Evaluation of lanreotide effects on human exocrine pancreatic secretion after a single dose: preliminary study.

BACKGROUND: Total parenteral nutrition and somatostatin or analogues represent a consolidated therapeutic approach for external fistulas, a frequent complication of major pancreatic surgery. AIMS: To establish the effects of the somatostatin analogue lanreotide on exocrine pancreatic secretion. METHODS: Eight patients, undergoing pancreaticoduodenectomy for malignancy, were enrolled in the trial. The volume and composition of pancreatic secretion were evaluated after one single subcutaneous injection of lanreotide 0.5 mg or placebo in a randomised, double-blind cross-over trial. RESULTS: In the seven patients completing the study, the 24-h output volume was 208.6+/-41.3 and 253.9+/-72.4 ml after lanreotide and placebo, respectively. During the first 6 hours values were 48.1+/-14.7 and 77.6+/-21.4 ml (p=0. 02). No significant difference between treatments was detected in the qualitative composition of 24-h pancreatic secretion, although bicarbonate secretion remained lower after the active drug at all the observation intervals. Peak lanreotide levels were detected 15-30 min after drug injection. Clinical and laboratory tolerability was good. CONCLUSIONS: Lanreotide induced a statistically significant reduction in the output volume with respect to placebo in the first 6 hours after administration, but not thereafter. The present results encourage a new study to be undertaken in a larger sample and with a multiple dosing scheme of treatment.

A single-institution experience with fistulojejunostomy for external pancreatic fistulas.

External pancreatic fistulas resistant to medical treatment are an indication for surgery. Over the period from May 1986 to March 1999, we operated on 17 patients suffering from a stabilized external pancreatic fistula as a result of surgical treatment for severe acute pancreatitis in 12 cases, chronic pancreatitis in 3, duodenopancreatectomy in 1, and islet cell tumor enucleation in 1. The surgical repair consisted of precise identification of the fistula tract around the drainage tube and its anastomosis with a Roux-en-Y jejunal loop (fistulojejunostomy). The surgical mortality was nil, and the postoperative outcome was uneventful in 12 patients. Four patients experienced surgical complications, all of which were treated conservatively. After a median follow-up of 93 months, 14 patients are still alive and healthy, 1 had died of neoplastic cachexia, and 2 were lost to follow-up. In our experience, fistulojejunostomy appears to be safe, easy to perform, and curative.

Cytoreductive surgery in advanced endocrine tumours of the pancreas.

Surgery still plays an important role even in advanced endocrine tumours of the pancreas, owing to their biological behaviour. Sometimes it is possible to attempt a radical approach, but more often only cytoreduction is feasible. In fact, when the malignancy is not completely resectable on account of vessel involvement or extensive liver metastases, surgical reduction of the tumour burden (debulking) can be proposed, aimed at improving the clinical conditions and survival of these patients. Forty-one patients suffering from advanced endocrine tumour of the pancreas were observed from 1985 to 1996. In 13 patients, the disease was locally advanced as far as concerns lymph node metastases and/or vessel involvement, while the other 28 patients presented liver metastases. In the former group, we performed 6 radical resections, in the latter we submitted 2 patients to radical resection and 12 patients to cytoreductive surgery, with complete removal of the pancreatic malignancy. The overall survival of the resected patients was 87% (7/8). Three patients (37.5%) are alive and free of disease, while the other 4 have subsequently developed liver metastases. One patient died with hepatic recurrence. Half the patients (6/12) undergoing cytoreductive surgery are alive, 3 with stable and 3 with progressive disease. The other 6 patients have died due to liver progression of the disease. As data in the literature concerning the role of debulking as regards the survival are conflicting, we have modified our surgical approach in patients with advanced disease. We perform cytoreductive surgery whenever complete removal of the pancreatic tumour is feasible. The rationale of this approach is to leave only a liver with residual disease, with a view to giving targeted adjuvant treatment.

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.

[Quality of life assessment in pancreatic carcinoma: results of an European multicentric study]. / Valutazione della qualità della vita nel carcinoma pancreatico: risultati di uno studio multicentrico europeo.

Quality of life (Qol) assessment is a mandatory endpoint of cancer clinical trials. Little research has been conducted on pancreatic cancer (Pc) and no disease specific Qol questionnaire exists. We report on the development of the European Organization for Research and Treatment of Cancer (EORTC) Pc Qol module to supplement the core cancer module (QLQ-C30). Literature research and qualitative interviews with 6 specialists and 34 patients in the UK were followed by construction of a questionnaire, a peer review by international specialists and EORTC. Administration of the QLQ-C 30, a provisional Pc module and a qualitative debriefing interview was performed on 78 patients in 8 countries stratified into groups by disease stage and treatment intention. Pretesting identified that 23/26 questions had an adequate internal reliability (Cronbach's alpha > 0.7) and construct validity (Pearson's r 0.4-0.6). The median time of completion was 12 mins. Qualitative analysis indicates that the module is easy to complete and cross culturally applicable. The EORTC QLO-PAN 26 includes 26 items covering symptoms, body image, sexuality and the emotional and social consequences of Pc. It is intended for use in patients undergoing clinical trials for pancreatic cancer including surgery, chemotherapy and radiotherapy and will allow the detection of small but clinically meaningful differences in clinical trials for Pc.

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.