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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Pancreatic Cancer - February 2002
National Cancer Institute®
Last Modified: February 1, 2002
Table of Contents
1
UI - 11558628
AU - Harris J; Bruckner H
TI -
Adjuvant and neoadjuvant therapies of pancreatic cancer: a review.
SO - Int J Pancreatol 2001;29(1):1-7
AD - Department of Internal Medicine, Rush Medical College, Chicago, IL
60612, USA.
The survival of patients diagnosed with pancreatic cancer is dismal. Few
patients on initial presentation are suitable for surgical resection.
This has prompted clinical studies with chemotherapy and/or radiotherapy
designed either to increase the number of patients eligible for surgery
(neoadjuvant therapy) or to prolong the survival of patients who had
undergone surgery (adjuvant therapy). None of these studies may at this
time be considered definitive. Wherever possible, patients felt eligible
for neoadjuvant or adjuvant therapy should be entered on clinical
trials. Where this is not possible, clinicians should exercise their
best judgment in offering this type of treatment to pancreatic cancer
patients under their care.
2
UI - 11560155
AU - Crane CH; Janjan NA; Evans DB; Wolff RA; Ballo MT; Milas L; Mason K;
TI -
Charnsangavej C; Pisters PW; Lee JE; Lenzi R; Vauthey JN; Wong A; Phan
T; Nguyen Q; Abbruzzese JL
Toxicity and efficacy of concurrent gemcitabine and radiotherapy for
locally advanced pancreatic cancer.
SO - Int J Pancreatol 2001;29(1):9-18
AD - Pancreatic Tumor Study Group, The University of Texas M.D. Anderson
Cancer Center, Houston 77030, USA. ccrane@mdanderson.org
BACKGROUND: Gemcitabine and radiotherapy are a potent combination. A
clinical assessment of the therapeutic ratio for locally advanced
pancreatic cancer patients has not yet been reported. AIM OF STUDY: To
assess the toxicity, survival, and pattern of failure of locally
advanced pancreatic cancer patients treated with concurrent
gemcitabine-based chemoradiation. Patients and Methods. Between the
unresectable adenocarcinoma of the pancreas were treated with concurrent
gemcitabine and radiotherapy at MDACC. Patients received 250-500 mg/m2
of gemcitabine weekly x7 over 30 min and 30-33 Gy in 10-11 fractions
over two weeks to the primary tumor and regional lymphatics. Severe
toxicity was defined as admission > 5 d, mucosal ulceration, > 3 dose
deletions of gemcitabine or toxicity resulting in surgical intervention
or that resulted in death. RESULTS: The median survival was 11 mo.
Overall, 37 of 51 patients had objective evidence of local progression.
The actuarial rate of local progression rate at 9 mo was 70%. The 9-mo
distant metastasis rate was 52%. Tumors > or = 10 cm2 had worse local
control, distant control, and overall survival. Six patients underwent
pancreaticoduodenectomy after therapy. After review of the imaging, only
four of these patients had minimal arterial involvement, one was
incorrectly staged, and one had initial inflammatory change on CT that
resolved. Twelve of 51 (24%) patients suffered severe acute toxicity,
and 17 of 51 (33%) patients were admitted for supportive care.
CONCLUSION: Concurrent gemcitabine and radiotherapy can be a very
difficult combination to administer safely. Our results do not suggest a
prolongation of median survival for patients with localized pancreatic
cancer treated with this therapy. It is possible that gemcitabine-based
chemoradiation contributes to the margin-negative resectability of a
small number of patients with minimal arterial involvement, but this
benefit is obscured by the frequent toxicity encountered in most
patients. Locally advanced pancreatic cancer patients should continue to
be enrolled on prospective studies investigating novel combinations of
cytotoxic and/or biologic agents with concurrent radiotherapy.
3
UI - 11815964
AU - Ryan DP; Kulke MH; Fuchs CS; Grossbard ML; Grossman SR; Morgan JA; Earle
TI -
CC; Shivdasani R; Kim H; Mayer RJ; Clark JW
A Phase II study of gemcitabine and docetaxel in patients with
metastatic pancreatic carcinoma.
