Search

Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor.We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor.Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor.Physicians often underrecognize smoking as a CP risk factor. Efforts are needed to raise awareness of the association between smoking and CP. and IAP.

Though an increased efficacy of carmustine and temozolomide (TMZ) has been demonstrated by inactivation of O(6)-methylguanine-DNA methyltransferase (MGMT) with O(6)-benzyl-guanine (BG) in human pancreatic tumors refractive to alkylating agents, the regulatory mechanisms have not been explored.The effects of TMZ and BG on apoptosis, cell growth, the mitotic index, cell cycle distribution, and protein expression were studied by TUNEL, cell counting, flow cytometry, and Western blot analysis, respectively.The wt-p53 human pancreatic tumor cell line Capan-2 and p53-efficient mouse embryonic fibroblasts (MEFs) were more responsive to treatment with TMZ + BG than mutant p53 Capan-1 and p53-null MEFs. S phase delay with a subsequent G2/M arrest was observed in Capans in response to BG + TMZ. The G1-to-S transition delay in Capan-2 was associated with p53-dependent apoptosis and was distinctly different from the presumed mismatch repair (MMR) killing operative during the G2/M arrest. The effect of p53 on BG + TMZ toxicity was supported by a marked change in apoptosis when p53 function was restored/inactivated. There was an early induction of MMR proteins in p53-efficient lines.p53 provokes a classic proapoptotic response by delaying G1-to-S progression, but it may also facilitate cell killing by enhancing MMR-related cell cycle arrest and cell death.

While several aberrant signaling pathways have been attributed to the formation and progression of pancreatic cancer, there is mounting evidence for the increased role of the Hedgehog (Hh) pathway in multiple aspects of pancreatic tumor development. The Hh pathway is a signaling cascade that plays an important role in cell patterning of multiple tissues and organs, including the development of the gastrointestinal system. While normal pancreatic tissue exhibits little Hh pathway activity, patients with pancreatic adenocarcinoma show high levels of Hh pathway signaling in both the tumor epithelia and the surrounding mesenchyme. Several recent studies have focused on this paracrine activation of Hh signaling in the tumor microenvironment and have provided evidence for how activation of this pathway may play roles in mediating cellular proliferation, metastasis, and resistance to therapy. Together, these findings present new insights into how modulation of this pathway may allow us to target multiple aspects of pancreatic tumor biology.

Background/Aims: Midgut formation in Drosophilamelanogasteris dependent upon the integrity of a signaling loop in the endoderm which requires the TGFβ-related peptide, Decapentaplegic, and the Hoxtranscription factor, Labial. Interestingly, although Labial-like homeobox genes are present in mammals, their participation in endoderm morphogenesis is not clearly understood. Methods: We report the cloning, expression, localization, TGFβ inducibility, and biochemical properties of the mammalian Labial-like homeobox, HoxA1, in exocrine pancreatic cells that are embryologically derived from the gut endoderm. Results: HoxA1 is expressed in pancreatic cell populations as two alternatively spliced messages, encoding proteins that share their N-terminal domain, but either lack or include the homeobox at the C-terminus. Transcriptional regulatory assays demonstratethat the shared N-terminal domain behaves as a strong transcriptional activator in exocrine pancreatic cells. HoxA1 is an early response gene for TGFβ 1 in pancreatic epithelial cell populations and HoxA1 protein co-localizes with TGFβ 1 receptors in the embryonic pancreatic epithelium at a time when exocrine pancreatic morphogenesis occurs (days E16 and E17). Conclusions: These results report a role for HoxA1 in linking TGFβ-mediated signaling to gene expression in pancreatic epithelial cell populations, thus suggesting a high degree of conservation for a TGFβ/labial signaling loop in endoderm-derived cells between Drosophila and mammals.

