• Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis.

• Recent advances in the surgical treatment of pancreatic cancer.

• Adjuvant therapy in pancreatic cancer.

• Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response

• Intrasurgical pancreas cytology.

• The effectiveness of breath-holding to stabilize lung and pancreas tumors during radiosurgery.

• Surgery for ductal adenocarcinoma of the pancreatic head: staging, complications, and survival after regional versus extended

• Re: Surgery for ductal adenocarcinoma of the pancreatic head.

• Renal cell carcinoma metastatic to the pancreas: results of surgical management.

• [Specific features of pancreatoduodenal resection in cancer of the head and unciform process of the pancreas]

• En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?

• A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer.

• A response of Panc-1 cells to cis-platinum, assessed with a cDNA array.

• Modified pancreaticoduodenectomy: experience with 81 cases, Wahab modification.

• Prognostic factors of long-term survival after resective procedures for pancreatic cancer.

• Influence of p53 status on radiation and 5-flourouracil synergy in pancreatic cancer cells.

• Is glucagonoma of the pancreas a curable disease?

1
UI - 12003425
AU - Arguedas MR; Heudebert GH; Stinnett AA; Wilcox CM
TI - Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis.
SO - Am J Gastroenterol 2002 Apr;97(4):898-904
AD - Division of Gastroenterology & Hepatology, School of Public Health, University of Alabama at Birmingham, 35294-0007, USA.
OBJECTIVES: Obstructive jaundice frequently complicates pancreatic carcinoma and is associated with complications such as malabsorption, coagulopathy, progressive hepatocellular dysfunction, and cholangitis in addition to disabling pruritus, which greatly interferes with terminal patients' quality of life. Endoscopic placement of biliary stents decreases the risk of these complications and is considered the procedure of choice for palliation for patients with unresectable tumors. We used decision analysis with Markov modeling to compare the cost-effectivenesses of plastic stents and metal stents in patients with unresectable pancreatic carcinoma. METHODS: A model of the natural history of unresectable pancreatic carcinoma was constructed using probabilities derived from the literature. Cost estimates were obtained from Medicare reimbursement rates and supplemented by the literature. Two strategies were evaluated: 1) initial endoscopic plastic stent placement and 2) initial endoscopic metal stent placement. We compared total costs and performed cost-effectiveness analysis in these strategies. The outcome measures were quality-adjusted life months. Sensitivity analyses were performed on selected variables. RESULTS: Our baseline analysis showed that initial plastic stent placement was associated with a total cost of $13,879/patient and 1.799 quality-adjusted life months. Initial placement of a metal stent cost $13,466/patient and conferred 1.832 quality-adjusted life months. Among the variables examined, expected patient survival was demonstrated by sensitivity analyses to have the most influence on the results of the model. CONCLUSION: Initial endoscopic placement of a metal stent is a cost-saving strategy compared to initial plastic stent placement, particularly in patients expected to survive longer than 6 months.

2
UI - 11819842
AU - Shankar A; Russell RC
TI - Recent advances in the surgical treatment of pancreatic cancer.
SO - World J Gastroenterol 2001 Oct;7(5):622-6
AD - Department of Surgery, The Middlesex Hospital, Mortimer Street, London, W1N 8AA,UK.

3
UI - 11819814
AU - Ghaneh P; Slavin J; Sutton R; Hartley M; Neoptolemos JP
TI - Adjuvant therapy in pancreatic cancer.
SO - World J Gastroenterol 2001 Aug;7(4):482-9
AD - Department of Surgery, University of Liverpool, 5th Floor UCD Building, Daulby Street, Liverpool, L69 3GA, UK.
The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

