in one case (15 sessions). Response assessment was classified according to the Response Evaluating Criteria in Solid Tumours. CT/MRI scans were performed as baseline before, during and after the end of treatment, and monthly ultrasound images for follow-up measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. Complete response was achieved in one (5.9%) patient and partial in eight (47.0%), and disease stabilization in 3(17.7%) patients; five (29.4%) did not respond. A 32-month median survival time was estimated in 12(70.5%). Nine of these 12 surviving had a mean target diameter shrinkage from 144 {+-} 81 to 60 {+-} 59 mm. Grade 1 erythro-, leuko- and thrombo-cytopenia occurred in three (17.6%) cases. In unresectable metastatic liver lesions positive for somatostatin receptors repeated, transhepatic high doses of {sup 111}In-DTPA-Phe{sup 1}-octreotide show an effective therapeutic outcome. Given the locoregional modality character of the administration technique plus the extremely short range of {sup 111}In Auger and internal conversion electrons emission, no nephro-, liver- or myelo-toxicity has so far been observed. (orig.)

  16. Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al.

    Deming, Dustin A

    2016-01-01

    Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to target cancers have evolved expediently over the last 5 years, especially the use of checkpoint inhibitors. Recently, a subset of patients whose colorectal cancers harbor a deficiency in mismatch repair proteins have demonstrated dramatic and durable response to checkpoint blockade. Unfortunately, the vast majority of colorectal cancers are mismatch repair proficient and resistant to these inhibitors. The tumor microenvironment has been implicated in the resistance to checkpoint block and ways to overcome these resistance mechanisms would be a major advance for the treatment of colorectal cancer. Here we provide commentary on a manuscript from Halama et al. examining CCL5/CCR5 as an immune biomarker and the potential role of anti-CCR5 agents for the treatment of patients with colorectal cancer.

  17. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray

    Rempei Yanagawa

    2001-01-01

    Full Text Available In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.

  18. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials.

    Wasan, Harpreet S; Gibbs, Peter; Sharma, Navesh K; Taieb, Julien; Heinemann, Volker; Ricke, Jens; Peeters, Marc; Findlay, Michael; Weaver, Andrew; Mills, Jamie; Wilson, Charles; Adams, Richard; Francis, Anne; Moschandreas, Joanna; Virdee, Pradeep S; Dutton, Peter; Love, Sharon; Gebski, Val; Gray, Alastair; van Hazel, Guy; Sharma, Ricky A

    2017-09-01

    Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m 2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m 2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary

  19. Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

    Bhagat, Nikhil, E-mail: nbhagat1@jhmi.edu; Reyes, Diane K., E-mail: dreyes@jhmi.edu [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States); Lin, Mingde, E-mail: ming.lin@philips.com [Philips Research North America, Clinical Informatics, Interventional, and Translational Solutions (CIITS) (United States); Kamel, Ihab [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States); Pawlik, Timothy M. [Johns Hopkins University Medical Center, Department of Surgery (United States); Frangakis, Constantine, E-mail: cfrangak@jhsph.edu [Johns Hopkins University, Department of Biostatistics, Bloomberg School of Public Health (United States); Geschwind, J. F., E-mail: jfg@jhmi.edu [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States)

    2013-04-15

    To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4-75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100-300 {mu}m beads loaded with {<=}100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

  20. Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

    Kälsch, Julia; Padden, Juliet; Bertram, Stefanie; Pott, Leona L; Reis, Henning; Westerwick, Daniela; Schaefer, Christoph M; Sowa, Jan-P; Möllmann, Dorothe; Fingas, Christian; Dechȇne, Alexander; Sitek, Barbara; Eisenacher, Martin; Canbay, Ali; Ahrens, Maike; Baba, Hideo A

    2017-05-01

    Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

  1. Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

    Bhagat, Nikhil; Reyes, Diane K.; Lin, Mingde; Kamel, Ihab; Pawlik, Timothy M.; Frangakis, Constantine; Geschwind, J. F.

    2013-01-01

    To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

  2. Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

    Lahrsow, Maximilian; Albrecht, Moritz H.; Bickford, Matthew W.; Vogl, Thomas J.

    2017-01-01

    PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10 −3  mm 2 /s) and no response (median 1.30 × 10 −3  mm 2 /s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

  3. Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

    Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Bickford, Matthew W. [Medical University of South Carolina, Department of Radiology and Radiological Science (United States); Vogl, Thomas J. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

  4. Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy.

    Lahrsow, Maximilian; Albrecht, Moritz H; Bickford, Matthew W; Vogl, Thomas J

    2017-06-01

    To use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment. Fifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions. One month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10 -3  mm 2 /s) and no response (median 1.30 × 10 -3  mm 2 /s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC. In patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

  5. Mathematical model of 5-[125I]iodo-2'-deoxyuridine treatment: continuous infusion regimens for hepatic metastases

    Sgouros, George; O'Donoghue, Joseph A.; Larson, Steven M.; Macapinlac, Homer; Larson, Justine J.; Kemeny, Nancy

    1998-01-01

    Purpose: Due to the cytotoxicity of DNA-bound iodine-125, 5-[ 125 I]Iodo-2'-deoxyuridine ([ 125 I]IUdR), an analog of thymidine, has long been recognized as possessing therapeutic potential. In this work, the feasibility and potential effectiveness of hepatic artery infusion of [ 125 I]IUdR is examined. Methods: A mathematical model has been developed that simulates tumor growth and response to [ 125 I]IUdR treatment. The model is used to examine the efficacy and potential toxicity of prolonged infusion therapy. Treatment of kinetically homogeneous tumors with potential doubling times of either 4, 5, or 6 days is simulated. Assuming uniformly distributed activity, absorbed dose estimates to the red marrow, liver and whole-body are calculated to assess the potential toxicity of treatment. Results: Nine to 10 logs of tumor-cell kill over a 7- to 20-day period are predicted by the various simulations examined. The most slowly proliferating tumor was also the most difficult to eradicate. During the infusion time, tumor-cell loss consisted of two components: A plateau phase, beginning at the start of infusion and ending once the infusion time exceeded the potential doubling time of the tumor; and a rapid cell-reduction phase that was close to log-linear. Beyond the plateau phase, treatment efficacy was highly sensitive to tumor activity concentration. Conclusions: Model predictions suggest that [ 125 I]IUdR will be highly dependent upon the potential doubling time of the tumor. Significant tumor cell kill will require infusion durations that exceed the longest potential doubling time in the tumor-cell population

  6. Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours

    Golubnitschaja, Olga; Yeghiazaryan, Kristina; Stricker, Helena; Trog, Daniela; Schild, Hans H.; Berliner, Leonard

    2016-01-01

    Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium 90 or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced

  7. Adenocarcinoid of the appendix presenting with metastases to the liver

    Bak, Martin; Jørgensen, L J

    1987-01-01

    A case of hepatomegalia due to multiple metastases of unknown origin to the liver is described. At autopsy the primary tumor, an adenocarcinoid tumor of the appendix, was identified along with multiple metastases to the lymph nodes and widespread peritoneal carcinoidosis. Hepatic metastases from...

  8. Significance of CT analysis of regional lymph node metastases in colorectal cancer; Bedeutung der CT fuer die Beurteilung regionaerer Lymphknotenmetastasen bei kolorektalen Karzinomen

    Gomille, T.; Christ, F. [Duesseldorf Univ. (Germany). Abt. fuer Radiologie und Nuklearmedizin; Aleksic, M.; Ulrich, B. [Krankenhaus Gerresheim (Germany). Chirurgische Klinik

    1998-12-01

    Purpose: For preoperative staging of colorectal cancer a CT scan is frequently performed. This report examines the sensitivity of CT for regional lymph node metastasis of colorectal cancer using different criteria. Materials and methods: Preoperative CT scans of 153 patients with colorectal cancer were analyzed using different criteria for N1. The results were then compared to the postoperative histological findings. Results: For N1=lymph nodes (LN)>1 cm the sensitivity was 47%. For N1=LN>1 cm or an increased number of LN<1 cm the sensitivity was 71%. In patients with a primary tumor seen on CT, sensitivity rose to 87%. Discussion: Evidence of regional nodal metastatic disease is only relevant for rectal cancer, colon polyps, and for locally excised tumors when considering present surgical concepts for the treatment of colorectal cancer. In these cases CT analysis using the broadened criteria for N1 proposes a valuable argument regarding possible preoperative radiotherapy or an operative revision. (orig.) [Deutsch] Die Sensitivitaet fuer den Nachweis regionaerer Lymphknotenmetastasen kolorektaler Karzinome wurde unter Anwendung verschiedener Kriterien fuer das N1-Stadium an Patienten mit histologisch gesichertem Lymphknotenbefund untersucht. Fuer das Kriterium N1=Lymphknoten (LK)>1 cm betrug die Sensitivitaet 47%. Fuer N1=LK>1 cm/vermehrte Anzahl LK<1 cm war sie 71%, bei erkennbarem Primaertumor sogar 87%. Unter Beruecksichtigung der derzeit geltenden operativen Therapiekonzepte ist der Nachweis von regionaeren Lymphknotenmetastasen nur bei Rektumkarzinom bzw. fuer Kolonpolypen oder fuer lokal exzidierte Karzinome fuer das therapeutische Vorgehen relevant. In diesen Faellen leistet die CT mit den erweiterten Kriterien fuer ein N1-Stadium trotz hoeherer falsch-positiver Raten eine wertvolle Hilfestellung fuer die Entscheidung ueber eine neoadjuvante Bestrahlung oder eine Nachresektion. (orig.)

  9. Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer

    Sudheer Nambiar

    2018-01-01

    Full Text Available Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.

