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Pancreatic islet autotransplantation combined with total pancreatectomy for the treatment of chronic pancreatitis--the Leicester experience.

Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving "transient" insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the "gold standard" for monitoring islet autograft function, may require reappraisal.

C-Peptide↗

Enhanced expression of insulin receptor substrate-2 and activation of protein kinase B/Akt in regenerating pancreatic duct epithelium of 60 %-partial pancreatectomy rats.

AIMS/HYPOTHESIS: Early compensatory mechanisms of regeneration following partial pancreatectomy involve ductal proliferation and, subsequently, differentiation into acinar and endocrine cell types, although it is not clear how these processes are regulated. We investigated the expression and roles of insulin receptor substrate-2 (IRS-2) and protein kinase B/Akt (Akt) in pancreatic regeneration that starts with the common duct epithelium using a non-diabetic model of beta cell adaptation and mass expansion, 60 %-pancreatectomy rats. METHODS: We used confocal immunofluorescence microscopy to study IRS-2 and Akt expression and activation in pancreatic common ducts at intervals after surgery. These proteins were studied in relation to proliferation markers and insulin immunostaining. RESULTS: In pancreatectomized rats, a short-term increase in proliferation was observed in the common duct epithelial lining ( approximately 4-fold) compared with sham-operated control rats which correlated with about a 1.8-fold increase in IRS-2 immunoreactivity 2 days after surgery. Interspersed with proliferating cells of the common duct, evaginations were rare single and clustered insulin immunopositive cells which expressed high levels of IRS-2 immunoreactivity. Epithelium of duct evaginations from 2-day post-Px rats exhibited striking phospho-Akt staining ( approximately 3.5-fold above control rats) without any detectable changes in total Akt staining. CONCLUSION/INTERPRETATION: Our data suggest that IRS-2 plays an important role in pancreatic regeneration and growth by mediating duct proliferation and by maintaining the differentiated beta cell. The restricted staining pattern of phospho-Akt to cells of the common duct evaginations suggests that it has a role in regulating post-mitotic events related to cell-specific gene expression or survival or both.

Animals↗

Pancreatic regeneration after near-total pancreatectomy in children with nesidioblastosis.

BACKGROUND: Nesidioblastosis is often resistant to medical therapy and requires near-total pancreatectomy. There is little information on the postoperative imaging findings of these patients. OBJECTIVE: To demonstrate by US the late imaging findings in these patients. MATERIALS AND METHODS: Children diagnosed with nesidioblastosis and who had undergone 90-95% pancreatectomy received preoperative, immediate-postoperative (within 10 days of surgery) and long-term annual US examinations. In the preoperative study, three anterior-posterior (AP) measurements were obtained of the head, body and tail of the pancreas. In the postoperative and long-term follow-up US, AP and transverse measurements of the pancreatic remnant were obtained. Pancreatic echogenicity was also assessed. The results were compared with normal pancreatic dimensions as a function of age. Glucose metabolism and pancreatic enzymes were also analysed. RESULTS: The study group comprised 22 patients (aged 9 days to 2 years). The pancreas was normal in all preoperative US examinations. The first postoperative examination showed, in all patients, a remnant of the pancreatic head measuring 8-13 mm. The last follow-up US was similar to the first postoperative study in 6 patients, and 12 showed complete pancreatic regeneration (normal size, echogenicity and function), and 4 had incomplete regeneration with head and body normal in size, but lack of a pancreatic tail. All patients were asymptomatic and showed normal laboratory tests. CONCLUSIONS: US measurements indicated normal age-dependent growth after near-total resection in 54% of patients. The function and echogenicity of the regenerated pancreas indicate that the increase in organ size was due to normal pancreatic tissue.

Child, Preschool↗

Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreas.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Adenocarcinoma↗

Are the results of pancreatectomy for pancreatic cancer improving?

