Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

Science.gov (United States)

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Surgical palliation of unresectable pancreatic head cancer in elderly patients

Science.gov (United States)

Hwang, Sang Il; Kim, Hyung Ook; Son, Byung Ho; Yoo, Chang Hak; Kim, Hungdai; Shin, Jun Ho

2009-01-01

AIM: To determine if surgical biliary bypass would provide improved quality of residual life and safe palliation in elderly patients with unresectable pancreatic head cancer. METHODS: Nineteen patients, 65 years of age or older, were managed with surgical biliary bypass (Group A). These patients were compared with 19 patients under 65 years of age who were managed with surgical biliary bypass (Group B). In addition, the results for group A were compared with those obtained from 17 patients, 65 years of age or older (Group C), who received percutaneous transhepatic biliary drainage to evaluate the quality of residual life. RESULTS: Five patients (26.0%) in Group A had complications, including one intraabdominal abscess, one pulmonary atelectasis, and three wound infections. One death (5.3%) occurred on postoperative day 3. With respect to morbidity, mortality, and postoperative hospitalization, no statistically significant difference was noted between Groups A and B. The number of readmissions and the rate of recurrent jaundice were lower in Group A than in Group C, to a statistically significant degree (P = 0.019, P = 0.029, respectively). The median hospital-free survival period and the median overall survival were also significantly longer in Group A (P = 0.001 and P < 0.001, respectively). CONCLUSION: Surgical palliation does not increase the morbidity or mortality rates, but it does increase the survival rate and improve the quality of life in elderly patients with unresectable pancreatic head cancer. PMID:19248198

Clinical impact of radiotherapy for locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Sawaki, Akira; Hoki, Noriyuki; Ito, Satoko

2009-01-01

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC. Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n=30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n=28, or gemcitabine, n=19, as a radiosensitizer) at Aichi Cancer Center Hospital. Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3-4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy. Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy. (author)

Beam angle selection for intensity-modulated radiotherapy (IMRT) treatment of unresectable pancreatic cancer: are noncoplanar beam angles necessary?

Science.gov (United States)

Chang, D S; Bartlett, G K; Das, I J; Cardenes, H R

2013-09-01

External beam radiation therapy with concurrent chemotherapy (CRT) is widely used for the treatment of unresectable pancreatic cancer. Noncoplanar (NCP) 3D conformal radiotherapy (3DCRT) and coplanar (CP) IMRT have been reported to lower the radiation dose to organs at risk (OARs). The purpose of this article is to examine the utility of noncoplanar beam angles in IMRT for the management of pancreatic cancer. Sixteen patients who were treated with CRT for unresectable adenocarcinoma of the pancreatic head or neck were re-planned using CP and NCP beams in 3DCRT and IMRT with the Varian Eclipse treatment planning system. Compared to CP IMRT, NCP IMRT had similar target coverage with slightly increased maximum point dose, 5,799 versus 5,775 cGy (p = 0.008). NCP IMRT resulted in lower mean kidney dose, 787 versus 1,210 cGy (p kidney dose, but did not improve other dose-volume criteria. The use of NCP beam angles is preferred only in patients with risk factors for treatment-related kidney dysfunction.

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok

2014-01-01

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

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Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2014-06-15

Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

Evaluation of multimodality treatment for advanced pancreatic cancer. Special reference to intraoperative vs. external radiation therapy

International Nuclear Information System (INIS)

Wakasugi, Hideyuki; Funakoshi, Akihiro; Seo, Yousuke; Iguchi, Haruo; Wada, Susumu

1999-01-01

Intraoperative radiation therapy (IORT)+postoperative external beam radiation therapy (ERT) with chemotherapy and ERT alone with chemotherapy have been performed in our hospital for unresectable, especially locally advanced, pancreatic cancer. We compared the former method with the latter. Chemotherapy was performed together with radiation, using 5-FU, CDDP, and MMC. IORT+ERT was successful in only half of the treated patients, while ERT alone was successful in almost all of the patients. As a result, the doses of radiation were often shorter in patients treated by the former method compared to the latter method. Both methods, when completed for locally advanced pancreatic cancer (stage IVa), produced good effects on tumor markers, tumor size and pain. Furthermore, the latter method was better than the former in improving the survival time and quality of life (QOL). Therefore, ERT is a practical and useful method for patients with locally advanced pancreatic cancer. (author)

Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

Directory of Open Access Journals (Sweden)

Okita Yoshihiro

2010-02-01

Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

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Chiorean, E. Gabriela, E-mail: gchiorea@uw.edu [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Department of Medicine, University of Washington, Seattle, Washington (United States); Schneider, Bryan P. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Akisik, Fatih M. [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Perkins, Susan M. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); Anderson, Stephen [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Johnson, Cynthia S. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States); DeWitt, John [Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana (United States); Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Deluca, Jill [Department of Radiation Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Bu, Guixue [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Shahda, Safi; Loehrer, Patrick J. [Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana (United States); Sandrasegaran, Kumar [Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Cardenes, Higinia R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2014-06-01

Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m{sup 2} intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m{sup 2} intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K{sup trans} in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival.

Phase 1 Pharmacogenetic and Pharmacodynamic Study of Sorafenib With Concurrent Radiation Therapy and Gemcitabine in Locally Advanced Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Chiorean, E. Gabriela; Schneider, Bryan P.; Akisik, Fatih M.; Perkins, Susan M.; Anderson, Stephen; Johnson, Cynthia S.; DeWitt, John; Helft, Paul; Clark, Romnee; Johnston, Erica L.; Spittler, A. John; Deluca, Jill; Bu, Guixue; Shahda, Safi; Loehrer, Patrick J.; Sandrasegaran, Kumar; Cardenes, Higinia R.

2014-01-01

Purpose: To define the safety, efficacy, and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy (CRT) in locally advanced pancreatic cancer. Methods and Materials: Patients received gemcitabine 1000 mg/m 2 intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT. Weekly gemcitabine 600 mg/m 2 intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions. Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily. The maximum tolerated dose cohort was expanded to 15 patients. Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms (VEGF-A and VEGF-R2 single nucleotide polymorphisms). Results: Twenty-seven patients were enrolled. No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT. The most common grade 3/4 toxicities were fatigue, hematologic, and gastrointestinal. The maximum tolerated dose was sorafenib 400 mg twice daily. The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months, respectively. The median overall survival for patients with VEGF-A -2578 AA, -1498 CC, and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months. Dynamic contrast-enhanced MRI demonstrated higher baseline K trans in responding patients. Conclusions: Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer. Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival

Results of intraoperative radiotherapy for pancreatic cancers

International Nuclear Information System (INIS)

Okazaki, Atsushi; Shinozaki, Jun; Noda, Masanobu

1991-01-01

Reported are the results and observations of the authors who, from July 1986 through December 1989, have used electron beam intraoperative radiotherapy (IORT) on 20 patients with locally advanced pancreatic cancers, said number including 3 patients given a resection. In 14 of the 17 unresected patients, a chief symptom was pain, and 8 patients were given a celiac plexus block at the same time. The results and observations are given below. Life-threatening complications occurred in two patients, i.e., an insufficient pancreatojejunostomy, and a perforative peritonitis. In 12 of 13 evaluable patients, pain control was achieved for a mean period of 5 months, indicating that an IORT with celiac plexus block may be useful for palliation. In the resected patients, the mean survival time was 6 months, whereas in the unresected patients, the mean survival time was 7 months. The common cause of death in the unresected patients was a metastatic dissemination. Finally, in 3 of the 5 unresected patients, marked effects such as massive fibrosis were seen in the pancreatic tumor on autopsy. (author)

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

Science.gov (United States)

2018-04-27

Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

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Shinoto, Makoto, E-mail: shinoto@saga-himat.jp [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yamada, Shigeru [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Terashima, Kotaro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yasuda, Shigeo [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shioyama, Yoshiyuki [Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Kamada, Tadashi; Tsujii, Hirohiko [Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Saisho, Hiromitsu [Department of Internal Medicine and Clinical Oncology, Kaken Hospital, Chemotherapy Research Institute, Chiba (Japan); Asano, Takehide; Yamaguchi, Taketo; Amano, Hodaka; Ishihara, Takeshi; Otsuka, Masayuki; Matsuda, Masamichi; Kainuma, Osamu; Funakoshi, Akihiro; Furuse, Junji; Nakagori, Toshio; Okusaka, Takuji; and others

2016-05-01

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

Investigation of treatment strategy for advanced cancer according to treatment of pancreatic cancer

Directory of Open Access Journals (Sweden)

XU Kecheng

2013-10-01

Full Text Available The majority of pancreatic cancer diagnoses are made at the advanced stage and when metastasis has already occurred, and the 1- and 5-year survival rates are extremely low. Cemcitabine remains the most frequently applied treatment option, yet the most effective chemotherapeutic agents and combinations with multiple agents and/or radiotherapy only marginally improve patient survival and may even establish an environment conducive to cancer cells with stem cell-like characteristics. An alternative treatment modality, cryoablation, is available and has been applied at our institute to patients with unresectable pancreatic cancer since 2001. In this article, we present our collective experience with patient outcome using cryoablation, alone or combined with other treatment modalities such as brachytherapy (125iodine seed implantation. The overall outcomes have been encouraging, suggesting that comprehensive therapy including cryoablation may prolong the survival of patients with advanced or metastatic pancreatic cancer, and we are achieving particular success with a novel combination of percutaneous cryoablation, cancer microvascular intervention with 125iodine seed implantation, and combined immunotherapy (3C applied using an individualized patient strategy (P. The 1- through 10-year survival rates of 145 patients treated with the so-called “3C+P model” are presented in support of this new strategy as a promising new treatment for advanced and metastatic cancer

Concurrent Chemotherapy and Pulsed High-Intensity Focused Ultrasound Therapy for the Treatment of Unresectable Pancreatic Cancer: Initial Experiences

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Lee, Jae Young; Choi, Byung Ihn; Ryu, Ji Kon; Kim, Yong Tae; Kim, Se Hyung; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of); Hwang, Joo Ha [University of Washington Medical Center, Seattle (United States)

2011-04-15

This study was performed to evaluate the potential clinical value of concurrent chemotherapy and pulsed high intensity focused ultrasound (HIFU) therapy (CCHT), as well as the safety of pulsed HIFU, for the treatment of unresectable pancreatic cancer. Twelve patients were treated with HIFU from October 2008 to May 2010, and three of them underwent CCHT as the main treatment (the CCHT group). The overall survival (OS), the time to tumor progression (TTP), the complications and the current performance status in the CCHT and non-CCHT groups were analyzed. Nine patients in the non-CCHT group were evaluated to determine why CCHT could not be performed more than twice. The OS of the three patients in the CCHT group was 26.0, 21.6 and 10.8 months, respectively, from the time of diagnosis. Two of them were alive at the time of preparing this manuscript with an excellent performance status, and one of them underwent a surgical resection one year after the initiation of CCHT. The TTP of the three patients in the CCHT group was 13.4, 11.5 and 9.9 months, respectively. The median OS and TTP of the non-CCHT group were 10.3 months and 4.4 months, respectively. The main reasons why the nine patients of the non-CCHT group failed to undergo CCHT more than twice were as follows: pancreatitis (n = 1), intolerance of the pain during treatment (n = 4), palliative use of HIFU for pain relief (n = 1) and a poor physical condition due to disease progression (n = 3). No major complications were encountered except one case of pancreatitis. This study shows that CCHT is a potentially effective and safe modality for the treatment of unresectable pancreatic cancer

Iodine-125 seed implantation for unresectable pancreatic carcinoma guided by intraoperative ultrasound

International Nuclear Information System (INIS)

Wang Junjie; Xiu Dianrong; Ran Weiqiang; Bai Jing; Zhu Lihong; Liu Jiangping

2005-01-01

Objective: To investigate the surgical technique, efficacy and side effects of 125 I seed interstitial implantation for pancreatic carcinoma. Methods: A total of 22 patients with biopsy proven unresectable adenocarcinoma of pancreas were treated with 125 I implants during laparotomy. Of them 11 patients were treated previously by a combination of bypass surgery. The stent was implanted in 2 cases 2 weeks before and 4 weeks after seed implantation. Seed needles were implanted parallelly to each other, with 1-1.5 cm apart. Mick applicator was being connected to each needle to implant seed. The radioactive activity ranged 0.40-0.70 mCi, the matched peripheral doses were 65-145 Gy. The mean number of 125 I seed was 11-78. Five cases received external beam irradiation with 3D-CRT, the doses were 39-70 Gy and 5 patients received 2 cycle of gemcitabine chemotherapy at 1000 mg/m 2 on dl and d8. Results: Pain was completely relieved in 12 cases, partially relieved in 2 cases, and no response was noted in one case, so the response rate was 93.33%. The median time was 2-3 d. Altogethe 27.27% of the cases died from local recurrence of pancreatic carcinoma and 50% from metastasis. The median survival time in these patients was 6 months, with a 2-year survival rate of 9.09%. The seed immigrated to liver in 3 cases. There were no serious side effects such as infection, pancreatitis, pancreatic fistula, etc. Conclusion: Radioactive seed implantation was safe, high local control, minidamage, satisfactory palliation of pain and without significant complications. (authors)

Effect of pretreatment psoas muscle mass on survival for patients with unresectable pancreatic cancer undergoing systemic chemotherapy.

Science.gov (United States)

Ishii, Noriko; Iwata, Yoshinori; Nishikawa, Hiroki; Enomoto, Hirayuki; Aizawa, Nobuhiro; Ishii, Akio; Miyamoto, Yuho; Yuri, Yukihisa; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Takata, Ryo; Iijima, Hiroko; Nishiguchi, Shuhei

2017-11-01

To the best of our knowledge, there are few previous studies that have investigated the effect of decreased skeletal muscle mass (DSMM) on survival in patients with unresectable advanced pancreatic cancer (APC) who are undergoing systemic chemotherapy. Thus, the present study aimed to investigate the impact of DSMM, as determined by the psoas muscle index (PMI) following computed tomography and prior to systemic chemotherapy, on the outcomes of patients with unresectable APC (n=61). The primary endpoint used was the overall survival (OS) rate. The OS rates in the PMI-High group (exceeds the median PMI value in each gender) were retrospectively compared with those in the PMI-Low group (below the median PMI value in each gender), and factors associated with OS were investigated using univariate and multivariate analyses. The study cohort included 31 male and 30 female patients with a median age of 72 years, 13 of whom were stage IVA, and 48 were stage IVB. The median PMI in males was 4.3 cm 2 /m 2 (range, 1.6-8.2 cm 2 /m 2 ), while that in females was 2.3 cm 2 /m 2 (range, 0.7-6.1 cm 2 /m 2 ). The proportion of patients with performance status 0 in the PMI-High group was significantly high, compared with that in the PMI-Low group [83.3% (25/30) vs. 58.1% (18/31); P=0.0486]. Body mass index in the PMI-High group was significantly higher compared with that in the PMI-Low group (P=0.0154). The 1-year cumulative survival rate was 43.3% in the PMI-High group and 12.9% in the PMI-Low group (P=0.0027). Following multivariate analysis, PMI (P=0.0036), prothrombin time (P=0.0044) and carbohydrate antigen 19-9 (P=0.0451) were identified to be significant predictors of OS. In conclusion, DSMM, as determined by the PMI, could be a significant predictor of prognosis in patients with unresectable APC who are receiving systemic chemotherapy.

Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

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Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center, Tokyo (Japan); Hirokawa, Naoki [Department of Radiology, Sapporo Medical University, Sapporo (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto (Japan); Kokubo, Masaki [Department of Radiation Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe (Japan); Ogo, Etsuyo [Department of Radiation Oncology, Kurume University, Kurume (Japan); Shibuya, Hitoshi [Department of Radiology, Tokyo Medical and Dental University, Tokyo (Japan); Saito, Tsutomu [Department of Radiation Oncology, Nihon University Itabashi Hospital, Tokyo (Japan); Onishi, Hiroshi [Department of Radiology, Yamanashi University, Yamanashi (Japan); Karasawa, Katsuyuki [Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University, Yamagata (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University School of Medicine, Osaka (Japan)

2012-06-01

Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

Intraoperative radio-frequency capacitive hyperthermia and radiation therapy for unresectable pancreatic cancer

International Nuclear Information System (INIS)

Nakazawa, M.; Yamashita, T.; Hashida, I.

1988-01-01

The authors have initiated intraoperative radiation therapy (IORT) and intraoperative radio-frequency capacitive hyperthermia (IOHT) for unresectable pancreatic cancer. After gastric (corpus) resection, IORT and IOHT were conducted and gastro-duodenostomy was performed IORT was delivered with 12 meV electron (25 Gy) and 10 MV Linac x-ray (7.5 Gy). IOHT was done with 13.56 MHz capacitive equipment aiming 43 0 C for over 30 min along with concurrent administration of 500 mg 5-FU. Five cases were heated by the conventional method and two additional cases were heated with a newly fabricated applicator. Attained temperatures monitored directly from tumor were 38.5 0 C-44.3 0 C (over 43 0 C in four cases, 40 0 C in one case, and below 40 0 C in two cass.) Pain relief was achieved in most cases. Using the new applicators, the authors could avoid unexpected hot spots and insufficient heating

Clinical efficacy of CT-guided 125I seed implantation therapy for advanced pancreatic cancer

International Nuclear Information System (INIS)

Wang Zhongmin; Lu Jian; Gong Ju; Zheng Yunfeng; Zhang Liyun; Huang Gang; Chen Kemin

2009-01-01

Objective: To discuss the clinical efficacy of CT-guided radioactive 125 I seed implantation treatment for unresectable pancreatic cancer. Methods: Forty patients with inoperable pancreatic cancer were enrolled in this study, including 25 males and 15 females with an median age of 69 years (38-89 years). Treatment planning system (TPS) was used to reconstruct 3-dimensional images of pancreatic tumor and to define the quantity and distribution of 125 I seeds. The radioactivity of 125 I seeds was 0.5 - 0.8 mCi / seed. The seeds were implanted into pancreatic tumor under CT guidance at intervals of 1 cm and were kept away from vessels, pancreatic duct and other adjacent important organs. The tumor matched peripheral dose (MPD) was 60-140 Gy. The median amount of implanted 125 I seeds was 36 (18-68) in number. CT scan was performed immediately after the procedure to check the quality of the seeds. In addition, 10 patients received concurrent chemotherapy with arterial infusion of gemcitabin and 5-fluororacil (5-Fu) for 3 to 4 therapeutic courses. Results: The median diameter of the tumors was 4.9 cm. The follow-up period was 2 to 28 months. After the treatment the refractory pain was significantly relieved (P 125 I seed implantation is a safe, effective and minimally-invasive brachytherapy for unresectable pancreatic cancer with reliable short-term efficacy. It has an excellent anti-pain effect. The curative results can be further improved when chemotherapy is employed together. However, its long-term efficacy needs to be observed. (authors)

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

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Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

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Alireza Tavassoli

2013-08-01

Full Text Available Introduction : Severepain is a major problem in patients with unresectable pancreatic cancer. The goal of this study is to evaluate the effects of Thoracoscopic Splanchnicectomy (TS on pain control in these patients suffering from unresectable pancreatic cancer. Methods:Between years 2000 to 2011, 20 patients suffering from unresectable pancreatic cancer underwent TS due to severe pain. They were studied in terms of age, sex, location of pancreas tumor, history of previous surgery, response to treatments for pain control (assessed with VAS scoring system and complications of surgery. Results:M/F = 14/6 with a mean age of 63 years. The most common tumour site was at the pancreas head (in 8 patients. The most cause of unresectability was local expansion to critical adjacent elements (in 10 patients. Surgery was performed successfully in all patients. Post-operative complication included only pleural effusion on the left side which was cured by proper treatment. There were no post-op mortalities.  15 patients had acceptable levels of pain at the end of a six month follow-up period. ConclusionTS provides good pain control, little side effects and minimal invasiveness, the technique is recommended for pain control in patients with unresectable pancreatic cancer.

Icotinib plus gemcitabine for metastatic pancreatic cancer: a case report.

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Zhao, Jing; Shen, Hong; Hu, Han-Guang; Huang, Jian-Jin

2015-03-21

A large majority of patients diagnosed with pancreatic cancer have advanced metastatic disease with unresectable malignancies. Despite treatment advances, the survival benefit from chemotherapeutic regimens and targeted drugs is limited. Moreover, their application is limited in China because of high toxicity and cost. Recently, inhibitors of epidermal growth factor receptor activity have shown promise for the treatment of solid cancers when used in combination with standard therapy. However, these drugs have not been evaluated extensively for the treatment of pancreatic cancer. Here, we report the treatment of a 64-year-old male with metastatic pancreatic cancer using a novel regimen of icotinib with gemcitabine. Marked shrinkage of the mass was observed after two treatment cycles, and partial remission was achieved. The abdominal pain was relieved. The adverse effects were tolerable and treatment cost was acceptable. This is the first reported case for the treatment of advanced pancreatic cancer with icotinib plus gemcitabine and demonstrates a promising therapeutic alternative.

Safety and efficacy of enzyme targeting intraoperative radiosensitization therapy (KORTUC-IORT) for advanced pancreatic cancer

International Nuclear Information System (INIS)

Nishioka, Akihito; Hamada, Norihiko; Kariya, Shinji; Ogawa, Yasuhiro

2012-01-01

We developed a new radiosensitizer injection containing hydrogen peroxide and sodium hyaluronate just followed by intraoperative radiotherapy (IORT) for locally advanced pancreatic cancer, named KORTUC-IORT (Kochi Oxydol-Radiation Therapy for Unresectable Carcinoma + IORT). Fourteen patients were treated with KORTUC-IORT, external beam radiotherapy (EBRT), and systemic chemotherapy. With KORTUC-IORT, the agent containing hydrogen peroxide and sodium hyaluronate, was injected into tumor tissue just prior to administration of IORT under ultrasonic guidance. All treatments related with KORTUC-IORT were well tolerated, with few adverse effects. One year survival rate is 67% and median survival period is 15 months. The present formulation can be delivered safely and effectively under the conditions used. (author)

Intraoperative radiation therapy for patients with pancreatic carcinoma

International Nuclear Information System (INIS)

Abe, Tetsuo; Itoh, Kei; Agawa, Senichiro; Ishihara, Yukio; Konishi, Toshiro

2001-01-01

We studied the efficacy and complications of intraoperative radiation therapy (IORT) in 40 subjects with unresected pancreatic carcinoma (Group A) and 8 with resected pancreatic carcinoma (Group B). These 2 groups were compared to groups not treated by IORT; 59 subjects with unresected pancreatic carcinoma (Group C) and 55 with resected pancreatic carcinoma (Group D). The 6-month survival in Group A was 55%, and 1-year survival 26% compared to 20% 6-month survival and 9% 1-year survival in Group C with a median survival of 7 months in Group A and 4 months in group C; all statistically significant. Pain control was 81.8% in Group A, reduction in tumor size was 50% and reduction of tumor marker, CA19-9 was 56.3% in Group A. Survival in Groups B and D did not differ significantly. The histological efficacy of IORT in Group A was confirmed in autopsy of fibrosis and scar formation in radiation fields of the pancreas. Two patients in Group B had major morbidity leading to death; 1 from leakage in the pancreatojejunal anastomosis accompanied by pancreatic necrosis and the other from duodenal perforation with rupture of the portal vein and hepatic artery. This study demonstrates the efficacy of IORT in patients with unresected pancreatic carcinoma. Prophylactic bypass and shielding of the residual pancreas with lead or reducing the IORT or external beam radiation therapy (EBRT) dose should be considered in patients with unresected or resected pancreatic carcinoma, however, to prevent serious complications due to radiation injury of the duodenum and pancreas. (author)

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

International Nuclear Information System (INIS)

Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

2013-01-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

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Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

Radiotherapy Technical Considerations in the Management of Locally Advanced Pancreatic Cancer: American-French Consensus Recommendations

International Nuclear Information System (INIS)

Huguet, Florence; Goodman, Karyn A.; Azria, David; Racadot, Severine; Abrams, Ross A.

2012-01-01

Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose

Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations.

Science.gov (United States)

Huguet, Florence; Goodman, Karyn A; Azria, David; Racadot, Severine; Abrams, Ross A

2012-08-01

Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity

Intraoperative ultrasound quided iodine-125 seed implantation for unresectable pancreatic carcinoma

International Nuclear Information System (INIS)

Wang Junjie; Liu Jiangping; Jiang Yuliang; Jiang Weijuan; Li Jinna; Xiu Dianrong; Ran Weiqiang

2007-01-01

Objective: To investigate the surgical technique, efficacy and side effects of intraoperative ultrasound quided 125 I seed interstitial implantation for pancreatic carcinoma. Methods: Twenty-seven patients with biopsy proven unresectable adenocarcinoma of pancreas were treated with 125 I implants during laparotomy. Eleven patients were treated by a combination of bypass surgery. Seed needles were implanted parallel to each other, at 1.0-1.5 cm apart and guided by ultrasound. Mick applicator was applied to each needle to implant seed at 1.0-1.5 cm apart. The radioactive activity ranged 0.40-0.70 mCi; the D 90 were 110-160 Gy. The mean number of 125 I seed were 11-78. Six patients also received external beam radiation at doses of 39-50 Gy. Five patients received 2-4 cycle DDP + gemCitabine chemotherapy also. Results: The incidence of perioperative mortality was 0%. Pain was complete relieved in 15 patients, partial relieved in two, but in the rest three patients there was no response. The response rate was 85%. The starting time of pain relief was 1-30 d, with a median of 5 days. The overall local control rate was 74%. Four patients have died of recurrence, 20 patients died of metastasis, 3 patients died of recurrence and metastasis. The median survival of II + III[ stage patients was 8 months, with a 1- and 2-year survival of 25% and 15%, respectively. The median survival time of IV stage patients was 5 months, with 1-year survival of 8%. The seeds immigrated into the liver in 3 patients. There are no serious side effects such as infection or pancreatic fistula. Conclusions: Intraoperative ultrasound quided 125 I seed implantation is safe, giving high local control, but minimal damage. It is a satisfactorily palliative for pain and causing little noticeable complications. (authors)

Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

Science.gov (United States)

Noronha, M; Dreiling, D A; Bordalo, O

1983-11-01

A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer

NARCIS (Netherlands)

Klompmaker, S.; de Rooij, T.; Korteweg, J. J.; van Dieren, S.; van Lienden, K. P.; van Gulik, T. M.; Busch, O. R.; Besselink, M. G.

2016-01-01

Pancreatic cancer involving the coeliac axis is considered unresectable by most guidelines, with a median survival of 6-11 months. A subgroup of these patients can undergo distal pancreatectomy with coeliac axis resection, but consensus on the value of this procedure is lacking. The evidence for

Palliative surgery for pancreatic carcinoma

International Nuclear Information System (INIS)

Khan, I.M.; Aurangzeb, M.

2010-01-01

To evaluate the role of palliative surgical treatment in patients with advanced pancreatic carcinoma. Study Design: Case series. Place and Duration of Study: Surgical Ward of Khyber Teaching Hospital, Peshawar, from January 2005 to January 2009. Methodology: The study included patients with pancreatic carcinoma admitted with advanced, unresectable carcinoma of the pancreas. Patients with resectable tumours and with previous history of gastric or biliary surgery were excluded. Palliative procedures were performed after assessment of the tumour and its confirmation as unresectable on ultrasound and CT scan + ERCP. Postoperatively all patients were referred to oncologist. Complications and mortality were noted. Results: There were 40 patients, including 24 males and 16 females with mean age 58.72 +- 6.42 years. The most common procedure performed was triple bypass in 21 (52.50%) patients followed by choledocho-, cholecysto-, hepaticoand gastro-jejunostomy in various combinations. Wound infection occurred in 7 patients and was more common in patients with co-morbidities. Biliary leakage occurred in 03 patients. Postoperative cholangitis occurred in 3 patients while 7 patients had minor leak from the drain site. Four patients developed UTI, while 5 patients had signs of delayed gastric emptying. Two patients had upper gastrointestinal bleeding. Three patients died due to septicemia and multiple organs failure. Rest of the patients were discharged in stable state. The mean hospital stay was 8.40 +- 3.48 days and median survival was 7.72 +- 2.39 months. Conclusion: Surgical palliation for the advanced carcinoma pancreas can improve the quality of life of patients and is associated with minimum morbidity and mortality. (author)

Irreversible electroporation of locally advanced solid pseudopapillary carcinoma of the pancreas: A case report

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Luciano Tarantino

2018-04-01

Full Text Available Introduction: Solid pseudopapillary Carcinoma (SPC is a rare pancreatic Tumor with variable, usually low, malignancy potential. Howewer, several SPC are associated with aggressive behavior, local vascular infiltration, organ invasion, distant metastasis, and can be unresectable. Irreversible Electroporation (IRE is an emerging non-thermal ablation technique for the treatment of locally advanced pancreatic carcinoma. We report the results of four year disease-free follow-up in a case of locally advanced unresectable SPC treated with IRE. Presentation of case: A 24-year female patient with SPC of the pancreas underwent IRE during laparotomy under general anesthesia with intubation. Computed Tomography (CT showed complete tumor thrombosis of splenic vein, encasement of celiac artery and mesenteric vein. Six insertions of 3–4 electrodes per insertion were performed. One month-CT-control showed shrinkage of the tumor. 6 months-post-treatment imaging showed complete regression of the mass, patent Splenic/mesenteric veins, absence of local recurrence or distant metastasis. Post treatment CTs at 12-18-24-30-36-42-48 months follow-up confirmed absence of local or distant recurrence. Discussion: Surgery is the first choice curative treatment of SPC. Howewer aggressive surgery (duodeno-pancreasectomy in unresectable cases, may have a high risk of recurrences, morbidities and death, and bring concerns about endocrine and exocrine insufficiency in a young patient. In these cases, IRE could be a safe and effective alternative treatment and could realize, in selected cases, the condition for a radical surgery, and a bridge to R-0 resection. Conclusions: IRE could represent an effective alternative therapy to surgery in local advanced, unresectable SPC. Keywords: Pancreatic neoplasm, Solid papillary carcinoma, Intraoperative ultrasound, Irreversible electroporation, Case report

Endoscopic Palliation for Pancreatic Cancer

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Mihir Bakhru

2011-04-01

Full Text Available Pancreatic cancer is devastating due to its poor prognosis. Patients require a multidisciplinary approach to guide available options, mostly palliative because of advanced disease at presentation. Palliation including relief of biliary obstruction, gastric outlet obstruction, and cancer-related pain has become the focus in patients whose cancer is determined to be unresectable. Endoscopic stenting for biliary obstruction is an option for drainage to avoid the complications including jaundice, pruritus, infection, liver dysfunction and eventually failure. Enteral stents can relieve gastric obstruction and allow patients to resume oral intake. Pain is difficult to treat in cancer patients and endoscopic procedures such as pancreatic stenting and celiac plexus neurolysis can provide relief. The objective of endoscopic palliation is to primarily address symptoms as well improve quality of life.

Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Morak, Marjolein J.M.; Richel, Dick J.; Eijck, Casper H.J. van; Nuyttens, Joost J.M.E.; Gaast, Ate van der; Vervenne, Walter L.; Padmos, Esther E.; Schaake, Eva E.; Busch, Olivier R.C.; Tienhoven, Geertjan van

2011-01-01

Background and purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. Material and methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 x 2.5 Gy radiotherapy combined with UFT 300 mg/m 2 per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

Analysis of the clinical benefit of 5-fluorouracil and radiation treatment in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Fisher, Barbara J.; Perera, Francisco E.; Kocha, Walter; Tomiak, Anna; Taylor, Marianne; Vincent, Mark; Bauman, Glenn S.

1999-01-01

Purpose: To assess the palliative benefit of 5-fluorouracil (5-FU) and radiotherapy in patients with surgically unresectable localized pancreatic cancer. Methods and Materials: Twenty-five patients with locally advanced surgically unresectable symptomatic pancreatic cancer received 5-FU chemotherapy and local radiation therapy. They were retrospectively reviewed in regard to their clinical benefit response (a composite of measurement of pain assessment, weight, and Karnofsky performance status [KPS]), as well as radiological response, time to progression, and overall survival. Results: Median survival for the 25 patients was 9 months and median progression-free survival was 6 months. Thirty-two percent of patients survived in excess of 1 year. Analgesic requirements increased >50% in 2 patients and KPS deteriorated in 10 patients. Of the 13 remaining patients, 2 sustained a >7% weight loss and 2 gained weight post-treatment. Six patients improved in one parameter of analgesic consumption, weight loss or KPS without deteriorating in any others. Thus, the clinical benefit response index for 5-FU-radiation was 6/25 (24%). In terms of tumor response, 8 patients (44%) demonstrated a reduction in tumor volume post-treatment, 4 of whom (22%) experienced a >50% reduction. Four additional patients had radiologically stable disease. Conclusion: In this retrospective analysis, the clinical benefit response index for 5-FU-radiation was 24%, a value similar to the 23.8% reported for single agent gemcitabine. The median survival of 7 months was also similar to the 5.65 months reported for gemcitabine. The radiological partial response rate of 22% and the 1-year survival of 32% were higher for 5-FU-radiation than the reported values for gemcitabine. A randomized trial would be necessary to compare 5-FU-radiation to gemcitabine directly; however, from this review it did not appear that the overall palliative benefit of 5-FU-radiation was inferior to gemcitabine

Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

Science.gov (United States)

Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

2018-03-01

Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

Alcohol and the pancreas. II. Pancreatic morphology of advanced alcoholic pancreatitis.