  10. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  11. Unresectable colorectal liver metastases. Percutaneous ablation using CT-guided high-dose-rate brachytherapy (CT-HDBRT); Nicht resektable kolorektale Lebermetastasen. Perkutane Ablation mittels CT-gesteuerter Hochdosisbrachytherapie (CT-HDBRT)

    Collettini, F.; Lutter, A.; Schnapauff, D.; Denecke, T.; Gebauer, B. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Diagnostic and Interventional Radiology; Hildebrandt, B. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Oncology; Puhl, G. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of General, Visceral and Transplantation Surgery; Wust, P. [Charite, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Radiation Oncology

    2014-06-15

    Purpose: To evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) of unresectable colorectal liver metastases (CRLMs). Materials and Methods: Retrospective analysis of all consecutive patients with unresectable CRLMs treated with CT-HDRBT between January 2008 and November 2012. Treatment was performed by CT-guided catheter placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed after 6 weeks and then every 3 months post-intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS). Results: 80 heavily pretreated patients with 179 metastases were available for MRI evaluation for a mean follow-up time of 16.9 months. The mean tumor diameter was 28.5 mm (range: 8 - 107 mm). No major complications were observed. A total of 23 (12.9%) local tumor progressions were observed. Lesions ≥ 4 cm in diameter showed significantly more local progression than smaller lesions (< 4 cm). 50 patients (62.5%) experienced systemic tumor progression. The median TTP was 6 months. 28 (43%) patients died during the follow-up period. The median OS after ablation was 18 months. Conclusion: CT-HDRBT is an effective technique for the treatment of unresectable CRLMs and warrants promising LTC rates compared to thermal ablative techniques. A combination with other local and systemic therapies should be evaluated in patients with lesions > 4 cm in diameter, in which higher progression rates are expected. (orig.)

  12. NKT cells act through third party bone marrow-derived cells to suppress NK cell activity in the liver and exacerbate hepatic melanoma metastases.

    Sadegh, Leila; Chen, Peter W; Brown, Joseph R; Han, Zhiqiang; Niederkorn, Jerry Y

    2015-09-01

    Uveal melanoma (UM) is the most common intraocular tumor in adults and liver metastasis is the leading cause of death in UM patients. We have previously shown that NKT cell-deficient mice develop significantly fewer liver metastases from intraocular melanomas than do wild-type (WT) mice. Here, we examine the interplay between liver NKT cells and NK cells in resistance to liver metastases from intraocular melanomas. NKT cell-deficient CD1d(-/-) mice and WT C57BL/6 mice treated with anti-CD1d antibody developed significantly fewer liver metastases than WT mice following either intraocular or intrasplenic injection of B16LS9 melanoma cells. The increased number of metastases in WT mice was associated with reduced liver NK cytotoxicity and decreased production of IFN-γ. However, liver NK cell-mediated cytotoxic activity was identical in non-tumor bearing NKT cell-deficient mice and WT mice, indicating that liver metastases were crucial for the suppression of liver NK cells. Depressed liver NK cytotoxicity in WT mice was associated with production of IL-10 by bone marrow-derived liver cells that were neither Kupffer cells nor myeloid-derived suppressor cells and by increased IL-10 receptor expression on liver NK cells. IL-10(-/-) mice had significantly fewer liver metastases than WT mice, but were not significantly different from NKT cell-deficient mice. Thus, development of melanoma liver metastases is associated with upregulation of IL-10 in the liver and an elevated expression of IL-10 receptor on liver NK cells. This impairment of liver NK activity is NKT cell-dependent and only occurs in hosts with melanoma liver metastases. © 2015 UICC.

  13. Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

    Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

    2011-01-01

    ; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

  14. Cardiac metastases

    A. Al-Mamgani (Abrahim); L. Baartman (Lizette); M. Baaijens (Margreet); I. de Pree (Ilse); L. Incrocci (Luca); P.C. Levendag (Peter)

    2008-01-01

    textabstractWe report a case of esophageal cancer with symptomatic metastases to the heart; the patient was treated with short-course radiotherapy with good symptomatic relief. We reviewed the current literature regarding the epidemiology, clinical presentation, diagnostic tools, treatment

  15. A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6.

    Marchiò, Serena; Soster, Marco; Cardaci, Sabrina; Muratore, Andrea; Bartolini, Alice; Barone, Vanessa; Ribero, Dario; Monti, Maria; Bovino, Paola; Sun, Jessica; Giavazzi, Raffaella; Asioli, Sofia; Cassoni, Paola; Capussotti, Lorenzo; Pucci, Piero; Bugatti, Antonella; Rusnati, Marco; Pasqualini, Renata; Arap, Wadih; Bussolino, Federico

    2012-11-01

    Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α(6) integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α(6) integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α(6) integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC. Copyright © 2012 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  16. Health-economic evaluation of three imaging strategies in patients with suspected colorectal liver metastases: Gd-EOB-DTPA-enhanced MRI vs. extracellular contrast media-enhanced MRI and 3-phase MDCT in Germany, Italy and Sweden

    Zech, C.J.; Grazioli, L.; Jonas, E.; Ekman, M.; Joensson, L.; Niebecker, R.; Kienbaum, S.; Gschwend, S.; Breuer, J.

    2009-01-01

    The purpose of this study was to perform an economic evaluation of hepatocyte-specific Gd-EOB-DTPA enhanced MRI (PV-MRI) compared to extracellular contrast-media-enhanced MRI (ECCM-MRI) and three-phase-MDCT as initial modalities in the work-up of patients with metachronous colorectal liver metastases. The economic evaluation was performed with a decision-tree model designed to estimate all aggregated costs depending on the initial investigation. Probabilities on the need for further imaging to come to a treatment decision were collected through interviews with 13 pairs of each a radiologist and a liver surgeon in Germany, Italy and Sweden. The rate of further imaging needed was 8.6% after initial PV-MRI, 18.5% after ECCM-MRI and 23.5% after MDCT. Considering the cost of all diagnostic work-up, intra-operative treatment changes and unnecessary surgery, a strategy starting with PV-MRI with 959 EUR was cost-saving compared to ECCM-MRI (1,123 EUR) and MDCT (1,044 EUR) in Sweden. In Italy and Germany, PV-MRI was cost-saving compared to ECCM-MRI and had total costs similar to MDCT. In conclusion, our results indicate that PV-MRI can lead to cost savings by improving pre-operative planning and decreasing intra-operative changes. The higher cost of imaging with PV-MRI is offset in such a scenario by lower costs for additional imaging and less intra-operative changes. (orig.)

  17. SU-F-J-224: Impact of 4D PET/CT On PERCIST Classification of Lung and Liver Metastases in NSLC and Colorectal Cancer

    Meier, J; Lopez, B; Mawlawi, O [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To quantify the impact of 4D PET/CT on PERCIST metrics in lung and liver tumors in NSCLC and colorectal cancer patients. Methods: 32 patients presenting lung or liver tumors of 1–3 cm size affected by respiratory motion were scanned on a GE Discovery 690 PET/CT. The bed position with lesion(s) affected by motion was acquired in a 12 minute PET LIST mode and unlisted into 8 bins with respiratory gating. Three different CT maps were used for attenuation correction: a clinical helical CT (CT-clin), an average CT (CT-ave), and an 8-phase 4D CINE CT (CT-cine). All reconstructions were 3D OSEM, 2 iterations, 24 subsets, 6.4 Gaussian filtration, 192×192 matrix, non-TOF, and non-PSF. Reconstructions using CT-clin and CT-ave used only 3 out of the 12 minutes of the data (clinical protocol); all 12 minutes were used for the CT-cine reconstruction. The percent change of SUVbw-peak and SUVbw-max was calculated between PET-CTclin and PET-CTave. The same percent change was also calculated between PET-CTclin and PET-CTcine in each of the 8 bins and in the average of all bins. A 30% difference from PET-CTclin classified lesions as progressive metabolic disease (PMD) using maximum bin value and the average of eight bin values. Results: 30 lesions in 25 patients were evaluated. Using the bin with maximum SUVbw-peak and SUVbw-max difference, 4 and 13 lesions were classified as PMD, respectively. Using the average bin values for SUVbw-peak and SUVbw-max, 3 and 6 lesions were classified as PMD, respectively. Using PET-CTave values for SUVbw-peak and SUVbw-max, 4 and 3 lesions were classified as PMD, respectively. Conclusion: These results suggest that response evaluation in 4D PET/CT is dependent on SUV measurement (SUVpeak vs. SUVmax), number of bins (single or average), and the CT map used for attenuation correction.

  18. SU-F-J-224: Impact of 4D PET/CT On PERCIST Classification of Lung and Liver Metastases in NSLC and Colorectal Cancer

    Meier, J; Lopez, B; Mawlawi, O

    2016-01-01

    Purpose: To quantify the impact of 4D PET/CT on PERCIST metrics in lung and liver tumors in NSCLC and colorectal cancer patients. Methods: 32 patients presenting lung or liver tumors of 1–3 cm size affected by respiratory motion were scanned on a GE Discovery 690 PET/CT. The bed position with lesion(s) affected by motion was acquired in a 12 minute PET LIST mode and unlisted into 8 bins with respiratory gating. Three different CT maps were used for attenuation correction: a clinical helical CT (CT_clin), an average CT (CT_ave), and an 8-phase 4D CINE CT (CT_cine). All reconstructions were 3D OSEM, 2 iterations, 24 subsets, 6.4 Gaussian filtration, 192×192 matrix, non-TOF, and non-PSF. Reconstructions using CT_clin and CT_ave used only 3 out of the 12 minutes of the data (clinical protocol); all 12 minutes were used for the CT_cine reconstruction. The percent change of SUVbw_peak and SUVbw_max was calculated between PET_CTclin and PET_CTave. The same percent change was also calculated between PET_CTclin and PET_CTcine in each of the 8 bins and in the average of all bins. A 30% difference from PET_CTclin classified lesions as progressive metabolic disease (PMD) using maximum bin value and the average of eight bin values. Results: 30 lesions in 25 patients were evaluated. Using the bin with maximum SUVbw_peak and SUVbw_max difference, 4 and 13 lesions were classified as PMD, respectively. Using the average bin values for SUVbw_peak and SUVbw_max, 3 and 6 lesions were classified as PMD, respectively. Using PET_CTave values for SUVbw_peak and SUVbw_max, 4 and 3 lesions were classified as PMD, respectively. Conclusion: These results suggest that response evaluation in 4D PET/CT is dependent on SUV measurement (SUVpeak vs. SUVmax), number of bins (single or average), and the CT map used for attenuation correction.