Pancreatic intraepithelial neoplasia (PanIN) is the most common noninvasive precursor to invasive pancreatic adenocarcinoma. Misexpression of microRNAs (miRNAs) is commonly encountered in invasive neoplasia; however, miRNA abnormalities in PanIN lesions have not been documented.Three candidate miRNAs (miR-21, miR-155, and miR-221) previously reported as overexpressed in pancreatic cancers were assessed in 31 microdissected PanINs (14 PanIN-1, 9 PanIN-2, 8 PanIN-3) using quantitative reverse transcription PCR (qRT-PCR). Subsequently, miR-155 was evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in PanIN tissue microarrays.Relative to microdissected non-neoplastic ductal epithelium, significant overexpression of miR-155 was observed in both PanIN-2 (2.6-fold, p = 0.02) and in PanIN-3 (7.4-fold, p = 0.014), while borderline significant overexpression of miR-21 (2.5-fold, p = 0.049) was observed in PanIN-3 only. In contrast, no significant differences in miR-221 levels were observed between ductal epithelium and PanIN lesions by qRT-PCR. LNA-ISH confirmed the aberrant expression of miR-155 in PanIN-2 (9 of 20, 45%) and in PanIN-3 (8 of 13, 62%), respectively, when compared with normal ductal epithelium (0 of 10) (p0.01).Abnormalities of miRNA expression are observed in the multistep progression of pancreatic cancer, with miR-155 aberrations demonstrable at the stage of PanIN-2, and miR-21 abnormalities at the stage of PanIN-3 lesions. and IAP.

Similar to the other von Hippel-Lindau (VHL)-related tumors such as renal cell carcinomas and capillary hemangioblastomas, serous cystadenomas (SCAs) of the pancreas are also characterized by clear cells. Over the years, we have also noticed that the tumor epithelium shows a prominent capillary network.Eighteen cases of SCA were reviewed histologically, and immunohistochemical analysis was performed for CD31 and vascular endothelial growth factor (VEGF) as well as the molecules implicated in clear-cell tumorigenesis: GLUT-1, hypoxia-inducible factor-1 (HIF-1alpha), and carbonic anhydrase IX (CA IX).There was an extensively rich capillary network that appears almost intraepithelially in all cases of SCA, which was confirmed by CD31 stain that showed, on average, 26 capillaries per every 100 epithelial cells. VEGF expression was identified in 10/18 cases. Among the clear-cell tumorigenesis markers, CA IX was detected in all cases, GLUT-1 and HIF-1alpha in most cases.As in other VHL-related clear-cell tumors, there is a prominent capillary network immediately adjacent to the epithelium of SCA, confirming that the clear-cell- angiogenesis association is also valid for this tumor type. Molecules implicated in clear-cell tumorigenesis are also consistently expressed in SCA. This may have biologic and therapeutic implications, especially considering the rapidly evolving drugs against these pathways. More importantly, SCA may also serve as a model of clear-cell-associated angiogenesis and tumorigenesis, and the information gained from this tumor type may also be applicable to other clear-cell tumors.

Objectives: In a matched analysis, we investigated clinical, histopathological, and survival characteristics of small (≤2 cm) pancreatic cancer (PaC) as compared to large PaC. Methods: From the Mayo pathology database, we identified 41 consecutive patients with small PaC and 94 matched controls with margin-negative PaC >2 cm. Two experienced pathologists, who were blinded to survival data, independently reviewed tumor stage and differentiation. Kaplan-Meier survival analysis and Cox proportional hazards models were applied for data analyses. Results: In patients with localized disease (stages I and II), survival was similar in small and large PaC but survival was significantly better in small PaC with regional nodal metastasis (stage III) as compared to similar stage large PaC (5-year survival 44 vs. 7%, median survival 58 vs.18 months, p < 0.001). Well-differentiated small and large PaC had similar median survival (76 vs. 74 months, p = NS). In multivariate analysis, tumor differentiation, not tumor size, was the only independent factor predicting survival in PaC (risk ratio, RR, for moderate vs. well- differentiated: 2.6,95% confidence interval, CI, 1.5-4.5, and RR for poorly differentiated vs. well-differentiated: 5.0, 95% CI 2.4–10.1). Conclusion: Tumor differentiation may be a better predictor of survival in resectable PaC than tumor stage.

