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The maxillary sinus floor elevation procedure has gained popularity with predictable results, and is a safe, acceptable technique for bone augmentation, providing a base for dental implant treatment. Faint radiopaque lesions at the base of the maxillary sinus are frequent diagnoses on radiographs and must be identified during dental implant planning. The use of autografts, xenografts, allografts, and alloplasts or a combination between them has been demonstrated to be effective for increasing bone height and bone volume in maxillary sinus. The objective of this study was to evaluate the outcome of subjects with considerable sinus membrane pathology (test group) undergoing maxillary sinus floor augmentation using Platelet Rich Fibrin (PRF) as a filling material, in association with the Bio-Oss and Sint-Oss and simultaneous implant placement in a one-stage surgical procedure. All patients reported no pain to percussion, no sign of tissue suffering to the soft peri-implant tissues, the presence of an optimal primary stability of the inserted implants, and the increase in the peri-implant bone density. No complications were encountered during follow-up periods in these patients, including no negative evolution in the sinusitis and all implants are functioning successfully. In conclusion, the use of PRF and Piezosurgery reduced the healing time, favoring optimal bone regeneration and allowing sinus membrane integrity to be maintained during surgical procedures, according to evidence-based dentistry.

Purpose Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696). Patients and Methods Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m2 weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2 added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral α .05, 355 events were needed and 400 patients planned. Results Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS ≥ 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity. Conclusion The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.

We previously identified serum creatinine values2 mg/dL (176.8 micromol/L) and pathological chest radiographs due to the presence of pleural effusions or pulmonary densifications as two early prognostic factors of life-threatening acute pancreatitis (AP). The aim of the present study was to validate their prognostic efficacy in combination.We analyzed as prognostic factors only the data obtained within 24 hours of admission in 539 cases of AP, including 163 patients (30.2%) with acute necrotizing pancreatitis (NP). Eleven patients (2%) presented with infected pancreatic necrosis, and 20 patients (3.7%) died.One hundred and nine cases (20.2%) presented pathological chest radiographs: 32 (5.9%) pulmonary densifications and 77 (14.3%) pleural effusions (18 right, 25 left, 34 bilateral). Fifty-one patients (9.5%) had serum creatinine values2 mg/dL. Pathological chest radiographs and serum creatinine values2 mg/dL were significantly associated both with mortality risk (P0.00001), with a diagnosis of NP (P0.00001), and with risk of developing infected necrosis (P0.0001). Considering positivity of either or both tests, the mortality risk sensitivity was 90% (95% confidence interval [CI] 70.7 to 98.3) with a specificity of 76% (CI 72.5 to 79.8), for the NP diagnosis the sensitivity was 60% (CI 52.5 to 67.4) and the specificity 88% (CI 85.0-91.5), whereas for the risk of infected necrosis the sensitivity was 73% (CI 42.2 to 92.6) and specificity 75% (CI 70.1 to 78.4). These data are comparable to those obtained with the Ranson or Glasgow scores at 24 hour in this patient group, with a cut-offor =3.Serum creatinine and chest radiographs are two indices capable of identifying, within 24 hour of admission, a subgroup of acute pancreatitis patients with a more severe or adverse clinical course.

The aim of the study was to establish whether correlations were discernible between calcification, smoking, and other variables--including alcohol intake--in chronic pancreatitis. A total of 637 patients with chronic pancreatitis diagnosed over the period of 1973-1989 were reviewed. Only patients who had had one or more instrumental tests (ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, plain film of the abdomen) every 3 years were included in the study. Onset of calcification was taken as the end point of the follow-up. No statistically significant correlation was found between alcohol intake and calcification. As regards smoking habits, patients were divided into two groups: nonsmokers and medium-to-heavy smokers (> or = 10 cigarettes/day). Of 637 patients, only 570 fulfilled our criteria. Three hundred seventy-six patients (66%) developed calcifications, whereas 64 (10%) already presented calcifications at the time of diagnosis. Smoking correlated with formation of calcifications (p < 0.004). The mean time to onset of calcification in smokers was 8 years as against 12 years in nonsmokers. The relative risk of calcification in smokers versus nonsmokers was 1.21 (95% confidence limits: 1.10-1.32). By the end of follow-up (17 years), 277 smokers (69%) with chronic pancreatitis had developed calcifications compared with only 93 nonsmokers (55%). The results show that, in this sample of chronic pancreatitis sufferers, smokers present a significantly increased risk of developing calcifications.

