• Inherited pancreatic cancer: surveillance and treatment strategies for affected families.

• Timing and extent of surgical intervention in patients from hereditary pancreatic cancer kindreds.

• Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in

• ["Three steps procedure" in the treatment of large pancreatic head cancer]

• Quality of life in patients with cancers of the upper gastrointestinal tract.

• Readmissions after pancreatoduodenectomy.

• Whipple's resection-proximal pancreaticoduodenectomy (PD).

• Short and long-term outcome of pancreatic surgery in a district general hospital.

• Radical resection of gastric carcinoma with pancreas and spleen preservation and functional cleaning of lymph nodes.

• Emerging biological therapies for pancreatic carcinoma.

• Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and

• Compassionate use of Gemzar in advanced pancreatic cancer: a Belgian experience.

• Pancreatic cancer: from genes to patient care.

• Resected adenocarcinoma of the pancreas--616 patients: results, outcomes, and prognostic indicators.

• Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer.

• Irinotecan in the management of patients with pancreatic cancer.

• Adjuvant therapy in operable pancreatic cancer.

• Endolaparoscopic rendezvous treatment: a satisfying therapeutic choice for cholecystocholedocolithiasis.

• Use of spontaneous Epstein-Barr virus-lymphoblastoid cell lines genetically modified to express tumor antigen as cancer vaccines:

• Pain management of patients with unresectable peripancreatic carcinoma.

• A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line

1
UI - 12120228
AU - Rulyak SJ; Brentnall TA
TI - Inherited pancreatic cancer: surveillance and treatment strategies for affected families.
SO - Pancreatology 2001;1(5):477-85
AD - Division of Gastroenterology, University of Washington, Seattle, Wash., USA.
BACKGROUND: Nearly 10% of pancreatic cancers are hereditary in origin, and in some individuals, the risk of pancreatic cancer approaches 50%. A number of defined syndromes can predispose families to pancreatic cancer, although many of the mechanisms that result in familial pancreatic cancers are unknown. This article reviews current knowledge regarding familial pancreatic cancers and highlights the rationale for screening and surveillance. Methods for screening and surveillance of these high-risk individuals are described that allow the detection of pancreatic dysplasia, the precursor to pancreatic cancer. We also describe a single-center experience with the management and surveillance of familial pancreatic cancer kindreds. METHODS: Thirty-five patients from 13 familial pancreatic cancer kindreds underwent screening and/or surveillance. Endoscopic ultrasound (EUS) is the initial test of choice. Endoscopic retrograde cholangiopancreatography (ERCP) is reserved for symptomatic individuals or to investigate abnormal findings on EUS. In the proper clinical setting, patients with abnormal findings on both EUS and ERCP are candidates for total pancreatectomy. RESULTS: Twelve of 35 patients were noted to have abnormal findings on EUS and ERCP. All of these individuals underwent pancreatectomy, 10 total and 2 partial. The patients who underwent partial pancreatectomy are currently awaiting resection of the pancreatic remnant. Histopathologic examination of all 12 specimens demonstrated pancreatic dysplasia (the precursor lesion to pancreatic cancer). These specimens had no evidence of pancreatic cancer; nor were any of the resected pancreata normal. Follow-up of the 35 high-risk patients at present varies from 1 to 48 months, and none of the patients under surveillance have developed pancreatic cancer. CONCLUSION: The screening and surveillance of high-risk members of familial pancreatic cancer kindreds using EUS and ERCP is an effective method for identifying individuals with pancreatic dysplasia prior to the onset of invasive pancreatic cancer. The surveillance needs to be performed by a team of specialists who have experience in dealing with pancreatic cancer and its precursors.