Activated stellate cells are considered the principal mediators of chronic alcoholic pancreatitis/fibrosis. However the mechanisms of alcohol action on pancreatic stellate cells (PaSCs) are poorly understood. The aims of this study were to determine the presence and role of the NADPH oxidase system in mediating alcohol effects on PaSCs with specific emphasis on proliferation.PaSC NADPH oxidase components mRNA and protein were determined by RT-PCR and Western blot. The NADPH oxidase activity was measured by detecting the production of reactive oxygen species using lucigenin-derived chemiluminescence assay. PaSC DNA synthesis, a measure of proliferation, was performed by determining the [3H] thymidine incorporation into DNA.mRNA for NADPH oxidase components Nox1, gp91(phox), Nox4, p22(phox), p47(phox) and p67(phox) and protein for NADPH oxidase subunits gp91(phox), p22(phox), p47(phox) and p67(phox) are present in PaSCs. Treatment with platelet-derived growth factor (PDGF) significantly increased the NADPH oxidase activity and DNA synthesis in cultured PaSCs. Alcohol treatment markedly augmented both the NADPH oxidase activity and the DNA synthesis caused by PDGF, which was prevented by antioxidant N-acetyl-L-cysteine, ROS scavenger tiron, and the NADPH oxidase inhibitor diphenylene iodium. The effects of PDGF on NADPH oxidase activity and DNA synthesis were prevented in PaSCs isolated from the pancreas of mice with a genetic deficiency of p47(phox).Ethanol causes proliferation of stellate cells by augmenting the activation of the cell's NADPH oxidase system stimulated by PDGF. These results provide new insights into the mechanisms of alcohol-induced fibrosing disorders.

Intraductal neoplasms are important precursors to invasive pancreatic cancer and provide an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging, as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized. Fifty-two intraductal papillary neoplasms, including 48 intraductal papillary mucinous neoplasms (IPMNs) and four intraductal tubulopapillary neoplasms (ITPNs), were subjected to the mutation assessment in 51 cancer-associated genes, using ion torrent semiconductor-based next-generation sequencing. P16 and Smad4 immunohistochemistry was performed on 34 IPMNs and 17 IPMN-associated carcinomas. At least one somatic mutation was observed in 46/48 (96%) IPMNs; 29 (60%) had multiple gene alterations. GNAS and/or KRAS mutations were found in 44/48 (92%) of IPMNs. GNAS was mutated in 38/48 (79%) IPMNs, KRAS in 24/48 (50%) and these mutations coexisted in 18/48 (37.5%) of IPMNs. RNF43 was the third most commonly mutated gene and was always associated with GNAS and/or KRAS mutations, as were virtually all the low-frequency mutations found in other genes. Mutations in TP53 and BRAF genes (10% and 6%) were only observed in high-grade IPMNs. P16 was lost in 7/34 IPMNs and 9/17 IPMN-associated carcinomas; Smad4 was lost in 1/34 IPMNs and 5/17 IPMN-associated carcinomas. In contrast to IPMNs, only one of four ITPNs had detectable driver gene (GNAS and NRAS) mutations. Deep sequencing DNA from seven cyst fluid aspirates identified 10 of the 13 mutations detected in their associated IPMN. Using next-generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms.

Objectives To conduct a systematic review of the existing literature regarding surgical therapy for oligometastatic lung cancer to the pancreas. Methods Data was collected on patients with singular pancreatic metastases from lung cancer from papers published between January 1970 and June 2014. This was performed following the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines. Kaplan–Meier and Cox Regression analyses were then used to determine and compare survival. Results There were 27 papers that fulfilled the search criteria, from which data on 32 patients was collected. Non-small cell lung cancer (NSCLC) was the most prevalent type of primary lung malignancy, and metachronous presentations of metastases were most common. Lesions were most frequently located in the pancreatic head and consequently the most common curative intent metastasectomy was pancreaticoduodenectomy. There was a statistically significant survival benefit for patients whose metastasis were discovered incidentally by surveillance CT as opposed to those whose metastasis were discovered during a work up for new somatic complaints (p = 0.024). The overall median survival for patients undergoing curative intent resection was 29 months, with 2-year and 5-year survivals of 65% and 21% respectively. Palliative surgery or medical only management was associated with a median survival of 8 months and 2-year and 5-year survivals of 25% and 8% respectively. Conclusions Curative intent resection of isolated pancreatic metastasis from lung cancer may be beneficial in a select group of patients.

