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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Pancreatic Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 11544826
AU - Kokhanenko NIu; Ignashov AM; Varga EV; Polkanova MS; Aleshina LA;
TI -
Kimbarovskaia AA; Osipenko SK; Lebedev EG
[Role of the tumor markers CA 19-9 and carcinoembryonic antigen (CEA) in
diagnosis, treatment and prognosis of pancreatic cancer]
SO - Vopr Onkol 2001;47(3):294-7
AD - I.P. Pavlov State Medical University, Consultative-Diagnostic Center No.
85, St. Petersburg.
The investigation was concerned with diagnostic sensitivity, specificity
and effectiveness of assay of CA 19-9 and carcinoembryonic antigen (CEA)
in the choice of treatment modality and evaluation of therapy pancreatic
carcinoma (PC). Either marker has been studied in 685 examinations for
PC, 68--chronic pseudotumorous pancreatitis and 24--intestinal cancer at
other sites since 1995. Tumor resection for PC was carried out in 31;
conservative treatment--67; chemotherapy--56 and radiotherapy--in 29
cases. In CA 19-9 examinations, diagnostic sensitivity was 90.2;
specificity--72.1 and effectiveness--85.3%, while in CEA determinations,
82.5; 30.9 and 68.5%, respectively. CA 19-9 and CEA levels proved to be
prognostic factors of survival. An inverse correlation was observed
between median survival and tumor marker concentrations: higher basal
(preoperative) level of marker in blood was matched by lower median
survival. A similar relationship was identified for CEA: 5-10--14.2
months; 10.1-20 ng/ml--8.0 months; 20.1-30 ng/ml--3.9 months, and more
than 30 ng/ml--4.8 months. There was a direct correlation between CA
19-9 level and tumor stage. The dynamics of tumor markers, particularly,
CA 19-9 correlated with treatment effectiveness during its course.
2
UI - 11544836
AU - Kokhanenko NIu; Amosov VI; Ignashov AM; Gladinova TS; Volkov ON;
TI -
Ignat'eva IA; Iakovleva ES; Osipenko SK; Savrasov VM; Tabidze IB; Sopiia
ER
[Results of radiotherapy and combined, comprehensive treatment of
pancreatic cancer]
SO - Vopr Onkol 2001;47(3):343-7
AD - I.P. Pavlov State Medical University, St. Petersburg.
The results of irradiation, combined and complex treatment of pancreatic
cancer have been evaluated versus stage, site and extent of surgery.
Radiotherapy was carried out in 63 patients (1988-1999): prior to
gastropancreaticoduodenectomy (GPDE)--7; after GPDE--12; for local
recurrence after GPDE--4, before and after left-sided resection--4,
before and after conservative surgery--19, and after diagnostic
verification (exploratory laparotomy or ultrasound-controlled
fine-needle biopsy)--17. Diagnosis was established on the basis of
clinical data and case histories, ultrasonographic, CT, histological,
cytological, biopsy, blood serum-marker CA 19-9 and CEA findings. Two
months after treatment, complete remission was registered in 5 (13%),
partial response--5 (13%), stabilization--13 (33%), tumor
progression--16 (41%). Before and after GPDE, tolerance to radiotherapy
was sufficient. Median survival in this group was 12.9 months,
controls--8.1 months; for conservative surgery--7.3 and 4.1 months,
respectively; radiotherapy + exploratory laparotomy alone--16.8 and 4.3
months, respectively. Irradiation of locally-advanced tumors of the body
and/or tail of pancreas proved effective: median survival was 7.3
months, control--2.2 months. Hence, radiotherapy made an important
contribution to treatment of locally-advanced and resectable pancreatic
tumors and longer survival.
3
UI - 11716876
AU - Abrams RA; Lillemoe KD; Piantadosi S
TI -
Continuing controversy over adjuvant therapy of pancreatic cancer.