  19. Hepatectomia para o tratamento de metástases colorretais e não-colorretais: análise comparativa em 30 casos operados Hepatectomy for metastasis from colorectal and non-colorectal origin: comparative analysis in 30 resectable cases

    Sergio Renato Pais Costa

    2009-06-01

    Full Text Available RACIONAL: Hepatectomia é a melhor opção terapêutica curativa para metástases hepáticas de origem colorretal. Mais recentemente, ressecção hepática também tem sido realizada para metástases de etiologia não-colorretal. OBJETIVO: Comparar os resultados em curto e longo prazo de uma série de hepatectomias para 20 doentes com metástase colorretal com uma série de 10 doentes com metástase não-colorretal realizadas pelo Serviço de Cirurgia Geral (Disciplina de Cirurgia do Aparelho Digestivo da Faculdade Medicina do ABC (Santo André - Brasil. MÉTODOS: Os dados completos de 30 doentes submetidos à hepatectomia por metástase metacrônica entre o período de Janeiro de 2001 e Setembro de 2007 foram avaliados. Vinte com metástase colorretal (Grupo 1 foram comparados com dez com metástase não-colorretal (Grupo 2. Foi realizada análise multivariada dos fatores prognósticos com o programa Epi-Info para Windows. RESULTADOS: Foram realizadas vinte hepatectomias maiores e dez hepatectomias menores. A morbidade foi similar entre os grupos (p >0,05. A mortalidade cirúrgica foi maior no Grupo 1 do que no Grupo 2 (5 % X 0 %, mas não houve significância estatística (p>0,05. Os índices de sobrevida global em 3 e 5 anos foram comparáveis entre os dois grupos (p>0,05. CONCLUSÃO: Nessa amostra, a ressecção hepática para metástase de etiologia não-colorretal apresenta resultados similares aos da metástase colorretal com sobrevida em cinco anos de 20 %. Foram fatores prognósticos adversos: mais que uma metástase e linfonodo positivo.BACKGROUND: Hepatectomy has presented the best curative therapeutic choice for hepatic metastatic colorectal cancer. More recently, hepatic resection has been performed for hepatic metastases from non-colorectal origin too. AIM: To compare both early and long-term surgical outcomes on 20 patients' series of colorectal with 10 patients' series of non-colorectal hepatic metastases realized by General

  20. Determinants of survival after liver resection for metastatic colorectal carcinoma.

    Parau, Angela; Todor, Nicolae; Vlad, Liviu

    2015-01-01

    Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

  1. Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

    Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

    2015-01-01

    Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Spontaneous regression of metastases from malignant melanoma: a case report

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; thi...

  3. Therapeutic response assessment using 3D ultrasound for hepatic metastasis from colorectal cancer: Application of a personalized, 3D-printed tumor model using CT images.

    Ye Ra Choi

    Full Text Available To evaluate accuracy and reliability of three-dimensional ultrasound (3D US for response evaluation of hepatic metastasis from colorectal cancer (CRC using a personalized 3D-printed tumor model.Twenty patients with liver metastasis from CRC who underwent baseline and after chemotherapy CT, were retrospectively included. Personalized 3D-printed tumor models using CT were fabricated. Two radiologists measured volume of each 3D printing model using 3D US. With CT as a reference, we compared difference between CT and US tumor volume. The response evaluation was based on Response Evaluation Criteria in Solid Tumors (RECIST criteria.3D US tumor volume showed no significant difference from CT volume (7.18 ± 5.44 mL, 8.31 ± 6.32 mL vs 7.42 ± 5.76 mL in CT, p>0.05. 3D US provided a high correlation coefficient with CT (r = 0.953, r = 0.97 as well as a high inter-observer intraclass correlation (0.978; 0.958-0.988. Regarding response, 3D US was in agreement with CT in 17 and 18 out of 20 patients for observer 1 and 2 with excellent agreement (κ = 0.961.3D US tumor volume using a personalized 3D-printed model is an accurate and reliable method for the response evaluation in comparison with CT tumor volume.

  4. [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

    Schmid, K W

    2015-11-01

    The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

  5. Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases.

    Hughes, Marybeth S; Zager, Jonathan; Faries, Mark; Alexander, H Richard; Royal, Richard E; Wood, Bradford; Choi, Junsung; McCluskey, Kevin; Whitman, Eric; Agarwala, Sanjiv; Siskin, Gary; Nutting, Charles; Toomey, Mary Ann; Webb, Carole; Beresnev, Tatiana; Pingpank, James F

    2016-04-01

    There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver. A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4-8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety. hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p PHP-Mel and 1.6 months for BAC (p PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC. This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.

  6. Liver Transplantation for Unresectable Metastases from Colon Adenocarcinoma

    Luis Armando Caicedo

    2017-01-01

    Full Text Available Liver transplantation is an option that improves quality of life and prolongs life expectancy in patients with different types of liver disease. Liver transplantation is controversial for colorectal metastases and is not recommended in clinical practice guidelines. In this case report, we present, to our knowledge, the first liver transplantation for colorectal metastases conducted in Colombia, with a successful follow-up of more than 2 years. Patients with these characteristics who underwent liver transplantation experience reduced mortality and exponentially improved quality of life.

  7. Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

    Wust Peter

    2010-05-01

    Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

  8. Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors.

    Sänger, Philipp Wilhelm; Freesmeyer, Martin

    2016-06-01

    Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga-DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga-DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization.

  9. The effectiveness of samarium-153 (153Sm) lexidronam (EDTMP) in treatment of bone metastases

    Ma Yubo; Huang Gang; Liu Jianjun

    2004-01-01

    Objectives: To evaluate the effectiveness of samarium-153 (153Sm) lexidronam (EDTMP) in treatment of bone metastases. Methods: 380 patients with bone metastases were studied (221 men, 159 women; average age 65.3 y; ranged 27-91 y; average weight 59.3 kg, ranged 39-95 kg). The tumor types were prostate carcinoma (n=155), pulmonary carcinoma (n=92), breast cancer (n=57), gastric carcinoma (n=12), colorectal carcinoma (n=22), nasopharyngeal carcinoma (n=8), lymphoma (n=8), hepatic carcinoma (n=6), ovary carcinoma (n=4) and others (n=16). All patients were received 135Sm-EDTMP 0.8 or 1.0 mCi/kg during 1 to 7 course of treatment. Patients and physician evaluations were used to assess pain relief. Numbers of metastatic foci and activity of ROIs were used to observe post-therapy change in bone scanning. Results: In 380 patients, pain relief was observed in 257 patients (67.6%). Persistence of pain relief was seen through 2 to 24 weeks. The mean relief time is 5.8±3.4 weeks. KPS score was higher 10% than pre-therapy (71.2%±9.6% Vs 80.9%±10.3%, p<0.001). Numbers of metastatic foci (11.2+8.8 Vs 8.4±5.7, p<0.001) and activity of ROIs (3.28±2.04 Vs 2.15±0.94, p<0.01) were less than pre-therapy. Bone marrow suppression was mild and reversible (5.87±1.56 Vs 4.94±1.16 x 109/L). Conclusions: 153Sm-EDTMP provided relief of pain associated with bone metastases and inhibition of metastatic foci. As a relief drug of painful bone metastases, 153Sm-EDTMP is safe and effective. (authors)

  10. Radiofrequency ablation of liver metastases-software-assisted evaluation of the ablation zone in MDCT: tumor-free follow-up versus local recurrent disease.

    Keil, Sebastian; Bruners, Philipp; Schiffl, Katharina; Sedlmair, Martin; Mühlenbruch, Georg; Günther, Rolf W; Das, Marco; Mahnken, Andreas H

    2010-04-01

    The purpose of this study was to investigate differences in change of size and CT value between local recurrences and tumor-free areas after CT-guided radiofrequency ablation (RFA) of hepatic metastases during follow-up by means of dedicated software for automatic evaluation of hepatic lesions. Thirty-two patients with 54 liver metastases from breast or colorectal cancer underwent triphasic contrast-enhanced multidetector-row computed tomography (MDCT) to evaluate hepatic metastatic spread and localization before CT-guided RFA and for follow-up after intervention. Sixteen of these patients (65.1 + or - 10.3 years) with 30 metastases stayed tumor-free (group 1), while the other group (n = 16 with 24 metastases; 62.0 + or - 13.8 years) suffered from local recurrent disease (group 2). Applying an automated software tool (SyngoCT Oncology; Siemens Healthcare, Forchheim, Germany), size parameters (volume, RECIST, WHO) and attenuation were measured within the lesions before, 1 day after, and 28 days after RFA treatment. The natural logarithm (ln) of the quotient of the volume 1 day versus 28 days after RFA treament was computed: lnQ1//28/0(volume). Analogously, ln ratios of RECIST, WHO, and attenuation were computed and statistically evaluated by repeated-measures ANOVA. One lesion in group 2 was excluded from further evaluation due to automated missegmentation. Statistically significant differences between the two groups were observed with respect to initial volume, RECIST, and WHO (p free and local-recurrent ablation zones with respect to the corresponding size parameters. A new parameter (lnQ1//28/0(volume/RECIST/WHO/attenuation)) was introduced, which appears to be of prognostic value at early follow-up CT.

  11. Palliative radiotherapy for liver metastases

    Eble, M.J.; Gademann, G.; Wannenmacher, M.

    1993-01-01

    The role of palliative irradiation was analysed in 55 patients with liver metastases from colorectal, breast and lung cancer, treated with irradiation doses more than 10 Gy. In 47 patients irradiation alone was done. In 29 patients the disease involved not only the liver, but was disseminated. A mean dose of 23.8 Gy was delivered, with daily fractions of 1.5, 1.8 or 2 Gy. Complete and near complete pain relief was obtained in six and nine patients. Normalized and near normalized values of bilirubin serum levels were obtained in five and seven patients. Relief of pain as well as normalisation of cholestasis were significantly correlated with the irradiation doses applied. Median survival was 36.5 days for patients with lung cancer, 70.5 and 73 days for patients with breast and colorectal cancer. Irradiation doses given and the status of disease were significantly correlated to prognosis. In the majority of our patients with clinical symptoms, i.e. pain or cholestase, irradiation alone was sufficient for palliation of these symptoms. Prognosis is limited because of the disseminated state of disease in 62% of the patients. In a group of patients, suffering from colorectal cancer with good prognostic criteria, the simultaneous application of radiotherapy and systemic chemotherapy was able to increase significantly the survival with minor toxicity. The use of a three-dimensional treatment planning could optimize the radiotherapy, due to the dose-volume histogram analysis. (orig./MG) [de

  12. Modern management of colorectal liver metastases

    Preoperative treatment. Chemotherapy. Modern chemotherapy regimens including oxaliplatin and irinotecan in addition to. 5-fluorouracil and leucovorin have achieved .... and type of drainage. It is not necessary to proceed doggedly along the above-outlined sequence of events for resection. e type of resection is guided.

