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Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by melanotic macules, gastrointestinal polyps and increased cancer risks. We discuss several common scenarios encountered in the diagnosis and management of PJS patients. If the diagnosis is unclear, all pathological material should be re-evaluated by an expert gastrointestinal pathologist. The PJS discussion email list-serve (patient managed) and the peutz-jeghers.com, geneclinics.org, stk11.com websites are useful resources for patients. Cancer surveillance is accepted as a method to increase survival for PJS patients, thus all PJS patients should be prescribed an individualized surveillance plan based on personal and family history as well as available health care resources while taking into consideration the preferences of the patient. Several recent incremental improvements in PJS care have been made including the use of magnetic resonance enterography (MRE) and double balloon endoscopy (DBE). MRE combines cancer and small intestinal polyp surveillance, which previously had required two or more separate tests. How and when to perform pancreatic cancer surveillance continues to be an unclear area in the management of PJS patients. Endoscopic ultrasound (EUS) is probably the most sensitive investigation for pancreatic cancer detection at an early stage when cure may be possible. However, EUS is limited by variability and false positive results. Female patients with PJS are at risk for two rare cancers that require regular surveillance, adenoma malignum and ovarian sex cord tumors with annular tubules. [ABSTRACT FROM AUTHOR]

Palladin is an actin associated protein serving as a cytoskeleton scaffold, and actin cross linker, localizing at stress fibers, focal adhesions, and other actin based structures. Recent studies showed that palladin plays a critical role in smooth muscle differentiation, migration, contraction, and more importantly contributes to embryonic development. This review will focus on the functions and possible mechanisms of palladin in smooth muscle and in pathological conditions such as cardiovascular diseases and cancers. [ABSTRACT FROM AUTHOR]

Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer ( n = 28), colon cancer ( n = 20) and lung cancer ( n = 11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69 years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis is a rare disease in childhood. However, when severe, a total pancreatectomy may be the only option to relieve pain and restore quality of life. An islet autotransplant performed at the time of pancreatectomy can prevent or minimize the postsurgical diabetes that would otherwise result from pancreatectomy alone. In this procedure, the resected pancreas is mechanically disrupted and enzymatically digested to separate the islets from the surrounding exocrine tissue, and the isolated islets are infused into the portal vein and engraft in the liver. Because patients are receiving their own tissue, no immunosuppression is required. Islet autotransplant is successful in two thirds of children—these patients are insulin independent or require little insulin to maintain euglycemia. Factors associated with a more successful outcome include a younger age at transplant (<13 years), more islets transplanted, and lack of prior surgical procedures on the pancreas (partial pancreatectomy or surgical drainage procedures). [ABSTRACT FROM AUTHOR]

Groove pancreatitis is a segmental chronic pancreatitis that affects the anatomical area between the pancreatic head, the duodenum, and the common bile duct, referred to as the groove area. Most patients with groove pancreatitis are males aged 40–50 years with a history of alcohol abuse. In about 20% of patients undergoing pancreaticoduodenectomy to treat chronic pancreatitis, groove pancreatitis is detected. The clinical symptoms are weight loss, upper abdominal pain, postprandial vomiting, and nausea due to duodenal stenosis. The pathogenesis of groove pancreatitis is thought to be anatomical or functional obstruction of the minor papilla. The viscosity of pancreatic juice increases due to excessive alcohol consumption and/or smoking, leading to calcification of the pancreatic duct. According to these conditions, pancreatitis in the groove area might arise due to impaired pancreatic juice outflow. The descending part of the duodenum is usually stenotic. Severe fibrosis and scarring are evident in the groove area. Characteristic pathological findings are cystic lesions in the duodenal wall, Brunner gland hyperplasia, dilation of Santorini’s duct and protein plaques in the pancreatic duct. A differential diagnosis of groove pancreatitis from peripancreatic cancer is clinically important. Cystic lesions in the duodenal wall and smooth stenosis of the bile duct are important findings of groove pancreatitis revealed by endoscopic ultrasonography, computed tomography and magnetic resonance imaging. Biopsy through the duodenum is also useful for diagnosis. Conservative treatment options include endoscopic stenting of the minor papilla, but long-term outcomes remain unclear. Pancreatoduodenectomy is a rational treatment for symptomatic groove pancreatitis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cystic dystrophy of heterotopic pancreas, groove pancreatitis, pancreatic hamartoma of the duodenum, paraduodenal wall cyst, and myoadenomatosis are all terms grouped together, from a pathological viewpoint, as definitions of paraduodenal pancreatitis (PP). The objective of the present study was to investigate the clinical characteristics, therapeutic strategies, and results in 58 patients undergoing pancreatic resection for PP. Methods: From January 1990 to December 2006 data were prospectively collected on 58 patients who were diagnosed with PP who then underwent pancreaticoduodenectomy. Results: In this patient cohort the median age was 44.7 years; only 4 patients were women, and only 3 had non-drinker and/or non smoker habits. The overall morbidity was 18.9%, and the median hospitalization was 11 days. There were no postoperative deaths. In a median follow-up of 96.3 months, all patients noted a decrease in the pain associated with PP; 35 patients (76%) had complete disappearance of pain, whereas occasional relapsing pain occurred in the remaining 11 (24%). Conclusions: Patients with PP have clinical characteristics similar to those of chronic pancreatitis. The diagnostic imaging modalities of choice are ultrasonographic endoscopy and magnetic resonance cholangiopancreaticography. Based on our surgical experience, pancreaticoduodenectomy seems to be a reasonable choice of treatment in patients with PP. [ABSTRACT FROM AUTHOR]