SO - Cancer 2002 Jan 1;94(1):97-103
AD - Gastrointestinal Cancer Center, Dana-Farber/Partners Cancer Care,
Boston, Massachusetts, USA. dpryan@partners.org
BACKGROUND: Patients with metastatic pancreatic carcinoma have a poor
survival. Chemotherapy with gemcitabine is the standard first-line
treatment. In a Phase II trial at one academic cancer center, the
clinical safety and activity of combining gemcitabine and docetaxel were
assessed. METHODS: Patients with previously untreated, advanced
pancreatic carcinoma were eligible. Bidimensionally measurable disease
or evaluable disease with an elevated tumor marker, good performance
status, and adequate organ function were required. Patients received
docetaxel 60 mg/m(2) on Day 1 and gemcitabine 600 mg/m(2) on Days 1, 8,
and 15 every 28 days. Ciprofloxacin was administered on Days 8-18. Dose
attenuations were made as indicated for toxicity. Patients were restaged
radiographically after every two cycles. RESULTS: Thirty-four patients
were enrolled, and 33 patients were evaluable for response. There were
23 men and 10 women among the evaluable patients. The median age was 63
years, and all patients had an Eastern Cooperative Oncology Group
performance status of 0 or 1. Three patients had received prior
chemoradiation for postresection adjuvant therapy. One hundred forty-six
cycles of chemotherapy were administered, and 5 cycles (3%) in 4
patients (12%) were complicated by febrile neutropenia. Twenty percent
and 11% of patients on Day 8 and Day 15 doses of gemcitabine,
respectively, were omitted for toxicity. The objective response rate was
18%, and the median survival was 8.9 months (95% confidence interval,
5.2-11.2 months). The 1-year survival rate was 29%. CONCLUSIONS: The
combination of gemcitabine and docetaxel in patients with advanced
pancreatic carcinoma is well tolerated and is associated with moderate
activity despite aggressive dose reduction. Whether combination regimens
are more effective than single agents in the treatment of patients with
pancreatic carcinoma awaits evaluation in randomized studies. Copyright
2002 American Cancer Society.
4
UI - 10615932
AU - Klinkenbijl JH; Jeekel J; Sahmoud T; van Pel R; Couvreur ML; Veenhof CH;
TI -
Arnaud JP; Gonzalez DG; de Wit LT; Hennipman A; Wils J
Adjuvant radiotherapy and 5-fluorouracil after curative resection of
cancer of the pancreas and periampullary region: phase III trial of the
EORTC gastrointestinal tract cancer cooperative group.
SO - Ann Surg 1999 Dec;230(6):776-82; discussion 782-4
AD - Department of Surgery, University Hospital Rotterdam-Dijkzigt, The
Netherlands.
OBJECTIVE: The survival benefit of adjuvant radiotherapy and
5-fluorouracil versus observation alone after surgery was investigated
in patients with pancreatic head and periampullary cancers. SUMMARY
BACKGROUND DATA: A previous study of adjuvant radiotherapy and
chemotherapy in these cancers by the Gastrointestinal Tract Cancer
Cooperative Group of EORTC has been followed by other studies with
conflicting results. METHODS: Eligible patients with T1-2N0-1aM0
pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically
proven adenocarcinoma were randomized after resection. RESULTS: Between
1987 and 1995, 218 patients were randomized (108 patients in the
observation group, 110 patients in the treatment group). Eleven patients
were ineligible (five in the observation group and six in the treatment
group). Baseline characteristics were comparable between the two groups.
One hundred fourteen patients (55%) had pancreatic cancer (54 in the
observation group and 60 in the treatment group). In the treatment arm,
21 patients (20%) received no treatment because of postoperative
complications or patient refusal. In the treatment group, only minor
toxicity was observed. The median duration of survival was 19.0 months
for the observation group and 24.5 months in the treatment group
(log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %,
respectively. The results when stratifying for tumor location showed a
2-year survival rate of 26% in the observation group and 34% in the
treatment group (log-rank, p = 0.099) in pancreatic head cancer; in
periampullary cancer, the 2-year survival rate was 63% in the
observation group and 67% in the treatment group (log-rank, p = 0.737).
No reduction of locoregional recurrence rates was apparent in the
groups. CONCLUSIONS: Adjuvant radiotherapy in combination with
5-fluorouracil is safe and well tolerated. However, the benefit in this
study was small; routine use of adjuvant chemoradiotherapy is not
warranted as standard treatment in cancer of the head of the pancreas or
periampullary region.
5
UI - 11066156
AU - Hoffman JP
TI -
Adjuvant radiotherapy and 5-fluorouracil after curative resection of
cancer of the pancreas and periampullary region.
SO - Ann Surg 2000 Nov;232(5):726-7
6
UI - 11066157
AU - Evans DB; Wolff RA; Hess KR
TI -
Adjuvant radiotherapy and 5-fluorouracil after curative resection of
cancer of the pancreas and periampullary region.
SO - Ann Surg 2000 Nov;232(5):727
7
UI - 11677990
AU - Gazzaniga GM; Cappato S; Papadia F; Mori L; Filauro M
TI -
D1 versus D2 pancreatoduodenectomy in surgical therapy of pancreatic
head cancer.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1471-8
AD - First Department of General Surgery, HPB Unit Galliera Hospital, Via
Volta, 8, 161-28 Genova. gazzaniga@galliera.it
BACKGROUND/AIMS: The aim of this study was to evaluate the influence of
standard pancreatoduodenectomy versus pancreatoduodenectomy with
extended lymphadenectomy and the role of adjuvant therapy on survival in
patients with ductal adenocarcinoma of the pancreatic head. In addition
the problems related to resection are discussed. METHODOLOGY: A total
number of 124 pts operated on between 1985 and 1999 were divided into
three groups according to our different strategies. Standard resection
(D1) was performed on 48 patients (group A), extended resection (D2) on
45 patients (group B) and combined treatment (extended resection plus
adjuvant therapy) on 31 patients. The outcome of these three groups was
compared with regard to postoperative morbidity and survival. RESULTS:
There was no significant difference in terms of survival between group A
and B, while adjuvant therapy (group C), achieved statistical
significance as factor influencing survival, together with tumor stage.