Despite recent diagnostic improvements and the possibility of benefiting from a more sophisticated form of intensive therapy, acute pancreatitis (AP) is still a major clinical problem with an overall mortality rate of 10 %, as has been the case now for the past 40 years or so [1,2].

Acute pancreatitis, like most conditions whose etiology and pathogenesis are not fully understood in detail, is not easily amenable to a satisfying and comprehensive classification. Generally speaking, some diseases are classified according to a staging which is the result of essentially “morphologic” or “pathologic” data; this is the case, for example, with cancer whose classification is aimed at a detailed description of the “intensity” and of the anatomical extension of the disease. On the other hand, one can focus on “clinical” issues classifying the disease according to the severity of the clinical conditions of the individual patient. In fact the latter assumes that the clinical conditions of a given patient suffering from AP are the actual effects of the pancreatitis itself, without considering that a high APACHE score could also be attained in a patient with an anatomically mild pancreatitis and inherited or acquired conditions reducing the physiological reserves of various organs.

The past decade has witnessed a steady increase in surgical operations on the pancreas for a variety of diseases. This has transformed the external pancreatic fistula (EPF) from a rare complication into a relatively frequent event: fistulas are a complication to be expected in any surgical procedure on the gland [1, 2].

The development of infective complications in patients with acute pancreatitits and pancreatic fistula is an unfavorable prognistic factor [1–4]. These complications are frequent (from 1 % [4] to 29 % [ 1]) and imply a high rate of morbidity and mortality [2–4]. The therapeutic management of such infections has been the subject of previous reviews [5–7]; however, the problem of the selection of appropriate antimicrobial agents in acute pancreatitis and its complications has not recently been addressed specifically, although new antibiotics have been introduced which are potentially useful for this indication. The present article summarizes the pharmacokinetic data on the penetration of antibiotics in pancreatic tissue and reviews the current information on the bacterial strains involved in this disease.

The possibility of exerting some kind of effect, whether pharmacologically or otherwise, on exocrine pancreatic secretion dates back to the time when the very first ideas regarding pancreatic physiology were proposed. In actual fact, our knowledge of the complexity of the mechanisms regulating pancreatic function has run parallel to the discovery of substances, mainly hormones, capable of inhibiting or potentiating such function. Moreover, the search for compounds or other measures capable of inhibiting pancreatic secretion is also the result of attempts to deal with diseases such as acute pancreatitis and external pancreatic fistulas, in which inhibition of secretion is the therapeutic goal. It is no accident that all drugs potentially capable of inhibiting pancreatic secretion have been tested to confirm their therapeutic and clinical validity in these diseases. It thus appears only logical to include a chapter on the subject in this monographic study.

Three paths have been followed in the attempt to propose the ideal treatment for acute necrotic-hemorrhagic pancreatitis (ANHP): Conservative surgical treatment, Medical treatment, Radical surgical treatmen.

The therapy of acute necrotic pancreatitis is chiefly surgical, but medical treatment of the associated shock and nutritional deficiences, and the reduction of pancreatic secretions are generally claimed as helpful or even life saving.

Radiographic Study of the Anatomy of the Pancreas.- Elements of Surgical Anatomy of the Pancreas.- Physiologic Control of the External Pancreatic Secretion in Man.- Pancreatic Malfunction - When, How, Why?.- Pancreatic Extracts in Chronic Pancreatitis: Which, How and When?.- Radiological Approach to Acute and Chronic Pancreatitis.- Diagnostic Algorithm for Pancreatic Disease.- Morphogenesis of Acute Pancreatitis.- The Role of Total Parenteral Nutrition in the Treatment of Pancreatic Diseases.- Conservative Surgical Treatment of Acute Necrotic-Haemorrhagic Pancreatitis.- Pancreatic Abscess.- One-Year Follow-Up to Acute Necrotic-Haemorrhagic Pancreatitis.- Surgical Treatment of Acute Pancreatitis.- Surgical Treatment of Acute Pancreatitis.- Morphology of Chronic Pancreatitis.- Indications for Surgical Treatment of Chronic Pancreatitis.- Intraoperative Cytodiagnosis in Pancreas Disease.- General Remarks to Chapters 19-21.- The Pancreas-jejunal shunts.- The Use of Resection in the Treatment of Chronic Pancreatitis.- Chronic Pancreatitis: Surgical Indications, Procedures and Limitations.- Long Term Results of Pancreaticoduodenalresection (PDR) in Chronic Pancreatitis.- The Endocrine Function of the Pancreatic Residue After Partial Duodenopancreatectomy.- Follow-up of Chronic Pancreatitis. Methodological Considerations.- Longterm Evolution of Chronic Pancreatitis: The Italian Experience.