2
UI - 12120232
AU - Kekis PB; Friess H; Kleeff J; Buchler MW
TI - Timing and extent of surgical intervention in patients from hereditary pancreatic cancer kindreds.
SO - Pancreatology 2001;1(5):525-30
AD - Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland.
Our knowledge of the molecular and genetic etiology of hereditary pancreatic cancer has expanded considerably and is steadily increasing. However, there are only a few hard data available regarding the clinical and surgical management of these patients. Surgery is currently performed when we detect dysplastic changes in the pancreas or when cancer is suspected. Of the available diagnostic modalities, endoscopic ultrasonography has proven so far to be the most useful for detecting dysplastic changes in the pancreases of patients from hereditary pancreatic cancer kindreds. It seems reasonable, once dysplasia has been diagnosed in a high-risk patient, to proceed to total pancreatectomy. The multifocal nature of dysplastic lesions precludes any type of operation that would leave behind pancreatic tissue. Currently, prophylactic whole-organ resection in the absence of premalignant lesions cannot be recommended since we do not know the exact risk for the development of cancer.

3
UI - 12118027
AU - Maisey N; Chau I; Cunningham D; Norman A; Seymour M; Hickish T; Iveson
TI - T; O'Brien M; Tebbutt N; Harrington A; Hill M Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer.
SO - J Clin Oncol 2002 Jul 15;20(14):3130-6
AD - Royal Marsden Hospital, Surrey, United Kingdom.
PURPOSE: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study. PATIENTS AND METHODS: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m(2)/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m(2) every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL). RESULTS: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P =.04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P =.14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P =.34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P <.01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms. CONCLUSION: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer.

4
UI - 11798764
AU - Ni Q; Zhang Q; Cao G
TI - ["Three steps procedure" in the treatment of large pancreatic head cancer]
SO - Zhonghua Yi Xue Za Zhi 2000 Apr;80(4):252-4
AD - Center for Pancreatic Cancer, Huashan Hospital, Shanghai Medical University, Shanghai 200040, China.
OBJECTIVE: To evaluate the feasibility and effectivity of "3 steps procedure" in the treatment of large pancreatic head cancer. METHODS: The "3 steps procedure" consisted of decompression of jaundice by simple cholecystotomy, intervenient (intra-arterial) chemotherapy (5-FU 1 approximately 1.5 g, mitomycin 8 approximately 14 mg, cisplatin 40 approximately 60 mg and octreatide 1 mu intravenously as near the superior and inferior pancreatic-duodenal arteries as possible), and then the reasonable regional pancreatic-duodenectomy. RESULTS: All 16 tumors were radically resected. Conventional and regional pancreatic-duodenectomy was done in 7 and 9 patients, respectively; of the later group, artificial prosthesis for portal vein bridge was done in 3 patients, end-to-end anastomosis in 4 and repair after partial resection of invaded vessel wall in 2. CONCLUSION: The "3 steps procedure" is feasible and effective in the treatment of large pancreatic head cancer.

5
UI - 12113032
AU - Blazeby JM; Vickery CW
TI - Quality of life in patients with cancers of the upper gastrointestinal tract.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):269-76
AD - University Division of Surgery, Bristol Royal Infirmary, Bristol, BS2 8HW, UK. jmblazeby@hotmail.com
Accurate assessment of health-related quality of life in patients with upper gastrointestinal cancers is essential to help determine treatment strategies. Questionnaires may be used to screen for physical and psychosocial morbidity, to evaluate new therapies and there is accumulating evidence to suggest that quality of life scores have prognostic value. There are well validated generic measures of quality of life suitable to use in patients with cancers of the upper gastrointestinal tract, but only two systems (EORTC QLQ-C30 and the FACT-G) have site-specific modules that have been constructed for this patient group. The future use of computer-assisted techniques to collect, analyze and interpret quality of life data will enable the implementation of quality of life results in clinical practice.

6
UI - 11952616
AU - King NK; Siriwardana HP; Siriwardena AK
TI - Readmissions after pancreatoduodenectomy.
SO - Br J Surg 2002 Apr;89(4):497-8

7
UI - 12109606
AU - Tait IS
TI - Whipple's resection-proximal pancreaticoduodenectomy (PD).
SO - J R Coll Surg Edinb 2002 Jun;47(3):528-40
AD - Department of Surgery & Molecular Oncology, Ninewells Hospital & Medical School, Dundee, UK. i.z.tait@dundee.ac.uk
Pancreatic resection offers the potential for long-term cure in 15% of patients with pancreatic cancer. This article describes the author's technique of pancreaticoduodenectomy (PD), together with guidelines for disease staging, pre-operative work-up and patient selection. The role of neo-adjuvant and adjuvant chemotherapy is currently under evaluation and all patients who have a curative resection should be considered for entry into the ESPAC 3 trial that aims to establish the definitive role of adjuvant chemotherapy in pancreatic cancer.