Although pancreatectomy is still performed in a few patients with pancreatic cancer, and nearly all patients who develop pancreatic cancer eventually die of their disease, significant improvements have been made recently. Pancreatectomy is now safer, with major morbidity (hemorrhage, pancreatic anastomotic leak, intraabdominal sepsis) occurring in only about 20% and operative mortality of less than 5%. Two (seemingly subtle) issues cannot be overemphasized when someone carefully studies the literature: (1) There is a crucial difference between actuarial and actual survival, with the former generally being higher whereas the latter is true; and (2) careful re-review of pathologic specimens (especially in long-term survivors) initially diagnosed as pancreatic cancer, preferably by an independent pathologist before publishing long-term results is essential. (Erroneous inclusion of patients with nonductal carcinoma substantially and artificially increases survival.) After curative resection, 5-year actual survival is realistically about 10% with median survivals of 12 to 18 months. In certain subgroups with favorable pathologic characteristics (neoplasms <2 cm without nodal or perineural invasion) the prognosis appears to be significantly better, with the 5-year survival about 20%. The recent improvements in postoperative morbidity and mortality and long-term outcome (resulting also in decreased cost of care of such patients) have occurred typically in centers with an invested interest in and proven record with pancreatic surgery. Further improvements in survival should be sought at the areas of earlier diagnosis and novel treatments designed to prevent locoregional recurrences; the role of extended resections must be determined by prospective, randomized trials.

Humans↗

Pylorus-preserving total pancreatectomy for pancreatic cancer.

Standard total pancreatectomy (TP) combined with gastric resection often results in uncontrollable diabetes and malnutrition. Pylorus-preserving total pancreatectomy (PPTP) and standard TP for pancreatic cancer were compared in terms of operative outcomes, nutritional recovery, and long-term survival. Twenty-four patients with pancreatic ductal adenocarcinoma (n = 14) or intraductal papillary mucinous carcinoma (N = 10) underwent PPTP (n = 10) or standard TP (n = 14). There were no significant differences in age, gender, or tumor type or stage between the PPTP and standard TP groups. Early (within 30 days of surgery) morbidity and mortality rates were 20% and 0% for PPTP and 29% and 7% for standard TP, respectively. Delayed gastric emptying occurred in 2 patients in each group. The incidence of late complications, including uncontrollable diabetes, diarrhea, and malnutrition, tended to be lower after PPTP (30%) than after standard TP (69%). Serum albumin and body weight at 6 months after surgery were significantly higher in the PPTP than in the standard TP group. Regardless of the tumor type, long-term survival did not differ significantly between patients receiving PPTP and those with standard TP. PPTP for pancreatic cancer improves nutritional recovery, without compromising long-term survival, compared with standard TP.

Adenocarcinoma↗

Stenting of the superior mesenteric artery as a preoperative treatment for total pancreatectomy.

The patient was 58-year-old male with mucinous cyst adenocarcinoma of the pancreas. Prior to total pancreatectomy, preoperative CT and angiography showed a high-grade arteriosclerotic stenosis of about 1.0 cm in length in the ostium of the superior mesenteric artery (SMA), as well as the development of collateral vessels in the area around the head of the pancreas. A stent was placed in the SMA stenosis to preserve intestinal blood flow in the SMA region after total pancreatectomy, which was performed 25 days after stent placement. The postoperative SMA blood flow was favorable, with no postoperative intestinal ischemia, and the patient had an uneventful postoperative course.

Blood Vessel Prosthesis Implantation↗

The feasibility and morbidity of distal pancreatectomy in extensive cytoreductive surgery for advanced epithelial ovarian cancer.