Opinions about the natural history of the pancreas years after an attack of necrotizing hemorrhagic pancreatitis (NHP) are contradictory. One side suggests development towards chronic pancreatitis, the other rejects this. In this study we want to evaluate the course of the disease according to functional and clinical findings. Thirty-one patients operated on because of NHP were followed up over a period of 1–5 years. The results of this study were partly published in 1984 [1].

Lactoferrin is one of the most represented and important bioactive proteins in human and mammal milk. In humans, lactoferrin is responsible for several actions targeting anti-infective, immunological, and gastrointestinal domains in neonates, infants, and young children. Evidence-based data vouch for the ability of supplemented lactoferrin to prevent sepsis and necrotizing enterocolitis in preterm infants and to reduce the burden of morbidity related to gastrointestinal and respiratory pathogens in young children. However, several issues remain pending regarding answers and clarification related to quality control, correct intakes, optimal schedules and schemes of supplementations, interactions with probiotics, and different types of milk and formulas. This review summarizes the current evidence regarding lactoferrin and discusses the areas in need of further guidance prior to the adoption of strategies that include a routine use of lactoferrin in neonates and young children.

Cigarette smoking is associated with a higher risk of developing chronic pancreatitis (CP) and increases the likelihood of developing pancreatic calcifications. The aim of this study was to know whether smoking cessation modifies the course of the disease.Patients with CP who had been followed up for more than 6 years from clinical onset and who had not developed calcifications after 5 years were analyzed. We studied smokers, never-smokers, and patients who had given up smoking within 5 years. For actuarial analysis, the sixth year was considered as time 0.Of the 360 patients, there were 43 women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was 19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients, hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212 patients (59.8%) developed calcifications. Concerning the risk of calcifications, never-smokers and ex-smokers had similar actuarial curves, and these were significantly different from the curve for smokers (P0.003). Considering never-smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0% confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10 cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P0.019), patients smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79 (95.0% CI, 1.1-2.9; P0.019). Alcohol cessation seems to have no influence.Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.

Management of the pancreatic stump following pancreaticoduodenectomy (PD) has always been a main source of concern among pancreatic surgeons. The present pilot study describes the reconstructive technique of anterior transgastric pancreaticogastrostomy (PG) after pylorus-preserving PD. Outcome in 50 patients with "soft" residual parenchyma treated with this technique is also reported. The average duration of the intervention was 351 minutes (range, 240-360); only two patients needed intraoperative transfusion with 2 units of blood. The postoperative period involved complications in 15 cases (30%). In particular, four patients developed pancreatic fistulas (8%), which were grade C in three cases (6%) and grade B in one patient (2%). Two patients (4%) presented with enteric fistula from erosion from a drain. Two patients experienced perianastomotic fluid collections associated with delayed gastric emptying (4%) and a clinically silent 5-cm abdominal collection was observed in an additional case. Bleeding of a gastric ulcer was treated in one case and four patients developed bronchopneumonia. None of the complications required a second surgical intervention and there were no deaths. One patient with a symptomatic fluid collection was treated by ultrasound-guided cutaneous drainage. The mean hospitalization time was 11.1 days (range, 8-25 days). The results obtained in this pilot study appear encouraging and merit further analysis in a randomized comparative trial.

Background Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. Patients and methods 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). Results Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. Conclusions Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.

Background In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the ‘gold standard’ imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. Patients and methods Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. Results SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. Conclusions Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.