CONCLUSIONS: Our data suggest that no further improvement can be
obtained on long-term survival by extended retroperitoneal dissection
while chemoradiotherapy showed a doubling of median survival.
8
UI - 11677991
AU - Yamaguchi K; Kishinaka M; Nagai E; Nakano K; Ohtsuka T; Chijiwa K;
TI -
Tanaka M
Pancreatoduodenectomy for pancreatic head carcinoma with or without
pylorus preservation.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1479-85
AD - Department of Surgery and Oncology, Graduate School of Medical Sciences,
Kyushu University, Fukuoka 812-82, Japan.
yamaguchi@surg1.med.kyushu-u.ac.jp
BACKGROUND/AIMS: With the concept of less invasive surgery, PpPD
(pylorus-preserving pancreatoduodenectomy) has taken the place of
conventional Whipple pancreatoduodenectomy (Whipple) as a standard
operation for pancreatic head carcinoma. The aim of this paper is to
compare early and late postoperative results of PpPD and Whipple for
pancreatic head carcinoma. METHODOLOGY: Postoperative clinical follow-up
data and outcome of 50 Japanese patients with pancreatic head carcinoma
who underwent pancreatoduodenectomy with or without pylorus preservation
were reviewed to scrutinize the demerits and merits of the pylorus
preservation. RESULTS: Preoperative and postoperative serum chemistry
was not different between the two groups. Mean operation time of the
Whipple group was 517 minutes, which was significantly shorter than 624
minutes of the PpPD group (P = 0.0006). Cumulative stage was not
different between the two groups. Cumulative curability of the PpPD
group was superior to the Whipple group; of the 27 patients with
Whipple, A in 4, B in 5 and C in 18, while of the 23 patients with PpPD,
A in 12, B in 2 and C in 9 (P = 0.0182). Gastric tube was removed on POD
6.0 in the Whipple group, while on POD 39 in the PpPD group (P <
0.0001). Oral intake was started on POD 14.0 in the Whipple group, while
on POD 28.3 in the PpPD group (P = 0.0018). Discharge was on POD 57.8 in
the Whipple group, while POD 86.9 in the PpPD group (P = 0.0023). At the
time of discharge and postoperative 6, 12, and 18 months, body weight
loss from the preoperative level was 1kg smaller in the PpPD group than
in the Whipple group. 1-year and 3-year survival rates of the Whipple
group was 53.8% and 15.8%, while 62.8% and 19.6% of the PpPD group,
showing no significant difference. CONCLUSIONS: These data show that
delayed gastric emptying is evident in the PpPD group, resulting in
longer hospital stay, while long-term body weight loss is smaller in
this group. The clinical outcome is similar between the two groups. PpPD
can be accepted as a standard operation for pancreatic head carcinoma.
9
UI - 11677992
AU - Machado MC; Penteado S; Cunha JE; Jukemura J; Herman P; Bacchella T;
TI -
Machado MA; Montagnini AL
Pancreatic head tumors with portal vein involvement: an alternative
surgical approach.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1486-7
AD - Department of Gastroenterology, University of Sao Paulo Medical School,
Brazil.
BACKGROUND/AIMS: One of the determining factors for the unresectability
of pancreatic head tumors is the involvement of the portal venous
system. Recent reports show that the resection of tumors with portal
vein involvement has similar results to lesions with same stage without
portal vein invasion. The aim of this study is to present a technique
that allows the resection of portal vein segments without the use of
grafts and with a shorter period of intraoperative venous occlusion.
METHODOLOGY: Fifteen patients with pancreatic head tumors and portal
vein involvement were submitted to pancreaticoduodenectomy according to
this technique. The main feature of the technique is starting the
pancreatic dissection at the posterior aspect of the head of the
pancreas. The superior mesenteric artery is completely dissected from
the pancreatic tissues leaving the section of the pancreas and the
resection of the portal vein to the last step. RESULTS: Portal vein flow
occlusion did not exceed 10 minutes. There were no major postoperative
complications or mortality. CONCLUSIONS: This maneuver allows an easier
resection of the mobilized portal vein with a shorter period of venous
clamping and reconstruction without the need of venous graft.
10
UI - 11572580
AU - Martinelli B; Pigni A; Fagnoni E; Chini C; Vallini I; Pinotti G
TI -
Personal experience in advanced pancreatic cancer: retrospective
analysis on the use of 5-fluorouracil or gemcitabine.