Introduction Acute pancreatitis (AP) is a complex disease with multiple aetiological factors, wide ranging severity, and multiple challenges to effective triage and management. Databases, data mining and machine learning algorithms (MLAs), including artificial neural networks (ANNs), may assist by storing and interpreting data from multiple sources, potentially improving clinical decision-making. Aims 1) Identify database technologies used to store AP data, 2) collate and categorise variables stored in AP databases, 3) identify the MLA technologies, including ANNs, used to analyse AP data, and 4) identify clinical and non-clinical benefits and obstacles in establishing a national or international AP database. Methods Comprehensive systematic search of online reference databases. The predetermined inclusion criteria were all papers discussing 1) databases, 2) data mining or 3) MLAs, pertaining to AP, independently assessed by two reviewers with conflicts resolved by a third author. Results Forty-three papers were included. Three data mining technologies and five ANN methodologies were reported in the literature. There were 187 collected variables identified. ANNs increase accuracy of severity prediction, one study showed ANNs had a sensitivity of 0.89 and specificity of 0.96 six hours after admission – compare APACHE II (cutoff score ≥8) with 0.80 and 0.85 respectively. Problems with databases were incomplete data, lack of clinical data, diagnostic reliability and missing clinical data. Conclusion This is the first systematic review examining the use of databases, MLAs and ANNs in the management of AP. The clinical benefits these technologies have over current systems and other advantages to adopting them are identified.

In pancreatic ductal adenocarcinoma patients with suspected venous infiltration, a R0 resection is most of the time not possible without venous resection (VR). To investigate this special kind of patients, this meta-analysis was conducted to compare mortality, morbidity and long-term survival of pancreatic resections with (VR+) and without venous resection (VR-).A systematic search was performed in Embase, Pubmed and Web of Science. Studies which compared over twenty patients with VR + to VR-for PDAC with ≥1 year follow up were included. Articles including arterial resections were excluded. Statistical analysis was performed with the random effect Mantel-Haenszel test and inversed variance method. Individual patient data was compared with the log-rank test.Following a review of 6403 papers by title and abstract and 166 by full text, a meta-analysis was conducted of 32 studies describing 2216 VR+ and 5380 VR-. There was significantly more post-pancreatectomy hemorrhage (6.5% vs. 5.6%), R1 resections (36.7% vs. 28.6%), N1 resections (70.3% vs. 66.8%) and tumors were significantly larger (34.6 mm vs. 32.8 mm) in patients with VR+. Of all VR + patients, 64.6% had true pathological venous infiltration. The 90-day mortality, individual patient data for overall survival and pooled multivariate hazard ratio for overall survival were similar.VR is a safe and feasible option in patients with pancreatic cancer and suspicion of venous involvement, since VR during pancreatic surgery has comparable overall survival and complication rates.

The European Pancreatic Club (EPC) was founded during a first symposium on December 9 and 10, 1965 in London (President H.T. Howat). The nine founding members were one biochemist (Jean Christophe, Belgium), one physiologist (Alfred A. Harper, UK), two surgeons (Andre Delcourt, Belgium, Yngve Edlund, Norway) and five physicians with special interest in the pancreas (Werner Creutzfeldt, Germany, Oliver Fitzgerald, Ireland, Karel Herfort, Czechoslovakia, Henry T. Howat, UK, Henri Sarles, France). It was the first scientific society worldwide which was concerned with the study of the pancreas. The idea was to bring basic scientists and clinicians together in an informal atmosphere to promote friendship and communication on research between them. The 2nd symposium was held in Marseilles in1967 (President H. Sarles). Until now there have nearly always been annual meetings, the one in 2005 is the 37th. In 1973 the EPC decided to lay down ‘Internal Rules’ and in 1992 new statutes were introduced. It became a member of the United European Gastroenterology Federation (UEGF) and is coorganizer of the United European Gastroenterology Week (UEGW). The official journal has been Pancreatology since 2001; previously the abstracts had been printed in Digestion since 1982. The officers of the EPC are the President, the Past President, the President Elect, the Secretary, the Treasurer and six Councillors from different European countries, three from basic and three from clinical science. A selection committee (4 basic and 4 clinical scientists) decides on the acceptance of papers. Officers and Presidents are elected by the General Assembly. At the meetings on average 150 contributions are accepted for presentation; the abstracts are printed in Pancreatology. Papers came from nearly all European countries and from overseas. In numbers Germany, France, the UK, Italy and Sweden are at the top. In total 4,837 scientific presentations were made from 1971 to 2004. Fifty-nine symposia and 245 invited lectures informed about the state of the art. Since 1991 a Young Researchers Corner given by international experts is especially designed to give information on new techniques of research. The European Study Group of Pancreatic Cancer (ESPAC) and the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) are affiliated with the EPC. Since 1999 a Newsletter of the EPC has been published. The website of the EPC is www.e-p-c.org.

