bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro sensitivity to 5-FU and gemcitabine in pancreatic cancer.
Authors: Franko J. , Bilimoria M. M. , Chalikonda S. , Iannitti D. A. 
Published: February 2017

312 Background: Gemcitabine and 5-fluorouracil (5-FU) represent the mainstay of chemotherapeutic options for pancreatic cancer. Currently, approximately 40% of patients with pancreatic cancer receive chemotherapy. Relapse is common after resection and adjuvant therapy, and response rates are low in patients with advanced/metastatic disease. The purpose of this study was to describe the prevalence of in vitro drug sensitivity or resistance to these agents in pancreatic cancer and explore the clinical implication of in vitro assessment. Methods: From August 2006 to January 2010, 74 specimens from patients with primary/metastatic pancreatic cancer were tested for response to gemcitabine, 5-FU, and their combination using an in vitro chemosensitivity assay (ChemoFx, Precision Therapeutics, Pittsburgh, PA). Tumors were classified as sensitive or resistant based on in vitro dose response curves. Results: Thirty-four of the 74 tumor specimens (46%) exhibited in vitro chemosensitivity to gemcitabine, 5-FU, or their combination. Fourteen tumors (19%) were sensitive to gemcitabine, and 12 (16%) to 5-FU. Of the 60 patient specimens resistant to gemcitabine, 4 (7%) were sensitive to 5-FU. Conversely, of the 62 specimens resistant to 5-FU, 6 (10%) were sensitive to gemcitabine. Eight of the 74 specimens (11%) were sensitive to both gemcitabine and 5-FU and 56 (76%) were resistant to both agents. Of these 56 specimens, 16 (29%) showed sensitivity to the gemcitabine/5-FU combination. Conclusions: The ChemoFx data indicates a high (76%) in vitro resistance rate to traditional chemotherapy. In vitro chemosensitivity to gemcitabine only partially overlaps with that of 5-FU and the gemcitabine/5-FU combination. Thus, tumors resistant to one drug, were not necessarily resistant to the other and vice versa. Further correlation with clinical outcomes is needed to determine the clinical efficacy of the ChemoFx assay. [Table: see text]
Epidermal growth factor receptor overexpression in resected pancreatic cancer.
Authors: Mahipal A. , McDonald M. J. , Witkiewicz A. , Carr B. I. 
Published: February 2017

317 Background: The effect of overexpression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is uncertain. In this study, we examine the association between EGFR overexpression (membrane and cytoplasmic) and histopathologic features and clinical outcomes in patients post resection. Methods: Seventy three patients underwent curative resection for pancreatic cancer from 4/08 to 4/10. Tumor EGFR expression was determined immunohistochemically using EGFR pharmDxTM kit. Cytoplasmic overexpression was considered positive if EGFR expression was seen in the cytoplasm in ≥10% of cells. Cell membrane staining scores were assigned: 0 (no membrane staining), 1+ (incomplete membrane staining in ≥ 10% of cells, 2+ (complete weak/moderate membrane staining in ≥ 10% of cells) and 3+ (complete heavy staining in ≥ 10% of cells). A score of 2+ and 3+ were considered as membrane overexpression. Comparisons between EGFR overexpression and clinicopathologic features were assessed by chi-square test with p-value < 0.05 as statistically significant. Proportional hazard regression was used to estimate progression free survival and overall survival. Results: Out of 73 patients, 43 (59%) and 50 (68%) patients had membrane and cytoplasmic EGFR overexpression respectively. AJCC stages were: stage I: 8, stage II: 63, stage III: 1 and stage IV: 1 patient. There was statistically significant correlation between cell membrane EGFR overexpression and lymph node positivity (p=0.04). Membrane EGFR overexpression was not significantly associated with local invasion, margin positivity, vascular invasion, perineural invasion, histologic grade or stage. Cytoplasmic EFGR overexpression was significantly associated with margin positivity (p=0.01) only. The hazard ratios (95% CI) for PFS and OS in patients with membrane EGFR overexpression was 1.37 (0.72-2.60) and 1.27 (0.62-2.61) respectively. The corresponding values for patients with cytoplasmic overexpression were 1.65 (0.80-3.37) and 1.25 (0.58-2.71) respectively. Conclusions: Membrane EGFR overexpression was associated with lymph node status and cytoplasmic EFGR overexpression with margin positivity. There was no association of EFGR expression and clinical outcomes. No significant financial relationships to disclose.
Resected pancreatic neuroendocrine tumors: Patterns of failure and disease-related outcomes with or without radiotherapy.
Authors: Zagar T. M. , White R. R. , Willett C. G. , Papavassiliou P. , Tyler D. S. , Papalezova K. , Guy C. , Clough R. , Czito B. G. 
Published: February 2017

