Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.     

Mutations in K-Ras linked to levels of osteoprotegerin and sensitivity to TRAIL-induced cell death in pancreatic ductal adenocarcinoma cells

Osteoprotegerin (OPG) is a soluble receptor expressed in the serum of patients with diabetes, arthritis and pancreatic cancer. While OPG has been considered a tumor survival factor for bone metastasizing breast and prostate cancers, the role of OPG in pancreatic cancer, which itself rarely metastasizes to bone, is not known. Pancreatic ductal adenocarcinoma (PDAC) cell lines were found to secrete OPG and the level of OPG production correlated with sensitivity to TRAIL-induced apoptosis. Silencing OPG sensitized cells to TRAIL-induced apoptosis. Interestingly, a positive correlation was noted between OPG production level and K-Ras mutation status. Earlier studies implicated K-Ras in conferring resistance to TRAIL-induced apoptosis in pancreatic cells and this study demonstrates that K-Ras mediated TRAIL resistance in pancreatic cancer cells occurs due to increased OPG production. Silencing K-Ras in pancreatic cancer cells decreased OPG levels and increased sensitivity to TRAIL-induced apoptosis. These observations indicate that OPG can play a role in both cell survival and in PDAC cell sensitivity to TRAIL-induced apoptosis, which may contribute to metastasis. Targeted inhibition of OPG binding to TRAIL may represent a therapeutic approach in the treatment of pancreatic cancer.     

Identifying patients with undetected pancreatic cancer in primary care: an independent and external validation of QCancer? (Pancreas)

Background

Despite its rarity, the prognosis of pancreatic cancer is very poor and it is a major cause of cancer mortality; being ranked fourth in the world, it has one of the worst survival rates of any cancer.

Aim

To evaluate the performance of QCancer^® (Pancreas) for predicting the absolute risk of pancreatic cancer in an independent UK cohort of patients, from general practice records.

Design and setting

Prospective cohort study to evaluate the performance QCancer (Pancreas) prediction models in 364 practices from the UK, contributing to The Health Improvement Network (THIN) database.

Method

Records were extracted from the THIN database for 2.15 million patients registered with a general practice surgery between 1 January 2000 and 30 June 2008, aged 30–84 years (3.74 million person-years), with 618 pancreatic cancer cases. Pancreatic cancer was defined as incident diagnosis of pancreatic cancer during the 2 years after study entry.

Results

The results from this independent and external validation of QCancer (Pancreas) demonstrated good performance data on a large cohort of general practice patients. QCancer (Pancreas) had very good discrimination properties, with areas under the receiver operating characteristic curve of 0.89 and 0.92 for females and males respectively. QCancer (Pancreas) explained 60% and 67% of the variation in females and males respectively. QCancer (Pancreas) over-predicted risk in both females and males, notably in older patients.

Conclusion

QCancer (Pancreas) is potentially useful for identifying undetected cases of pancreatic cancer in primary care in the UK.     

A practical approach to the clinico-pathological diagnosis of panniculitis

Panniculitides are a group of diseases characterized by an inflammatory process that originates primarily in the subcutaneous tissue. Histopathological classification of panniculitides in mostly septal or lobular types, according to the predominant localization of the infiltrate, is complemented with the eventual identification of vasculitis and the consideration of the vessel size. Additional steps involve the characterization of the inflammatory infiltrate and other findings, such as, the type of adipocyte necrosis or the presence of sclerosis, crystals and foreign bodies. Apart from this purely histopathological characteristics, clinico-pathological correlation is often required to encompass the clinical, histopathological and laboratory data in order obtain the correct diagnosis. We will review the classification of panniculitis, useful histopathological clues for their diagnosis and diagnostic algorithms that can be applied when sclerosis is present or the inflammatory infiltrate is mostly neutrophilic.     

Adjuvant/Perioperative Therapy in Pancreatic and Periampullary Cancer

The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic adenocarcinoma was initially shown to be beneficial based on a prospective, randomized trial published 30 years ago. Since then, oncologists have debated whether chemotherapy alone, chemoradiation, or both are optimal adjuvant therapies following pancreatectomy for pancreatic ductal adenocarcinomas (PDAC). No global consensus has emerged, and there is no one superior modality despite randomized trials in part, to poor trial design, poor patient selection, and poor therapy options itself. We need to have a disciplined approach to the selection of patients for pancreatectomy, pathologic assessment of surgical resection margins, and postoperative (pre-treatment) imaging. In the era of the multidetector CT optimized for pancreatic imaging, tumors of “borderline resectability” have emerged as a distinct subset of PDAC. The attempt to standardize the definition of borderline resectable is a work in progress and modified with time. This distinction (between resectable and borderline resectable) is essential to minimize potentially confounding results of clinical trials. Additionally, preoperative therapy is not only preferred but mandatory in a large population of borderline resectable patients. Ultimately, as we develop more effective systemic therapies for PDAC, proceeding with surgery after a period of induction therapy will be even more compelling especially if there is a clear positive impact on overall survival.     

Persistent reduction of pancreatic Beta-cell mass after a limited period of protein-energy malnutrition in the young rat

Summary Kwashiorkor, the human disease of protein-energy malnutrition, has been implicated in the aetiology of malnutrition-related diabetes mellitus, a form of diabetes not uncommon in developing countries. We have previously demonstrated that temporary protein-energy malnutrition in young rats causes a persisting impairment of insulin secretion. The present study investigates whether this secretory deficiency is accompanied by structural alterations of the endocrine pancreas. Three-week-old rats were weaned onto semi-synthetic diets containing either 15% or 5% protein and these diets were maintained for 3 weeks. From 6 weeks of age all rats were fed a commercial chow containing 18% protein. The endocrine pancreas was investigated by light and electron microscopic morphometry at 3, 6 and 12 weeks of age. In rats not subjected to protein-energy malnutrition there was a progressive increase, with age, of total pancreatic Beta-cell weight and individual Beta-cell size. In 6-week-old rats fed the low protein diet total pancreatic Beta-cell weight and individual Beta-cell size were diminished. In 12-week-old rats previously fed the low protein diet total Beta-cell weight remained lower compared to control rats. It is concluded that protein-energy malnutrition early in life may result in a diminished reserve for insulin production. This may predispose to glucose intolerance or even diabetes in situations with an increased insulin demand.This work was presented in part at the 26th Annual Meeting of the European Association for the Study of Diabetes in Copenhagen, Denmark 10–13 September 1990     

A novel approach using liquid embolic agent for the treatment of pancreatic-cutaneous fistulas: Report of a case

Pancreatic fistula formation remains one of the most dreadful complications after pancreaticoduodenectomies, resulting in extended hospital stays, increased healthcare costs, along with significantly increased morbidity and mortality. Little is mentioned in the literature about the use of percutaneous techniques to resolve this complication when conservative treatments fail. Thus, we developed a novel technique for treating pancreatic-cutaneous fistulas that develop post-pancreaticoduodenectomy. This work describes a novel approach of using a liquid embolic agent to treat a high-output pancreatic-cutaneous fistula after a Whipple procedure, which to the best of our knowledge after extensive literature searches, has not been performed before.     

Pancreatic cancer surgery and nutrition management: a review of the current literature

Surgery remains the only curative treatment for pancreaticobiliary tumors. These patients typically present in a malnourished state. Various screening tools have been employed to help with preoperative risk stratification. Examples include the subjective global assessment (SGA), malnutrition universal screening tool (MUST), and nutritional risk index (NRI). Adequate studies have not been performed to determine if perioperative interventions, based on nutrition risk assessment, result in less morbidity and mortality. The routine use of gastric decompression with nasogastric sump tubes may be unnecessary following elective pancreatic resections. Instead, placement should be selective and employed on a case-by-case basis. A wide variety of feeding modalities are available, oral nutrition being the most effective. Artificial nutrition may be provided by temporary nasal tube (nasogastric, nasojejunal, or combined nasogastrojejunal tube) or surgically placed tube [gastrostomy (GT), jejunostomy (JT), gastrojejunostomy tubes (GJT)], and intravenously (parenteral nutrition, PN). The optimal tube for enteral feeding cannot be determined based on current data. Each is associated with a specific set of complications. Dual lumen tubes may be useful in the presence of delayed gastric emptying (DGE) as the stomach may be decompressed while feeds are delivered to the jejunum. However, all feeding tubes placed in the small intestine, except direct jejunostomies, commonly dislodge and retroflex into the stomach. Jejunostomies are associated with less frequent, but more serious complications. These include intestinal torsion and bowel necrosis. PN is associated with septic, metabolic, and access-related complications and should be the feeding strategy of last-resort. Enteral feeds are clearly preferred over parental nutrition. A sound understanding of perioperative nutrition may improve patient outcomes. Patients undergoing pancreatic cancer surgery should undergo multidisciplinary nutrition screening and intervention, and the surgical/oncological team should include nutrition professionals in managing these patients in the perioperative period.