SO - Lancet 2001 Nov 10;358(9293):1565-6
AD - Department of Oncology, Johns Hopkins Hospital and School of Medicine,
Baltimore, MD 21231, USA. abramro@jhmi.edu
4
UI - 11716884
AU - Neoptolemos JP; Dunn JA; Stocken DD; Almond J; Link K; Beger H; Bassi C;
TI -
Falconi M; Pederzoli P; Dervenis C; Fernandez-Cruz L; Lacaine F; Pap A;
Spooner D; Kerr DJ; Friess H; Buchler MW; European Study Group for
Pancreatic Cancer
Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic
cancer: a randomised controlled trial.
SO - Lancet 2001 Nov 10;358(9293):1576-85
AD - Department of Surgery, Liverpool University, Liverpool, UK.
j.p.neoptplemos@liverpool.ac.uk
BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains
uncertain. The European Study Group for Pancreatic Cancer (ESPAC)
assessed the roles of chemoradiotherapy and chemotherapy in a randomised
study. METHODS: After resection, patients were randomly assigned to
adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks
with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after
2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and
folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months).
Clinicians could randomise patients into a two-by-two factorial design
(observation, chemoradiotherapy alone, chemotherapy alone, or both) or
into one of the main treatment comparisons (chemoradiotherapy versus no
chemoradiotherapy or chemotherapy versus no chemotherapy). The primary
endpoint was death, and all analyses were by intention to treat.Findings
541 eligible patients with pancreatic ductal adenocarcinoma were
randomised: 285 in the two-by-two factorial design (70
chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); a further
68 patients were randomly assigned chemoradiotherapy or no
chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median
follow-up of the 227 (42%) patients still alive was 10 months (range
0-62). Overall results showed no benefit for adjuvant chemoradiotherapy
(median survival 15.5 months in 175 patients with chemoradiotherapy vs
16.1 months in 178 patients without; hazard ratio 1.18 [95% CI
0.90-1.55], p=0.24). There was evidence of a survival benefit for
adjuvant chemotherapy (median survival 19.7 months in 238 patients with
chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66
[0.52-0.83], p=0.0005).Interpretation This study showed no survival
benefit for adjuvant chemoradiotherapy but revealed a potential benefit
for adjuvant chemotherapy, justifying further randomised controlled
trials of adjuvant chemotherapy in pancreatic cancer.
5
UI - 11830551
AU - Arlt A; Vorndamm J; Muerkoster S; Yu H; Schmidt WE; Folsch UR; Schafer H
TI -
Autocrine production of interleukin 1beta confers constitutive nuclear
factor kappaB activity and chemoresistance in pancreatic carcinoma cell
lines.
SO - Cancer Res 2002 Feb 1;62(3):910-6
AD - Laboratory of Molecular Gastroenterology, Department of Medicine,
University of Kiel, Schittenhelmstrasse 12, D-24105 Kiel, Germany.
We have recently shown that several pancreatic carcinoma cell lines are
resistant to topoisomerase IIalpha inhibitors due to elevated basal
nuclear factor kappaB (NF-kappaB) activity, and blockade of this
activity by various means strongly increased chemosensitivity. In search
of possible mechanisms leading to exaggerated NF-kappaB activity, we
identified interleukin (IL)-1beta as a key mediator of this activation
in two of the chemoresistant cell lines (A818-4 and PancTu-1). These
cells express and secrete high levels of IL-1beta, as demonstrated by
reverse transcription-PCR, immunocytochemistry, and ELISA. Culture
supernatants from both cell lines induced NF-kappaB activity in
chemosensitive PT45-P1 pancreatic carcinoma cells and significantly
attenuated etoposide-induced apoptosis in a NF-kappaB-dependent fashion,
similar to that seen in PT45-P1 cells treated with recombinant IL-1beta.
Treatment of these cells with IL-1beta also changed the DNA damage
characteristics toward those observed in A818-4 and PancTu-1 cells.