  13. Colorectal polyps

    Intestinal polyps; Polyps - colorectal; Adenomatous polyps; Hyperplastic polyps; Villous adenomas; Serrated polyp; Serrated adenoma; Precancerous polyps; Colon cancer - polyps; Bleeding - colorectal polyps

  14. Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents

    Kauffman, W.M.; Jenkins, J.J. III; Helton, K.; Rao, B.N.; Winer-Muram, H.T.; Pratt, C.B.

    1995-01-01

    This paper describes the imaging features of ovarian metastases from adenocarcinoma of the colon in adolescent females. We reviewed retrospectively abdominal and pelvic computed tomographic and pelvic ultrasound examinations, histologic slices, and clinical charts of six adolescent females with ovarian metastases secondary to adenocarcinoma of the colon. One patient had ovarian metastasis at presentation and was presumed to have a primary ovarian tumor. The ovarian metastases were either solid (n = 3), complex with both solid and cystic components (n = 2), or multilocular cysts (n = 1). The ovarian lesions were large, ranging from 6 cm to 18 cm in diameter. Colorectal carcinoma in adolescent females is frequently associated with ovarian metastases. One imaging characteristic differs in adult and adolescent ovarian metastases, although they do have features in common: in adolescents, a smaller proportion of colorectal ovarian metastases are multicystic (17%) compared with the adult series (45%). These lesions are frequently large and may be complex, multicystic, or solid. Although it is a rare disease, the differential dignosis of adnexal masses in adolescent females should include ovarian metastases from adenocarcinoma of the colon. (orig.)

  15. Evolving concepts in staging and treatment of colorectal cancer

    Sloothaak, D.A.M.

    2015-01-01

    For localized colorectal cancer (CRC), lymph node metastases are the most powerful prognostic factor for disease specific and overall survival. In the first part of the thesis, we explore the prognostic role of lymph nodes in patients with stage I/II colon cancer. In these patients, nodal metastases

  16. Synchronous resection of colorectal liver metastasis- a case report ...

    We present a case report of a young patient of. Carcinoma sigmoid colon with multiple liver metastases who was managed with synchronous resection of colorectal liver metastasis. The patient had an ulceroproliferative growth in the sigmoid colon 18 cm from the anal verge with multiple bilobar liver metastases. The CEA

  17. Tailored treatment of metastatic colorectal cancer: clinical and pre-clinical developments

    Kuijpers, A.M.J.

    2015-01-01

    Colorectal cancer is the third leading cause of cancer-related death in males and females in developed countries. Metastases in distant organs, which develop in 50% of colorectal cancer patients, are responsible for the majority of colorectal cancer deaths. Treatment of metastatic disease should

  18. Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future DirectionsSummary

    Luai R. Zarour

    2017-03-01

    Full Text Available In patients with colorectal cancer (CRC that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver. Our multidisciplinary group held a state-of-the-science symposium this past year to review advances in this rapidly evolving field. Herein, we present a discussion around the issues facing treatment of patients with CRC liver metastases, including the relationship of discrete gene signatures with prognosis. We also discuss the latest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. As we continue to advance clinically and technologically in the field of colorectal tumor biology, our goal should be continued refinement of predictive and prognostic studies to decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailored multidisciplinary approach to cancer care. Keywords: Colorectal Cancer Liver Metastasis, Biomarkers, Hepatic Arterial Infusion, High-Risk Colorectal

  19. The impact of 18F-FDG PET/CT in patients with liver metastases

    Chua, Siew C.; Groves, Ashley M.; Kayani, Irfan; Menezes, Leon; Gacinovic, Svetislav; Du, Yong; Bomanji, Jamshed B.; Ell, Peter J.

    2007-01-01

    The aim of this study was to assess the performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) versus dedicated contrast-enhanced CT (CECT) in the detection of metastatic liver disease. All patients that presented to our Institution with suspected metastatic liver disease who underwent 18 F-FDG PET/CT and CECT within 6 weeks of each other, were retrospectively analyzed, covering a 5-year period. One hundred and thirty-one patients (67 men, 64 women; mean age 62) were identified. Seventy-five had colorectal carcinoma and 56 had other malignancies. The performance of CECT and that of 18 F-FDG-PET/CT in detecting liver metastases were compared. The ability of each to detect local recurrence, extrahepatic metastases and to alter patient management was recorded. The final diagnosis was based on histology, clinical and radiological follow-up (mean 23 months). In detecting hepatic metastases, 18 F-FDG-PET/CT yielded 96% sensitivity and 75% specificity, whilst CECT showed 88% sensitivity and 25% specificity. 18 F-FDG-PET/CT and CECT were concordant in 102 out of 131 patients (78%). In the colorectal group 18 F-FDG-PET/CT showed 94% sensitivity and 75% specificity, whilst CECT had 91% sensitivity and 25% specificity. In the noncolorectal group 18 F-FDG-PET/CT showed 98% sensitivity and 75% specificity whilst CECT had 85% sensitivity and 25% specificity. Overall, 18 F-FDG-PET/CT altered patient management over CECT in 25% of patients. CECT did not alter patient management over 18 F-FDG-PET/CT alone in any patients. 18 F-FDG-PET/CT performed better in detecting metastatic liver disease than CECT in both colorectal and noncolorectal malignancies, and frequently altered patient management. The future role of CECT in these patients may need to be re-evaluated to avoid potentially unnecessary duplication of investigation where 18 F-PET/CT is readily available. (orig.)

  20. Brain metastasis from colorectal cancer

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  1. Metastatic paediatric colorectal carcinoma.

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  2. Diagnosis of colorectal tumors

    Vogl, T.J.; Pegios, W.; Jacobi, V.; Schaefer, S.; Abolmaali, N.; Luboldt, W.

    2003-01-01

    With the introduction of multislice CT extensive volumetric data sets can be quickly acquired in high spatial resolution. The high spatial resolution reduces partial volume effects and enables multiplanar reconstructions. Regarding the colorectum this means that the colon can be assessed if the colon is sufficiently cleaned and distended, and that transmural infiltration of colorectal carcinoma and liver metastases can be better detected. T-staging of colon cancer is less important than T-staging of rectal cancer. Based on the higher contrast MRI is superior to CT in T-staging of rectal cancer and in the differentiation between scarring tissue and recurrence of carcinoma. (orig.) [de

  3. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  4. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  5. Laparoscopic left lateral segmentectomy for metachronic metastases of small intestine adenocarcinoma: a case report

    Sergio Renato Pais-Costa

    2011-12-01

    Full Text Available Hepatectomy has been the standard treatment for metachronic metastases of non-colorectal (NCR origin, mainly when the disease-free interval is more than two years. Laparoscopic hepatectomy has become the golden standard mainly for left side resections, due to lower morbidity, shorter hospital stay, early recovery and good cosmetic outcome. The authors report the case of a female patient with two metachronic metastases (ten years of disease-free survival, of non-colorectal origin (adenocarcinoma of small intestine, treated by laparoscopic left lateral segmentectomy (left hepatic lobectomy with success. The postoperative progress was satisfactory. To date, the patient has presented no tumoral recurrence (six months of follow-up period. Laparoscopic left lateral segmentectomy can be satisfactorily performed in selected cases of hepatic metastasis. This approach presents low morbidity and good cosmetic result. The lack of alternative treatments and the poor prognosis of untreated cases have justified surgical resection in order to increase overall survival. Nevertheless, this approach should be performed by hepatic surgery expertise teams trained on advanced laparoscopic procedures.A hepatectomia tem sido o tratamento padrão para metástase de origem não colorretal (NCR metacrônica, principalmente quando o intervalo livre de doença é maior do que dois anos. A hepatectomia por laparoscopia tem se tornado padrão principalmente para as ressecções à esquerda, haja vista a menor morbidade, menor tempo de internação, reabilitação precoce e melhor resultado estético. Os autores relatam um caso de paciente com duas metástases metacrônicas (10 anos de sobrevida livre de doença, de etiologia não colorretal (adenocarcinoma de intestino delgado, tratada com segmentectomia lateral esquerda (lobectomia hepática esquerda laparoscópica. Paciente apresentou boa evolução pós-operatória sem recidiva (seis meses de seguimento. Segmentectomia

  6. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  7. Early post-treatment FDG PET predicts survival after {sup 90}Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    Sabet, Amir; Aouf, Anas; Sabet, Amin; Ghamari, Shahab; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Meyer, Carsten; Pieper, Claus C. [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2014-10-29

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with {sup 90}Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent {sup 18}F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUV{sub max}) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p < 0.001) with a median OS of 10 months (95 % CI 3-16) versus 4 months (95 % CI 2-6). Hepatic tumour burden also had significant impact on treatment outcome (p < 0.001) with a median OS of 5 months (95 % CI, 3-7) for patients with >25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using {sup 18}F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  8. Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer

    Jiang, Bo; Zhang, Xin; Du, Li-Li; Wang, Yan; Liu, Dong-Bo; Han, Cun-Zhi; Jing, Jie-Xian; Zhao, Xian-Wen; Xu, Xiao-Qin

    2014-01-01

    AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay (ELISA). In the meantime, their body mass index (BMI) and waist-to-hip ratio (WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients (P 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease. PMID:24587638

  9. Spontaneous regression of metastases from malignant melanoma: a case report

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...