Twenty percent of all acute pancreatitis patients present with necrotizing pancreatitis. Infected necrosis is responsible for 80% of deaths in the course of the disease though, thanks to antibiotic prophylaxis, the infection rate is decreasing. When infection occurs, the prognosis is poor, and the need for debridement and drainage of the necrosis is mandatory. The aim of this study was to review the most recent literature in order to present an update of open surgical management of infected necrosis.

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.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.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.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.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.

Background Mortality in severe pancreatitis is as high as 40% if infected pancreatic necrosis supervenes. Whenever possible prevention of infection has become the relevant end point for pancreatologist researchers. The ‘ideal’ drug should be characterised by a specific activity against the bacteria known to be responsible for infected pancreatic necrosis and be able to penetrate the pancreas in sufficient concentrations. Methods Several studies strongly suggest the rational background to antibiotic choice. To date there have been eight prospective trials and one each on selective decontamination and enteral nutrition. Results Three of the eight were carried out in the mid-1970s and show disappointing results but using drugs now known as not able to penetrate the gland and unsuitable against the usual flora involved. All the other studies report a significant reduction of infected necrosis and pancreatic abscess incidence during severe pancreatitis apart from the only one in which mortality seems to be significantly influenced. Discussion Among the several options aimed at reducing infected pancreatic necrosis and pancreatic abscess the prophylactic use of antibacterial drugs is the only one to be tested up to now in more than one prospective and randomised trial. Strong consideration should be given to treating patients with severe pancreatitis with broad-spectrum antibiotics.

Septic complications owing to infection of necrotic areas are the main cause of mortality during severe acute pancreatitis. The necrotic tissue, originally sterile, constitutes an ideal pabulum for se

Naturally occurring somatostatin and, even more so, its analogue, octreotide, by virtue of its greater manageability, are used extensively today in various pancreatic and gastrointestinal disorders, where their potent secretion-inhibiting capacity is exploited. In a number of conditions such as pancreatic fistulas the beneficial efficacy of the hormone is now definitely established both for therapeutic and for prophylactic purposes, whereas, in the other disease areas analyzed here, its use appears to be as an adjuvant to more specific and more radical procedures. Future clarification as to indications, dosage regimens and treatment times may reveal more strictly curative uses of octreotide in its own right, though, even as things stand at present, its efficacy as a complementary measure is so self-evident as to prompt its inclusion in treatment schedules both for enterocutaneous fistulas and for ascites and pancreatic pseudocysts.

Background: Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their biological features have been scarcely investigated. Aim: To compare clinical and pathological features of resected non-functioning sporadic CPETs (NF-CPETs) with solid pancreatic endocrine tumors (SPETs) in a single-institution experience. Methods: All patients with a pathologically confirmed diagnosis of sporadic non-functioning pancreatic endocrine tumors who underwent curative resection between 1990 and 2008 were included. A comparison of demographic, clinical and pathological characteristics between CPETs and SPETs was made. Univariate and multivariable analyses were performed to identify preoperative predictors of carcinoma (non-functioning pancreatic endocrine carcinoma). Results: Twenty-one (11.5%) patients with a histological diagnosis of NF-CPET were identified. The median age was 60 years (IQR 46.5–73.5 years) and a diagnosis of carcinoma (non-functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the comparison with NF-SPETs, no differences were found in terms of gender (p = 0.75), age (p = 0.81), presenting symptoms (p = 0.43), localization of the tumors (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning pancreatic endocrine carcinoma was significantly lower in the NF-CPET versus the NF-SPET group (14.3 vs. 40.4%, p = 0.04). By univariate analysis, preoperative predictors of non-functioning pancreatic endocrine carcinoma included the presence of symptoms (OR 3.96, 95% CI 2.06–7.63) and an increase in the absolute value of radiological diameter (OR 1.05, 95% CI 1.03–1.07). A cystic morphology of the lesion turned out to be a negative predictor of carcinoma (OR 0.25, 95% CI 0.70–0.87). These results were confirmed by multivariable analysis. Conclusions: NF-CPETs have a measurable propensity to be benign. In those patients affected by small and asymptomatic NF-CPET a more conservative surgical approach or a follow-up policy could be considered.