8
UI - 12109608
AU - Hutchins RR; Kojodjojo P; Ho R; Bani-Hani A; Snooks SJ
TI - Short and long-term outcome of pancreatic surgery in a district general hospital.
SO - J R Coll Surg Edinb 2002 Jun;47(3):548-51
AD - Department of Surgery, King George Hospital, Essex, UK.
Pancreatic surgery is a formidable undertaking with historically high mortality and poor prognosis for periampullary lesions. This has led to recommendations that all pancreatic surgery should be performed in specialist centres. There is no doubt from large series that a low mortality can be achieved in these centres, but there has been no direct comparison between results from these specialist centres and district general hospitals with an interest in pancreatic disease. We present a retrospective, seven-year experience with a 3% 30 day mortality, 39% morbidity and 14 month median survival for malignant disease. Comparison with the UK survey of specialist pancreatic units shows that pancreatic surgery can be safely performed in the setting of a district general hospital with low morbidity and mortality, and good long-term outcome.

9
UI - 12133545
AU - Qin H; Lin C
TI - Radical resection of gastric carcinoma with pancreas and spleen preservation and functional cleaning of lymph nodes.
SO - Chin Med J (Engl) 2002 May;115(5):736-9
AD - Department of Surgery, Shanghai Sixth People's Hospital, Shanghai 200233, China.
OBJECTIVE: To study the clinical value of radical resection of gastric carcinoma with pancreas and spleen preservation (PSP) and functional cleaning of lymph nodes (LNs) of the spleen hillus and along the splenic artery. METHODS: Pancreas and spleen involvement was retrospectively reviewed among 439 cases of resectable carcinoma of the gastric cardia, gastric corpus and total stomach. During gastric surgery, 2 ml of methylene blue was injected into the subserosal space of the gastric cardia or corpus to observe the spread of lymphatic flow in 54 cases of gastric carcinoma. The metastatic rate of LNs in splenic hillus and along the trunk of the splenic artery (No10, No11), postoperative complications and survival rates were investigated in 63 gastric carcinoma patients that had received gastrectomy with pancreas and spleen preservation (PSP). These were compared with the pancreas preservation (PP) group and pancreas and spleen combined resection (PSR) group. RESULTS: Among these 439 cases, only 25 cases were observed with direct invasion to the pancreas (5.7%), and 10 cases with direct invasion to the spleen (2.3%). After pathological examination of the pancreatic body and tail, we found 22 cases with pancreas and spleen combined resection, 4 cases (18.2%, 4/22) with direct invasion of the capsule and 2 with invasion to the superficial parenchyma (9.1%, 2/22), without metastasis to the lymph nodes within the pancreas and spleen. The metastatic rate of No10, No11 lymph nodes were 17.5% (11/63) and 19.1% (12/63) in the PSP group, 20.8% (45/216) and 25% (54/216) in the PP group, and 20% (6/30) and 23.3% (7/30) in the PSR group. There were no statistically significant differences (P > 0.05). Injection of methylene blue into the subserosal space of the stomach did not diffuse into the spleen or pancreatic parenchyma. Postoperative complications, diabetes and mortality in PSP (0%, 0%, 0%) were lower than in PP (4.2%, 0.9%, 0.9%) or PSR (40%, 10%, 3.3%). The 5-year survival rate (5-YSR) and 10-YSR in PSP (57.5%, 52.0%) were higher than in PSR (37.5%, 30.0%). Those patients with stage II and III(a) treated by PSP, improved markedly. CONCLUSIONS: The surgical procedure of pancreas and spleen preservation for gastric cancer is a safe and organ function protected method. Postoperative complications were lower and survival rates were higher, the radicality was not reduced. These results indicate that PSP is preferred in patients with gastric carcinoma of stage II or III(a).