  10. Colorectal Cancer

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  11. Hepatic Encephalopathy

    Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

  12. The hepatic bridge.

    Sugarbaker, Paul H

    2018-07-01

    The hepatic bridge forms a tunnel of liver parenchyma that may obscure peritoneal metastases associated with the round ligament. Visualization and then resection of nodules associated with this structure is necessary. The incidence of a hepatic bridge and the extent that it covered the round ligament was determined in consecutive patients. Extent of coverage of the round ligament by the hepatic bridge was determined: Class 1 indicates up to one-third of the round ligament obscured, Class 2 up to two-thirds and Class 3 more than two-thirds. In 102 patients in whom the round ligament of the liver could be completely visualized, 50 had a hepatic bridge. Class 1 was 22 (44%) of the bridges, Class 2 was 16 (32%) and Class 3 was 12 (24%). A hepatic bridge was more frequently present in 28 of 45 male patients (62%) vs. 22 of 57 female patients (38%). Approximately one-half of our patients having cytoreductive surgery for peritoneal metastases were observed to have a hepatic bridge. Up to 56% of these patients have Class 2 or 3 hepatic bridge and may require division of the hepatic bridge to completely visualize the contents of the tunnel created by this structure. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  13. Liver metastases of breast carcinoma detected on /sup 99m/Tc-methylene diphosphonate bone scan

    Baumert, J.E.; Lantieri, R.L.; Horning, S.; McDougall, I.R.

    1980-01-01

    The accumulation of bone-seeking radiopharmaceuticals has been reported in liver metastases from colon carcinoma and oat cell carcinoma of the lung. Two patients with breast carcinoma in whom hepatic metastases were visualized on /sup 99m/Tc-methylene diphosphonate bone images are described. This has not been previously reported

  14. Colorectal Cancer Screening

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  15. Colorectal Cancer Prevention

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  16. Cortical bone metastases

    Davis, T.M. Jr.; Rogers, L.F.; Hendrix, R.W.

    1986-01-01

    Twenty-five cases of bone metastases involving the cortex alone are reviewed. Seven patients had primary lung carcinoma, while 18 had primary tumors not previously reported to produce cortical bone metastases (tumors of the breast, kidney, pancreas, adenocarcinoma of unknown origin, multiple myeloma). Radiographically, these cortical lesions were well circumscribed, osteolytic, and produced soft-tissue swelling and occasional periosteal reaction. A recurrent pattern of metadiaphyseal involvement of the long bones of the lower extremity (particularly the femur) was noted, and is discussed. Findings reported in the literature, review, pathophysiology, and the role of skeletal radiographs, bone scans, and CT scans in evaluating cortical bone metastases are addressed

  17. Skeletal metastases from primary hepatocellular carcinoma

    Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

    1988-01-01

    In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

  18. MR-guided percutaneous cryotherapy of liver metastases

    Haage, P.; Tacke, J.

    2001-01-01

    The prognosis for patients with liver metastases depends on the therapeutic options regarding the treatment of the primary tumor, co-existing extrahepatic metastases and the extent and treatment possibilities of the hepatic metastases themselves. Numerous curative or palliative oncological therapeutic concepts have been introduced in case of non-resectable liver metastases to prolong survival while maintaining a highest possible quality of life. Cryotherapy, which can be performed percutaneously and under magnetic resonance guidance, is one of these manifold therapeutic modalities, combining the inherent advantages of MRI with minimal invasiveness. Excellent visualization of the frozen liver tissue, precise tumor ablation, as well as an almost painless intervention due to the analgetic effect of the ice are implicating percutaneous cryotherapy as an attractive alternative to other ablation techniques. First clinical results are promising. However, meticulous and extensive long-term evaluation on a broad clinical scale is required. (orig.) [de

  19. Colorectal cancer complicating Crohn's disease.

    Freeman, H J

    2001-04-01

    Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  20. Colorectal Cancer Complicating Crohn's Disease

    Hugh J Freeman

    2001-01-01

    Full Text Available Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%. All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%, no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

  1. Metastasizing leiomyoma to heart.

    Consamus, Erin N; Reardon, Michael J; Ayala, Alberto G; Schwartz, Mary R; Ro, Jae Y

    2014-01-01

    Cardiac smooth muscle tumors are rare. Three different clinical settings for these tumors have been reported, including benign metastasizing leiomyoma from the uterus, primary cardiac leiomyoma and leiomyosarcoma, and intravenous cardiac extension of pelvic leiomyoma, which is the most common. We present a case of a 55-year-old woman with a benign metastasizing leiomyoma to the heart 17 years after hysterectomy and 16 years after metastasis to the lung. Immunohistochemical stains for smooth muscle actin, desmin, and estrogen and progesterone receptors were positive, indicating a smooth muscle tumor of uterine origin. To our knowledge, this is only the fourth reported case of benign metastasizing leiomyoma to the heart and the first case of long-delayed cardiac metastasis after successful treatment of pulmonary metastasis. It illustrates that benign metastasizing leiomyoma should be included in the differential diagnosis of cardiac tumors in patients with a history of uterine leiomyoma, especially when associated with pulmonary metastasis.

  2. Immune responses to metastases

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  3. Screening of colorectal early cancer by radiology

    Matsukawa, M.; Usui, Y.; Kobayashi, S.

    1988-01-01

    The incidence of colorectal cancer has been gradually increasing in Japan, and if the present rate of increase is maintained it has been estimated that it will become the most common of all malignant neoplasms by the year 2000. It has been proved that colorectal cancer can be completely cured, if it is treated in its early phase. Early cancer of the large bowel is defined as a cancer which is limited to the mucosal membrane or submucosal layer, regardless of lymph node and distant metastases. Detection of early cancer improves the overall curability of colorectal cancer. The greatest number of early cancers of the large bowel are polypoid lesions in their macroscopic form, and depressed lesions are rarely encountered. Accordingly, the first step in the detection of early cancer starts with the screening of polypoid lesion by radiology and endoscopy. This paper is concerned with diagnostic accuracy of radiology in the screening of colorectal cancer with endoscopic correlation

  4. Antioxidant oils and Salmonella enterica Typhimurium reduce tumor in an experimental model of hepatic metastasis

    Sorenson BS

    2011-05-01

    Full Text Available Brent S Sorenson, Kaysie L Banton, Lance B Augustin, Arnold S Leonard, Daniel A SaltzmanDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAAbstract: Fruit seeds high in antioxidants have been shown to have anticancer properties and enhance host protection against microbial infection. Recently we showed that a single oral dose of Salmonella enterica serovar Typhimurium expressing a truncated human interleukin-2 gene (SalpIL2 is avirulent, immunogenic, and reduces hepatic metastases through increased natural killer cell populations in mice. To determine whether antioxidant compounds enhance the antitumor effect seen in SalpIL2-treated animals, we assayed black cumin (BC, black raspberry (BR, and milk thistle (MT seed oils for the ability to reduce experimental hepatic metastases in mice. In animals without tumor, BC and BR oil diets altered the kinetics of the splenic lymphocyte response to SalpIL2. Consistent with previous reports, BR and BC seed oils demonstrated independent antitumor properties and moderate adjuvant potential with SalpIL2. MT oil, however, inhibited the efficacy of SalpIL2 in our model. Based on these data, we conclude that a diet high in antioxidant oils promoted a more robust immune response to SalpIL2, thus enhancing its antitumor efficacy.Keywords: antioxidants, colorectal cancer, tumor models, metastasis

  5. The impact of surgical resection of the primary tumor on the development of synchronous colorectal liver metastasis: a systematic review.

    Pinson, H; Cosyns, S; Ceelen, Wim P

    2018-05-22

    In recent years different therapeutic strategies for synchronously liver metastasized colorectal cancer were described. Apart from the classical staged surgical approach, simultaneous and liver-first strategies are now commonly used. One theoretical drawback of the classical approach is, however, the stimulatory effect on liver metastases growth that may result from resection of the primary tumour. This systematic review, therefore, aims to investigate the current insights on the stimulatory effects of colorectal surgery on the growth of synchronous colorectal liver metastases in humans. The systematic review was conducted according to the PRISMA statement. A literature search was performed using PubMed and Embase. Articles investigating the effects of colorectal surgery on synchronous colorectal liver metastases were included. Primary endpoints were metastatic tumor volume, metabolic and proliferative activity and tumour vascularization. Four articles meeting the selection criteria were found involving 200 patients. These studies investigate the effects of resection of the primary tumour on synchronous liver metastases using histological and radiological techniques. These papers support a possible stimulatory effect of resection of the primary tumor. Some limited evidence supports the hypothesis that colorectal surgery might stimulate the growth and development of synchronous colorectal liver metastases.

  6. CLINICAL CASE OF A MASSIVE ISOLA TED METASTATIC ADRENAL LESION IN COLORECT AL CANCER

    I. P. Moshurov

    2015-01-01

    Full Text Available AbstractThe liver, lungs, parietal and visceral peritoneum have traditionally been considered to be the main target organs of metastatic colorectal cancer. The isolated adrenal metastasis in colorectal cancer is rare, in the literature there are single observations of clinical cases of successful surgical treatment of such patients. This article presents the clinical observation of successful surgical treatment of patients with colorectal cancer with massive isolated adrenal metastases.

  7. Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision

    Bertelsen, Claus A; Kirkegaard-Klitbo, Anders; Nielsen, Mingyuan

    2016-01-01

    BACKGROUND: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE: The purpose of this study was to describe the pattern of mesocolic lymph node...... metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection. DATA SOURCES: EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip...... node; lymph node resection colon; and complete or total and mesocolic excision. STUDY SELECTION: Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were...

