[Risk-adapted anticoagulation in atrial fibrillation in Germany, Austria and Switzerland - an analysis from the PREFER-in-AF study]. / Risikoadaptierte Antikoagulation zur Schlaganfallprävention bei Vorhofflimmern in Deutschland, Österreich und der Schweiz.

BACKGROUND: The management of patients with atrial fibrillation (AF) has substantially improved in recent years, among others due to the introduction of new risk scores for the stratification of patients, as well as the availability of the non-vitamin K oral antagonists (NOAC). The PREFER-in-AF study aimed to document the management of AF patients with particular focus on stroke prevention on the basis of anticoagulants. METHODS AND RESULTS: In Germany, Austria and Switzerland a total of 1771 patients were enrolled between January 2012 and January 2013 (mean age 71.9 ±â€…9.2 years; 63 % males).At inclusion, the mean time since AF diagnosis was 4.8 ±â€…5.3 years. Paroxysmal AF was present in 30.7 %, persistent in 11 %, long standing persistent in 4.7 % and permanent AF in 53.3 % of the patients. 25.1 % of the Patients were in sinus rhythm. Mean CHA2DS2-VASc Score was 3.7 ±â€…1.8 points (0 points in 3.0 %, 1 point in 7.1 %, ≥ 2 points in 89.9 %).For the prevention of thromboembolic events 68.1 % of patients received vitamin K antagonists (VKA, mainly phenprocoumon), 11.6 % received a NOAC (mainly rivaroxaban or dabigatran), 7.6 % an antiplatelet agent, and 7.7 % a combination of VKA plus an antiplatelet agent. 5.0 % of patients did not receive any anticoagulant. During the 12 months prior to inclusion, interruption of VKA therapy due to an interventions was reported in 29.7 %. In the group of patients with known INR values and available CHA2DS2-VASc score, 75.1 % were adequately controlled (defined as at least 2 of 3 INR values in the range of 2.0-3.0).Bleeding propensity or bleedings in patient history were reported for 5.1 % of the patients, hospitalizations due to major bleeding events in the past 12 months for 1.9 %. Possible risk factors associated with anticoagulation were present in 76.7 %. Mean HAS-BLED score was 2.1 ±â€…1.1 points. CONCLUSION: The rates of AF patients who received oral anticoagulation were about 90 % and substantially higher compared to previous observational studies. NAOCs were administered to 11.7 % of patients.

The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity.

BACKGROUND: Pancreatic neuropathy in chronic pancreatitis (CP) and pancreatic cancer (PCa) is characterized by pancreatic neuropathy, i.e. increased neural density and hypertrophy, which are associated with neuropathic pain. To better understand the mechanism of these neuropathic alterations, we aimed at achieving an in-vitro simulation of the intrapancreatic neuroplasticity. METHODS: Dissociated myenteric plexus (MP) and dorsal root ganglia (DRG) neurons of newborn rats were treated with normal human pancreas (NP), CP or PCa tissue extracts. Furthermore, MP and DRG neurons were cultured in supernatants from different pancreatic cancer cell lines (PCC) and human pancreatic stellate cells (hPSC) obtained from either CP or PCa tissues. For analysis, the neurite density, outgrowth, neuronal branching capacity and perikaryonal size were quantified. KEY RESULTS: Myenteric plexus and DRG neurons grown in CP and PCa tissue extracts built denser networks than in NP extracts. Both neuronal types showed a strong neurite outgrowth, more complex branching pattern and a somatic hypertrophy in CP and PCa extracts. Pancreatic cancer cell supernatants induced a prominent neurite outgrowth, increased neurite density and perikaryonal hypertrophy in MP and DRG neurons. Supernatants of CP-derived hPSC strongly stimulated neurite outgrowth. Glial density in MP cultures was strikingly increased by PCa tissue extracts. CONCLUSIONS & INFERENCES: Intrapancreatic microenvironment in CP and PCa induces neuroplastic alterations under in-vitro conditions, leading to increased neural density and hypertrophy. Thus, due to its neurotrophic attributes, the intrapancreatic microenviroment in CP and PCa seems to be a key player in the generation of pancreatic neuropathy and neuroplasticity.