4
UI - 12011133
AU - Pisters PW; Wolff RA; Janjan NA; Cleary KR; Charnsangavej C; Crane CN;
TI - Lenzi R; Vauthey JN; Lee JE; Abbruzzese JL; Evans DB Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome.
SO - J Clin Oncol 2002 May 15;20(10):2537-44
AD - Pancreatic Tumor Study Group, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ppisters@mdanderson.org
PURPOSE: To evaluate the toxicity of a preoperative regimen of paclitaxel and concurrent external-beam radiation therapy, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 30 Gy external-beam radiation therapy and concomitant weekly 3-hour infusions of paclitaxel (60 mg/m(2)). Radiographic restaging was performed 4 to 6 weeks after chemoradiation, and patients with localized disease underwent pancreatectomy with EB-IORT. RESULTS: Thirty-five patients completed chemoradiation; 16 (46%) experienced grade 3 toxicity. Four patients (11%) required hospitalization for dehydration due to grade 3 nausea and vomiting. Twenty (80%) of 25 patients who underwent surgery underwent pancreatectomy; EB-IORT was used in 13 patients. There were no histologic complete responses to preoperative therapy; 21% of specimens demonstrated more than 50% nonviable cells (grade 2b treatment effect). With a median follow-up period of 46 months, the 3-year overall survival rate with chemoradiation and pancreatectomy was 28%. CONCLUSION: Preoperative paclitaxel-based concurrent chemoradiation is feasible. The toxicity of this regimen seems greater than that with fluorouracil. The histologic responses and survival are similar, suggesting no advantages to paclitaxel-based preoperative treatment.

5
UI - 11854628
AU - Schramm H; Urban H; Arnold F; Penzlin G; Bosseckert H
TI - Intrasurgical pancreas cytology.
SO - Pancreas 2002 Mar;24(2):210-4
AD - Wald-Klinikum gGmbh, Chirurgisches Zentrum, Departement fur Allgemeine, Viszerale und Kinderchirurgie, Strasse des Friedens 122, D-07548 Gera, Germany.
INTRODUCTION: A differential therapy of chronic pancreatitis and carcinoma calls for evaluation of the validity of findings. Presurgical suspicion of a carcinoma often requires intrasurgical diagnostics such as excisional biopsies, punch biopsies, and fine-needle aspiration cytology (FNAC) for confirmation. AIMS: To evaluate FNAC as an intraoperative diagnostic method of very high probability. METHODOLOGY: Intrasurgical fine-needle aspiration biopsy and cytologic assessment were carried out in 474 patients. The indications for operative therapy and FNAC were suspicion of pancreatic tumor, chronic pancreatitis even without suspicion of tumor, and pathologic alterations found during other surgeries in the upper abdomen. RESULTS: The level of sensitivity was 93.1%, specificity was 99.1%, predictive value of positive results was 99.2% and of negative results was 92.1%. CONCLUSION: FNAC is a suitable method for intrasurgical confirmation of pancreatic carcinoma. It can be performed safely, effectively, and rapidly.

6
UI - 12023152
AU - Murphy MJ; Martin D; Whyte R; Hai J; Ozhasoglu C; Le QT
TI - The effectiveness of breath-holding to stabilize lung and pancreas tumors during radiosurgery.
SO - Int J Radiat Oncol Biol Phys 2002 Jun 1;53(2):475-82
AD - Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA. martin@reyes.stanford.edu
PURPOSE: To evaluate the effect of breath-holding on the short-term reproducibility and long-term variability of tumor position during image-guided radiosurgery. METHOD: Thirteen patients have undergone single-fraction radiosurgery treatments during which the tumor was repeatedly imaged radiographically to observe its position. The imaging data were used to monitor the efficacy of breath-holding and to periodically readjust the alignment of the treatment beam with the tumor. These measurements have allowed the effects of breathing, heartbeat, patient movement, and instrumental uncertainties to be separately identified in the record of tumor position. RESULTS: During inspiration breath-holding, the lung tumor position was reproducible to within 1 mm, on average, in the direction of maximum displacement during regular breathing, and to within 1.8 mm in three dimensions overall. The pancreas tumor position in three dimensions was reproducible to within 2.5 mm on average. Some patients showed a slow, steady drift of tumor position during the extended sequence of breath-holds, which was compensated by periodic retargeting of the treatment beam. CONCLUSION: Breath-holding can allow the reduction of tumor motion dosimetry margins to 2 mm or less for lung cancer treatments, provided that the treatment system can detect and adapt to long-term variations in the mean tumor position during a lengthy treatment fraction.

