In vivo octreotide administration acutely reduces exocrine granule size in the human pancreas.

BACKGROUND: Octreotide has been found to be effective in the prevention of postoperative complications of pancreatic surgery, but the benefit of preoperative octreotide administration has not been assessed. AIMS: To evaluate the ability of octreotide in reducing the amount of digestive enzymes in the pancreas before surgery, a morphometric ultrastructural study of the gland was undertaken in patients undergoing demolitive pancreatic surgery. METHODS: Twenty-three inpatients received saline (n = 8) or octreotide (100 micrograms s.c.) before surgery either once (n = 5), or three (n = 5) or six (n = 5) times at 8-hour intervals. At surgery, biopsies of the pancreas were taken and processed for electron microscopy. Several parameters were assessed in exocrine cells by means of ultrastructural morphometry. RESULTS: A single administration of octreotide significantly reduced the exocrine granule number and the mean and total granular surface sectional area, and the ratio between granule area and cytoplasmic area. Repeated octreotide administrations were associated with partial (3 administrations) and complete (6 administrations) recovery of all parameters to control values. CONCLUSION: Preoperative administration of octreotide, the synthetic analogue of somatostatin, acutely reduces exocrine granule number and size in the pancreatic cell. This finding can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery. Such an effect is not maintained over multiple administrations of the somatostatin analogue. Possible explanations for this latter finding are discussed.

Resection in chronic pancreatitis: anastomosis with the jejunum or with the stomach?

Even in centers where the first choice in the surgical treatment of chronic pancreatitis is a derivative procedure some selected patients require resection. The most popular solution of gastrointestinal reconstruction still seems to be pancreaticojejunostomy but, the review of the reported experiences, suggests a general trend towards anastomosis with the stomach as a recent policy. A reliable comparison between pancreaticogastrostomy and pancreaticojejunostomy is difficult because the reported series are seldom related to chronic pancreatitis patients only, but are reporting mixed date concerning mainly periampullary cancer. Moreover with only one exception no prospective randomised clinical trails are available; unfortunately the positive trend in favour of pancreaticogastrostomy reported in uncontrolled studies is not confirmed in the randomized setting. Also the comparison between the experiences achieved by the present authors working in centers with different approach to the pancreatic anastomosis does not show statistical significant difference for both morbidity and mortality. In conclusion nowadays the best confidence and experience with any of the two methods represents the basis of choice.

Changes in pancreatic resection for chronic pancreatitis over 28 years in a single institution.

BACKGROUND: Because of advances in knowledge over recent years there is reason to believe that surgical attitudes towards patients with chronic pancreatitis may have changed. METHODS: Some 547 patients were treated surgically for chronic pancreatitis from 1971 to June 1998. Anastomoses were performed in 80 per cent (438 patients) and resections in 20 per cent (109 patients). Indications and type of operation were analysed, as were mortality and morbidity rates and long-term follow-up results, in patients undergoing resection both over the period as a whole and after dividing the series into two subperiods of 14 years. RESULTS: In the second 14-year period, there was a significant reduction in the percentage of resections compared with anastomoses (28 per cent (69 of 244 patients) versus 13 per cent (40 of 303); P < 0.0001), and a significant change in the type of resection with a substantial increase in resections of the head compared with those of the body and tail. Statistically significant reductions occurred in operating times, number of units of blood transfused (mean(s.d.) 4.7(3.6) versus 1.2(1.6) units; P = 0.0001) and mean hospital stay (18 versus 14 days for pylorus-preserving and 12 versus 8 days for left pancreatectomy with splenectomy; P < 0. 01); mortality and morbidity rates also tended to decrease, but not significantly. CONCLUSION: A different pattern has emerged over the years as regards both the type and number of resections performed.

Role of octreotide in the treatment of external pancreatic pure fistulas: a single-institution prospective experience.