Background Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can lead to local and systemic complications. Repeated attacks of AP can lead to chronic pancreatitis, which markedly increases the probability of developing pancreatic cancer. Although many researchers have attempted to identify the pathogenesis involved in the initiation and aggravation of AP, the disease is still not fully understood, and effective treatment is limited to supportive therapy. Methods We aim to summarize available literature focused on phytochemicals (berberine, chlorogenic acid, curcumin, emblica officinalis, ellagic acid, cinnamtannin B-1, resveratrol, piperine and lycopene) and discuss their effectiveness and therapeutic value for improving AP. Results This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. Conclusions Many phytochemicals hold potential in improving AP symptoms and may be a valuable and effective addition to standard treatment of AP. It has already been proven that the crucial factor for reducing the severity of AP is stimulation of apoptosis along with/or inhibition of necrosis. Supplementation of phytochemicals, which target the balance between apoptosis and necrosis can be recommended in ongoing clinical studies.

The paper presents the international guidelines for imaging evaluation of chronic pancreatitis. The following consensus was obtained: Computed tomography (CT) is often the most appropriate initial imaging modality for evaluation of patients with suspected chronic pancreatitis (CP) depicting most changes in pancreatic morphology. CT is also indicated to exclude other potential intraabdominal pathologies presenting with symptoms similar to CP. However, CT cannot exclude a diagnosis of CP nor can it be used to exclusively diagnose early or mild disease. Here magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP) is superior and is indicated especially in patients where no specific pathological changes are seen on CT. Secretin-stimulated MRCP is more accurate than standard MRCP in the depiction of subtle ductal changes. It should be performed after a negative MRCP, when there is still clinical suspicion of CP. Endoscopic ultrasound (EUS) can also be used to diagnose parenchymal and ductal changes mainly during the early stage of the disease. No validated radiological severity scoring systems for CP are available, although a modified Cambridge Classification has been used for MRCP. There is an unmet need for development of a new and validated radiological CP severity scoring system based on imaging criteria including glandular volume loss, ductal changes, parenchymal calcifications and parenchymal fibrosis based on CT and/or MRI. Secretin-stimulated MRCP in addition, can provide assessment of exocrine function and ductal compliance. An algorithm is presented, where these imaging parameters can be incorporated together with clinical findings in the classification and severity grading of CP.

Background Glucagon Like Peptide 1 (GLP-1) mimetic drugs or degradation inhibitors mimic the action of native GLP-1 as a incretin hormone and have become a common second line of therapy for Type 2 diabetes. However, an important clinical issue is whether these drugs increase the incidence of pancreatitis and pancreatic cancer. Objective This paper reviews the physiology of GLP-1 including its synthesis, secretion and action of the peptide. Reported effects of the mimetic drugs on the exocrine pancreas in animal studies are also reviewed. Results GLP-1 is synthesized in a specific class of enteroendocrine cell, the L-cell, by post-translational processing of proglucagon. It is released in response to the presence of nutrients in the small intestine and stimulates vagal afferent nerve endings as well as entering the blood where it is rapidly degraded by dipeptidyl peptidase IV. Its actions are mediated by specific G-protein coupled receptors. The major target tissues are the pancreatic islet beta cells, the brain and the heart but GLP-1 also affects gastrointestinal motility and secretion including the exocrine pancreas where its major systemic action is to inhibit secretion. In some animal, as well as human studies, the GLP-1 mimetic drugs are associated with pancreatitis or precursor lessions to pancreatic cancer but a mechanism is not clear. The most common occurrence of pathology in rodents is when the drugs are combined with a high fat diet. Conclusions There is nothing in the physiology of GLP-1 or animal toxicology studies to support a mechanism of action or a major concern about the action of GLP-1 mimetic drugs on the exocrine pancreas. Further studies are warranted using animal models of disease and high fat diets.