SO - Dig Liver Dis 2001 Aug-Sep;33(6):503
11
UI - 11787374
AU - Barthet M
TI -
[Palliative endoscopic treatment of pancreatic carcinoma]
SO - Gastroenterol Clin Biol 2001 Sep;25 Spec No 2():C15-8
AD - Service de Gastroenterologie, Hopital Nord, Chemin des Bourrely, 13915
Marseille. mbarthet@mail.ap-hm.fr
12
UI - 11787375
AU - Levy P
TI -
[Resectability of pancreatic head adenocarcinoma]
SO - Gastroenterol Clin Biol 2001 Sep;25 Spec No 2():C19-23
AD - Federation medico-chirurgicale d'hepatogastroenterologie, Hopital
Beaujon, 92118 Clichy. philippe.levy@bjn.ap-hop-paris.fr
13
UI - 11787383
AU - Borie F; Rodier JG; Guillon F; Millat B
TI -
[Palliative surgery of pancreatic adenocarcinoma]
SO - Gastroenterol Clin Biol 2001 Sep;25 Spec No 2():C7-14
AD - Service de Chirurgie Digestive, Hopital St Eloi, 34295 Montpellier.
14
UI - 11740694
AU - Bunk A; Pistorius S; Konopke R; Ockert D; Kuhlisch E; Saeger HD
TI -
[The value of colour duplex sonography in the assessment of surgical
resectability of pancreatic tumors]
SO - Ultraschall Med 2001 Dec;22(6):265-73
AD - Klinik und Poliklinik fur Viszeral-, Thorax- und Gefasschirurgie,
Universitatsklinikum Carl Gustav Carus an der TU Dresden, Germany.
The Value of Colour Duplex Sonography in the Assessment of Surgical
Resectability of Pancreatic Tumors. AIM: The aim of this study was to
evaluate the assessment by modern colour duplex imaging (CDI) concerning
the relation between tumour and vessels including haemodynamic
parameters in the main abdominal arteries and the portal system, and to
evaluate the influence of these results on surgical decision making.
the pancreas were included in a prospective study. Tumour contact to
vessels and to the retroperitoneum, data on the flow in the main
abdominal arteries and the portal circulation (regional topography) as
well as the detection of liver metastases, enlarged lymph nodes and
peritoneal carcinomatosis were defined as representing criteria of
resectability. The results were compared with the intraoperative
situation and with the definite histological findings. RESULTS: In 57
resectable tumours, the portal system was found to be infiltrated by the
tumour up to a length of 1.5 cm. The flow velocity reached between 4 and
53 cm/s (mean flow) and 9 to 105 cm/s (maximum flow). Out of 146
pancreatic tumours, 89 were found as being non-resectable. In these
cases, the measured parameters differed depending on the degree of
tumour infiltration in to the portal circulation. We measured values
from 0 to 96 cm/s (mean flow) and from 0 to 201 cm/s (maximum flow) with
loss of breath-dependent modulation. The contact area between tumor and
portal vessel was longer than 2 cm. Pathological flow in the main
abdominal arteries was only found in 2 of 13 cases. The local situation
was assessed correctly in 140 out of 146 cases by CDI (sensitivity of
93.0 %, specificity of 97.8 %, positive predictive value of 96.4 %,
negative predictive value of 95.6 %). Regarding the complete oncological
status (local situation, metastases, lymph node involvement and
peritoneal carcinomatosis), a sensitivity of 82.5 % and a specificity of
92.1 % (positive predictive value of 87.0 %, negative predictive value
of 89.1 %) was found. CONCLUSION: Modern CDI can reliably assess the
resectability of pancreatic tumours by the evaluation of morphological
and haemodynamic parameters. There are still difficulties in the
assessment of lymph node involvement as well as in the detection of
small liver metastases and of peritoneal carcinomatosis without ascites.
15
UI - 11781662
AU - Wesseling JG; Yamamoto M; Adachi Y; Bosma PJ; van Wijland M; Blackwell
TI -
JL; Li H; Reynolds PN; Dmitriev I; Vickers SM; Huibregtse K; Curiel DT
Midkine and cyclooxygenase-2 promoters are promising for adenoviral
vector gene delivery of pancreatic carcinoma.
SO - Cancer Gene Ther 2001 Dec;8(12):990-6
AD - Department of Experimental Hepatology, Academic Medical Center,
University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Midkine (MK), a heparin binding growth factor, and cyclooxygenase-2
(COX-2), a key enzyme in the conversion of arachidonic acid to
prostaglandin, are both up-regulated at the mRNA or protein level in
many human malignant tumors. Here, we investigated the tumor specificity
of both MK and COX-2 promoters in human pancreatic cancer, with the aim
to improve the selectivity of therapeutic gene expression. We
constructed recombinant adenoviral (Ad) vectors containing either the
luciferase (Luc) reporter gene under the control of the COX-2 or MK
promoter or the herpes simplex virus thymidine kinase (HSV Tk) gene
under the control of the COX-2 promoter and compared the expression with
the cytomegalovirus (CMV) promoter. AdMKLuc achieved moderate to
relatively high activity upon infection to both primary and established
pancreatic carcinoma cells. Of the two COX-2 promoter regions (COX-2M
and COX-2L), both revealed a high activity in primary pancreatic
carcinoma cells, whereas in the established pancreatic carcinoma cell
lines, COX-2L has an approximately equal high activity compared to CMV.