NF-kappaB activation and the gain of chemoresistance in PT45-P1 cells on
treatment with supernatants from both chemoresistant cell lines was
abolished in the presence of a blocking anti-IL-1 receptor (I) antibody.
Furthermore, this antibody decreased the resistance of A818-4 and
PancTu-1 cells to etoposide treatment along with reduced NF-kappaB
activity. Blockade of NF-kappaB activation by MG132, sulfasalazine, or
an IkappaBalpha superrepressor disrupted the IL-1beta-mediated
amplification loop and the accompanying chemoresistance. Our data
provide insights into an autocrine mechanism involving IL-1beta by which
pancreatic carcinoma cells develop chemoresistance that could serve as a
molecular target in anticancer therapy.
6
UI - 11872274
AU - Horst E; Seidel M; Micke O; Rube C; Glashorster M; Schafer U; Willich NA
TI -
Accelerated radiochemotherapy in pancreatic cancer is not necessarily
related to a pathologic pancreatic function decline in the early period.
SO - Int J Radiat Oncol Biol Phys 2002 Feb 1;52(2):304-9
AD - Department of Radiation Oncology, University of Munster, Munster,
Germany. horste@uni-muenster.de
PURPOSE: To evaluate the functional effects of ionizing radiation in
patients with unresectable pancreatic cancer in the early period after
accelerated radiochemotherapy (ART). METHODS AND MATERIALS: To analyze
the exocrine component, the amino acid consumption test and fecal
elastase 1 were performed in 13 patients immediately before and 4-8
weeks after ART. Pancreatic duct morphology was evaluated before
therapy. Weight loss and clinical steatorrhea were recorded. Endocrine
parameters were examined according to standardized criteria. RESULTS:
The relative change of the amino acid consumption test results and the
median elastase concentration was 41.2% and 56.4%, respectively. Five
patients still had normal test results after ART and 5 patients
developed pathologic values. The median relative weight loss of the
total body weight was 7.7% +/- 4.5%. No steatorrhea occurred. Of the 5
patients with normal values, 3 had a mean organ dose of <40 Gy. Of the 5
patients with pathologic values, 4 had a mean organ dose of >41 Gy. The
endocrine function measurements remained unchanged. CONCLUSION: Although
a nominal reduction of exocrine function parameters occurred in most
patients, ART was not necessarily related to a pathologic level in the
early period. Diabetes was not established. The functional impairment
that was existent in the patient population presumably contributed to
the weight loss. Pancreatic enzyme preparations may also play a role in
maintaining an anabolic state during and after radiochemotherapy.
7
UI - 11550487
AU - Wellner I; Banga P; Haulik L; Racz I; Kecskes G
TI -
[Surgical resection of tumors in the distal duodenum]
SO - Magy Seb 2001 Aug;54(4):215-8
AD - Sebeszeti Osztaly, Petz Aladar Megyei Oktato Korhaz, Gyon.
We present six cases of successfully resected primary tumors of the
distal part of duodenum (third and fourth segment). Average age of the
four male and two female patients was 59 years (47-80). Distal segmental
resection were performed in four, pylorus-preserving
pancreatoduodenectomy in two cases. Histologically the tumors were five
adenocarcinomas, and one gastrointestinal stromal tumor. This tumor
causing massive bleeding. In two patients, local lymph nodes were tumor
positive, and in one patient synchronous metastasis of the greater
omentum was excised during a palliative resection. There was no
operative mortality. During a mean follow-up period of 17 months two
patients died. Our results support the fact, that radical surgical
resection of these tumors, even by segmental resection, provides a more
favorable prognosis for duodenal carcinoma than for pancreatic tumors.
8
UI - 11822959
AU - Urbach DR; Swanstrom LL; Hansen PD
TI -
The effect of laparoscopy on survival in pancreatic cancer.
SO - Arch Surg 2002 Feb;137(2):191-9
AD - Division of General Surgery, University Health Network, Department of
Surgery, University of Toronto, Toronto, Ontario, Canada.