10
UI - 12099644
AU - Gilliam AD; Watson SA
TI - Emerging biological therapies for pancreatic carcinoma.
SO - Eur J Surg Oncol 2002 Jun;28(4):370-8
AD - Academic Unit of Cancer Studies, Department of Surgery Univertisy of Nottingham, Nottingham, NG7 2UH, UK. andrew.gilliam@nottingham.ac.uk
AIMS: The incidence of pancreatic carcinoma remains approximately equal to its mortality, with the vast majority of patients having advanced disease at presentation. This review is an update of the promising novel approaches involving biological therapy that may be used in conjunction with new chemotherapeutic agents in the near future. MEHTODS: A literature review was performed using the National Library of Medicine's Pubmed database, combined with recently published data from the AGA and ASCO conferences. RESULTS: Rapid progress is being made in gene and molecular technology potentially enabling us to inhibit pancreatic carcinogenesis and to reduce disease progression. Different targets include signal transduction inhibitors, gene therapy, genetic prodrug activation therapy, antisense therapy, immunotherapy, matrix metalloproteinase and cyclo-oxygenase-2 inhibition and hormonal manipulation. CONCLUSION: A variety of biological agents are currently undergoing clinical trials, targeting different areas of the pancreas'neoplastic process. .

11
UI - 12028639
AU - Kouloulias VE; Kouvaris JR; Nikita KS; Golematis BC; Uzunoglu NK;
TI - Mystakidou K; Papavasiliou C; Vlahos L Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma.
SO - Int J Hyperthermia 2002 May-Jun;18(3):233-52
AD - Department of Radiotherapy, Medical School, University of Athens, Aretaieion Hospital, 76 Vas. Sophias Avenue, 11528 Athens, Greece. vkouloul@cc.ece.ntua.gr
The aim of this study was to evaluate the potential role of intraoperative hyperthermia (IOHT) in the management of stage IV pancreatic adenocarcinoma. Twenty-seven patients (group A) received pre-operative chemotherapy (5-FU), by-pass surgery with intraoperative bolus infusion of 5-FU and post-operatively multi-agent chemotherapy plus sandostatin and external beam irradiation (45Gy, 25 fractions, 5 days a week). In a non-randomized way, 10 patients (group B) received an additional single session of IOHT (43-45 degrees C, 1h) performed directly on the tumour using a waveguide applicator (433MHz) with interstitial measurements of temperature measured. A brief instrument was developed for evaluating patients' quality of life. No progressive disease (PD) was noticed in group B vs 11% (3/27) of PD in group A. There was also a significant increase of overall survival (OS) in group B vs A patients (p = 0.029, log-rank test). Moreover, there was a significant improvement for group B vs A patients regarding Karnofsky performance status (p < 0.001, Mann-Whitney test), pain score (p < 0.001, Mann-Whitney test) and quality of life score (p = 0.031, Mann-Whitney test). A significant correlation was noticed between OS and thermal parameters such as average T(min) (p = 0.043), average T(max) (p = 0.027) and cumulative minutes T(90) >or= 44 degrees C (p < 0.001). Combined IOHT with chemotherapy (pre-, intra- and post-operative) and external beam post-operative radiotherapy seem to have a potential benefit in the management of unresectable adenocarcinoma of the pancreas, concerning local response, OS and quality of life. Further clinical studies to evaluate the benefit of IOHT suggested in this study are warranted.