Herpes simplex virus sepsis and acute liver failure.

Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended.

[Middle segmental pancreatic resection: an organ-preserving option for benign lesions]. / Pankreassegmentresektion : Organerhaltende Option bei benignen Läsionen.

Benign and low malignant tumors of the middle pancreatic segment can be resected by extended pancreaticoduodenectomy or distal pancreatic resection. Both procedures involve unavoidably extensive loss of normal pancreatic parenchyma, leading to deteriorated endocrine and exocrine pancreatic function. Segmental pancreatic resection represents an organ-preserving surgical procedure. Normal pancreatic tissue can be preserved as only the tumor with a pancreatic segment is resected. Several reports confirm lower mortality and minimal risk of postoperative endocrine or exocrine insufficiency than with standard pancreatic resections. The indication should be limited exclusively to benign or low malignant pancreatic tumors, metastases from other tumors, and focal chronic pancreatitis, as this type of resection cannot be deemed oncologic. Segmental pancreatic resections are technically more demanding and therefore should be performed in experienced centers.

An audit of outcomes of a series of periampullary carcinomas.

BACKGROUND: Non-pancreatic periampullary carcinoma such as ampullary carcinoma (AmpCA), distal cholangiocellular carcinoma (CholCA) and duodenal carcinoma (DuoCA) have a better prognosis than pancreatic head adenocarcinoma (PanCA). This study describes the outcome and parameters, which predict survival of non-pancreatic periampullary carcinoma after resection. METHODS AND PATIENTS: Data from 148 consecutive patients with non-pancreatic periampullary carcinomas were recorded prospectively between 1993 and 2005 and analyzed using univariate and multivariate models. RESULTS: One hundred thirty-three of 148 (90%) patients were resected for histologically proven non-pancreatic periampullary carcinomas. R0 resection was achieved for 92% of AmpCA, for 88% of CholCA and for all the DuoCA. The lowest recurrence rate was seen in DuoCA with 18%, followed by AmpCA with 21% and CholCA with 46%. The mean survival time was 60.9 months for AmpCA patients, 42.9 months for CholCA and 45.4 months for DuoCA patients. Five-year survival was 50.5%, 29.9% and 24.5% for AmpCA, CholCA and DuoCA, respectively. Multivariate analysis identified low bilirubin levels (<100 micromol/l), R0 resections and absence of surgical complications to be strong independent predictors of survival (p<0.05). In AmpCA low tumor stages are also an independent predictor of long-term survival (p<0.01). For T1/T2 AmpCA the 5-year survival rate was 61%, whereas none of the patients with a T3/T4 tumor survived 5 years. CONCLUSION: Only T1/T2 ampullary carcinomas have a good prognosis, whereas T3/T4 ampullary tumors show aggressiveness similar to that of pancreatic head adenocarcinomas. Absence of surgical complications determines long-term outcome. Therefore, the combination of a complication-free and radical resection is essential for long-term survival.

DUHOCAMIS: a dual hollow cathode ion source for metal ion beams.

In this paper we describe a novel ion source named DUHOCAMIS for multiply charged metal ion beams. This ion source is derived from the hot cathode Penning ion gauge ion source (JINR, Dubna, 1957). A notable characteristic is the modified Penning geometry in the form of a hollow sputter electrode, coaxially positioned in a compact bottle-magnetic field along the central magnetic line of force. The interaction of the discharge geometry with the inhomogeneous but symmetrical magnetic field enables this device to be operated as hollow cathode discharge and Penning discharge as well. The main features of the ion source are the very high metal ion efficiency (up to 25%), good operational reproducibility, flexible and efficient operations for low charged as well as highly charged ions, compact setup, and easy maintenance. For light ions, e.g., up to titanium, well-collimated beams in the range of several tens of milliamperes of pulsed ion current (1 ms, 10/s) have been reliably performed in long time runs.

Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.

