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Ductal carcinoma of the pancreas. Rationales for total pancreatectomy.

In order to evaluate total pancreatectomy as a surgical procedure for ductal carcinoma of the pancreas, a histopathological analysis was made on 18 resected specimens with special regard to the pattern of cancer growth in the pancreatic tissue. In five of them there was no lymphatic involvement or extrapancreatic invasion, but cancer extended continuously to the tail along with the pancreatic ducts and reached the end of the ducts in three cases. All 11 patients treated with Whipple's procedure died of recurrence, while of four total pancreatectomized patients, one with continuously invasive cancer to the end of the pancreatic duct has been living more than eight years postoperatively. We believe that total pancreatectomy for this type of "intraductal spreading cancer" without invasion beyond the pancreas is indicated as a radical procedure.

Aged↗

Islet cell autotransplantation after pancreatectomy for chronic pancreatitis. Its limitations.

Of 12 patients operated on for intractable pain from chronic pancreatitis, only the three with adequate preoperative insulin reserve were selected to undergo islet-cell replantation after subtotal pancreatectomy. Fourteen, nine, and four months postoperatively, they require no therapy with insulin. Since most techniques for obtaining islet cells have been performed with normal pancreata, chronic pancreatitis was produced in ten dogs by ligating the main and accessory pancreatic ducts. These dogs 162.6 +/- 15.8 days later underwent total pancreatectomy. The scarred pancreatic fragments were dissociated with collagenase for 20 minutes in five dogs or subjected to two intermittent digestions of ten minutes in the other five dogs and were autotransplanted to the liver. One dog from each group became normoglycemic within one week of replantation, and their percent per minute decreases of serum glucose level were 2.72 and 3.46, respectively. Our experimental and clinical data suggest that (1) present techniques for dissociating fibrotic tissue are unsatisfactory and lead to a very low yield of islet cells; (2) postoperative assessment of islet-cell function involves complicated invasive procedures (portal and hepatic vein cannulation) to determine accurately the source of insulin; and (3) careful preoperative evaluation of beta-cell function is needed.

Adult↗

Chronic pancreatitis. Results of Whipple's resection and total pancreatectomy.

The aim of our study was to determine the success of radical pancreatic resection in relieving the pain of chronic pancreatitis. From 1974 to 1985, 30 consecutive patients underwent radical pancreatic resection for the treatment of debilitating pain (15 underwent Whipple's resection and 15 underwent total pancreatectomy). Patients were not randomized but were subjected to the procedure deemed indicated for their clinical presentation; thus, the two groups were not strictly comparable. There was no operative mortality; major morbidity occurred in three patients (20%) in each group (four patients experienced anastomotic bile leak and two experienced abdominal sepsis). Following Whipple's resection, mean follow-up was 6.2 years (range, 1.5 to 12.1 years). Complete pain relief occurred in eight patients (53%) and significant relief in an additional four (27%). Endocrine insufficiency developed in six patients and exocrine insufficiency in eight. Following total pancreatectomy, mean follow-up was 9.1 years (range, 2.1 to 13.1 years). Complete pain relief occurred in only four patients (27%) and significant relief in an additional six (40%). Significant pain persisted in about 33% of patients after total pancreatic resection. We concluded that radical pancreatic resection can be performed safely in patients with chronic pancreatitis but with gratifying results in only 67% to 80% of patients. Whipple's resection may be preferable for disease located primarily in the head of the gland.

Adult↗

Clinical experience with regional pancreatectomy for adenocarcinoma of the pancreas.

Twenty patients with adenocarcinoma of the pancreas underwent a regional pancreatectomy, including resection of the pancreas, regional lymphadenectomy, duodenectomy, antrectomy, and sleeve resection of the portal vein. Three patients required mesenteric arterial reconstruction. Adjunctive radiotherapy was administered to 17 patients, with 11 patients receiving intraoperative radiation and six patients receiving postoperative external-beam-radiation. Complications developed in 11 patients (55%), including infectious and septic events (five patients), biliary or enteric fistulas (two patients), mesenteric vascular thrombosis (two patients), and other complications (two patients). Four patients (20%) suffered treatment-related deaths. The overall median survival was 12.0 months. Survival at one year was 50% and, at three years, 10%. Two patients died of causes unrelated to cancer at 18 and 39 months, and one patient remains alive and free of disease 50 months following therapy. Morbidity and survival did not differ among patients who received intraoperative, conventional postoperative, or no radiation therapy. Although occasional patients may benefit with survivals of longer than three years, regional pancreatectomy carries major morbidity and produces little survival benefit for most patients with pancreatic cancer.