In addition, both AdCOX-2M Tk and AdCOX-2L Tk induced marked cell death
in response to ganciclovir (GCV) in three of four established pancreatic
carcinoma cell lines. From these results, and because it has been
reported that AdMKTk and AdCOX-2L Tk in combination with GCV did not
reveal significant liver toxicity, we conclude that the MK as well as
the COX-2 promoters are promising tumor-specific promoters for Ad
vector-based gene therapy of pancreatic cancer.
16
UI - 9424859
AU - Zieniewicz K; Krawczyk M; Nyckowski P; Plaszczyk D
TI -
[Pancreatoduodenectomy in treatment of inflammatory tumors of the
pancreatic head]
SO - Wiad Lek 1997;50 Suppl 1 Pt 2():127-9
AD - Katedry i Kliniki Chirurgii Ogolnej i Chorob Watroby Akademii Medycznej
w Warszawie.
On the basis of their own experience the authors present indications and
results of pancreatoduodenectomy for chronic pancreatitis. In a group of
18 patients. With appropriate evaluation of patients, meticulous
surgical technique and postoperative care the complications aren't
life-threatening. The long-term results are fully satisfactory.
17
UI - 9383356
AU - Haarmann W; Busing M; Reith HB; Wysocki P; Kozuschek W
TI -
The oncological approach to pylorus preserving pancreatoduodenectomy
(PPPD) in pancreas malignancies.
SO - Wiad Lek 1997;50 Suppl 1 Pt 2():140-4
AD - Department of Surgery, Ruhr-University Bochum, Knappschafts-Krankenhaus,
FRG.
There has been a considerable debate about whether pylorus preservation
significantly detracts from the radicality in a palliative procedure
where a conventional Whipple operation would have been curative. We know
now, that the extending radicality of the Whipple operation does not
improve the long-term survival rates. Our results of 127 PPPD and 54
Whipple procedures in pancreas malignancies from 1985 to 1996 showed the
nutritional benefits of the PPPD group as compared to the standard
Whipple group. 84% (99/121) vs. 24% (13/50) were able to gain
postoperatively. The long-term survival rates of both groups and the
results in the literature are similar.
18
UI - 9424864
AU - Plaszczyk D; Zieniewicz K; Krawczyk M; Karwowski A
TI -
[Complications after pancreatoduodenectomy in material from clinics in
the years 1989-1996]
SO - Wiad Lek 1997;50 Suppl 1 Pt 2():150-3
AD - Katedry i Kliniki Chirurgii Ogolnej i chorob Watroby Akademii Medycznej
w Warszawie.
On the basis of 101 pancreatoduodenectomies the authors present early
postoperative complications. Cancer was surgical indication for
pancreatoduodenectomy in 87 patients and inflammatory tumor of
pancreatic head in 14 patients. Complications occurred in 37 cases. The
most frequent complications were pancreatic fistula and disturbances of
stomach emptying, in most cases treated conservatively. Mortality rate
was 6.9%.
19
UI - 9424865
AU - Knast W; Wierzbicki J; Markocka-Maczka K; Lewandowski A; Wozniak S;
TI -
Geneja M
[Intraoperative portography in operations for resection of pancreas
neoplasms]
SO - Wiad Lek 1997;50 Suppl 1 Pt 2():154-7
AD - Katedry i Kliniki Chirurgii Przewodu Pokarmowego Akademii Medycznej we
Wroclawiu.
Since 1993 during pancreatic resection routine intraoperative
portography has been employed. Thus we are able to establish
infiltration engaging portal vein and its branches. Facilitating
decision making about resectability of the tumor. 29 portographies were
performed. In eight cases malignant infiltration on portal vein was
established. Because of that in seven cases no radical resection was
undertaken.
20
UI - 9424867
AU - Bednarz W; Szydlowski Z; Wojczys R; Woldan J; Forkasiewicz Z; Kornafel P
TI -
[Pancreatoduodenectomy by Whipple's method--a method of dealing with the
pancreatic stump]
SO - Wiad Lek 1997;50 Suppl 1 Pt 2():162-5
AD - I Katedry i Kliniki Chirurgii Akademii Medycznej we Wroclawiu.
Different methods of pancreatic stump management are possible to perform
after pancreaticoduodenectomy. The group of 24 patients after
pancreaticoduodenectomy with pancreaticojejunostomy,
pancreaticogastrostomy and occlusion of the pancreatic duct by Neopren
or Ethiblock were analysed. According to the literature and own results
pancreatogastrostomy or occlusion of the pancreatic duct seems to be the
safer procedure, but sometimes the choice is made intraoperatively.