325 Background: Pancreatic neuroendocrine tumors (NET) are rare with improved prognosis compared to adenocarcinomas. Surgical resection remains the standard of care although many patients present with unresectable/metastatic disease. While many resected patients will fail distantly, little is known regarding the use of adjuvant radiotherapy. To define this and establish specific patterns of failure, an analysis of resected patients from a single institution was performed. Methods: From 1994 to 2009, 33 patients with NET of the pancreatic head underwent resection with curative intent at Duke University. Sixteen patients were treated with surgical resection alone, and an additional 17 underwent resection with adjuvant (n=10) or neoadjuvant (n=7) radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. Results: Patients receiving radiation therapy were more likely to have involved nodes (47% vs 19%, p=0.09), more mitoses per high power field (p=0.10) and involved margins (47% vs 31%, p=0.20) compared to surgery alone patients. Median survival for the whole cohort was 52 months. Two-year survival was 68% for the CMT group and 93% for the surgery alone group (p=0.03). Two-year local control was 85% for the CMT and 90% for the surgery group (p=0.49). Two-year metastasis-free survival was 45% and 69% for the CMT and surgery patients, respectively (p=0.02). Conclusions: Patients receiving CMT were more likely to have adverse pathologic features compared to surgery-alone patients. Survival outcomes were high in both groups, although less so in the CMT group. Distant metastasis development dominated patterns of failure. Local failure following resection of NETs is uncommon, and the role of adjuvant radiotherapy in this setting remains unclear. No significant financial relationships to disclose.
Concurrent chemoradiotherapy for unresectable hilar choloangiocarcinoma: A single-institution experience.
Authors: Hunag P. , Chao Y. , Li C. , Lee R. , Wang L. , Yen S. 
Published: February 2017

326 Background: Hilar cholangiocarinoma (Klatskin tumor) is a rare malignancy which is best managed with surgical resection. The majority of patients, however, is unresectable at the time of diagnosis and generally has a poor outcome. The purpose of this study was to retrospectively evaluate the role of chemoradiotherapy (CCRT) for patients with unresectable hilar choloangiocarcinoma at a single institution. Methods: Between 2001 and 2008, a total of 33 patients with unresectable, nonmetastatic hilar cholangiocarcinoma treated at Taipei Veterans General Hospital were reviewed. All patients were to receive 3D-CRT with a median dose of 50.4 Gy (range, 39.6- 60) at 1.8-2 Gy per fraction per day. Sixteen patients also received bolus 5-fluorouracil (5-FU) CCRT (500 mg/m2/d for 3 days repeated every 2 weeks during radiotherapy for 6 weeks). Survivals were estimated by the Kaplan-Meier method and compared by log-rank test. Results: There were 21 males and 12 females, with a median age of 71 years (range, 29 - 81). The median follow-up time was 10.4 months (range, 1 – 42.3) for all patients with the 1- and 2-year survival rates of 45% and 12%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 13.5 months and 10.2 months for the CCRT group, and 10.4 months and 6.5 months for the RT alone group (p = 0.36 and p = 0.28, respectively). Adverse events were similar in thetwo groups with 14 patients (42%) developed grade 1-2 gastrointestinal toxicity during RT. Locoregional progression was observed in 26 patients (79%) and distant metastases in 9 patients (27%). All patients experienced disease progression and had died at time of analysis. Conclusions: The outcome remains poor for unresectable hilar cholangiocarcinoma despite aggressive combined modality treatment. Although not statistically significant, our data showed CCRT provides longer OS and PFS in patients with unresectable hilar cholangiocarcinoma compared to RT alone. Locoregional progression is the main problem for this disease and the efficacy of adding chemotherapy or biologic agents needs to be further investigated. No significant financial relationships to disclose.
Is pancreaticoduodenectomy performed at a comprehensive community cancer center comparable to tertiary centers' results?
Authors: Cheng C. , Duppler D. , Koczon-Jaremko B. 
Published: February 2017