Parenchyma-preserving resections (PPRs), including enucleation and middle pancreatectomy (MP), are accepted procedures for insulinomas, but their role in the treatment of nonfunctioning pancreatic endocrine tumors (NF-PETs) is debated. The aim of this study was to evaluate perioperative and long-term outcomes after PPRs for NF-PETs.All patients who underwent PPRs for NF-PETs between 1990 and 2005 were included. Patients with multiple endocrine neoplasia type 1 were excluded.Overall, 50 patients (23 men, 27 women, median age 59 years) underwent 26 enucleations and 24 MP. A total of 58\% of NF-PETs were incidentally discovered. Median size of the tumors was 13.5 mm with no preoperative suspicion of malignancy in all patients. Overall morbidity and pancreatic fistula rates were 58 and 50\%, respectively. Reoperation rate was 4\%, with no mortality. Postoperative complications were higher in the MP group. At pathology, there were 34 (68\%) benign lesions, 13 (26\%) neoplasms of uncertain behavior, and 3 (6\%) well-differentiated carcinomas. Forty-one patients (82\%) had tumors < or =2 cm in size. Only eight patients (16\%) had at least one lymph node removed. After a median follow-up of 58 months, no patient died of disease. Overall, four patients (8\%) experienced tumor recurrence after a mean of 68 months. The incidence of exocrine/endocrine insufficiency was 8\%.PPRs are generally safe and effective procedures for treating small NF-PETs. However, better selection criteria must be identified, and lymph node sampling should be performed routinely to avoid understaging. Long-term follow-up evaluation (>5 years) is of paramount importance given the possible risk of late recurrence.

Background Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease. Methods Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test. Results The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0·028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P < 0·001). Exocrine insufficiency was more common after PD (P < 0·001) and LP (P = 0·009) than after AR. The probability of developing both endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0·001). Conclusion Different pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications.

Non-functioning pancreatic endocrine tumours (NF-PETs) are an aggressive gastroenteropancreatic neoplasm. The present study assessed survival, value of World Health Organisation (WHO) classification and prognostic utility of clinicopathological parameters at diagnosis.From 1990 to 2004, 180 patients with NF-PETs were entered in a prospective database, and predictors of prognosis were tested in uni- and multivariate models.There were 25 (14%) benign lesions, 38 (21%) neoplasms of uncertain behaviour, 100 well-differentiated carcinomas (56%) and 17 poorly differentiated carcinomas (9%). Radical resection was possible in 93 cases (51.6%). Overall 5-, 10- and 15-year survival rates were 67%, 49.3% and 32.8%, respectively, and were significantly higher in radically resected patients (93%, 80.8% and 65.2%, respectively; P0.00001). By multivariate analysis, poor differentiation [hazard ratio (HR) 7.3; P = 0.0001], nodal metastases (HR 3.05; P = 0.02), liver metastases (HR 3.29; P = 0.003), K(i)-675% (HR 2.5; P = 0.012) and weight loss (HR 3.06; P = 0.001) were significantly associated with mortality.This study confirms the good long-term survival of patients with NF-PETs and the prognostic value of WHO classification, liver metastases, poor differentiation, Ki-67, nodal metastases and weight loss. These latter two parameters have a prognostic value similar to that of liver metastases and Ki-67.

In recent years, there has been a marked increase of incidentally discovered cystic and endocrine neoplasms of the pancreas.1,2 Although the natural history of these lesions is unclear, the malignant potential of some of them is well known and this has led to more pancreatic resections.1–3 In this setting, neoplasms in the neck or in the proximal body of the pancreas represent a challenge for surgeons and are usually treated by either an extended right or, most often, an extended left pancreatectomy. These extended resections performed for a benign or borderline neoplasms result in removal of normal pancreatic tissue, increasing the risk of loss of exocrine and endocrine function.4–6 While enucleation is an option in some of these lesions, it should be avoided in neoplasms embedded deep in the substance of the gland, in those measuring more than 2 cm, and when neoplasms are not clearly benign and margins cannot be compromised.7,8 Middle pancreatectomy (MP), also known as central or medial pancreatectomy, has been proposed as an alternative technique in these cases, preserving pancreatic parenchyma and reducing the risk of exocrine and endocrine insufficiency.4,7–11 Since 1984, when Dagradi and Serio performed the first MP with an oncologic indication,12 nearly 200 cases have been reported,5,9 with only one collective series describing more than 50 patients.13 Because of the small number of cases and the short follow-up of most of these patients, both oncologic and functional long-term results of MP have not been clearly defined. The primary endpoint of this study is to describe a large series of MP from 2 high-volume centers for pancreatic surgery, analyzing indications, operative morbidity, and long-term results regarding tumor recurrence and exocrine and endocrine function. To better evaluate the latter, we compared these outcomes with a control group that underwent extended left pancreatectomy (ELP) during the same time period.