Background/purpose This paper investigates the history of pancreas in classical and late antiquity with the intent to correlate it to the modern medical knowledge. Furthermore, an attempt is made to understand the true meaning of the term “kallikreas”. Methods Only primary textual sources are used in the transcription of ancient references of “pancreas” and/or “kallikreas”. All of the references are analyzed and interpreted under a modern prism for better understanding the ancient anatomy proposed. Results The ancient references describe the actual organ, its position and the blood vessels related to it. An attempt if made to correlate the ancient physiology of the organ to the modern one. Finally, the problematic issue of the ancient terminology is studied. Conclusions Textual proofs are offered that the knowledge that exists and that travelled through the ages concerning the identification of pancreas with “kallikreas”, from which the hormone kallikrein took its name, is erroneous and that the term refers instead to the mesentery.

Background/Aims: Branch-type intraductal papillary mucinous neoplasms (BT-IPMNs) are a subset of non-inflammatory mucinous lesions of the pancreas. Selected BT-IPMNs can be managed conservatively by surveillance because of their lower malignant potential. This review aims to update the reader on advances in our knowledge of BT-IPMNs since the consensus guidelines published in 2006. Methods: A Pubmed search for BT-IPMNs was undertaken and relevant papers were reviewed. Results: Due to the relative scarcity of this condition, still little is known about the natural history, the best method of surveillance or the surgical and non-surgical options. Conclusion: A national database of BT-IPMNs would enable a large enough cohort of patients to be followed up and valid conclusions drawn regarding the best method of treatment or surveillance.

Chronic pancreatitis is mainly managed with drugs, but surgery is required in selected groups of patients. The Partington procedure is still the procedure of choice for patients with a dilated main pancreatic duct but without an inflammatory pancreatic head mass. The same equivalent can be achieved by laparoscopic approach. Laparoendoscopic single-site surgery gained tremendous attention in the past few years. Complex surgeries are being reported using this technique. We report in this paper the first laparoendoscopic single-site lateral pancreaticojejunostomy (LPJ) for chronic calcific pancreatitis with dilated pancreatic duct.The procedure was performed on a 32-year-old female diagnosed to have chronic calcific pancreatitis. A single vertical 2.5-cm umbilical incision and one 10-mm and two 5-mm ports were made. The procedure was completed in 220 min without any intraoperative complication. There were no postoperative complications, and the patient was discharged on day 5 when she started taking routine diet.This preliminary experience suggests that single-incision laparoscopic LPJ is feasible and safe when performed by an experienced laparoscopic surgeon. It has a cosmetic advantage over laparoscopic LPJ. However, it remains to be determined if this technique offers additional advantages of decreased analgesia, decreased hospital stay or cost effectiveness. Further studies are required to analyze these factors.

Alcohol use is one of the two main aetiologies of acute pancreatitis. Detection of excessive alcohol consumption is problematic, illustrated by the fact that self-reports of alcohol consumption account for only approximately 50% of the reported sales of alcohol. To improve the reliability, structured questionnaires and various biochemical markers have been developed to estimate alcohol consumption objectively. Further, the pattern of drinking and level of consumption within the past 2 weeks may alter the clinical picture of the acute pancreatitis. The aim of this paper is to remind the clinician of the importance of accurate and complete history, the need to document the actual alcohol consumption, pattern of drinking, clinical signs of alcoholism and to use biochemical tests and sometimes questionnaires.

This paper provides a summary of the effects of alcohol abuse on the pathobiologic responses that occur during acute and chronic pancreatitis considering both the human disease and animal/tissue models. The effects are multiple and include ones on cell death leading to necrosis; on inflammation resulting in a sensitized response to pancreatic stress; and fibrosis through effects of ethanol on pancreatic stellate cells and the plasminogen system. Although the effects of alcohol are multiple and complex, it is likely that a combination of a few key effects on these pathobiologic responses drive the increased sensitivity of the pancreas to acute pancreatitis with pancreatic stress and the promotion of chronic pancreatitis with pancreatic injury occurring during acute pancreatitis.