Adenocarcinoma↗

Fibrin glue sealing for the prevention of pancreatic fistulas following distal pancreatectomy.

OBJECTIVE: To evaluate the use of fibrin glue sealing of the pancreatic stump for the prevention of postoperative pancreatic fistulas. DESIGN: A prospective, randomized clinical trial. PATIENTS AND METHODS: Fibrin glue is a biologic adhesive consisting of highly concentrated human fibrinogen, thrombin, and factor VIII. Twenty-six of 56 patients who underwent distal pancreatectomy for gastric cancer or pancreatic disease were randomly assigned to the fibrin glue group. Fibrin glue was applied to the suture line of the pancreatic stump with the ligated main pancreatic duct. Pancreatic fistula was defined as a pancreatic fluid discharge for over 7 post-operative days diagnosed by local findings, with amylase concentration in the discharge fluid more than three times the serum amylase concentration, a level low enough that even a small pancreatic leakage could be diagnosed. RESULTS: The overall incidence of pancreatic fistula was 28.6%. Postoperative pancreatic fistulas occurred in four patients (15.4%) in the fibrin glue group and 12 (40.0%) in the control group (P = .04). The lower pancreatic fistula rate was seen in the fibrin glue group also when analyzing patients with gastric cancer or pancreatic disease only, although there was no statistically significant difference. CONCLUSIONS: Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.

Adult↗

Pancreatic fistula complicating pancreatectomy for malignant disease.

The incidence of pancreatic fistula in a series of 178 pancreatic resections was 25 per cent and was influenced by the type of pancreatectomy, the management of the remaining pancreas and the size of the pancreatic duct. Thus, fistulas appeared in 52 per cent of patients undergoing pancreatoduodenectomy as compared to only 7 per cent of those undergoing distal pancreatectomy (P less than 0.001). Ligation of the pancreatic, duct in pancreatoduodenectomy led to a 70 per cent incidence; the incidence was 33 per cent if the pancreas was anastomosed to the jejunum instead (P less than 0.001). Fistulas were rare in patients who had dilated pancreatic ducts. Fistulas, once they were established, were rarely influenced by treatment. One out of 5 patients developing pancreatic fistula died, while fistulas were responsible for half of the operative deaths. The study indicated that pancreatojejunostomy is safe in the presence of ductal dilatation; it does not, however, protect from fistula if the pancreatic duct is normal. It also indicated that radiation of the pancreatic remnant in selected patients with persistent fistulas might be a useful therapeutic alternative.

Duodenum↗

Total pancreatectomy in the MEN-1 syndrome.

A family with the multiple endocrine neoplasia Type 1 (MEN-1) syndrome, followed over three generations, is presented. In the first generation, one family member died after a history indicating Zollinger-Ellison syndrome. In the second generation endocrine pancreatic tumours were diagnosed or suspected in three out of five members. In the third generation, five out of seven members were investigated and four of these had positive tests at hormonal screening. Of particular diagnostic value in this family was the determination of peripheral serum levels of proinsulin and C-peptide, which were used as tumour markers both for diagnosis and in the postoperative follow-up. Two members in the third generation have been successfully managed by total pancreatectomy. A MEN-1 patient with malignant pancreatic tumours should be considered for total pancreatectomy if the pancreatic disease has caused high morbidity and mortality within the family. This is especially pertinent if the patient has multiple malignant tumours.

Adult↗

Distal pancreatectomy for gunshot injuries of the distal pancreas.

This study comprised 57 patients with gunshot injury of the distal pancreas. There were 16 grade II, 29 grade III and 12 grade IV pancreatic injuries. The intraoperative mortality rate was 12 per cent. Patients with the most severe grade II injuries and all those with grade III and IV injuries had distal pancreatectomy and splenectomy, with a 14 per cent fistula formation rate and 2.3 per cent postoperative mortality rate directly related to the pancreatic injury. The remaining patients with grade II injuries were managed by debridement and drainage; there were no fistulas or deaths. The method of closure of the pancreatic resection margin is unrelated to fistula formation, and identification of the duct for ligation is unnecessary. Liberal use of distal pancreatectomy with splenectomy for gunshot injuries of the distal pancreas is suggested.

Adult↗

Extended lymph node dissection without routine spleno-pancreatectomy for treatment of gastric cancer: low morbidity and mortality rates in a single center series of 250 patients.