Science.gov (United States)

Noronha, M; Bordalo, O; Dreiling, D A

1981-08-01

The histopathology of advanced chronic alcoholic pancreatitis is dominated by cellular degeneration, atrophy and fibrosis. Sequential changes in the histopathology of alcoholic pancreatic disease has been defined and traced from initial injury to end-stage disease. These sequential histopathologies have been correlated with clinical syndrome and secretory patterns. The data are more consistent with a toxic-metabolic pathogenesis of alcoholic pancreatitis than the previous Big Duct and Small Duct hypotheses.

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Esnaola, Nestor F.; Chaudhary, Uzair B.; O'Brien, Paul; Garrett-Mayer, Elizabeth; Camp, E. Ramsay; Thomas, Melanie B.; Cole, David J.; Montero, Alberto J.; Hoffman, Brenda J.; Romagnuolo, Joseph; Orwat, Kelly P.; Marshall, David T.

2014-01-01

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved

Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

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Esnaola, Nestor F. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Chaudhary, Uzair B.; O' Brien, Paul [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Garrett-Mayer, Elizabeth [Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Camp, E. Ramsay [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Thomas, Melanie B. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Cole, David J. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Montero, Alberto J. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Hoffman, Brenda J.; Romagnuolo, Joseph [Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Orwat, Kelly P. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States)

2014-03-15

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

Science.gov (United States)

2013-06-03

Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Carcinoma of the pancreas: results of irradiation for unresectable lesions

International Nuclear Information System (INIS)

Komaki, R.; Wilson, J.F.; Cox, J.D.; Kline, R.W.

1980-01-01

From 1973 to 1977, 20 patients who had histologically proven unresectable adenocarcinoma of the pancreas with no distant metastases were irradiated at the Medical College of Wisconsin Affiliated Hospitals. The patients received megavoltage external irradiation to minimum tumor doses ranging between 3000 rad in 4 weeks and 5700 rad in 7 weeks (median 4600 rad in 6 weeks); their actuarial survival was 54% at 12 months and 21% at 24 months. Fourteen patients who received 4500 rad or more in 6 to 7 weeks had a median survival of 13 months. Six patients received less than 4500 rad in 3 to 6 weeks, and their median survival was 7 months. At this writing, three patients are alive and apparently disease free more than 2 years after treatment. Complications were seen in two patients. One died from GI bleeding 2 months after completion of radiation therapy, and the other patient developed pancreatic insufficiency. These results and recent reports in the literature show that aggressive irradiation can result in long-term disease free survival in a small proportion of patients with unresectable pancreatic adenocarcinoma. Further exploitation of this approach alone or combined with chemotherapy is warranted

Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma

International Nuclear Information System (INIS)

Lind, Pehr A.; Bystroem, Per; Isaksson, Bengt; Almstroem, Markus; Permert, Johan; Johnsson, Anders; Albiin, Nils

2008-01-01

Background. The optimal care for patients with unresectable, non-metastatic pancreatic adenocarcinoma (PAC) is debated. We treated 17 consecutive cases with preoperative radiochemotherapy (RCT) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods. The patients had biopsy proven, unresectable, non-metastatic PAC which engaged ≥ 50% of the circumference of a patent mesenteric/portal vein for a distance ≥ 2 cm and/or 2 d1; capecitabine 2 000 mg/m 2 d1-14 q 3 w) followed by 3-D conformal radiotherapy (50.4 Gy; 1.8 Gy fractions) with reduced Xelox (d1-5 q 1 w X 6). Results. No incident of RCT-related CTC Grade 3-4 haematologic and six cases of non-haematologic side-effects were diagnosed. Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post-RCT. Five cases were diagnosed with new metastases to the liver. Eleven patients were accepted for surgery whereof eight underwent a curative R 0 -resection. The median overall survival for the latter group was 29 months, which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC (median OS: 16 months; RO-rate: 75%). Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer (576 vs. 477 min) and the op blood loss was greater (3288 vs. 1460 ml) in the RCT-cohort (p < 0.05). The 30-day mortality was zero in both groups. Conclusion. Preoperative RCT in patients with locally advanced PAC resulted in a high rate of curative resections and promising median survival in our treatment series. This trimodality approach merits further exploration in new studies, which are currently underway at our Dept

Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

LENUS (Irish Health Repository)

Teo, Minyuen

2013-03-01

A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer.

Science.gov (United States)

Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M

2012-12-01

Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

A current perspective on stereotactic body radiation therapy for pancreatic cancer.

Science.gov (United States)

Hong, Julian C; Czito, Brian G; Willett, Christopher G; Palta, Manisha

2016-01-01

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

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Robertson, John M., E-mail: jrobertson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Jury, Robert P. [Department of Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Hardy-Carlson, Maria [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX (United States); Marvin, Kimberly S.; Wallace, Michelle; Ye Hong [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

2012-02-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

International Nuclear Information System (INIS)

Robertson, John M.; Margolis, Jeffrey; Jury, Robert P.; Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura; Hardy-Carlson, Maria; Marvin, Kimberly S.; Wallace, Michelle; Ye Hong

2012-01-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0–2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m 2 ) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Extended Distal Pancreatectomy with En Bloc Resection of the Celiac Axis for Locally Advanced Pancreatic Cancer: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Patrick H. Alizai

2012-01-01

Full Text Available Due to a lack of early symptoms, pancreatic cancers of the body and tail are discovered mostly at advanced stages. These locally advanced cancers often involve the celiac axis or the common hepatic artery and are therefore declared unresectable. The extended distal pancreatectomy with en bloc resection of the celiac artery may offer a chance of complete resection. We present the case of a 48-year-old female with pancreatic body cancer invading the celiac axis. The patient underwent laparoscopy to exclude hepatic and peritoneal metastasis. Subsequently, a selective embolization of the common hepatic artery was performed to enlarge arterial flow to the hepatobiliary system and the stomach via the pancreatoduodenal arcades from the superior mesenteric artery. Fifteen days after embolization, the extended distal pancreatectomy with splenectomy and en bloc resection of the celiac axis was carried out. The postoperative course was uneventful, and complete tumor resection was achieved. This case report and a review of the literature show the feasibility and safety of the extended distal pancreatectomy with en bloc resection of the celiac axis. A preoperative embolization of the celiac axis may avoid ischemia-related complications of the stomach or the liver.

Therapeutic management of locally unresectable pancreatic cancer

International Nuclear Information System (INIS)

Lombard-Bohas, C.; Saurin, J.C.; Mornex, F.

1997-01-01

Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10 % of patients can undergo surgery with an overall 5-year survival rate of less than 2 %. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used. (author)

Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Directory of Open Access Journals (Sweden)

Bin Li

2015-01-01

Full Text Available Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited. Complementary and alternative medicines represent exciting adjunctive therapies. In this study, we ascertained the beneficial and adverse effects of Chinese herbal medicine (CHM in combination with conventional therapy for inoperable pancreatic cancer by using meta-analysis methods for controlled clinical trials. We extracted data for studies searched from six electronic databases that were searched and also assessed the methodological quality of the included studies. We evaluated the following outcome measures: 6-month and 1-year survival rate, objective response rate, disease control rate, quality of life, and adverse effects. The final analysis showed CHM is a promising strategy as an adjunctive therapy to treat advanced or inoperable pancreatic cancer and that CHM in combination with conventional therapy is a promising strategy for resistant disease. However, convincing evidence must be obtained and confirmed by high-quality trials in future studies.

Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors

Science.gov (United States)

2017-07-15

Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Pancreatic Adenocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Gallbladder Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pancreatic Cancer; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Cancer

Safety and Efficacy of Radiofrequency Ablation in the Management of Unresectable Bile Duct and Pancreatic Cancer: A Novel Palliation Technique

Directory of Open Access Journals (Sweden)

Paola Figueroa-Barojas

2013-01-01

Full Text Available Objectives. Radiofrequency ablation (RFA has replaced photodynamic therapy for premalignant and malignant lesions of the esophagus. However, there is limited experience in the bile duct. The objective of this pilot study was to assess the safety and efficacy of RFA in malignant biliary strictures. Methods: Twenty patients with unresectable malignant biliary strictures underwent RFA with stenting between June 2010 and July 2012. Diameters of the stricture before and after RFA, immediate and 30 day complications and stent patency were recorded prospectively. Results. A total of 25 strictures were treated. Mean stricture length treated was 15.2 mm (SD = 8.7 mm, Range = 3.5–33 mm. Mean stricture diameter before RFA was 1.7 mm (SD = 0.9 mm, Range = 0.5–3.4 mm while the mean diameter after RFA was 5.2 mm (SD = 2 mm, Range = 2.6–9 mm. There was a significant increase of 3.5 mm (t = 10.8, DF = 24, P value = <.0001 in the bile duct diameter post RFA. Five patients presented with pain after the procedure, but only one developed mild post-ERCP pancreatitis and cholecystitis. Conclusions: Radiofrequency ablation can be a safe palliation option for unresectable malignant biliary strictures. A multicenter randomized controlled trial is required to confirm the long term benefits of RFA and stenting compared to stenting alone.

Concurrent chemoradiotherapy for advanced pancreatic cancer. 1,000 mg/m{sup 2} gemcitabine can be administered using limited-field radiotherapy

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Yamazaki, Hideya [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Radiation Oncology; National Hospital Organization, Osaka National Hospital, Osaka (Japan). Dept. of Radiology; Nishiyama, Kinji; Koizumi, Masahiko; Tanaka, Eiichi [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Radiation Oncology; Ioka, Tatsuya; Uehara, Hiroyuki; Iishi, Hiroyasu; Nakaizumi, Akihiko [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Internal Medicine; Ohigashi, Hiroaki; Ishikawa, Osamu [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Surgery

2007-06-15

Purpose: To examine the feasibility of concurrent use of full-dose gemcitabine (GEM) and radiotherapy for advanced pancreatic cancer. Patient and Methods: 22 patients with advanced pancreatic cancer were subjected to concurrent chemoradiotherapy (GEM 1,000 mg/m2 weekly, three times during 4 weeks). They received limited-field irradiation by three-dimensional radiotherapy planning. Results: Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation and at least three times concurrent administration of 1 g/m{sup 2} GEM). One patient with unresectable tail cancer showed peritonitis carcinomatosa and both chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of GEM was necessary in another four patients. In addition, radiotherapy was discontinued in one patient for fatigue. Grade 3 hematologic toxicity was detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia) in one patient (5%). In total, the response rate amounted to 32% (seven partial responses), and the median survival time (MST) was 16 months. Among the twelve patients who received preoperative chemoradiotherapy, nine underwent surgery and showed a survival rate of 78% at 1 year. Another 13 patients without surgery showed 14 months of MST. No regional lymph node failure has appeared so far. Conclusion: Limited-field radiotherapy enables the safe concurrent administration of 1,000 mg/m{sup 2} GEM.

Computed tomography-guided cryoablation of local recurrence after primary resection of pancreatic adenocarcinoma

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Claudio Pusceddu

2015-06-01

Full Text Available The optimal management of local recurrences after primary resection of pancreatic cancer still remains to be clarified. A 58-yearold woman developed an isolated recurrence of pancreatic cancer six year after distal pancreatectomy. Re-resection was attempted but the lesion was deemed unresectable at surgery. Then chemotherapy was administrated without obtaining a reduction of the tumor size nor an improvement of the patient’s symptoms. Thus the patient underwent percutaneous cryoablation under computed tomography (CT-guidance obtaining tumor necrosis and a significant improvement in the quality of life. A CT scan one month later showed a stable lesion with no contrast enhancement. While the use of percutaneous cryoblation has widened its applications in patients with unresectable pancreatic cancer, it has never been described for the treatment of local pancreatic cancer recurrence after primary resection. Percutaneous cryoablation deserves further studies in the multimodality treatment of local recurrence after primary pancreatic surgery.

Radiology of pancreatic neoplasms: An update.

Science.gov (United States)

de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

2014-09-15

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis.

A current perspective on stereotactic body radiation therapy for pancreatic cancer

Directory of Open Access Journals (Sweden)

Hong JC

2016-10-01

Full Text Available Julian C Hong, Brian G Czito, Christopher G Willett, Manisha Palta Department of Radiation Oncology, Duke University, Durham, NC, USA Abstract: Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT, which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies. Keywords: pancreatic cancer, stereotactic body radiation therapy, SBRT, radiation therapy

Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer

International Nuclear Information System (INIS)

Forero-Torres, Andres; Infante, Jeffrey R; Waterhouse, David; Wong, Lucas; Vickers, Selwyn; Arrowsmith, Edward; He, Aiwu Ruth; Hart, Lowell; Trent, David; Wade, James; Jin, Xiaoping; Wang, Qiang; Austin, TaShara; Rosen, Michael; Beckman, Robert; Roemeling, Reinhard von; Greenberg, Jonathan; Saleh, Mansoor

2013-01-01

Tigatuzumab is the humanized version of the agonistic murine monoclonal antibody TRA-8 that binds to the death receptor 5 and induces apoptosis of human cancer cell lines via the caspase cascade. The combination of tigatuzumab and gemcitabine inhibits tumor growth in murine pancreatic xenografts. This phase 2 trial evaluated the efficacy of tigatuzumab combined with gemcitabine in 62 chemotherapy-naive patients with histologically or cytologically confirmed unresectable or metastatic pancreatic cancer. Patients received intravenous tigatuzumab (8 mg/kg loading dose followed by 3 mg/kg weekly) and gemcitabine (1000 mg/m 2 once weekly for 3 weeks followed by 1 week of rest) until progressive disease (PD) or unacceptable toxicity occurred. The primary end point was progression-free survival (PFS) at 16 weeks. Secondary end points included objective response rate (ORR) (complete responses plus partial responses), duration of response, and overall survival (OS). Safety of the combination was also evaluated. Mean duration of treatment was 18.48 weeks for tigatuzumab and 17.73 weeks for gemcitabine. The PFS rate at 16 weeks was 52.5% (95% confidence interval [CI], 39.3–64.1%). The ORR was 13.1%; 28 (45.9%) patients had stable disease and 14 (23%) patients had PD. Median PFS was 3.9 months (95% CI, 2.2–5.4 months). Median OS was 8.2 months (95% CI, 5.1–9.6 months). The most common adverse events related to tigatuzumab were nausea (35.5%), fatigue (32.3%), and peripheral edema (19.4%). Tigatuzumab combined with gemcitabine was well tolerated and may be clinically active for the treatment of chemotherapy-naive patients with unresectable or metastatic pancreatic cancer

Metallic stents provide better QOL than plastic stents in patients with stricture of unresectable advanced esophageal cancer

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Ohta, Kazuki; Nagahara, Akihito; Iijima, Katsuyori

2006-01-01

The aim of this study was to elucidate the utility and safety of treatment with esophageal stents (plastic and metallic stents) for unresectable advanced esophageal cancer. Between 1992 and 2002, 14 cases of unresectable advanced esophageal cancer were treated with esophageal stents (the plastic stent group, 7 cases; and the metallic stent group, 7 cases). Of these, 10 cases had a history of chemotherapy and or radiotherapy. An improvement in oral intake and performance status (PS), survival time, periods at home, and adverse events were compared between the two groups. After stenting, oral intake and PS were significantly improved in the metallic stent group. Follow-up at home was possible in 71.4%. There was no significant difference in survival or duration of time at home between the two groups. All adverse events were controllable and there was no difference between the two groups. Stenting not only improved oral intake and PS but also allowed a stay at home, resulting in a marked improvement in patients' quality of life (QOL). Stenting was performed safely even in cases with a history of radiotherapy. There was no difference in survival, ratios of staying at home, and safety between the two groups, but QOL was significantly improved in the metallic stent group. These outcomes indicate that placement of metallic stents should be actively considered to treat stricture due to advanced esophageal cancer. (author)

Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

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Chuong, Michael D. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Springett, Gregory M. [Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Freilich, Jessica M.; Park, Catherine K. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Weber, Jill M. [Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Mellon, Eric A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Hodul, Pamela J.; Malafa, Mokenge P.; Meredith, Kenneth L. [Gastrointestinal Tumor Program, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Hoffe, Sarah E. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Shridhar, Ravi, E-mail: ravi.shridhar@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida (United States)

2013-07-01

Purpose: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. Methods and Materials: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%). Conclusions: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer.

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Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Ohno, Izumi; Takahashi, Hideaki; Suzuki, Hidetaka; Irisawa, Ai; Kuwata, Takeshi; Ochiai, Atsushi

2018-05-18

Acyl ghrelin is an orexigenic peptide. Active ghrelin ratio, the ratio of acyl ghrelin to total ghrelin, has an important role in physiological functions and gastrointestinal symptoms. However, low active ghrelin ratio-related characteristics, gastrointestinal symptoms, and chemotherapy-induced gastrointestinal toxicity in patients with advanced pancreatic cancer have not been previously evaluated. The goal of this study was to identify low active ghrelin ratio-related factors in treatment-naïve advanced pancreatic cancer patients. Patients with treatment-naïve advanced pancreatic cancer were eligible for inclusion in this study. Active ghrelin ratio and clinical parameters of patients were prospectively recorded. Factors correlated with low active ghrelin ratio and survival were analyzed. In total, 92 patients were analyzed. Low active ghrelin ratio-related factors were advanced age (P advanced pancreatic cancer.

Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

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Tiago Nunes da Silva

2018-04-01

Full Text Available Non-functional pancreatic neuroendocrine tumours (NETs can present with advanced local or distant (metastatic disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

Computed tomographic appearance of resectable pancreatic carcinoma

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Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

1982-01-01

Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT

Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

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Qingxi Yue

2017-01-01

Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

Everolimus for Advanced Pancreatic Neuroendocrine Tumors.

NARCIS (Netherlands)

Yao, James C.; Shah, Manisha H.; Ito, Tetsuhide; Bohas, Catherine Lombard; Wolin, Edward M.; Van Cutsem, Eric; Hobday, Timothy J.; Okusaka, Takuji; Capdevila, Jaume; de Vries, Elisabeth G. E.; Tomassetti, Paola; Pavel, Marianne E.; Hoosen, Sakina; Haas, Tomas; Lincy, Jeremie; Lebwohl, David; Oberg, Kjell

2011-01-01

Background: Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. Methods: We randomly assigned 410

Three cases of unresectable locally advanced breast cancer treated with local injection of the new radiosensitization (KORTUC)

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Shimbo, Taijyu; Yosikawa, Nobuhiko; Yoshioka, H.; Tanaka, Y.; Yoshida, Ken; Uesugi, Yasuo; Narumi, Yoshifumi; Inomata, Taisuke

2013-01-01

New radiosensitization therapy named Kochi Oxydol-Radiation Therapy for Unresectabe carcinomas (KORTUC) using a new agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate is the world first treatment developed in Japan. The agent was injected into tumor two times per week under ultrasonographic guidance. Unresectable locally advanced breast cancer is radiation resistance. The local control is difficult in a conventional radiation therapy. In 3 cases, KORTUC was enforced safety, and remarkable effects was admitted. (author)

The efficacy discussion of interventional therapy for advanced pancreatic carcinoma

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Song Tian; Yin Shimeng; Sun Rongyue; Shen Lan; Qian Yu

2008-01-01

Objective: To evaluate the efficacy of interventional therapy for advanced pancreatic carcinoma. Methods: 33 cases of advanced pancreatic carcinoma accepted interventional therapy from April 2005 were retrospectively analyzed. All patients were unoperable and accepted one or more times of celiac and superior mesenteric arterial chemotheraputics perfusion with dosage of 2:1. The embolization was further introduced with the addition of liver invasion. The repetition interval was kept at 6 weeks with no severe complications. Results: The one with follow-up CT imagings showed obvious decrease of the lesion size, together with release or disappearance of the sensation of abdominal pain and abdominal distention. The life span prolonged with average survival of 13 months, including the longest of 22 months and the life quality improved. Conclusions: The interventional therapy could be the first method of choice in the management of advanced pancreatic carcinoma. (authors)

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

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Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

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Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R.; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M.; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M.

2012-01-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥1500/mm 3 , platelets ≥100,000/mm 3 , creatinine 2 /100 min intravenously) was given on days −22 and −15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥3, neutropenic fever, or deterioration in performance status to ≥3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

Recent Advances in Pancreatic Cancer Surgery of Relevance to the Practicing Pathologist

NARCIS (Netherlands)

van Rijssen, Lennart B.; Rombouts, Steffi J. E.; Walma, Marieke S.; Vogel, Jantien A.; Tol, Johanna A.; Molenaar, Isaac Q.; van Eijck, Casper H. J.; Verheij, Joanne; van de Vijver, Marc J.; Busch, Olivier R. C.; Besselink, Marc G. H.

2016-01-01

Recent advances in pancreatic surgery have the potential to improve outcomes for patients with pancreatic cancer. We address 3 new, trending topics in pancreatic surgery that are of relevance to the pathologist. First, increasing awareness of the prognostic impact of intraoperatively detected

Intraoperative radiotherapy for pancreatic carcinoma

International Nuclear Information System (INIS)

Nishimura, Akira; Iida, Koyo; Sato, Shigehiro; Sakata, Suo

1986-01-01

Twenty-eight patients with pancreatic carcinoma, 23 (82 %) of whom had Stage III or IV, received intraoperative radiotherapy (IOR) with curative or non-curative surgery. Electron beams (10 to 18 MeV) with doses of 20 to 40 Gy were delivered to the tumor. Eight of 26 patients with unresectable tumor had postoperative external irradiation of 10.5 to 50 Gy. Abdominal and back pain relief was achieved after IOR in 12 (71 %) and in 6 (60 %) of the 26 patients, respectively. Appetite was promoted in 11 patients. In the case of unresectable carcinoma, survival time tended to prolong in the 8 patients receiving both IOR and postoperative external irradiation. One patient developed perforation of the colon probably caused by IOR. (Namekawa, K.)

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

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Leung, Henry W. C.; Liu, Chung-Feng; Chan, Agnes L. F.

2016-01-01

Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

Current radiotherapeutic approaches to pancreatic cancer

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Dobelbower, R.R. Jr.

1981-01-01

Adenocarcinoma of the pancreas is not a radioresistant neoplasm, as was once believed. The data now suggest that in some instances this cancer may be radiocurable. This fact seems to justify the risk of pancreatic biopsy even in the face of unresectable disease, for it is well known that many benign conditions imitate pancreatic cancer. Clinical benefit from radiation for pancreatic cancer treatment is dose related. Careful delineation of tumor margins, precision treatment planning, and precision dose delivery can minimize damage to adjacent normal tissues. Interstitial implantation and intraoperative electron beam therapy are being studied as methods of accurate dose delivery for pancreatic cancer. Fractionation studies and high LET studies are in embryonic stages. Combined modality regimens may have much to offer in terms of improved palliation and survival for patients with localized adenocarcinoma of the pancreas

Intra-operative navigation of a 3-dimensional needle localization system for precision of irreversible electroporation needles in locally advanced pancreatic cancer.

Science.gov (United States)

Bond, L; Schulz, B; VanMeter, T; Martin, R C G

2017-02-01

Irreversible electroporation (IRE) uses multiple needles and a series of electrical pulses to create pores in cell membranes and cause cell apoptosis. One of the demands of IRE is the precise needle spacing required. Two-dimensional intraoperative ultrasound (2-D iUS) is currently used to measure inter-needle distances but requires significant expertise. This study evaluates the potential of three-dimensional (3-D) image guidance for placing IRE needles and calculating needle spacing. A prospective clinical evaluation of a 3-D needle localization system (Explorer™) was evaluated in consecutive patients from April 2012 through June 2013 for unresectable pancreatic adenocarcinoma. 3-D reconstructions of patients' anatomy were generated from preoperative CT images, which were aligned to the intraoperative space. Thirty consecutive patients with locally advanced pancreatic cancer were treated with IRE. The needle localization system setup added an average of 6.5 min to each procedure. The 3-D needle localization system increased surgeon confidence and ultimately reduced needle placement time. IRE treatment efficacy is highly dependent on accurate needle spacing. The needle localization system evaluated in this study aims to mitigate these issues by providing the surgeon with additional visualization and data in 3-D. The Explorer™ system provides valuable guidance information and inter-needle distance calculations. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Treatment of pancreatic neuroendocrine tumor with liver metastases

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LI Zhao

2015-05-01

Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

Covered Metal Stenting for Malignant Lower Biliary Stricture with Pancreatic Duct Obstruction: Is Endoscopic Sphincterotomy Needed?

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Kazunari Nakahara

2013-01-01

Full Text Available Aims. To evaluate the need for endoscopic sphincterotomy (EST before covered self-expandable metal stent (CSEMS deployment for malignant lower biliary stricture with pancreatic duct obstruction. Methods. This study included 79 patients who underwent CSEMS deployment for unresectable malignant lower biliary stricture with pancreatic duct obstruction. Treatment outcomes and complications were compared between 38 patients with EST before CSEMS deployment (EST group and 41 without EST (non-EST group. Results. The technical success rates were 100% in both the EST and the non-EST group. The incidence of pancreatitis was 2.6% in the EST, and 2.4% in the non-EST group (. The incidences of overall complications were 18.4% and 14.6%, respectively, (. Within the non-EST groups, the incidence of pancreatitis was 0% in patients with fully covered stent deployment and 3.6% in those with partially covered stent deployment (. In the multivariate analysis, younger age (, OR 12 and nonpancreatic cancer (, OR 24 were significant risk factors for overall complications after CSEMS deployment. EST was not identified as a risk factor. Conclusions. EST did not reduce the incidence of pancreatitis after CSEMS deployment in patients of unresectable distal malignant obstruction with pancreatic duct obstruction.

Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

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Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

2012-01-01

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

SU-E-T-256: Radiation Dose Responses for Chemoradiation Therapy of Pancreatic Cancer: An Analysis of Compiled Clinical Data Using Biophysical Models.

Science.gov (United States)

Moraru, I; Tai, A; Erickson, B; Li, X

2012-06-01

We have analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer in order to examine possible benefits from radiotherapy (RT) dose escalation as well as to propose possible dose escalated fractionation schemes. A modified linear quadratic (LQ) model was used to fit clinical tumor response data from chemoradiation treatments using different fractionations. Biophysical radiosensitivy parameters, a and α/β, tumor potential doubling time, Td, and delay time for tumor doubling during treatment, Tk, were extracted from the fits and were used to calculate feasible fractionation schemes for dose escalations. Examination of published data from 20 institutions showed no clear indication of improved survival with raised radiation dose. However, an enhancement in tumor response was observed for higher irradiation doses, an important and promising clinical Result with respect to palliation and quality of life. The radiobiological parameter estimates obtained from the analysis are: α/β = 10 ± 3 Gy, a = 0.010 ± 0.003 Gŷ-1, Td = 56 ± 5 days and Tk = 7 ± 2 days. Possible dose escalation schemes are proposed based on the calculation of the biologically equivalent dose (BED) required for a 50% tumor response rate. From the point of view of tumor response, escalation of the administered radiation dose leads to a potential clinical benefit, which when combined with normal tissue complication analyses may Result in improved treatments for certain patients with advanced pancreatic cancer. Based on this analysis, a dose escalation trial with 2.25 Gy/fraction up to 69.75 Gy is being initiated for unresectable pancreatic cancer at our institution. Partially supported by MCW Cancer Center Meinerz Foundation. © 2012 American Association of Physicists in Medicine.

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: A phase I-II study

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Brade, Anthony; Brierley, James; Oza, Amit; Gallinger, Steven; Cummings, Bernard; MacLean, Martha; Pond, Gregory R.; Hedley, David; Wong Shun; Townsley, Carol; Brezden-Masley, Christine; Moore, Malcolm

2007-01-01

Purpose: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. Methods and Materials: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m 2 within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m 2 ) and 52.5 Gy RT within 6 weeks. Results: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. Conclusion: Biweekly gemcitabine (40 mg/m 2 ) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer

Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

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Cho, Kwan Ho

2004-01-01

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas

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Medina, Jose Antonio; Rueda, Antonio; Sacchetti de Pasos, Antonio; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asuncion; Alba, Emilio

2006-01-01

Background and purpose: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. Material and methods: A total of 94 patients (median age, 58 years) with UICC stage III (n=19) and IV (n=75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m 2 weekly, for the first 4 weeks. Results: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Conclusions: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

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Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Mathew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Simeone, Diane M.; Sonnenday, Christopher [Department of Surgery, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Khan, Gazala; Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States)

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local

Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

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Pompen, Marjolein; Gok, Murat; Novák, Annoesjka; van Wuijtswinkel, Rob; Biesma, Bonne; Schramel, Franz; Stigt, Jos; Smit, Hans; Postmus, Pieter

2009-04-01

Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on

Management of advanced pancreatic cancer in daily clinical practice.

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Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Three dimensional-conformal radiotherapy combined with capecitabine chemotherapy for locally advanced (unresectable) rectal cancer

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Zhu Yaqun; Tian Ye; Zhang Junning; Wang Bin

2010-01-01

Objective: To evaluate the compliance and efficacy of chemoradiotherapy for locally advanced (unresectable) rectal cancer. Methods: Thirty eight patients with locally advanced (T4 or recurred) rectal cancer received three dimensional-conformal radiotherapy (for 46 ∼ 50Gy/5 weeks and was boosted to the tumor 16 ∼ 18Gy/2 weeks, 2Gy/fraction, 5 days/week) in combination with capecitabine 1 650mg · m -2 · d -1 , day 1-14, every 3 weeks. Results: The overall response rate was 57.9%, with CR 5 (13.2%), PR 17(44.7%), SD 10 (26.3%), PD 6 (15.8%), median survival time, the 1-year overall survival rate and the 2-year overall survival rate were 18 months, 64.43%, 18.78%, respectively. The remission rate of pain and improvement rate of performance status were 100% and 52.8%. Treatment-related toxicity mainly showed at diarrhea, neutrocytopenia and hand-foot syndrome, the incidence of grade 3 toxicity were 15.8%, 15.8%, 7.9%, respectively. there were no grade 4 toxicity and treatment-related death. Conclusion: Combination of three dimensional-conformal radiotherapy with capecitabine is active in advanced rectal cancer, It is a well-tolerated regimen. (authors)

Radiation dose responses for chemoradiation therapy of pancreatic cancer: an analysis of compiled clinical data using biophysical models.

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Moraru, Ion C; Tai, An; Erickson, Beth; Li, X Allen

2014-01-01

We analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer (LAPC) in order to examine possible benefits from radiation therapy dose escalation. A modified linear quadratic model was used to fit clinical tumor response and survival data of chemoradiation treatments for LAPC reported from 20 institutions. Biophysical radiosensitivity parameters were extracted from the fits. Examination of the clinical data demonstrated an enhancement in tumor response with higher irradiation dose, an important clinical result for palliation and quality of life. Little indication of improvement in 1-year survival with increased radiation dose was observed. Possible dose escalation schemes are proposed based on calculations of the biologically effective dose required for a 50% tumor response rate. Based on the evaluation of tumor response data, the escalation of radiation dose presents potential clinical benefits which when combined with normal tissue complication analyses may result in improved treatment outcome for locally advanced pancreatic cancer patients. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Pancreatic adenocarcinoma: combination of MR imaging, MR angiography and MR cholangiopancreatography for the diagnosis and assessment of resectability

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Catalano, C.; Pavone, P.; Laghi, A.; Panebianco, V.; Scipioni, A.; Fanelli, F.; Brillo, R.; Passariello, R.

1998-01-01

The purpose of this study was to determine the possibility of integrating MR cholangiopancreatography (MRCP) and MR angiography (MRA) to conventional MR images in the diagnosis and assessment of resectability of pancreatic adenocarcinoma. Twenty-three patients with pancreatic adenocarcinoma were prospectively examined with MR. Conventional MR images were acquired in all patients. Three-dimensional MRCP and MRA images were acquired in all patients with suspected biliary and vascular involvement. Acquisition time was less than 45 min in all cases. Images were independently evaluated by two radiologists, with final reading decided by consensus among readers. Diagnosis was confirmed with surgery in 16 patients and with percutaneous biopsy in 7. Concordance among readers was high with a kappa value of 0.83. Pancreatic adenocarcinoma was observed in all patients. Correct assessment of unresectability due to vascular involvement was found in 22 of 23 patients. Biliary obstruction was evident in 13 patients, involving the biliary and pancreatic ducts in 9 and the biliary ducts only in 4. Technical advances permit extensive use of MRI in the evaluation of abdominal pathologies. The combination of MR imaging, MRCP, and MRA can provide sufficient information for the diagnosis and assessment of resectability of pancreatic adenocarcinoma, which otherwise would require three different exams. (orig.)

Therapeutic effect of transcatheter arterial infusion chemotherapy in the treatment of advanced pancreatic cancer

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Lin Junhua; Song Mingzhi; Zhang Yuanyuan; Xu Yiyu; Chen Jing

2001-01-01

Objective: To evaluate the clinical efficacy of transcatheter arterial infusion (TAI) or transcatheter arterial chemo-embolization (TACE) in the treatment of advanced pancreatic cancer. Methods: 36 cases of advanced pancreatic cancer were divided into two groups, 18 cases were treated with TAI or TACE (group A), other 18 cases were treated with systemic chemotherapy (group B). Results: The clinical benefit response rate of the group A was 55.6% (10/18) and that of the group B was 16.7%(3/18), respectively (P 0.05). Conclusions: In the transcatheter arterial infusion group, no survival advantage could be demonstrated when compared with the controls, but TAI could effectively increase clinical benefit response and improve the quality of life of advanced pancreatic cancer

Impact of different treatment methods on survival in advanced pancreatic cancer

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Brasiuniene, B.; Juozaityte, E.; Barauskas, G.