12
UI - 11887632
AU - Humblet Y; Van Cutsem E; Dubois C; Gillard P
TI - Compassionate use of Gemzar in advanced pancreatic cancer: a Belgian experience.
SO - Acta Gastroenterol Belg 2001 Oct-Dec;64(4):305-8
AD - Cliniques Universitaires St Luc, Avenue Hippocrate, 10, B-1200 Bruxelles. humblet@onco.ucl.ac.be
Gemzar is a nucleoside analog that has been shown to be superior to 5-fluorouracil for the treatment of advanced pancreatic cancer in terms of both clinical benefit and survival. This open label program enrolled 214 patients. Patients eligible for this program had advanced or metastatic pancreatic cancer, received up to one previous chemotherapy, a baseline Karnofsky performance status (KPS) of at least 50, measurable or evaluable disease, adequate organ function defined as: absolute leucocyte count > 3 x 10(9)/L, platelet count > 100 x 10(9)/L, hemoglobin > 9 gr/dL, total bilirubin < 2 x upper limit of normal (ULN), creatinine < 2 x ULN, ALT and AST levels < 5 x ULN and were at least 18 years. A 1000 mg/m2 of Gemzar was administered weekly up to 7 weeks followed by a week of rest, then once weekly for 3 weeks out of every 4 weeks. The median age at inclusion was 64 years, 52% of the patients were male, 27% were 70 year or older, 66% had stage IV disease, 66% had a KPS of 80 or higher and 34% had received no prior chemotherapy. The overall response rate is 7%. A time-to-first-serious-event analysis was performed since only a limited number of dates of death were available. The first serious event (FSE) was considered as the earliest of the following: increase by at least 2 of the pain score, deterioration of KPS of at least 20, documentation of progressive disease or death. The median time to FSE was 4 months, the free FSE rate at 1 year was 14%. We conclude that the results observed in this program confirm the established efficacy of Gemzar in pancreatic cancer.

13
UI - 12086895
AU - Hruban RH
TI - Pancreatic cancer: from genes to patient care.
SO - J Gastrointest Surg 2001 Nov-Dec;5(6):583-7
AD - Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231-2410, USA.

14
UI - 12086909
AU - Forgensen J
TI - Resected adenocarcinoma of the pancreas--616 patients: results, outcomes, and prognostic indicators.
SO - J Gastrointest Surg 2001 Nov-Dec;5(6):681; discussion 681

15
UI - 12165642
AU - Anderson KE; Johnson TW; Lazovich D; Folsom AR
TI - Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer.
SO - J Natl Cancer Inst 2002 Aug 7;94(15):1168-71
AD - Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454, USA. andeson_k@epi.umn.edu
Laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit pancreatic cancer, but epidemiologic data to support this finding are limited. We conducted a prospective study from 1992 through 1999 among 28 283 postmenopausal women who lived in Iowa to examine the association between the self-reported use of aspirin and other NSAIDs and the incidence of pancreatic cancer. Eighty incident cases of pancreatic cancer were identified during 7 years of follow-up. The multivariate-adjusted relative risk of pancreatic cancer associated with any current use of aspirin versus no use was 0.57 (95% confidence interval = 0.36 to 0.90). There was a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week (P(trend) =.005). Nonaspirin NSAID use was not associated with incident pancreatic cancer. These data indicate that aspirin might be chemopreventive for pancreatic cancer.

16
UI - 11200146
AU - Green MR; Harper M; Safa A; Sherman CA; Mushtaq CM; Bahadori H; Brescia
TI - FJ; Rocha Lima CM Irinotecan in the management of patients with pancreatic cancer.
SO - Oncology (Huntingt) 2000 Dec;14(12 Suppl 14):31-3
AD - Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA. greenmrk@musc.edu
Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan (Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with previously untreated pancreatic cancer were given irinotecan and gemcitabine were promising, with two of three patients achieving a partial response. Because of the favorable outcome of the phase I study, a multicenter phase II trial was undertaken in previously untreated patients with pancreatic carcinoma. Data from other sites entering patients in this phase II study have been analyzed, and a multicenter phase III trial of single-agent gemcitabine vs the irinotecan combination in first-line treatment of patients with locally advanced or metastatic pancreatic cancer is underway.

17
UI - 12013694
AU - Wente MN; Buchler P; Friess H; Buchler MW
TI - Adjuvant therapy in operable pancreatic cancer.
SO - Swiss Surg 2002;8(2):74-80
AD - Department of General Surgery, University of Heidelberg, Germany.
Adenocarcinoma of the pancreas remains a highly lethal disease with one of the worst mean survival rates of all solid malignancies. Even with improvements in surgical techniques in the last decades, the five-year survival rate of patients following resection is still under 20 percent. Various additional treatment concepts have been introduced based on encouraging results for adjuvant chemoradiotherapy obtained in a small randomized-controlled trial more than 15 years ago. The purpose of this article is to review the results of several trials investigating adjuvant therapy for pancreatic cancer. We will discuss recent studies of EORTC (European Organization for Research and Treatment of Cancer), ESPAC (European Study Group for Pancreatic Cancer) and others and will also focus on future alternative treatment options for pancreatic cancer.