BACKGROUND: Duodenum-preserving pancreatic head resection according to Beger and the pylorus-preserving Whipple (ppWhipple) procedure were compared in patients with chronic pancreatitis (CP) in a randomized clinical trial. Perioperative data and short-term outcome have been reported previously. The present study evaluated long-term follow-up. METHODS: Forty patients were enrolled originally, 20 in each group. Long-term follow-up included mortality, morbidity, pain status, occupational rehabilitation, quality of life (QoL), and endocrine and exocrine function at median follow-up of 7 and 14 years. RESULTS: One patient who had a ppWhipple procedure was lost to follow-up. There were five late deaths in each group. No differences were noted in pain status and exocrine pancreatic function. Loss of appetite was significantly worse in the ppWhipple group at 14 years' follow-up, but there were no other differences in QoL parameters examined. After 14 years, diabetes mellitus was present in seven of 15 patients who had the Beger procedure and 11 of 14 patients after ppWhipple resection (P = 0.128). CONCLUSION: After long-term follow-up of up to 14 years early advantages of the Beger procedure were no longer present.

Fast track--different implications in pancreatic surgery.

Concepts in "fast-track" surgery, which provide optimal perioperative care, have been proven to significantly reduce complication rates and decrease hospital stay. This study explores whether fast-track concepts can also be safely applied and improve the outcomes of major pancreatic resections. Perioperative data from 255 consecutive patients, who underwent pancreatic resection by means of fast-track surgery in a high-volume medical center, were analyzed using univariate and multivariate models. Of the 255 patients, 180 received a pancreatic head resection and 51 received distal, 15 received total, and 9 received segmental pancreatectomies. The patients were discharged on median day 10 with a 30-day readmission rate of 3.5%. The in-hospital mortality was 2%, whereas medical and surgical morbidities were 17 and 25%, respectively. Fast-track parameters, such as first stools, normal food, complete mobilization, and return to normal ward, correlated significantly with early discharge (p < 0.05). Patients' age, operation time, and early extubation proved to be independent factors of early discharge, shown through multivariate analysis (odds ratio: 4.0, 2.0, and 2.8, respectively; p < 0.05). Low readmission, mortality, and morbidity rates demonstrate that fast-track surgery is in fact feasible and safe and promotes earlier discharge without compromising patient outcomes.

[Kausch-Whipple pancreaticoduodenectomy. Technique and results]. / Operation nach Kausch-Whipple. Technik und Ergebnisse.

The Kausch-Whipple operation is the standard procedure for resection of pancreatic head cancer, distal bile duct cancer, and periampullary cancers. It is also used for some cases of chronic pancreatitis. Traditionally, this operation is associated with high perioperative morbidity and mortality. The aim of our study was to present our current technique for Kausch-Whipple pancreaticoduodenectomy and to demonstrate that acceptable perioperative and long-term outcomes can be achieved by a standardised technique in a high-volume centre.

Influence of high-dose pancreatic enzyme treatment on pancreatic function in healthy volunteers.