  8. Hepatitis C

    ... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

  9. LFA-1 expression in a series of colorectal adenocarcinomas.

    Papas, Maria G; Karatzas, Pantelis S; Papanikolaou, Ioannis S; Karamitopoulou, Evanthia; Delicha, Eumorphia M; Adler, Andreas; Triantafyllou, Konstantinos; Thomopoulou, Georgia-Heleni; Patsouris, Efstratios; Lazaris, Andreas C

    2012-09-01

    LFA-1 is an adhesion molecule which belongs to the β2-integrin family. Overexpression of LFA-1 in hepatic natural killer cells has been associated with increased apoptosis of neoplastic cells in colorectal cancer (CRC); moreover, studies in CRC have linked LFA-1 overexpression in neoplastic cells with vascular intrusion through adhesion to endothelial cells, thus implying a possible role in creation of metastases. We studied the expression of LFA-1 in a series of 82 patients with CRC. A standard three-step immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded tissue sections. An IgG2a anti-CD11a monoclonal antibody was used. Cases were characterized according to clinicopathological variables including sex, age, tumor localization, size, grade, Dukes stage, wall invasion, and presence of metastatic lymph nodes (mLNs) or distal metastases. LFA-1 was expressed at the primary tumor site in 51 cases and 6/33 cases with metastatic lymphnodes. In Dukes D cases (n = 4), only one case was LFA-1(+). LFA-1 expression at the primary tumor site was associated with the absence of metastatic disease and with Dukes B stage. However, in those cases with LFA-1 expression in cancer cells in mLNs, this was associated with its expression at the primary tumor site. The positive association of LFA-1 expression in mLNs when the primary tumor site is also LFA-1(+) could imply an adaptation advantage of this specific cellular clone to its micro-environment, predisposing it to creation of mLNs, pointing to a role for LFA-1 in creation of mLNs in CRC.

  10. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  11. Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas.

    Malhotra, Sandeep; Kim, Teresa; Zager, Jonathan; Bennett, Joseph; Ebright, Michael; D'Angelica, Michael; Fong, Yuman

    2007-04-01

    Oncolytic cancer therapy using herpes simplex viruses (HSV) that have direct tumoricidal effects and cancer immunotherapy using the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have each been effective in preclinical testing. NV1034 is a multimutated oncolytic HSV carrying the gene for murine GM-CSF that attempts to combine these 2 anticancer strategies. The purpose of this study was to compare NV1034 to NV1023, the parent HSV mutants lacking GM-CSF, to determine if such combined oncolytic and immunotherapy using a single vector has advantages over oncolytic therapy alone. Expression GM-CSF in vitro did not alter the infectivity, cytotoxicity, or replication of NV1034 compared to the noncytokine-secreting control. Tumors infected with NV1034 produced GM-CSF in picogram quantities. In vivo efficacy of the viruses against murine colorectal carcinoma CT26 and murine hepatoma Hepa l-6 was then tested in subcutaneous tumors in syngeneic Balb/c and C57 L/J mice, respectively. In these immune-competent models, NV1034 and NV1023 each demonstrated potent antitumor activity. Treatment with NV1034 had significantly better antitumor effect compared to treatment with NV1023. Furthermore, there was no difference in the antitumor efficacy of these viruses in mice depleted of CD4+ and CD8+ T lymphocytes. Viral vectors combining oncolytic and immunotherapy are promising agents in treatment of colorectal carcinoma and hepatoma.

  12. Management of Brain Metastases.

    Jeyapalan, Suriya A.; Batchelor, Tracy

    2004-07-01

    Advances in neurosurgery and the development of stereotactic radiosurgery have expanded treatment options available for patients with brain metastases. However, despite several randomized clinical trials and multiple uncontrolled studies, there is not a uniform consensus on the best treatment strategy for all patients with brain metastases. The heterogeneity of this patient population in terms of functional status, types of underlying cancers, status of systemic disease control, and number and location of brain metastases make such consensus difficult. Nevertheless, in certain situations, there is Class I evidence that supports one approach or another. The primary objectives in the management of this patient population include improved duration and quality of survival. Very few patients achieve long-term survival after the diagnosis of a brain metastasis.

  13. T1 Colorectal Cancer with Synchronous Liver Metastasis

    Kiichi Sugimoto

    2013-06-01

    Full Text Available The patient was a 68-year-old man who was admitted to our hospital with a liver tumor. Abdominal ultrasonography and computed tomography revealed a liver tumor 30 mm in diameter. On colonoscopy, a pedunculated tumor with a central depression (20 mm in diameter was observed in the ascending colon, and this tumor was considered to be invading deeply into the submucosal layer. Right hemicolectomy with D3 lymphadenectomy and partial hepatectomy were performed simultaneously. On histopathological examination of the resected specimen, the tumor was a well-differentiated tubular adenocarcinoma with 3,000 μm invasion of the submucosal layer. The liver tumor showed histological findings similar to those of the primary colorectal carcinoma. The pathological stage according to the 7th edition of the TNM classification was stage IV (T1N0M1. Nine months after the operation, computed tomography revealed hepatic hilar lymph node metastases and a great deal of ascites. The patient ultimately died 14 months after the operation.

  14. Review of the Clinical Evidence for the Use of DEBIRI in the Treatment of Colorectal Metastatic Disease

    Young, Shamar, E-mail: youn1862@umn.edu; D’Souza, Donna; Flanagan, Siobhan; Golzarian, Jafar [University of Minnesota, Department of Radiology, Division of Interventional Radiology (United States)

    2017-04-15

    Colorectal cancer is a common malignancy that most commonly metastasizes to the liver. There has been considerable effort in developing new treatment options for these patients. One method that has been developed for the treatment of colorectal metastases to the liver is irinotecan-loaded drug-eluting bead (DEBIRI) embolization. This article reviews the current literature on DEBIRI and discusses the state of current knowledge and possible areas of future investigation.

  15. Inguinal metastases from testicular cancer

    Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

    2006-01-01

    To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

  16. Colorectal tuberculosis

    Nagi, B.; Kochhar, R.; Bhasin, D.K.; Singh, K.

    2003-01-01

    Our objective was to evaluate the incidence of colorectal tuberculosis in our series and to study its radiological spectrum. A total of 684 cases of proven gastrointestinal tuberculosis with positive barium contrast findings seen over a period of more than one decade were evaluated. The study did not include cases where colon was involved in direct contiguity with ileo-caecal tuberculosis. Seventy-four patients (10.8%) had colorectal tuberculosis. Commonest site involved was transverse colon, closely followed by rectum and ascending colon. Radiological findings observed were in the form of strictures (54%), colitis (39%) and polypoid lesions (7%). Complications noted were in the form of perforations and fistulae in 18.9% of cases. Colorectal tuberculosis is a very common site for gastrointestinal tuberculosis. Typical findings of colorectal tuberculosis are strictures, signs of colitis and polypoid lesions. Common complications are perforation and fistulae. (orig.)

  17. Colorectal Cancer

    ... possible. Research will help us better understand whether chemotherapy can benefit elderly colorectal cancer patients. Such patients often do not receive chemotherapy due to concerns about side effects. We will ...

  18. Focal eosinophilic necrosis of the liver in patients with underlying gastric or colorectal cancer: CT differentiation from metastasis

    Jang, Hyun Jung; Lee, Won Jae; Lee, Soon Jin; Kim, Seung Hoon; Lim, Hyo K.; Lim, Jae Hoon [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-12-01

    To determine the helical CT findings which help differentiate between focal eosinophilic necrosis (FEN) of the liver and metastasis in patients with underlying gastric or colorectal cancer. In 21 patients with underlying gastric and colorectal cancer examined during a recent 18-month period, the presence of FEN (n=90) was proven at CT. The diagnosis was verified by biopsy in eight patients and by the transient nature of the findings related to peripheral eosinophilia (>10%) in the remainder. For comparison, 20 consecutive patients with pathologically proven hepatic metastasis from gastric or colorectal cancer (n=158) were selected. Single-phase helical CT images (7-mm collimation, pitch 1:1) were independently analyzed in a random order by two blinded readers. The parameters evaluated included the margin (depicted border, fuzzy), shape (spherical, non-spherical), attenuation (subtle hypoattenuation, hypoattenuation), and the presence or absence of rim enhancement. FEN far more frequently showed a fuzzy margin (81%, 84%), subtle hypoattenuation (89%, 91%), and a non-spherical shape (84% for both readers) than metastasis, for which the respective findings were 6%, 22%; 20%, 39%; and 15%, 23%. Rim enhancement was seldom found in FEN (0%, 2%), but was recognized by both readers in 40% of metastases. For all parameters, the results were statistically significant (p < .01), and showed that both readers correctly differentiated FEN from metastasis in 78% of the patients (32/41). Interobserver agreement was, in addition, excellent ({kappa}= 0.66). When focal hepatic lesions with a fuzzy margin, non-spherical shape and subtle hypoattenuation without rim enhancement are found, the possibility of FEN should be considered even in patients with underlying gastrointestinal malignancy.

  19. HIPEC treatment of peritoneal carcinomatosis in colorectal and gastric cancer

    Braam, H.J.W.

    2015-01-01

    This thesis focuses on the treatment of peritoneal metastases of gastric and colorectal cancer, specifically using cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). A large part of this thesis is based on retrospective analysis of patients treated with CRS

  20. Management of Liver Metastasis from Colo-Rectal Carcinoma with ...

    Background: Worldwide, colo-rectal carcinoma is the second most common cancer with liver metastases as its major cause of mortality.This malignant condition is now seen more frequently in our environment typically at a late stage with distant metastasis especially to the liver. This study aims at highlighting the current use ...

  1. Bone metastases from gastric cancer

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

    1983-01-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

  2. Hepatic Encephalopathy

    Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

  3. Hepatic Encephalopathy

    Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

  4. A gamma camera method to monitor the use of degradable starch microspheres in hepatic arterial chemotherapy

    Britten, A.; Fleming, J.; Flowerdew, A.; Hunt, T.; Taylor, I.; Ackery, D.

    1989-01-01

    A gamma camera method to quantify the haemodynamic effects of degradable starch microspheres (DSM) in intra arterial hepatic therapy is described. Results are presented from ten patients with colorectal liver metastases. Intra hepatic arterio venous shunting was present in 1 patient prior to DSM and in 2 subjects after three 300 mg DSM fractions. DSM reduced the rate of flow of injectate to the lung in all cases. Conversely, an increased rate of flow of injectate to gut or spleen occurred with 300 mg fractions of DSM in 7/9 cases. Lower dose DSM fractions are indicated. At 2-3 min after DSM injection the mean fraction of the activity retained in the liver was 0.22. A DSM induced enhancement of tumour relative to normal tissue perfusion was obtained in four out of five tumour regions identified. All indices showed a wide variation between patients and between individual DSM doses, and the high incidence of extra hepatic shunting confirms the need for monitoring when using intra arterial microspheres. (orig.)