2005-01-01

The aim of the study was to evaluate the impact of different treatment methods on survival of patients treated for advanced pancreatic cancer at Kaunas University of Medicine Hospital from 1987 to 2003. Data on 262 patients with advanced pancreatic cancer treated from 1987 to 2003 were analyzed retrospectively. Four groups of patients were analyzed. One hundred eighty patients underwent palliative bypass or endoscopic bile duct stenting or observation alone. Forty three patients in addition to surgery were treated by radiotherapy. Twenty five patients received gemcitabine in standard doses and schedules. Fourteen patients received concomitant chemoradiotherapy (with gemcitabine or 5-fluorouracil). All patients were grouped by treatment method and median survival was analyzed. Median survival of patients treated by palliative surgery only or observation alone was 1.9 month, and for patients treated by palliative surgery and radiotherapy was 6.1 months (p=0.00007). Median survival of patients treated with gemcitabine was 9.5 months (p<0.001), and median survival of patients treated with concomitant chemoradiotherapy was 8.5 months (p=0.00003). Patients diagnosed with advanced pancreatic cancer in addition to surgical treatment should be treated by chemotherapy, concomitant chemoradiotherapy or radiotherapy. (author)

Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

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Kanai, Keita; Maruyama, Masahiro; Kameko, Fumiko; Kawasaki, Kenji; Asano, Junpei; Oguchi, Takaya; Watanabe, Takayuki; Ito, Tetsuya; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Arakura, Norikazu; Kawa, Shigeyuki

2016-09-01

Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection

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Delpero, J.R.; Turrini, O.

2006-01-01

Induction chemoradiotherapy (CRT) may down-stage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a RO resection. Patients and methods. We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neo-adjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. Results. The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The RO resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. Conclusion. Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease

Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey

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Ogawa, Kazuhiko; Ito, Yoshinori; Karasawa, Katsuyuki; Ogawa, Yoshihiro; Onishi, Hiroshi; Kazumoto, Tomoko; Shibuya, Keiko; Shibuya, Hitoshi; Okuno, Yoshishige; Nishino, Shigeo; Ogo, Etsuyo; Uchida, Nobue; Karasawa, Kumiko; Nemoto, Kenji; Nishimura, Yasumasa

2010-01-01

Purpose: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. Methods and Materials: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. Results: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treated with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. Conclusion: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas

International Nuclear Information System (INIS)

Kawakami, Hiroyuki; Uno, Takashi; Isobe, Kouichi; Ueno, Naoyuki; Aruga, Takashi; Sudo, Kentaro; Yamaguchi, Taketo; Saisho, Hiromitsu; Kawata, Tetsuya; Ito, Hisao

2005-01-01

Purpose: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. Materials and Methods: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. Results: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). Conclusions: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects

Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma

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Shi Haifeng; Jin Zhengyu; Yang Ning; Liu Wei; Pan Jie; Cai Lixing; Zhao Yupei; Zhou Zhiqiang

2002-01-01

Objective: To retrospectively analyze the effectiveness of transarterial infusion chemotherapy of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma. Methods: Twenty-two patients with advanced pancreatic carcinoma were treated with transarterial infusion chemotherapy. Gemcitabine and 5-fluorouracil was administered to the patients via an interarterial catheter. Then the tumor response rate and clinical benefit were observed. Results: A clinical benefit was obtained in 8 patients (36.4%). The tumor response rate was 13.6%. Median survival for all the patients was 6.1 months. Median time to tumor progression was 2.9 months. Conclusion: Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil appears to have good clinical benefit and may prolong the survival time of patients with advanced pancreatic carcinoma

Fast neutron irradiation for locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

1981-01-01

Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials

Fast neutron irradiation for locally advanced pancreatic cancer

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Smith, F.P. (Georgetown Univ. Medical Center, Washington, DC); Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

1981-11-01

Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

Defect in assimilation following combined radiation and chemotherapy in patients with locally unresectable pancreatic carcinoma

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Barkin, J.S.; Kalser, M.H.; Thomsen, S.; Redlhammer, D.

1982-01-01

The relative contributions of high-dose irradiation and/or chemotherapy to the nutritional problems of patients with inoperable pancreatic carcinoma were evaluated by study of pancreatic exocrine function and jejunal function and morphologic findings in ten patients before and after treatment. Nutrient assimilation studies included determination of serum carotene levels, D-xylose absorption and fat absorption. Crosby capsule biopsy specimen of jejunal mucosa were evaluated with light microscopy. Fat assimilation was the only parameter of nutritional function to significantly worsen after therapy. Low serum carotene levels present in the patients before therapy remained low but did not significantly change after treatment. D-xylose absorption and the morphologic structure of the jejunal mucosa were normal before and after treatment. These findings support the previous observations that the nutritional problems of the patient with inoperable pancreatic carcinoma are due to pancreatic insufficiency and that high dose irradiation and chemotherapy can exacerbate the pancreatic insufficiency but do not produce jejunal dysfunction. Therefore, it is suggested that pancreatic exocrine replacement therapy may improve the nutritional status of these patients

A Comparison of Helical Intensity-Modulated Radiotherapy, Intensity-Modulated Radiotherapy, and 3D-Conformal Radiation Therapy for Pancreatic Cancer

International Nuclear Information System (INIS)

Poppe, Matthew M.; Narra, Venkat; Yue, Ning J.; Zhou Jinghao; Nelson, Carl; Jabbour, Salma K.

2011-01-01

We assessed dosimetric differences in pancreatic cancer radiotherapy via helical intensity-modulated radiotherapy (HIMRT), linac-based IMRT, and 3D-conformal radiation therapy (3D-CRT) with regard to successful plan acceptance and dose to critical organs. Dosimetric analysis was performed in 16 pancreatic cases that were planned to 54 Gy; both post-pancreaticoduodenectomy (n = 8) and unresected (n = 8) cases were compared. Without volume modification, plans met constraints 75% of the time with HIMRT and IMRT and 13% with 3D-CRT. There was no statistically significantly improvement with HIMRT over conventional IMRT in reducing liver V35, stomach V45, or bowel V45. HIMRT offers improved planning target volume (PTV) dose homogeneity compared with IMRT, averaging a lower maximum dose and higher volume receiving the prescription dose (D100). HIMRT showed an increased mean dose over IMRT to bowel and liver. Both HIMRT and IMRT offer a statistically significant improvement over 3D-CRT in lowering dose to liver, stomach, and bowel. The results were similar for both unresected and resected patients. In pancreatic cancer, HIMRT offers improved dose homogeneity over conventional IMRT and several significant benefits to 3D-CRT. Factors to consider before incorporating IMRT into pancreatic cancer therapy are respiratory motion, dose inhomogeneity, and mean dose.

Clinical experience with intravenous radiosensitizers in unresectable sarcomas

International Nuclear Information System (INIS)

Kinsella, T.J.; Glatstein, E.

1987-01-01

Traditionally, adult bone and soft tissue sarcomas have been considered to be ''radioresistant.'' Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear

Recent Advances in Managing Acute Pancreatitis [version 1; referees: 2 approved

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Nigeen Janisch

2015-12-01

Full Text Available This article will review the recent advances in managing acute pancreatitis. Supportive care has long been the standard of treatment for this disease despite extensive, but ultimately unsuccessful, efforts to develop disease-specific pharmacologic therapies. The primary interventions center on aggressive fluid resuscitation, initiation of early enteral nutrition, targeted antibiotic therapy, and the management of complications. In this article, we will detail treatment of acute pancreatitis with a focus on intravenous fluid resuscitation, enteral feeding, and the current evidence behind the use of antibiotics and other pharmacologic therapies.

CT-guided radioactive 125I-seed implantation for the treatment of pancreatic carcinoma: a clinical observation of 19 cases

International Nuclear Information System (INIS)

Lu Jian; Zheng Yunfeng; Zhang Huan; Wang Zhongmin; Chen Kemin

2010-01-01

Objective: To explore the dynamic changes of serum tumor markers after CT-guided radioactive 125 I-seed implantation treatment in patients with pancreatic carcinoma and to assess the therapeutic effectiveness of 125 I-seed implantation. Methods: CT-guided radioactive 125 I-seed implantation was performed in 19 patients with unresectable advanced pancreatic cancer. Treatment planning system was used to reconstruct 3-dimentional images of the tumor, and the quantity and distribution of 125 I-seeds to be implanted were thus determined. Under CT guidance 125 I-seeds were embedded into pancreatic cancer. Before and after the 125 I-seed implantation the levels of serum tumor markers, including CEA, CA19-9 and CA50, were determined by using radioimmunoassay method. The clinical effects were observed and the therapeutic results were statistically analyzed. Results: The pain stared to be relieved 2 to 5 days after implantation. The total effective rate (CR + PR) at one and three months after treatment was 68.42% (13 /19) and 63.16% (12 /19) respectively. One month after 125 I-seed implantation, the levels of serum CEA, CA19-9 and CA50 were significantly different to that determined before implantation in all cases (P 125 I-seed implantation is a safe and effective interventional treatment for advanced pancreatic cancer with reliable short-term result and remarkable pain-relieving effect. Moreover, this therapy can significantly lower the levels of many serum tumor markers, which play some suggestive roles in evaluating the clinical curativeness. (authors)

Palliative radiotherapy in asymptomatic patients with locally advanced, unresectable, non-small cell lung cancer

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Reinfuss, M.; Skolyszewski, J.; Kowalska, T.; Rzepecki, W.; Kociolek, D.

1993-01-01

Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were referred to short-time, split-course palliative thoracic radiotherapy. The group consisted of patients with locally advanced (III o ), unresectable cancer, not suitable for curative radiotherapy, asymptomatic or having only minimal symptoms related to intrathoracic tumor. The therapeutic plan involved two series of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily fractions over five treatment days. There were four weeks interval between series. Of 332 patients initially qualified to thoracic radiotherapy only 170 patients received the treatment; the other 162 patients were not irradiated because of treatment refusal or logistic problems concerning therapy. They made the control group of the study, receiving the best possible symptomatic care. Twelve-month survivals in the radiotherapy and control groups were 32.4% and 9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of survival after palliative thoracic radiotherapy was observed only in patients with clinical stage IIIA and Karnofsky's performance status (KPS) ≥ 70. (orig.) [de

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Directory of Open Access Journals (Sweden)

Seo Kang

2007-11-01

Full Text Available Abstract Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA and mucin-1 (MUC-1 with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM (PANVAC-V and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F. Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%. Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002. Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.

Chemoradiation of unresectable pancreatic carcinoma: impact of pretreatment hemoglobin level on patterns of failure

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Morganti, A.G.; Macchia, G. [Dept. of Radiation Therapy, Univ. Cattolica del S. Cuore, Campobasso (Italy); Forni, F. [Dept. of Biochemistry and Clinical Biochemistry, Policlinico A. Gemelli, Univ. Cattolica del S. Cuore, Rome (Italy); Valentini, V.; Smaniotto, D.; Trodella, L.; Balducci, M.; Cellini, N. [Dept. of Radiation Therapy, Policlinico A. Gemelli, Univ. Cattolica del S. Cuore, Rome (Italy)

2003-02-01

Aim: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. Patients and Methods: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m{sup 2}/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs cN1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis ({>=} 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs {>=} 40 mm). Results: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb {<=} 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb {<=} 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0.010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb {<=} 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb {<=} 11.5 and > 11.5 g/dl, respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). Conclusion: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed

The first report from Sapporo Tsukisamu Hospital. Chemotherapy and Chemoradiotherapy for patients with advanced pancreatic cancer

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Yamamitsu, Susumu; Kimura, Hiromichi; Yamada, Yoshiyuki; Inui, Noriaki; Hiyama, Shigemi; Hirata, Koichi; Kimura, Yasutoshi; Koito, Kazumitsu; Shirasaka, Tetsuhiko

2007-01-01

The remedy, especially chemotherapy, for advanced pancreatic cancer is hardly ever successful in terms of efficacy rate and survival period, because it is virtually unable to contribute to the improvement of median survival time (MST). Thus, we devised a new intermittent dosage regimen utilizing the cell cycle difference of normal gastrointestinal (GI) tract, bone marrow cell and pancreatic cancer cell, making use of 5-FU (→S-1), cisplatin (CDDP) and paclitaxel in March 2002. Ten patients with advanced pancreatic cancer (4 in Stage IVa and 6 in Stage IVb) were treated with this new regimen. As a result, an efficacy ratio of 50.0% and a 1-year survival ratio of 60.0% were achieved. However, 2-year survival ratio of 12.0% was low, and there was no 3-year survivor. The MST was 19 months as of December 31, 2006. All of the non-hematological toxicities were under grade 2. Eight patients had hematological toxicities over grade 3 and most of them were anemia and neutropenia. Only 2 cases had thrombocytopenia. Although adverse effects related to this regimen were clinically manageable, it was difficult to improve MST of patients with advanced pancreatic cancer with chemotherapy alone including this regimen. Hence, we devised another regimen with the joint use of radiotherapy along with the same chemotherapy regimen in January 2003. Twenty patients with advanced pancreatic cancer (Stage IV) were treated with this regimen. It is presently under way, and an efficacy ratio of 35.0%, 1-year survival ratio of 86.3% and 2-year survival ratio of 64.0% were obtained by May 2005, showing that this may contribute to the extension of survival time of Stage IV pancreatic cancer patients. (author)

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

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Hoyer, Morten; Roed, Henrik; Sengelov, Lisa; Traberg, Anders; Ohlhuis, Lars; Pedersen, Jorgen; Nellemann, Hanne; Kiil Berthelsen, Anne; Eberholst, Frey; Engelholm, Svend Aage; Maase, Hans von der

2005-01-01

Background and purpose: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. Patients and methods: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. Results: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. Conclusions: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma

Therapy of pancreatic cancer

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Takeda, Yutaka; Kitagawa, Toru; Nakamori, Shoji

2009-01-01

Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

Computed tomography findings after radiofrequency ablation in locally advanced pancreatic cancer

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Rombouts, Steffi J. E.; Derksen, Tyche C.; Nio, Chung Y.; van Hillegersberg, Richard; van Santvoort, Hjalmar C.; Walma, Marieke S.; Molenaar, Izaak Q.; van Leeuwen, Maarten S.

2018-01-01

The purpose of the study was to provide a systematic evaluation of the computed tomography(CT) findings after radiofrequency ablation (RFA) in locally advanced pancreatic cancer(LAPC). Eighteen patients with intra-operative RFA-treated LAPC were included in a prospective case series. All CT-scans

Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

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Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

2017-08-07

The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

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Brunner, Thomas B.; Grabenbauer, Gerhard G.; Klein, Peter; Baum, Ulrich; Papadopoulos, Thomas; Bautz, Werner; Hohenberger, Werner; Sauer, Rolf

2003-01-01

Purpose: Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT). We used a time-dependent schedule to determine the maximal-tolerated dose and dose-limiting toxicities (DLTs; Grade 4 hematologic or Grade 3 other toxicity). Methods and Materials: Patients with pancreatic cancer (n=33), periampullary carcinoma (n=1), or bile duct cancer (n=2) were treated with 3-day conformal RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost. Concurrent cisplatin (20 mg/m 2 /d on Days 1-5 and 29-33) and gemcitabine (initially 600 mg/m 2 , weekly on Fridays 68 h before RT) were administered. Because of DLT, the doses were reduced to 500 mg/m 2 weekly and then 500, 400, or 300 mg/m 2 on Days 2, 5, 26, 33. Results: DLT occurred at all dose levels of gemcitabine >300 mg/m 2 . Fourteen patients were treated at the recommended Phase II dose of gemcitabine (300 mg/m 2 ) without DLT. The response to chemoradiation allowed 10 of 30 initially unresectable patients with primary pancreatic carcinoma to undergo radical surgery, including a complete response in 2 cases. Conclusions: At the recommended Phase II dose, chemoradiation with gemcitabine and cisplatin can be administered safely in pancreatic carcinoma. However, at higher dose levels, toxicity is severe and frequent. Patients with a chance for conversion to resection could benefit from this schedule

Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

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Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

2011-01-01

Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

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Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05

Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

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Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

2017-01-01

BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV mal...

Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

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Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

2011-01-01

Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

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Yufeng Zhou

2014-01-01

Full Text Available Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered.

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas

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Thompson, Reid F.; Zhai, Huifang; Both, Stefan; Metz, James M.; Plastaras, John P.; Ben-Josef, Edgar, E-mail: Edgar.Ben-Josef@uphs.upenn.edu [University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Mayekar, Sonal U. [Thomas Jefferson University, Philadelphia, Pennsylvania 19107 (United States); Apisarnthanarax, Smith [University of Washington, Seattle, Washington 98109 (United States)

2014-08-15

Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

International Nuclear Information System (INIS)

Ikeda, Osama; Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

2007-01-01

Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median ± SD, 16.0 ± 3.7 vs. 8.0 ± 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced pancreatic

Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

Directory of Open Access Journals (Sweden)

Jill P Smith

2010-03-01

Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types III and IV hilar cholangiocarcinoma.

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Wang, Yu; Cui, Wei; Fan, Wenzhe; Zhang, Yingqiang; Yao, Wang; Huang, Kunbo; Li, Jiaping

2016-08-16

To assess the feasibility and safety of percutaneous intraductal radiofrequency ablation (RFA) for unresectable Bismuth types III and IV hilar cholangiocarcinoma. Percutaneous intraductal RFA combined with metal stent placement was successful in all patients without any technical problems; the technical success rate was 100%. Chemotherapy was administered to two patients. After treatment, serum direct bilirubin levels were notably decreased. Six patients died during the follow-up period. Median stent patency from the time of the first RFA and survival from the time of diagnosis were 100 days (95% confidence interval (CI), 85-115 days) and 5.3 months (95% CI, 2.5-8.1 months), respectively. No acute pancreatitis, bile duct bleeding and perforation, bile leakage, or other severe complications occurred. Four cases of procedure-related cholangitis, three cases of postoperative abdominal pain, and five cases of asymptomatic transient increase in serum amylase were observed. One patient who presented with stent blockage 252 days' post-procedure underwent repeat ablation. Between September 2013 and May 2015, nine patients with unresectable Bismuth types III and IV hilar cholangiocarcinoma who were treated with percutaneous intraductal RFA combined with metal stent placement after the percutaneous transhepatic cholangial drainage were included in the retrospective analysis. Procedure-related complications, stent patency, and survival after treatment were investigated. Percutaneous intraductal RFA combined with metal stent placement is a technically safe and feasible therapeutic option for the palliative treatment of unresectable Bismuth types III and IV hilar cholangiocarcinoma. Its long-term efficacy and safety is promising, but needs further study via randomized and prospective trials that include a greater number of patients.

The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer.

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Parsons, Henrique A; Baracos, Vickie E; Hong, David S; Abbruzzese, James; Bruera, Eduardo; Kurzrock, Razelle

2016-04-12

Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,pcancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.

Surgical Management of Chronic Pancreatitis.

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Parekh, Dilip; Natarajan, Sathima

2015-10-01

Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

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Fontana E

2014-06-01

Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC

A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

Science.gov (United States)

Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

2010-07-01

Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

Directory of Open Access Journals (Sweden)

Kraft Matthias

2012-07-01

Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

Autoimmune pancreatitis can develop into chronic pancreatitis

Science.gov (United States)

2014-01-01

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

Autoimmune pancreatitis can develop into chronic pancreatitis.

Science.gov (United States)

Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

2014-05-21

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

"Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report".

Science.gov (United States)

Fragulidis, Georgios P; Vezakis, Αntonios; Dellaportas, Dionissios; Sotirova, Ira; Koutoulidis, Vassilis; Kontis, Elliseos; Polydorou, Andreas

2015-01-01

Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessful. A surgical therapy was considered and a longitudinal pancreaticojejunostomy (modified Puestow procedure) in both patients was performed with excellent results. Over the last 30 years, endoscopic procedures are developed to manage pancreatic duct strictures and calculi of the main pancreatic duct in CP patients. In both of our cases endoscopic therapy was first attempted but failed to extract the pancreatic duct stones, due to their size and speculations. Modified Puestow procedure was performed for both and it was successful for long term pain relief. Despite advancement in endoscopic interventions and less invasive therapies for the management of chronic lithiasic pancreatitis we consider that classic surgical management can be appropriate in certain cases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

Science.gov (United States)

Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

2014-11-14

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

Platinum-based chemotherapy with or without thoracic radiation therapy in patients with unresectable thymic carcinoma

International Nuclear Information System (INIS)

Nakamura, Yoichi; Kunitoh, Hideo; Kubota, Kaoru

2000-01-01

Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival. (author)

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A.; Fortpied, C.; Koutsodontis, G.; Avgeris, M.; Kroupis, C.; Goutas, N.; Menis, J.; Herman, L.; Giurgea, L.; Remenar, E.; Degardin, M.; Pateras, I.S.; Langendijk, J.A.; Herpen, C.M.L. van; Awada, A.; Germa-Lluch, J.R.; Kienzer, H.R.; Licitra, L.; Vermorken, J.B.

2017-01-01

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel : a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenar, E; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF over PF, in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable HNSCC. We conducted a retrospective analysis of prospectively collected data aiming to

Acute pancreatitis: recent advances through randomised trials.

Science.gov (United States)

van Dijk, Sven M; Hallensleben, Nora D L; van Santvoort, Hjalmar C; Fockens, Paul; van Goor, Harry; Bruno, Marco J; Besselink, Marc G

2017-11-01

Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Associations between ABO blood groups and pancreatic ductal adenocarcinoma: influence on resection status and survival.

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El Jellas, Khadija; Hoem, Dag; Hagen, Kristin G; Kalvenes, May Britt; Aziz, Sura; Steine, Solrun J; Immervoll, Heike; Johansson, Stefan; Molven, Anders

2017-07-01

Both serology-based and genetic studies have reported an association between pancreatic cancer risk and ABO blood groups. We have investigated this relationship in a cohort of pancreatic cancer patients from Western Norway (n = 237) and two control materials (healthy blood donors, n = 379; unselected hospitalized patients, n = 6149). When comparing patient and blood donor ABO allele frequencies, we found only the A 1 allele to be associated with significantly higher risk for pancreatic ductal adenocarcinoma (PDAC) (23.8% vs. 17.9%; OR = 1.43, P = 0.018). Analyzing phenotypes, blood group A was more frequent among PDAC cases than blood donors (50.8% vs. 40.6%; OR = 1.51, P = 0.021), an enrichment fully explained by the A 1 subgroup. Blood group O frequency was lower in cases than in blood donors (33.8% vs. 42.7%; OR = 0.69, P = 0.039). This lower frequency was confirmed when cases were compared to hospitalized patients (33.8% vs. 42.9%; OR = 0.68, P = 0.012). Results for blood group B varied according to which control cohort was used for comparison. When patients were classified according to surgical treatment, the enrichment of blood group A was most prominent among unresected cases (54.0%), who also had the lowest prevalence of O (28.7%). There was a statistically significant better survival (P = 0.04) for blood group O cases than non-O cases among unresected but not among resected patients. Secretor status did not show an association with PDAC or survival. Our study demonstrates that pancreatic cancer risk is influenced by ABO status, in particular blood groups O and A 1 , and that this association may reflect also in tumor resectability and survival. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

Directory of Open Access Journals (Sweden)

Golden Daniel W

2012-09-01

Full Text Available Abstract Background Unresectable pancreatic cancer (UPC has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS. Methods From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy. All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other and 24 received adjuvant chemotherapy. Results 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy. Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT Conclusions CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9

Development of pancreatic cancer is predictable well in advance using contrast-enhanced CT: a case-cohort study

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Gonoi, Wataru; Hayashi, Takana Yamakawa; Okuma, Hidemi; Ohtomo, Kuni [The University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); Akahane, Masaaki [The University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); NTT Medical Centre Tokyo, Department of Radiology, Tokyo (Japan); Nakai, Yousuke; Mizuno, Suguru; Tateishi, Ryosuke; Isayama, Hiroyuki; Koike, Kazuhiko [The University of Tokyo, Department of Gastroenterology, Graduate School of Medicine, Tokyo (Japan)

2017-12-15

To investigate the radiological findings prognostic for the development of pancreatic adenocarcinoma in a cohort of patients with hepatocellular carcinoma, using multiphasic computed tomography (CT). A case-cohort study performed in a single university hospital. A database of patients who received hepatocellular carcinoma (HCC) treatment and trimonthly follow-up with four-phase dynamic CT was used (n = 1848). The cohort group was randomly extracted from the database (n = 103). The case group comprised nine patients from the database who developed pancreatic adenocarcinoma. The radiological findings were assessed during follow-up (average, 32 months). The incidence of pancreatic mass, inhomogeneous parenchyma, loss of fatty marbling and main pancreatic duct dilatation gradually increased from 4 to 13 months before the diagnosis of pancreatic adenocarcinoma. There was a significantly higher incidence of pancreatic mass, inhomogeneous parenchyma and loss of fatty marbling on CT at baseline (average, 34 months before diagnosis) in the case group compared with the cohort group (P values < 0.01) and those findings at baseline were revealed as prognostic factors for pancreatic carcinogenesis, respectively (log-rank test, P values < 0.001). Several radiological findings observed on multiphasic CT can assist in predicting pancreatic carcinogenesis well in advance. (orig.)

Systemic therapy of pancreatic cancer

International Nuclear Information System (INIS)

Andrezalova Vochyanova, I.; Salek, T.

2012-01-01

Pancreatic cancer is the fourth comment cause of cancer-related death in men. Most patients with pancreatic cancer are diagnosed at advanced, non-resectable stage. Late detection, early metastases, difficult surgical approached, cancer resistant to systemic chemo and radiotherapy - all contribute to its in faust prognosis. Only about 5 % of patients will live 5 years after diagnosis. Gemcitabine - based combination treatments is the standard for advanced pancreatic cancer. The combination of fluorouracil, folinic acid, irinotecan and oxaliplatin led to median survival of 11 months. No standard second-line treatment exists for pancreatic cancer. (author)

“Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report”

Science.gov (United States)

Fragulidis, Georgios P.; Vezakis, Αntonios; Dellaportas, Dionissios; Sotirova, Ira; Koutoulidis, Vassilis; Kontis, Elliseos; Polydorou, Andreas

2015-01-01

Introduction Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. Presentation of cases A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessful. A surgical therapy was considered and a longitudinal pancreaticojejunostomy (modified Puestow procedure) in both patients was performed with excellent results. Discussion Over the last 30 years, endoscopic procedures are developed to manage pancreatic duct strictures and calculi of the main pancreatic duct in CP patients. In both of our cases endoscopic therapy was first attempted but failed to extract the pancreatic duct stones, due to their size and speculations. Modified Puestow procedure was performed for both and it was successful for long term pain relief. Conclusion Despite advancement in endoscopic interventions and less invasive therapies for the management of chronic lithiasic pancreatitis we consider that classic surgical management can be appropriate in certain cases. PMID:26318135

Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

Directory of Open Access Journals (Sweden)

Mulet-Margalef N

2012-09-01

Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

Phase I study evaluating the treatment of patients with locally advanced pancreatic cancer with carbon ion radiotherapy: the PHOENIX-01 trial

International Nuclear Information System (INIS)

Combs, Stephanie E; Debus, Jürgen; Habermehl, Daniel; Kieser, Meinhard; Dreher, Constantin; Werner, Jens; Haselmann, Renate; Jäkel, Oliver; Jäger, Dirk; Büchler, Markus W

2013-01-01

Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy as well as radiotherapy. In many cases, surgical resection is not possible, and therefore treatment alternatives have to be performed. Chemoradiation has been established as a convincing treatment alternative for locally advanced pancreatic cancer. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 1.16 and 2.46 depending on the pancreatic cancer cell line as well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with pancreatic cancer. The present PHOENIX-01 trial evaluates carbon ion radiotherapy using the active rasterscanning technique in patients with advanced pancreatic cancer in combination with weekly gemcitabine and adjuvant gemcitabine. Primary endpoint is toxicity, secondary endpoints are overall survival, progression-free survival and response. The physical and biological properties of the carbon ion beam promise to improve the therapeutic ratio in patients with pancreatic cancer: Due to the inverted dose profile dose deposition in the entry channel of the beam leads to sparing of normal tissue; the Bragg peak can be directed into the defined target volume, and the sharp dose fall-off thereafter again spares normal tissue behind the target volume. The higher RBE of carbon ions, which has been shown also for pancreatic cancer cell lines in the preclinical setting, is likely to contribute to an increase in local control, and perhaps in OS. Early data from Japanese centers have shown promising results. In conclusion, this is the first trial to evaluate actively delivered carbon

Localized Unresectable Pancreatic Cancer Treated with High Energy Neutrons and Chemotherapy at Fermilab - Preliminary Results

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Saroja, K. R. [Unlisted, US, IL; Cohen, Lionel [Unlisted, US, IL; Hendrickson, Frank R. [Unlisted, US, IL; Mansell, JoAnne [Fermilab

1990-01-01

Between January 1985 and July 1989 a total of thirty-eight patients with locally advanced pancreatic cancer were treated with high energy neutrons at Fermilab. Twenty-one patients received only neutrons and seventeen were given chemotherapy in addition, either concurrently or subsequently following the completion of neutron irradiation. This is a retrospective study. Data were analyzed for tolerance, complications and survival. Three of the twenty-one (14%) patients who received only neutron beam therapy developed Grade ID or greater complications in the RTOG/EORTC scale. The median survival was 6.4 months. One of these patients is alive 10 months post treatment. Of seventeen patients who also received chemotherapy, five (29%) had severe complications. However, median survival was 13.5 months. Four of these seventeen patients are still alive at the time of this analysis. The preliminary results show that there is improvement in the survival of patients treated with combined neutron irradiation and chemotherapy. A pilot study to further evaluate these results in a larger group of patients is underway. Details of complications and chemotherapy regimen will be preseqted.

Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer

NARCIS (Netherlands)

Rombouts, S. J. E.; Vogel, J. A.; van Santvoort, H. C.; van Lienden, K. P.; van Hillegersberg, R.; Busch, O. R. C.; Besselink, M. G. H.; Molenaar, I. Q.

2015-01-01

BackgroundLocally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic

Pancreatic Cancer—Patient Version

Science.gov (United States)

Pancreatic cancer can form in exocrine cells and neuroendocrine cells. The exocrine type is more common and is usually found at an advanced stage. Pancreatic neuroendocrine tumors are less common but have a better prognosis. Start here to find information on pancreatic cancer treatment, research, and statistics.

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

Science.gov (United States)

Singhi, Aatur D; Zeh, Herbert J; Brand, Randall E; Nikiforova, Marina N; Chennat, Jennifer S; Fasanella, Kenneth E; Khalid, Asif; Papachristou, Georgios I; Slivka, Adam; Hogg, Melissa; Lee, Kenneth K; Tsung, Allan; Zureikat, Amer H; McGrath, Kevin

2016-06-01

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI

Therapeutic management of locally unresectable pancreatic cancer; Adenocarcinomes du pancreas localement evolues: modalites therapeutiques actuelles

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Lombard-Bohas, C.; Saurin, J.C. [Centre Hospitalier Universitaire Edouard-Herriot, 69 - Lyon (France); Mornex, F. [Centre Hospitalier Universitaire Lyon-Sud, 69 - Pierre-Benite (France)

1997-12-31

Pancreatic cancer still have bad prognosis. At the time of diagnosis, less than 10 % of patients can undergo surgery with an overall 5-year survival rate of less than 2 %. For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and chemotherapy has been shown to control symptoms and to enhance patient survival. This treatment should be proposed to all the patients with good performance status and without icterus. Pain management should be optimized and often need morphinic and co-antalgic (anticonvulsants, steroids) consumption. The celiac plexus block with alcohol gives an excellent pain relief and should be more frequently used. (author)

Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

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Wild, Aaron T. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Herman, Joseph M.; Dholakia, Avani S.; Moningi, Shalini [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Lu, Yao [Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rosati, Lauren M.; Hacker-Prietz, Amy; Assadi, Ryan K.; Saeed, Ali M. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy M. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Jaffee, Elizabeth M.; Laheru, Daniel A. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Weiss, Matthew J.; Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ford, Eric [Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington (United States); Grossman, Stuart A. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ye, Xiaobu [Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah G., E-mail: sbatkoy2@jhmi.edu [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2016-03-01

Purpose: Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods and Materials: Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. Results: Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm{sup 3}) than in CRT (344.6 cm{sup 3}; P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm{sup 3} vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002). Conclusions: SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling

A clinical study on combined modality therapy, radio-hyperthermo-chemotherapy, for pancreatic cancer

International Nuclear Information System (INIS)

Yamamoto, Yoshikazu

1989-01-01

A new multimodality therapy, radio-hyperthermo-chemotherapy, has been performed in a total of 31 pancreatic cancer patients with the purpose of improving treatment outcome. Combination of hyperthermia and chemotherapy was given as a pre-irradiation therapy in 7 resectable cancer patients. Among 24 unresectable cancer patients, 17 had irradiation in combination with hyperthermia and chemotherpay. Although both degeneration and necrosis of cancer cells were observed in all resectable cases at biopsy, these were not predictive of a better outcome. Of evaluable 17 patients with unresectable cancer, tumor regression was observed in 5 (29.4%). Although 22 patients had pain before therapy, 8 and 5 patients had remarkable and moderate pain relief, respectively, with therapy. Performance status was improved in 7 patients (29.2%). Survival rate at 12 months was still low (8.3%). However, the radio-hyperthermo-chemotherapy appears to help in increasing the quality of life in view of pain relief. (N.K.)