Urbach@uhn.on.ca
HYPOTHESIS: Exposure to laparoscopy influences survival in patients with
unresected pancreatic cancer who have a diagnostic or staging surgical
procedure. METHODS: We used the Surveillance, Epidemiology, and End
Results Medicare-linked database to identify a cohort of persons 65
years and older, who were newly diagnosed with primary pancreatic cancer
between 1991 and 1996 and who had a diagnostic laparoscopy or laparotomy
during the course of their disease. Patients with a prior malignancy and
those who had a pancreatic resection were excluded. We used
proportional-hazards regression to adjust risk estimates for demographic
factors, medical comorbidities, tumor characteristics, and the use of
other treatment modalities. RESULTS: We identified 112 individuals with
pancreatic cancer who had a laparoscopic procedure and 791 who had only
conventional surgery. More patients who had laparoscopic surgery had
distant metastases at diagnosis (67.9% vs 41.2%; P =.001). Median
duration of survival in the laparoscopic surgery group was 4.8 months
(95% confidence interval [CI], 4.1-6.8) compared with 5.3 months in the
group that had only open surgery (95% CI, 4.9-5.6; P =.83). Compared
with patients who only had a laparotomy, patients who had laparoscopic
surgery did not have an increased rate of death when adjusted for the
effects of age, sex, tumor size, grade, the presence of nodal and
distant metastases at diagnosis, and the use of radiation, chemotherapy,
therapeutic endoscopic retrograde cholangiopancreatography, and biliary
and gastric bypass (adjusted hazard ratio, 0.93; 95% CI, 0.62-1.40).
CONCLUSION: Exposure to laparoscopic surgery did not adversely affect
survival in a cohort of elderly patients with pancreatic cancer who had
a diagnostic procedure but no pancreatic resection.
9
UI - 11885380
AU - Pirro N; Sielezneff I; Cesari J; Consentino B; Gregoire R; Brunet C;
TI -
Sastre B
[Cephalic pancreaticoduodenectomy for adenocarcinoma of the head of the
pancreas: does pylorus preservation change morbidity and prognosis?]
SO - Ann Chir 2002 Feb;127(2):95-100
AD - Service de chirurgie digestive, hopital Sainte-Marguerite, 270,
boulevard de Sainte-Marguerite, 13274 Marseille, France.
nicolaspirro@yahoo.fr
STUDY AIM: To evaluate the influence of a pylorus-preserving on the
morbidity and prognosis of patient with pancreaticoduodenectomy for
adenocarcinoma of pancreas. PATIENTS AND METHODS: Between 1985 and 1999,
183 patients were operated on for pancreatic adenocarcinoma. Among them,
63 patients (40 men, mean age 63 years, range 41-77 years) had curative
resection and were included in this retrospective study. They were
classified according to the type of resection. In the group I, the
procedure included a pylorus-preserving pancreaticoduodenectomy (n =
35). In the group II, the procedure included polar inferior gastrectomy
(n = 28). The prognosis was compared. Parameters for comparison were
rate of local recurrence, rate of metastatic evolution and duration of
survival. RESULTS: The operative length and mortality rate (group I: 0%,
group II: 3%), general (p = 0.37) and specific morbidity (p = 0.30),
frequency of delayed gastric emptying were similar in the 2 groups
(group I: 20%, group II: 35%, p = 0.88). The duration of naso-gastic
aspiration was shorter in the group I (6 days vs 8, p = 0.01). The
prognosis was the same in the 2 groups (metastasis: group I: 39%, group
II: 56%, p = 0.12, local recurrence: group I: 58%, group II: 43%, p =
0.09, mean survival: group I: 18 months, group II: 19 months, p = 0.77).
CONCLUSION: These results suggest that pylorus preserving
pancreatoduodenectomy could be performed for patients with
adenocarcinoma of the head of the pancreas and does not compromise
survival.
10
UI - 11893105
AU - Sheehan MK; Beck K; Creech S; Pickleman J; Aranha GV
TI -
Distal pancreatectomy: does the method of closure influence fistula
formation?