CONCLUSIONS: Adaptive changes in exocrine and endocrine pancreatic function, as well as changes in pancreas size and morphology, were not observed after 4-wk of oral pancreatic enzyme application. These findings suggest that the normal pancreas does not significantly adapt--either morphologically or functionally--to a 4-wk oral application of high-dose pancreatic enzymes. BACKGROUND: The control of exocrine pancreatic enzyme secretion is not completely understood. Although it has been established that exocrine pancreatic secretion is mainly regulated in the short-term by the amount of pancreatic enzymes in the proximal small intestine, it is not known whether long-term application of pancreatic enzymes causes changes in exocrine pancreatic secretion in humans. METHODS: Twelve healthy male volunteers (median age 27 yr) participated in a prospective, randomized, placebo-controlled, double-blind study. Six were placed in the treatment group and six in the placebo group. Over a 4-wk period, the six subjects in the treatment group took 18 capsules of Panzytrat (20,000 units of lipase, 18,000 units of amylase, and 1000 units of protease per capsule) daily. Before (wk 0), 4 wk following pancreatic enzyme application and 2 wk afterward, a secretin-cerulein test was carried out in all subjects to study exocrine pancreatic function (trypsin, chymotrypsin, bicarbonate content, and total pancreatic fluid secretion in the duodenum). One day following the secretin-cerulein test, a standard test meal was given to all subjects to analyze endocrine pancreatic function. Additionally, before starting the treatment, once per week during treatment and 2 wk afterward, an ultrasound examination of the pancreas was carried out to see whether there was any change in pancreas size and morphology. RESULTS: Trypsin content in the duodenal aspirates following simultaneous stimulation with secretin and cerulein after 4 wk of high-dose pancreatic enzyme application was 92% in the treatment group and 82% in the placebo group compared with the wk 0 test results (100%). Two weeks after enzyme application, the secretin/cerulein-stimulated trypsin content was 88% in the treatment group and 107% in the placebo group. None of these changes was statistically significant. The same results were seen for chymotrypsin content, amylase, and bicarbonate content as well as for total pancreatic fluid secretion. Additionally, no change in the endocrine pancreatic function could be observed after 4 wk of pancreatic enzyme treatment. Pancreas ultrasonography revealed no alteration in pancreas size or parenchymal structure during the 4 wk of treatment and the following 2 wk.

[Membrane injuries of pancreatic acinar cells are the first changes in early stage acute experimental pancreatitis]. / Membranverletzungen von Pankreasazinuszellen stellen eine der ersten Veränderungen im Frühstadium der akuten experimentellen Pankreatitis dar.

We tested the hypothesis that membrane wounding of acinar cells is one of the earliest changes during the induction of acute pancreatitis. Wounding of cell membranes was detected by the penetration of the animals own albumin into cells. The pancreatitis was induced by the intraperitoneal injection of supramaximal doses of caerulein. The controls received saline. Fifteen to 180 min. after the injection the animals were perfused with buffer followed by fixative. Frozen sections of pancreas were processed identically for immunocytological localization of albumin. The intensity of staining was quantified by image analysis. Animals receiving caerulein consistently display significantly greater (p < 0.001) anti-albumin immunostaining in the cytoplasm of acinar cells than controls. The penetration of albumin into acinar cells indicates that wounding of their plasma membrane occurs during the onset of acute pancreatitis. Wounding of membranes may allow the exit of molecules such as enzymes from the acinar cells during this period.

Gastric emptying following pylorus-preserving Whipple and duodenum-preserving pancreatic head resection in patients with chronic pancreatitis.

BACKGROUND: After pylorus-preserving Whipple (PPW), delayed gastric emptying (DGE) is reported in up to 50% of these patients. We analyzed gastric emptying and hormonal adaptation of cholecystokinin (CCK), pancreatic polypeptide (PP), and gastrin following two surgical procedures for chronic pancreatitis (CP): the PPW and the duodenum-preserving pancreatic head resection (DPPHR). METHODS: Ten patients underwent DPPHR and 10 underwent PPW for CP. Preoperatively and 10 days and 6 months postoperatively, gastric emptying (paracetamol absorption test) and CCK, gastrin, and PP were measured using a test meal stimulation. RESULTS: The area under the serum paracetamol time curve for 0 to 120 minutes (AUC) showed no preoperative difference. Ten days postoperatively, the AUC was significantly reduced (P <0.05) after PPW but not after DPPHR. Six months postoperatively, AUC was comparable with the preoperative findings in DPPHR and PPW. The integrated 180-minute PP release was significantly reduced 10 days and 6 months postoperatively in both groups. The integrated 180-minute CCK release was decreased 10 days after PPW, but failed to be significant (P = 0.053). Gastrin levels were postoperatively unchanged. CONCLUSION: Following DPPHR we found no delay in gastric emptying. In contrast, DGE occurs early after PPW. Our data may help explain the slower recovery in PPW patients with regard to weight gain and relief from pain, which may be due to the functional alteration of gastric emptying and motility after this type of surgery.

Duodenum-preserving pancreatic head resection: Long-term results.

