PANCREAS ALERTS
Int J Radiat Oncol Biol Phys 2003; 56(4):974-80. (AN 22434985, PMID 12829132)
Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study.
Van Laethem JL, Demols A, Gay F, Closon MT, Collette M, Polus M, et al.
Medico-Surgical Department of Gastroenterology, Erasme University Hospital. Brussels, Belgium.
The addition of radiation to adjuvant 5-fluorouracil for the treatment of pancreatic cancer has not yet shown any definite benefit. Gemcitabine has potential activity in advanced pancreatic cancer and is a powerful radiosensitizer.
In this study the Authors evaluated the feasibility of postoperative administration of gemcitabine alone, followed by concurrent gemcitabine and irradiation after curative resection for pancreatic adenocarcinoma.
Gemcitabine 1000 mg/m2 on days 1 and 8 every 21 days for three courses was given within 8 weeks after surgery and was followed by gemcitabine 300 mg/m2 weekly +40 Gy in a split course.
For gemcitabine alone, all patients received the three planned courses, with dose reductions in 7 (32%) of 22 patients. All patients, except two, completed full chemoradiation: one received only 20 Gy because of both World Health Organization Grade 4 vomiting and thrombopenia; the other stopped radiotherapy after 32 Gy because of early disease progression.
After a median follow-up of 15 months, 11 patients were alive, and 2 patients had died of causes unrelated to their disease or toxicity, The median disease-free survival and overall survival was 6 and 15 months, respectively.
This adjuvant regimen was well tolerated and can be easily administered after curative surgery for pancreatic cancer. Its intensification with continuous radiotherapy is currently being investigated.
Twenty-two patients (median age 59 years, range 39-74, Performance Status 0-1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included.
No reduction in gemcitabine during radiotherapy was necessary; no toxic death was noted. World Health Organization Grade 3-4 hematologic and nonhematologic toxicities occurred in 8 (36%) and 7 nausea/vomiting in 7 (32%) of 22 patients, respectively. No late toxicity developed.
Eur J Cancer 2003; 39(10):1377-83. (AN 22710691, PMID 12826040)
A phase II/III study comparing intravenous ZD9331 with gemcitabine in patients with pancreatic cancer.
Smith D, Gallagher N.
Clatterbridge Centre for Oncology. Bebington, Wirral, Cheshire, United Kingdom.
ZD9331 is a novel antifolate inhibitor of thymidylate synthase. This multicentre, randomised, phase II/III study compared the efficacy and safety of ZD9331 with gemcitabine in 55 patients with chemonaive, locally advanced or metastatic pancreatic cancer.
Thirty patients received intravenous ZD9331, on days 1 and 8 of a 3-week cycle and 25 patients received intravenous gemcitabine, once a week for 7 weeks followed by a 1-week rest, then on days 1, 8 and 15 of a 4-week cycle.
Objective tumour response and clinical benefit response were similar for both groups. More ZD9331 patients were alive at the data cut-off point compared with gemcitabine patients (13% and 8%, respectively). Median survival (152 versus 109 days, respectively) and time to progression (70 versus 58 days, respectively) were longer in the ZD9331 group. Nausea and vomiting (grade 1-2) were the most common toxicities in both groups.
The Authors concluded that, in pancreatic cancer, ZD9331 is equivalent to gemcitabine and may offer a promising alternative to current therapies.
Am J Clin Oncol 2003; 26:151-4. (AN 22599263, PMID 12714886)
Phase II trial of the use of gemcitabine and 5-fluorouracil in the treatment of advanced pancreatic and biliary tract cancer.
Murad AM, Guimaraes RC, Aragao BC, Rodrigues VH, Scalabrini-Neto AO, Padua CA, Moore FC.
Oncology Section, Hospital das Clinicas da Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.
In this phase II trial, the Authors used the combination of gemcitabine and 5-fluorouracil to treat 26 patients (15 males, 57.7%; 11 females, 42.3%; median age 58 yrs, range, 39-68; median performance status 2, range 1-3. Seventeen patients (65%) had advanced pancreatic adenocarcinoma and 9 (35%) had advanced biliary tract adenocarcinoma: 10 locally advanced and 16 metastatic.