INTRODUCTION: Pancreatic metastasis of ovarian cancer is extremely rare and its therapeutic approach is not well documented. The objective of this study is to evaluate the feasibility and morbidity of pancreatic resection as a component of extensive cytoreductive surgery in epithelial ovarian cancer (EOC) patients with pancreas metastasis. METHODS: Between December 2000 and February 2003, 98 EOC patients were treated with primary cytoreduction. Six (6.12%) of these patients had pancreatic tail metastasis and were operated on using the distal pancreatectomy. RESULTS: Preoperatively, only 1 (16.7%) of the 6 patients had signs of metastasis to the pancreas on computed tomography (CT). Optimal cytoreduction (absent or < or =1 cm macroscopic residual tumor size) was achieved in all patients. In the early postoperative period, there were 4 patients (66.7%) with complications and no perioperative mortality. In 1 patient (16.7%), glucose intolerance as a late complication of pancreatic resection was detected. All patients received six cycles of platinum-based adjuvant chemotherapy following a cytoreductive operation. Mean follow-up was 27 months (range 9-36), and 3 (50%) patients are still alive at the end of the study period. The two-year survival rate was 66.7%. CONCLUSION: In conclusion, if optimal cytoreduction is foreseen in advanced epithelial ovarian cancer with pancreatic tail metastasis, distal pancreatectomy should be kept in mind. This procedure has acceptable morbidity and seems to be an attribute for survival.

Adenocarcinoma↗

Laparoscopic distal pancreatectomy. Three cases of insulinoma.

BACKGROUND: Surgery for benign pancreatic disease has traditionally required a major laparotomy however the minimal-access approach is now being applied to a wide variety of procedures, and surgery of the pancreas need not be excluded. METHODS: Laparoscopic distal pancreatectomy was performed on three patients presenting with insulinomas found on preoperative investigation to lie within the tail of the pancreas. RESULTS: All three patients had an excellent clinical outcome and returned to a state of normoglycemia. All of them made a rapid recovery with no major complications. CONCLUSION: Laparoscopic distal pancreatectomy is a viable technique for removing insulinoma of the tail of the pancreas.

Adult↗

Initial experience with hand-assisted laparoscopic distal pancreatectomy.

BACKGROUND: Hand-assisted laparoscopic distal pancreatectomy, with or without splenectomy, is gradually gaining acceptance, although its ultimate benefit is yet to be confirmed. This study aimed to report our initial experience with hand-assisted laparoscopic distal pancreatectomy. METHODS: A retrospective review of a prospectively collected database including 17 patients during the period 2002-2004 was conducted. The median age was 60 years (range, 29-85 years), and the female-to-male ratio was 13:4. The preoperative diagnoses included benign and malignant conditions. Besides two to three ports, a hand port was placed in the upper midline to aid in dissection. The pancreas was divided with a stapler in all the patients, and drains were placed in 10 patients (70%). RESULTS: One patient was found to be unresectable because of celiac artery involvement, and 2 of the remaining 16 patients underwent conversion to an open procedure. The median operating time was 196 min (range, 128-235 min). The mean tumor size was 4 cm (range, 2-7 cm), and the estimated blood loss was 125 ml (range, 50-1,250 ml). The median time to resumption of a regular diet was 3.5 days (range, 2-9 days), and the time to conversion to oral pain medications was 3 days (range, 2-9 days). The length of hospital stay was 5.5 days (range, 4-18 days), with a majority of the patients (11 patients, 78%) staying less than 7 days. There were no mortalities. The overall postoperative morbidity rate was 25%, and the morbidities consisted of pancreatic leak/fistula (2 patients, 14%) and fever (1 patient). The margins were negative in 10 (76%) of the relevant 13 patients. At a median follow-up period of 3.8 months (range, 5-14 months), 11 (84%) of 13 patients had no evidence of disease recurrence. CONCLUSIONS: The minimally invasive approach to pancreatic disease is safe and technically feasible. Further large studies with longer follow-up periods are necessary to determine the role of laparoscopic surgery in the management of pancreatic disease.

Adult↗

Laparoscopic distal pancreatectomy as the total biopsy of the pancreas: tool of minimally invasive surgery.