SO - Am Surg 2002 Mar;68(3):264-7; discussion 267-8
AD - Department of Surgery, Loyola University Medical Center, Maywood,
Illinois, USA.
The appropriate closure of the pancreatic remnant after distal
pancreatectomy is still debated. Suture techniques, stapled closure, and
pancreaticoenteric anastomosis all have their supporters. In this study
we have reviewed our data from distal pancreatectomy to determine
whether the type of remnant closure or underlying pathologic process had
any relation to postoperative fistula formation. We performed a
retrospective chart review of patients undergoing distal pancreatectomy
at our institution between 1993 and 2001. The charts were reviewed for
morbidity and mortality. These were then related to the type of closure
of the pancreatic stump. From 1993 to 2001 a total of 86 patients
underwent distal pancreatectomy. Data were available on 85 patients.
Indications for surgery were pancreatic tumor (69%), pancreatitis (14%),
trauma (7%), and extra pancreatic disease (9%). Pancreatic fistula
occurred in 14 per cent (N = 12), intra-abdominal abscess in 8 per cent
(N = 7), and wound infection in 2 per cent (N = 2). There was no
mortality in the series. The incidence of pancreatic fistula formation
was not related to method of closure of the pancreatic remnant nor to
the underlying pathologic process. Postoperative pancreatic fistulas
will close spontaneously even without total parenteral nutrition.
11
UI - 11893108
AU - Afsari A; Zhandoug Z; Young S; Ferguson L; Silapaswan S; Mittal V
TI -
Outcome analysis of pancreaticoduodenectomy at a community hospital.
SO - Am Surg 2002 Mar;68(3):281-4; discussion 284-5
AD - Department of Surgery, Providence Hospital, Southfield, Michigan 48075,
USA.
There is an ongoing debate about the proposed regionalization of
pancreaticoduodenectomies. The purpose of our study is to demonstrate
that good outcomes can be achieved in a well-managed low-volume
community hospital. We retrospectively analyzed pathologic findings,
morbidity, mortality, and one-year survival in 32 patients who underwent
pancreaticoduodenectomy at Providence Hospital over a 10-year period and
compared these results with data collected at Johns Hopkins, and the
Mayo Clinic. The patients had a mean age of 68.5 +/- 2.96 years; 56.3
per cent were female and 71.9 per cent were white. Overall in our series
90.6 per cent of specimens were found to be malignant, which is
statistically higher than the 68 per cent at Johns Hopkins (P = 0.013)
and not significantly different from Mayo Clinic (76%). The 30-day
mortality rate at Providence Hospital was 3.1 per cent, which is not
statistically different from Johns Hopkins (1.3%) and Mayo Clinic
(3.6%). One-year survival rate at Providence Hospital was 59.4 per cent,
which is significantly different from 79 per cent at Johns Hopkins (P =
0.016). The one-year survival rate at Providence Hospital is higher than
an approximately 50 per cent average reported nationally. The
postoperative complication rate was 62.5 per cent; the most common
complication was delayed early gastric emptying (28.1%). A statistical
difference in morbidity exists between Providence Hospital and Johns
Hopkins (P = 0.027) but not between Providence Hospital and Mayo Clinic
(46%). The higher rate of malignant disease treated in the population at
Providence Hospital may contribute to a higher complication rate and
lower one-year survival rate than the reported rates at Johns Hopkins
because of the poorer health of cancer patients. However, statistical
analysis of mortality rates for pancreaticoduodenectomy at Providence
Hospital show no difference from mortality rates at Johns Hopkins and
Mayo Clinic. Therefore in low-volume community hospitals
pancreaticoduodenectomy can be performed safely as evidenced by a
comparable low mortality rate and a high one-year survival rate.
12
UI - 11727085
AU - Menack MJ; Spitz JD; Arregui ME
TI -
Staging of pancreatic and ampullary cancers for resectability using
laparoscopy with laparoscopic ultrasound.