There were 8 objective responses, plus 1 complete response not confirmed by second-look laparotomy, thus the overall objective response rate was 30.7% (95% CI 12-47%). Among the patients with biliary tract carcinoma, 33% (3/9) had partial response. Six (23%) patients had stable disease.
One patient developed reversible World Health Organization grade IV febrile neutropenia. Grade III neutropenia was observed in 11 (11%) cycles; grade III thrombocytopenia in 7 (7%) cycles; grade III mucositis in 7 (7%) cycles; and grade III diarrhea in 10 (10%) cycles. Asthenia grades I and II occurred in 30% of cycles and flulike syndrome grade II in 11 (11%) cycles.
The combination of gemcitabine and 5-fluorouracil in patients with advanced pancreatic or biliary tract cancer produces promising activity and tolerability with the added potential for clinical benefit, and thus warrants further investigation.
A total of 102 cycles were administered (median, 4 per patient).
All 8 responders and 3 of the patients with stable disease experienced clinical benefit (42%). The median overall survival was 9 months (range, 6-38), and the 1-year survival rate was 30%. The regimen was very well tolerated.
Am J Respir Crit Care Med 2003; 168(2):148-57. (AN 22732847, PMID 12851244)
Compartmentalization of the inflammatory response during acute pancreatitis: correlation with local and systemic complications.
Dugernier TL, Laterre PF, Wittebole X, Roeseler J, Latinne D, Reynaert MS, Pugin J.
Department of Intensive Care and Emergency Medicine, St. Luc University Hospital. Brussels, Belgium.
Local and systemic inflammation has been implicated in the pathogenesis of acute pancreatitis and secondary multisystem organ failure.
To assess the pro- and anti-inflammatory response, the site of mediator production, and their route of diffusion, the Authors sampled simultaneously ascites, thoracic lymph, and blood at the onset of end-organ dysfunction and for the following 6 days in 60 patients with acute pancreatitis.
Immunoassays were used to measure pro- and anti-inflammatory cytokines and cell-based bioassays were utilized to assess the net pro- and anti-inflammatory activity elicited by the biological fluids.
Tumor necrosis factor-alpha and interleukin-1beta were detected in less than 15% of blood and lymph samples. Secondary pro- and antiinflammatory cytokines were found to be elevated early and throughout the sampling period in all compartments. Cytokine levels decreased from ascites to lymph to blood, suggesting a splanchnic origin. Prolonged diversion of ascites and lymph did not alter cytokine gradients, suggesting mediator transfer via the splanchnic blood circulation.
Although a net pro-inflammatory activity ascribed to interleukin-1beta was detected in ascites, a net antiinflammatory activity was measured in virtually all lymph and blood samples, suggesting that the pancreas and the splanchnic area are sites of a pro-inflammatory response and that an early, dominant, and sustained anti-inflammatory activity takes place in circulating compartments.
Eur Radiol 2003; 13(4):897-902. (AN 22549415, PMID 12664132)
Colonic involvement in non-necrotizing acute pancreatitis: correlation of CT findings with the clinical course of affected patients.
Wiesner W, Studler U, Kocher T, Degen L, Buitrago-Tellez CH, Steinbrich W.
Institute of Diagnostic Radiology, University of Basel. Basel, Switzerland.
The purpose of this study was to describe CT findings of colonic involvement in acute non-necrotizing pancreatitis and to analyze the correlation between colonic wall thickening at CT and the clinical course of these patients.
The CT examinations of 19 consecutive patients with acute non-necrotizing pancreatitis who were not treated with antibiotics initially were analyzed retrospectively.
Seven of 11 patients with a CT severity index of 4 showed a colonic wall thickening, whereas the 8 patients with a CT severity index less than 4 (5 patients with CT severity index of 3 and 3 patients with CT severity index of 2) showed no colonic abnormalities at CT.
It is well known that translocation of the colonic flora may significantly influence the clinical course of patients with acute pancreatitis, and these results indicate that patients with acute pancreatitis who present with colonic wall thickening at CT have an increased risk for a complicated clinical course regarding systemic infection.
The severity of acute pancreatitis was categorized according to the CT severity index and the presence of colonic wall thickening at the initial CT was compared with the clinical course of all patients.
