M Janot

Indications and early outcomes for total pancreatectomy at a high-volume pancreas center.

Background. This study aimed to analyse the most common current indications for total pancreatectomy (TP) at a high-volume pancreas center. Method. Prospectively collected data on indications and short-term outcome of all TPs performed from January 2004 until June 2008 were analysed. Results. The total pancreatectomies (TP) were 63, i.e., 6.7% of all pancreatic procedures (n = 948). Indications for TP were classified into 4 groups: tumors of advanced stage, n = 23 (36.5%), technical problems due to soft pancreatic tissue, n = 18 (28.6%), troubles due to perioperative surgical complications, n = 15 (23.8%), and therapy-resistant pain due to chronic pancreatitis, n = 7 (11.1%). Surgical complications occurred in 23 patients (36.5%). The mortality in elective TP was 6.25%. Median postoperative stay was 21 days. Mortality, morbidity and the other perioperative parameters differed substantially according to the indication for pancreatectomy. Conclusion. Total pancreatectomy is definitely indicated for a limited range of elective and emergency situations. Indications can be: size or localisation of pancreatic tumor, trouble, technical diffuculties and therapy-refractory pain in chronic pancreatitis. A TP due to perioperative complications (troubles) after pancreatic resections is doomed by extremely high morbidity and mortality and should be avoided.

Preoperative Pancreatic Resection (PREPARE) score: a prospective multicenter-based morbidity risk score.

Objectives:Development of a simple preoperative risk score to predict morbidity related to pancreatic surgery. Background:Pancreatic surgery is standardized with little technical diversity among institutions and unchanging morbidity and mortality rates in recent years. Preoperative identification of high-risk patients is potentially one of the rare avenues for improving the clinical course of patients undergoing pancreatic surgery. Methods:Using a prospectively collected multicenter database of patients undergoing pancreatic surgery (n = 703), surgical complications were classified according to the Clavien-Dindo classification. A new scoring system for preoperative identification of high-risk patients that included only objective preoperatively assessable variables was developed using a multivariate regression model. Subsequently, this scoring system was prospectively validated from 2011 to 2013 (n = 429) in a multicenter setting. Results:Eight independent preoperatively assessable variables were identified and included in the scoring system: systolic blood pressure, heart rate, hemoglobin level, albumin level, ASA (American Society of Anesthesiologists) score, surgical procedure, elective surgery or not, and disease of pancreatic origin or not. On the basis of 3 subgroups (low risk, intermediate risk, high risk), the proposed scoring system reached an accuracy of 75% for correctly predicting occurrence or nonoccurrence of major surgical complications in 80% of all analyzed patients within the validation cohort (c-statistic index = 0.709, P < 0.001, 95% confidence interval = 0.657–0.760). Conclusions:We present an easily applied scoring system with convincing accuracy for identifying low-risk and high-risk patients. In contrast to other systems, the score is exclusively based on objective preoperatively assessable characteristics and can be rapidly and easily calculated.

Rare Solid Tumors of the Pancreas as Differential Diagnosis of Pancreatic Adenocarcinoma

CONTEXT Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer. OBJECTIVE The aim of this study was to report our experience in the treatment of patients with rare tumor lesions of the pancreas and to discuss clinical and pathological characteristics in the context of the role of surgery. DESIGN Data from patients of our prospective data-base with rare benign and malignant tumors of the pancreas, treated in our division from January 2004 to August 2010, were analyzed retrospectively. RESULTS One-thousand and ninety-eight patients with solid tumors of the pancreas underwent pancreatic surgery. In 19 patients (10 women, 9 men) with a mean age of 57 years (range: 20-74 years) rare pancreatic tumors (metastasis, solid pseudopapillary tumor, teratoma, hemangioma, accessory spleen, lymphoepithelial cyst, hamartoma, sarcoidosis, yolk sac tumor) were the reason for surgical intervention. CONCLUSION If rare benign and malignant pancreatic tumors, intrapancreatic metastasis, as well as pancreatic malformations or other abnormalities, present themselves as solid masses of the pancreas, they constitute an important differential diagnosis to primary pancreatic neoplasia, e.g. pancreatic ductal adenocarcinoma. Clinical imaging techniques cannot always rule out malignancy, thus operative exploration often remains the treatment of choice to provide the correct diagnosis and initiate adequate surgical therapy.

