Exocrine pancreatic insufficiency in adults:A shared position statement of the Italian association for the study of the pancreas

This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases associated with exocrine pancreatic insufficiency(EPI)which are of common interest to internists/gastroenterologists,oncologists and surgeons,fully aware that EPI may also occur together with many other diseases,but less frequently.A preliminary manuscript based on an extended literature search(Medline/PubMed,Cochrane Library and Google Scholar)of published reports was prepared,and key recommendations were proposed.The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012.Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached.The final draft of the manuscript was then sent to the AISP Council for approval and/or modification.All concerned parties approved the final version of the manuscript in June 2013.

Pancreatic steatosis: Is it related to either obesity or diabetes mellitus?

The accumulation of fat in the pancreatic gland has been referred to using various synonyms,such as pancreatic lipomatosis,fatty replacement,fatty infiltration,fatty pancreas,lipomatous pseudohypertrophy,non-alcoholic fatty pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis is the best description of fat accumulation in the pancreatic gland without fat replacement,and this term also describes the possibility that the fat accumulation is a reversible process.A review of the existing literature was carried out,and it was found that there was notable evidence from both the pathological and the imaging point of view that pancreatic steatosis is an increasing problem due to the increasing incidence of obesity.The conclusion was that pancreatic steatosis was easily detectable using modern imaging techniques,such as ultrasonography,endoscopic ultrasonography,computed tomography and magnetic resonance imaging.Pancreatic steatosis was not due to the presence of diabetes mellitus but was highly associated with the metabolic syndrome.The possible presence of steatopancreatitis should be better evaluated,especially regarding the inflammatory cascade,and additional studies are needed which are capable of assessing whether non-alcoholic steatopancreatitis really exists as does non-alcoholic steatohepatitis.Finally,the presence of exocrine pancreatic function should be extensively evaluated in patients with pancreatic steatosis.

Etiology of chronic pancreatitis:Has it changed in the last decade?

The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported previously. It has further conf irmed that heavy alcohol consumption and smoking are independent risk factors for chronic pancreatitis. Autoimmune pancreatitis accounts for 2%-4% of all forms of chronic pancreatitis, but this frequency will probably increase over the next few years. The rise in idiopathic chronic pancreatitis, especially in India, represents a black hole in recently published surveys. Despite the progress made so far regarding the possibility of establishing the hereditary forms of chronic pancreatitis and the recognition of autoimmune pancreatitis, it is possible that we are more inaccurate today than in the past in identifying the factors associated with chronic pancreatitis in our patients.

Is the pancreas affected in patients with septic shock?——a prospective study

BACKGROUND:Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock.This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls. METHODS:The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock All patients also underwent radiological examination to detect pancreatic abnormalities. RESULTS:The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period while the serum activity of lipase was similar to that of the control subjects.Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock.None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis CONCLUSION:The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage,and the management of these patients should be dependent on the clinical situation and not merely the biochemical results.

ERCP in acute pancreatitis:What takes place in routine clinical practice?

AIM:To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute pancreatitis sponsored by the Italian Association for the Study of the Pancreas.METHODS:Of the 1 173 patients enrolled in our survey,the most frequent etiological category was biliary forms(69.3%) and most patients had mild pancreatitis(85.8%).RESULTS:344/1 173(29.3%) underwent endoscopic retrograde cholangiopancreatography(ERCP).The mean interval between the onset of symptoms and ERCP was 6.7 ± 5.0 d;only 89 examinations(25.9%) were performed within 72 h from the onset of symptoms.The main indications for ERCP were suspicion of common bile duct stones(90.3%),jaundice(44.5%),clini cal worsening of acute pancreatitis(14.2%) and cho langitis(6.1%).Biliary and pancreatic ducts were visua lized in 305 patients(88.7%) and in 93 patients(27.0%) respectively.The success rate in obtaining a cholangio gram was statistically higher(P = 0.003) in patients with mild acute pancreatitis(90.6%) than in patients with severe disease(72.2%).Biliary endoscopic sphinc terotomy was performed in 295 of the 305 patients(96.7%) with no difference between mild and severe disease(P = 0.985).ERCP morbidity was 6.1% and mortality was 1.7%;the mortality was due to the complications of acute pancreatitis and not the endoscopic procedure.CONCLUSION:The results of this survey,as with those carried out in other countries,indicate a lack of compliance with the guidelines for the indications for interventional endoscopy.