Patients with colonic wall thickening presented more often with fever, showed higher levels of infectious parameters, needed more often antibiotic therapy, and had more requests for additional CT examinations and CT-guided fluid aspirations, as well as, a longer duration of hospital stay as compared with patients without colonic wall involvement, even if the latter presented with the same CT severity index initially.
AIDS Read 2003; 13(7):344-8. (AN 22752430, PMID 12889452)
Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy.
Butt AA.
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pancreatitis and lactic acidosis are severe and life-threatening adverse events associated with nucleoside analogue antiretroviral therapy used to treat HIV infection. The drug from this class most commonly associated with these adverse events is stavudine, although zidovudine and didanosine have also been implicated.
A case of fatal lactic acidosis and pancreatitis is described in an HIV-infected patient coinfected wtih hepatitis C on a didanosine-containing antiretroviral regimen after treatment of hepatitis C was initiated with ribavirin and pegylated interferon alfa-2b.
Extreme caution should be exercised when didanosine and ribavirin are used concomitantly because of the increased risk of mitochondrial toxicity and the syndrome of severe metabolic acidosis with elevated lactic acid levels.
Ribavirin is a nucleoside analogue used in combination with interferon alfa to treat hepatitis C. Because of similar mechanisms of action, the combination of these 2 drugs could potentially increase such toxicity.
Surgery 2003; 134(1):53-62. (AN 22757120, PMID 12874583)
Outcome after duodenum-preserving pancreatic head resection is improved compared with classic Whipple procedure in the treatment of chronic pancreatitis.
Witzigmann H, Max D, Uhlmann D, Geissler F, Schwarz R, Ludwig S, et al.
Department of Abdominal, Transplantation and Vascular Surgery, University of Leipzig. Leipzig Germany.
There is no consensus in the surgical management of chronic pancreatitis as to whether techniques preserving the duodenum are superior to pancreatoduodenectomy. This prospective study compared the outcome of standard pancreatoduodenectomy and duodenum-preserving pancreatic head resection in treatment of selected patients with chronic pancreatitis.
Inclusion criteria for this prospective controlled, nonrandomized study were patients suffering from chronic pancreatitis centered in the head and with severe pain. Seventy consecutive patients were studied: 38 underwent duodenum-preserving pancreatic head resection and 32, classic pancreatoduodenectomy.
A multidimensional, psychometric questionnaire was used to measure the quality of life. quality of life was compared with that of the general German population. Pain intensity was evaluated on the basis of the frequency of pain attacks, analgesic medication, and self-assessed pain score. Assessment of endocrine and exocrine function as well as nutritional status included oral glucose tolerance test, fecal elastase, stool frequency, and body mass index. The median follow-up was 34 months.
Multiple clinical characteristics did not differ between the two groups except for age (P=0.04), the tumor marker carbohydrate antigen 19-9 (P=0.02), and the parameter suspicion of malignancy. There was no hospital mortality. Surgical morbidity was 19% in the pancreatoduodenectomy group and 8% in the duodenum-preserving pancreatic head resection group (P=0.60). pancreatoduodenectomy resulted in a longer median hospital stay than duodenum-preserving pancreatic head resection (19 vs 15 days, P=0.04). Complications of adjacent organs were definitively treated in 100% after pancreatoduodenectomy and in 97% after duodenum-preserving pancreatic head resection. Postoperative pain intensity as self-assessed by the patients was significantly less in the duodenum-preserving pancreatic head resection group (P<0.001), whereas the frequency of acute episodes (P=0.27) and analgesic medication (P=0.43) did not differ between the two groups. After surgery, symptom and functional scales of the duodenum-preserving pancreatic head resection group were significantly better than those in the pancreatoduodenectomy group and were similar to those of the overall German population. No significant difference was found between the two groups with regard to endocrine and exocrine function. Postoperative increase of body mass index was significantly higher in the duodenum-preserving pancreatic head resection group (P<0.001).
The Authors concluded that duodenum-preserving pancreatic head resection provides better results in the treatment of chronic pancreatitis than pancreatoduodenectomy in terms of quality of life, pain intensity as self-assessed by the patients, nutritional status, and length of hospital stay.