We report an interesting case of a patient with neither family nor personal history for pancreatic diseases that was admitted to our department in 1982, at the age of 25 years. At that time, medical history, absence of alcohol abuse, and radiological imaging suggested a diagnosis of idiopathic chronic pancreatitis. The patient underwent a left-pancreatectomy, with histological confirmation of chronic pancreatitis. He was asymptomatic until 1988, when episodes of pain arose, requiring a pancreatico-jejunostomy. No further problems ensued until 2004 when radiological investigation following pain-related symptoms revealed enormous dilation of the pancreatic duct. A pylorus-preserving pancreaticoduodenectomy resulting in total pancreatectomy was performed. Histological examination revealed an intraductal papillary mucinous non-invasive carcinoma. Review of the previously resected specimen revealed former misdiagnosis. This tumour usually affects an elderly population and nowadays is recognised as a possible cause of chronic obstructive pancreatitis. This report represents a slippery case of misdiagnosis and demonstrates that follow-up is always mandatory following a diagnosis of idiopathic chronic pancreatitis.

Although surgical resections of metastatic lesions to the liver, lungs, and brain improve survival and quality of life, management of pancreatic metastases has not been defined clearly. Over the past few years, however, an improvement in morbidity and mortality after surgical resection of the pancreas has enabled patients with metastatic disease to be treated with radical intent. 3,4 We present a patient with pancreatic metastasis from a leiomyosarcoma of the broad ligament of the uterus, and discuss the clinical features of pancreatic metastases and possible surgical indications.

Intraductal papillary mucinous neoplasms (IPMNs) may present with clinical and radiological pictures resembling those of chronic pancreatitis (CP).To compare the clinical and epidemiological characteristics of patients suffering from CP with those of patients suffering from IPMN. To assess whether CP is associated with an increased risk of developing IPMN.In our departments, from 1981 to 1998, we prospectively followed 473 patients suffering from CP, including 93 cases of chronic obstructive pancreatitis (COP), and 45 patients with a histologically confirmed diagnosis of IPMN. Another 6 patients had an initial diagnosis of CP and a subsequent diagnosis of IPMN.Patients with IPMN were more often female (females 53 vs. 15%; p0.001), were older (mean age 63.1 vs. 42.8 years; p0.001), drank less alcohol (19 vs. 107 g/day; p0.001) and smoked fewer cigarettes (mean 8 vs. 21 cigarettes/day) than CP patients. These results were also confirmed when considering only patients with COP. The 6 patients with a subsequent diagnosis of IPMN were males (p n.s.) with a mean age of 51.4 years (p0.05). Only 1 patient was a drinker (p0.05) and 4 were smokers (p n.s.). Comparing CP and IPMN, logistic regression analysis selected sex, age, alcohol and smoking, whereas only sex and age were selected when comparing COP vs. IPMN.In general patients with IPMN present different epidemiological characteristics than those with CP and the subgroup with COP. The clinical and pathological features suggest that in most cases IPMN is the cause of CP and not vice versa.