21
UI - 11704461
AU - Hsiung-Stripp DC; McDonough J; Masters HM; Levin WP; Hahn SM; Jones HA;
TI -
Metz JM
Comparative treatment planning between proton and X-ray therapy in
pancreatic cancer.
SO - Med Dosim 2001 Fall;26(3):255-9
AD - Department of Radiation Oncology, University of Pennsylvania,
Philadelphia 19104, USA. stripp@xrt.upenn.edu
With the utilization of new biologic agents and experimental
chemotherapy in the treatment of pancreatic cancer, the issue of
local-regional control will become increasingly important. This study
was undertaken to determine the feasibility of dose escalation using
proton therapy, as compared to conventional 3-dimensional conformal
radiation, by minimizing the dose to normal tissues. The photon
treatment plans of 4 patients with unresectable pancreatic cancer
treated on a biologic therapy trial were utilized. Each patient was
treated using a 3- or 4-field photon plan with 45 Gy to the clinical
target volume (CTV), followed by a boost of 14.4 Gy to the gross target
volume (GTV). Using a Helax treatment planning system, proton plans were
generated to encompass the same CTV and GTV to the same prescribed dose.
Dose-volume histograms (DVHs) were generated for the GTV, CTV, spinal
cord, liver, and right and left kidneys. Each DVH was compared between
the photon and proton plans. Proton plans utilized either a 2- or
3-field technique. Available energies included 130 or 180 MeV. Range
modulators and bolus were used as needed to conform to the target
volume. With the CTV and GTV receiving the same dose from the proton and
photon plans, all individual proton plans were superior to the photon
plans in reduction of normal tissue dose. For the 4 patients, the
average dose reduction to 50% of the organ at risk was 78% to spinal
cord (p = 0.003), 73% to left kidney (p = 0.025), 43% to right kidney (p
= 0.059), and 55% to liver (p = 0.061). These comparative treatment
plans show proton therapy results in significant reductions of dose to
normal tissue compared to conventional photons while treating the same
target volumes. This allows for the design of dose-escalation protocols
using protons in combination with new biologic therapies and
chemotherapy.
22
UI - 11833306
AU - de Claviere G; Paye F; Fteriche S; Terris B; Belghiti J; Sauvanet A
TI -
[Medial pancreatectomy: results of a series of 11 patients]
SO - Ann Chir 2002 Jan;127(1):48-54
AD - Service de chirurgie digestive, hopital Beaujon, 100, boulevard du
General-Leclerc, 92110 Clichy, France.
AIM OF THE STUDY: To report a new series of medial pancreatectomy (MP),
with analysis of early and long-term results. PATIENTS AND METHODS: From
1990 to 1999, 11 patients (mean age = 53 years, extremes:
28-70)--including 10 non-diabetic--underwent MP for neuroendocrine tumor
(n = 5), intraductal papillary mucinous tumor (IPMT) (n = 3), serous
cystadenoma, metastasis from renal cell carcinoma, and focal
pancreatitis. The procedure included medial resection of variable
extent, frozen section, and suture of the cephalic stump. The caudal
stump was either anastomosed to the posterior gastric wall (n = 9), or
closed when atrophic or very small (n = 2). RESULTS: The mean length of
resection was 7 cm (extremes: 4-15). The diagnosis suspected
preoperatively was confirmed in 10 cases. In one patient, a suspected
adenocarcinoma was actually a focal pancreatitis. No postoperative death
occurred. Seven patients experienced complications: one delayed gastric
emptying and 6 pancreatic fistulas (54%), including 3 associated with
intraabdominal collection. Two patients were reoperated to drain a
pancreatic fistula. The mean hospital stay was 14 days (extremes: 10-21)
without complications, and 30 days (extremes: 11-90) after
complications. After a mean follow-up of 45 months (extremes: 7-130),
only one patient initially non-diabetic experienced post-operative
diabetes and needs enzyme therapy after a 15 cm-resection for IPMT. No
patient developed isolated intrapancreatic recurrence. CONCLUSIONS: MP
preserves efficiently pancreatic function and is associated with a low
risk of intrapancreatic recurrence. Conversely, MP is associated with an
high risk of pancreatic fistula.
23
UI - 11583197
AU - Ramanathan RK; Cnaan A; Hahn RG; Carbone PP; Haller DG
TI -
Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell
carcinoma. Study of the Eastern Cooperative Oncology Group-E6282.
SO - Ann Oncol 2001 Aug;12(8):1139-43
AD - University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
ramanathanrk@msx.upmc.edu
BACKGROUND: A phase II study of dacarbazine (DTIC), was conducted to
determine the response rate, duration of response, toxicity and overall
survival of patients with advanced pancreatic islet cell tumors.