Groove pancreatitis is a distinct form of chronic pancreatitis characterized by inflammation and fibrous tissue formation, affecting the groove area between the head of the pancreas, the duodenum and the common bile duct. It is manifested on imaging by a sheet-like mass in the groove area near the minor papilla. Thickening of the duodenal wall and cystic transformation in the duodenal wall also represent common imaging features. Pathogenesis is still unclear, and clinical presentation is not specific. Endoscopic ultrasonography (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate imaging findings consistent with the disease in typical cases, but specific diagnosis is challenging in a number of patients where biopsy is required. The disease may mimic pancreatic, common bile duct or duodenal wall cancer that requires prompt and excessive surgical intervention, as opposed to groove pancreatitis where initial conservative treatment is suggested. The clinical, histopathological and radiological features on cross-sectional imaging of this entity are discussed in this review, and differential diagnostic clues are given. [ABSTRACT FROM AUTHOR]

This report presents a case of Japanese familial pancreatic cancer (FPC) with multifocal pancreatic intraepithelial neoplasia (PanIN) lesions of the branch ducts probably associated with lobular parenchymal atrophy. The risk of pancreatic cancer is significantly increased in those associated with FPC, and this risk increases with increasing numbers of affected first-degree relatives, but there have been four Japanese cases reported. A 63-year-old Japanese male was referred to the hospital for evaluation and treatment of a pancreatic head tumor. His family history included pancreatic cancer in two-first-degree relatives and three-second-degree relatives. A pylorus-preserving pancreatoduodenectomy with a regional lymphadenectomy and intraoperative radiotherapy were performed. The histological findings of the main tumor showed a moderately differentiated tubular adenocarcinoma in the head of the pancreas without metastasis of the resected lymph nodes. Interestingly, multifocal PanIN lesions in the branch ducts were individually developed and some of these lesions were probably associated with small lesions of lobular parenchymal atrophy. He remained in good condition for 37 months after the operation. Although the concept of FPC has not been clearly established in Japan, nationwide registries of FPC are probably useful for management of FPC patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Hereditary pancreatitis (HP) is a rare cause of chronic pancreatitis (CP; 1%) and more than 25 mutations in the PRSS1 gene have been detected. HP patients with the p.R122H mutation have a 35% lifetime risk of developing pancreatic cancer, but the oncogenetic process remains unknown. We have investigated the histopathological features and frequency of BRAF and KRAS2 mutations in 2 patients with PRSS1 mutations (p.A121T, p.R122H) and patients with CP (n = 11). Methods: Pancreatic tissue was stained with hematoxylin-eosin and examined by light microscopy. Mutational analysis of the BRAF (exon 5, 11) and KRAS2 (exon 1) genes was performed using PCR and direct DNA sequencing. Results: Histopathological features revealed similar results in both patients, pancreata showed strong fibrosis and ducts with signs of distortion, irregular size and noticeable dilatations. We identified one BRAF mutation (p.V600E) in the p.R122H patient and two KRAS2 (p.G12D; p.G12C) mutations in CP controls. Conclusions: Our results sustain the knowledge about the clinical phenotype of patients with PRSS1 mutations who have a high risk of pancreatic cancer. Whether the histopathological picture or the BRAF mutation is specific for patients with PRSS1 mutations or plays a specific role in the tumorigenesis of patients with HP needs to be further evaluated. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a reprint of the article "Biology and Management of Pancreatic Cancer," by P. Ghaneh, E. Costello, and J. P. Neoptolemos which appeared in the August 2007 issue of "Gut." Discussions on the active mutation of Kras, a GTP binding protein, epidermal growth factor receptor (EGFR), use of cetuximab, erlotinib, and transcription factor p53 are presented. It also concludes that endoluminal ultrasonogaphy and chemoradiotherapy can help in early diagnosis and treatment.

The article investigates the use of artificial neural networks for diagnostic and prognostic purposes in pancreatic disease, especially acute pancreatitis and pancreatic cancer. It shows that conventional linear models have limitations in terms of diagnosis and prediction of outcome. The article recommends ways to improve the management of acute pancreatitis and pancreatic cancer.

This report describes an unusual pancreatic tumor in a 3-year-old boy. He presented with abdominal pain secondary to pancreatitis and was found to have a complex, multicystic lesion within the head of the pancreas. He subsequently underwent a pancreatoduodenectomy. Grossly, the mass was 3 cm, multicystic, and well demarcated. Histologically, there were numerous variably sized, dilated ducts lined by tall columnar mucinous cells surrounded by a stroma that exhibited foci of cellular condensations resembling primitive pancreatic mesenchyme. Acinar and endocrine cells were often seen budding into the ducts forming ''ductulo-insular bodies.'' As a result of its superficial resemblance to Stocker type 2 cystic adenomatoid malformation of the lung, we are proposing the name ''multicystic adenomatoid hamartoma'' for this lesion. [ABSTRACT FROM AUTHOR]

The article presents information on familial pancreatic cancer (FPC). FPC is inherited as an autosomal dominant disease with involvement of different genes and modifying genes. It is believed that tobacco smoking could be responsible for 14% of all pancreatic cancer cases. Cystic fibrosis gives a 32% higher risk of pancreatic cancer. Chronic pancreatitis is responsible for 5% of the pancreatic cancer cases.

This article discusses a study on the association of myeloperoxidase (MPO) and superoxide dismutase polymorphisms with an increased risk of developing pancreatic adenocarcinoma. The author researchers examined patients with pancreatic cancer for polymorphisms of the MPO. They confirmed the association and also found that oxidative stress may play an important role in pancreatic cancer carcinogenesis.

The article details a study which reviewed published papers from 1966 to 2007 that described genetic factors involved in modulating the risk of pancreatic cancer. It discusses the aetiology of pancreatic ductal adenocarcinoma and the role of tobacco smoking and gene-environment interaction in the progression of pancreatic cancer. It also examines the role of DNA repair in the development of pancreatic cancer.

The article discusses the factors concerning the pathogenesis of pancreatic cancer. It is stated that genetic aspect is often associated to the invasion of pathogens. Here, it highlights the difficulties in recognizing pancreatic-cancer prone families such as deleterious mutation, phenotypic expression as well as environmental exposures to cancer-causing agents.

Introduction: More than 90% of patients with pancreatic cancer present either with incurable locally advanced or metastatic disease or relapse following surgery. For these patients systemic therapy offers the only prospect of salvage, but pancreatic cancer is one of the most chemoresistant of tumors; current chemotherapy can only delay progression in a limited proportion of patients and survival rates are poor. There is therefore a pressing need for more effective therapy. Capecitabine is a new oral prodrug of fluorouracil, which has shown activity in pancreatic cancer particularly when used in combination with gemcitabine. Aims: To review the emerging evidence for the clinical effectiveness of capecitabine in the management of carcinoma of the pancreas. Evidence review: There is evidence from phase II testing that capecitabine is active in pancreatic cancer. The Swiss Group for Clinical Cancer Research/Central European Cooperative Oncology Group (SAKK/CECOG) phase III trial found that the combination of gemcitabine and capecitabine did not improve overall median survival as compared with gemcitabine alone (8.4 vs 7.3 months, respectively; P=0.314) but subgroup analysis in patients with good performance score [Karnofsky Performance Scores (KPS) ⩾90] revealed a significant survival improvement with the combination arm (10.1 months) compared with single-agent gemcitabine (7.5 months; P=0.033). Preliminary data from the GemCap phase III trial indicated significantly improved response rates and survival for the combination of gemcitabine with capecitabine (7.4 months) compared with gemcitabine alone (6 months; P=0.026) but analysis of the mature data with adequate follow-up awaits reporting. Clinical potential: The addition of capecitabine to gemcitabine may represent a small step forward in the management of advanced pancreatic cancer but further data are required in order to determine its full impact. [ABSTRACT FROM AUTHOR]

The article offers information about research findings for the biological and clinical management of pancreatic cancer. Details on the sophisticated approach in the diagnosis of pancreatic cancer with the use of imaging methods are discussed. It also gives an account of improved methods in palliative care treatments for the disease including the use of endoscopic stent placement with less than effective pain relief and pancreatic enzyme supplementation.

A case of solid pancreatic hamartoma in a 58-year-old Japanese woman is presented. She had no symptoms, and a pancreatic mass was incidentally found on screening ultrasonography 4 months before admission. The patient was not alcoholic and had no history of pancreatitis. Physical examination and laboratory data were unremarkable. Preoperative imaging demonstrated a nodule in the body of the pancreas, measuring 2.0 cm in maximum diameter, which showed marked delayed enhancement during dynamic CT. The patient underwent a distal pancreatectomy under the preoperative diagnosis of pancreatic endocrine tumor and had an uneventful postoperative course. A well-demarcated solid nodule, 1.9 cm in diameter, was evident in the body of the pancreas. Microscopically, the lesion was composed of non-neoplastic, disarranged acinar cells and ducts embedded in a sclerotic stroma with elongated spindle cells, lacking discrete islets. The stromal spindle cells were immunoreactive for CD34 and CD117. The histological diagnosis was solid hamartoma of the pancreas. There was no recurrence 5 months after surgery. Herein is reported a case of solid hamartoma of the pancreas and review of the literature. A search through the literature found only two cases of solid hamartoma of the pancreas, among the 14 cases previously reported as pancreatic hamartoma. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is caused by mutations in serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been connected to P53 pathway. Methods: PJS probands with STK11 mutation were included in the function analysis. P53 activity elevated by STK11 mutants was investigated using dual-luciferase reporter assay in vitro after constructing expression vectors of STK11 wild type and mutants generated by site-directed substitution. The association between the P53 activity and clinicopathological factors was analysis, especially the cancer history. Results: Thirteen probands with STK11 mutations were involved, and within the mutations, c.G924A was novel. P53 activity elevation caused by 6 truncating mutations were significantly lower than that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5 families. Within them, P53 activity was reduced and cancer occurred before 40 in 2 families, while it was not significantly changed and cancers happened after 45 in the other 3 families. Conclusions: The affected P53 activity caused by STK11 mutations in PJS patients is significantly associated with protein truncation, while cancer risk in PJS can be elevated through pathways rather than P53 pathway. P53 activity test is probably a useful supporting method to predict cancer risk in PJS, which could be helpful in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pancreatic hamartomas are extremely rare and may be misdiagnosed as malignant tumors. We report herein a case of a small, solid-type pancreatic hamartoma.Case Presentation: A 72-year-old female was incidentally detected pancreatic lesion by ultrasonography. Computed tomography and magnetic resonance imaging revealed a 2.0-cm solid lesion. The main pancreatic duct (MPD) was obstructed by the lesion in the head of the pancreas, and the upstream MPD was dilated. 18F-fluorodeoxyglucose (FDG) accumulated avidly in the lesion and increased in FDG intensity from the early to the delayed images. The histopathological studies confirmed the diagnosis of pancreatic hamartoma. Immunohistochemically, the cell membrane of the accessory glands and ducts showed homogeneous expression of glucose transporter type I and hexokinase II.Conclusion: Pancreatic hamartomas causing dilatation of the MPD are extremely rare, and this appears to be the first case of a hamartoma to take up FDG avidly. It was a rare occurrence and should be noted that pancreatic hamartomas can cause an obstruction of the MPD and show avid FDG uptake, thereby mimicking malignant pancreatic tumors. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Is a Program Description a Research Paper?"

A letter to the editor is presented in response to the article "Determinants of Treatment Adherence Among Smear-Positive Pulmonary Tuberculosis Patients in Southern Ethiopia," by E. B. Shargie and B. Lindtjørn.

A letter to the editor is presented in response to the article "XDR-TB in South Africa: No Time for Denial or Complacency," by J. A. Singh, R. Upshur and N. Padayatchi in the 2007 issue.

A response by Michael Callaham to a letter to the editor about his article "The Relationship of Previous Training and Experience of Journal Peer Reviewers to Subsequent Review Quality" is presented.

A letter to the editor is presented in response to the article "Why Most Published Research Findings Are False," by J. P. A. Ioannidis.

A letter to the editor is presented in response to the article "XDR-TB in South Africa: No Time for Denial or Complacency," by J. A. Singh, R. Upshur and N. Padayatchi in the 2007 issue.

A letter to the editor is presented in response to the article "XDR-TB in South Africa: No Time for Denial or Complacency," by J. A. Singh, R. Upshur and N. Padayatchi in the 2007 issue.

A letter to the editor is presented in response to the article "XDR-TB in South Africa: No Time for Denial or Complacency," by J. A. Singh, R. Upshur and N. Padayatchi in the 2007 issue.