Cost-effectiveness of modern radiotherapy techniques in locally advanced pancreatic cancer.

Science.gov (United States)

Murphy, James D; Chang, Daniel T; Abelson, Jon; Daly, Megan E; Yeung, Heidi N; Nelson, Lorene M; Koong, Albert C

2012-02-15

Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer. A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity. SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT. The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by

Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

Directory of Open Access Journals (Sweden)

S. K. Seelig

2010-01-01

Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

“Puestow modified procedure in the era of advanced endoscopic interventions for the management of chronic lithiasic pancreatitis. A two cases report”

OpenAIRE

Georgios P. Fragulidis; Αntonios Vezakis; Dionissios Dellaportas; Ira Sotirova; Vassilis Koutoulidis; Elliseos Kontis; Andreas Polydorou

2015-01-01

Introduction: Pancreatic duct calculi in chronic pancreatitis (CP) patients are the main cause of intractable pain which is their main symptom. Decompression options of for the main pancreatic duct are both surgical and advanced endoscopic procedures. Presentation of cases: A 64-year-old male with known CP due to alcohol consumption and a 36-year-old female with known idiopathic CP and pancreatic duct calculi were managed recently in our hospital where endoscopic procedures were unsuccessf...

Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

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Shinohara, Eric T., E-mail: eric.t.shinohara@vanderbilt.edu [Department of Radiation Oncology, The Vanderbilt Clinic, Nashville, TN (United States); Kassaee, Alireza [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Vapiwala, Neha; Plastaras, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Drebin, Jeff [Department of Surgery, University of Pennsylvania, Philadelphia, PA (United States); Wan, Fei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Metz, James M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

2012-06-01

Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System's localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

International Nuclear Information System (INIS)

Shinohara, Eric T.; Kassaee, Alireza; Mitra, Nandita; Vapiwala, Neha; Plastaras, John P.; Drebin, Jeff; Wan, Fei; Metz, James M.

2012-01-01

Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System’s localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

Clinical benefit response of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Okusaka, Takuji; Okada, Shuichi; Ishii, Hiroshi

1998-01-01

Pancreatic cancer is a highly virulent disease with a poor prognosis. Although objective tumor response to chemotherapy and/or radiotherapy is low, some patients show an improvement in their symptoms after treatments, without obvious tumor regression. We assessed the clinical benefit of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer. Sixteen patients were enrolled in this study. The clinical benefit response to the chemoradiotherapy was evaluated by 2 indicators, including pain (intensity of pain and consumption of morphine) and performance status. A patient was defined to be a clinical benefit responder if 1 of these 2 variables was positive, and the other variable was positive or stable. Seven patients (44%) responded. Six patients (38%) were classified as stable, and 3 (19%) as nonresponders. The survival period in responders was significantly longer than that in nonresponders and stable patients. Concurrent external-beam radiation therapy, with protracted 5-fluorouracil infusion, may be a meaningful treatment for locally advanced pancreatic cancer. (author)

Accelerated radiochemotherapy in pancreatic cancer is not necessarily related to a pathologic pancreatic function decline in the early period

International Nuclear Information System (INIS)

Horst, Eckehard; Seidel, Matthias; Micke, Oliver; Ruebe, Christian; Glashoerster, Marco; Schaefer, Ulrich; Willich, Normann A.

2002-01-01

Purpose: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). Methods and Materials: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. Results: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% ± 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of 41 Gy. The endocrine function measurements remained unchanged. Conclusion: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy

ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children

NARCIS (Netherlands)

Taylor, Christopher J.; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E.; Mehta, Devendra; Orabi, Abrahim I.; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J.; Husain, Sohail Z.; Wilschanski, Michael

The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available

The specific localization of advanced glycation end-products (AGEs) in rat pancreatic islets.

Science.gov (United States)

Morioka, Yuta; Teshigawara, Kiyoshi; Tomono, Yasuko; Wang, Dengli; Izushi, Yasuhisa; Wake, Hidenori; Liu, Keyue; Takahashi, Hideo Kohka; Mori, Shuji; Nishibori, Masahiro

2017-08-01

Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

International Nuclear Information System (INIS)

Petrelli, Fausto; Comito, Tiziana; Ghidini, Antonio; Torri, Valter; Scorsetti, Marta; Barni, Sandro

2017-01-01

Purpose: Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results: A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions: The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.

Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

Energy Technology Data Exchange (ETDEWEB)

Petrelli, Fausto, E-mail: faupe@libero.it [Oncology Unit, Department of Oncology, ASST Bergamo Ovest, Treviglio (Italy); Comito, Tiziana [Department of Radiosurgery and Radiotherapy, Istituto Clinico Humanitas Cancer Center and Research Hospital, Milan (Italy); Ghidini, Antonio [Oncology Unit, Igea Hospital, Milan (Italy); Torri, Valter [Department of Biomedical Sciences, Humanitas University and Radiotherapy and Radiosurgery Department-Humanitas Research Hospital, Milan (Italy); Scorsetti, Marta [Department of Radiosurgery and Radiotherapy, Istituto Clinico Humanitas Cancer Center and Research Hospital, Milan (Italy); Barni, Sandro [Oncology Unit, Department of Oncology, ASST Bergamo Ovest, Treviglio (Italy)

2017-02-01

Purpose: Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results: A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions: The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.

Results of Definitive Chemoradiotherapy for Unresectable Esophageal Cancer

International Nuclear Information System (INIS)

Noh, O Kyu; Je, Hyoung Uk; Kim, Sung Bae

2008-01-01

To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) (42-46 Gy) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to 54-66 Gy, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, 9-12 Gy/3 -4 fx). Two cycles of concurrent FP chemotherapy (5-FU 1,000 mg/m2/day, days 2-6, 30-34, cisplatin 60 mg/m2/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range 1-149 months)]. The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range 44.4-66) and a total radiation dose, including BT, of 60 Gy (range 44.4-72), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29

Results of Definitive Chemoradiotherapy for Unresectable Esophageal Cancer

Energy Technology Data Exchange (ETDEWEB)

Noh, O Kyu; Je, Hyoung Uk; Kim, Sung Bae [Ulsan University College of Medicine, Seoul (Korea, Republic of)] (and others)

2008-12-15

To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) (42-46 Gy) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to 54-66 Gy, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, 9-12 Gy/3 -4 fx). Two cycles of concurrent FP chemotherapy (5-FU 1,000 mg/m2/day, days 2-6, 30-34, cisplatin 60 mg/m2/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range 1-149 months)]. The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range 44.4-66) and a total radiation dose, including BT, of 60 Gy (range 44.4-72), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29

Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

Science.gov (United States)

Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

2011-01-01

Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

Recent Progress in Pancreatic Cancer

Science.gov (United States)

Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

2013-01-01

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

Intraoperative radiotherapy (IORT) in malignant pancreatic tumors - first experiences gained at the Grosshadern Hospital

International Nuclear Information System (INIS)

Willich, N.; Krimmel, K.; Naujokat, B.; Wendt, T.; Rohloff, R.; Teichmann, R.; Denecke, H.

1988-01-01

15 patients with locally unresectable pancreatic carcinomas were treated by IORT and bypass surgery. 13 patients without distant metastases were additionally treated by external beam irradiation. Although only one patient had a local failure, the median survival was only eight months. Severe complications were seen in eight patients, gastro-intestinal bleeding occurred in six patients and was the cause of death in three patients. The stop of weight loss and the impressive pain relief within ten days after IORT demonstrate the significance of this treatment modality with respect to palliative effects. (orig.) [de

The diameter of main pancreatic duct on endoscopic retrograde pancreatography and the appearance of main pancreatic duct on computed tomography

International Nuclear Information System (INIS)

Tanno, Naoaki; Yamazaki, Hideo; Toyota, Takayoshi; Nakanome, Chiyuki; Sasaki, Masayoshi; Sato, Waichi; Komatsu, Kanji.

1990-01-01

We have carried out a comparative study of the diameter of main pancreatic duct (MPD) on endoscopic retrograde pancreatography (ERP) with the fequency of detection of MPD by computed tomography (CT) in order to clarify the importance of MPD appearance on CT in the pancreatic and biliary diseases. The normal MPD on ERP was demonstrated by CT in a low frequency. MPD was most frequently observed in the pancreatic body on CT. The dilatation of MPD on ERP was found in both moderate and advanced pancreatitis group. However, the significant demonstration of MPD by CT was found in advanced group alone. We observed that CT finding of dilated duct correlated with that on ERP in advanced group alone. (author)

Comparison of Outcomes for Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Treated With Induction Chemotherapy Followed By Concurrent Chemoradiation vs. Concurrent Chemoradiation Alone

International Nuclear Information System (INIS)

Huang, Eugene H.; Liao Zhongxing; Cox, James D.; Guerrero, Thomas M.; Chang, Joe Y.; Jeter, Melinda; Borghero, Yerko; Wei Xiong; Fossella, Frank; Herbst, Roy S.; Blumenschein, George R.; Moran, Cesar; Allen, Pamela K.; Komaki, Ritsuko

2007-01-01

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung

Advances in the endoscopic management of pancreatic collections.

Science.gov (United States)

Ruiz-Clavijo, David; de la Higuera, Belen González; Vila, Juan J

2015-04-16

Treatment of pancreatic collections has experienced great progress in recent years with the emergence of alternative minimally invasive techniques comparing to the classic surgical treatment. Such techniques have been shown to improve outcomes of morbidity vs surgical treatment. The recent emergence of endoscopic drainage is noteworthy. The advent of endoscopic ultrasonography has been crucial for treatment of these specific lesions. They can be characterized, their relationships with neighboring structures can be evaluated and the drainage guided by this technique has been clearly improved compared with the conventional endoscopic drainage. Computed tomography is the technique of choice to characterize the recently published new classification of pancreatic collections. For this reason, the radiologist's role establishing and classifying in a rigorously manner the collections according to the new nomenclature is essential to making therapeutic decisions. Ideal scenario for comprehensive treatment of these collections would be those centers with endoscopic ultrasound and interventional radiology expertise together with hepatobiliopancreatic surgery. This review describes the different types of pancreatic collections: acute peripancreatic fluid collection, pancreatic pseudocysts, acute necrotic collection and walled-off necrosis; the indications and the contraindications for endoscopic drainage, the drainage technique and their outcomes. The integrated management of pancreatic collections according to their type and evolution time is discussed.

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

Directory of Open Access Journals (Sweden)

Chien Chih-Yen

2011-03-01

Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

New Insights into the Pathogenesis of Pancreatitis

Science.gov (United States)

Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

2014-01-01

Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

Management of acute pancreatitis in children.

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Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

2017-10-01

Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

Clinical predictors of resectability of pancreatic adenocarcinoma.

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Almadi, Majid A; Alharbi, Othman; Azzam, Nahla; Altayeb, Mohannad; Javed, Moammed; Alsaif, Faisal; Hassanain, Mazen; Alsharabi, Abdulsalam; Al-Saleh, Khalid; Aljebreen, Abdulrahman M

2013-01-01

Identifying patient-related factors as well as symptoms and signs that can predict pancreatic cancer at a resectable stage, which could be used in an attempt to identify patients at an early stage of pancreatic cancer that would be appropriate for surgical resection and those at an unresectable stage be sparred unnecessary surgery. A retrospective chart review was conducted at a major tertiary care, university hospital in Riyadh, Saudi Arabia. The study population included individuals who underwent a computed tomography and a pancreatic mass was reported as well as the endoscopic reporting database of endoscopic procedures where the indication was a pancreatic mass, between April 1996 and April 2012. Any patient with a histologically confirmed diagnosis of adenocarcinoma of the pancreas was included in the analysis. We included patients' demographic information (age, gender), height, weight, body mass index, historical data (smoking, comorbidities), symptoms (abdominal pain and its duration, anorexia and its duration, weight loss and its amount, and over what duration, vomiting, abdominal distention, itching and its duration, change in bowel movements, change in urine color), jaundice and its duration. Other variables were also collected including laboratory values, location of the mass, the investigation undertaken, and the stage of the tumor. A total of 61 patients were included, the mean age was 61.2 ± 1.51 years, 25 (41%) were females. The tumors were located in the head (83.6%), body (10.9%), tail (1.8%), and in multiple locations (3.6%) of the pancreas. Half of the patients (50%) had Stage IV, 16.7% stages IIB and III, and only 8.3% were stages IB and IIA. On univariable analysis a lower hemoglobin level predicted resectability odds ratio 0.65 (95% confidence interval, 0.42-0.98), whereas on multivariable regression none of the variables included in the model could predict resectability of pancreatic cancer. A CA 19-9 cutoff level of 166 ng/mL had a

Imaging in pancreatic transplants

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Heller, Matthew T; Bhargava, Puneet

2014-01-01

Pancreatic transplantation, performed alone or in conjunction with kidney transplantation, is an effective treatment for advanced type I diabetes mellitus and select patients with type II diabetes mellitus. Following advancements in surgical technique, postoperative management, and immunosuppression, pancreatic transplantation has significantly improved the length and quality of life for patients suffering from pancreatic dysfunction. While computed tomography (CT) and magnetic resonance imaging (MRI) have more limited utility, ultrasound is the preferred initial imaging modality to evaluate the transplanted pancreas; gray-scale assesses the parenchyma and fluid collections, while Doppler interrogation assesses vascular flow and viability. Ultrasound is also useful to guide percutaneous interventions for the transplanted pancreas. With knowledge of the surgical anatomy and common complications, the abdominal radiologist plays a central role in the perioperative and postoperative evaluation of the transplanted pancreas

Chemoradiation for unresectable gall bladder cancer: time to review historic nihilism?

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Engineer, Reena; Wadasadawala, Tabassum; Mehta, Shaesta; Mahantshetty, Umesh; Purandare, Nilendu; Rangarajan, Venkatesh; Kishore Shrivastava, Shyam

2011-12-01

Treatment of unresectable locally advanced gallbladder cancers (LAGBC) usually consists of various palliative strategies which provide only a modest survival benefit. Here, we present a series of three patients of LAGBC-treated consecutively at our center with preoperative chemoradiation using tomotherapy and concurrent gemcitabine. All three cases were reported to be adenocarcinoma by biopsy or fine-needle aspiration cytology. All the patients underwent positron emission tomography with computerized tomography scan to rule out distant metastasis and also to map the extent of disease for radiotherapy planning. Preoperative chemoradiation consisted of gemcitabine at 300 mg/m(2) weekly and tomotherapy with daily image guidance with MVCT over 5 weeks to a dose of 57 Gy in 25 fractions to the gross tumor and 45 Gy in 25 fractions to the clinical target volume to cover the areas of microscopic spread. Complete metabolic and radiologic response was observed for 2 patients and partial response for 1 patient. Two patients underwent complete surgical excision of which 1 patient had complete pathological response and 1 patient had small residual tumor at the primary and no nodal metastasis. The third patient could not undergo surgery due to medical reasons. The clinical outcome for unresectable LAGBC with preoperative chemoradiation in terms of feasibility, safety, and survival is encouraging. This treatment strategy has a curative potential for the otherwise fatal disease.

Activation of NLRP3 Inflammasome by Advanced Glycation End Products Promotes Pancreatic Islet Damage

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Xiang Kong

2017-01-01

Full Text Available Accumulation of advanced glycation end products (AGEs contributes to ageing and age-related diseases, especially type 2 diabetes. The NLRP3 inflammasome, as a vital component of the innate immune system, is implicated in the pathogenesis of type 2 diabetes. However, the role of the NLRP3 inflammasome in AGE-induced pancreatic islet damage remains largely unclear. Results showed that administration of AGEs (120 mg/kg for 6 weeks in C57BL/6J mice induced an abnormal response to glucose (as measured by glucose tolerance and insulin release, pancreatic β-cell ultrastructural lesion, and cell death. These effects were associated with an excessive superoxide anion level, significant increased protein expression levels for NADPH oxidase 2 (NOX2, thioredoxin-interacting protein (TXNIP, NLRP3, and cleaved IL-1β, enhanced caspase-1 activity, and a significant increase in the levels of TXNIP–NLRP3 protein interaction. Ablation of the NLRP3 inflammasome or treatment with antioxidant N-acetyl-cysteine (NAC clearly ameliorated these effects. In conclusion, our results reveal a possible mechanism for AGE-induced pancreatic islet damage upon NLRP3 inflammasome activation.

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

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Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-01-01

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

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Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

2009-01-01

Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m 2 /wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m 2 ) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p 2 /wk vs. 296 ± 15 mg/m 2 /wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP

[Prognostic factors of mortality in the malignant biliary obstruction unresectable after the insertion of an endoscopic stent].

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Hernández Guerrero, Angélica; Sánchez del Monte, Julio; Sobrino Cossío, Sergio; Alonso Lárraga, Octavio; Delgado de la Cruz, Lourdes; Frías Mendívil, M Mauricio; Frías Mendívil, C Mauricio

2006-01-01

To determine the factors prognostics of early mortality in the malignant billary estenosis after the endoscopic derivation. The surgical, percutaneous or endoscopic derivation is the alternative of palliative treatment in the biliary obstruction unresectable. The factors prognostic the early mortality after surgical derivation are: hemoglobin 10 mg/dL and serum albumin ictericia, pain and prurito. 61 cases of distal obstruction and 36 with proximal obstruction. Twenty deaths (25.9%) happened within the 30 later days to the treatment. The bilirubin > 14 mg/dL and the proximal location were like predicting of early mortality. The obstruction biliary more frequent is located in choledocho distal and is of pancreatic origin. The main factors associated to early mortality are: the bilirubin > of 14 mg/dL and the proximal location reason why is important the suitable selection of patient candidates to endoscopic derivation. The survival is better in the distal obstruction.

Surgical and molecular pathology of pancreatic neoplasms.

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Hackeng, Wenzel M; Hruban, Ralph H; Offerhaus, G Johan A; Brosens, Lodewijk A A

2016-06-07

Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.

Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

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Smith, Ross C; Smith, Sarah F; Wilson, Jeremy; Pearce, Callum; Wray, Nick; Vo, Ruth; Chen, John; Ooi, Chee Y; Oliver, Mark; Katz, Tamarah; Turner, Richard; Nikfarjam, Mehrdad; Rayner, Christopher; Horowitz, Michael; Holtmann, Gerald; Talley, Nick; Windsor, John; Pirola, Ron; Neale, Rachel

2016-01-01

Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy. Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

Chronic pancreatitis: diagnosis, classification, and new genetic developments.

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Etemad, B; Whitcomb, D C

2001-02-01

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

Outcome of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy for inoperable locally advanced pancreatic cancer

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Lu Ningning; Jin Jing; Li Yexiong; Yu Zihao; Liu Xinfan; Wang Weihu; Wang Shulian; Song Yongwen; Liu Yuping

2009-01-01

Objective: To evaluate the outcome of radiotherapy for locally advanced pancreatic cancer. Methods: From January 2000 to December 2007, 41 patients with inoperable locally advanced (stage III) pancreatic cancer were treated with three-dimensional conformal radiation therapy(3DCRT) or intensity-modulated radiation therapy (IMRT). Among these patients, 30 received concurrent radio-chemo-therapy. Results: The median survival time(MST) and 1-year overall survival were 9.2 months and 23%. Patients with pretreatment KPS ≥ 80, no regional lymph nodes metastasis, and CR/PR after radiotherapy had better prognosis. The corresponding MSTs were 11.1 months vs 5.8 months (χ 2 =7.50, P=0.006), 10.8 months vs 6.5 months(χ 2 =5.67, P=0.017), and 19.5 months vs 9.1 months (χ 2 =7.28, P=0.007), respectively. Concurrent radio-chemotherapy tended to improve the overall survival(χ 2 =3.25, P=0.072). After radiotherapy, 18 patients had clinical benefit response, mainly being abdominal pain relief. Neither grade 4 hematologic nor grade 3 non-hematologic toxicities were observed. Conclusions: For patients with locally advanced pancreatic cancer, both 3DCRT and IMRT are effective in alleviation of disease-related symptoms. Patients with better performance status before treatment, no regional lymph nodes metastasis, and better response to radiotherapy may have better prognosis. Concurrent radio-chemotherapy trend to improve overall survival when compared with radiotherapy alone. (authors)

A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

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Ma Yue

2011-03-01

Full Text Available Abstract Background The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC. Methods We performed a computerized search using combinations of the following keywords: "chemotherapy", "gemcitabine", "trial", and "pancreatic cancer". Results Thirty-five trials were included in the present analysis, with a total of 9,979 patients accrued. The analysis showed that the gemcitabine-based combination therapy was associated with significantly better overall survival (OS (ORs, 1.15; p = 0.011, progression-free survival (PFS (ORs, 1.27; p Conclusions Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC.

Diagnostic Management of Pancreatic Cancer

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Dabizzi, Emanuele [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States); Assef, Mauricio Saab [Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesário Motta Jr. #61 Cep: 01221-020, São Paulo (Brazil); Raimondo, Massimo, E-mail: raimondo.massimo@mayo.edu [Division of Gastroenterology and Hepatology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, Florida 32224 (United States)

2011-01-31

Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used.

Diagnostic Management of Pancreatic Cancer

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Dabizzi, Emanuele; Assef, Mauricio Saab; Raimondo, Massimo

2011-01-01

Pancreatic cancer is one of the most deadly solid tumors, with an overall 5-year survival rate of less than 5%. Due to a non-specific clinical presentation, it is often diagnosed at an advanced stage and is rarely amenable for curative treatment. Therefore early diagnosis and appropriate staging are still essential to define the best care and to improve patient survival. Several imaging modalities are currently available for the evaluation of pancreatic cancer. This review focuses on different techniques and discusses the diagnostic management of patients with pancreatic cancer. This review was conducted utilizing Pubmed and was limited to papers published within the last 5 years. The search key words pancreatic cancer, pancreatic adenocarcinoma, pancreatic tumors, diagnosis, radiology, imaging, nuclear imaging, endoscopy, endoscopic ultrasound and biochemical markers were used

The Role of Radiation Therapy in the Unresectable Rectal Cancers

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Kim, Woo Cheol; Seong, Jin Sil; Kim, Gwi Eon

1995-01-01

Purpose : Unresectable rectal cancer has a grave prognosis, regardless of the therapy used and median survival is less than 1 year. Also, it is reported by many authors that 50-80% of unresectable lesions were rendered respectable by radiation therapy and the median survival time for the completely resected patients were better than that of the unresected patients. So we analyzed retrospectively our data for the better treatment outcome in these patients. Materials and Methods : From 1980 to 1992, 45 patients with initially unresectable tumors in the rectum were treated with radiation therapy with/without surgery in Department of Radiation Oncology, Yonsei Cancer Center. 10 MV radiation and multiple field technique( box or AP/PA) were used. The total dose was 8-70 Gy and median dose was 48 Gy. We evaluated the lesion status at 45-50 Gy for operability. If the lesions appeared to be respectable, the patients were operated on 4-6 weeks after radiation therapy. But if the lesions were still fixed, the radiation dose was increased to 60-65 Gy. Results : For all patients, the 2-year actuarial survival was 13.3% and median survival was 9.5 months. Of 6 patients who had received less than 45 Gy, only 17% of patients responded, but in the patients who had received more than 45 Gy, 60% of response rate was achieved. Six of the 24 patients(25%) underwent surgical resections following RT. For patients undergoing curative resection, the two-year survival was 50%, but that of the patients without resection was 9.5% (p<0.01). Survival of patients with complete response following RT was 50% at 2 years. Survival of patients with partial response, stable disease and progressive disease after RT was 13.4%, 15.4%, 0% respectively (p<0.05). Conclusion: Our data suggests that the efforts which can increase the response rate and aggressive surgical approach are needed to achieve the better local control and survival in unresectable rectal cancers

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

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Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-06-01

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

Recent advances in 3D computed tomography techniques for simulation and navigation in hepatobiliary pancreatic surgery.

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Uchida, Masafumi

2014-04-01

A few years ago it could take several hours to complete a 3D image using a 3D workstation. Thanks to advances in computer science, obtaining results of interest now requires only a few minutes. Many recent 3D workstations or multimedia computers are equipped with onboard 3D virtual patient modeling software, which enables patient-specific preoperative assessment and virtual planning, navigation, and tool positioning. Although medical 3D imaging can now be conducted using various modalities, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography (US) among others, the highest quality images are obtained using CT data, and CT images are now the most commonly used source of data for 3D simulation and navigation image. If the 2D source image is bad, no amount of 3D image manipulation in software will provide a quality 3D image. In this exhibition, the recent advances in CT imaging technique and 3D visualization of the hepatobiliary and pancreatic abnormalities are featured, including scan and image reconstruction technique, contrast-enhanced techniques, new application of advanced CT scan techniques, and new virtual reality simulation and navigation imaging. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Prevention of pancreatic cancer

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Stefan Kuroczycki-Saniutycz

2017-02-01

Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

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Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

2011-02-01

A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

Chemical strategies for pancreatic β cell differentiation, reprogramming, and regeneration.

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Ma, Xiaojie; Zhu, Saiyong

2017-04-01

Generation of unlimited functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes mellitus. Recent advances have suggested several promising directions, including directed differentiation of pancreatic β cells from pluripotent stem cells, reprogramming of pancreatic β cells from other types of somatic cells, and stimulated proliferation and enhanced functions of existing pancreatic β cells. Small molecules are useful in generating unlimited numbers of functional pancreatic cells in vitro and could be further developed as drugs to stimulate endogenous pancreatic regeneration. Here, we provide an updated summary of recent major achievements in pancreatic β cell differentiation, reprogramming, proliferation, and function. These studies will eventually lead to significant advances in the field of pancreatic biology and regeneration. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vaccination with poly(IC:LC and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer

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Shikhar Mehrotra

2017-04-01

Full Text Available Abstract Background Dendritic cells (DCs enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC. Methods We generated autologous DCs from the peripheral blood of HLA-A2+ patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1 human telomerase reverse transcriptase (hTERT, TERT572Y, 2 carcinoembryonic antigen (CEA; Cap1-6D, and 3 survivin (SRV.A2. Patients received four intradermal injections of 1 × 107 peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42. Concurrently, patients received intramuscular administration of Poly-ICLC at 30 μg/Kg on vaccination days (i.e., day 0, 14, 28, and 42, as well as on days 3, 17, 21, 31, 37, and 45. Our key objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells. Results Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I –tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease. Conclusion Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and

Interventional radiological treatment in complications of pancreatitis

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Memis, Ahmet E-mail: ahmemis@yahoo.com; Parildar, Mustafa

2002-09-01

Percutaneous interventional therapy plays an important role in treating complications of acute and chronic pancreatitis. With the development of cross-sectional imaging and advanced interventional techniques, percutaneous drainage has become the preferred treatment for pancreatic fluid collections such as acute collections, pseudocysts and abscesses. Abscess and pancreatic hemorrhage are the most life threatening complications of pancreatitis. Massive hemorrhage is rare but frequently lethal. As a rule, bleeding complications of pancreatitis require prompt diagnosis and an aggressive surgical approach. In unstable patients with a severely bleeding pseudoaneurysm, hemostasis can be obtained by occlusion with mechanical devices.

Interventional radiological treatment in complications of pancreatitis

International Nuclear Information System (INIS)

Memis, Ahmet; Parildar, Mustafa

2002-01-01

Percutaneous interventional therapy plays an important role in treating complications of acute and chronic pancreatitis. With the development of cross-sectional imaging and advanced interventional techniques, percutaneous drainage has become the preferred treatment for pancreatic fluid collections such as acute collections, pseudocysts and abscesses. Abscess and pancreatic hemorrhage are the most life threatening complications of pancreatitis. Massive hemorrhage is rare but frequently lethal. As a rule, bleeding complications of pancreatitis require prompt diagnosis and an aggressive surgical approach. In unstable patients with a severely bleeding pseudoaneurysm, hemostasis can be obtained by occlusion with mechanical devices

Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma.

Science.gov (United States)

Kumar, Jayant; Reccia, Isabella; Sodergren, Mikael H; Kusano, Tomokazu; Zanellato, Artur; Pai, Madhava; Spalding, Duncan; Zacharoulis, Dimitris; Habib, Nagy

2018-03-20

Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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.

Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

International Nuclear Information System (INIS)

Takahashi, Hidenori; Ohigashi, Hiroaki; Goto, Kunihito; Marubashi, Shigeru; Yano, Masahiko; Ishikawa, Osamu

2013-01-01

During the period from 2002 to 2011, a total of 240 consecutive patients with resectable pancreatic cancer received preoperative chemoradiation therapy (CRT). Among 240 patients, 201 patients underwent the subsequent pancreatectomy (resection rate: 84%). The 5-year overall survival of resected cases was 56% and the median survival of 39 unresected cases was 11 months. The 5-year locoregional recurrence rate of resected cases was 15%. The 5-year overall survival of the entire cohort (n=240) was 47%. The preoperative CRT and subsequent pancreatectomy provided a favorable surgical result, which was contributed by several characteristics of preoperative CRT: the prominent locoregional treatment effect with lower incidence of locoregional recurrence, and the discrimination between patients who are likely to benefit from subsequent surgery and those who are not. (author)

Single-stage intraoperative transhepatic biliary stenting in patients with unresectable hepatobiliary pancreatic tumors.

Science.gov (United States)

Iwasaki, Yoshimi; Kubota, Keiichi; Kita, Junji; Katoh, Masato; Shimoda, Mitsugi; Sawada, Tokihiko; Iso, Yukihiro

2013-02-01

The current study was conducted to evaluate the safety and utility of intraoperative transhepatic biliary stenting (ITBS) in patients with unresectable malignant biliary obstruction (UMBO) diagnosed intraoperatively. In this study, 50 patients who underwent ITBS for UMBO between April 2001 and May 2009 were retrospectively reviewed. For 26 patients who underwent preoperative percutaneous transhepatic biliary drainage (PTBD), the expandable metallic stent (EMS) was inserted intraoperatively by the PTBD route in a single stage. For 24 patients, the intrahepatic bile ducts were intentionally dilated by injection of saline via the endoscopic nasobiliary drainage or the percutaneous transhepatic gallbladder drainage route, and the puncture was performed under intraoperative ultrasound guidance followed by guidewire and catheter insertion. Thereafter, the EMS was placed in the same manner. The initial postoperative complications and long-term results of ITBS were evaluated. In all cases, ITBS was technically successful. Stenting alone was performed in 22 patients and stenting combined with other procedures in 28 patients. Hospital mortality occurred for three patients (6 %), and complication-related mortality occurred in two cases (4 %). There were nine cases (18 %) of postoperative complications. The median survival time was 179 days, and the EMS patency time was 137 days. During the follow-up period, EMS occlusion occurred in 23 cases (46 %). Best supportive care was a significant independent risk factor for early mortality within 100 days after ITBS (p = 0.020, odds ratio, 9.398). Single-stage ITBS is feasible for palliation of UMBO and seems to have a low complication rate.

Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

International Nuclear Information System (INIS)

Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

2012-01-01

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic cancer: from the laboratory to the clinic

International Nuclear Information System (INIS)

Symon, Zvi; Davis, Mary; McGinn, Cornelius J.; Zalupski, Mark M.; Lawrence, Theodore S.

2002-01-01

Purpose: We have reported that gemcitabine and concurrent radiation is a promising therapy for patients with pancreatic cancer. We investigated whether the addition of cisplatin, which may increase the systemic efficacy of gemcitabine, would be synergistic with gemcitabine and/or radiation in human pancreatic cancer cell lines. Methods and Materials: BxPc3 and Panc-1 human pancreatic cancer cells were treated with three different schedules before radiation: (A) a sequential incubation of gemcitabine for 2 h followed by cisplatin for 2 h, (B) gemcitabine for 2 h, followed by washout of drug, replenishment of media for a 24-h incubation, followed by cisplatin for 2 h, and (C) gemcitabine for 24 h with a concurrent incubation of cisplatin for the last 2 h. Cells were assessed for clonogenic survival using a standard assay. Synergism was evaluated by the median effect analysis. Results: The schedule shown to be maximally synergistic for both cell lines was the consecutive 2-h gemcitabine, 2-h cisplatin exposure, particularly at surviving fractions of <0.5. Cisplatin did not produce radiosensitization nor did it affect gemcitabine-mediated radiosensitization. Conclusion: Cisplatin produces synergistic cytotoxicity with gemcitabine without compromising gemcitabine-mediated radiosensitization. On the basis of these laboratory and previous clinical observations, we have initiated a Phase I trial of cisplatin plus gemcitabine and radiotherapy in patients with unresectable pancreatic cancer

SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

International Nuclear Information System (INIS)

Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

2014-01-01

Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

Energy Technology Data Exchange (ETDEWEB)

Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den [UMC Utrecht, Utrecht, Utrecht (Netherlands)

2014-06-01

Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS)

NARCIS (Netherlands)

Hartwig, Werner; Vollmer, Charles M.; Fingerhut, Abe; Yeo, Charles J.; Neoptolemos, John P.; Adham, Mustapha; Andrén-Sandberg, Ake; Asbun, Horacio J.; Bassi, Claudio; Bockhorn, Max; Charnley, Richard; Conlon, Kevin C.; Dervenis, Christos; Fernandez-Cruz, Laureano; Friess, Helmut; Gouma, Dirk J.; Imrie, Clem W.; Lillemoe, Keith D.; Milićević, Miroslav N.; Montorsi, Marco; Shrikhande, Shailesh V.; Vashist, Yogesh K.; Izbicki, Jakob R.; Büchler, Markus W.