PATIENTS AND METHODS: Fifty patients with advanced pancreatic islet cell
tumors, having progressive symptoms or evidence of rapidly advancing
disease were entered on this study. DTIC was given by IV infusion at a
dose of 850 mg/m2, over 60-90 minutes, repeated every four weeks.
RESULTS: The response rate was 33% in 42 patients who had measurable
tumor, and 34% in the 50 patients (90% confidence interval (90% CI):
23%-47%). The majority of the responses were seen in patients without
prior chemotherapy. Median overall survival was 19.3 months. There were
two lethal toxicities on the study, one septic shock and one myocardial
infarction. Grade 4 toxicities were, hematological (5 patients), sepsis,
neurological (depression and paranoid behavior) and bleeding (1 patient
each). The most common toxicity was vomiting, grade 3 in 13% of
patients. CONCLUSIONS: DTIC has activity in advanced previously
untreated pancreatic islet cell tumors.
24
UI - 11702956
AU - Berlin JD; Rothenberg M
TI -
Chemotherapy for resectable and advanced pancreatic cancer.
SO - Oncology (Huntingt) 2001 Oct;15(10):1241-9, 1254; discussion 1254-64
AD - Division of Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt
University, Nashville, Tennessee, USA.
jordan.berlin@mcmail.vanderbilt.edu
This article will review the pertinent data on the use of chemotherapy
for all stages of pancreatic cancer. For patients with metastatic
disease, fluorouracil (5-FU) was the standard of care for several
decades until a single randomized trial established that gemcitabine
(Gemzar) produced a greater clinical benefit response, median survival,
and 1-year survival. Among the currently available chemotherapy agents,
the taxanes, fluoropyrimidines, and camptothecins are being evaluated in
clinical trials alone or in combination with gemcitabine. Newer agents
that are not classically cytotoxic are also under investigation and hold
promise for the future. In patients with locally advanced unresectable
disease, chemotherapy is commonly used to sensitize the cancer to
radiation. Current investigations focus on trying to improve
chemotherapy as a radiation sensitizer, using, for example, infusional
5-FU and gemcitabine. Early-stage, surgically resectable patients may
benefit from the combination of chemotherapy and radiation, although
more recent trials conducted in Europe raise some doubt. However, flaws
in trial design do not allow firm conclusions to be drawn about the
benefits of adjuvant therapy. Both chemotherapy and chemoradiation are
under further investigation. Significant improvements in the survival of
patients with pancreatic cancer will be achieved as more effective
systemic therapies are developed, including agents with novel cellular
targets.
25
UI - 11721113
AU - Srivastava S; Sikora SS; Kumar A; Saxena R; Kapoor VK
TI -
Outcome following pancreaticoduodenectomy in patients undergoing
preoperative biliary drainage.
SO - Dig Surg 2001;18(5):381-7
AD - Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate
Institute of Medical Sciences, Lucknow, India.
OBJECTIVE: To assess the role of preoperative biliary drainage (PBD) in
the early outcome following pancreaticoduodenectomy (PD) for
periampullary tumors. DESIGN: Retrospective analysis of prospective
database. PATIENTS AND METHODS: 121 PDs were performed for periampullary
tumors between 1989 and 1998. 54 patients were operated following a PBD
(group A) while 67 patients were operated without PBD. 50 patients
underwent internal biliary drainage while 4 patients underwent external
biliary drainage. Of the 67 patients without PBD, serum bilirubin was
>10 mg% in 41 patients (group B) while 26 patients had bilirubin level
of <10 mg% (group C). RESULT: Patients were well matched for age, sex
distribution, presence of medical risk factors, duration of surgery,
operative blood loss and stage of disease. Group A patients had a higher
incidence of wound infection (43 vs. 24%; p = 0.03), intra-abdominal
abscess (28 vs. 15%; p = 0.06), pancreaticojejunal anastomotic leak (20
vs. 5%; p = 0.01) and overall infective complications (52 vs. 29%; p =
0.01) compared to group B patients, and a higher overall infective
complication rate than group C patients (52 vs. 27%; p = 0.02). Group B
patients had a higher incidence of intra-abdominal bleeding compared to
group A (20 vs. 6%; p = 0.01) and group C patients (20 vs. 4%; p =
0.03). Reoperation rate was significantly higher in group B compared to
group A patients (27 vs. 13%; p = 0.04). The mortality rates were not
significantly different in the three groups. CONCLUSION: Patients with
jaundice (>10 mg%) have a higher risk of bleeding complications while
those with PBD have more infective complications. PBD should be
judicially employed in selected patients. Copyright 2001 S. Karger AG,
Basel
26
UI - 11747327
AU - Evans JD; Stark A; Johnson CD; Daniel F; Carmichael J; Buckels J; Imrie
TI -
CW; Brown P; Neoptolemos JP
A phase II trial of marimastat in advanced pancreatic cancer.
SO - Br J Cancer 2001 Dec 14;85(12):1865-70
AD - Department of Surgery, Queen Elizabeth Hospital, Birmingham, UK.