7
UI - 10787083
AU - Henne-Bruns D; Vogel I; Luttges J; Kloppel G; Kremer B
TI - Surgery for ductal adenocarcinoma of the pancreatic head: staging, complications, and survival after regional versus extended lymphadenectomy.
SO - World J Surg 2000 May;24(5):595-601; discussion 601-2
AD - Department of General and Thoracic Surgery, University of Kiel, Germany.
The purpose of this study was to evaluate the influence of regional versus extended lymphadenectomy on survival after partial 72 patients with histologically proven ductal adenocarcinoma of the pancreatic head were treated. Partial pancreaticoduodenectomy with regional lymphadenectomy was performed in 26 patients. In 46 patients lymphadenectomy was expanded to include extended retroperitoneal lymphatic and connective tissue clearance. Comparing these two groups and including only patients with R0 resections (n = 58) no significant differences in long-term survival could be shown. The following parameters were shown to have a significant or nearly significant influence on long-term survival: (1) stage of the disease: The 5-year survival of patients with stage I/II pancreatic head cancer was 63%, compared to 15% in patients with stage III/IV a + b of the disease (p = 0.0087). (2) Grading: The 1-year survival of patients with well or moderately differentiated tumors was 55%, compared to 0% for patients with poorly differentiated ductal adenocarcinoma (p = 0.0022). (3) N stage: The 5-year survival of patients in N0 stage was 46.9%, compared with 15% for N1 stage patients. The difference was not quite significant (p = 0.081). (4) Portal vein involvement: The 1-year survival was 0% in patients with R0 resections and histologically proven tumor infiltration of the portal vein, compared to 63% for patients with curative resections without portal vein involvement (p = 0.0063). In conclusion our data indicate that extensive retroperitoneal tissue clearance during pancreaticoduodenectomy for ductal pancreatic cancer does not improve survival compared to regional lymphadenectomy restricted to the right side of the mesenteric artery.

8
UI - 11344412
AU - Pisters PW; Evans DB; Leung DH; Brennan MF
TI - Re: Surgery for ductal adenocarcinoma of the pancreatic head.
SO - World J Surg 2001 Apr;25(4):533-4

9
UI - 11985973
AU - Sohn TA; Yeo CJ; Cameron JL; Nakeeb A; Lillemoe KD
TI - Renal cell carcinoma metastatic to the pancreas: results of surgical management.
SO - J Gastrointest Surg 2001 Jul-Aug;5(4):346-51
AD - Department of Surgery, The Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, MD 21287, U.S.A.
Metastatic tumors to the pancreas are uncommon. Renal cell carcinoma is one of the few tumors known to metastasize to the pancreas. The purpose of the current report is to evaluate the surgical management and long-term outcome of patients with metastatic renal cell carcinoma. A retrospective review of patients undergoing pancreatic resection for renal cell carcinomas metastatic to the pancreas or periampullary region initial presentation, other metastatic sites, surgical outcomes, and long-term survival were evaluated. During the 10-year time period, 10 patients underwent pancreatic resection for renal cell carcinoma metastases. Of those, six underwent pancreaticoduodenectomy and two underwent distal pancreatectomy, whereas the two remaining patients underwent total pancreatectomy for extensive tumor involvement throughout the entire gland. The mean time from nephrectomy for resection of the primary tumor to reoperation for periampullary recurrence was 9.8 years (median 8.5 years). The range was 0 to 28 years, with one patient presenting with a synchronous metastasis. The mean age of the patients was 61.2 years with 60% of patients being male and 90% being white. Pathologic findings included histologically negative lymph nodes and negative surgical margins in all patients. One patient had tumor involving the retroperitoneal soft tissue, but final margins were negative. The mean live patient follow-up was 30 months (median = 15 months), with eight patients remaining alive. The Kaplan-Meier actuarial 5-year survival was 75%, with the longest survivor still alive 117 months following resection. The patient with retroperitoneal soft tissue involvement died 4 months after resection. The pancreas is an uncommon site of metastasis for renal cell carcinoma, typically occurring years after treatment of the primary tumor. When the metastatic focus is isolated and the tumor can be resected in its entirety, patients can experience excellent 5-year survival rates. The current report suggests that pancreatic metastases from renal cell carcinoma should be managed aggressively with complete resection when possible.