2014-01-01

Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to

Diagnosis and management of chronic pancreatitis

OpenAIRE

Gupta, V; Toskes, P

2005-01-01

Chronic pancreatitis represents a condition that is challenging for clinicians secondary to the difficulty in making an accurate diagnosis and the less than satisfactory means of managing chronic pain. This review emphasises the various manifestations that patients with chronic pancreatitis may have and describes recent advances in medical and surgical therapy. It is probable that many patients with chronic abdominal pain are suffering from chronic pancreatitis that is not appreciated. As the...

Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Naumann, P.; Habermehl, D.; Welzel, T.; Combs, S.E. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Debus, J. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum, Heidelberg (Germany)

2013-09-15

Background: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. Methods: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. Results: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. Conclusions: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future. (orig.)

Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Naumann, P.; Habermehl, D.; Welzel, T.; Combs, S.E.

2013-01-01

Background: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. Methods: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. Results: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. Conclusions: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future. (orig.)

Imaging in the diagnosis of chronic pancreatitis

Directory of Open Access Journals (Sweden)

Vasile D. Balaban

2014-12-01

Full Text Available Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until late stages and have significant limitations, there is an incresing interest in the role of imaging techniques for the diagnosis of chronic pancreatitis. In this article we review the utility and accuracy of different imaging methods in the diagnosis of chronic pancreatitis, focusing on the role of advanced imaging (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Saltz, Leonard; Guillem, Jose G.; Paty, Philip B.; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Bass, Joanne; Conti, John

1997-01-01

Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response

Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

Science.gov (United States)

Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

2014-02-01

To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

A pilot study of the experience of family caregivers of patients with advanced pancreatic cancer using a mixed methods approach.

Science.gov (United States)

Sherman, Deborah W; McGuire, Deborah B; Free, David; Cheon, Joo Young

2014-09-01

Pancreatic cancer presents a wide spectrum of significant symptomatology. The high symptom burden, coupled with a rapidly fatal diagnosis, limits preparation or time for adjustment for both patients and their family caregivers. From the initial diagnosis and throughout the illness experience, the physical and emotional demands of caregiving can predispose caregivers themselves to illness and a greater risk of mortality. Understanding the negative and positive aspects of caregiving for patients with advanced pancreatic cancer will inform interventions that promote positive caregiver outcomes and support caregivers in their role. To provide feasibility data for a larger, mixed methods, longitudinal study focused on the experience of family caregivers of patients with advanced pancreatic cancer and preliminary qualitative data to substantiate the significance of studying this caregiver population. This was a mixed methods study guided by the Stress Process Model. Eight family caregivers of patients with advanced pancreatic cancer from oncology practices of a university-affiliated medical center were surveyed. The pilot results supported the ability to recruit and retain participants and informed recruitment and data collection procedures. The qualitative results provided preliminary insights into caregiver experiences during the diagnosis and treatment phases. Key findings that substantiated the significance of studying these caregivers included the caregiving context of the history of sentinel symptoms, the crisis of diagnosis, the violation of assumptions about life and health, recognition of the circle of association, and contextual factors, as well as primary and secondary stressors, coping strategies, resources, discoveries, gains and growth, associated changes/transitions, and unmet caregiver needs. Findings indicated caregivers' willingness to participate in research, highlighted the negative and positive aspects of the caregiver experience, and reinforced the

[Pancreatic ultrasonography].

Science.gov (United States)

Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

2015-04-01

Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

Science.gov (United States)

Sangchan, Apichat; Chaiyakunapruk, Nathorn; Supakankunti, Siripen; Pugkhem, Ake; Mairiang, Pisaln

2014-01-01

Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis

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Hoekstra, H.J.; Restrepo, C.; Kinsella, T.J.; Sindelar, W.F.

1988-01-01

Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor

Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic retrograde cholangiopancreatography.

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Yuki Ishikawa-Kakiya

Full Text Available Advanced techniques have been developed to overcome difficult cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP. Pancreatic duct guidewire placement method (PGW is performed in difficult cannulation cases; it is possible that it places patients at risk of post-ERCP pancreatitis (PEP. The mechanism of PEP is still unclear, but pancreatic duct pressure and injury of pancreatic duct are known causes of PEP. Therefore, we hypothesized a relationship between pancreatic duct diameter and PEP and predicted that PGW would increase the risk of PEP in patients with non-dilated pancreatic ducts. This study aimed to investigate whether PGW increased the risk of PEP in patients with pancreatic duct diameter ≤ 3 mm.We analyzed 332 patients with pancreatic duct ≤ 3 mm who performed first time ERCP session. The primary endpoint was the rate of adverse event of PEP. We evaluated the risk of PEP in patients who had undergone PGW compared to those who had not, using the inverse probability of treatment weighting (IPTW analysis.PGW was found to be an independent risk factor for PEP by univariate analysis (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.12-5.38; p = 0.03 after IPTW in patients with pancreatic duct diameter ≤ 3 mm. Adjusted for all covariates, PGW remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33-7.33; p = 0.01.Our results indicate that PGW in patients with pancreatic duct diameter ≤ 3 mm increases the risk of PEP.

CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

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2018-05-22

Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer

Diabetes, pancreatic cancer, and metformin therapy

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Jun eGong

2014-11-01

Full Text Available Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1, and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.

New insights into pancreatic cancer biology.

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Hidalgo, M

2012-09-01

Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

Upper gastrointestinal tract injuries by intraoperative radiotherapy for pancreatic cancer

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Tabata, I; Isawa, T; Satomi, T; Tazima, T [Tokyo Metropolitan Komagome Hospital (Japan)

1981-08-01

Twenty-one patients with unresectable carcinoma of the pancreas were treated by intraoperative irradiation with a large electron dose of 1500 - 3000 rads and upper gastrointestinal complications were encountered in five cases. All of those five cases were for carcinoma of the pancreatic head, and were seen for gastrointestinal tract injuries of the duodenum as follows, gastric ulcer in 2 cases, ulcer of the 1st duodenal portion in one case and ulcer with severe stenosis of the 2nd or 3rd duodenal portion in one case, respectively. Endoscopic features of these postirradiation gastrointestinal ulcers were characterized by deep, punched-out ulcers with grayish bases and sharp margins. Clinically these ulcers and stenosis were very difficult to treat, so by-pass operations were performed in two cases, resulting in prolonged survival.

Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

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Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

2015-09-01

The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

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F. de Clerck

2015-01-01

Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

Extended Pancreatectomy: Does It Have a Role in the Contemporary Management of Pancreatic Adenocarcinoma?

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Kaiser, Joerg; Hackert, Thilo; Büchler, Markus W

2017-01-01

Pancreatic cancer is a low-incident but highly mortal disease. Surgery is still the preferred treatment option for resectable pancreatic cancer as it offers the only realistic chance for cure. As many patients present with locally advanced disease, which is generally considered as not amenable to surgical treatment, it is important to know the limits of surgical therapy in this disease. In this review, the indication and outcomes of extended pancreatectomies as well as the alternative treatment options for locally advanced pancreatic cancer are described. Furthermore, controversies as well as ongoing and future directions for the treatment options of locally advanced pancreatic cancer are discussed. Extended pancreatectomy can be performed with higher morbidity and mortality rates in patients with locally advanced pancreatic cancer compared to patients undergoing formal pancreatic resections. These procedures offer significant advantages with respect to both perioperative results and to long-term outcome when compared to chemotherapy. Due to the higher morbidity and mortality rates, these operations should be limited to specialist units with great experience in pancreatic surgery as well as experience in peri- and post-operative management of patients with pancreatic diseases. © 2017 S. Karger AG, Basel.

The cost of unresectable stage III or stage IV melanoma in Italy

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Maio Michele

2012-11-01

Full Text Available Abstract Background In recent decades, melanoma incidence has been increasing in European countries; in 2006, there were approximately 60,000 cases leading to 13,000 deaths. Within Europe there is some geographical variation in the incidence of melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000 inhabitants per year and the lowest in the Mediterranean countries (5 to 7 cases per 100,000 inhabitants per year. Methods The present article is based on the information collected in the MELODY study (MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal survey. In that study, the medical charts of patients were reviewed to document current treatment patterns and to analyse information on patients, disease characteristics and healthcare resource utilization related to the treatment of advanced melanoma regarding patients who presented with a diagnosis of malignant melanoma (stage I to IV at participating sites between 01 July, 2005 and 30 June, 2006. Results Summarizing, though the length of the follow-up period varies among sample patients, an amount of the yearly cost per patient can be estimated, dividing the average per patient total cost (€ 5.040 by the average follow-up duration (17.5 months and reporting to one year; on these grounds, unresectable stage III or stage IV melanoma in Italy would cost € 3,456 per patient per year.

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

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Burgmans, Mark C., E-mail: m.c.burgmans@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands); Leede, Eleonora M. de, E-mail: e.m.de-leede@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Martini, Christian H., E-mail: c.h.martini@lumc.nl [Leiden University Medical Centre, Department of Anesthesiology (Netherlands); Kapiteijn, Ellen, E-mail: h.w.kapiteijn@lumc.nl [Leiden University Medical Centre, Department of Medical Oncology (Netherlands); Vahrmeijer, Alexander L., E-mail: a.l.vahrmeijer@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Erkel, Arian R. van, E-mail: a.r.van-erkel@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands)

2016-06-15

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

International Nuclear Information System (INIS)

Burgmans, Mark C.; Leede, Eleonora M. de; Martini, Christian H.; Kapiteijn, Ellen; Vahrmeijer, Alexander L.; Erkel, Arian R. van

2016-01-01

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

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Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

2015-06-01

To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma

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Wagner, Mathilde; Lucidarme, Oliver [Sorbonne Universites, UPMC, Department of Radiology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Antunes, Celia [Coimbra University Hospital, Department of Radiology, Coimbra (Portugal); Pietrasz, Daniel [Sorbonne Universites, UPMC, Department of Digestive and Hepatobiliary Surgery, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Cassinotto, Christophe [Centre Hospitalier Universitaire de Bordeaux, Department of Diagnostic and Interventional Imaging, Hopital Haut Leveque, Bordeaux (France); Zappa, Magaly [Hopitaux Universitaires Paris Nord Val de Seine, Department of Radiology, Hopital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy (France); Sa Cunha, Antonio [Hopitaux Universitaires Paris Sud, Department of Hepatobiliary Surgery, Liver Transplant Center, Hopital Paul Brousse, Villejuif (France); Bachet, Jean-Baptiste [Sorbonnes Universites, UPMC, Department of Gastroenterology and Digestive Oncology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France)

2017-07-15

To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included. Two radiologists reviewed baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer Network) classification, largest axis, product of the three axes (P3A), and arterial/venous involvement were studied and compared to pathological response and resection status and to disease-free survival (DFS). Thirty-one patients had R0 resection, including only six exhibiting a downstaging according to the NCCN classification. After treatment, the largest axis and P3A decreased (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0 resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in case of complete pathological response (P = 0.011/P = 0.016). A decrease of the arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05). Progression of the vascular involvement was seen in two (5 %) patients and led to a shorter DFS. In BR/LA pancreatic adenocarcinoma after the neoadjuvant FOLFIRINOX regimen (± chemoradiotherapy), significant tumour size decreases were observed on CT. However, CT staging was not predictive of resectability and pathological response. (orig.)

Effect of high-intensity focused ultrasound (HIFU combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and evaluation of side effects

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Jing Li

2017-02-01

Full Text Available Objective: To study the effect of high-intensity focused ultrasound (HIFU combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and the corresponding side effects. Methods: A total of 84 patients with advanced pancreatic cancer treated in our hospital between May 2013 and March 2016 were selected and randomly divided into HIFU group and IGRT group, HIFU group accepted high-intensity focused ultrasound combined with radiotherapy and IGRT group received radiotherapy alone. 4 weeks after treatment, the levels of tumor markers, liver and kidney function indexes, perineural invasionrelated molecules and cytokines in serum as well as the levels of immune cells in peripheral blood were determined. Results: 4 weeks after treatment, serum CA199, CA242, OPN, NGAL, RBP4, NGF, TrkA, p75, BDNF and TrkB levels of HIFU group were significantly lower than those of IGRT group, serum IL-2, TNF-毩, IFN-γ and IL-13 levels as well as peripheral blood NKT cell and CD4+T cell levels were significantly higher than those of IGRT group, and serum ALT, AST, Cr and BUN levels were not significantly different from those of IGRT group. Conclusion: HIFU combined with radiotherapy treatment of advanced pancreatic cancer can more effectively kill cancer cells, inhibit pancreatic cancer cell invasion to the peripheral nerve and enhance the antitumor immune response mediated by NKT cells and CD4+T cells.

Pancreatic islet regeneration: Therapeutic potential, unknowns and controversy

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Ingrid L. Cockburn

2015-07-01

Full Text Available Glucose homeostasis in mammals is primarily maintained by the insulin-secreting β-cells contained within pancreas-resident islets of Langerhans. Gross disruption of this glucose regulation as a result of pancreatic dysfunction frequently results in diabetes, which is currently a major health concern in South Africa, as well as globally. For many years, researchers have realised that the pancreas, and specifically the islets of Langerhans, have a regenerative capacity, as islet mass has frequently been shown to increase following induced pancreatic injury. Given that gross β-cell loss contributes significantly to the pathogenesis of both type 1 and type 2 diabetes, endogenous pancreatic islet regeneration has been investigated extensively as a potential β-cell replacement therapy for diabetes. From the extensive research conducted on pancreatic regeneration, opposing findings and opinions have arisen as to how, and more recently even if, pancreatic regeneration occurs following induced injury. In this review, we outline and discuss the three primary mechanisms by which pancreatic regeneration is proposed to occur: neogenesis, β-cell replication and transdifferentiation. We further explain some of the advanced techniques used in pancreatic regeneration research, and conclude that despite the technologically advanced research tools available to researchers today, the mechanisms governing pancreatic regeneration may remain elusive until more powerful techniques are developed to allow for real-time, live-cell assessment of morphology and gene expression within the pancreas.

Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

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Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected. All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001). S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.

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Wilts, I T; Hutten, B A; Meijers, J C M; Spek, C A; Büller, H R; Kamphuisen, P W

2017-06-01

Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer. The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models. We analysed 477 patients (protein C tertiles: C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07). Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

The value of positron emission tomography/computed tomography for evaluating metastatic disease in patients with pancreatic cancer.

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Kim, Mi-Jin; Lee, Kwang Hyuck; Lee, Kyu Taek; Lee, Jong Kyun; Ku, Bon-Ho; Oh, Cho-Rong; Heo, Jin Seok; Choi, Seong-Ho; Choi, Dong Wook

2012-08-01

Routine application of positron emission tomography/computed tomography (PET/CT) for pancreatic cancer staging remains a controversial approach. The purpose of this study was to reassess the clinical impact of PET/CT for the detection of distant metastasis of pancreatic cancer. From January 2006 to June 2009, 125 patients with histologically proven pancreatic cancer that had undergone PET/CT at our hospital were retrospectively reviewed. To evaluate the clinical efficacy of PET/CT on the management plan, the post-PET/CT management plans were compared with the pre-PET/CT management plans. After the conventional staging workup, we determined that 76 patients (60.8%) had resectable lesions, whereas 48 patients had unresectable lesions. One patient underwent explorative laparotomy due to equivocal resectability. Positron emission tomography/computed tomography diagnosed distant metastasis in only 2 (2.6%) of the 76 patients with resectable lesions, and these patients did not undergo unnecessary surgical treatment. Complete resection was not performed in 8 of the 74 operative patients because they had distant metastasis detected during the operative procedure. Positron emission tomography/computed tomography diagnosed distant metastasis in 32 of the 44 patients with metastatic lesions that were histologically shown to have sensitivity of 72.7%. Positron emission tomography/computed tomography has a limited role in the evaluation of metastatic disease from pancreatic cancer.

Use of Respiratory-Correlated Four-Dimensional Computed Tomography to Determine Acceptable Treatment Margins for Locally Advanced Pancreatic Adenocarcinoma

International Nuclear Information System (INIS)

Goldstein, Seth D.; Ford, Eric C.; Duhon, Mario; McNutt, Todd; Wong, John; Herman, Joseph M.

2010-01-01

Purpose: Respiratory-induced excursions of locally advanced pancreatic adenocarcinoma could affect dose delivery. This study quantified tumor motion and evaluated standard treatment margins. Methods and Materials: Respiratory-correlated four-dimensional computed tomography images were obtained on 30 patients with locally advanced pancreatic adenocarcinoma; 15 of whom underwent repeat scanning before cone-down treatment. Treatment planning software was used to contour the gross tumor volume (GTV), bilateral kidneys, and biliary stent. Excursions were calculated according to the centroid of the contoured volumes. Results: The mean ± standard deviation GTV excursion in the superoinferior (SI) direction was 0.55 ± 0.23 cm; an expansion of 1.0 cm adequately accounted for the GTV motion in 97% of locally advanced pancreatic adenocarcinoma patients. Motion GTVs were generated and resulted in a 25% average volume increase compared with the static GTV. Of the 30 patients, 17 had biliary stents. The mean SI stent excursion was 0.84 ± 0.32 cm, significantly greater than the GTV motion. The xiphoid process moved an average of 0.35 ± 0.12 cm, significantly less than the GTV. The mean SI motion of the left and right kidneys was 0.65 ± 0.27 cm and 0.77 ± 0.30 cm, respectively. At repeat scanning, no significant changes were seen in the mean GTV size (p = .8) or excursion (p = .3). Conclusion: These data suggest that an asymmetric expansion of 1.0, 0.7, and 0.6 cm along the respective SI, anteroposterior, and medial-lateral directions is recommended if a respiratory-correlated four-dimensional computed tomography scan is not available to evaluate the tumor motion during treatment planning. Surrogates of tumor motion, such as biliary stents or external markers, should be used with caution.

PKD signaling and pancreatitis

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Yuan, Jingzhen; Pandol, Stephen J.

2016-01-01

Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

Acute Pancreatitis and Ileus Postcolonoscopy

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Hin Hin Ko

2009-01-01

Full Text Available Postpolypectomy bleeding and perforation are the most common complications of colonoscopy. A case of acute pancreatitis and ileus after colonoscopy is described. A 60-year-old woman underwent a gastroscopy and colonoscopy for investigation of iron deficiency anemia. Gastroscopy was normal; however, the colonoscope could not be advanced beyond the splenic flexure due to a tight angulation. Two polypectomies were performed in the descending colon. After the procedure, the patient developed a distended, tender abdomen. Bloodwork was remarkable for an elevated amylase level. An abdominal x-ray and computed tomography scan showed pancreatitis (particularly of the tail, a dilated cecum and a few air-fluid levels. The patient improved within 24 h of a repeat colonoscopy and decompression tube placement. The patient had no risk factors for pancreatitis. The causal mechanism of pancreatitis was uncertain but likely involved trauma to the tail of the pancreas during the procedure. Our patient developed ileus, likely secondary to pancreatitis. The present case is the first report of clinical pancreatitis and ileus associated with colonoscopy.

New tapered metallic stent for unresectable malignant hilar bile duct obstruction.

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Sakai, Yuji; Tsuyuguchi, Toshio; Nishikawa, Takao; Sugiyama, Harutoshi; Sasaki, Reina; Sakamoto, Dai; Watanabe, Yuto; Nakamura, Masato; Yasui, Shin; Mikata, Rintaro; Yokosuka, Osamu

2015-10-16

To examine the usefulness of a new tapered metallic stent (MS) in patients with unresectable malignant hilar bile duct obstruction. This new tapered MS was placed in 11 patients with Bismuth II or severer unresectable malignant hilar bile duct obstruction, as a prospective study. The subjects were six patients with bile duct carcinoma, three with gallbladder cancer, and two with metastatic bile duct obstruction. Stenosis morphology was Bismuth II: 7, IIIa: 3, and IV: 1. UMIN Clinical Trial Registry (UMIN000004758). MS placement was 100% (11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4% (4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. The tapered MS proved useful in patients with unresectable malignant hilar bile duct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred.

[Latest advances in acute pancreatitis].

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de-Madaria, Enrique

2013-10-01

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

OpenAIRE

George H Sakorafas; Vasileios Smyrniotis

2012-01-01

Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

Endoscopic ultrasound features of chronic pancreatitis

DEFF Research Database (Denmark)

Rana, Surinder Singh; Vilmann, Peter

2015-01-01

As endoscopic ultrasound (EUS) is the most sensitive imaging modality for diagnosing pancreatic disorders, it can demonstrate subtle alterations in the pancreatic parenchymal and ductal structure even before traditional imaging and functional testing demonstrate any abnormality. In spite...... of this fact and abundant literature, the exact role of EUS in the diagnosis of chronic pancreatitis (CP) is still not established. The EUS features to diagnose CP have evolved over a period from a pure qualitative approach to more advanced and complicated scoring systems incorporating multiple parenchymal...... to define the exact role of these criteria. The measurement of strain ratio using quantitative EUS elastography and thus allowing quantification of pancreatic fibrosis seems to be a promising new technique....

Advances in treatment of autoimmune pancreatitis

Directory of Open Access Journals (Sweden)

LI Ji

2013-07-01

Full Text Available Autoimmune pancreatitis (AIP is a type of chronic pancreatitis characterized by an autoimmune inflammatory process. Treatment protocols for AIP are still evolving. According to the articles about AIP treatment in recent years, the indications for steroid therapy include specific clinical manifestations (jaundice, abdominal pain, etc., markedly abnormal imaging findings, and extrapancreatic organ involvement. The initial dose of steroid (prednisone is usually 0.6 mg·kg-1·d-1 or 30-40 mg/d; after 3 weeks to 1 month of treatment with the initial dose, the dose is decreased by 5-10 mg every 1-2 weeks until it drops to 2.5-5 mg/d; this dose is maintained for 6 months to 3 years. No consensus has been reached on the adverse effect of steroid on diabetes mellitus complicating AIP. Immunosuppressive agents should be used for the patients with disease relapses or with important extrapancreatic organs involved. Rituximab might become one of the therapies for refractory AIP. Although some patients achieved remission after surgical treatment, surgery is still not recommended as a routine treatment protocol due to the complications after surgery.

Animal models for investigating chronic pancreatitis

Science.gov (United States)

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

Laparoscopic stomach-partitioning gastrojejunostomy with reduced-port techniques for unresectable distal gastric cancer.

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Hirahara, Noriyuki; Matsubara, Takeshi; Hyakudomi, Ryoji; Hari, Yoko; Fujii, Yusuke; Tajima, Yoshitsugu

2014-03-01

The improvement of quality of life is of great importance in managing patients with far-advanced gastric cancer. We report a new cure and less invasive method of creating a stomach-partitioning gastrojejunostomy in reduced-port laparoscopic surgery for unresectable gastric cancers with gastric outlet obstruction. A 2.5-cm vertical intraumbilical incision was made, and EZ Access (Hakko Co., Ltd., Tokyo, Japan) was placed. After pneumoperitoneum was created, an additional 5-mm trocar was inserted in the right upper abdomen. A gastrojejunostomy was performed in the form of an antiperistaltic side-to-side anastomosis, in which the jejunal loop was elevated in the antecolic route and anastomosed to the greater curvature of the stomach using an endoscopic linear stapler. The jejunal loop together with the stomach was dissected with additional linear staplers just proximal to the common entry hole so that a functional end-to-end gastrojejunostomy was completed. At the same time, the stomach was partitioned using a linear stapler to leave a 2-cm-wide lumen in the lesser curvature. Subsequently, jejunojejunostomy was performed 30 cm distal to the gastrojejunostomy, and the stomach-partitioning gastrojejunostomy resembling Roux-en Y anastomosis was completed. All patients resumed oral intake on the day of operation. Neither anastomotic leakage nor anastomotic stricture was observed. Our less invasive palliative operation offers the utmost priority to improve quality of life for patients with unresectable gastric cancer.

Preoperative biliary drainage using a fully covered self-expandable metallic stent for pancreatic head cancer: A prospective feasibility study.

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Togawa, Osamu; Isayama, Hiroyuki; Kawakami, Hiroshi; Nakai, Yousuke; Mohri, Dai; Hamada, Tsuyoshi; Kogure, Hirofumi; Kawakubo, Kazumichi; Sakamoto, Naoya; Koike, Kazuhiko; Kita, Hiroto

2018-01-01

The role of endoscopic preoperative biliary drainage (PBD) for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. This study was performed to evaluate the feasibility and safety of PBD using a fully covered self-expandable metallic stent (FCSEMS). This multicenter prospective study involved 26 patients treated for pancreatic head cancer with distal bile duct obstruction from April 2011 to March 2013. An FCSEMS was endoscopically placed in 24 patients. Among these, 7 patients were diagnosed with unresectable cancer, and 17 underwent surgery at a median of 18 days after FCSEMS placement. The main outcome measure was preoperative and postoperative adverse events. Two adverse events (cholecystitis and insufficient resolution of jaundice) occurred between FCSEMS placement and surgery (12%). Postoperative adverse events occurred in eight patients (47%). The cumulative incidence of stent-related adverse events 4 and 8 weeks after FCSEMS placement among the 24 patients who underwent this procedure were 19%. PBD using an FCSEMS is feasible in patients with resectable pancreatic head cancer. Placement of an FCSEMS can be an alternative PBD technique when surgery without delay is impossible. A larger randomized controlled trial is warranted.

CT-guided high-dose-rate brachytherapy of unresectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Collettini, Federico; Schreiber, Nadja; Schnapauff, Dirk; Denecke, Timm; Hamm, Bernd; Gebauer, Bernhard; Wust, Peter; Schott, Eckart

2015-01-01

The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable hepatocellular carcinoma (HCC). Over a 6-year period, 98 patients with 212 unresectable HCC underwent CT-HDRBT applying a 192 Ir source at our institution. Magnetic resonance imaging (MRI) follow-up was performed 6 weeks after the intervention and then every 3 months. The primary endpoint was local tumor control (LTC); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Patients were available for MRI evaluation for a mean follow-up of 23.1 months (range 4-64 months; median 20 months). Mean tumor diameter was 5 cm (range 1.8-12 cm). Eighteen of 212 (8.5 %) tumors showed local progression after a mean LTC of 21.1 months. In all, 67 patients (68.4 %) experienced distant tumor progression. The mean PFS was 15.2 months. Forty-six patients died during the follow-up period. Median OS was 29.2 months. Actuarial 1-, 2-, and 3-year OS rates were 80, 62, and 46 %, respectively. CT-HDRBT is an effective therapy to attain local tumor control in patients with unresectable HCC. Prospective randomized studies comparing CT-HDRBT with the standard treatments like Radiofrequency ablation (RFA) and chemoembolization (TACE) are mandatory. (orig.) [de

Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence; Chang, Stephanie; Kuo, Timothy; Ford, James M.; Fisher, George A.; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Greco, Ralph; Yang, George P.; Koong, Albert C.

2008-01-01

Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant

Characterization of Pancreatic Tumor Motion Using Cine MRI: Surrogates for Tumor Position Should Be Used With Caution

International Nuclear Information System (INIS)

Feng, Mary; Balter, James M.; Normolle, Daniel; Adusumilli, Saroja; Cao Yue; Chenevert, Thomas L.; Ben-Josef, Edgar

2009-01-01

Purpose: Our current understanding of intrafraction pancreatic tumor motion due to respiration is limited. In this study, we characterized pancreatic tumor motion and evaluated the application of several radiotherapy motion management strategies. Methods and Materials: Seventeen patients with unresectable pancreatic cancer were enrolled in a prospective internal review board-approved study and imaged during shallow free-breathing using cine MRI on a 3T scanner. Tumor borders were agreed on by a radiation oncologist and an abdominal MRI radiologist. Tumor motion and correlation with the potential surrogates of the diaphragm and abdominal wall were assessed. These data were also used to evaluate planning target volume margin construction, respiratory gating, and four-dimensional treatment planning for pancreatic tumors. Results: Tumor borders moved much more than expected. To provide 99% geometric coverage, margins of 20 mm inferiorly, 10 mm anteriorly, 7 mm superiorly, and 4 mm posteriorly are required. Tumor position correlated poorly with diaphragm and abdominal wall position, with patient-level Pearson correlation coefficients of -0.18-0.43. Sensitivity and specificity of gating with these surrogates was also poor, at 53%-68%, with overall error of 35%-38%, suggesting that the tumor may be underdosed and normal tissues overdosed. Conclusions: Motion of pancreatic tumor borders is highly variable between patients and larger than expected. There is substantial deformation with breathing, and tumor border position does not correlate well with abdominal wall or diaphragmatic position. Current motion management strategies may not account fully for tumor motion and should be used with caution.

Contemporary Management of Localized Resectable Pancreatic Cancer.

Science.gov (United States)

Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ma, Wen Wee; Mahipal, Amit

2018-01-20

Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15-20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

Inaugural Meeting of North American Pancreatic Cancer Organizations: Advancing Collaboration and Communication.

Science.gov (United States)

Kenner, Barbara J; Fleshman, Julie M; Goldberg, Ann E; Rothschild, Laura J

2015-11-01

A meeting of North American Pancreatic Cancer Organizations planned by Kenner Family Research Fund and Pancreatic Cancer Action Network was held on July 15-16, 2015, in New York City. The meeting was attended by 32 individuals from 20 nonprofit groups from the United States and Canada. The objectives of this inaugural convening were to share mission goals and initiatives, engage as leaders, cultivate potential partnerships, and increase participation in World Pancreatic Cancer Day. The program was designed to provide opportunities for informal conversations, as well as facilitated discussions to meet the stated objectives. At the conclusion of the meeting, the group agreed that enhancing collaboration and communication will result in a more unified approach within the field and will benefit individuals diagnosed with pancreatic cancer. As a first step, the group will actively collaborate to participate in World Pancreatic Cancer Day, which is planned for November 13, 2015, and seeks to raise the level of visibility about the disease globally.

Molecular biology of pancreatic cancer.

Science.gov (United States)

Zavoral, Miroslav; Minarikova, Petra; Zavada, Filip; Salek, Cyril; Minarik, Marek

2011-06-28

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syndromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

The side effects and complications of percutaneous iodine-125 seeds implantation under CT-guide for patients with advanced pancreatic cancer.

Science.gov (United States)

Lv, Wei-Fu; Lu, Dong; Xiao, Jing-Kun; Mukhiya, Gauri; Tan, Zhong-Xiao; Cheng, De-Lei; Zhou, Chun-Ze; Zhang, Xing-Min; Zhang, Zheng-Feng; Hou, Chang-Long

2017-12-01

The present study investigates the side effects and complications of computed tomography (CT)-guided percutaneous iodine-125 (I-125) seeds implantation for advanced pancreatic cancer. The clinical data were retrospectively analyzed for patients treated with implantation of I-125 seeds under CT-guide in our hospital from May 2010 to April 2015. The side effects and complications were collected and their possible reasons were analyzed. A total of 78 patients were enrolled. The side effects were categorized as fever in 29 cases (37.18%), abdominal pain in 26 cases (33.33%), nausea and vomiting in 9 cases (11.54%), diarrhea in 5 cases (6.41%), and constipation in 4 cases (5.13%). Complications were composed of pancreatitis in 9 cases (11.54%), infection in 5 cases (6.41%), seed migration in 2 cases (2.56%), intestinal perforation in 1 case (1.28%), and intestinal obstruction in 1 case. The incidence of complication was 23.08% (18/78). The difference in incidence of complication was statistically significant between patients implanted with ≤27 seeds and those with >27 seeds (P = .032). The side effects and complications frequently occur in implantation of I-125 seeds for patients with advanced pancreatic cancer. More concern should be given to the patients treated by this technique. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

International Nuclear Information System (INIS)

Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

2013-01-01

In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma

International Nuclear Information System (INIS)

Lou, Emil; Peters, Katherine B; Sumrall, Ashley L; Desjardins, Annick; Reardon, David A; Lipp, Eric S; Herndon, James E II; Coan, April; Bailey, Leighann; Turner, Scott; Friedman, Henry S; Vredenburgh, James J

2013-01-01

Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6–10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m 2 on days 1–5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 nonhematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials

Pancreatic Stones: Treat or Ignore?