18
UI - 11972193
AU - Tricarico A; Cione G; Sozio M; Di Palo P; Bottino V; Tricarico T;
TI - Tartaglia A; Iazzetta I; Sessa E; Mosca S; De Nucci C; Falco P Endolaparoscopic rendezvous treatment: a satisfying therapeutic choice for cholecystocholedocolithiasis.
SO - Surg Endosc 2002 Apr;16(4):585-8
AD - Emergency Department, Laparoscopic Surgery, A.O.R.N. Cardarelli, Via A. Cardarelli, 80100 Naples, Italy.
BACKGROUND: There are many different strategies for the treatment of the main bile duct lithiasis. When lithiasis of the biliary tract is suspected at a preoperative stage, we can treat patients with sequential treatment: endoscopic netrograde cholangiopancreatography followed by laparoscopic cholecystectomy. If common bile duct-lithiasis is recognized at an intraoperative stage, many options for treatment exist, one of which is intraoperative retrograde endoscopic sphincterotomy (ES) (laparoendorendezvous). METHODS: We report our experience using the aforementioned technique with 58 patients affected by cholelithiasis and complex Common bile duct disease who underwent laparoscopic cholecystocholedocolithiasis: 12 by previously described lithiasis plus stenosant papillitis, 2 also by a pancreas head cancer, and 1 by cancer of the papilla. RESULTS: The combined technique was performed in 86% of the cases. Six patients required conversion to open surgery. In two other patients, laparoscopic choledocotomy was performed with positioning of a Kehr-tube for an ampulla-impacted lithiasis. CONCLUSIONS: Intraoperative ES offers a valid approach to the treatment of cholecystocholedocolithiasis in one session. Furthermore, it represents a valid alternative to transcholedocical laparoscopic treatment of cholelithiasis and complex common bite duct pathology.

19
UI - 11975848
AU - Kubuschok B; Schmits R; Hartmann F; Cochlovius C; Breit R; Konig J;
TI - Pistorius G; Schilling M; Renner C; Pfreundschuh M Use of spontaneous Epstein-Barr virus-lymphoblastoid cell lines genetically modified to express tumor antigen as cancer vaccines: mutated p21 ras oncogene in pancreatic carcinoma as a model.
SO - Hum Gene Ther 2002 May 1;13(7):815-27
AD - Department of Internal Medicine I, University of Saarland Medical School, D-66421 Homburg/Saar, Germany.
Spontaneous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (SP-LCLs) can be easily obtained from latently EBV-infected cancer patients and used as a source of antigen-presenting cells (APCs) for immunotherapy. Using point-mutated (codon 12) p21(ras) (muRas) as a model tumor antigen, we evaluated the practicability of using genetically modified SP-LCLs as cancer vaccines for patients with pancreatic cancer expressing mutated Ras (muRas). The repeated stimulation of peripheral blood mononuclear cells (PBMCs) from patients with muRas-LCLs elicited a strong, muRas-specific T cell response. A significant cytotoxic activity against EBV virus proteins or components of the expression vector was not observed. The T cells were able to recognize naturally presented muRas, as shown by their cytotoxicity against muRas (Gly-12 to Val-12 or Asp-12)-expressing tumor cells. The T cell response was mainly MHC class I restricted, and peptides containing amino acids 5 to 14 of muRas-Val-12 and muRas-Asp-12 were identified as immunogenic peptides for HLA-A2. In contrast to the situation in patients with putatively muRas-primed T cells, muRas-LCLs were not able to prime naive T lymphocytes from healthy controls. Vaccination of a pancreatic cancer patient with muRas-LCL induced muRas-specific T cells in PBMCs after 4 weeks. We conclude that genetically modified muRas-LCLs can efficiently present tumor antigens to the immune system and induce antigen-specific cytotoxic T cell responses in vitro and in vivo.