334 Background: We maintained a prospective database covering the period from 2001 to 2010. Outcome data are analyzed. We believe that the outcome achieved at a small cancer center is comparable to a tertiary cancer center. Methods: Our study measures the outcome of pancreaticoduodenectomy. Data were compared to the published literature. Results: There are 62 patients with histology-proven pancreatic cancer; ampullary adenocarcinoma and other histology types were included in the study. PPPD was performed in 41 patients. Twenty patients had classic PD. Three patients had portal venorrhaphy. Fifty patients had malignancy, whereas 11 had a benign histology. One case had dual histology (ductal carcinoma and neuroendocrine). The average age of patients was 63. Mean preoperative CA19-9 for exocrine pancreatic malignancies was 638, whereas for benign lesions and endocrine tumors it was 122. Average operative time is 6 hours 25 minutes for surgeries before 2005 and 5 hrs 48 minutes for surgeries performed after 2005. Blood transfusion was rare with 15 patients received blood product. There was one perioperative death due to ischemic bowel (4.3%). Average length of stay in the hospital was 15 days (range 0-87 days). There was no pancreatic leak among any of the patients. Two bile leaks were identified, one controlled with the drainage tube and the other one required repeat surgery. 30 days mortality rate was calculated at 10%. To date, 27 patients have died, with two from causes unrelated to carcinoma. Mean survival during our study period is 30.6 months. In comparison to published literature, the mortality, morbidity, and survival are similar. In the literature five year survival for pancreatic cancer patients treated with pancreaticoduodenectomy ranges from 10% to 29%. Conclusions: In our study 5-yr survival was 45%. Despite overall poor outcome for patients with pancreatic and biliary malignancies, surgery can be performed in community hospitals with special interest in treating pancreatic disorder, offering patients prolonged survival and quality of life. Pancreaticoduodenectomy is effective and safe with low hospital mortality and with acceptable complication rates. No significant financial relationships to disclose.
Prognostic implication of intraoperative radiotherapy for unresectable pancreatic cancer.
Authors: Fujii T. , Nagai S. , Kodera Y. , Kanda M. , Sahin T. T. , Sugimoto H. , Nomoto S. , Takeda S. , Morita S. , Nakao A. 
Published: February 2017

346 Background: There is no established treatment strategy for unresectable pancreatic cancer, and the prognostic effect of intraoperative radiotherapy (IORT) is considered to be limited. Methods: We reviewed 614 surgical cases of pancreatic cancer and selected 198 cases that did not undergo pancreatectomy because of distant metastasis or locally advanced disease, at the Department of Surgery II, between July 1981 and June 2009. Liver metastasis was observed in 70 patients and peritoneal metastasis in 44. Treatment for those who were feasible consisted of IORT and/or postoperative chemotherapy. Overall survival and prognostic factors were evaluated for all patients and for each pattern of disease spread. Results: IORT was performed in 120 patients (61%), and chemotherapy was indicated in 80 (40%). Overall survival in the non-treatment group was significantly inferior to that for IORT alone and IORT plus gemcitabine (GEM)-based chemotherapy (median survival time: 3.2 months vs. 6.1 and 7.9 months; P = 0.0001 and <0.0001, respectively). After multivariate analysis, IORT and GEM-based chemotherapy were identified as independent prognostic factors [hazard ratio (HR) = 0.51, P < 0.001; HR = 0.43, P < 0.001]. IORT was an independent prognostic determinant for patients with peritoneal metastasis (HR = 0.24, P = 0.011), whereas it was not for those with liver metastasis (HR = 0.78, P = 0.381). Conclusions: The prognostic value of IORT is most prominent in the peritoneal disease. IORT followed by GEM-based chemotherapy is possibly one of the most recommended treatment strategies in unresectable pancreatic cancer. No significant financial relationships to disclose.
Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) for malignant obstructive jaundice (OJ) in advanced digestive cancers.
Authors: Iruarrizaga E. , Azkona E. , Martinez M. , Iza E. , Lopez-Vivanco G. , Munoz Llarena A. , Ferreiro J. , Ballesteros D. , Fernandez R. , Rubio I. 
Published: February 2017