The majority of deaths from acute pancreatitis are a consequence of multiple organ dysfunction syndrome (MODS). In order to influence the outcome of this condition, we need to have a better understanding of the natural history of acute pancreatitis, particularly when complicated by MODS. This paper reviews the recent literature dealing with the natural history of acute pancreatitis and the relationship between MODS, pancreatic necrosis and mortality.

The role of endosonography in diagnosing and staging pancreatic adenocarcinoma is evolving. The aim of this review is to present recently published material comparing the performance of endosonography relative to other imaging modalities when evaluating a patient with a suspected or known carcinoma of the pancreas.Medline was searched using the terms 'endosonography' and 'pancreas neoplasms'. References from retrieved papers were reviewed to identify other reports. Emphasis was placed on peer-reviewed material published within the past 3 years that included comparison with other imaging modalities.Despite advances in cross-sectional imaging modalities, endosonography remains the most sensitive and specific method to identify pancreatic mass lesions. Resectability determination of pancreatic carcinoma is best done with dual-phase helical CT, although endosonography may have slightly improved accuracy for lymph node assessment. Endosonography-guided fine-needle aspiration biopsy has high sensitivity (93%) and specificity (100%) when employed in patients with masses in whom pancreatic cancer is suspected but prior biopsies are negative.Endosonography can aid in diagnosing patients with pancreatic neoplasms through definitive inclusion or exclusion of a mass lesion as well as biopsy confirmation of malignancy. The role of endosonography in determination of resectability has been eclipsed by dual-phase helical CT.

When begun in 1989, the 15-year, 3-billion-dollar human genome project included a component for research regarding its ethical, social and legal implications. The decision was prescient, particularly given the clarity of hindsight. Although genetics may not raise new ethical questions, it does highlight some important ethical and policy questions about medical decision making and the implications of medical information for third parties. These issues are made more complex by the fact that genetic testing is far more advanced than our ability to treat and that it can serve many different purposes depending upon whether it is performed on healthy individuals, pregnant women, ‘at risk’ individuals or symptomatic individuals. In this paper, I want to provide a brief overview of six ethical and policy issues raised by genetic testing and the procurement of genetic information.

Background: Few reports exist in the literature regarding neuroendocrine tumors either presenting as, or associated with, chronic pancreatitis. We report a case of chronic pancreatitis with a coexisting neuroendocrine tumor (gastrinoma) of the body of the pancreas. The available literature is reviewed. Methods: Patient data including history, surgical procedure, histology and radiology investigations were collected and summarized. A Medline search using the key words ‘pancreatitis’ and ‘neuroendocrine tumors’ was performed for the years 1966–1999. Cited references in the relevant papers not listed in Medline databases were also evaluated. Results: A 64-year-old female patient was operated on for unclear cystic lesions in the head and tail of the pancreas. Intraoperatively, a gastrinoma was incidentally discovered in the body of the pancreas. It did not appear to be obstructing the main pancreatic duct. The patient underwent a distal pancreatectomy with pancreatico-jejunostomy. Four months postoperatively, she is doing well with no signs of tumor recurrence. The Medline search revealed 125 publications, of which only 17 dealt with either acute or chronic pancreatitis associated with neuroendocrine tumors. When all available data were included, there were 26 cases of neuroendocrine tumors associated with acute pancreatitis. Additionally, 11 cases were associated with chronic pancreatitis, of which only 3 appear to be merely coexistent with chronic pancreatitis without an apparent cause-and-effect relationship between these two entities. Conclusion: We report the rare co-existence of chronic pancreatitis and a neuroendocrine tumor (gastrinoma) of the pancreas. The cause-and-effect relationship between neuroendocrine tumors of the pancreas and chronic pancreatitis continues to be uncertain. However, when the etiology of chronic pancreatitis is unclear, rare neuroendocrine tumors of the pancreas might be considered. Questions remain with regard to the potential role of chronic pancreatitis in the pathogenesis of pancreatic neuroendocrine tumors.