Because of recent progress in imaging modalities, the opportunities to detect pancreatic cystic neoplasms are increasing. However, serous cystadenoma is still uncommon. We report a case of serous cystadenoma treated by laparoscopic distal pancreatectomy. A 52-year-old woman presented with mild upper abdominal pain. Dynamic computed tomography (CT) revealed a solitary cystic lesion 3 cm in diameter in the pancreatic tail. Endoscopic ultrasound showed a honeycomb pattern, indicative of serous cystadenoma. To obtain the final diagnosis of the tumor, we performed laparoscopic distal pancreatectomy. A histopathological study showed microcystadenoma with no evidence of malignancy.

Cystadenoma, Serous↗

Surgical management for the prevention of pancreatic fistula following distal pancreatectomy.

Although the mortality rate related to pancreatic surgery has been reduced recently, the postoperative morbidity is still high, because of various complications. Pancreatic fistula is one of the most common complications following distal pancreatectomy, and is generally hard to cure. Several surgical techniques and devices, such as the use of fibrin-glue sealing, stapler closure, an ultrasonic dissector, or an ultrasonically activated scalpel have been advocated to prevent pancreatic fistula. In the present review we provide an overview of several devices used for the prevention of pancreatic fistula following distal pancreatectomy.

Fibrin Tissue Adhesive↗

Peritoneal "pillowcase" for the displaced spleen post-distal pancreatectomy.

BACKGROUND PURPOSE: Spleen-preserving distal pancreatectomy, although rarely performed, has become an option for treatment of distal pancreatic neoplasms. However, the spleen, once mobilised, is often free to tort. A reliable method of fixing the spleen would be a useful adjunct to this procedure. METHODS: We describe the use of a new technique to fix the spleen using a peritoneal "pillowcase" to envelop the spleen, thus preventing its torsion. RESULTS: This patient has done well, with no problems encountered intraoperatively or postoperatively, using this new technique of spleen fixation. CONCLUSIONS: The use of a peritoneal "pillowcase" to envelope the spleen following distal pancreatectomy has proven a useful adjunct to this somewhat difficult surgical procedure. It may be applied in other cases where spleen fixation is necessary.

Cystadenocarcinoma↗

Limited pancreatectomy: significance of postoperative maintenance of pancreatic exocrine function.

This study attempted to clarify whether limited pancreatectomy (duodenum-preserving total pancreatic head resection [DPTPHR], or medial pancreatectomy [MP], maintain pancreatic exocrine function more than conventional pancreaticoduodenectomy (Whipple) or pylorus-preserving pancreaticoduodenectomy (PPPD). A total of 125 patients (18 with Whipple, 71 with PPPD, 13 with DPTPHR, and 23 with MP) were studied. Fecal chymotrypsin and p-type amylase, and pancreatic function diagnostant (PFD) tests were used for evaluation. There were no differences in preoperative background. Pancreatic function was seen to be significantly lower after surgery than before surgery in patients who underwent the Whipple procedure and PPPD (P < 0.05), but there was no difference between pre- and postoperative pancreatic function in patients who underwent DPTPHR and MP. Postoperative pancreatic function was shown to be significantly worse in Whipple procedure and PPPD patients than in those with DPTPHR and MP (P < 0.05). Patients who underwent the Whipple procedure and PPPD showed significantly lower pancreatic function than patients who underwent DPTPHR and MP (P < 0.05). There was no difference in pancreatic function between patients who underwent DPTPHR and those with MP. DPTPHR and MP, both of which preserve the entire duodenum, maintain pancreatic function more than the Whipple procedure and PPPD.

Aged↗

A new reconstructive procedure after segmental pancreatectomy: an experimental study of pancreatic end-to-end (duct-to-duct) anastomosis.