348 Background: OJ is a relatively frequent complication in patients with advanced malignancies that usually causes refractory symptoms and can make chemotherapy (CT) treatment difficult. In the last years, the use of different non-surgical techniques, such as PTBD or ERCP, is increasing. Methods: From Sep-05 to Aug-10, patients with OJ due to advanced digestive cancers who underwent ERCP or PTBD were included. Baseline characteristics, acute and late complications and outcome were retrospectively collected. Jaundice resolution was recognized if bilirubin value decreased to at least grade 1, after the procedure. Overall survival (OS) was calculated from the date of the technique to the date of death or last follow-up. Results: Seventy-six consecutive patients were collected. Male/Female: 52p/24p; Mean age 63.5 y-o (range: 33-85); ECOG performance status 0/1/2/3: 1/37/27/11; Primary tumour: pancreas 30, biliary tract 18, colorectal 16, gastric 7, and gall bladder 5, and of them, 13% were unresectable locally advanced and 87% metastatic. ERCP was used in 59% of the patients and PTBD in 49% and the proportion of intrahepatic and extrahepatic causes were 1:1. Mean hospital stay was 11.3 days (95% CI 1-21). Twenty- six patients (32%) suffered a complication during the hospital stay: 9 cholangitis, 7 catheter obstruction, 2 bleeding, 2 acute pancreatitis and 6 other, and 8 died of procedure-related adverse event. After hospital discharge there were 34% infections, 17% catheter obstruction and 8% other. After the technique OJ was solved (bilirubin nadir) in 49% of the patients and 55% underwent palliative CT. Median OS was 30 weeks (95% CI: 17-42). Conclusions: PTBD and ERCP are appropriate techniques in patients with malignant OJ and can resolve an absolute contraindication for palliative CT. However, major complications are frequent and a relatively high mortality rate should be expected. Therefore an adequate patient selection is crucial to prevent adverse events. No significant financial relationships to disclose.
Stage I nonfunctioning neuroendocrine tumors of the pancreas: Surgery or surveillance?
Authors: Strosberg J. R. , Cheema A. , Kvols L. K. 
Published: February 2017

349 Background: An increasing number of nonfunctioning, early-stage pancreatic neuroendocrine tumors are detected incidentally as patients undergo radiographic procedures for unrelated indications. Endoscopic sonography with fine-needle aspiration now enables nonoperative biopsy of tumors smaller than 1 cm in diameter. It is unclear whether the risks of partial pancreatectomy or enucleation exceed the risks of surveillance in patients with these neoplasms. Methods: We performed a database search of patients with pancreatic neuroendocrine tumors treated at the H. Lee Moffitt Cancer Center in order to evaluate outcomes of patients with stage I tumors who did not undergo surgical resection. Results: Four patients were identified who elected to undergo surveillance of their stage I tumors instead of surgical resection. All had been diagnosed via endoscopic ultrasound-guided fine-needle aspiration. The tumor sizes were 7 mm, 12 mm, 13 mm, and 15 mm at initial diagnosis. Three tumors were cystic and one was solid. Three were located in the body of the pancreas and one in the tail. In two patients, the Ki-67 index was measured and was <1%. With a median of follow-up of two years, none of the patients experienced tumor growth. All three patients with cystic tumors experienced shrinkage of their tumors following the diagnostic needle aspiration and did not experience subsequent increase in size (Table). Conclusions: Surveillance may be an appropriate strategy for management of incidentally discovered, stage I pancreatic neuroendocrine tumors. [Table: see text] No significant financial relationships to disclose.
Adjuvant therapy for gallbladder cancer: An institutional perspective.
Authors: Wang M. L. 
Published: February 2017

353 Background: Gallbladder carcinoma is a rare malignancy of the gastrointestinal tract. While radical surgery remains the only potentially curative treatment modality, relapse rates are high. Due to the paucity of data on the effectiveness of adjuvant therapy, only patients with high risk factors are referred for adjuvant therapy at our institution. We evaluate the effect of adjuvant chemoradiotherapy on the outcome of this group of patients. Methods: Records of patients who underwent adjuvant radiotherapy at our institution from January 1, 2001, to December 31, 2009, were reviewed. All patients had stage II disease. Patients received adjuvant radiotherapy (dosage 4,500 to 5,040 cGy in 25 to 28 fractions) with concomitant capecitabine or 5-fluorouracil chemotherapy. The effect of adjuvant therapy on disease-free survival (DFS) and overall survival (OS) was evaluated. Results: A total of 11 patients were included in the analysis, of which nine (82%) were females. Patients had stage IIA (27%) or IIB (73%) disease. Surgical margins were clear in 3 (27%), close (<1 mm) in 3 (27%) and positive in 5 patients (45%), including 1 with R2 resection. Ten patients underwent chemoradiotherapy with the exception of one, who received chemotherapy followed by consolidation radiotherapy. With a median follow-up of 46.2 months for surviving patients at the point of analysis, 4 patients were still alive. Eight patients had developed disease recurrence, with the first site being locoregional in 1 (12%), distant in 4 (50%) and both in 3 patients (38%). All relapse occurred within 20 months of surgery, with 88% within 12 months. The median time to relapse was 7.4 months. The estimated disease- free survival rate at 1 and 3 years was 36% and 27%, respectively. The estimated overall survival of the group at 1 and 3 years was 36% and 27%, respectively. Conclusions: Data from numerous studies have shown varied results with regard to the use of adjuvant therapy in gallbladder carcinoma. There are studies where adjuvant therapy have produced 5-year OS rates of up to 70% in patients with negative surgical margins. From our results, patients with high-risk disease may benefit from aggressive adjuvant therapy. A combination of chemoradiotherapy followed by further chemotherapy may be useful. No significant financial relationships to disclose.
Gemcitabine, oxaliplatin, and bevacizumab (GEMOX-B): A promising regimen for the treatment of advanced biliary tract cancers.
Authors: Mahipal A. , Rosato E. , Littman S. J. , Hargrove H. , Bapat A. R. , Doria C. , Mitchell E. P. 
Published: February 2017

355 Background: Biliary-tract cancers (BTCs) arise from the epithelium of the gallbladder and bile ducts and are relatively rare, affecting 9-12,000 people in the United States annually. Peak incidence is in the seventh decade of life. Prognosis of advanced BTCs is poor with median overall survival of approximately 10 months. There has been no standard treatment regimen because of lack of randomized clinical trials data. Phase II trials have demonstrated the efficacy of the combination of gemcitabine and oxaliplatin with the response rate of ∼50%. In a recently published phase II trial, the addition of bevacizumab to this regimen (GEMOX-B) resulted in 63% progression-free survival (PFS) at 6 months. In this retrospective study, we evaluated the efficacy of GEMOX-B in patients with advanced biliary tract cancers treated at Thomas Jefferson University. Methods: All patients received treatment on day 1 and 15 of 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m2 and oxaliplatin 85 mg/m2. All patients were administered diphenhydramine, dexamethasone, and ondansetron prior to chemotherapy. Response was assessed using the RECIST criteria. PFS was measured from start of chemotherapy to disease progression or death. Results: A total of 6 patients with BTCs were treated with GEMOX-B. One patient was male and 5 were female. The median age was 45 years (40-64 years). All patient had ECOG performance score 0-1. Three patients had progressed on prior therapy. A total of 65 cycles were administered with the median being 9 (range: 7-21) cycles. Two patients (33%) had partial response and 4 patients (66%) had stable disease. One patient progressed after 6.4 months of therapy. One patient died due to pneumonia but had stable disease at time of death. One patient developed encephalopathy, likely due to bevacizumab. Two patients are still receiving treatment. The median PFS has not been reached (range: 6-42 months). Conclusions: This retrospective study further suggests that GEMOX-B is an active regimen in BTCs. Additional studies are needed to further evaluate the toxicity and efficacy of this regimen and understand molecular pathways governing sensitivity to chemotherapy. No significant financial relationships to disclose.