Pancreatic cancer has a poor response to conventional chemotherapy and
radiotherapy. Inhibition of matrix metalloproteinase activity involved
in tumour invasion and metastases is a novel biological approach for
cancer treatment. This multicentre phase II clinical trial assessed
marimastat, an oral matrix metalloproteinase inhibitor, in patients with
advanced pancreatic cancer. A total of 113 patients received marimastat
for 28 days at 100 mg b.d. (n = 9), 25 mg o.d. (n = 90) or 10 mg b.d. (n
= 14). Patients with a response to treatment could continue marimastat
beyond 28 days. Of 113 patients, 90 (80%) completed the 28-day study and
83 (73%) continued treatment. The principal side effect was arthralgia
in 14 (12%) patients at 28 days and 33 (29%) patients over the whole
study. There were 31 patients (27%) who required dose modification. Of
76 patients with evaluable CA19-9 levels, 23 (30%) showed no increase or
fall in CA19-9. Of 83 patients with radiologically assessable disease,
41 (49%) had stable disease. The median survival was 245 days for those
with a stable or falling CA19-9 level 128 days in those with rising
CA19-9. The overall survival was 3.8 months. 5.9 months for stage II,
4.7 months for stage III and 3 months for stage IV disease. Of 90
patients, 46 (51%) had stabilization or reduction in pain, mobility and
analgesia scores. Further development and clinical evaluation of matrix
metalloproteinase inhibitors for the treatment of pancreatic cancer is
warranted.
27
UI - 11748467
AU - Yamada T; Okajima F; Akbar M; Tomura H; Narita T; Yamada T; Ohwada S;
TI -
Morishita Y; Kondo Y
Cell cycle arrest and the induction of apoptosis in pancreatic cancer
cells exposed to adenosine triphosphate in vitro.
SO - Oncol Rep 2002 Jan-Feb;9(1):113-7
AD - Second Department of Surgery, Gunma University, Showamachi, Gunma
371-8511, Japan. yamadat@showa.gunma-u.ac.jp
Adenosine triphosphate (ATP) has been shown to be an inhibitory or a
stimulatory agent for cell growth in various types of cells. Here, we
studied the effects of extracellular ATP on two pancreatic cancer cell
lines, PK-1 and YAPC established by us. In both cell lines, ATP
inhibited cell growth in a time- and dose-dependent manner, whereas the
same doses of ATP stimulated DNA synthesis. Flow cytometric analysis of
the cells incubated with or without ATP demonstrated the ATP-induced
striking increase in cells at S-phase. The same analysis showed also the
increase in sub-G0/G1 population in the same analysis and the
electrophoretic pattern of DNA showed the occurrence of ATP-induced cell
disintegration likely to be apoptosis. We suggest that extracellular ATP
is cytotoxic for pancreatic cancer cells because of its induction of
cell cycle arrest at S-phase and cell death, possibly apoptosis,
overcoming the promotion of the entry into S-phase.
28
UI - 11775730
AU - Yilmaz S; Kirimlioglu V; Katz DA; Kayaalp C; Caglikulekci M; Ara C
TI -
Randomised clinical trial of two bypass operations for unresectable
cancer of the pancreatic head.
SO - Eur J Surg 2001 Oct;167(10):770-6
AD - Inonu University Medical School, General Surgery Department, Malatya,
Turkey. syilmaz@inonu.edu.tr
OBJECTIVE: To compare two different types of prophylactic gastric bypass
in patients with cancer of the pancreatic head who were not suitable for
curative resection. DESIGN: Prospective study. SETTING: University
hospital, Turkey. SUBJECTS: 44 patients with unresectable cancer of the
pancreatic head without duodenal obstruction who presented between May
patients had an antecolic, isoperistaltic gastrojejunostomy,
jejunojejunostomy, and hepaticojejunostomy after cholecystectomy. The
remaining 22 had a hepaticojejunostomy and antecolic, antiperistaltic
gastrojejunostomy procedure after cholecystectomy. MAIN OUTCOME
MEASURES: Mortality, morbidity, postoperative course, and survival.
RESULTS: There were no significant differences between the groups in the
incidence of postoperative complications, time until restoration of oral
diet, relaparotomy rate, late upper gastrointestinal bleeding,
mortality, duration of hospital stay, and survival. The isoperistaltic
operation took significantly longer than the antiperistaltic operation
(p < 0.001) and there was less delayed gastric emptying in the
antiperistaltic group but not significantly so. Both operations caused a
significant lengthening in the postoperative gastric emptying time (p =
0.04 and p = 0.01, respectively). CONCLUSION: Both procedures are
suitable for patients with unresectable carcinoma of the pancreatic head
without impending duodenal obstruction. There was a trend towards better
clinical results with the isoperistaltic procedure.
29
UI - 11832469
AU - Schmid RM
TI -
HMG-CoA reductase inhibitors for the treatment of pancreatic cancer.
SO - Gastroenterology 2002 Feb;122(2):565-7
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