INTRODUCTION: Octreotide was studied in the treatment of pure external pancreatic fistulas. METHODS: Eighteen cases (12 males, 6 females) were prospectively observed. Six patients (four after radical surgery for periampullary cancer, one endocrine tumor enucleation and one pancreojejunostomy in chronic pancreatitis) were treated as outpatients with octreotide alone because of low basal fistula output (mean+/-SD: 96.6+/-27.4 cc/24 h). Twelve (five radical surgery for cancer, five surgery for severe pancreatitis, one enucleation and one pancreojejunostomy) were treated as inpatients with octreotide plus total parenteral nutrition because of the high output (mean+/-SD: 448.4+/-248.2 cc/24 h). RESULTS: Ten of the 12 high-output fistulas healed in 27.8+/-27.7 days, whereas all low-output fistulas healed in 12.1+/-6.6 days. CONCLUSION: Octreotide appears useful in the treatment of external pancreatic fistulas. For optimal results to be achieved, there must be no local infection and no mechanical or anatomical obstacles to the free flow of juice.

Management of digestive tract fistulas. A review.

Digestive tract fistulas are a complex subject in terms both of classification and management. There is still a lack of firm epidemiological data regarding the their incidence, though the prognostic factors conditioning the prognosis of these patients are now well known. They are related mainly to the nutritional status of the patients and to the presence or otherwise of sepsis. Instrumental investigations should be aimed not merely at identifying the complication, but also at guiding clinicians in their choice of therapeutic management. According to the various situations arising, the treatment will be surgical, endoscopic or conservative medical. In the latter case, the clinician should establish first of all whether, as a result of the site of the fistula or the nutritional status, the patient requires total parenteral or enteral artificial nutrition, whenever possible. In those cases in which parenteral nutrition is indicated, the ideal drug with the best proven ability to shorten healing times and reduce the number of complications when used in combination with parenteral nutrition is naturally occurring somatostatin at the dose of 250 micrograms/h over 24 h. In all other cases, if the fistula is clinically important, its synthetic analogue, octreotide, should be the drug of choice and can be administered subcutaneously. The amount of octreotide administered ranges from 300 to 600 micrograms/day in 3 or 4 daily doses.

Incidence of cancer in the course of chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis patients appear to present an increased incidence of pancreatic cancer. The aim of the study was to compare the incidence of cancer, whether pancreatic or extrapancreatic, in our chronic pancreatitis cases with that in the population of our region. METHODS: We analyzed 715 cases of chronic pancreatitis with a median follow-up of 10 yr (7287 person-years); during this observation period they developed 61 neoplasms, 14 of which were pancreatic cancers. The cancer incidence rates were compared, after correction for age and gender, with those of a tumour registry. RESULTS: We documented a significant increase in incidence of both extrapancreatic (Standardized Incidence Ratio [SIR], 1.5; 95% confidence interval [CI], 1.1-2.0; p <0.003) and pancreatic cancer (SIR, 18.5; 95% CI, 10-30; p <0.0001) in chronic pancreatitis patients. Even when excluding from the analysis the four cases of pancreatic cancer that occurred within 4 yr of clinical onset of chronic pancreatitis, the SIR is 13.3 (95% CI, 6.4-24.5; p <0.0001). If we exclude these early-onset cancers, there would appear to be no increased risk of pancreatic cancer in nonsmokers, whereas in smokers this risk increases 15.6-fold. CONCLUSIONS: The risks of pancreatic and nonpancreatic cancers are increased in the course of chronic pancreatitis, the former being significantly higher than the latter. The very high incidence of pancreatic cancer in smokers probably suggests that, in addition to cigarette smoking, some other factor linked to chronic inflammation of the pancreas may be responsible for the increased risk.

Assessment and treatment of severe pancreatitis. Protease inhibitor.