10
UI - 11837003
AU - Kokhanenko NIu; Savrasov VM
TI - [Specific features of pancreatoduodenal resection in cancer of the head and unciform process of the pancreas]
SO - Vestn Khir Im I I Grek 2001;160(5):66-71
Pancreato-duodenal resections (PDR) were made in 134 patients with cancer of the pancreas, in 31 (23.1%) of them the tumor was localized in the unciform process of the pancreas. In 7 patients the destructive pancreatitis which complicated cancer PDR was completed by the external drainage of the pancreatic duct. Combined PDR were fulfilled in 14 (10.4%) patients including 9 (29.0%) of 31 patients who had cancer of the unciform process. In 48 (35.8%) patients PDR was followed by complications. The most frequent of them were acute pancreatitis of the stump (32.1%) and incompetent pancreatoenteroanastomosis (18.7%). Postoperative lethality after PDR was 6.7%. During the recent six years no lethal outcomes have been observed after 45 PDR. Cancer of the uniform process of the pancreas is the least favorable localization. Combined PDR are followed by a great number of intraoperative, postoperative complications and high lethality rate. If the patients had mechanical jaundice, the use of double step PDR gave better results. If there were intraoperative signs of acute pancreatitis it was necessary to drain the pancreatic duct outside. The using of intraoperative occlusions of the pancreatic ducts is hardly justified because of a high risk of the development of acute pancreatitis.

11
UI - 11992799
AU - Sasson AR; Hoffman JP; Ross EA; Kagan SA; Pingpank JF; Eisenberg BL
TI - En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?
SO - J Gastrointest Surg 2002 Mar-Apr;6(2):147-57; discussion 157-8
AD - Department of Surgical Oncology, Temple University School of Medicine, Philadelphia, PA 19111, USA.
The benefit of radical surgical resection of contiguously involved structures for locally advanced pancreatic cancer is unclear. The aim of this study was to examine patient outcome after extended pancreatic resection for locally advanced tumors and to determine if any subset of extended resection affected outcome. We retrospectively reviewed the records of 116 patients with adenocarcinoma of the pancreas, who underwent extirpative pancreatic surgery between 1987 and 2000. Of the 116 patients, 37 (32%) required resection of surrounding structures (group I), and 79 patients (68%) underwent standard pancreatic resections (group II). In all cases, all macroscopic disease was excised. In group I a total of 46 contiguously involved structures were resected: vascular in 25 patients (54%), mesocolon in 16 (35%) (colic vessels in 3, colon in 13), adrenal in three (7%), liver in one (2%), stomach in one (2%) (for a tumor in the tail of the pancreas), and multiple structures in four. Excision of regional blood vessels included the superior mesenteric vein and/or portal vein in 16, hepatic artery in five, and celiac axis in four. No differences between groups I and II were detected for any of the following parameters: age, sex, history of previous operation, estimated blood loss, or hospital stay. For the entire cohort the morbidity and mortality were 38% and 1.7%, respectively, and these rates were similar in the two groups. Adjuvant therapy was administered to more than 90% of patients in both groups. However, patients in group I were more likely to have received neoadjuvant therapy (76% vs. 42%, P = 0.001). Total pancreatectomy and distal pancreatectomy were more often performed in group I (P = 0.005). Additionally, the median operative time was longer (8.5 hours compared to 6.9 hours (P = 0.0004)). Both groups had similar rates of microscopically positive margins and involved lymph nodes, as well as total number of lymph nodes removed. The median survival was 26 months for patients in group I and 16 months for patients in group II (P = 0.08). The median disease-free survival for groups I and II was 16 months and 14 months, respectively (P = 0.88). In comparing patients in group I, who underwent vascular resection vs. mesocolon (colon or middle colic vessels) resection, the median survival was 26 months and 19 months, respectively (P = 0.12). We were unable to detect a difference in outcome for patients with locally advanced cancers requiring extended pancreatic resections compared to patients with standard resections. En bloc resection of involved surrounding structures, to completely extirpate all macroscopic disease, may be of benefit in selected patients with locally advanced disease, particularly when combined with preoperative chemoradiation therapy.

