UI - 12120228
AU - Rulyak SJ; Brentnall TA
Inherited pancreatic cancer: surveillance and treatment strategies for
SO - Pancreatology 2001;1(5):477-85
AD - Division of Gastroenterology, University of Washington, Seattle, Wash.,
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.
UI - 12120232
AU - Kekis PB; Friess H; Kleeff J; Buchler MW
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.
UI - 12118027
AU - Maisey N; Chau I; Cunningham D; Norman A; Seymour M; Hickish T; Iveson
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.
UI - 11798764
AU - Ni Q; Zhang Q; Cao G
["Three steps procedure" in the treatment of large pancreatic head
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.
UI - 12113032
AU - Blazeby JM; Vickery CW
Quality of life in patients with cancers of the upper gastrointestinal
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):269-76
AD - University Division of Surgery, Bristol Royal Infirmary, Bristol, BS2
8HW, UK. email@example.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.
UI - 11952616
AU - King NK; Siriwardana HP; Siriwardena AK
Readmissions after pancreatoduodenectomy.
SO - Br J Surg 2002 Apr;89(4):497-8
UI - 12109606
AU - Tait IS
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. firstname.lastname@example.org
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.
UI - 12109608
AU - Hutchins RR; Kojodjojo P; Ho R; Bani-Hani A; Snooks SJ
Short and long-term outcome of pancreatic surgery in a district general
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.
UI - 12133545
AU - Qin H; Lin C
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
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).
UI - 12099644
AU - Gilliam AD; Watson SA
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. email@example.com
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. .
UI - 12028639
AU - Kouloulias VE; Kouvaris JR; Nikita KS; Golematis BC; Uzunoglu NK;
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
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.
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
UI - 11887632
AU - Humblet Y; Van Cutsem E; Dubois C; Gillard P
Compassionate use of Gemzar in advanced pancreatic cancer: a Belgian
SO - Acta Gastroenterol Belg 2001 Oct-Dec;64(4):305-8
AD - Cliniques Universitaires St Luc, Avenue Hippocrate, 10, B-1200
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.
UI - 12086895
AU - Hruban RH
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.
UI - 12086909
AU - Forgensen J
Resected adenocarcinoma of the pancreas--616 patients: results,
outcomes, and prognostic indicators.
SO - J Gastrointest Surg 2001 Nov-Dec;5(6):681; discussion 681
UI - 12165642
AU - Anderson KE; Johnson TW; Lazovich D; Folsom AR
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. firstname.lastname@example.org
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.
UI - 11200146
AU - Green MR; Harper M; Safa A; Sherman CA; Mushtaq CM; Bahadori H; Brescia
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. email@example.com
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.
UI - 12013694
AU - Wente MN; Buchler P; Friess H; Buchler MW
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
UI - 11972193
AU - Tricarico A; Cione G; Sozio M; Di Palo P; Bottino V; Tricarico T;
Tartaglia A; Iazzetta I; Sessa E; Mosca S; De Nucci C; Falco P
Endolaparoscopic rendezvous treatment: a satisfying therapeutic choice
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.
UI - 11975848
AU - Kubuschok B; Schmits R; Hartmann F; Cochlovius C; Breit R; Konig J;
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.
UI - 12053225
AU - van Geenen RC; Keyzer-Dekker CM; van Tienhoven G; Obertop H; Gouma DJ
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.
UI - 12107836
AU - Bramhall SR; Schulz J; Nemunaitis J; Brown PD; Baillet M; Buckels JA
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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