Objective: To compare the results of pancreaticogastrostomy versus pancreaticojejunostomy following pancreaticoduodenectomy in a prospective and randomized setting. Background Data: While several techniques have been proposed for reconstructing pancreatico-digestive continuity, only a limited number of randomized studies have been carried out. Methods: A total of 151 patients undergoing pancreaticoduodenectomy with soft residual tissue were randomized to receive either pancreaticogastrostomy (group PG) or end-to-side pancreaticojejunostomy (group PJ). Results: The 2 treatment groups showed no differences in vital statistics or underlying disease, mean duration of surgery, and need for intraoperative blood transfusion. Overall, the incidence of surgical complications was 34% (29% in PG, 39% in PJ, P = not significant). Patients receiving PG showed a significantly lower rate of multiple surgical complications (P = 0.002). Pancreatic fistula was the most frequent complication, occurring in 14.5% of patients (13% in PG and 16% in PJ, P = not significant). Five patients in each treatment arm required a second surgical intervention; the postoperative mortality rate was 0.6%. PG was favored over PJ due to significant differences in postoperative collections (P = 0.01), delayed gastric emptying (P = 0.03), and biliary fistula (P = 0.01). The mean postoperative hospitalization period stay was comparable in both groups. Conclusions: When compared with PJ, PG did not show any significant differences in the overall postoperative complication rate or incidence of pancreatic fistula. However, biliary fistula, postoperative collections and delayed gastric emptying are significantly reduced in patients treated by PG. In addition, pancreaticogastrostomy is associated with a significantly lower frequency of multiple surgical complications.

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan–Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for ≤ 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P 2% vs 90.1% for ≤ 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for ≤ 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.

Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms that have been the object of few studies that have involved only small numbers of patients. This study was carried out to obtain a comprehensive and up-to-date clinical picture of these tumors.A total of 184 patients with NFPT admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis of NFPT was confirmed histologically using conventional and immunohistochemical techniques. Data were obtained from the medical charts or directly from the patients.There were 85 men (46.2%) and 99 women (53.8%). The mean age at diagnosis was 55.2 yr (range 17-82 yr). The percentage of smokers and alcohol drinkers was similar to that in the general population. Seven patients (3.9%) had a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the diagnosis was made after workup for pain or other symptoms, in the remaining 64 cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group survival was significantly greater than it was for the symptomatic patients (p=0.0043). Survival was also found to be improved by tumor resection (p0.0001), absence of metastases (p0.0001), and small tumor size (or =3 cm) (p0.0007).NFPTs were slightly more frequent in women and were diagnosed most often in middle-aged individuals. No risk factors other than a family history of exocrine pancreatic carcinoma were found. Tumor discovery while patients were still asymptomatic, tumor resection, absence of metastases, and tumor sizeor =3 cm significantly prolonged survival.

Gastrointestinal fistulae most frequently occur as complications after abdominal surgery (75-85%) although they can also occur spontaneously--for example, in patients with inflammatory bowel disease (IBD) such as diverticulitis or following radiation therapy. Abdominal trauma can also lead to fistula formation although this is rare. Postoperative gastrointestinal fistulae can occur after any abdominal procedure in which the gastrointestinal tract is manipulated. Regardless of the cause, leakage of intestinal juices initiates a cascade of events: localised infection, abscess formation and, as a result of a septic focus, fistulae formation. The nature of the underlying disease may also be important, with some studies showing that fistula formation is more frequent following surgery for cancer than for benign disease. Fistula formation can result in a number of serious or debilitating complications, ranging from disturbance of fluid and electrolyte balance to sepsis and even death. The patient will almost always suffer from severe discomfort and pain. They may also have psychological problems, including anxiety over the course of their disease, and a poor body image due to the malodorous drainage fluid. Postoperative fistula formation often results in prolonged hospitalisation, patient disability, and enormous cost. Therapy has improved over time with the introduction of parental nutrition, intensive postoperative care, and advanced surgical techniques, which has reduced mortality rates. However, the number of patients suffering from gastrointestinal fistulae has not declined substantially. This can partially be explained by the fact that with improved care, more complex surgery is being performed on patients with more advanced or complicated disease who are generally at higher risk. Therefore, gastrointestinal fistulae remain an important complication following gastrointestinal surgery.