20
UI - 12053225
AU - van Geenen RC; Keyzer-Dekker CM; van Tienhoven G; Obertop H; Gouma DJ
TI - Pain management of patients with unresectable peripancreatic carcinoma.
SO - World J Surg 2002 Jun;26(6):715-20
AD - Department of Surgery, Academic Medical Center, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
In patients with unresectable peripancreatic carcinoma, pain is generally treated with pain medication or with a celiac plexus blockade. Radiotherapy has also been reported to reduce pain. The efficacy of these treatment modalities is still under discussion. The aim of this study was to analyze the effects of the various types of pain management on patients who underwent palliative bypass surgery for unresectable 1998 a series of 98 patients underwent palliative bypass surgery, mostly for unresectable disease found during exploration. Patients were divided into three groups: palliative bypass surgery (BP), palliative bypass surgery with an intraoperative celiac plexus blockade (CPB), and palliative bypass surgery with or without celiac plexus blockade followed by high-dose conformal radiotherapy (RT). Radiotherapy was performed only in selected patients with locally advanced disease and without metastases, implying a better prognosis of the last group. The pain medication consumption, pain medication-free survival, hospital-free survival, and overall survival were analyzed. The preoperative consumption of pain medication was significantly higher in the CPB group than in the BP or RT group. The postoperative consumption of pain medication in the CPB, BP, and RT groups increased during follow-up from 15%, 17%, and 13% before surgery to 52%, 57%, and 46%, respectively, at three-fourths of the survival time (NS). This increase in consumption of pain medication was not different in the three groups. In the RT group the median pain medication-free survival was significantly longer than in the BP or CPB group (9.3 vs. 3.1 and 3.3 months; p = 0.02). The median hospital-free survival and median overall survival were significantly longer in the RT group than in the CPB group (10.3 vs. 6.8 months, p = 0.01; and 7.1 vs. 10.8 months, p = 0.01). Celiac plexus blockade as pain management did not result in an increase of the pain medication-free survival or overall survival. Therefore a positive effect of a celiac plexus blockade on pain could not be confirmed in the present study. Radiotherapy resulted in increased pain-medication survival, hospital-free survival, and overall survival compared to celiac plexus blockade. These effects are probably partly related to patient selection.

21
UI - 12107836
AU - Bramhall SR; Schulz J; Nemunaitis J; Brown PD; Baillet M; Buckels JA
TI - A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.
SO - Br J Cancer 2002 Jul 15;87(2):161-7
AD - Department of Surgery, Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. S.R.Bramhall@bham.ac.uk
Pancreatic cancer is the fifth most common cause of cancer death in the western world and the prognosis for unresectable disease remains poor. Recent advances in conventional chemotherapy and the development of novel 'molecular' treatment strategies with different toxicity profiles warrant investigation as combination treatment strategies. This randomised study in pancreatic cancer compares marimastat (orally administered matrix metalloproteinase inhibitor) in combination with gemcitabine to gemcitabine alone. Two hundred and thirty-nine patients with unresectable pancreatic cancer were randomised to receive gemcitabine (1000 mg m(-2)) in combination with either marimastat or placebo. The primary end-point was survival. Objective tumour response and duration of response, time to treatment failure and disease progression, quality of life and safety were also assessed. There was no significant difference in survival between gemcitabine and marimastat and gemcitabine and placebo (P=0.95 log-rank test). Median survival times were 165.5 and 164 days and 1-year survival was 18% and 17% respectively. There were no significant differences in overall response rates (11 and 16% respectively), progression-free survival (P=0.68 log-rank test) or time to treatment failure (P=0.70 log-rank test) between the treatment arms. The gemcitabine and marimastat combination was well tolerated with only 2.5% of patients withdrawn due to presumed marimastat toxicity. Grade 3 or 4 musculoskeletal toxicities were reported in only 4% of the marimastat treated patients, although 59% of marimastat treated patients reported some musculoskeletal events. The results of this study provide no evidence to support a combination of marimastat with gemcitabine in patients with advanced pancreatic cancer. The combination of marimastat with gemcitabine was well tolerated. Further studies of marimastat as a maintenance treatment following a response or stable disease on gemcitabine may be justified.

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