BACKGROUND AND OBJECTIVES: To verify the hypothesis that avoidance of routine splenectomy and distal pancreatectomy in a modified D-2 resection for gastric cancer can significantly lower the complications rate of this procedure in a population of Western patients. METHODS: A series of 250 consecutive Italian patients suffering from localized, histology-proven gastric cancer was submitted to gastrectomy and extended D-2 lymphadenectomy for treatment of their disease during an 8-year period (1994-2002) at the European Institute of Oncology in Milano, Italy. Caudal pancreas and spleen were routinely preserved, unless the tumor was not closely adjacent to or directly invading these organs. Postoperative morbidity, overall mortality, and length of hospital stay were recorded. RESULTS: One hundred forty patients underwent total gastrectomy and 110 a subtotal distal one; splenectomy was performed in 8 cases and spleno-pancreatectomy in 15. The postoperative morbidity rate was 18%, the mortality rate was 1.2% and 9 patients experienced re-operation. The median length of stay was 14.8 days. CONCLUSIONS: These results compete favorably with those reported after standard D-1 gastrectomy in Western patients series. D-2 gastrectomy with spleen and pancreas routine preservation can be considered a safe treatment for gastric cancer in Western patients, at least in experienced centers.

Adult↗

Effect of L-364,718 on pancreatic endocrine function following partial pancreatectomy.

This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.

Animals↗

Subtotal pancreatectomy in five different rat strains: incidence and course of development of diabetes.

The incidence and course of development of diabetes was studied for 12 months after subtotal pancreatectomy in five strains of rats. Operations were performed on 5-7-week old-male animals weighing 100-140 g, and, subsequently, rats with fasting blood glucose levels greater than 8.3 mmol/l were considered to be diabetic. In Füllinsdorf Albino rats, the proportion of diabetic animals gradually increased during the course of the experiment to a maximum of 83%. In Holtzman and Piebald rats, the highest incidence (58% and 28% respectively) was observed 2-3 months after surgery, after which partial remission of their diabetes occurred. Spontaneously hypertensive rats completely recovered from an initially mild diabetic state within 6 months of the operation. In Lewis rats, only a small number of animals (15%) became diabetic towards the end of the experiment. The severity of diabetes also differed considerably between strains. The pancreatic insulin content in diabetic rats was 2%-7% and in operated non-diabetic rats 17%-26% of values in non-operated control animals of the same age and strain. However, in the operated non-diabetic rats, glucose tolerance and the insulin response to glucose were also impaired. It is concluded that there are marked inter-strain differences in rats concerning the incidence and development of diabetes following subtotal pancreatectomy.

Animals↗

An appraisal of segmental pancreatectomy for benign tumors of the pancreatic body: a report of two cases.

To preserve pancreatic and splenic function, segmental pancreatectomy with pancreatojejunostomy was performed on two patients with benign pancreatic tumors, and a 3-year follow-up study was conducted. The pancreatic endocrine functions assessed by 75 g oral glucose tolerance test were normal 3 years after surgery, and the exocrine functions returned to within the normal range 1 month after surgery according to a pancreatic function diagnostant (PFD) test. The platelet count increased transiently to 48.9 x 10(4)/mm3, and 70.5 x 10(4)/mm3, in the two patients, respectively, but returned to the preoperative value 1 month postoperatively. The operative times were 7 h 51 min and 5 h 3 min, which included the time taken for intraoperative ultrasonography and frozen section diagnosis, and the blood losses were 183 ml and 212 ml. The postoperative hospitalization period averaged 39 days and no complications developed in either patient. The method of performing segmental pancreatectomy, initially reported by Letton and Wilson for cases of pancreatic trauma, was evaluated and successfully applied to benign pancreatic tumors.

Adenoma, Islet Cell↗

Role of endogenous hypergastrinemia in regenerating endocrine pancreas after partial pancreatectomy.

We studied the possible role of endogenous gastrin in the regenerating pancreas. Male Wistar rats underwent sham operation or 90% partial pancreatectomy (Px). Lansoprazole (30 mg/kg body wt), a proton pump inhibitor (PPI), was given p.o. for 3 weeks after surgery. Plasma glucose levels were higher in Px rats than in shams. Lansoprazole lowered plasma glucose levels in the Px rats. In addition, integrated insulin secretion during an oral glucose tolerance test (2 g/kg body wt) was significantly (p < 0.01) higher in lansoprazole-treated Px rats than in control Px rats, while lansoprazole did not affect insulin secretion in shams. Fasting serum gastrin levels were higher (p < 0.01) in lansoprazole-treated animals than in controls both in sham rats and in Px rats. Furthermore, lansoprazole increased the pancreas weight per body weight and elevated the insulin content of the pancreas in Px rats. These results suggest that endogenous hypergastrinemia has a trophic effect on endocrine pancreas during regenerating processes and that administration of PPI may be clinically beneficial to the remnant pancreas after pancreatectomy if the whole stomach is preserved.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pancreatectomy for carcinoma of the head of the pancreas associated with multiple anomalies including the preduodenal portal vein.