Endoscopic sphincterotomy in acute biliary pancreatitis:A question of anesthesiological risk

Two consecutive surveys of acute pancreatitis in Italy,based on more than 1000 patients with acute pancreatitis,reported that the etiology of the disease indicates biliary origin in about 60% of the cases.The United Kingdom guidelines report that severe gallstone pancreatitis in the presence of increasingly deranged liver function tests and signs of cholangitis(fever,rigors,and positive blood cultures) requires an immediate and therapeutic endoscopic retrograde cholangiopancreatography(ERCP).These guidelines also recommend that patients with gallstone pancreatitis should undergo prompt cholecystectomy,possibly during the same hospitalization.However,a certain percentage of patients are unfit for cholecystectomy because advanced age and presence of comorbidity.We evaluated the early and longterm results of endoscopic intervention in relation to the anesthesiological risk for 87 patients with acute biliary pancreatitis.All patients underwent ERCP and were evaluated according to the American Society of Anesthesiology(ASA) criteria immediately before the operative procedure.The severity of acute pancreatitis was positively related to the anesthesiological grade.There was no significant relationship between the frequency of biliopancreatic complications during the follow-up and the ASA grade.The frequency of cholecystectomy was inversely related to the ASA grade and multivariate analysis showed that the ASA grade and age were significantly related to survival.Finally,endoscopic treatment also appeared to be safe and effective in patients at high anesthesiological risk with acute pancreatitis.These results further support the hypothesis that endoscopic sphincterotomy might be considered a definitive treatment for patients with acute biliary pancreatitis and an elevated ASA grade.

Pancreatic ductal adenocarcinoma screening:New perspectives

Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome;therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective;having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.

A prospective study on radiofrequency ablation locally advanced pancreatic cancer

BACKGROUND:Radiofrequency ablation(RFA)has been suggested as a new treatment option for patients with locally advanced cancer.This study aimed to prospectively evaluate the efficacy and safety of intraoperative RFA in patients with unresectable,locally advanced,non-metastatic carcinoma of the pancreatic head.METHODS:RFA was the first step of the surgical procedure and was carried out on the mobilized pancreatic head followed by biliary by-pass and gastrojejunal-anastomosis.Intra-and post-operative morbidity and mortality,performance status, pain control,quality of life,and survival at 24 months were evaluated.RESULTS:Seven patients(3 men and 4 women;median age 66 years,range 47-80 years)were studied and 4 were eligible for treatment.The RFA procedure was carried out in 3 of the 4 patients;in one patient it was not carried out because of the upstaging of the neoplasm.In all 3 patients RFA achieved complete necrosis of the lesion.A biliary fistula developed 7 days after the procedure in one patient;all 3 patients developed ascites 8.6 days(range 7-9 days)on average after RFA.All patients died respectively,at 3,4,and 5 months after the treatment.CONCLUSIONS:In our experience,RFA is a feasible procedure, but it presents a very high rate of postoperative complications.Moreover,pain control,life quality and survival rate are poor.The few data suggest no impact on survival.

Acute recurrent pancreatitis:An autoimmune disease?

In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with "idiopathic" pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis.

Exocrine pancreatic function assessed by secretin cholangio-Wirsung magnetic resonance imaging

BACKGROUND:Magnetic resonance cholangiopancreato-graphy (MRCP) is useful to assess exocrine pancreatic function by combining rapid imaging acquisition with the administration of secretin, a gastrointestinal hormone that stimulates the secretion of bile and pancreatic juice. However, extensive data on this method are lacking. This study aimed to determine whether MRCP with secretin administration is able to simultaneously detect alterations of both the pancreatic ducts and exocrine pancreatic function. METHODS:All subjects older than 18 years who underwent magnetic resonance imaging (MRI) and cholangio-Wirsung magnetic resonance imaging (CWMRI) for suspicion of benign or malignant pancreatic diseases from January 2006 to December 2006 were enrolled in the study. MRI and CWMRI were carried out using a dedicated apparatus. RESULTS:Eighty-seven patients (46 males, 41 females, mean age 59.7±14.6, range 27-87 years) were enrolled. Of the 87 patients, 39 had a normal pancreas on imaging, 20 had an intrapapillary mucinous tumor (IPMT), and the rest had chronic pancreatitis (7), serous cystadenoma (6), a previous attack of acute biliary pancreatitis (5), congenital ductal abnormalities (5), mucinous cystadenoma (3), previous pancreatic head resection for autoimmune pancreatitis (1), or cholangiocarcinoma (1). Morphologically, we found two pseudocysts (one of the 7 patients with chronic pancreatitis, and one of the 5 patients after an attack of acute pancreatitis;the latter pseudocyst communicated with the main pancreatic duct). Calcifications were found in 3 of the 7 patients with chronic pancreatitis. All patients with IPMT and mucinous cystadenoma and 3 patients with serous cystadenoma were histologically confirmed. The remaining patients were followed up adequately to confirm the diagnosis by imaging. According to the Matos criteria, 73 patients (83.9%) were of grade 3, 8 grade 2, 4 grade 1, and 2 grade 0. The only pancreatic diseases which impaired the exocrine pancreatic secretion stimulated by secretin were chronic pancreatitis (57.1% of the patients, grade 0-1) and the IPMT mixed type in 2 of the 4 patients was grade 1. CONCLUSION:Secretin MRCP is a useful technique to simultaneously detect the presence of alterations of the pancreatic ducts and exocrine pancreatic function.