SO - Surg Endosc 2001 Oct;15(10):1129-34
AD - Division of Surgery, New York United Hospital Medical Center, 406 Boston
Post Road, Port Chester, NY 10573, USA.
BACKGROUND: Cancers of the pancreas and periampullary region are rarely
curable. We set out to determine the efficacy of laparoscopy with
laparoscopic ultrasound in the staging of pancreatic and ampullary
(LS) of tumors already deemed resectable by standard radiologic criteria
in 27 patients using laparoscopy with laparoscopic ultrasound (LUS).
Patients found to be resectable by LS evaluation underwent laparotomy
(LA). We then compared the results of the LS and LA findings. RESULTS:
Of the 27 patients evaluated, 17 were men and 10 were women. Their mean
age was 66 years. Preoperative computerized tomography (CT) scans were
done in all 27 patients (100%), and transabdominal and endoscopic
ultrasound (EUS) was done in 21 (78%). By LS, seven patients (26%) were
found to have unresectable disease. Two patients with mesenteric tumor
infiltration (one with peritoneal implants, and one with a visible liver
metastasis) were judged to be unresectable by laparoscopy alone. LUS
revealed that one patient had portal vein (PV) occlusion and two had
metastases to the lymph nodes or liver that were not revealed by
preoperative studies or laparoscopy alone. Among 20 patients (74%)
deemed resectable by LS, two (10%) were found to be unresectable at LA,
one due to PV involvement and the other due to local tumor extension
with superior mesenteric lymph node metastasis. Eighteen of those in
whom resection was attempted (90%) were resectable, with no unexpected
findings of distant lymph node or hepatic metastasis. Pathology
examination showed that eight had regional metastases (44%). The
sensitivity of LS in determining unresectability was 77% (seven true
positives and two false negatives). The negative predictive value
(reflecting resectability) was 90%. Laparoscopy alone had a sensitivity
of 44%, with a negative predictive value of 78%. The sensitivity and
positive predictive value of LS was 100%, reflecting no false positive
examinations. CONCLUSIONS: LS can effectively stage most patients and
reliably predict which of them will benefit from LA. Intervention for
unresectable patients can then be limited to laparoscopic or endoscopic
bypass. The main limitation is that LS may underestimate PV and regional
lymph node involvement.
13
UI - 11854576
AU - Rabitti PG; Germano D
TI -
Pancreatic head mass: how can we treat it? Tumor: conservative
treatment.
SO - JOP 2000 Sep;1(3 Suppl):162-70
AD - 11th Division, Internal Medicine Department and Oncology Unit,
Cardarelli Hospital, Napoli, Italy. pgrabitti@katamail.com
14
UI - 11854577
AU - Tihanyi TF; Pulay I; Winternitz T; Flautner L
TI -
Pancreatic head mass: how can we treat it? Tumor: surgical treatment.
SO - JOP 2000 Sep;1(3 Suppl):171-7
AD - 1(st) Department of Surgery, Faculty of Medicine, Semmelweis University,
Budapest, Hungary. tt@seb1.sote.hu
Pancreatic carcinoma is a devastating disease. Untreated 5-year survival
is 0%. The only possibility of being cured is given by surgical removal
of the tumor. Pancreatoduodenectomy previously involved high morbidity
and mortality rates until it was postulated that palliation gave better
results. Today, morbidity and mortality rates have been decreased to an
acceptable level, mortality rates in specialized centers being under 5%.
Prognostic factors determining survival were found to be the size of the
tumor, grade, lymph node involvement and stage. In order to be able to
compare results of the different centers, standardization of the
surgical technique is mandatory. It is unanimously accepted that in
order to improve survival in pancreatic carcinoma, the radicality of the
surgical procedure should be increased to include lymphadenectomy.
Postoperative adjuvant therapy could also be a determinant factor.
Prospective randomized clinical trials will give an answer to these
still unanswered questions.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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