Bacteribilia with resistant microorganisms after preoperative biliary drainage – the influence of bacteria on postoperative outcome

Abstract Background. In pancreatic surgery, preoperative biliary drainage (PBD) leads to bacteribilia. Whether positive bile duct cultures are associated with a higher postoperative morbidity might be related to the resistance of the species isolated from bile. Study. Intraoperative bile duct cultures were collected from all patients who underwent pancreatic surgery. Postoperative morbidity was analyzed according to the species and the resistance found on bile duct cultures. Results. Fifty-five percent (166/301) of patients had PBD, while 45% (135/301) underwent primary operation. PBD was associated with a positive bile duct culture in 87% (144/166) versus 21% (28/135) in patients without PBD (p = 0.001) and polymicrobial infections in 53% (88/166) versus 6% (8/135) (p = 0.001). Postoperative morbidity was 40% (121/301); mortality was 3% (9/301). PBD was not associated with morbidity and mortality, but resistant species on bile duct cultures lead to significantly more postoperative complications, 54% (25/46) versus 38% (96/255) (p = 0.033), with significantly more antibiotic therapies. Conclusion. PBD is associated with polymicrobial infections with resistant microorganisms, resulting in more postoperative complications. Since PBD cannot always be avoided, surgeons and gastroenterologists must be aware of their institutional surveillance data to identify patients at risk for postoperative complications.

Redo-Surgery following Curative Resection of Pancreatic Carcinoma: The Difference between True and Suspected Recurrence

Background: Improving results have led to an extension of indications for re-resection of recurrent pancreatic carcinoma. Methods: Among 410 patients who received surgery for histologically proven pancreatic cancer, 17 underwent re-resection for a suspected local recurrence and were evaluated for overall survival, clinicopathological and perioperative data. Results: At the initial operation, resection was curative (R0/R1) in all 17 patients. Indication for re-resection was a suspected or proven recurrence of pancreatic cancer in all patients. Re-resection was possible in 5 patients. The remaining patients received a redo of the pancreaticojejunostomy or bilioenteric anastomosis (n = 2), exploration with biopsy (n = 4), and a palliative bypass (n = 6). Perioperative mortality was 6%. Median overall survival was 25 months (range 10–152 months) and 7 months following re-resection (5–29 months). In 5 of 17 patients, histology showed chronic pancreatitis (n = 4) or a benign stricture at the hepaticojejunostomy (n = 1), whereas all other patients had histologically proven recurrence. Re-resection or redo of the anastomosis was possible in 5 of 5 patients with chronic pancreatitis but only in 2 of 12 patients with true recurrence (p = 0.003). Conclusions: Curative reoperation for recurrent pancreatic carcinoma is rarely feasible. Due to the potential for chronic pancreatitis or benign strictures as an underlying pathology, operable patients should be explored.

The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium.

Purpose: The c-Jun N-terminal kinases (JNK) are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS) model of chronic colitis. Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%). Mice in the intervention groups received subcutaneous administration of 1 μg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4+ and CD8+ cells was also carried out. Results: Administration of 1 μg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS). As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4+ and CD8+ cells was reduced in mice treated with D-JNKI-1 (not significant). Conclusion: Administration of D-JNKI-1 resulted in a clinical attenuation of chronic DSS colitis, and a therapeutic effect of D-JNKI-1 must therefore be assumed. The decrease in CD4+ and CD8+ cells may reflect the influence of D-JNKI-1 on T-cell activation, differentiation, and migration.

Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6

Introduction The c-Jun N-terminal kinases (JNKs) are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS) model in JNK1 knockout mice (Mapk8−/−), JNK2 knockout mice (Mapk9−/−), and wild-type controls (WT1, WT2). Methods The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and transforming growth factor β1 (TGFB1) expression was carried out using LightCycler® real-time polymerase chain reaction. Results Cyclic administration of low-dose DSS (1%) was not able to induce features of chronic colitis in Mapk8−/− WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9−/− mice. In Mapk9−/− mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout. Conclusion Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9−/− mice. The reason for this disease-inducing effect resulting from the loss of JNK2 remains to be elucidated. Expression of TNFα, IL-6, and TGFB1 does not appear to be involved; proapoptotic JNK2 may prolong the activity of proinflammatory immune cells, leading to perpetuation of the inflammation.