Directory of Open Access Journals (Sweden)

DA Howell

1999-01-01

Full Text Available Painful, chronic pancreatitis is of complex etiology, but increasing clinical experience suggests that removal of pancreatic duct stones in many cases significantly improves patients’ symptoms. The development and refinement of therapeutic endoscopic retrograde choledochopancreatography have permitted improved access to the pancreatic duct, which makes the development of new techniques of stone fragmentation and fragment removal a much more successful nonsurgical intervention. A major step forward has been the understanding of the safety and efficacy of pancreatic sphincterotomy, which is necessary for the removal of these difficult stones. The recognition that extracorporeal shock wave lithotripsy can be delivered safely with good efficacy has revolutionized the nonsurgical management of pancreatic duct stones. Nevertheless, advanced and sophisticated therapeutic endoscopy is necessary to achieve clearance of the duct, which can generally be accomplished in the majority of selected patients. State-of-the-art treatments are described, and some new approaches using pancreatoscopy and electrohydrolic lithotripsy are discussed. Newly recognized long term complications are reviewed. Finally, it must be recognized that chronic pancreatitis is an ongoing disease that does not have a simple treatment or cure, and frequently represents a process of remissions and relapses requiring interventions and problem solving.

Pancreatic Tuberculosis or Autoimmune Pancreatitis

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Ayesha Salahuddin

2014-01-01

Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

Effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue

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Lei Liu

2016-11-01

Full Text Available Objective: To study the effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue. Methods: A total of 144 patients with locally advanced gastric cancer receiving surgical resection after neoadjuvant chemotherapy in our hospital between May 2012 and August 2015 were selected and randomly divided into experimental group who received preoperative oral S-1 combined with regional intra-arterial chemotherapy and control group who received preoperative intravenous systemic chemotherapy. The levels of serum tumor markers were determined after chemotherapy, and the expression levels of tumor suppressor genes and cell cycle-related molecules in tumor tissue were determined after surgical resection. Results: After neoadjuvant chemotherapy, the serum G-17, TK-1, CEA, CA19-9, CA12-5, CA72-4 and CK, CK-MB, ALT, AST levels of experimental group were significantly lower than those of control group; after surgical resection, the p16, p27, PTEN and TXNIP mRNA levels in tumor tissue of experimental group were significantly higher than those of control group while CyclinB2, CyclinD1, CyclinE, CDK1 and CDK2 mRNA levels were significantly lower than those of control group. Conclusions: Preoperative oral S-1 combined with regional intra-arterial chemotherapy can more effectively kill gastric cancer cells, reduce tumor load, inhibit cell cycle and promote cell apoptosis.

PANCREATIC CANCER

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Alojz Pleskovič

2003-12-01

Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

DEFF Research Database (Denmark)

Bjerregaard, Jon K; Mortensen, Michael B; Jensen, Helle A

2009-01-01

BACKGROUND: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior...... underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months. CONCLUSION: CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients...

Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity

International Nuclear Information System (INIS)

Nichols, R. Charles Jr.; Huh, Soon; Ho, Meng Wei; Mendenhall, Nancy P.; Morris, Christopher G.; Hoppe, Bradford S.; George, Thomas J.; Zaiden, Robert A. Jr.; Awad, Ziad T.; Asbun, Horacio J.

2013-01-01

Background: To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods: From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results: Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion: Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease

Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity

Energy Technology Data Exchange (ETDEWEB)

Nichols, R. Charles Jr.; Huh, Soon; Ho, Meng Wei; Mendenhall, Nancy P.; Morris, Christopher G.; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: rnichols@floridaproton.org; George, Thomas J.; Zaiden, Robert A. Jr. [Dept. of Hematology and Medical Oncology, Univ. of Florida, Gainesville and Jacksonville (United States); Awad, Ziad T. [Dept. of Surgery, Univ. of Florida, Jacksonville (United States); Asbun, Horacio J. [Dept. of Surgery, Mayo Clinic, Jacksonville (United States)

2013-04-15

Background: To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods: From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results: Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion: Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

Science.gov (United States)

Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

2011-06-15

Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

Advances in surgical treatment of chronic pancreatitis.

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Ni, Qingqiang; Yun, Lin; Roy, Manish; Shang, Dong

2015-02-08

The incidence of chronic pancreatitis (CP) is between 2 and 200 per 100,000 persons and shows an increasing trend year by year. India has the highest incidence of CP in the world at approximately 114 to 200 per 100,000 persons. The incidence of CP in China is approximately 13 per 100,000 persons. The aim of this review is to assist surgeons in managing patients with CP in surgical treatment. We conducted a PubMed search for "chronic pancreatitis" and "surgical treatment" and reviewed relevant articles. On the basis of our review of the literature, we found that CP cannot be completely cured. The purpose of surgical therapy for CP is to relieve symptoms, especially pain; to improve the patient's quality of life; and to treat complications. Decompression (drainage), resection, neuroablation and decompression combined with resection are commonly used methods for the surgical treatment of CP. Before developing a surgical regimen, surgeons should comprehensively evaluate the patient's clinical manifestations, auxiliary examination results and medical history to develop an individualized surgical treatment regimen.

SURGICAL TREATMENT OF CHRONIC CYSTIC PANCREATITIS

Directory of Open Access Journals (Sweden)

O. N. Sled

2016-01-01

Full Text Available Increasing the number of patients with complicated forms of chronic pancreatitis and pancreatic cysts observed in recent decades. Mostly people of working age are susceptible to disease. This makes the issue a social importance.The article presents a modern view of the choice of method of surgical treatment of chronic pancreatitis and cystic optimal terms of therapy, depending on the degree of “maturity” of pancreatic cysts. A detailed analysis of both traditional surgery and advanced minimally invasive treatment for pancreatic cysts is performed in this review of the literature.Emphasis is placed on radical methods of treatment, particularly in the duodenum-preserving operations. Pathogenic study is carried out. The problem of choosing the most radical and at the same time the organ-preserving technique, helping to improve the immediate and long-term results, the quality of life and social and labor rehabilitation, has not lost its relevance. Studies carried out in this area are currently important.

Unresectable Carcinoma of the Paranasal Sinuses: Outcomes and Toxicities

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Nelson, Carl J.; Gomez, Daniel R.; Stegman, Lauren D.; Wu, Abraham J.; Wolden, Suzanne L.; Pfister, David G.; Zelefsky, Michael J.; Shah, Jatin P.; Kraus, Dennis H.; Lee, Nancy Y.

2008-01-01

Purpose: To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy. Methods and Materials: Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy (n = 35, 90%) or with radiotherapy alone (n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy (n = 18, 46%), intensity-modulated radiotherapy (n = 12, 31%), or conventional radiotherapy (n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy (n = 32, 82%) and/or concomitant boost radiotherapy (n = 29, 74%). Results: With a median follow-up of 90 months, the 5-year local progression-free survival, regional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse (n = 25, 64%), mostly within the irradiated field (n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression-free survival and overall survival was a biologically equivalent dose of radiation ≥65 Gy. Conclusions: Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control

Pancreatic Cancer: Multicenter Prospective Data Collection and Analysis by the Hungarian Pancreatic Study Group.

Science.gov (United States)

Lakatos, Gábor; Balázs, Anita; Kui, Balázs; Gódi, Szilárd; Szücs, Ákos; Szentesi, Andrea; Szentkereszty, Zsolt; Szmola, Richárd; Kelemen, Dezső; Papp, Róbert; Vincze, Áron; Czimmer, József; Pár, Gabriella; Bajor, Judit; Szabó, Imre; Izbéki, Ferenc; Halász, Adrienn; Leindler, László; Farkas, Gyula; Takács, Tamás; Czakó, László; Szepes, Zoltán; Hegyi, Péter; Kahán, Zsuzsanna

2016-06-01

Pancreatic cancer is a devastating disease with poor prognosis. There is very limited information available regarding the epidemiology and treatment strategies of pancreatic cancer in Central Europe. The purpose of the study was to prospectively collect and analyze data of pancreatic cancer in the Hungarian population. The Hungarian Pancreatic Study Group (HPSG) organized prospective, uniform data collection. Altogether 354 patients were enrolled from 14 Hungarian centers. Chronic pancreatitis was present in 3.7% of the cases, while 33.7% of the patients had diabetes. Family history for pancreatic cancer was positive in 4.8%. The most frequent presenting symptoms included pain (63.8%), weight loss (63%) and jaundice (52.5%). The reported frequency of smoking and alcohol consumption was lower than expected (28.5% and 27.4%, respectively). The majority of patients (75.6%) were diagnosed with advanced disease. Most patients (83.6%) had a primary tumor located in the pancreatic head. The histological diagnosis was ductal adenocarcinoma in 90.7% of the cases, while neuroendocrine tumor was present in 5.3%. Biliary stent implantation was performed in 166 patients, 59.2% of them received metal stents. Primary tumor resection was performed in 60 (16.9%) patients. Enteral or biliary bypass was done in 35 and 49 patients, respectively. In a multivariate Cox-regression model, smoking status and presence of gemcitabine-based chemotherapy were identified as independent predictors for overall survival. We report the first data from a large cohort of Hungarian pancreatic cancer patients. We identified smoking status and chemotherapy as independent predictors in this cohort.

Clinical experience with chronomodulated infusional 5-fluorouracil chemoradiotherapy for pancreatic adenocarcinoma

International Nuclear Information System (INIS)

Keene, Kimberly S.; Rich, Tyvin A.; Penberthy, David R.; Shepard, Robert C.; Adams, Reid; Jones, R. Scott

2005-01-01

Purpose: To evaluate retrospectively the efficacy and chronic toxicities of concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in patients with pancreatic adenocarcinoma. Methods and Materials: Twenty-eight patients with pancreatic adenocarcinoma were treated between January 1997 and May 2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of chemotherapy was chosen on the basis of a lower toxicity profile in the treatment of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men and 16 were women. Eight patients had unresectable disease and 20 were treated after pancreatic resection. The median radiation dose was 50.4 Gy given in 28 fractions. The median field length and width was 10.6 cm and 10.9 cm, respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a median total dose of 8.4 g/m 2 (300 mg/m 2 /d). Chronomodulated 5-FU delivery consisted of a low basal infusion for 16 h followed by an 8-h escalating-deescalating infusion peaking at 10 PM. Survival and recurrence data were evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using the Radiation Therapy Oncology Group grading system. Results: The median follow-up for all patients was 26 months (range, 4-68 months). The median overall survival for the 20 patients treated postoperatively was 34 months, with a 3- and 5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients with carcinoma of the ampulla were removed from the data set, the mean overall survival in the resected patients was 34 months, with a 3-year and 5-year actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients had a median overall survival of 14 months, and none lived past 2 years. No patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five patients had nausea and dehydration requiring i.v. fluids; only one (4%) was hospitalized. Four patients required a dose reduction

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

Science.gov (United States)

Cahen, Djuna L; Gouma, Dirk J; Laramée, Philippe; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Fockens, Paul; Kuipers, Ernst J; Pereira, Stephen P; Wonderling, David; Dijkgraaf, Marcel G W; Bruno, Marco J

2011-11-01

A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study.

Science.gov (United States)

Jiang, Ni; Qiao, Guoliang; Wang, Xiaoli; Morse, Michael A; Gwin, William R; Zhou, Lei; Song, Yuguang; Zhao, Yanjie; Chen, Feng; Zhou, Xinna; Huang, Lefu; Hobeika, Amy; Yi, Xin; Xia, Xuefeng; Guan, Yanfang; Song, Jin; Ren, Jun; Lyerly, H Kim

2017-09-01

Purpose: Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy. Experimental Design: Consecutive patients ( n = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care. Results: DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days), or supportive care only (52 and 43 days; P < 0.001). After adjusting for competing risk factors, DC-CIK combined with S-1 and receipt of 2 or more cycles of DC-CIK treatment remained independent predictors of disease-free and overall survival ( P < 0.05). Phenotypic analysis of PBMCs demonstrated that the CD3 + , CD3 + /CD4 + , and CD8 + /CD28 + T-cell subsets were elevated ( P < 0.05), while the CD3 + /CD8 + , CD3 + /CD16 + /CD56 + and CD4 + /CD25 + cell subsets were significantly decreased after DC-CIK cell therapy ( P < 0.05). There were no grade 3 or 4 toxicities. In addition, the mutational frequency in cell-free tumor DNA (cfDNA) declined in 4 of 14 patients who received DC-CIK, and was associated with a more favorable survival. Conclusions: Treatment of advanced pancreatic cancer with combined DC-CIK infusions and S-1 was safe, resulted in favorable PFS and OS, and modulated the peripheral blood immune repertoire. Clin Cancer Res; 23(17); 5066-73. ©2017 AACR . ©2017 American Association for Cancer Research.

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

Science.gov (United States)

Grignani, Giovanni; Palmerini, Emanuela; Ferraresi, Virginia; D'Ambrosio, Lorenzo; Bertulli, Rossella; Asaftei, Sebastian Dorin; Tamburini, Angela; Pignochino, Ymera; Sangiolo, Dario; Marchesi, Emanuela; Capozzi, Federica; Biagini, Roberto; Gambarotti, Marco; Fagioli, Franca; Casali, Paolo Giovanni; Picci, Piero; Ferrari, Stefano; Aglietta, Massimo

2015-01-01

Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374. We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Although the combination of sorafenib and everolimus showed activity as a further-line treatment

ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

Directory of Open Access Journals (Sweden)

P. V. Novokhatny

2014-02-01

Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer

International Nuclear Information System (INIS)

Ishikawa, Kazuki; Nakamatsu, Kiyoshi; Shiraishi, Osamu; Yasuda, Takushi; Nishimura, Yasumasa

2015-01-01

The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m 2 + 5-FU 700 mg/m 2 /d x 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/ 25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year locoregional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer. (author)

Value of intraoperative radiotherapy in locally advanced rectal cancer

NARCIS (Netherlands)

Ferenschild, Floris T. J.; Vermaas, Maarten; Nuyttens, Joost J. M. E.; Graveland, Wilfried J.; Marinelli, Andreas W. K. S.; van der Sijp, Joost R.; Wiggers, Theo; Verhoef, Cornelis; Eggermont, Alexander M. M.; de Wilt, Johannes H. W.

PURPOSE: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. METHODS: Between 1987 and 2002, 123 patients with initial unresectable

Esophageal bypass after failed chemoradiotherapy for unresectable esophageal cancer

International Nuclear Information System (INIS)

Matono, Satoru; Tanaka, Toshiaki; Mori, Naoki; Nagano, Takeshi; Fujita, Hiromasa; Shirouzu, Kazuo

2013-01-01

Esophageal stenosis and/or fistula often occur after chemoradiotherapy (CRT) for unresectable esophageal cancer. In such patients, an esophageal stent can help achieve oral intake. However an esophageal stent cannot be inserted where there is complete stenosis or where the tumor is located. In such cases, esophageal bypass surgery may be necessary. Here, we investigated the clinical characteristics and outcomes in patients who underwent esophageal bypass surgery in our institution. We reviewed 10 cases of esophageal bypass surgery (gastric tube in 8 cases, colon in 2 cases) after CRT for unresectable esophageal cancer, between 2001 and 2009. There were 5 of stenosis-only cases, 4 fistula-only cases, and 1 case of stenosis and fistula. There were postoperative complications in 5 cases (50%), and all these were treated conservatively and healed. The median survival from surgery to peroral intake was 20 days (range 9-90 days), and the median survival after starting peroral intake was 130 days (range 48-293 days). Esophageal bypass surgery can achieve good performance status and improve peroral intake. (author)

Radiation therapy for unresectable locally advanced breast cancer

International Nuclear Information System (INIS)

Horikawa, Noriko; Inoue, Masayoshi; Uehara, Tomoko; Miyasaka, T.; Miyasaka, M.; Tabata, Yoji; Sakamoto, Nobuyuki; Nakagawa, Y.

2013-01-01

Thirteen cases of inoperable advanced breast cancer were treated with radiotherapy between 2002 to 2012 at Nara Prefectural Hospital. All cases were treated by radiotherapy and chemo-endocrine therapy. Patients received 60-81 Gy (median 60 Gy) to the primary breast tumor. Response of the breast tumors were complete response in 3 cases (23%), partial response in 8 cases (62%) and stable disease in 2 cases (15%) (response rate: 85%). All breast tumors had been controlled and skin troubles were reduced. Radiotherapy for breast cancer is useful for primary tumor control and improved quality of life (QOL). Radiotherapy should be considered to be useful modality in the treatment of advanced breast cancer. (author)

MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

Science.gov (United States)

Madzak, Adnan; Olesen, Søren Schou; Lykke Poulsen, Jakob; Bolvig Mark, Esben; Mohr Drewes, Asbjørn; Frøkjær, Jens Brøndum

2017-11-01

The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

Biliary stenting and anti-cancer therapy for unresectable hilar bile duct carcinomas

International Nuclear Information System (INIS)

Saito, Hiroya; Hokotate, Hirofumi; Takeuchi, Shyuhei; Takamura, Akio

2007-01-01

At present, although imaging diagnosis has been developed, most hilar bile duct cancer is still diagnosed at an advanced stage and its prognosis is generally poor. In hilar bile duct cancer, radiotherapy and other several therapies, for example-chemotherapy, arterial-infusion chemotherapy, photodynamic therapy, etc-are being performed for non-operative cases. But standard therapies for this cancer has not been established yet. On the other hand, metallic stents (MS) have been widely used to relieve biliary obstructions as an alternative to plastic prostheses and conventional drainage. The use of MS offers good palliation in hilar bile duct cancer, but patients selection is a key to obtain good results. In this article we reviewed previous studies and clinical trials regarding the anti-cancer therapy and biliary stenting for unresectable hilar bile duct cancer. And optimal therapeutic strategy for hilar bile duct cancer is proposed, primarily based on present views. (author)

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

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Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

2011-02-24

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

International Nuclear Information System (INIS)

Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

2011-01-01

Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Hurt, Christopher N.; Mukherjee, Somnath; Bridgewater, John; Falk, Stephen; Crosby, Tom; McDonald, Alec; Joseph, George; Staffurth, John; Abrams, Ross A.; Blazeby, Jane M.; Bridges, Sarah; Dutton, Peter; Griffiths, Gareth; Maughan, Tim; Johnson, Colin

2015-01-01

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

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Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Mukherjee, Somnath [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Bridgewater, John [UCL Cancer Institute, London (United Kingdom); Falk, Stephen [Bristol Haematology and Oncology Centre, Bristol (United Kingdom); Crosby, Tom [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); McDonald, Alec [Beatson West of Scotland Cancer Centre, Glasgow, Scotland (United Kingdom); Joseph, George [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); Staffurth, John [Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales (United Kingdom); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Blazeby, Jane M. [Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol (United Kingdom); Bridges, Sarah [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Dutton, Peter [Centre for Statistics in Medicine, University of Oxford, Oxford (United Kingdom); Griffiths, Gareth [Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton (United Kingdom); Maughan, Tim [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Johnson, Colin [University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton (United Kingdom)

2015-11-15

Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

Science.gov (United States)

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-08-02

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

International Nuclear Information System (INIS)

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-01-01

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient’s symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted

Hedgehog signaling and therapeutics in pancreatic cancer.

LENUS (Irish Health Repository)

Kelleher, Fergal C

2012-02-01

OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

Application of multidisciplinary treatment using chemoradiotherapy for advanced esophageal cancer and problems thereof

International Nuclear Information System (INIS)

Osaka, Yoshiaki; Takagi, Yuu; Hoshino, Sumito; Shinohara, M.; Ogata, Takashi; Tsuchida, Akihiko; Aoki, Tatsuya

2007-01-01

Application of multidisciplinary treatment using chemoradiotherapy (CRT) for advanced esophageal cancer and the problems thereof were examined by stage. Subjects consisted of 169 cases of patients with advanced esophageal cancer who underwent CRT from 1998 to 2004 (stage III/IVa/IVb: 102/55/12 cases). Mean age was 63.4 years old, and male-to-female ratio was 145: 24. In all cases, low dose FP+radiation 40 Gy (4 weeks) was performed. Surgery was performed for resectable cases, and additional irradiation of 20-30 Gy for unresectable cases and those who refused surgery. Considerations included percentage of effectiveness, side effects, and prognosis. Side effects: Low white blood cell (WBC) was 65.1%, esophagitis was 30.2%, anemia was 21.3%, and thrombocytopenia was 12.4%. Stage III: Percentage of effectiveness was 52.0%. Survival rate of 5: 51.0% for resected cases (n=69) and 16.8% for unresected cases (n=33) (p=0.0002). Reasons for unresection: 17 cases of refusal of surgery, 11 cases comprising physical reasons, and 5 cases of others. Stage IVa: The percentage of effectiveness was 45.4%. Survival rate of 5: 23.1% in resected cases (n=13), and 9.8% in unresected cases (n=42). Stage IVb (all cases unresected): The percentage of effectiveness was 25.0%. Survival rate of 1: 11.7%. Survival rate of 2: 0%. In stage III, if prognosis of resected cases after CRT was good and resection was possible after CRT, surgery was desirable. In stage IVa, if it is a single organ T4 case, resection is possible after CRT, which is a good application of CRT. The stage IVb prognosis is poor, so chemotherapy with new regimens should be considered. (author)

Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

Science.gov (United States)

A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

[Three Cases of Unresectable, Advanced, and Recurrent Colorectal Cancer Associated with Gastrointestinal Obstruction That Were Treated with Small Intestine-Transverse Colon Bypass Surgery].

Science.gov (United States)

Ida, Arika; Miyaki, Akira; Miyauchi, Tatsuomi; Yamaguchi, Kentaro; Naritaka, Yoshihiko

2016-11-01

Herein, we report 3cases of unresectable, advanced, and recurrent colorectal cancer associated with gastrointestinal obstruction. The patients were treated with small intestine-transverse colon bypass surgery, which improved the quality of life (QOL)in all cases. Case 1 was an 80-year-old woman who presented with subileus due to ascending colon cancer. After surgery, her oral intake was reestablished, and she was discharged home. Case 2 was an 89-year-old woman whose ileus was caused by cecal cancer with multiple hepatic metastases. After surgery, the patient was discharged to a care facility. Case 3 was an 83-year-old man whose ileus was caused by a local recurrence and small intestine infiltration after surgery for rectosigmoid cancer. He underwent surgery after a colonic stent was inserted. His oral intake was re-established and he was discharged home. Small bowel-transverse colon bypass surgery can be used to manage various conditions rostral to the transverse colon. It is still possible to perform investigations in patients whose general condition is poorer than that of patients who undergo resection of the primary lesion. This avoids creating an artificial anus and allows continuation of oral intake, which are useful for improving QOL in terminal cases.

Locally advanced pancreatic duct adenocarcinoma: pancreatectomy with planned arterial resection based on axial arterial encasement.

Science.gov (United States)

Perinel, J; Nappo, G; El Bechwaty, M; Walter, T; Hervieu, V; Valette, P J; Feugier, P; Adham, M

2016-12-01

Pancreatectomy with arterial resection for locally advanced pancreatic duct adenocarcinoma (PDA) is associated with high morbidity and is thus considered as a contraindication. The aim of our study was to report our experience of pancreatectomy with planned arterial resection for locally advanced PDA based on specific selection criteria. All patients receiving pancreatectomy for PDA between October 2008 and July 2014 were reviewed. The patients were classified into group 1, pancreatectomy without vascular resection (66 patients); group 2, pancreatectomy with isolated venous resection (31 patients), and group 3, pancreatectomy with arterial resection for locally advanced PDA (14 patients). The primary selection criteria for arterial resection was the possibility of achieving a complete resection based on the extent of axial encasement, the absence of tumor invasion at the origin of celiac trunk (CT) and superior mesenteric artery (SMA), and a free distal arterial segment allowing reconstruction. Patient outcomes and survival were analyzed. Six SMA, two CT, four common hepatic artery, and two replaced right hepatic artery resections were undertaken. The preferred arterial reconstruction was splenic artery transposition. Group 3 had a higher preoperative weight loss, a longer operative time, and a higher incidence of intraoperative blood transfusion. Ninety-day mortality occurred in three patients in groups 1 and 2. There were no statistically significant differences in the incidence, grade, and type of complications in the three groups. Postoperative pancreatic fistula and postpancreatectomy hemorrhage were also comparable. In group 3, none had arterial wall invasion and nine patients had recurrence (seven metastatic and two loco-regional). Survival and disease-free survival were comparable between groups. Planned arterial resection for PDA can be performed safely with a good outcome in highly selected patients. Key elements for defining the resectability is based on

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

Energy Technology Data Exchange (ETDEWEB)

Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Kohno, Ryosuke; Kawashima, Mitsuhiko; Arahira, Satoko; Nishio, Teiji [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Tahara, Makoto [Division of Gastrointestinal Oncology and Endoscopy, National Cancer Center Hospital East, Chiba (Japan); Hayashi, Ryuichi [Division of Head and Neck Surgery, National Cancer Center Hospital East, Chiba (Japan); Kishimoto, Seiji [Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo (Japan); Ogino, Takashi [Division of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan)

2011-12-01

Purpose: The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. Results: Median patient age was 57 years (range, 22-84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n = 26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). Conclusion: These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

International Nuclear Information System (INIS)

Zenda, Sadamoto; Kohno, Ryosuke; Kawashima, Mitsuhiko; Arahira, Satoko; Nishio, Teiji; Tahara, Makoto; Hayashi, Ryuichi; Kishimoto, Seiji; Ogino, Takashi

2011-01-01

Purpose: The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. Results: Median patient age was 57 years (range, 22–84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n = 26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). Conclusion: These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

The Epidemiology of Pancreatitis and Pancreatic Cancer

Science.gov (United States)

Yadav, Dhiraj; Lowenfels, Albert B.

2013-01-01

Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

[Management of localized, locally advanced and metastatic pancreatic adenocarcinoma].

Science.gov (United States)

Delpero, Jean-Robert; Turrini, Olivier; Raoul, Jean-Luc

2015-03-01

Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.

Research advances in the prevention and treatment of pancreatitis after endoscopic retrograde cholangiopancreatography

Directory of Open Access Journals (Sweden)

ZHANG Weifeng

2018-03-01

Full Text Available Endoscopic retrograde cholangiopancreatography (ERCP is an important technique for the diagnosis and treatment of biliary and pancreatic diseases and post-ERCP pancreatitis (PEP is the most common complication of ERCP. Since the birth of ERCP, the prevention and treatment of PEP has become the focus of international research. In recent years, much progress has been made in the aspects of risk factors, pharmacological prevention, and prophylactic stent implantation in the pancreatic duct. Since these research findings are not consistent, further clinical studies are needed to demonstrate such findings.

Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Koong, Albert C.; Christofferson, Erin; Le, Quynh-Thu; Goodman, Karyn A.; Ho, Anthony; Kuo, Timothy; Ford, James M.; Fisher, George A.; Greco, Ralph; Norton, Jeffrey; Yang, George P.

2005-01-01

Purpose: To determine the efficacy of concurrent 5-fluorouracil (5-FU) and intensity-modulated radiotherapy (IMRT) followed by body stereotactic radiosurgery (SRS) in patients with locally advanced pancreatic cancer. Methods and Materials: In this prospective study, all patients (19) had pathologically confirmed adenocarcinoma and were uniformly staged. Our treatment protocol consisted of 45 Gy IMRT with concurrent 5-FU followed by a 25 Gy SRS boost to the primary tumor. Results: Sixteen patients completed the planned therapy. Two patients experienced Grade 3 toxicity (none had more than Grade 3 toxicity). Fifteen of these 16 patients were free from local progression until death. Median overall survival was 33 weeks. Conclusions: Concurrent IMRT and 5-FU followed by SRS in patients with locally advanced pancreatic cancer results in excellent local control, but does not improve overall survival and is associated with more toxicity than SRS, alone

The epidemiology of pancreatitis and pancreatic cancer.

Science.gov (United States)

Yadav, Dhiraj; Lowenfels, Albert B

2013-06-01

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

International Nuclear Information System (INIS)

Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

1995-01-01

To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

Role of 18F-fluorodeoxyglucose positron emission tomography imaging in surgery for pancreatic cancer

Institute of Scientific and Technical Information of China (English)

Hisao Wakabayashi; Yoshihiro Nishiyama; Tsuyoshi Otani; Takanori Sano; Shinichi Yachida; Keiichi Okano; Kunihiko Izuishi; Yasuyuki Suzuki

2008-01-01

AIM:To evaluate the role of positron emission tomo- graphy using 18F-fluorodeoxyglucose (FDG-PET) in the surgical management of patients with pancreatic cancer,including the diagnosis, staging, and selection of patients for the subsequent surgical treatment.METHODS: This study involved 53 patients with proven primary pancreatic cancer. The sensitivity of diagnosing the primary cancer was examined for FDG-PET, CT,cytological examination of the bile or pancreatic juice,and the serum levels of carcinoembrionic antigens (CEA) and carbohydrate antigen 19-9 (CA19-9). Next, the accuracy of staging was compared between FDG-PET and CT. Finally, FDG-PET was analyzed semiquantitatively using the standard uptake value (SUV). The impact of the SUV on patient management was evaluated by examining the correlations between the SUV and the histological findings of cancer.RESULTS: The sensitivity of FDG-PET, CT, cytological examination of the bile or pancreatic juice, and the serum levels of CEA and CA19-9 were 92.5%, 88.7%, 46.4%, 37.7% and 69.8%, respectively. In staging, FDG-PET was superior to CT only in diagnosing distant disease (bone metastasis). For local staging, the sensitivity of CT was better than that of FDG-PET. The SUV did not correlate with the pTNM stage, grades, invasions to the vessels and nerve, or with the size of the tumor. However, there was a statistically significant difference (4.6±2.9 vs 7.8±4.5, P = 0.024) in the SUV between patients with respectable and unresectable disease. CONCLUSION: FDG-PET is thus considered to be useful in the diagnosis of pancreatic cancer. However, regarding the staging of the disease, FDG-PET is not considered to be a sufficiently accurate diagnostic modality. Although the SUV does not correlate with the patho-histological prognostic factors, it may be useful in selecting patients who should undergo subsequent surgical treatment.

Hereditary chronic pancreatitis in a patient with type 1 diabetes mellitus

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Varalakshmi Muthukrishnan

2018-01-01

Full Text Available In this case report, we present a young patient with type 1 diabetes who had hereditary chronic pancreatitis. We evaluated him for the cause of pancreatitis, but it was inconclusive and finally the genetic testing was done for him, which revealed heterozygous missense mutation in exon 3 of the PRSS1 gene (protease serine 1 gene on chromosome 7. Hence, we were able to make the diagnosis of hereditary chronic pancreatitis. Chronic pancreatitis secondary to any cause can lead to permanent diabetes, which is typically difficult to control. However, in this case, the episodes of recurrent pancreatitis were present after the onset of type 1 diabetes as compared to the usual presentation of diabetes after the advancement of chronic pancreatitis.

Palliative treatment with radiation-emitting metallic stents in unresectable Bismuth type III or IV hilar cholangiocarcinoma.

Science.gov (United States)

Lu, Jian; Guo, Jin-He; Zhu, Hai-Dong; Zhu, Guang-Yu; Wang, Yong; Zhang, Qi; Chen, Li; Wang, Chao; Pan, Tian-Fan; Teng, Gao-Jun

2017-01-01

The emerging data for stenting in combination with brachytherapy in unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma. Consecutive patients who underwent percutaneous placement with REMS or uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III or IV hilar cholangiocarcinoma between September 2011 and April 2016 were identified into this retrospective study. Data on patient demographics and overall survival, functional success, stent patency and complications were collected at the authors' hospital. A total of 59 patients were included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The median overall survival was 338 days in the REMS group and 141 days in the SEMS group (philar cholangiocarcinoma, and seems to prolong survival as well as patency of stent in these patients.

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

Energy Technology Data Exchange (ETDEWEB)

Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

2009-10-15

Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

Pancreatic islet transplantation

Directory of Open Access Journals (Sweden)

Corrêa-Giannella Maria

2009-09-01

Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

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Sakorafas, George H; Smyrniotis, Vasileios

2012-07-10

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the

Pancreatic Exocrine Insufficiency in Pancreatic Cancer

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Miroslav Vujasinovic

2017-02-01

Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

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Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

2017-02-23

Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

CT diagnosis of pancreatic carcinoma and chronic pancreatitis

International Nuclear Information System (INIS)

Luan Baoqing; Jin Erhu; Zhang Lizhen; Jiang Haibin

1997-01-01

To improve the diagnostic accuracy of pancreatic carcinoma and chronic pancreatitis. The CT findings of 154 cases with pancreatic carcinoma, chronic pancreatitis and mis-diagnosed other pancreatic diseases proven clinically and pathologically were analysed. Slice thickness of 8 mm and slice interval of 8 mm were used and thin-section scan and enhancement study were performed in some cases. The main signs in degassing and differential diagnosis between pancreatic carcinoma and chronic pancreatitis included: (1) focal or diffuse enlargement and density abnormality of pancreas; (2) dilated common bile duct was suddenly obstructed, peripancreatic blood vessels were invaded and cancerous thrombus was revealed, enlargement of abdominal lymph nodes and metastasis in the liver were discovered; (3) calcium deposit in the pancreatic duct area and dilated pancreatic duct which passed through the lesion or not; (4) presence and location of pancreatic cyst and its relationship to pancreatic contour. CT is the imaging modality of choice in the diagnosis of pancreatic carcinoma and chronic pancreatitis at present. The diagnostic accuracy of CT was over 90% in this series

Advances in endoscopic retrograde cholangiopancreatography

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WANG Xiangping

2018-03-01

Full Text Available Endoscopic retrograde cholangiopancreatography (ERCP is a well-established advanced endoscopic technique for the diagnosis and treatment of pancreatobiliary diseases. New advances have been made in the treatment concept and techniques of ERCP in recent years. This article elaborates on the recent advances in ERCP, including the application of pancreatic duct stent, non-steroidal anti-inflammatory drugs, and aggressive hydration to prevent postoperative pancreatitis, covered metal stent for the treatment of benign bile duct stenosis, intraluminal radiofrequency ablation for malignant bile duct stenosis, extracorporeal shockwave lithotripsy and covered metal stent for the treatment of chronic pancreatitis, peroral choledochoscopy for qualitative diagnosis of bile duct stenosis and huge refractory stones, definition of difficult intubation, timing of pre-cut technique, and ERCP after gastrointestinal reconstruction.

Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy.

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An, Mingrui; Lohse, Ines; Tan, Zhijing; Zhu, Jianhui; Wu, Jing; Kurapati, Himabindu; Morgan, Meredith A; Lawrence, Theodore S; Cuneo, Kyle C; Lubman, David M

2017-04-07

Pancreatic cancer is the third leading cause of cancer-related death in the USA. Despite extensive research, minimal improvements in patient outcomes have been achieved. Early identification of treatment response and metastasis would be valuable to determine the appropriate therapeutic course for patients. In this work, we isolated exosomes from the serum of 10 patients with locally advanced pancreatic cancer at serial time points over a course of therapy, and quantitative analysis was performed using the iTRAQ method. We detected approximately 700-800 exosomal proteins per sample, several of which have been implicated in metastasis and treatment resistance. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified eight proteins that show global treatment-specific changes. We then tested the effect of patient-derived exosomes on the migration of tumor cells and found that patient-derived exosomes, but not healthy controls, induce cell migration, supporting their role in metastasis. Our data show that exosomes can be reliably extracted from patient serum and analyzed for protein content. The differential loading of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.

Chronic pancreatitis

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Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

The evolution of the surgical treatment of chronic pancreatitis.

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Andersen, Dana K; Frey, Charles F

2010-01-01

To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

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Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

2011-01-01

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. PMID:21747084

A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer.

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Perán, Macarena; López-Ruiz, Elena; García, María Ángel; Nadaraia-Hoke, Shorena; Brandt, Ralf; Marchal, Juan A; Kenyon, Julian

2017-10-25

Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP's anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies

DEFF Research Database (Denmark)

Grande, Enrique; Kreissl, Michael C; Filetti, Sebastiano

2013-01-01

Vandetanib has recently demonstrated clinically meaningful benefits in patients with unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). Given the potential for long-term vandetanib therapy in this setting, in addition to treatment for disease-related symptoms, effective...

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

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Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

2008-01-01

Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors.

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Norton, Jeffrey A; Kivlen, Maryann; Li, Michelle; Schneider, Darren; Chuter, Timothy; Jensen, Robert T

2003-08-01

There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node

Intraoperative radiotherapy in pancreatic cancer: A systematic review

International Nuclear Information System (INIS)

Ruano-Ravina, Alberto; Almazan Ortega, Raquel; Guedea, Ferrran

2008-01-01

Background and purpose: Intraoperative radiotherapy (IORT) has been considered for treatment of pancreas cancer since local recurrence rates are very high. This study assesses the efficacy and safety of IORT in pancreatic cancer. Materials and methods: We conducted a systematic review of scientific literature from January 1995 to February 2007, including Medline, Embase, ISI Web of Science and HTA (Health Technology Assessment). By applying a series of inclusion criteria, two independent reviewers selected those studies in which a minimum of 30 patients received IORT and which furnished survival results based on a minimum 3-month follow-up. Results: Fourteen papers were included, one was an IORT assessment report, 5 were cohort studies, and the remaining 8 were case series studies, 2 of which belonged to the same series. In general, these studies showed that IORT could slightly increase survival among patients with pancreatic cancer in localized stages. However, the results were not conclusively in favor of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There were no published studies that assessed quality of life. Conclusions: There is no clear evidence to indicate that IORT is more effective than other therapies in treating pancreatic cancer in locally advanced and metastatic stages

Chronic Pancreatitis.

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Stram, Michelle; Liu, Shu; Singhi, Aatur D

2016-12-01

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Pancreatic cancer risk in hereditary pancreatitis

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Frank Ulrich Weiss

2014-02-01

Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases.

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Nakamura, T; Takebe, K; Kudoh, K; Ishii, M; Imamura, K; Kikuchi, H; Kasai, F; Tandoh, Y; Yamada, N; Arai, Y

1995-01-01

Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.

Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer

International Nuclear Information System (INIS)

Yavuz, A. Aydin; Aydin, Fazil; Yavuz, Melek N.; Ilis, Esra; Ozdemir, Feyyaz

2001-01-01

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer. Methods and Materials: Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m 2 (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m 2 (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m 2 increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m 2 and 90 mg/m 2 . The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m 2 . Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease. Conclusion: A dose of TW-G at a level of 90 mg/m 2 produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m 2 dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma

Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer.

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Hartwig, W; Gluth, A; Hinz, U; Koliogiannis, D; Strobel, O; Hackert, T; Werner, J; Büchler, M W

2016-11-01

In the recent International Study Group of Pancreatic Surgery (ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer. A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan-Meier analysis. The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival. Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable

Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

International Nuclear Information System (INIS)

Miller, Robert C.; Iott, Matthew J.; Corsini, Michele M.

2009-01-01

Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

Pancreatitis - discharge

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Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

International Nuclear Information System (INIS)

Serizawa, Itsuko; Kagei, Kenji; Kamada, Tadashi; Imai, Reiko; Sugahara, Shinji; Okada, Tohru; Tsuji, Hiroshi; Ito, Hisao; Tsujii, Hirohiko

2009-01-01

Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm 3 and 1,194 cm 3 (median 525 cm 3 ). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.

SU-E-J-136: Multimodality-Image-Based Target Delineation for Dose Painting of Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Dalah, E; Paulson, E; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2014-06-01

Purpose: Dose escalated RT may provide improved disease local-control for selected unresectable pancreatic cancer. Accurate delineation of the gross tumor volume (GTV) inside pancreatic head or body would allow safe dose escalation considering the tolerances of adjacent organs at risk (OAR). Here we explore the potential of multi-modality imaging (DCE-MRI, ADC-MRI, and FDG-PET) to define the GTV for dose painting of pancreatic cancer. Volumetric variations of DCE-MRI, ADC-MRI and FDG-PET defined GTVs were assessed in comparison to the findings on CT, and to pathology specimens for resectable and borderline reseactable cases of pancreatic cancer. Methods: A total of 19 representative patients with DCE-MRI, ADC-MRI and FDG-PET data were analyzed. Of these, 8 patients had pathological specimens. GTV, inside pancreatic head/neck, or body, were delineated on MRI (denoted GTVDCE, and GTVADC), on FDG-PET using SUV of 2.5, 40% SUVmax, and 50% SUVmax (denoted GTV2.5, GTV40%, and GTV50%). A Kruskal-Wallis test was used to determine whether significant differences existed between GTV volumes. Results: Significant statistical differences were found between the GTVs defined by DCE-MRI, ADC-MRI, and FDG-PET, with a mean and range of 4.73 (1.00–9.79), 14.52 (3.21–25.49), 22.04 (1.00–45.69), 19.10 (4.84–45.59), and 9.80 (0.32–35.21) cm3 (p<0.0001) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of GTVs based on DCE-MRI, ADC-MRI, SUV2.5, 40% SUVmax, and 50% SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. Conclusion: Differences exists between DCE, ADC, and PET defined target volumes for RT of pancreatic cancer. Further studies combined with pathological specimens are required to identify the optimal imaging modality and/or acquisition method to

Early Detection of Sporadic Pancreatic Cancer

Science.gov (United States)

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Pancreatic cancer surgery: past, present, and future.

Science.gov (United States)

Griffin, James F; Poruk, Katherine E; Wolfgang, Christopher L

2015-08-01

The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.

Epidermal Growth Factor Receptor in Pancreatic Cancer

International Nuclear Information System (INIS)

Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

2011-01-01

Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

Concurrent chemotherapy and radiation therapy for unresectable locally advanced carcinoma of the esophagus. Phase II study and clinical review on literature

International Nuclear Information System (INIS)

Fritz, P.; Stoll, P.; Wannenmacher, M.; Zierhut, D.

2003-01-01

Background: Neither surgical advances nor those in therapeutic radiology have been able to significantly reduce the mortality related to esophageal carcinomas. The results of combining: first surgery, then radiation therapy, which have been dissatisfactory for decades, encourage therapeutic concepts involving a variety of modalities. Patients and Methods: For 50 patients with unresectable locally advanced esophageal carcinomas, a palliative concurrent chemotherapy and radiation therapy was carried out according to the ''intent to treat'' principle. The aim was a minimal dose of 40 Gy. The concurrent chemotherapy was carried out using cisplatin/5-FU during the 1st and 4th weeks of radiation therapy. In the case of partial or complete remission, the chemotherapy was to be continued as maintenance therapy with a maximum of four cycles. In the case of no change or minor response, instead of maintenance chemotherapy, the dose of local radiation was to be increased by means of brachytherapy. Results: The median survival rate for the entire population under study was 8.7 months. The survival rates of 1, 2, 3, 4, and 5 years were, respectively, 38%, 20.5%, 13.7%, 6.8%, and 6.8%. The remission rates were as follows: NC: 14 patients (28%), PR: 32 patients (64%), CR: 4 patients (8%). 17 patients (34%) tolerated the full concurrent chemotherapy; only twelve patients (24%) tolerated supportive chemotherapy. The following factors exhibited a significant correlation to survival: the intensity of the chemotherapy, the Karnofsky index, the age of the patients, and the improvement of oral food intake. Conclusions: The concurrent chemotherapy was toxic and the benefit to the patients questionable. At best, meta-analyses of randomized studies along the lines of ''evidence-based medicine'' demonstrate for concurrent chemotherapy and radiation therapy an improvement of 2-year survival rates, but with these also involving a high level of toxicity. Due to the heterogeneous data available

Role of staging laparoscopy in the management of Pancreatic Duct Carcinoma (PDAC): Single-center experience from a tertiary hospital in Brazil.

Science.gov (United States)

de Jesus, Victor Hugo Fonseca; da Costa Junior, Wilson Luiz; de Miranda Marques, Tomás Mansur Duarte; Diniz, Alessandro Landskron; de Castro Ribeiro, Héber Salvador; de Godoy, André Luis; de Farias, Igor Correia; Coimbra, Felipe José Fernandez

2018-03-06

Proper staging is critical to the management of pancreatic ductal carcinoma (PDAC). Laparoscopy has been used to stage patients without gross metastatic disease with variable success. We aimed to identify the frequency of patients diagnosed by laparoscopy with occult metastatic disease. Also, we looked for variables related to a higher chance of occult metastasis. Patients with PDAC submitted to staging laparoscopy either immediately before pancreatectomy or as a separate procedure between January 2010 and December 2016 were included. None presented gross metastatic disease at initial staging. We used logistic regression to search for variables associated with metastatic disease. The study population consisted of 63 patients. Among all patients, nine (16.7%) had occult metastases at laparoscopy. Unresectable tumor (Odds ratio = 18.0, P = 0.03), increasing tumor size (Odds ratio = 1.36, P = 0.01), and abdominal pain (Odds ratio = 5.6, P = 0.04) significantly predicted the risk of occult metastases in univariate analysis. In multivariate analysis, only tumor size predicted the risk of occult metastases. Laparoscopy remains a valuable tool in PDAC staging. Patients with either large or unresectable tumors, or presenting with abdominal pain present the highest risk for occult intra-abdominal metastases. © 2018 Wiley Periodicals, Inc.

Pancreatic Enzymes

Science.gov (United States)

... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

A novel monoclonal antibody targeting carboxymethyllysine, an advanced glycation end product in atherosclerosis and pancreatic cancer.

Directory of Open Access Journals (Sweden)

Ulrika Wendel

Full Text Available Advanced glycation end products are formed by non-enzymatic reactions between proteins and carbohydrates, causing irreversible lysine and arginine alterations that severely affect protein structure and function. The resulting modifications induce inflammation by binding to scavenger receptors. An increase in advanced glycation end products is observed in a number of diseases e.g. atherosclerosis and cancer. Since advanced glycation end products also are present in healthy individuals, their detection and quantification are of great importance for usage as potential biomarkers. Current methods for advanced glycation end product detection are though limited and solely measure total glycation. This study describes a new epitope-mapped single chain variable fragment, D1-B2, against carboxymethyllysine, produced from a phage library that was constructed from mouse immunizations. The phage library was selected against advanced glycation end product targets using a phage display platform. Characterization of its binding pattern was performed using large synthetic glycated peptide and protein libraries displayed on microarray slides. D1-B2 showed a preference for an aspartic acid, three positions N-terminally from a carboxymethyllysine residue and also bound to a broad collection of glycated proteins. Positive immunohistochemical staining of mouse atherosclerotic plaques and of a tissue microarray of human pancreatic tumors confirmed the usability of the new scFv for advanced glycation end product detection in tissues. This study demonstrates a promising methodology for high-throughput generation of epitope-mapped monoclonal antibodies against AGE.

The role of intraoperative radiation therapy in patients with pancreatic cancer.

Science.gov (United States)

Palta, Manisha; Willett, Christopher; Czito, Brian

2014-04-01

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer. © 2013 Published by Elsevier Inc.

Inhibition of pancreatic tumoral cells by snake venom disintegrins.

Science.gov (United States)

Lucena, Sara; Castro, Roberto; Lundin, Courtney; Hofstetter, Amanda; Alaniz, Amber; Suntravat, Montamas; Sánchez, Elda Eliza

2015-01-01

Pancreatic cancer often has a poor prognosis, even when diagnosed early. Pancreatic cancer typically spreads rapidly and is rarely detected in its early stages, which is a major reason it is a leading cause of cancer death. Signs and symptoms may not appear until pancreatic cancer is quite advanced, and complete surgical removal is not possible. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. The importance of integrins in several cell types that affect tumor progression has made them an appealing target for cancer therapy. Some of the proteins found in the snake venom present a great potential as anti-tumor agents. In this study, we summarize the activity of two integrins antagonist, recombinant disintegrins mojastin 1 and viridistatin 2, on human pancreatic carcinoma cell line (BXPC-3). Both recombinant disintegrins inhibited some essential aspects of the metastasis process such as proliferation, adhesion, migration, and survival through apoptosis, making these proteins prominent candidates for the development of drugs for the treatment of pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management of pancreatic cancer in the elderly.

Science.gov (United States)

Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

2016-01-14

Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

Management of Inflammatory Fluid Collections and Walled-Off Pancreatic Necrosis.

Science.gov (United States)

Shah, Apeksha; Denicola, Richard; Edirisuriya, Cynthia; Siddiqui, Ali A

2017-12-01

Pancreatic fluid collections are a frequent complication of acute pancreatitis. The revised Atlanta criterion classifies chronic fluid collections into pseudocysts and walled-off pancreatic necrosis (WON). Symptomatic PFCs require drainage options that include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, minimally invasive endoscopic drainage has now become the preferred approach. An endoscopic ultrasonography (EUS)-guided approach for pancreatic fluid collection drainage is now the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WON. Direct endoscopic necrosectomy is often required in WON. Lumen apposing metal stents allow for direct endoscopic necrosectomy and debridement through the stent lumen and are now preferred in these patients. Endoscopic retrograde cholangiopancreatography with pancreatic duct exploration should be performed concurrent to PFC drainage in patients with suspected PD disruption. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Ideally, pancreatic ductal disruption should be bridged with endoscopic stenting.

Out-FOXing Pancreatic Cancer | Center for Cancer Research

Science.gov (United States)

Pancreatic cancer is one of the most lethal cancer types worldwide with increasing incidence and mortality rates in the United States. Consequently, it is projected to become the second leading cause of cancer death by 2020. Poor patient outcomes are due to a combination of diagnosis at an advanced stage and a lack of effective treatments. However, a better understanding of the molecular pathways at work in pancreatic cancers may lead to the identification of novel therapeutic targets.

Nutritional status of patients with locally advanced pancreatic cancer: a pilot study.

Science.gov (United States)

Ferrucci, Leah M; Bell, Diana; Thornton, Jennifer; Black, Glenda; McCorkle, Ruth; Heimburger, Douglas C; Saif, Muhammad Wasif

2011-11-01

Nutritional status may influence quality of life and prognosis among pancreatic cancer patients, yet few studies describe measures of nutritional status during treatment. We evaluated the nutritional status of locally advanced pancreatic cancer (LAPC) patients undergoing chemoradiotherapy who received baseline nutritional assessment and counseling. Fourteen newly diagnosed LAPC patients enrolled in phase I/II trials of capecitabine with concomitant radiotherapy were assessed for baseline clinical nutrition measures (body mass index, albumin, weight loss, total energy, and protein intake). Participants completed the Anorexia/Cachexia Subscale (A/CS) questionnaire at baseline and during the 6 weeks of treatment. We evaluated associations between baseline characteristics and subsequent A/CS scores with linear regression and changes in A/CS were assessed with the paired t test. We observed a statistically significant increase in mean A/CS between baseline [24.9, standard deviation (SD) = 9.7] and end of treatment (29.9, SD = 6.2). Controlling for baseline A/CS score, only weight loss greater than 5% of body weight over 1 month was associated with A/CS scores at 6 weeks (β = 10.558, standard error = 3.307, p value = 0.009) and mean A/CS scores during the last 3 weeks of treatment (β = 12.739, standard error = 2.251, p value = 0.001). After 6 weeks of chemoradiotherapy, LAPC patients reported a statistically significant improvement in appetite and weight concerns. Increases in AC/S scores were associated with higher baseline A/CS scores and weight loss of 5% or more during 1 month. Further research is needed to determine the impact of nutritional support during treatment, as improvements in this domain may impact LAPC patients' overall quality of life.

Some Current Views on Pancreatitis

African Journals Online (AJOL)

The past decade has seen few dramatic advances in the diagnosis and ... But there has been a broadening in the understanding of the classifica- tion, diagnostic features, natura:! history and surgical management of the disease. PATHOGENESIS .... as one of the more important diagnostic aids in pancreatic disease, but our ...

77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Science.gov (United States)

2012-04-26

...The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from manufacturers of local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g., ablation, radiotherapy, or embolization devices). Scientific information is being solicited to inform our Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma, which is currently being conducted by the Evidence-based Practice Centers for the AHRQ Effective Health Care Program. Access to published and unpublished pertinent scientific information on this device will improve the quality of this comparative effectiveness review. AHRQ is requesting this scientific information and conducting this comparative effectiveness review pursuant to Section 1013 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, Public Law 108-173.

Analysis of enzyme targeting intraoperative radiosensitization therapy (KORTUC-IORT) for abdominal malignant tumors

International Nuclear Information System (INIS)

Nishioka, Akihito; Kariya, Shinji; Kataoka, Y.; Miyatake, Kana; Tadokoro, Michiko; Hamada, Norihiko; Kubota, Kei; Ogawa, Yasuhiro

2013-01-01

We developed a new radiosensitizer injection containing hydrogen peroxide and sodium hyaluronate just followed by intraoperative radiotherapy (IORT) for locally advanced pancreatic cancer, named KORTUC-IORT (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas+IORT). Fourteen patients were treated with KORTUC-IORT, external beam radiotherapy, and systemic chemotherapy. All treatments related with KORTUC-IORT were well tolerated, with few adverse effects. The 1- and 2-year survival rates were 75% and 25%, respectively. The median survival period is 15 months. The present formulation can be delivered safely and effectively under the conditions used. (author)

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

Directory of Open Access Journals (Sweden)

J. Iglesias García

Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

Endoscopic ultrasound in the diagnosis and staging of pancreatic cancer

Directory of Open Access Journals (Sweden)

J. Iglesias García

2009-09-01

Full Text Available Pancreatic cancer is the 5th leading cause of cancer-related death in Western countries. The 5-year survival rate is approximately 4%, without significant changes over the last 50 years. This poor survival rate and bad prognosis are associated with the diagnosis of advanced-stage disease, which precludes the only potential curative treatment - surgical resection. In this setting, the main objective in the management of pancreatic cancer is to perform an early diagnosis and a correct staging of the disease. Endoscopic ultrasonography (EUS appears to be an essential tool for the diagnosis and staging of pancreatic cancer. EUS diagnostic accuracy for detecting pancreatic tumors ranges from 85 to 100%, clearly superior to other imaging techniques. EUS accuracy for the local staging of pancreatic cancer ranges from 70 to 90%, superior or equivalent to other imaging modalities. EUS-guided fine-needle aspiration allows a cyto-histological diagnosis in nearly 90% of cases, with a very low complication rate. At present, the formal indications for EUS-guided fine-needle aspiration are the necessity of palliative treatment or whenever the possibility of neoadjuvant treatment is present. It could be also indicated to differentiate pancreatic adenocarcinoma from other pancreatic conditions, like lymphoma, metastasis, autoimmune pancreatitis or chronic pancreatitis. We can conclude that EUS is an essential tool in the management of patients with pancreatic tumors.

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

NARCIS (Netherlands)

T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

2008-01-01

textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

Science.gov (United States)

Philip, Philip A; Lutz, Manfred P

2015-10-01

Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

Science.gov (United States)

2015-10-01

The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review

Institute of Scientific and Technical Information of China (English)

Saad M Ibrahim; Robert J Lewandowski; Kent T Sato; Vanessa L Gates; Laura Kulik; Mary F Mulcahy; Robert K Ryu; Reed A Omary; Riad Salem

2008-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. The majority of patients with HCC present with unresectable disease. These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies. Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses, limiting the use of external beam radiation. Because of these limitations, novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization) represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused, these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles. Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor. Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight twocurrently available radioembolic devices (90Y, 188Rh) and provide the reader with a recent review of the literature.

Radioactive self-expanding stents for palliative management of unresectable esophageal cancer: a systematic review and meta-analysis.

Science.gov (United States)

Chen, Hong-Lin; Shen, Wang-Qin; Liu, Kun

2017-05-01

Stent insertion is a feasible and safe palliative management for advanced unresectable esophageal cancer. The aim of this study is to assess the efficacy of radioactive stent for unresectable esophageal cancer compared with conventional stent. Systematic searches of the PubMed and Web of science are dated from their beginning to January 25, 2016. Studies that compared radioactive stent with conventional stent for unresectable esophageal cancer were included. The outcomes were postimplantation survival, relief of dysphagia, and complications related to stent implant. Six studies with 539 patients were included. All of them used stent equipped with radioactive iodine beads as a radioactive stent. The pooled weighted mean difference for median survival was 2.734 months (95% CI 1.710-3.775; Z = 5.21, P = 0.000) between two groups. The 1,3,6 month survival rates were higher in radioactive stents than conventional stent, with the pooled ORs 3.216 (95% CI 1.293-7.999; Z = 2.51, P = 0.012), 3.095 (95% CI 1.908-5.020; Z = 4.58, P = 0.000), and 7.503 (95% CI 2.206- 25.516; Z = 3.23, P = 0.001, respectively). The pooled hazard ratio was 0.464 (95% CI 0.328-0.655; Z = 4.35, P = 0.000) between two groups. For relief of dysphagia, two stents all have good relief of the dysphagia effect, but radioactive stent showed a better effect at 3, 6 months follow-up after implantation. For complications related to stent implant, no significant differences were found between two stents in terms of severe chest pain (30.0% vs. 35.7%, OR 0.765, 95% CI 0.490-1.196), gastroesophageal reflux (18.6% vs. 16.1%, OR 1.188, 95% CI 0.453-3.115), fever (12.1% vs. 12.1%, OR 1.014, 95% CI 0.332-3.097), bleeding (16.7% vs. 14.2%, OR 1.201, 95% CI 0.645-2.236), perforation or fistula (6.1% vs. 9.0%, OR 0.658, 95% CI 0.291-1.486), pneumonia (10.7% vs. 14.1%, OR 0.724, 95% CI 0.343-1.526), stent migration (7.0% vs. 10.2%, OR 0.651, 95% CI 0.220-1.924), and restenosis (24.2% vs. 20.6%, OR 1.228, 95% CI 0

Gemcitabine and oxaliplatin combination chemotherapy in 30 patients with advanced pancreatic carcinoma%吉西他滨联合奥沙利铂治疗晚期胰腺癌30例

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Objective: To evaluate the activity and safety of combination chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen) in patients of advanced pancreatic carcinoma. Methods: 30 patients with advanced pancreatic cancer were enrolled into this study. All patients received gemcitabine 1000 mg/m2, given by 30-minute intravenous infusion, on days 1 and 8 of each 21-day cycle. Oxaliplatin 100 mg/m2 was administered as a 2 h infusion on day 1 of each 21 day. Clinical outcomes for patients treated with two cycles of chemotherapy were evaluated according to WHO criteria. Results: All 30patients were eligible for effectiveness and safety analysis. Objective response rate was approximately 20.0%. Clinical benefit response (CBR) was a composite of assessment of pain, performance status and body weight. The pain relief rate, improvement rate of performance status and body weight were 53.3%, 46.7% and 36.7%, respectively. The main adverse effects were bone marrow depression, peripheral nerve toxicity and gastrointestinal reaction. There was no treatment-related death during the chemotherapy. Conclusion: The high response rate with low toxicity observed in this study suggests that GEMOX regimen may be an effective alternative curative treatment for patients with advanced pancreatic carcinoma and can be used more extensively in clinical practice.

[Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

Science.gov (United States)

Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

2016-02-01

One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

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

Science.gov (United States)

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

Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Schellenberg, Devin; Kim, Jeff; Christman-Skieller, Claudia; Chun, Carlene L.; Columbo, Laurie Ann; Ford, James M.; Fisher, George A.; Kunz, Pamela L.; Van Dam, Jacques; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Hsu, Annie; Maxim, Peter G.; Xing, Lei; Goodman, Karyn A.; Chang, Daniel T.; Koong, Albert C.

2011-01-01

Purpose: This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. Conclusion: Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

Effect of Radiotherapy Planning Complexity on Survival of Elderly Patients With Unresected Localized Lung Cancer

International Nuclear Information System (INIS)

Park, Chang H.; Bonomi, Marcelo; Cesaretti, Jamie; Neugut, Alfred I.; Wisnivesky, Juan P.

2011-01-01

Purpose: To evaluate whether complex radiotherapy (RT) planning was associated with improved outcomes in a cohort of elderly patients with unresected Stage I-II non-small-cell lung cancer (NSCLC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 1998 patients aged >65 years with histologically confirmed, unresected stage I-II NSCLC. Patients were classified into an intermediate or complex RT planning group using Medicare physician codes. To address potential selection bias, we used propensity score modeling. Survival of patients who received intermediate and complex simulation was compared using Cox regression models adjusting for propensity scores and in a stratified and matched analysis according to propensity scores. Results: Overall, 25% of patients received complex RT planning. Complex RT planning was associated with better overall (hazard ratio 0.84; 95% confidence interval, 0.75-0.95) and lung cancer-specific (hazard ratio 0.81; 95% confidence interval, 0.71-0.93) survival after controlling for propensity scores. Similarly, stratified and matched analyses showed better overall and lung cancer-specific survival of patients treated with complex RT planning. Conclusions: The use of complex RT planning is associated with improved survival among elderly patients with unresected Stage I-II NSCLC. These findings should be validated in prospective randomized controlled trials.

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

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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.

Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

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Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

2016-01-01

Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

an extended pancreatic normal subjects and ~in pancreatItIs In ...

African Journals Online (AJOL)

function . . patIents. N. H. GILlNSKY, A. S. MEE, I. N. MARKS. Summary. Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by ... hormones, the Lundh meal and an oral pancreatic function test .... is any different from that of the cells in me normal gland.

Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

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Sala Abdalla

2016-01-01

Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

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Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

2018-04-01

An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

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Zhiwen Xiao

2014-01-01

Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

Advanced glycation end products impair glucose-induced insulin secretion from rat pancreatic β-cells.

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Hachiya, Hiroyuki; Miura, Yoshikazu; Inoue, Ken-Ichi; Park, Kyung Hwa; Takeuchi, Masayoshi; Kubota, Keiichi

2014-02-01

Advanced glycation end products (AGEs) are derivative compounds generated from non-enzymatic glycosylation and oxidation. In comparison with glucose-derived AGEs (Glu-AGEs), glyceraldehyde-derived AGEs (Glycer-AGEs) have stronger toxicity to living systems. In this study, we compared the effects of Glu-AGE and Glycer-AGE on insulin secretion. Rat pancreatic islets were isolated by collagenase digestion and primary-cultured in the presence of 0.1 mg/ml bovine serum albumin (BSA) or 0.1 mg/ml Glu-AGE or Glycer-AGE-albumin. After 48 h of culture, we performed an insulin secretion test and identified the defects by a battery of rescue experiments [corrected]. Also, mRNA expression of genes associated with insulin secretion was measured. Insulin secretion induced by a high glucose concentration was 164.1 ± 6.0, 124.4 ± 4.4 (P < 0.05) and 119.8 ± 7.1 (P < 0.05) μU/3 islets/h in the presence of BSA, Glu-AGE, and Glycer-AGE, respectively. Inhibition of insulin secretion by Glu-AGE or Glycer-AGE was rescued by a high extracellular potassium concentration, tolbutamide and α-ketoisocaproic acid, but not by glyceraldehyde, dihydroxacetone, methylpyruvate, glucagon-like peptide-1 and acetylcholine. Glu-AGE or Glycer-AGE reduced the expression of the malate dehydrogenase (Mdh1/2) gene, which plays a critical role in the nicotinamide adenine dinucleotide (NADH) shuttle. Despite its reported cytotoxicity, the effects of Glycer-AGE on insulin secretion are similar to those of Glu-AGE. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

The docetaxel radiosensitization experience for the treatment of unresectable esophageal cancer

International Nuclear Information System (INIS)

Maruyama, Shoji; Maruyama, Michio; Tanami, Hideaki

2005-01-01

Docetaxel is an increasingly important drug for the treatment of esophageal cancer. The docetaxel radiosensitization has been established in cancer cell lines. The therapeutic response and toxicity of a weekly docetaxel in combination with radiotherapy for unresectable esophageal cancer were examined. Ten patients with locally advanced or metastatic squamous cell esophageal cancer were recruited in the following protocol. The median age was 65.7 years. Patients received radiation in 2 Gy single daily fractions to a total dose of 60 Gy. Docetaxel (10 mg/m 2 ) was administered weekly for 6 consecutive weeks. One patient could not be evaluated. The overall response rate was 77% with 11% complete response (CR) and 66% partial response (PR). Mild grade 2 leukocytes toxicity was observed in 2/10 patients, which enforced the treatment absence for 7-14 days. Grade 2 stomatitis was noted in one patient. No severe grade 3 adverse effects were observed. It is concluded that low-dose docetaxel with radiotherapy is feasible and, a high response rate can be expected. Toxicity is modest, and this protocol may be useful for the outpatients or neoadjuvant chemotherapy. (author)

Pancreatic trauma.

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Lahiri, R; Bhattacharya, S

2013-05-01

Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

Autoimmune pancreatitis

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Davorin Dajčman

2007-05-01

Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

Endocrine pancreatic function changes after acute pancreatitis.

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Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

2011-10-01

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Pancreatitis in Children.

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Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

2016-11-01

Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

Curative resection for locally advanced sigmoid colon cancer using neoadjuvant chemotherapy with FOLFOX plus panitumumab: A case report

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Kenji Tomizawa

2017-01-01

Conclusion: To our knowledge, this is the first report of a successful curative resection in a patient with initially unresectable, locally advanced colorectal cancer who was treated with FOLFOX4 combined with panitumumab.

Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach.

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Lee, Tae Yoon; Cheon, Young Koog; Shim, Chan Sup

2016-04-01

This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p hilar CC. Lower pre-PDT bilirubin levels were associated with longer survival in all patients.

A "rendezvous technique" for treating a pancreatic fistula after distal pancreatectomy.

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Imai, Daisuke; Yamashita, Yo-ichi; Ikegami, Toru; Toshima, Takeo; Harimoto, Norifumi; Yoshizumi, Tomoharu; Soejima, Yuji; Shirabe, Ken; Ikeda, Tetsuo; Maehara, Yoshihiko

2015-01-01

Pancreatic fistulae are a major complication of distal pancreatectomy (DP). Some cases of severe pancreatic fistula require invasive procedures. There have been some reports concerning the effectiveness of pancreatic duct drainage through an endoscopic transpapillary approach for pancreatic fistulae. We herein present a case of a pancreatic fistula after DP that was successfully treated with percutaneous pancreatic duct drainage, which was performed using a combined percutaneous and endoscopic approach, named the "rendezvous technique". In our case, we performed distal pancreatectomy with celiac artery resection for a locally advanced pancreatic body cancer. On postoperative day (POD) 7, the drain amylase level increased up to 37,460 IU/l. Computed tomography (CT) revealed peripancreatic fluid collections. On POD 10, we placed a catheter in the main pancreatic duct using the rendezvous technique. CT on POD 14 revealed a decrease in the size of the peripancreatic fluid collection, and contrast imaging from the drains on POD 22 revealed almost complete disappearance of the fluid collection. We withdrew the pigtail catheter on POD 27 and the percutaneous pancreatic duct drain on POD 36. This patient was discharged from our hospital on POD 40. We herein report a new approach called the "rendezvous technique" for the management of pancreatic fistulae after DP that can be used instead of a stressful nasopancreatic tube.

[Chronic pancreatitis: Retrospective review of 121 cases].