Is diabetes mellitus a risk factor for pancreatic cancer?

The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long period of time.The importance of this topic is due to two main causes:the possible use of recent onset diabetes as a marker of the disease and,in particular,as a specific marker of pancreatic cancer,and the selection of a population at risk for pancreatic cancer.Thus,we decided to make an in-depth study of this topic;thus,we carried out an extensive literature search in order to re-assess the current knowledge on this topic.Even if diabetes is found a decade before the appearance of pancreatic cancer as reported in meta-analytic studies,we cannot select those patients already having non detectable pancreatic cancer,at least with the imaging and biological techniques available today.We believe that more studies are necessary in order to definitively identify diabetes mellitus as a risk factor for pancreatic cancer taking into consideration that approximately 10 years are needed to diagnose symptomatic pancreatic cancer.At present,the answer to the as to whether diabetes and pancreatic cancer comes first similar to the adage of the chicken and the egg is that diabetes is the egg.

Chronic pancreatitis: Maldigestion, intestinal ecology and intestinal inflammation

Exocrine pancreatic insufficiency caused by chronic pancreatitis results from various factors which regulate digestion and absorption of nutrients. Pancreatic function has been extensively studied over the last 40 years, even if some aspects of secretion and gastrointestinal adaptation are not completely understood. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption, known as steatorrhea, which consists of fecal excretion of more than 6 g of fat per day, weight loss, abdominal discomfort and abdominal swelling sensation. Fat malabsorption also results in a deficit of fat-soluble vitamins (A, D, E and K) with consequent clinical manifestations. The relationships between pancreatic maldigestion, intestinal ecology and intestinal inflammation have not received particular attention, even ifin clinical practice these mechanisms may be responsible for the low efficacy of pancreatic extracts in abolishing steatorrhea in some patients. The best treatments for pancreatic maldigestion should be re-evaluated, taking into account not only the correction of pancreatic insufficiency using pancreatic extracts and the best duodenal pH to permit optimal efficacy of these extracts, but we also need to consider other therapeutic approaches including the decontamination ofintestinal lumen, supplementation of bile acids and, probably, the use of probiotics which may attenuate intestinal inflammation in chronic pancreatitis patients.

Needle-based confocal endomicroscopy in the discrimination of mucinous from non-mucinous pancreatic cystic lesions

BACKGROUND Pancreatic cystic lesions(PCLs)are considered a precursor of pancreatic cancer.Needle-based confocal endomicroscopy(nCLE)is an imaging technique that enables visualization of the mucosal layer to a micron resolution.Its application has demonstrated promising results in the distinction of PCLs.This study evaluated the utility of nCLE in patients with indeterminate PCLs undergoing endoscopic ultrasound fine-needle aspiration(EUS-FNA)to distinguish mucinous from non-mucinous lesions.AIM To evaluate the accuracy of nCLE in indeterminate PCLs undergoing EUS-FNA to distinguish mucinous from non-mucinous lesions.METHODS Patients who required EUS-FNA between 2015 and 2017 were enrolled prospectively.During EUS-FNA,confocal imaging,analyses of the tumor markers carcinoembryonic antigen and amylase,and cytologic examination were conducted.All patients were followed for at least 12 mo and underwent laboratory testing and computed tomography scanning or magnetic resonance imaging.nCLE videos were independently reviewed by 6 observers to reach a final diagnosis(mucinous vs non-mucinous)based on criteria derived from previous studies;if there was disagreement>20%,a final diagnosis was discussed after consensus re-evaluation.The sensitivity,specificity,and accuracy of nCLE were calculated.Adverse events were recorded.RESULTS Fifty-nine patients were included in this study.Final diagnoses were derived from surgery in 10 patients,cytology in 13,and imaging and multidisciplinary team review in 36.Three patients were excluded from final diagnosis due to problems with nCLE acquisition.Fifty-six patients were included in the final analysis.The sensitivity,specificity,and accuracy of nCLE were 80%[95%confidence interval(CI):65-90],100%(95%CI:72-100),and 84%(95%CI:72-93),respectively.Postprocedure acute pancreatitis occurred in 5%.CONCLUSION EUS-nCLE performs better than standard EUS-FNA for the diagnosis of indeterminate PCL.