12
UI - 12017272
AU - Yoshida Y; Tomizawa M; Bahar R; Miyauchi M; Yamaguchi T; Saisho H;
TI - Kadomatsu K; Muramatsu T; Matsubara S; Sakiyama S; Tagawa M A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer.
SO - Anticancer Res 2002 Jan-Feb;22(1A):117-20
AD - Division of Pathology, Chiba Cancer Center Research Institute, Japan.
We examined a possible application of regulatory regions of the midkine (MK) gene for suicide gene therapy of pancreatic cancer. The expression of MK has been demonstrated in human pancreatic cancer tissues but scarcely in normal adult tissues. Northern blot analysis confirmed that human pancreatic cancer cell lines expressed the MK gene. A 609-bp genomic fragment in the 5'-regulatory region of the MK gene, when transfected into human pancreatic cancer cells, activated the transcription of a fused reporter gene to an extent greater than the SV40 promoter. In contrast, the 609-bp fragment-mediated promoter activity tested in fibroblast cells was significantly weak. Human pancreatic cancer cells (AsPC-1) that were transduced with the herpes simplex virus-thymidine kinase gene linked with the 609-bp promoter markedly increased their sensitivity to a prodrug, ganciclovir, compared with untransduced cells. The present study suggests that preferential cytotoxic effects for pancreatic tumors can be achieved by using the MK promoter.

13
UI - 12017337
AU - Anderson KM; Alrefai WA; Anderson CA; Ho Y; Jadko S; Ou D; Wu YB; Harris
TI - JE A response of Panc-1 cells to cis-platinum, assessed with a cDNA array.
SO - Anticancer Res 2002 Jan-Feb;22(1A):75-81
AD - Department of Medicine, Rush Medical College, Chicago, IL 60612, USA. Kanderso@rush.edu
BACKGROUND: The problem posed by the lack of response of cells in most solid cancers to current chemotherapy generally remains intractable. MATERIALS AND METHODS: The use of cDNA arrays represents one global approach to identifying reasons for this failure. A messenger RNA response of pancreatic cancer (Panc-1) cells after culture for 24 hours with 12 microM cis-platinum was analyzed with a commercial cDNA array. RESULTS: Major drug-induced events included inhibition of messenger RNAs associated with cell proliferation and up-regulation of generally countervailing DNA repair, cellular stress, heat shock protein, glutathione stress-related and multiple drug resistance enzyme messenger RNAs, accompanied by a limited programmed cell death response. CONCLUSION: Induction of widespread normal stress-induced countervailing mRNAs by comparatively non-selective agents such as cis-platinum strongly biases against a successful therapeutic outcome. This paradoxical result of a therapeutic intent provides a further compelling argument for the use of specifically-targeted therapy such as growth factor receptor, tyrosine kinase and other discretely focused agents, probably employed in combinations based on expression of their targets in an individual patient's cancer, as identified by cDNA or proteonomic arrays.