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Berger F, Zoltán; Mancilla A, Carla

2016-12-01

Chronic pancreatitis (CP) is a rare disease in Chile, without a clear explanation for this low prevalence. To analyze the characteristics of our patients with pancreatitis. Retrospective analysis of a database of patients with pancreatitis of a clinical hospital. Morphological proof of diagnosis (calcifications/calculi, alterations of ducts, local complication or histology) was obtained for every patient. History of acute pancreatitis was recorded and exocrine-endocrine function was assessed. We retrieved information of 121 patients with pancreatitis (86 males) in a period of 20 years. The number of cases increased markedly every five years. The calculated incidence and prevalence was 0.8/100,000/year and 6/100,000, respectively. Pancreatic calcifications were initially observed in 93 patients and became evident during the follow-up in another six patients. Severe pain or local complications occurred in 27 patients, requiring surgery in 10 or endoscopic treatment in 15. During the years of follow-up, 55 patients were free of symptoms. Exocrine and endocrine insufficiency was demonstrated and treated in 81 and 67 patients, respectively. Alcoholic etiology was evident in 40% of patients. In 29% no etiology was identified. Mapuche origin was exceptional. Late diagnosis of CP is common, since most of our patients presented with advanced stages. Even though CP is increasingly diagnosed in our hospitals, the number of cases is still far fewer when compared to other countries. Underdiagnosis alone cannot explain this difference and genetic factors might be of importance.

Early diagnosis of chronic pancreatitis: understanding the factors associated with the development of chronic pancreatitis.

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Yamabe, Akane; Irisawa, Atsushi; Shibukawa, Goro; Sato, Ai; Fujisawa, Mariko; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Abe, Yoko; Igarashi, Ryo; Maki, Takumi; Yamamoto, Shogo

2017-04-28

The prognosis of advanced chronic pancreatitis (CP) is poor with the mortality rate approximately two-fold higher than the general population according to a survey of the prognosis of CP.　From this standpoint, the concept of early CP was propagated in Japan in 2009 to encourage the medical treatment for the earlier stages of CP.　That is, picking up the patients suspicious for early CP and then providing medical treatment for them are very important not only for patients, but also for health care economics.　In this review, we described some potential factors associated with the development of CP (alcohol, smoking, past history of acute pancreatitis, aging, gallstone, and gender) that are extremely important to discover patients with early-stage CP.

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

International Nuclear Information System (INIS)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I.; Gerber, D.A.; Mazariegos, G.V.; Reyes, J.

2000-01-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

Intrahepatic chemoembolization in unresectable pediatric liver malignancies

Energy Technology Data Exchange (ETDEWEB)

Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I. [Department of Radiology, Children' s Hospital of Pittsburgh, PA (United States); Gerber, D.A.; Mazariegos, G.V.; Reyes, J. [Department of Transplant Surgery, Children' s Hospital of Pittsburgh, PA (United States)

2000-11-01

Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma

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Higashi, Tatsuya; Nishii, Ryuichi [Shiga Medical Center Research Institute, Moriyama City, Shiga (Japan); Hatano, Etsuro; Ikai, Iwao; Seo, Satoru; Kitamura, Koji; Takada, Yasuji; Kamimoto, Shinji [Kyoto University Graduate School of Medicine, Department of Gastroenterological Surgery, Sakyo-ku, Kyoto (Japan); Nakamoto, Yuji; Ishizu, Koichi; Suga, Tsuyoshi; Kawashima, Hidekazu; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, Sakyo-ku, Kyoto (Japan)

2010-03-15

To elucidate the prognostic role of post-therapeutic {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET), we conducted a retrospective cohort study analysing the clinical factors that affect overall survival after non-operative therapy for unresectable hepatocellular carcinoma (HCC). Sixty-seven cases with unresectable HCC who received non-operative therapy (transcatheter arterial chemoembolization: n=24, transcatheter arterial infusion chemotherapy: n=31, radiofrequency ablation: n = 5 or systemic chemotherapy: n = 7) and had received FDG PET for the evaluation of the therapeutic effect within 1 month after the end of the therapy were evaluated. Overall survival rate was evaluated using the univariate and multivariate analyses of relevant clinical and laboratory parameters before and after therapy, including visual PET analysis and quantitative analysis using maximum standardized uptake value (SUV). Visual PET diagnosis of post-therapeutic lesions was a good predictor of overall survival of unresectable HCC patients. The low FDG group showed significantly longer survival (average: 608 days) than that (average: 328 days) of the high FDG group (p<0.0001). Multivariate analysis showed four significant prognostic factors for the survival: post-therapeutic alpha-fetoprotein ({alpha}FP) level (=400 ng/ml, p=0.004), post-therapeutic visual PET diagnosis (p=0.006), post-therapeutic clinical stage (UICC stage IV, p=0.04) and post-therapeutic Milan criteria (p=0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET (5.0 or more) or others did not show significance. The present study suggests that post-therapeutic PET performed within 1 month after non-operative therapy can be a good predictor of overall survival in unresectable HCC patients, while pre-therapeutic evaluation including PET, tumour markers and clinical staging may not be useful. (orig.)

Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

Science.gov (United States)

Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

2017-09-01

Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Fenghua Liu

Full Text Available OBJECTIVE: To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC versus systemic chemotherapy for stage III/IV pancreatic cancer. METHODS: Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP, and China National Knowledge Infrastructure (CNKI electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2 statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. RESULTS: Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR with regional intra-arterial chemotherapy (RIAC, whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment, clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment, total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment, and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment. The median survival time with RIAC (5-21 months was longer than for systemic chemotherapy (2.7-14 months. Similarly, one year survival rates with RIAC (28.6%-41.2% were higher than with systemic chemotherapy (0%-12.9%.. CONCLUSION: Regional intra-arterial chemotherapy is more effective and has fewer complications than

Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

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Liu, Fenghua; Tang, Yong; Sun, Junwei; Yuan, Zhanna; Li, Shasha; Sheng, Jun; Ren, He; Hao, Jihui

2012-01-01

To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer. Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP), and China National Knowledge Infrastructure (CNKI) electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2) statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR) with regional intra-arterial chemotherapy (RIAC), whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment), clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment), total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment), and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment). The median survival time with RIAC (5-21 months) was longer than for systemic chemotherapy (2.7-14 months). Similarly, one year survival rates with RIAC (28.6%-41.2%) were higher than with systemic chemotherapy (0%-12.9%.). Regional intra-arterial chemotherapy is more effective and has fewer complications than systemic chemotherapy for treating advanced

Neonatal pancreatic pericytes support β-cell proliferation

Directory of Open Access Journals (Sweden)

Alona Epshtein

2017-10-01

Conclusions: This study introduces pancreatic pericytes as regulators of neonatal β-cell proliferation. In addition to advancing current understanding of the physiological β-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes.

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

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Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation.

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Swords, Douglas S; Mone, Mary C; Zhang, Chong; Presson, Angela P; Mulvihill, Sean J; Scaife, Courtney L

2015-10-01

Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown. This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC. Of 313 patients, 98 (31.3 %) had an initial misdiagnosis. Misdiagnosed patients were younger, 62.8 ± 12.6 vs. 68.0 ± 10.1 (p < 0.001). The most common initial misdiagnoses were: gallbladder disease, gastroesophageal reflux disease, and peptic ulcer disease. After excluding patients with prior cholecystectomy, 14.2 % were misdiagnosed with gallbladder disease and underwent cholecystectomy before PDAC diagnosis. Misdiagnosed patients had higher rates of abdominal pain (p < 0.001), weight loss (p = 0.04), and acute pancreatitis (p < 0.001) and lower rate of jaundice (p < 0.001). Median time between symptoms to PDAC diagnosis was longer in misdiagnosed: 4.2 months vs. 1.4 (p < 0.001). Median time from contact with medical provider to axial imaging was longer in misdiagnosed (p < 0.001). Rate of stages III-IV disease at diagnosis was higher in misdiagnosed: 61.2 vs. 43.7 % (p = 0.004), with a 1.4 (95 % confidence interval (CI), 1.12-1.74) higher risk of stages III-IV disease at diagnosis; however, there was no difference in median overall survival in misdiagnosed patients (9.6 months in misdiagnosed vs. 10.3 months in correctly diagnosed, p = 0.69). Initial misdiagnosis of patients with proximal PDAC is associated with delay in diagnosis and higher risk of locally advanced or advanced disease at time of PDAC diagnosis.

A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

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Gustav J Ullenhag

Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

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Konski, Andre; Meyer, Joshua E.; Joiner, Michael; Hall, Michael J.; Philip, Philip; Shields, Anthony; McSpadden, Erin; Choi, Minsig; Adaire, Beth; Duncan, Gail; Meropol, Neal J.; Cescon, Terrence P.; Cohen, Steven J.

2014-01-01

Purpose: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 and 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. Conclusion: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients

Solitary main pancreatic ductal calculus of possible biliary origin causing acute pancreatitis.

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Chaparala, Ramakrishna Prasad Chowdary; Patel, Rafiuddin; Guthrie, James Ahsley; Davies, Mervyn Huw; Guillou, Pierre J; Menon, Krishna V

2005-09-10

Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. A 59-year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) revealed a calculus in the main pancreatic duct in the head of the pancreas causing acute pancreatitis. There were no features suggestive of chronic pancreatitis on CT scanning. The episode acute pancreatitis was managed conservatively. ERCP extraction of the calculus failed as the stone was impacted in the main pancreatic duct resulting in severe acute pancreatitis. Once this resolved, a transduodenal exploration and extraction of the pancreatic ductal calculus was performed successfully. Crystallographic analysis revealed the composition of the calculus was different to that seen in chronic pancreatitis, but more in keeping with a calculus of biliary origin. This could be explained by migration of the biliary calculus via the common channel into the main pancreatic duct. Following the operation the patient made an uneventful recovery and was well at two-year follow up. Acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Failing endoscopic extraction, transduodenal exploration and extraction is a safe option after resolution of acute pancreatitis.

The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis.

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Miskiewicz, Andrzej; Szparecki, Grzegorz; Durlik, Marek; Rydzewska, Grażyna; Ziobrowski, Ireneusz; Górska, Renata

2015-12-01

The aim of this study was to establish the correlation between the occurrence of Q705K and F359L polymorphisms in patients diagnosed with pancreatic diseases and periodontal conditions of various degrees of severity. The above-mentioned genetic markers were assessed in patients with pancreatic cancer (n = 18) and chronic pancreatitis (n = 39) as well as in a healthy control group (n = 115). The established inclusion criteria were the following: Caucasian descent, non-smoking, and age range 20-80, with different levels of periodontitis activity according to S. Offenbacher's scale. The genotyping reactions were performed by means of an RT-PCR with the use of TaqMan(®) genotyping assay. Results of the study revealed that the state of periodontium was significantly worse in patients with chronic pancreatitis. The Q705K and F359L polymorphisms were associated with more advanced cases of periodontitis measured by clinical attachment level, whereas the Q705K was associated with intensified bleeding index. Furthermore, the F359L single-nucleotide polymorphism was significantly higher in the group with chronic pancreatitis (p periodontitis, pancreatic cancer, and chronic pancreatitis. These findings might constitute the basis for a new diagnostic and therapeutic approach.

Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis.

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Kahaleh, M; Brock, A; Conaway, M R; Shami, V M; Dumonceau, J M; Northup, P G; Tokar, J; Rich, T A; Adams, R B; Yeaton, P

2007-04-01

The current treatment model for the management of malignant biliary obstruction is to place a plastic stent for unstaged pancreatic cancer. In patients with unresectable disease but a life expectancy of more than 6 months, self-expandable metal stents (SEMS) are favored because of their more prolonged patency. We analyzed the efficacy and cost-effectiveness of covered SEMS (CSEMS) in patients with pancreatic cancer and distal biliary obstruction without regard to surgical resectability. Between March 2001 and March 2005, 101 consecutive patients with obstructive jaundice secondary to pancreatic cancer underwent placement of a CSEMS. Patients with resectable tumor were offered pancreaticoduodenectomy. A model was developed to compare the costs of CSEMS and polyethylene and DoubleLayer stents. A total of 21 patients underwent staging laparoscopy, of whom 16 had a resection (76%). The 85 patients who did not have a resection had a mean survival of 5.9 months (range 1-25 months) and a mean CSEMS patency duration of 5.5 months (range 1-16 months). Life-table analysis demonstrated CSEMS patency rates of 97% at 3 months, 85% at 6 months, and 68% at 12 months. In a cost model that accounted for polyethylene and DoubleLayer stent malfunction and surgical resections, initial CSEMS placement (3177 euros per patient) was a less costly intervention than either DoubleLayer stent placement (3224 euros per patient) or polyethylene stent placement with revision (3570 euros per patient). Covered SEMS are an effective treatment for distal biliary obstructions caused by pancreatic carcinoma. Their prolonged patency and removability makes them an attractive option for biliary decompression, regardless of resectability. The strategy of initial covered SEMS placement might be the most cost-effective strategy in these patients.

Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

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Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

2017-07-01

Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

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Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

2016-05-01

Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. Based on a retrospective analysis of patients admitted to Dutch hospitals, a first

A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors.

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Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se Hoon; Ahn, Jin Seok; Park, Keunchil; Moon, Seung Hwan; Ahn, Myung-Ju

2015-12-01

We conducted a prospective phase II study of cisplatin plus cremophor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors to determine the efficacy and tolerability of the combination therapy. Patients were treated with cisplatin (70 mg/m) and Genexol-PM (230 mg/m) on day 1 of a 3-week cycle as first-line palliative chemotherapy. The primary end point of this study was objective response rate, and the secondary end points included toxicity, progression-free survival (PFS), overall survival, correlation between early 18F-fluorodeoxyglucose positron emission tomography/computed tomography response and PFS, and correlation between baseline flurododeoxyglucose uptake and histology. Forty-two patients with unresectable thymoma (n = 14) or thymic carcinoma (n = 28) were enrolled between May 2012 and October 2014. The median age was 59 years (range: 25-77) and 30 patients (71%) were male, and 39 patients (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range: 1-6). For 40 assessable patients, the objective response rate was 62.5% (95% confidence interval [CI]: 47.6-77.4) with rates of 46% (95% CI: 23.3-76.9) for advanced thymoma (n = 13) and 70% (95% CI: 52.0-82.1) for thymic carcinoma (n = 27). With a median follow-up of 15.5 months, the median PFS for all 42 patients was 9.8 months (11.4 months for thymoma versus 8.1 months for thymic carcinoma). The 2-year overall survival was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Eight patients (19%) experienced grade 2 hypersensitivity reactions. There was no correlation between early positron emission tomography response and PFS, but tumor histology (thymoma versus thymic carcinoma) was correlated with SUVmax before chemotherapy. These data suggest that combination of cisplatin and Genexol-PM is highly effective and

Environmental risk factors for chronic pancreatitis and pancreatic cancer.

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Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

2011-01-01

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

Acute Pancreatitis and Pregnancy

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... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

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Wilson, J; Connock, M; Song, F; Yao, G; Fry-Smith, A; Raftery, J; Peake, D

2005-07-01

To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments. Electronic databases. As there were no randomised trials that have directly compared imatinib with the current standard treatment in patients with advanced GIST, this review included non-randomised controlled studies, cohort studies, and case series that reported effectiveness results of treatment with imatinib and/or other interventions in patients with advanced GIST. The effectiveness assessment was based on the comparison of results from imatinib trials and results from studies of historical control patients. Economic evaluation was mainly based on an assessment and modification (when judged necessary) of a model submitted by Novartis. Evidence from published uncontrolled trials involving 187 patients, and from abstracts reporting similar uncontrolled trials involving 1700 patients, indicates that approximately 50% of imatinib-treated individuals with advanced GIST experience a dramatic clinical response in terms of at least a 50% reduction in tumour mass. At present, although useful data are accumulating, it is not possible to predict which patients may respond in this way. Fifteen studies where possible GIST patients had been treated with therapies other than imatinib or best supportive care were also identified. All imatinib-treated patients experienced adverse effects, although they were relatively mild. Overall, imatinib was reported to be well tolerated. The most common serious events included unspecified haemorrhage and neutropenia. Skin rash, oedema and periorbital oedema were the common adverse events observed. Patients on the highest dose regimen (1000 mg per day in one trial) may experience dose-limiting drug toxicity. A structured assessment was carried out of the Novartis economic evaluation of imatinib for unresectable and/or metastatic GIST

Contrast-enhanced CT in determining resectability in patients with pancreatic carcinoma: a meta-analysis of the positive predictive values of CT

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Somers, Inne; Bipat, Shandra [University of Amsterdam, Department of Radiology, Academic Medical Centre, Amsterdam (Netherlands)

2017-08-15

To obtain a summary positive predictive value (sPPV) of contrast-enhanced CT in determining resectability. The MEDLINE and EMBASE databases from JAN2005 to DEC2015 were searched and checked for inclusion criteria. Data on study design, patient characteristics, imaging techniques, image evaluation, reference standard, time interval between CT and reference standard, and data on resectability/unresectablity were extracted by two reviewers. We used a fixed-effects or random-effects approach to obtain sPPV for resectability. Several subgroups were defined: 1) bolus-triggering versus fixed-timing; 2) pancreatic and portal phases versus portal phase alone; 3) all criteria (liver metastases/lymphnode involvement/local advanced/vascular invasion) versus only vascular invasion as criteria for unresectability. Twenty-nine articles were included (2171 patients). Most studies were performed in multicentre settings, initiated by the department of radiology and retrospectively performed. The I{sup 2}-value was 68%, indicating heterogeneity of data. The sPPV was 81% (95%CI: 75-86%). False positives were mostly liver, peritoneal, or lymphnode metastases. Bolus-triggering had a slightly higher sPPV compared to fixed-timing, 87% (95%CI: 81-91%) versus 78% (95%CI: 66-86%) (p = 0.077). No differences were observed in other subgroups. This meta-analysis showed a sPPV of 81% for predicting resectability by CT, meaning that 19% of patients falsely undergo surgical exploration. (orig.)

Acute pancreatitis.

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Talukdar, Rupjyoti; Vege, Santhi S

2015-09-01

To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

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Ito, Tetsuhide; Hijioka, Susumu; Masui, Toshihiko; Kasajima, Atsuko; Nakamoto, Yuji; Kobayashi, Noritoshi; Komoto, Izumi; Hijioka, Masayuki; Lee, Lingaku; Igarashi, Hisato; Jensen, Robert Thomas; Imamura, Masayuki

2017-01-01

Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy ( 111 In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

Circumportal Pancreas-a Must Know Pancreatic Anomaly for the Pancreatic Surgeon.

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Luu, Andreas Minh; Braumann, C; Herzog, T; Janot, M; Uhl, W; Chromik, A M

2017-02-01

Circumportal pancreas is a rare congenital pancreatic anomaly with encasement of the portal vein and/or the superior mesenteric vein by pancreatic tissue. It is often overlooked on cross-sectional imaging studies and can be encountered during pancreatic surgery. Pancreatic head resection with circumportal pancreas is technically difficult and bears an increased risk of postoperative pancreatic fistula. A retrospective chart review of our data base for all patients who had undergone pancreatic head resection between 2004 and 2015 was performed. We identified six patients out of 1102 patients who had undergone pancreatic head surgery in the study period. CT-scan and MRI were never able to identify circumportal pancreas prior to surgery. The right hepatic an artery derived from the superior mesenteric artery in four cases (67%). Additional resection of the pancreatic body was always performed. Postoperative course was uneventful in all cases without occurrence of pancreatic fistula. Circumportal pancreas is a rare entity every pancreatic surgeon should be aware of. It is difficult to identify on cross-sectional imaging studies. A right hepatic artery arising from the superior mesenteric artery should raise suspicion of circumportal pancreas. Additional pancreatic tissue resection should be performed during pancreatic head resections to avoid pancreatic fistula.

Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth

International Nuclear Information System (INIS)

Ohkura, Yu; Sasaki, Kazunari; Matsuda, Masamichi; Hashimoto, Masaji; Fujii, Takeshi; Watanabe, Goro

2015-01-01

Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think

Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT

International Nuclear Information System (INIS)

Smith, S.L.; Rajan, P.S.

2004-01-01

Pancreatic adenocarcinoma is the fourth most frequent cause of cancer-related death. The incidence is increasing and the overall survival has altered little in recent years. Moreover, patients usually present late with inoperable disease and curative resection by standard pancreatico-duodenectomy (Whipple's procedure) is associated with significant morbidity. It should only be attempted in that small group of patients lacking radiological evidence of advanced disease. Despite the recent advances in body magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), computed tomography (CT) is the mainstay of staging in most centres and the recent development of multidetector CT machines (MDCT) has raised hope of an improvement in preoperative staging. This review focuses on the CT of pancreatic adenocarcinoma with particular emphasis on examination technique and on those criteria that determine resectability

Imaging of pancreatic adenocarcinoma with emphasis on multidetector CT

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Smith, S.L. E-mail: simon.smith@ipsh-tr.anglox.nhs.uk; Rajan, P.S

2004-01-01

Pancreatic adenocarcinoma is the fourth most frequent cause of cancer-related death. The incidence is increasing and the overall survival has altered little in recent years. Moreover, patients usually present late with inoperable disease and curative resection by standard pancreatico-duodenectomy (Whipple's procedure) is associated with significant morbidity. It should only be attempted in that small group of patients lacking radiological evidence of advanced disease. Despite the recent advances in body magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), computed tomography (CT) is the mainstay of staging in most centres and the recent development of multidetector CT machines (MDCT) has raised hope of an improvement in preoperative staging. This review focuses on the CT of pancreatic adenocarcinoma with particular emphasis on examination technique and on those criteria that determine resectability.

Treatment of Pancreatic Cancer by Neutrons and Chemotherapy

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Cohen, Lionel [Fermilab; Hendrickson, Frank [Fermilab; Lennox, Arlene [Fermilab; Kroc, Tom [Fermilab; Hatcher, Madeline [Fermilab; Bennett, Barbara [Fermilab

1995-01-01

Background: Between 1977 and 1994, 173 patients with unresectable adenocarcinoma of the exocrine pancreas were treated, 106 with neutrons alone and 67 with concomitant 5-fluorouracil. Ths report is designed to explore the efficacy of neutron therapy in these patients and to evaluate the effect of concomitant chemotherapy with 5-FU on survival. Methods: All subjects were followed at two-month intervals until death. At each follow-up visit the clinical status was recorded, noting the presence of overt metastasis and the onset of any significant complications. Actuarial (Kaplan-Meier) survival tables were computed for both groups. Results: Median survival times in the two groups were 6 months for neutrons alone and 9 months for the combined treatment, with actuarial survival rates at 3 years of zero and 7%, and significant reactions (RTOG level 3) in 18% and 25% respectively. Severe complications (level 4) occurred in 5% of patients in both groups. Most deaths were due to metastatic disease rather than local failure. Conclusions: Neutrons obliterate local disease at the primary site but have no impact on long-term survival. With more effective therapy for systemic disease, local control would become a major determinant of outcome. Combined high-LET irradiation and systemic chemotherapy remains a promising approach to treatment for pancreatic cancer.

Local radiotherapy for patients with unresectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Won; Lim, Do Hoon; Paik, Seung Woon; Koh, Kwang Cheol; Choi, Moon Seok; Park, Cheol Keun; Yoo, Byung Chul; Lee, Jeong Eun; Kang, Min Kyu; Park, Young Je; Nam, Hee Rim; Ahn, Yong Chan; Huh, Seung Jae

2005-01-01

Purpose: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. Methods and materials: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy 10 using the α/β ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy 10 had a significant response; CR or PR was 72.8% with >50 Gy 10 and 46.7% with ≤50 Gy 10 (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. Conclusions: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

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Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Schomberg, Paula J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Stafford, Scott L., E-mail: Stafford.scott@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)

2012-05-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

International Nuclear Information System (INIS)

Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

2012-01-01

Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4–56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm 3 (range, 0.7–26.7). The median tumor margin dose was 15 Gy (range, 12–20). The median follow-up was 8.0 years (range, 0.5–15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

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Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

2017-09-01

Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

Repurposing Established Compounds to Target Pancreatic Cancer Stem Cells (CSCs

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Bernhard W. Renz

2017-06-01

Full Text Available The diagnosis of pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis, in particular, when patients present with unresectable disease. While significant progress has been made in understanding the biology of PDAC, this knowledge has not translated into a clear clinical benefit and current chemotherapeutic strategies only offer a modest improvement in overall survival. Accordingly, novel approaches are desperately needed. One hypothesis that could—at least in part—explain the desolate response of PDAC to chemotherapy is the so-called cancer stem cell (CSC concept, which attributes specific traits, such as chemoresistance, metastatic potential and a distinct metabolism to a small cellular subpopulation of the whole tumor. At the same time, however, some of these attributes could make CSCs more permissive for novel therapeutic strategies with compounds that are already in clinical use. Most recently, several publications have tried to enlighten the field with the idea of repurposing established drugs for antineoplastic use. As such, recycling drugs could present an intriguing and fast-track method with new therapeutic paradigms in anti-cancer and anti-CSC treatments. Here, we aim to summarize important aspects and novel findings of this emerging field.

Advances in the treatment of pancreatic cancer. Limitations of surgery and evaluation of new therapeutic strategies

International Nuclear Information System (INIS)

Yokoyama, Yukihiro; Nagino, Masato; Nimura, Yuji

2009-01-01

Pancreatic ductal carcinoma is one of the most dismal malignancies of the gastrointestinal system. Even after curative resection, the actual 5-year survival is only 10%-20%. Of all the treatments used against pancreatic cancer, surgery is still the only one that can achieve complete cure. Pancreatic cancer spreads easily to the adjacent tissues and distant metastasis is common. Typically, this cancer invades the retropancreatic neural tissue, duodenum, portal vein (PV), and superior mesenteric vein (SMV), or regional lymph nodes. For this reason, aggressive surgery that removes the cancerous lesion completely is recommended. Several retrospective and prospective studies have been conducted to validate the usefulness of aggressive surgery for pancreatic cancer in the past few decades. Surprisingly, the survival benefits of aggressive surgery have been denied by most randomized controlled trials (RCTs). This implies that surgery alone is not enough. Thus, adjuvant therapy, such as radiotherapy and chemotherapy, has been given in combination with surgery to improve survival. Although the benefits of radiotherapy alone are limited, the results of chemotherapy are promising. Other newly evolving molecular targeting drugs may also improve the treatment outcomes of pancreatic cancer. (author)

Pancreatic Cancer

Science.gov (United States)

... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

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Rafi, Shoaib; Piduru, Sarat M. [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States); El-Rayes, Bassel; Kauh, John S. [Emory University School of Medicine, Department of Hematology and Medical Oncology (United States); Kooby, David A.; Sarmiento, Juan M. [Emory University School of Medicine, Department of Surgical Oncology in Surgery (United States); Kim, Hyun S., E-mail: kevin.kim@emory.edu [Emory University School of Medicine, Division of Interventional Radiology and Image Guided Medicine, Department of Radiology (United States)

2013-04-15

To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 {+-} 193 [95 % confidence interval (CI) 374-1130] and 345 {+-} 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 {+-} 190 (95 % CI 78-822) and 345 {+-} 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 {+-} 309 (95 % CI 0-1010) days versus 345 {+-} 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.

A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemo therapy-radiotherapy in unresectable non small cell carcinoma of the lung

Directory of Open Access Journals (Sweden)

Dasgupta Anirban

2006-01-01

Full Text Available Purpose: Treatment of advanced Non small cell lung cancer (NSCLC often produces dismal results. Combination of available treatment modalities has reportedly improved the outcome. A prospectively randomized trial was conducted, comparing combined treatment modalities versus radiotherapy alone, in treatment of unresectable NSCLC. Materials and Methods: A total of 103 patients were randomized to three groups. In group ′A′, 32 patients received radiotherapy alone (6500 cGy/30 fraction. In group ′B′, 35 patients received neoadjuvant chemotherapy (Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1-3 intravenously q3 weeks for 3 cycles, followed by radiotherapy (6000 cGy/30 fractions and 3 more cycles of Chemotherapy, with the same regimen. In group ′C′, 36 patients received radiotherapy (5000 cGy/25 fractions with concurrent chemotherapy (ciplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1-5 and day 22-26, followed by 2 more cycles of chemotherapy,q3 weeks with the same regimen. Results: Initial treatment responses were significantly higher in group ′B′ ( P P Conclusion: Addition of chemotherapy with radiation in unresectable NSCLC improves response rates, time to tumour progression and disease free survival, though the same effect is not translated in overall survival.

Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments.

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Stevens, Tyler; Conwell, Darwin L; Zuccaro, Gregory

2004-11-01

In the past several decades, four prominent theories of chronic pancreatitis pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis hypothesis. Although these traditional theories are formulated based on compelling scientific observations, substantial contradictory data also exist for each. Furthermore, the basic premises of some of these theories are directly contradictory. Because of the recent scientific progress in the underlying genetic, cellular, and molecular pathophysiology, there have been substantial advances in the understanding of chronic pancreatitis pathogenesis. This paper will provide an evidence-based review and critique of the traditional pathogenic theories, followed by a discussion of the new advances in pancreatic fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to each of the known etiologies.

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

Science.gov (United States)

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.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

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Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

2008-04-15

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

International Nuclear Information System (INIS)

Pacella, Claudio M.; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico

2008-01-01

Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival

Potential protective role of hydrogen against cisplatin- induced side ...

African Journals Online (AJOL)

1Department of Radiation Oncology, Sichuan Cancer Hospital, 2Department of Oncology, Chengdu First People's ... Molecular hydrogen has been shown to .... in signal transduction and biological activities .... unresectable pancreatic cancer.

Pancreatic Cysts

Science.gov (United States)

... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

Science.gov (United States)

Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

2011-01-01

Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

Laparoscopic pancreatic cystogastrostomy.

Science.gov (United States)

Obermeyer, Robert J; Fisher, William E; Salameh, Jihad R; Jeyapalan, Manjula; Sweeney, John F; Brunicardi, F Charles

2003-08-01

The purpose of the review was to evaluate the feasibility and outcome of laparoscopic pancreatic cystogastrostomy for operative drainage of symptomatic pancreatic pseudocysts. A retrospective review of all patients who underwent laparoscopic pancreatic cystogastrostomy between June 1997 and July 2001 was performed. Data regarding etiology of pancreatitis, size of pseudocyst, operative time, complications, and pseudocyst recurrence were collected and reported as median values with ranges. Laparoscopic pancreatic cystogastrostomy was attempted in 6 patients. Pseudocyst etiology included gallstone pancreatitis (3), alcohol-induced pancreatitis (2), and post-ERCP pancreatitis (1). The cystogastrostomy was successfully performed laparoscopically in 5 of 6 patients. However, the procedure was converted to open after creation of the cystgastrostomy in 1 of these patients. There were no complications in the cases completed laparoscopically and no deaths in the entire group. No pseudocyst recurrences were observed with a median followup of 44 months (range 4-59 months). Laparoscopic pancreatic cystgastrostomy is a feasible surgical treatment of pancreatic pseudocysts with a resultant low pseudocyst recurrence rate, length of stay, and low morbidity and mortality.

[Pancreatic anastomosis in operative treatment of chronic pancreatitis].

Science.gov (United States)

Bellon, E; Izbicki, J R; Bockhorn, M

2017-01-01

Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V‑shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.

Basal metabolic state governs AIF-dependent growth support in pancreatic cancer cells

International Nuclear Information System (INIS)

Scott, Andrew J.; Wilkinson, Amanda S.; Wilkinson, John C.

2016-01-01

Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. In addition to supporting the survival of healthy cells, AIF also plays a contributory role to the development of cancer through its enzymatic activity, and we have previously shown that AIF preferentially supports advanced-stage prostate cancer cells. Here we further evaluated the role of AIF in tumorigenesis by exploring its function in pancreatic cancer, a disease setting that most often presents at an advanced stage by the time of diagnosis. A bioinformatics approach was first employed to investigate AIF mRNA transcript levels in pancreatic tumor specimens vs. normal tissues. AIF-deficient pancreatic cancer cell lines were then established via lentiviral infection. Immunoblot analysis was used to determine relative protein quantities within cells. Cell viability was measured by flow cytometry; in vitro and Matrigel™ growth/survival using Coulter™ counting and phase contrast microscopy; and glucose consumption in the absence and presence of Matrigel™ using spectrophotometric methods. Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. AIF expression was then suppressed in a panel of five pancreatic cancer cell lines that display diverse metabolic phenotypes. AIF ablation selectively crippled the growth of cells in vitro in a manner that directly correlated with the loss of mitochondrial respiratory chain subunits and altered glucose metabolism, and these effects were exacerbated in the presence of Matrigel™ substrate. This suggests a critical metabolic role for AIF to pancreatic tumorigenesis, while the spectrum of sensitivities to AIF ablation depends on basal cellular metabolic phenotypes. Altogether these data indicate that AIF supports the growth and survival of metabolically defined

CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

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Ishan Roy

Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

Normal pancreatic exocrine function does not exclude MRI/MRCP chronic pancreatitis findings.

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Alkaade, Samer; Cem Balci, Numan; Momtahen, Amir Javad; Burton, Frank

2008-09-01

Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.

Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

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Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

2017-08-01

We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

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Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

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Hu, Wenyan; Fu, Ling

2013-05-01

Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells