E. Caldiron

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.

Prospective randomised pilot study of management of the pancreatic stump following distal resection

Background Numerous surgical techniques have been described in the literature for pancreatic stump management following left resection, but there is only one prospective, randomised study. A prospective randomised pilot study was designed to assess five different pancreatic stump management techniques after distal resection in an attempt to identify which was the most effective in terms of complications and ease of execution. Methods Sixty-nine consecutive patients were randomly assigned to five different treatment groups: manual suturing, suturing plus fibrin glue, suturing plus polypropylene mesh, pancreaticojejunostomy and suturing with a stapler. All presented a soft residual pancreas. Results The overall incidence of pancreatic fistula was 19%, ranging from 7% to 33% in the different treatment groups. None of the techniques Significantly reduced the incidence of postoperative complications. Discussion On weighing the complications observed against ease and speed of execution, the construction of a pancreaticojejunostomy and closure of the stump with a mechanical stapler may be regarded as the procedures to be tested in future.

Pancreatic cystic manifestations in von Hippel-Lindau disease

SummaryConclusionIn 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.BackgroundVon 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 ResultsWe 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.

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.

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

Abstract 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.

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.

Management of Digestive Tract Fistulas

: 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.

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 µg 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.

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.

Assessment and Treatment of Severe Pancreatitis

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.