14
UI - 11813575
AU - Abdel-Wahab M; Sultan A; elGwalby N; Fathy O; AboElenen A; Zied MA;
TI - Fouad A; Allah TA; el-Ebiedy G; Gad-ElHak N; Elfiky A; Ezzat F Modified pancreaticoduodenectomy: experience with 81 cases, Wahab modification.
SO - Hepatogastroenterology 2001 Nov-Dec;48(42):1572-6
AD - Gastroenterology Center, Mansoura University, Mansoura, Egypt. Wahabmeg@yahoo.com
BACKGROUND/AIMS: Now pancreaticoduodenectomy is considered a safe and acceptable line of treatment for periampullary tumors. In spite of improvements in the surgical technique it still has a high morbidity rate. In this study we introduce new technical modifications for the original procedure aiming to decrease the incidence of morbidity. METHODOLOGY: Between 1994-2000, 210 pancreaticoduodenectomies were done in the Gastroenterology Center, Mansoura University, Egypt for periampullary tumor. Eighty-one of these patients were subjected to modified pancreaticoduodenectomy. They were 57 men and 34 women with a mean age of 54 (+/- 8) years. Pancreatic carcinoma represented 54%, ampullary tumor 30%, bile duct carcinoma 5% and duodenal carcinoma 1.2%. The mean operative time was 3.7 +/- 0.5 hours and mean estimated blood loss during surgery was 733 +/- 48 mL. RESULTS: Hospital mortality occurred in 3.7% with an overall morbidity rate of 32%. The most common complications were delayed gastric emptying 8.9%, pancreatic fistulae 3.8%, wound infection 6.4%, biliary leakage 3.8% and bleeding 5%. The mean postoperative hospital stay was 9.4 +/- 1 days, with mean time for starting oral feeding 6 +/- 0.9 days. Late mortality occurred in 46% for the entire group with mean follow-up 22 +/- 19 months with actuarial survival for 1, 2, 3, 4, and 5 years being 80, 45, 25, 15, and 10%, respectively. CONCLUSIONS: It was found that this new modification made the operation easier with shorter operative time, less blood transfusion, low incidence of morbidity and short hospital stay. Moreover, it takes the advantages of lowering the incidence of biliary gastritis, cholangitis and peptic ulcer.

15
UI - 11813619
AU - Kedra B; Popiela T; Sierzega M; Precht A
TI - Prognostic factors of long-term survival after resective procedures for pancreatic cancer.
SO - Hepatogastroenterology 2001 Nov-Dec;48(42):1762-6
AD - Ist Department of General and GI Surgery, Jagiellonian University, Ul. Kopernika 40, 31-501 Krakow, Poland.
BACKGROUND/AIMS: Five-year survival rates following surgical resection of pancreatic cancer reported by the leading medical centers do not exceed 25%. It necessitates further extensive research in this area. The aim of the study was to determine prognostic factors of long-term survival after surgical treatment for pancreatic cancer. METHODOLOGY: From 1980 to 1999, 212 patients underwent surgical resection for pancreatic carcinoma. Statistical analysis of prognostic factors of long-term survival after pancreatic cancer surgery estimated by Kaplan-Meier method was carried out using multiple regression model. RESULTS: A group of 212 patients underwent surgery, where 98 had Whipple's resection, 50 Traverso, 35 total pancreatic resections, 25 left subtotal resections, and the remaining 4 segmental pancreatic body resections. Perioperative mortality was below 8%, 5-year survival approximately 15%, increasing to 65% in patients with early cancer. It was observed, that the following prognostic factors influenced the long-term survival rate: tumor size, localization, histopathologic type, and metastases to lymph nodes. The type and extent of surgery was of significance in the case of small neoplasms. CONCLUSIONS: Based on the analysis carried out, the authors conclude that the main prognostic factors for long-term survival after pancreatic cancer surgery are related to the tumor itself and show associations with the natural development biology.

