ObjectiveTo assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. Summary Background DataPancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. MethodsESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. ResultsOf 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. ConclusionsResection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.
Diabetes occurs frequently in patients with pancreatic cancer. To investigate the impact to tumour removal, seven patients were studied before and after 85 per cent subtotal pancreatectomy for adenocarcinoma of the pancreas. The frequency of diabetes was determined by the oral glucose tolerance test. Fasting levels of C peptide and insulin were measured in plasma, and insulin secretion was investigated by hyperglycaemic glucose clamp and glucagon stimulation. Six of the seven patients were diabetic before surgery and four required insulin treatment. Improvements in diabetic status and glucose metabolism were found in all seven patients after operation, as demonstrated by increased glucose metabolic capacity during hyperglycaemia. This occurred despite a postoperative reduction in insulin secretion and is explained by the observed augmentation of whole-body insulin sensitivity after surgery. A diabetogenic factor may be produced by pancreatic adenocarcinoma that may be responsible, directly or indirectly, for the high frequency of diabetes in patients with pancreatic cancer.
In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis, the effects of treatment with a granulated pancreatic enzyme preparation (Pankreon) were compared with those of placebo administration. One week of treatment with each preparation was preceded by one week without any medication. The patients kept daily records of their symptoms, plotting the severity of pain on an analog scale. Weekly assessments of the mean pain level were also made by an examiner questioning the patients. Recordings of body weights and pancreas and liver laboratory tests were done weekly. Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment (P less than 0.05). The average reduction of pain, as calculated for all patients, was 30% as evaluated by both patients (P less than 0.01) and the examiner (P less than 0.05). No differences were found in other parameters examined. A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin.
During the late 1960s total pancreatectomy was advocated on theoretic grounds as an operation superior to subtotal (Whipple) resection in patients with pancreatic cancer. There are, however, no prospective randomized studies and only few institutional comparisons between the two operations. The aim of the present paper was to report the clinical outcome of total and subtotal pancreatectomy, respectively, in a consecutive series of patients with exocrine pancreatic cancer. The short- and long-term results of 89 consecutive patients who underwent total pancreatectomy (1959-1984) for pancreatic cancer were retrospectively compared with a similar group of 36 patients who had a subtotal pancreatectomy (1985-1992) for the same diagnosis. The clinical characteristics were on the whole similar in the two groups. Postoperative mortality and morbidity, the amount of intraoperative bleeding, operation time, reoperation rate, postoperative days in the intensive care unit, and duration of hospital stay were statistically significantly increased after total pancreatectomy. The 5-year survival rate was lower after total pancreatectomy when hospital deaths were included in the analysis. At multivariate analysis total pancreatectomy adversely influenced long-term survival compared to subtotal resection, as did positive lymph nodes and poor histologic differentiation. Better early and long-term results were found after subtotal than after total pancreatectomy in patients with exocrine pancreatic cancer. Although the two operations were done during different time periods, we believe the results suggest that total pancreatectomy cannot be recommended as a routine treatment for this patient group.
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