Total pancreatectomy was performed for carcinoma of the head of the pancreas associated with multiple anomalies in the peripancreatic region and of the pancreas. The anomalies were preduodenal portal vein, annular pancreas with agenesis of the dorsal pancreas, left-sided gallbladder, polysplenia and high mobile right colon. The surgical implications of pancreatectomy for such anatomical abnormalities, especially preduodenal portal vein, and the usefulness of ultrasonography for the preoperative evaluation are given attention.

Abnormalities, Multiple↗

Segmental autotransplantation of the pancreas after total pancreatectomy for advanced periampullary carcinoma--a case report.

A case is reported here in which segmental autotransplantation of the pancreas was performed after total pancreatectomy for advanced periampullary carcinoma in an attempt to preserve pancreatic endocrine function. The postoperative course was uneventful. The requirement of insulin decreased after the operation and the daily profile examination, done 5 months following surgery, showed a permissive fluctuation of blood sugar levels without insulin injection. Thus, segmental autotransplantation of the pancreas offers a method of preserving pancreatic endocrine function after total pancreatectomy for periampullary carcinoma in selected patients.

Carcinoma↗

Glucagon levels and ketogenesis in human diabetes following total or partial pancreatectomy and severe chronic pancreatitis.

In three groups of patients with insulin-dependent diabetes following total (n = 5) or partial (n = 5) pancreatectomy or chronic pancreatitis (n = 7) and in a group of idiopathic diabetics, ketogenic capacity following insulin withdrawal and during a 24-h fast was studied. Basal glucagon values were significantly increased in all diabetic groups with no significant intergroup differences. Basal ketone body values and their increase during starvation and insulin withdrawal were high and not different in totally pancreatectomized and primary diabetics, both showing unmeasurable C-peptide levels. On the contrary, ketogenesis was reduced in partially pancreatectomized and in pancreatitis diabetics with persistent levels of C-peptide. Our data confirmed the persistence of immunoreactive glucagon after pancreatectomy and demonstrated that ketogenesis is not suppressed in pancreatectomized diabetics and depends above all on residual B-cell function. A possible ketogenic effect of extra-pancreatic glucagon-like substances cannot be excluded.

Chronic Disease↗

Effect of insulin treatment on the regeneration of the remnant pancreas after major pancreatectomy in dogs.

The effect of exogenous insulin treatment on the pancreatic regeneration after major pancreatectomy was evaluated in dogs. More than 92% of the pancreas was removed near the duodenum with the main pancreatic duct left intact. All 26 dogs developed diabetes mellitus (DM) immediately after surgery, and these dogs were divided into two groups: insulin-treated group (n = 19) and noninsulin-treated group (n = 7). All seven dogs in the noninsulin-treated group died within seven weeks after surgery, whereas all dogs in the insulin-treated group survived until the twelfth week, except for six dogs sacrificed on the seventh week, and finally seven (53.8%) of 13 dogs recovered from DM. DNA and polyamine syntheses in the remnant pancreatic tissue at the third day increased more significantly in the insulin-treated group than in the noninsulin-treated group. Sigma IRI in IV-GTT was maintained more significantly in the insulin-treated group, and the regeneration rate at the seventh week was also significantly higher in the insulin-treated group than in the noninsulin treated group. Furthermore, the regeneration rate of the remnant pancreas at seventh week correlated well with DNA synthesis and ornithine decarboxylase activity on the third day. The exogenous insulin treatment after major pancreatectomy enhanced the proliferation of the remnant pancreas within the first week, and it maintained endogenous insulin secretion, promoting pancreatic regeneration.

Animals↗

Influence of pancreatic neurotomy on regeneration of residual pancreas after major pancreatectomy in rats.

This study was performed to examine the influence of pancreatic neurotomy (N) on pancreatic regeneration after 90% pancreatectomy (P), excluding the parabiliary segment. One hundred and fifty male Wistar rats were divided into three groups, consisting of the PN, P, and laparotomy (L) groups. The ratios of wet wt of residual pancreas to body wt in groups with P increased after the procedures. The ratios in the P group reached their maximum at 10 d, and then decreased slightly, whereas those in the PN group rose gradually for a 60 d period. Regarding changes in the labeling indices in autoradiograms using 3H-thymidine and mitotic indices in exocrine cells, those indices in groups with P reached a peak at 3 d after the procedures, and then rapidly declined. Both indices in the PN group were lower during the first 10 d and thereafter higher than those in the P group. These results suggest that following pancreatic neurotomy, the potential for pancreatic regeneration continues over a longer period after major pancreatectomy.

Acetylcholinesterase↗