  5. Radiotherapy of choroidal metastases

    Hoogenhout, J; Gasteren, J J.M. van; Brink, H M.A.; Verbeek, A M; Beex, L V.A.M.

    1989-05-01

    With binocular indirect ophthalmoscopy, fluorescin angiography and ultrasonography 68 choroidal metastases in 52 eyes of 39 patients were diagnosed. The primary tumors were mainly breast cancer (81%) and lung cancer (10%). After radiation treatment the visual acuity improved in 17 eyes (38%), stabilized in 15 eyes (33%), whereas in 13 eyes (29%) deterioration could not be prevented (seven eyes unknown). Regression of the lesions or its accompanying secondary retinal detachment was seen in 78% of the eyes treated. Acute transient side effects of radiation therapy were keratoconjunctivitis (nine patients) and acute glaucoma in one patient. No cataractous changes of the lens were observed in the post radiation period (one to 42 months). Irradiation of choroidal metastases can contribute to improvement of the quality of life with a treatment scheme of 30 Gy in ten daily fractions.

  6. Transarterial chemoembolization of liver metastases in patients with uveal melanoma

    Huppert, P.E., E-mail: huppert@klinikum-darmstadt.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Fierlbeck, G., E-mail: gerhard.fierlbeck@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Pereira, P., E-mail: philippe.pereira@slk-kliniken.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Schanz, S., E-mail: stefan.schanz@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Duda, S.H., E-mail: stephan.duda@t-online.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Wietholtz, H., E-mail: hubertus.wietholtz@klinikum-darmstadt.d [Department of Internal Medicine II, Klinikum Darmstadt, Darmstadt (Germany); Rozeik, C., E-mail: rozeik.christoph@klinloe.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Claussen, C.D., E-mail: claus.claussen@med.uni-tuebingen.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany)

    2010-06-15

    Summary: Metastases from uveal melanoma are often confined to the liver. Palliative hepatic chemoembolization has been considered to be a reasonable treatment approach. We enrolled 14 patients with hepatic metastases from uveal melanoma into a pilot trial of transarterial chemoembolization (TACE). All patients received additional systemic immuno-chemotherapy or best supportive care. In 31 procedures 100 mg/m{sup 2} of cisplatine was continuously infused by means of a power injector preceding embolization by manual injection of polyvinyl alcohol particles. In three procedures cisplatine was replaced by 200 mg/m{sup 2} carboplatine because of increased serum creatinine levels. Tumor response was evaluated using RECIST criteria. Fourteen patients received 34 TACE's (mean: 2.4 treatments). Eight patients (57%) achieved partial response (PR), four patients (29%) had stable disease and two patients (14%) tumor progression. Median time to progression was 8.5 months (5-35 months). Median survival after first TACE was 14.5 months in responders compared to 10 months in non-responders (p = 0.18, not significant) and 11.5 months (3-69 months) in all patients. In seven patients with metastases occupying less than 25% of liver volume median survival was 17 months compared to 11 months in seven patients with tumor involvement of more than 25% (p = 0.02) with partial response rate of 86% and 29%, respectively. TACE of liver metastases from uveal melanoma is well tolerated and may prolong survival in patients with limited tumor extension.

  7. Intravascular pulmonary metastases

    Shepard, J.A.O.; Moore, E.H.; Templeton, P.A.; McLoud, T.C.

    1988-01-01

    The diagnosis of intravascular metastatic tumor emboli to the lungs is rarely made. The authors present a characteristic radiographic finding of intravascular lung metastases that they observed in four patients with diagnoses or right atrial myoxoma, invasive renal cell carcinoma, invasive pelvic osteosarcoma, and recurrent pelvic chondrosarcoma. Substantiation of intravascular pulmonary metastases was achieved by means of autopsy, pulmonary artery biopsy, and surgical documentation of tumor invasion of the inferior vena cava or pelvic veins. In all four cases, chest computed tomography (CT) demonstrated branching, beaded opacities extending from the hila into the periphery of the lung in the distribution of pulmonary arteries. In one case, similar findings were observed in magnetic resonance (MR) images of the chest. Follow-up studies in three cases showed progressive enlargement and varicosity of the abnormal pulmonary artery consistent with proliferation of intravascular tumor. In the case of metastatic osteosarcoma, intraluminal ossification was also observed at CT. In three of four cases, pulmonary infarction was demonstrated in the distribution of the abnormal pulmonary arteries seen at CT as small, peripheral, wedge-shaped opacities. The demonstration of progressively dilated and beaded pulmonary arteries in patients with extrathoracic malignancies is suggestive of intravascular lung metastases, particularly when accompanied by peripheral infarction

  8. Bone scintiscanning in metastases

    Cayla, J.; Basset, J.Y.

    1986-01-01

    The three fold interest of bone scintiscanning is discussed in relation to 182 cases of bone metastases of various origins. Firstly, this technic facilitates early diagnosis of invasion of the bone by the detection of metastatic lesions which, in 7.7% of cases are still infraradiologic, or even of reflex algodystrophy of the legs, which can be detected only from a scintiscan, long before X-ray plates can show the lumbar metastasis which is responsible. Secondly, the method is able to pick up more metastasic sites in 54.4% of cases than can be detected by X-ray; this is confirmed by investigation of the S/R ratio (ratio of the number of strongly binding sites to the number of sites showing radiologic damage) which is greater than unity for a considerable period. Thirdly, repeated scintiscanography provides a prognosis, because the survival time appears to be fairly closely correlated with the regression, stability or extension of strongly binding sites, although a ''flare phenomenon'' may give the erroneous impression that the metastatic process has deteriorated. Repeated scintiscanography also provides a good way of evaluating the efficacy of medical treatment, particularly in the case of bone metastases of mammary or prostatic origin. Sometimes, the decision for or against prophylactic or palliative orthopedic surgery may be based to a considerable extent on data provided by scintiscan [fr

  9. Hemorrhagic brain metastases

    Takahashi, Motoichiro; Takekawa, S.D.; Suzuki, Kenzo

    1986-01-01

    Tumor hemorrhage on computed tomography (CT) was found in 14 patients with brain metastases (7 % of two hundred patients with brain metastases), from April 1979 to July 1983. Primary foci of these lesions were the lung (6 patients), breast (2), kidney (2), uterus (2), colon (1) and adrenal gland (1). ''Stroke'' syndrome was the initial presenting symptom in 3 patients; neurological focal sign or symptoms of increased intracranial pressure in the remaining patients. CT demonstrated peritumoral hemorrhage in all patients with solid mass, intratumoral hemorrhage in a few patients and also cerebral or ventricular hemorrhage, which was fatal complication, in 2 patients (colon and breast cancers). A cystic mass with fluid-blood level was noted in a patient with breast cancer. Several predisposing factors including chemotherapy, thrombocytopenia, radiotherapy or combination of these were recognized in 8 patients. Of these, chemotherapy was the most causative factor of tumor hemorrhage. Brain irradiation for hemorrhagic brain metastases was effective for prolongation of mean survival time of these patients as follows; 10 months in irradiated group, whereas 1.5 months in non-irradiated group. (author)

  10. MRI-guided laser-induced thermotherapy (LITT) of liver metastases: clinical evaluation

    Vogl, T.J.; Weinhold, N.; Mueller, P.; Mack, M.; Scholz, W.; Philipp, C.; Roggan, A.; Felix, R.

    1996-01-01

    The goal was to perform an evaluation of MRI-guided laser-induced thermotherapy (LITT) of liver metastases as a clinical method. In a prospective study, 50 patients with liver metastases of colorectal carcinoma (35 patients), or other primary tumors (15 patients) were treated with LITT. For preparation and intermittent controls of therapy, standardized MRI examinations were made. Online monitoring during the the LITT was done with temperature-sensitive T1-weighted sequences (FLASH-2D, TurboFLASH). All in all, 83 metastases of a volume between 1 and 282 cubic centimeters (median = ± 10 cm 3 ) were treated.During performance of the LITT, a decrease of signal intensity in the thermosensitive sequences was measured for the application area, and was correlated with fluorine-optical temperature measurements. The MRI-guided LITT is a novel, potential modality for treatment of liver metastases, and poses only minimal clinical risks. (orig./VHE) [de

  11. The value of radiotherapy in colorectal and anal carcinomas, judged on the basis of radiation results obtained in Wuerzburg between 1977 and 1985

    Aydin, H.

    1987-01-01

    Investigations were carried out into the effectiveness of radiotherapy in colorectal and anal carcinomas as well as metastases formed by those tumours. The relevance of changes in CT findings and CEA values is discussed in detail. (MBC) [de

  12. Risks of Colorectal Cancer Screening

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  13. Spinal cord compression secondary to bone metastases from hepatocellular carcinoma

    Doval, Dinesh Chandra; Bhatia, Komal; Vaid, Ashok Kumar; Pavithran, Keechelat; Sharma, Jai Bhagwan; Hazarika, Digant; Jena, Amarnath

    2006-01-01

    Bone metastases are rare in primary hepatocellular carcinoma (HCC). Spinal cord compression (SCC) due to bone metastases occur commonly in patients with lung and breast carcinomas, and metastatic HCC is an unusual cause of SCC. Spinal cord compression is an oncologic emergency and treatment delays can lead to irreversible consequences. Thus, the awareness that SCC could be a potential complication of bone metastases due to HCC is of significance in initiation of early treatment that can improve the quality of life and survival of the patients, if diagnosed earlier. This paper describes four cases of primary HCC with varied manifestations of SCC due to bone metastases. The first patient presented primarily with the symptoms of bone pains corresponding to the bone metastases sites rather than symptoms of associated hepatic pathology and eventually developed SCC. The second patient, diagnosed as having HCC, developed extradural SCC leading to paraplegia during the course of illness, for which he underwent emergency laminectomy with posterior fixation. The third patient developed SCC soon after the primary diagnosis and had to undergo emergency laminectomy. Post laminectomy he had good neurological recovery. The Fourth patient presented primarily with radicular pains rather than frank paraplegia as the first manifestation of SCC. PMID:16937544

  14. Actual role of radiofrequency ablation of liver metastases

    Pereira, Philippe L. [Eberhard-Karls-University of Tuebingen, Department of Diagnostic Radiology, Tuebingen (Germany)

    2007-08-15

    The liver is, second only to lymph nodes, the most common site for metastatic disease irrespective of the primary tumour. More than 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improved survival in patients with colorectal metastases, only approximately 20% of patients are eligible for surgery. Thermal ablation and especially radiofrequency ablation emerge as an important additional therapy modality for the treatment of liver metastases. RF ablation shows a benefit in life expectancy and may lead in a selected patient group to cure. Percutaneous RF ablation appears safer (versus cryotherapy), easier (versus laser), and more effective (versus ethanol instillation and transarterial chemoembolisation) compared with other minimally invasive procedures. RF ablation can be performed by a percutaneous, laparoscopical or laparotomic approach, and may be potentially combined with chemotherapy and surgery. At present ideal candidates have tumours with a maximum diameter less than 3.5 cm. An untreatable primary tumour or a systemic disease represents contraindications for performing local therapies. Permanent technical improvements of thermal ablation devices and a better integration of thermal ablation in the overall patient care may lead to prognosis improvement in patients with liver metastases. (orig.)