Exocrine pancreatic function during the early recovery phase of acute pancreatitis

BACKGROUND:Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis,but the data are scarce and conflicting.This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding. METHODS:Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their first episode of the disease.They were 75 patients including 60(80.0%)patients with mild acute pancreatitis and 15(20.0%)patients with severe acute pancreatitis. Etiologically 61 patients(81.3%)had biliary disease,1(1.3%) had alcoholic disease and 3(4.0%)had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients(13.3%).The mean(±SD)refeeding time after the attack of acute panereatitis was 11.2±10.2 days. RESULTS:Pathological values of FE-1 were found in 9 of the 75 patients(12.0%):7(9.3%)patients with mild pancreatitis and 2(2.7%)patients with severe pancreatitis(P=1.000). The frequency of the pathological values of fecal elastase-1 was significantly different from that of various etiologies of the disease(P=0.030).It was significantly lower in patients with biliary pancreatitis(9.8%;P=0.035)than in one patient with alcoholic pancreatitis(P=0.126),one patient with hypertriglyceridemia-induced pancreatitis(33.3%; P=0.708),and one patient with idiopathic pancreatitis (10.0%;P=0.227).Pathological fecal elastase-1 was not significantly related to sex,age or day of refeeding.CONCLUSION:Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.

Pathophysiology of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4(IgG4)-related disease. In addition, the pancreas o a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation(CD) 4or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that thepolymorphic genes encoding cytotoxic T lymphocyteassociated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses.

Serum tumor markers not useful in screening patients with pancreatic mucinous cystic lesions associated with malignant changes

BACKGROUND: Serum cancer antigen 19-9 (CA19-9) pro-vides additional information about mucinous cystic pancre-atic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determina-tions provide additional information such as the presence of invasive carcinoma in MPN patients. METHODS: Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL. RESULTS: Thirty-ifve patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) conifrmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High se-rum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.010). In the 7 MPN patients associated with histological-ly conifrmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA. CONCLUSION: Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.

Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis

Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas.Ger-man authors have defined this area as a"groove".We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space.A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 paperswere considered for the present study;there were 19 cohort studies and 40 case reports.The majority of patients having groove pancreatitis were middle aged.Mean age was significantly higher in patients having groove carcinoma.The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multi-detector computer tomography,magnetic resonance imaging and endoscopic ultrasonography.These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating"groove pancreatitis"from "groove adenocarcinoma".In conclusion,chronic pan-creatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and,in the majority of them,the pan-creatitis had calcifications.

Quality of life in chronic pancreatitis

In an era such as the present one in which there is a high demand for health services with the associated pressure of controlling spending, health care organizations are concerned about the cost-effectiveness of quality improvement interventions. On the other hand, the impact of the disease and the treatment on the patient’s overall well-being and functioning has become a topic of growing interest not only in clinical research but also in practice. The clinical evaluation of the benefits of specific treatments for chronic, debilitating and incurable diseases should increasingly include formal assessment of patient activity and well-being. Thus, health-related quality of life as subjectively perceived by the patient, is becoming a major issue in the evaluation of any therapeutic intervention, mainly in patients with chronic or difficult diseases where the aim of the intervention is to keep patients either symptom-free and capable of living in the community for a long time or to reduce the discomfort caused by the disease. In this paper, we review the current knowledge on the quality of life assessment in chronic pancreatitis patients.

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD.

Patient-reported outcomes in subjects with neuroendocrine tumors of the pancreas

AIM: To assess the patient-reported outcomes (PROs) of pancreatic neuroendocrine tumor (PNET) patients. METHODS: Fifty-one consecutive patients (21 male, 30 female, 61.0 ± 10.3 years) with proven PNETs were studied. An SF-12 questionnaire capable of exploring the physical (PCS) and mental (MCS) aspects of daily life was used. Four questionnaires were also used [12 items General Health Questionnaire (GHQ-12) for non-psychotic psychiatric disorders, State Trait AnxietyInventory (STAI) Y-1 and Y-2 for anxiety and BDI-for depressive symptoms] to explore the psychological aspects of the disease. Forty-four sex-and age-matched Italian normative subjects were included and evaluated using the SF-12, STAI Y-1 and Y-2 questionnaires.RESULTS: Seven patients refused to participate to the study; they were clinically similar to the 44 participants who agreed to complete the questionnaires. PNET patients had a PCS score (44.7 ± 11.0) were not signifi cantly different from the norms (46.1 ± 9.9, P = 0.610), whereas the MCS score was signifi cantly lower in patients (42.4 ± 13.0) as compared to the norms (48.2 ± 9.8, P = 0.036). GHQ-12 identified 11 patients (25.0%) as having non-psychotic psychiatric disorders.The STAI scores were similar in the patients and inthe normative population. Finally, BDI-identifiedeight patients (18.2%) with moderate depression and 9 (20.5%) with mild depression whereas 27 patients (61.4%) had no depression.CONCLUSION: The PNET patients had a good physical but an impaired mental component of their quality of life; in addition, mild or moderate depressive symptoms are present in about 40% of PNET patients.