Early and late results from 298 patients with chronic pancreatitis who were surgically treated by means of duodenum-preserving pancreatic head resection (DPPHR) were prospectively analyzed. The aim of this operative procedure is to treat complications of chronic pancreatitis caused by inflammatory enlargement of the pancreatic head by decompressing the common bile duct, the pancreatic duct, the duodenum, and the retropancreatic intestinal vessels. End points of the study were early and late postoperative outcome. The follow-up period ranged from 1 to 22 years with a median follow-up of 6 years. In-hospital mortality was 1%, postoperative morbidity was 28.5%, and the rate of repeat laparotomy was 5.7%. Diabetes mellitus developed early in the postoperative period in six patients (2%). After a median follow-up of 6 years, late mortality was 8.9%. In the late follow-up period 88% of our patients were completely free of pain or had infrequent episodes and 63% were able to return to work. DPPHR might be considered as an alternative surgical technique in the treatment of chronic pancreatitis if the dominant lesion is in the pancreatic head.

[Duodenum preserving resection of the head of the pancreas: a new standard operation in chronic pancreatitis]. / Die duodenumerhaltende Pankreaskopfresektion: Eine neue Standardoperation bei chronischer Pankreatitis.

Between 1972 and 1993, 298 patients with chronic pancreatitis underwent a duodenum-preserving pancreatic head resection (DPPHR). The early and late outcomes were prospectively analyzed. An operative mortality rate of 1%, a postoperative morbidity rate of 28.5% and a relaparotomy rate of 5.7% for the DPPHR were competitive with the rates for Whipple resection. After a median late follow-up of 6 years (range: 1 to 22 years), late mortality was 9%; 88% of the patients had no or infrequent episodes of pain and 63% were completely rehabilitated professionally. Only 6 patients developed diabetes mellitus early postoperatively. Our study proves that the duodenum-preserving pancreatic head resection provides better results than the Whipple resection. Therefore, this operation should be adopted as a new standard operation in patients with chronic pancreatitis.

Maldigestion after total gastrectomy is associated with pancreatic insufficiency.

OBJECTIVES: Subsequent to total gastrectomy, many patients develop maldigestion and weight loss. The mechanisms that underlie these changes are not known. Therefore, in a prospective study, we have analyzed endocrine and exocrine pancreatic function in patients before and 3 months after total gastrectomy. METHODS: In 15 patients (12 male, three female, median age 62.4 yr) undergoing total gastrectomy due to gastric cancer, a direct exocrine pancreatic function test (secretin-cerulein test) was performed. In addition, a standard test meal was given to all patients to study endocrine pancreatic function and the pattern of hormones that influence exocrine pancreatic secretion. In nine patients, both function tests were repeated 3 months after total gastrectomy. Before and at 11 points after the application of the test meal, blood samples were taken for the measurement of glucose, insulin, glucagon, gastrin, pancreatic polypeptide, and cholecystokinin. In addition, a secretin-cerulein test was performed to analyze trypsin, chymotrypsin, amylase, bicarbonate, and the juice volume in the duodenal aspirates. RESULTS: Three months after total gastrectomy, all patients exhibited severe primary exocrine pancreatic insufficiency. Secretin-cerulein tests revealed that pancreatic juice secretion, trypsin, chymotrypsin, and amylase were significantly reduced by 76%, 89%, 91%, and 72%, respectively, 3 months after total gastrectomy and secretin and cerulein stimulation. Post-operatively, the patients had a pathological glucose tolerance with increased postprandial insulin and glucagon secretion. The baseline and postprandial gastrin and pancreatic polypeptide secretion were significantly decreased after total gastrectomy. In contrast, early postprandial cholecystokinin secretion was significantly increased postoperatively. CONCLUSIONS: After total gastrectomy, patients develop severe primary exocrine pancreatic insufficiency with decreased gastrin, decreased late postprandial pancreatic polypeptide, and increased cholecystokinin levels. These findings may explain why many patients with total gastrectomy have maldigestion and weight loss postoperatively. Therefore, gastrectomized patients should be given pancreatic enzymes to avoid these symptoms.