  15. Actual role of radiofrequency ablation of liver metastases

    Pereira, Philippe L.

    2007-01-01

    The liver is, second only to lymph nodes, the most common site for metastatic disease irrespective of the primary tumour. More than 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improved survival in patients with colorectal metastases, only approximately 20% of patients are eligible for surgery. Thermal ablation and especially radiofrequency ablation emerge as an important additional therapy modality for the treatment of liver metastases. RF ablation shows a benefit in life expectancy and may lead in a selected patient group to cure. Percutaneous RF ablation appears safer (versus cryotherapy), easier (versus laser), and more effective (versus ethanol instillation and transarterial chemoembolisation) compared with other minimally invasive procedures. RF ablation can be performed by a percutaneous, laparoscopical or laparotomic approach, and may be potentially combined with chemotherapy and surgery. At present ideal candidates have tumours with a maximum diameter less than 3.5 cm. An untreatable primary tumour or a systemic disease represents contraindications for performing local therapies. Permanent technical improvements of thermal ablation devices and a better integration of thermal ablation in the overall patient care may lead to prognosis improvement in patients with liver metastases. (orig.)

  16. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    Miyata, Akinori; Ishizawa, Takeaki; Kamiya, Mako; Shimizu, Atsushi; Kaneko, Junichi; Ijichi, Hideaki; Shibahara, Junji; Fukayama, Masashi; Midorikawa, Yutaka; Urano, Yasuteru; Kokudo, Norihiro

    2014-01-01

    Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed

  17. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    Akinori Miyata

    Full Text Available Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10 under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases, photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical

  18. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. Copyright © 2016. Published by Elsevier Inc.

  19. Imaging of renal metastases

    Bruneton, J.N.; Normand, F.; Balu-Maestro, C.; Rogopoulos, A.; Drouillard, J.; Laurent, F.

    1988-01-01

    Metastases are the most frequent malignant tumors of the kidney, but these lesions are of late onset in neoplastic disease. The 19 cases reported here were all investigated with various imaging techniques (CT 12 cases, ultrasonography 12 cases, urography 8 cases, angiography 2 cases, MRI 1 case). The most common primary malignancies were lung cancer, melanoma and cancer of the controlateral kidney. In this series, 8 of the lesions were solitary, and 9 were unilateral. Tumor vascularity was evaluated in 15 cases: 14 of these lesions were hypovascular. The differential diagnosis includes small cysts, lymphoma, bilateral renal cancer, multiple small abscesses and multiple small infarcts [fr

  20. Scanning of bone metastases

    Robillard, J.

    1977-01-01

    The Centers against cancer of Caen, Angers, Montpellier, Strasbourg and 'the Curie Foundation' have confronted their experience in detection of bone metastases by total body scanning. From the investigation by this procedure, of 1,467 patients with cancer, it results: the confrontation between radio and scanning shows a rate of false positive and false negative identical to the literature ones; the countage scanning allows to reduce the number of false positive; scanning allows to direct bone biopsy and to improve efficiency of histological examination [fr

  1. Extraneural metastases in medulloblastoma

    V M F Muoio

    2011-01-01

    Full Text Available Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature.

  2. Hepatic Encephalopathy

    Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

  3. Viral Hepatitis

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  4. Hepatitis B

    ... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

  5. Hyperthermia, immunity and metastases

    Lopatin, V.F.

    1983-01-01

    The analysis of literature data concerning local hyperthermia effects shows that temperatures over 41-42 deg C (in the whole tumor volume), causing tumor growth inhibition and cell injury, can change antigenic nature of a malignant tissue. The tumor injured by thermal effect is able probably the full length of time of injured tissue resorption to maintain at a sufficiently high level antitumoral immunity and lay obstacles to emergence of metastases or even cause regression of those tumoral foci which have not been exposed to direct effect of the injuring agent. The facts of tumoral foci regression take place also upon radiation effect which is associated as well with participation of immune mechanisms. In.experiments with animals an essential increase of immunogenic character of malignant cells exposed to ionizing radiation effect has been observed. It follows that radiation injury of tumoral tissue as well as thermal one is able to stimulate antitumoral immunity and reduce the probability of emergence of metastases. But in case of radiotherapy immunosuppression effect of ionizing radiation (at the expense of inhibition of proliferation and death of immunocompetent cells) can essentially overlap immunostimulating effect related to the changes in antigenic character of tumoral cells

  6. Breast metastases from rectal carcinoma

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  7. Colorectal cancer

    Akiba, Suminori

    1992-01-01

    This paper describes colorectal cancer risk in relation to A-bomb radiation. The RERF Life Span Study has revealed the incidence of colorectal cancer to be significantly high in the group of A-bomb survivors than the control group. With regard to relative risk or excess relative risk, there is no definitive difference among sites in the colon. Risk for colon cancer is found to be linearly increased with increasing radiation doses, and in younger A-bomb survivors at the time of exposure. Risk associated with one Gy is estimated to be increased by double. There is no definitive variation between sex and between Hiroshima and Nagasaki. Excess relative risk would be increased rapidly with aging in the whole group of A-bomb survivors and with the cancer-prone age in younger A-bomb survivors at the time of exposure. (N.K.)

  8. Spinal metastases of malignant gliomas

    Materlik, B.; Steidle-Katic, U.; Feyerabend, T.; Richter, E.; Wauschkuhn, B.

    1998-01-01

    Purpose: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. Patients and Method: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. Results: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. Conclusions: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms. (orig.) [de

  9. Characterization of liver metastases: the efficacy of biphasic magnetic resonance imaging with ferucarbotran-enhancement

    Hong, H.S.; Byun, J.H.; Won, H.J.; Kim, K.W.; Lee, S.S.; Lee, M.G.; Yun, S.C.

    2010-01-01

    Aim: To retrospectively evaluate the efficacy of biphasic magnetic resonance imaging (MRI) of the liver with ferucarbotran-enhancement for the characterization of hepatic metastases. Materials and methods: Thirty-six patients underwent MRI of the liver with separate acquisition of double-contrast enhancement consisting of gadolinium and ferucarbotran. A total of 106 focal hepatic lesions (51 metastases, 31 cysts, 23 haemangiomas, and one eosinophilic abscess) were included. Two sets of MRI were analysed: (1) ferucarbotran set: ferucarbotran-enhanced T1-weighted (T1W) dynamic imaging combined with ferucarbotran-enhanced T2*-weighted (T2*W) delayed imaging and (2) double set: gadolinium-enhanced T1W dynamic imaging combined with ferucarbotran-enhanced T2*W delayed imaging. The diagnostic accuracy of the two sets was evaluated using alternative free-response receiver operating characteristic curve analysis. Sensitivity and specificity were compared using the McNemar test. The enhancement pattern of focal hepatic lesions was analysed on gadolinium and ferucarbotran-enhanced T1W dynamic imaging. Results: There was no significant difference in the accuracy of characterizing hepatic metastases between the two sets. Sensitivity and specificity were not significantly different between the sets (p > 0.05). Peripheral rim enhancement was exhibited in 57% of metastatic lesions on ferucarbotran-enhanced T1W dynamic imaging. The majority (96%) of hepatic haemangiomas demonstrated typical peripheral nodular enhancement with progression on ferucarbotran-enhanced T1W dynamic imaging and were easily differentiated from metastases. Conclusion: Biphasic MRI of the liver with ferucarbotran-enhancement alone provided comparable diagnostic efficacy to double-contrast MRI for the characterization of hepatic metastases.

  10. Modern management of colorectal liver metastases -e liver is the ...

    Continuing Medical Education. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 31, No 6 (2013) >. Log in or Register to get access to full text downloads.

  11. Occurrence and survival of synchronous pulmonary metastases in colorectal cancer

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Jorgensen, Lars N

    2014-01-01

    Cancer Group's (DCCG's) database between May 2001 and December 2011. The recorded data were merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable logistic- and extended Cox regression analyses were used to adjust for confounding variables. RESULTS: In total...... this association (adjusted OR=1.81 (95% CI: 1.46-2.25, Pmodalities were combined. CONCLUSIONS: The occurrence...

  12. The microenvironment of liver metastases from Colorectal adenocarcinoma

    Eefsen, Rikke Løvendahl

    drugs such as the vascular endothelial growth factor (VEGF) inhibitor bevacizumab or the epidermal growth factor receptor inhibitors (e.g. cetuximab or panitumumab). KRAS and NRAS mutational status predicts efficacy of EGFR-inhibitors, but a predictive marker for bevacizumab is lacking. Three...

  13. Liver transplantation for non-resectable colorectal liver metastases ...

    2017-06-06

    Jun 6, 2017 ... The request was urgent as Patient A required transplant work-up, so the matter was ... it offers hope of saving life, re-establishing health or alleviating ... making this decision, several points of ethics were deliberated. Scarcity of ... A. Recognising the imperative to balance the best interests of listed patients ...

  14. Australian contemporary management of synchronous metastatic colorectal cancer.

    Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

    2018-01-01

    This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred