AUTOIMMUNE PANCREATITIS

Autoimmune Pancreatitis (AIP) is a new nosological entity that was first reported by Sarles et al. in 1961 and then named by Yoshida et al. in 1995 in Japan. It was then ignored by many Western researchers and now, in the last decade; it appears to have been recognized worldwide. AIP is a distinct form a chronic pancreatitis with an immune mediated fibroinflammatory process that has unique histopathologic features that makes it distinguishable from other forms of pancreatitis. Moreover, AIP is the only type of pancreatitis that responds to steroid administration. The Honolulu consensus document that has recently been published by Chari et al. described the histopathologic and clinical subtypes of AIP. Indeed, it appears that there are two forms of AIP, with different prevalence in Europe and Asia and distinct clinical profiles. The first subtype, the most common type in Asia, has recently been named Lymphoplasmocytic sclerosing pancreatitis (LPSP) or type I AIP because of its histological features and its association with elevated IgG serum levels and various autoantibodies. The second one is called idiopathic duct centric pancreatitis, IDCP, or type II AIP, that barely exists in Japan, but more accounted in Caucasian people. IDCP is recognized by its particular histology that is a granulocytic epithelial lesion (GEL) which makes some people call it AIP with GEL. Still nowadays, the diagnosis of AIP is a challenge. AIP can only be definitively diagnosed by histological examination. The main differential diagnosis of AIP is, except chronic pancreatitis, pancreatic cancer. That explains why there are still some unnecessary resections. Several groups have proposed diagnostic criteria for AIP as in Japan, Korea, Germany, Italy and the United States. Thus, it is important to find an international consensus. Above all, it is important to find new criteria as specific markers in the serum and the pancreatic tissues, for example using proteomics, to be able to diagnosis both types of AIP, and distinguish AIP from pancreatic cancer in order to avoid surgical resection in patients with AIP. The aim of this project is to review all relevant studies about AIP and to document all the available diagnostic tools.

Pancreatitis subtypes survey in 852 childhood-onset systemic lupus erythematosus patients: a multicenter cohort

Pancreatitis is a rare and a life-threatening SLE manifestation in childhood-onset systemic lupus erythematosus (c-SLE). The objective of this study was to systematically classify pancreatitis in c-SLE according to the International Study Group of Pediatric Pancreatitis (INSPPIRE) and determine the overall prevalence, clinical features, laboratory and first episode outcomes. A multicenter cohort study in 10 Pediatric Rheumatology centers, including 852 cSLE patients. Pancreatitis was diagnosed in 22/852 (2.6%) cSLE patients. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%) and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration [1(0-10) vs. 4(0-23) years, p < 0.0001] and higher median of SLEDAI-2K [21(0-41) vs. 2(0-45), p < 0.0001]. The frequencies of fever (p < 0.0001), weight loss (p < 0.0001), serositis (p < 0.0001), nephritis (p < 0.0001), arterial hypertension (p < 0.0001), acute renal failure (p < 0.0001), macrophage activation syndrome (p < 0.0001) and death (p = 0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (p < 0.0001) and the median of prednisone dose [55(15-60) vs. 11(1-90)mg/day, p < 0.0001] were significantly higher in patients with pancreatitis. Of note, the two patients with acute recurrent pancreatitis had two episodes, with pain-free interval of 1 and 4 years. This was the first study characterizing pancreatitis using the INSPPIRE standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.

International Consensus Guidelines for Nutrition Therapy in Pancreatitis

Guidelines for nutrition support in pancreatitis have been inconsistently adapted to clinical practice. The International Consensus Guideline Committee (ICGC) established a pancreatitis task force to review published guidelines for pancreatitis in nutrition support. A PubMed search using the terms pancreatitis, acute pancreatitis, chronic pancreatitis, nutrition support, parenteral nutrition, enteral nutrition, and guidelines was conducted for the period from January 1999 to May 2011. Eleven guidelines were identified for review. The ICGC used the following process to develop unified guideline statements: summarize the strength of evidence (grading) of the guidelines; establish level of evidence for ICGC statements as high, intermediate, and low; assign published guideline levels of evidence; and define an ICGC grading system. International Pancreatitis Guideline Grades were established as follows: platinum-high level of evidence and consistent agreement among the guidelines; gold-acceptable level of evidence and no conflicting statements in guidelines; and silver-single existing guideline statement with no conflict in other guidelines. Eighteen ICGC statements were derived from the 11 published pancreatitis guidelines. Uniform agreement from widely disparate groups (United States, Europe, Japan, and China) resulted in 4 platinum-level guideline statements for nutrition in pancreatitis: nutrition support therapy (NST) is generally not needed for mild to moderate disease, NST is needed for severe disease, enteral nutrition (EN) is preferred over parenteral nutrition (PN), and use PN when EN is contraindicated or not feasible. This methodology provides a template for future ICGC nutrition guideline development. (JPEN J Parenter Enteral Nutr. 2012;36:284-291)

Lymphotoxin β receptor signaling promotes development of autoimmune pancreatitis

Little is known about the pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis. Current treatment options are limited and disease relapse is frequent. We investigated factors that contribute to the development of AIP and new therapeutic strategies.

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Groove pancreatitis a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Management of canine diabetes

The majority of diabetic dogs appear to have a form of type 1 diabetes analogous to the latent autoimmune diabetes of adults (LADA) in humans. Evidence of acute or chronic pancreatitis occurs in about 40% of diabetic dogs. Blindness caused by cataract formation eventually occurs in the majority of diabetic dogs and is not dependent on glycemic control. Insulin is the mainstay of therapy for diabetic dogs, and a conservative approach to insulin therapy is crucial. Most diabetic dogs require twice-daily dosing with lente or NPH insulin to adequately control their clinical signs. The diet fed should primarily be palatable and nutritionally balanced. Improved glycemic control may be achieved in some dogs if the diet contains increased insoluble fiber.

Impact of Nervous System Hyperalgesia on Pain, Disability, and Quality of Life in Patients With Knee Osteoarthritis: A Controlled Analysis

Objective. Refractory, disabling pain associated with knee osteoarthritis (OA) is usually treated with total knee replacement. However, pain in these patients might be associated with central nervous sensitization rather than peripheral inflammation and injury. We evaluated the presence of hyperalgesia in patients scheduled for a total knee replacement due to knee osteoarthritis with refractory pain, and we assessed the impact of pressure pain threshold measurements (PPT) on pain, disability, and quality of life of these patients. Methods. Sixty-two female patients were compared with 22 age-matched healthy controls without reported pain for the last year. PPT was measured at the lower extremities subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus lumborum and popliteus muscles and at the supraspinous ligaments from L1-L5, over the L5-S1 and S1-S2 sacral areas and at the pes anserinus bursae and patellar tendon. Results. Patients with knee OA had significantly lower PPT over all evaluated structures versus healthy control subjects (P < 0.001). Lower PPT values were correlated with higher pain intensity, higher disability scores, and with poorer quality of life, except for the role-emotional and general health status. Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome and at the adductor longus muscle were the best predictors for visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores. Conclusion. Patients with pain due to osteoarthritis who were scheduled for total knee replacement showed hyperalgesia of nervous system origin that negatively impacted pain, knee functional capacity, and most aspects of quality of life.

Frequency of Strongyloides stercoralis Infection in Alcoholics

Several studies have shown that chronic alcoholics have increased susceptibility to infections due to higher exposure to infectious agents as well as breakdown in their immune defenses. As Strongyloides stercoralis infection is usually more relevant in immunocompromised patients, the aim of this study was to evaluate the frequency of S. stercoralis infection in alcoholics. Thus, coproparasitological examination was carried out in 145 subjects, from which 45 were chronic alcoholics (mean age of 45.7 ± 11.0 years), 10 were nonalcoholic cirrhotic patients (mean age of 50.2 ± 13.1 years), and 90 were asymptomatic nonalcoholic subjects (mean age of 46.7 ± 10.1 years), which served as controls. From the alcoholics, 9 had hepatic cirrhosis, 9 had chronic pancreatitis and 27 had neither cirrhosis nor pancreatitis. For the diagnosis of strongyloidiasis, the Baermann-Moraes and Lutz methods were used in three fecal samples from each subject. Samples were collected at alternated days, and three slides of each sample were analyzed for each method, thus totalizing 2,610 slides examined. The frequency of strongyloidiasis in the total alcoholic group (33.3%) and in the subgroups of alcoholics, i.e., patients with hepatic cirrhosis (44.4%), with chronic pancreatitis (33.3%), and those with no cirrhosis or pancreatitis (29.6%) was statistically higher than that found in the control group (5.5%). None of the individuals with nonalcoholic hepatic cirrhosis had S. stercoralis infection. Our results showed that the chronic alcoholism itself is an important factor that predisposes to strongyloidiasis.

Potential target antigens for immunotherapy in human pancreatic cancer.

BACKGROUND: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. METHODS: Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. RESULTS: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. CONCLUSIONS: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.

Hémorragie par le canal de Wirsung: forme rare d'hémorragie digestive haute. A propos d'une observation [Hemorrhage through Wirsung's duct: rare form of upper gastrointestinal hemorrhage. A case report].

The case of a 41-year-old alcoholic patient who presented with massive upper gastrointestinal bleeding is reported. The diagnosis was established rapidly by endoscopy which revealed bleeding through the papilla of Vater. Selective angiography of the superior mesenteric artery opacified the pancreatic duct as well as the duodenum. CT scan showed signs of chronic pancreatitis. Because of the recurrence of bleeding and shock, an urgent operation was necessary and a Whipple procedure was performed. Recovery was complete. The clinical presentation, the etiology, the diagnostic modalities and the treatment of this particular condition are discussed. Usually, hemorrhage through the pancreatic duct presents as repeated episodes of upper gastrointestinal bleeding with no source found at endoscopy. The presence of chronic pancreatitis or of epigastric pain during bleeding should suggest the diagnosis. Upper gastrointestinal endoscopy and angiography are the principal diagnostic tools. Definitive treatment requires surgery, and resection in most of the cases.

Hemosuccus pancreaticus: causa rara de hemorragia digestiva maciça

Hemosuccus pancreaticus is a unusual syndrome manifested by hemorrhage into the pancreatic duct and by blood loss through the ampulla of Vater: It may be caused by tumors, arteriovenous malformation, pancreatic lithiasis, aneurism rupture from adjacent vessels, or erosion of pancreatic and peripancreatic vessels due to chronic pancreatitis. The authors describe a case of massive and recurrent gastrointestinal upper hemorrhage in a 26-year-old man without known risk factors for pancreatitis. This man underwent urgent surgery due to gastrointestinal bleeding during the ínvestigation. During the procedure, blood was found in the intestinal lumen and a tumor in the head of pancreas with two centimeters of diameter: A gastroduodenopancreatectomy was performed. Histological study showed chronic pancreatitis with a fistula from the pancreatic vessels to the Wirsung duct. The patient was discharged without postoperative complications and after months, remains assymptomatic.

Anastomose duodenoduodenal na pancreatoduodenectomia por pancreatite crônica

Literature has been showing a tendency of reducing the limits of Whipple's resection. The main technical advance was the pylorus preserving resection, technique proposed by Traverso and Longmire in 1978. The pancreticoduodenectomy for chronic pancreatitis, is probably the best opportunity to apply this type of procedure. In these specific patients, the author preserved the pylorus and the third portion of the duodenum. The gastrointestinal transit was reconstructed by the duodenumduodenal anastomosis and the bile duct and the pancreas were drained in a Roux-en-way loop . Follow-up showed no important complication, with no problems related to gastric emptying and without pain.

Pseudotumor pancreático

The decrease in morbidity and mortality of pancreaticoduodenectomy in reference centers has increased the incidence of benign histopathologic diagnosis in cases where a pre-operative diagnosis of pancreatic ductal carcinoma was expected (9,2%). Recent reports have shown that autoimune pancreatitis, an entity that can lead to a pathologic diagnosis of sclerosing lymphoplasmatic pancreatitis has been the cause of about 2,5% of wrong preoperative diagnosis. Clinical and image definitive diagnosis is still uncertain on those borderline cases. An increase in IgG4 has been reported as frequent in patients with autoimune pancreatitis which can respond to steroid treatment. In doubtful cases, four diagnosis can be expected: 1. Pancreatic ductal carcinoma; 2. Chronic alcoholic pancreatitis; 3. "Chronic pancreatitis secondary to choledocal lithiasis"; 4. Sclerosing lymphoplasmatic pancreatitis. Modern medical literature sugests that evaluation of IgG4 in doubtful cases of pancreatic tumor (pseudotumor of the pancreas) could avoid unnecessary pancreaticoduodenectomies in the future.

Hospital strain colonization by Staphylococcus epidermidis

The skin and mucous membranes of healthy subjects are colonized by strains of Staphylococcus epidermidis showing a high diversity of genomic DNA polymorphisms. Prolonged hospitalization and the use of invasive procedures promote changes in the microbiota with subsequent colonization by hospital strains. We report here a patient with prolonged hospitalization due to chronic pancreatitis who was treated with multiple antibiotics, invasive procedures and abdominal surgery. We studied the dynamics of skin colonization by S. epidermidis leading to the development of catheter-related infections and compared the genotypic profile of clinical and microbiota strains by pulsed field gel electrophoresis. During hospitalization, the normal S. epidermidis skin microbiota exhibiting a polymorphic genomic DNA profile was replaced with a hospital-acquired biofilm-producer S. epidermidis strain that subsequently caused repetitive catheter-related infections.