From the theoretical point of view, antiproteolytic therapy would seem to be the rationale for acute pancreatitis management. Unfortunately, clinical human trials studying the role of antiproteases in the treatment of acute pancreatitis differ in several respects in terms of their basic design. As a consequence, any form of homogeneous analysis of the reported data as a whole is impossible. Considering the data emerging from a meta-analysis of five trials a rational use of antiproteases may result in a reduction of complications requiring surgery and of patient management costs only in selected cases, meaning by that severe and necrotic forms. As regards presumptive applications, over 400 patients were prospectively tested versus placebo in a double-blind trial with the aim of preventing acute pancreatitis after ERCP. The complication incidence was significantly lower among the pretreated patients; anyway, also in this field of protease inhibitor clinical application it is necessary to identify the patients with the greatest risk to develop post-ERCP acute pancreatitis. In conclusion, antiproteases can still play a role when given prophylactically or when used in the very early phases of the disease; moreover a 'multiple drugs approach' (including, for example, suitable antibiotics) seems to represent nowadays the most modern and rational treatment of acute pancreatitis.

To what extent is surgery superior to endoscopic therapy in the management of chronic pancreatitis?

The surgeon was the only figure involved in the management of chronic pancreatitis patients unresponsive to medical treatment, until a few years ago. Nowadays, because of less invasive, endoscopy offers a seductive alternative to surgery. Up to now no clinical prospective and randomized data comparing the results of the two different approaches are available. Surgery seems to be the only solution for chronic pancreatitis with duodenal stenosis and the last chance of eliminating diagnostic uncertainty. Also in the case of biliary tract involvement surgery should be regarded as the procedure of choice, inasmuch as the stenosis is benign and generally long-lasting, and endoscopic treatment would have to be repeated several times; endoscopy, in this indication, should be reserved only for patients who present contraindicating surgery conditions (such as severe jaundice, colangitis etc.); the endoscopist should assess whether to insert a stent or a naso-biliary drainage tube referring the patient back to the surgeon once good clinical conditions have been restored. Endoscopy and surgery should be regarded not as adversaries in the management of chronic pancreatitis and its complications, but as complementary procedures in an integrated approach. The maximum degree of complementarity should be achieved in the management of pseudocysts and in cases presenting severe, incapacitating pain. In selected cases endoscopy can play a definitive role. The generally good surgical outcomes, moreover, should convince endoscopists not to insist with repeated, hazardous manoeuvres in cases of failure. Particularly interesting is the possibility of performing endoscopic sphincterotomy combined with extracorporeal shock-wave lithotripsy prior to surgical treatment in cases of chronic calcifying calcific pancreatitis. The crushing of the calculi and partial clearance of the duct have simplified surgery and complete clearance of the duct in those patients receiving such treatment in our experience.

Surgical treatment of pancreatic metastases from renal cell carcinomas.

Pancreatic metastases from a renal cell carcinoma are rare and may occur long after manifestation of the primary disease. Resection of the metastases should be regarded as the best treatment. In our center, owing to the slow evolution of these secondaries, we perform resections capable of limiting the destruction of the pancreatic parenchyma as far as possible. The use of 'atypical' resections of the pancreas is characterized by a higher incidence of postoperative complications, particularly fistulas. Despite this, we believe that adjusted resection is to be advocated because of the possibility of additional remote secondaries, the shorter duration of surgery, the preservation of the glandular parenchyma and intact adjacent organs, such as duodenum, stomach, and spleen, and the fact that there have been no reports on local recurrences.

Pancreatic cystic manifestations in von Hippel-Lindau disease.

CONCLUSION: In view of the frequent absence of symptoms related to pancreatic lesions, screening tests for VHL should always include assessment of the pancreas and, considering the frequency of polycystic manifestations, VHL should always be borne in mind in the differential diagnosis of multiple pancreatic cysts, especially when occurring in young patients and in the absence of a positive history of pancreatic disease. BACKGROUND: Von Hippel-Lindau disease (VHL) is a hereditary disease transmitted with an autosomal dominant character and characterized by hemangioblastomas of the central nervous system and retina, renal tumors and cysts, and pheochromocytoma. Pancreatic manifestations of VHL are reported in the literature with incidences ranging from 16 to 29% of cases and consist mainly in cystadenomas of the serous type and in multiple cystic lesions, often with complete replacement of the gland. METHODS AND RESULTS: We report five cases of VHL with a polycystic pancreas as the main or only manifestation, all devoid of symptoms related to involvement of the pancreas, who were referred to our Pancreatic Surgery center with diagnoses of multiple pancreatic pseudocysts of undefined origin.

The role of surgery in the major early complications of severe acute pancreatitis.

The early complications of severe acute pancreatitis may constitute a dramatic clinical dilemma in the first 2 weeks of the disease, when the surgical approach is made even more difficult by failure to define the precise extent of the necrotic component of the disease. Moreover, the surgical indication itself is not always based on clear guidelines to which the clinician can refer, and this is due to factors of two types: (i) the intrinsic complexity of the pancreatitis syndrome in its early toxic stages and (ii) the difficulty in understanding the relevant information reported in the literature in this connection, which is often incomplete and based on confused terminology. While the surgical indication is universally accepted in the case of infection of the necrotic tissue (an event, however, which is by no means frequent in the early stages of severe pancreatitis), the development of multi-organ failure despite adequate intensive care is a potential indication which not all specialists go along with, at least not as regards the ideal timing of the intervention. Other surgical indications which have emerged are evidence of complete rupture of the main pancreatic duct and the presence of very extensive sterile necrosis. As things stand at present, however, we are witnessing a general tendency to postpone surgery, since delayed surgery is associated with a lower incidence of complications than is the case with early surgery. If, as is known, the role of surgery is aimed mainly at the treatment of superinfections and severe multi-organ failures, targeted antibiotic prophylaxis and earlier, more complete anti-enzymatic therapy may, as suggested by a number of pilot studies, offer a promising alternative to invasive procedures which are sometimes risky, though indispensable, in an attempt to save patients who would otherwise have no chance of survival.

Somatostatin analogues and pancreatic fistulas.

Consideration is given to the characterisation of pancreatic fistulas (PFs), the rationale for their treatment, and supportive and specific treatment measures. Choice of treatment should be based not only on the percentage of closures achieved, but also on their time and cost. The combined use of parenteral nutrition (TPN) and somatostatin inhibits pancreatic secretion well; no therapy can inhibit it completely. Presumptive use of octreotide, a subcutaneous formulation of somatostatin, in patients undergoing elective pancreatic surgery, reduced postoperative complications, mainly PFs, in about 500 patients in two controlled double-blind clinical studies, confirming the use of octreotide both in prophylaxis and treatment. Octreotide has been tested on out-patients after a brief hospitalisation period, at a dose of 100 mg three times a day. Home treatment does not involve co-administration of TPN, thus lowering not only costs but also risks. Optimal doses and the types of fistula amenable to this therapy need to be established and we only use out-patient treatment for chronic low-output fistulas.

[Closed surgical treatment in acute severe pancreatitis]. / Il trattamento chirurgico chiuso della pancreatite acuta severa.

Between 1976 and 1994, 318 patients underwent surgical closed retro-endoperitoneal drainage and post-operative lavage for acute necrotizing severe pancreatitis. The main indication was sepsis (66.4%). The ratio between operated on and the overall number of observed patients has been progressively shifting towards medical treatment. Furthermore in the operated group the timing of surgery has been delayed step by step. The Authors discuss improvements in the understanding of the etiological and therapeutical aspects of the disease which has had a better outcome in recent years, survival rate of 91.4%. The personal option for the closed surgical approach is based on the progressive improvement of the technique and on the good results obtained both in terms of mortality and associated morbidity; as regards the latter problem the open techniques seems to be related to a higher complication rate than the closed one.