Introduction: In the general population, cholecystectomy, diabetes, and chronic pancreatitis seem to be associated with an increased risk of developing pancreatic cancer. Aims: We assessed whether previous cholecystectomy, gastrectomy, or diabetes mellitus may be risk factors for pancreatic cancer in patients with chronic pancreatitis. Methodology: We analyzed 853 patients with chronic pancreatitis (110 women, 743 men) with a median follow-up period of 14 years with particular reference to establishing which patients had previously undergone cholecystectomy or distal gastric resection (Billroth II anastomosis) or had diabetes or gallstone disease and the respective time scales involved. Results: Pancreatic cancer developed in 17 patients with chronic pancreatitis after a median period of 8 years from onset of pancreatitis symptoms (range, 3-38 years). Excluding two cholecystectomies performed 1 year before diagnosis of cancer, cholecystectomy was performed in 7/17 (41%) patients with pancreatic cancer and in 381/836 (46%) of the other patients with chronic pancreatitis. Forty-nine (10%) patients with chronic pancreatitis and no pancreatic cancer had undergone cholecystectomy during the years before the onset of chronic pancreatitis, whereas none of the patients in whom a pancreatic malignancy developed had undergone cholecystectomy before the onset of chronic pancreatitis symptoms. Gastrectomies were performed in 116 patients (14%), 47 before the onset of chronic pancreatitis. Only 2/17 patients with pancreatic cancer had undergone previous gastrectomy, though in both cases only shortly before diagnosis of the cancer. Diabetes was diagnosed in 353 patients, but only in 30 (4%) before onset of chronic pancreatitis. Only 1/17 patients (6%) with pancreatic cancer had long-standing diabetes, whereas diabetes developed in 3/17 shortly before diagnosis of pancreatic cancer. Conclusions: Cholecystectomy, gastrectomy, and diabetes are not major risk factors for the development of pancreatic cancer in patients with chronic pancreatitis.

Because the mortality of severe pancreatitis is higher when infected necrosis supervenes, prevention of infections has become a relevant endpoint for management. The "ideal" drug should be characterized by specific activity against the bacteria known to be responsible for infection and should be able to penetrate the gland in a sufficient concentration. To date there have been eight prospective trials with antibiotics, one on selective digestive decontamination, and others with enteral nutrition. A meta-analysis regarding experiences with antimicrobial drugs reports a significant reduction in the incidence of infected necrosis and pancreatic abscesses during severe pancreatitis. In conclusion, among the several options aimed at reducing infections during necrotizing pancreatitis, the prophylactic use of antibacterial drugs is the only one to have been tested to date in several randomized studies. Strong consideration should be given to treating patients with severe pancreatitis with broadspectrum antibiotics, selective digestive decontamination, and enteral nutrition.

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.

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.

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.

Radical resection of ductal adenocarcinoma of the pancreas affords the only realistic chance of cure. Despite some reports, in particular from Japan, suggesting an improvement in the long-term prognosis, this is true only in subgroups of selected patients. In actual fact, the overall long-term survival of resected patients is still below 10%. How meaningful is a more extended resection? The lack of randomized prospective trials involving a sufficient number of cases does not enable us to make any final conclusions. The only controlled data, recently reported by an Italian multicenter study, suggested that extended lymphadenectomy improved prognosis not in the whole population of resected patients, but only in a subgroup of patients with lymph node involvement. No definitive judgments can be made without further prospective controlled clinical trials involving a greater number of patients. The suspicion arises that surgery alone, even when extensive, may not be the best treatment for pancreatic ductal cancer.

A different stage grouping of TNM factors can improve the predictivity of the UICC TNM classification for pancreatic cancer. Nevertheless, the Japanese Pancreas Society (JPS) classification maintains a higher prognostic value.The use of a reliable staging classification facilitates the evaluation of anticancer treatments and the correct management of patients. The aim of the present study was to evaluate the prognostic value of three modified UICC TNM classifications, obtained by different stage grouping of the UICC TNM factors, comparing their predictivity to the standard UICC and the JPS classifications.Clinical material consisted of 228 patients who underwent resection for pancreatic cancer. The reliability of the classifications was analyzed by the following methods: univariate analysis of stage survival curves; multivariate analysis of each classification after adjusting for grading and radicality; and correlation between the patients' distribution in the stages of each classification and in survival classes.The following modified UICC classification allowed a better differentiation of stage II and III survival (P = 0.08) than standard UICC (P = 0.74): stage I: T1N0M0; stage II: T1N1M0/T2N0M0: stage III: T2N1M0/T3 any NM0; stage IV: M1. The JPS classification better discriminated between the different stages (P0.001). All classifications had an independent prognostic value by multivariate analysis. The correlation between stages and survival classes was higher for the JPS classification than either UICC TNM classification or the modified UICC classifications.

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.