We produced experimental models of pancreatic end-to-end anastomosis, including ductal end-to-end anastomosis (with or without stent) and pancreaticojejunostomy, using mongrel dogs, with a view to evaluating reconstructive procedures after segmental pancreatectomy. We examined macroscopic findings, pancreatograms, and microangiographic and histopathological findings to determine whether pancreatic end-to-end anastomosis was as practicable as pancreaticojejunostomy. Macroscopic findings showed no suture failure in any animal in the end-to-end anastomosis group. Pancreatography revealed obstruction of the stent tube in the stent subgroup, but good patency in the no-stent subgroup. On the imaging of the microvasculature in the end-to-end anastomosis group, proliferation of neovascular vessels and formation of communicating vessels were detected. Histopathologically, no suture failure was detected, and the viability of the pancreatic end-to-end anastomosis was confirmed. From this experiment, we concluded it that it was possible to employ pancreatic end-to-end anastomosis after segmental pancreatectomy in the clinical situation.

Anastomosis, Surgical↗

Management of a rare case of fulminant hemobilia due to arteriobiliary fistula following total pancreatectomy.

Hemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 76-year-old patient with massive hemobilia due to intrahepatic bleeding from the segment 8 hepatic artery without evidence of a true aneurysm, abscess, or metastatic disease 4 weeks following pylorus-preserving total pancreatectomy for pancreatic cancer. Gastroduodenoscopy suggested hemorrhage from the duodenojejunostomy but failed to achieve hemostasis, and the patient underwent exploratory laparotomy. It was realized intraoperatively that the bleeding originated from the intrahepatic biliary tract. Bleeding was controlled by blocking the right hepatic bile duct with a Fogarty catheter and subsequent transarterial embolization. Computed tomography did not reveal any local liver or vascular pathology. Retrospectively, the cause of delayed profuse hemobilia was most likely a traumatic intrahepatic pseudoaneurysm following endoscopic bile duct stenting 3 weeks before the pancreatectomy. The reported case is exceptional and of particular interest because of the absence of a typical history or cause of hemobilia, preoperative misleading diagnostic results in an altered anatomic situation, and the operative management to achieve bleeding control in this emergency setting.

Acute Disease↗

Removal of a splenic artery with a large aneurysm adhered to the pancreas without pancreatectomy: report of a case.

Splenic artery aneurysms account for about 60% of all visceral aneurysms. The treatment include surgical procedures that sometimes require pancreatectomy. This report describes the case of a 64-year-old woman who had multiple splenic artery aneurysms with various visceral artery dilatations. Because there was no obvious cause for the splenic artery aneurysms and other arterial abnormalities, we suspected an anomaly of the connective tissue, which was subsequently confirmed by a postoperative histopathologic examination. Thus, we decided to remove the whole splenic artery, to eliminate the formation of any further aneurysms, as well as a splenectomy. During the operation, the largest splenic artery aneurysm was found to be adhered to the pancreas too tightly to ablate. It initially appeared that pancreatectomy would be necessary, but considering the associated risk of postoperative complications, we tried to avoid this. Thus, we cut open the aneurysm and excised it, leaving the anterior wall which was adhered to the pancreas. Our procedure proved the best way to preserve the pancreas and eliminate further aneurysmal formation.

Aneurysm↗

Total pancreatectomy for ductal carcinoma of the head of the pancreas: current status.

Because of dismal results after pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas, a review was made of patients treated by total pancreatectomy for this condition. Although the early experience with total pancreatic resection was disappointing, the results during the past decade have been encouraging. Among the forty-two patients reported on with sufficient detail for analysis the operative mortality has been 17 per cent, and the morbidity has been 21 per cent. Sixty-five per cent of these patients (20 of 30) have survived at least one year and 53 per cent (16 of 30) have lived at least two years after surgery. The management of the diabetes and pancreatic insufficiency has not been difficult. Total pancreatectomy appears to be preferable to pancreaticoduodenectomy in the treatment of ductal carcinoma of the head of the pancreas.

Aged↗