16
UI - 12014658
AU - Mohiuddin M; Chendil D; Dey S; Alcock RA; Regine W; Mohiuddin M; Ahmed
TI - MM Influence of p53 status on radiation and 5-flourouracil synergy in pancreatic cancer cells.
SO - Anticancer Res 2002 Mar-Apr;22(2A):825-30
AD - Department of Radiation Medicine, University of Kentucky Medical Center, Lexington 40536-0293, USA.
BACKGROUND: While p53 protein plays an important role in the regulation of radiosensitivity and chemosensitivity in many tumors, the role of p53 in the combined management of tumors that harbor mutations in the p53 gene have not been fully defined. This study was undertaken to evaluate the impact of wild-type or mutant p53 status on the synergistic effects of 5-Fluorouracil (5-FU) and radiation (XRT) in pancreatic tumors. MATERIALS AND METHODS: Three pancreatic tumor cell lines, one containing wild-type functional p53 (Capan-2) and two containing mutant p53 (Panc-1 and MIA PaCa-2), were used in this study. Radiation-induced p53 and p21(waf1/cip1) protein expression was determined by Western blot analysis. Radiation induced Thymidylate Synthase (TS) mRNA expression was determined by 32P-RT-PCR. The effect of 5-FU, radiation, and radiation +5-FU on the growth and colony-forming ability of Capan-2, Panc-1 and MIA PaCa-2 was determined by clonogenic assays respectively. RESULTS: Radiation elevated p53 and p21(waf1/cip1) levels in Capan-2 cells. No elevation of p53 and p21(waf1/cip1) was evident in Panc-1. MIA PaCa-2 cells showed down-regulation of p21(waf1/cip1) with no elevation of p53 protein. Clonogenic assays showed enhanced radiosensitizing effect when 5-Fluorouracil was added to cell lines lacking functional p53. In wild-type p53 Capan-2 cells, radiation up-regulated TS mRNA levels. High basal levels of TS mRNA were detected in p53 mutant cell lines with no evident induction by radiation. CONCLUSION: Our results confirm that p53 status has a significant impact on radiation sensitivity with wild-type p53 cells being significantly more radiosensitive than mutant cell lines. When XRT and 5-FU were combined, this led only to an additive effect in wild-type cell lines and a synergistic effect in mutant cell lines.

17
UI - 12067219
AU - Chu QD; Al-kasspooles MF; Smith JL; Nava HR; Douglass HO Jr; Driscoll D;
TI - Gibbs JF Is glucagonoma of the pancreas a curable disease?
SO - Int J Pancreatol 2001;29(3):155-62
AD - Department of Surgical Oncology, Roswell Park Cancer Institute, State University of New York at Buffalo, 14263-0001, USA.
BACKGROUND: Glucagonomas are rare neuroendocrine tumors of the pancreas. Because of its rarity, its natural history is not well understood. AIM: We evaluated the natural history of glucagonomas treated at a tertiary care cancer center. METHODS: A retrospective analysis of 12 patients during 1970 to 2000 was performed. Six patients (50%) had a tumor located in the head of the pancreas. RESULTS: Abdominal pain (83%) and weight loss (75%) were the most common symptoms. Median tumor size was 6 cm (range 0.04-10). Seven patients (58%) had liver metastases. Five patients (42%) underwent curative resection. Overall median survival was 66 mo, and 5-yr overall survival was 66%. Five-yr overall survival was 83% for patients who had resection versus 50% for the non-resected patients (p = 0.04). Patients who were disease-free had a complete resection of the primary tumor and no liver involvement. CONCLUSIONS: Glucagonomas generally present with liver metastases at the time of diagnosis. Cure is only possible if the disease is localized and completely resected.

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