Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies.

BACKGROUND: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)-1 have become the current standard of care and first-line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety. OBJECTIVES: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC. METHODS: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non-progressing or stable under active therapy, were eligible for inclusion. RESULTS: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration. CONCLUSION: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials.

SAR user guide to the rectal MR synoptic report (primary staging).

Rectal MR is the key diagnostic exam at initial presentation for rectal cancer patients. It is the primary determinant in establishing clinical stage for the patient and greatly impacts the clinical decision-making process. Consequently, structured reporting for MR is critically important to ensure that all required information is provided to the clinical care team. The SAR initial staging reporting template has been constructed to address these important items, including locoregional extent and factors impacting the surgical approach and management of the patient. Potential outputs to each item are defined, requiring the radiologist to commit to a result. This provides essential information to the surgeon or oncologist to make specific treatment deisions for the patient. The SAR Initial Staging MR reporting template has now been officially adopted by the NAPRC (National Accreditation Program for Rectal Cancer) under the American College of Surgery. With the recent revisions to the reporting template, this user guide has been revamped to improve its practicality and support to the radiologist to complete the structured report. Each line item of the report is supplemented with clinical perspectives, images, and illustrations to help the radiologist understand the potential implications for a given finding. Common errors and pitfalls to avoid are highlighted. Ideally, rectal MR interpretation should not occur in a vacuum but in the context of a multi-disciplinary tumor board to ensure that healthcare providers use common terminology and share a solid understanding of the strengths and weaknesses of MR.

Increased tumour cell PD-L1 expression, macrophage and dendritic cell infiltration characterise the tumour microenvironment of ulcerated primary melanomas.

BACKGROUND: Primary melanoma ulceration is an unfavourable prognostic factor included in current staging systems. Yet, the immunological and molecular alterations responsible for this adverse outcome have not been fully elucidated. OBJECTIVES: We aimed to identify immunological differences between ulcerated and non-ulcerated primary melanomas concerning both innate and adaptive immunity and to correlate these with clinical outcome. METHODS: Formalin-fixed paraffin-embedded primary melanomas from 112 patients (pts) were analysed by immunohistochemistry. The expression of various markers identifying tumour-infiltrating lymphocytes, macrophages and dendritic cells was evaluated semi-quantitatively by three independent investigators. Tumour cell expression of programmed death-ligand 1 (PD-L1), transporter of antigen processing 1 and the MxA protein was also analysed. RESULTS: Recurrence occurred in 21/56 pts (37.5%) with ulcerated vs. 14/56 pts (25.0%) with non-ulcerated tumours (P = 0.15). Tumour ulceration was associated with more frequent development of brain metastasis (17.6 vs. 3.6% of pts, P = 0.015). Immunohistochemistry showed an association of ulceration with the presence of intratumoural CD68+ macrophages (P = 0.028) as well as with increased numbers of intratumoural CD11c+ dendritic cells (P = 0.014) and CD163+ macrophages (P = 0.001). PD-L1 positivity (expression in >1% of tumour cells) was more frequent in ulcerated than non-ulcerated tumours [40 (72.7%) vs. 25 (44.6%), P = 0.003]. A positive correlation between intratumoural CD11c+ (Spearman's correlation coefficient ρ: 0.42) and CD163+ (ρ: 0.31) cell count and frequency of tumour cell PD-L1 expression was detected. CONCLUSIONS: Our results confirm the adverse clinical outcome associated with primary melanoma ulceration, particularly concerning the risk of recurrence and subsequent development of brain metastases. The observed immunological differences suggest a conceivable role of increased intratumoural macrophage and dendritic cell counts associated with enhanced tumour cell PD-L1 expression potentially contributing to the immunosuppressive, growth-promoting microenvironment of ulcerated primary melanomas.

Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease.

Monocytes play an important role in inducing host systemic immunity against invading pathogens and inflammatory responses. After activation, monocytes migrate to tissue sites, where they initiate both innate and adaptive immune responses, and become macrophages. Although mucosal macrophages produce inflammatory cytokines in response to pathogens, the perturbations in innate immune signaling pathway have been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE). In this review, we focus on the role of human macrophages in intestinal innate immune responses, homeostasis, and SLE disease. We further discuss sex differences in the intestinal macrophages and their role in the physiology and pathogenesis of SLE.

[Application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma: a report of 33 cases].

Objective: To analyze the application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma. Methods: The clinical data of 33 patients with vascular invasion of pancreatic carcinoma who underwent radical resection from April 2013 to April 2017 in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital were retrospectively analyzed. There were 14 males and 19 females with age of (62.5±10.6)years(ranging from 35 to 78 years). Vascular replacement technique with allogenic blood vessel was used on all patients who underwent radical resection for pancreatic carcinoma. The operation procedure was made according to the specific location of the carcinoma, and the allogenic blood vessel was selected according to the type of vascular invasion. The matching vessel was selected for replacement to the patient who was invaded only one vessel. And the "Y" type of iliac vein was selected for replacement to the patient who was invaded the confluence of portal vein, splenic vein and superior mesenteric vein. After the operation, the patients were followed up by telephone and outpatient review. Results: All of 33 patients were successfully completed the operations. There were 28 patients underwent pancreaticoduodenectomy with vascular replacement, and 5 patients underwent total pancreatectomy with vascular replacement. All the patients were confirmed pancreatic carcinoma and R0 resection according to the postoperative pathology. There were 16 patients with the carcinoma invasion the confluence of portal vein, splenic vein and superior mesenteric vein, 12 patients with the carcinoma invasion the superior mesenteric vein, and 5 patients with the carcinoma invasion the portal vein. There was no perioperative death in this group and no complications related to allogenic blood vessel. The incidence of postoperative complications was 18.2% (6/33), and the incidence of pancreatic fistula was 6.1% (2/33), all of which were biochemical fistula. There were 32 patients were followed up, and the follow-up rate was 96.9%. The median survival time was 14.6 months. The half-year, 1-year and 2-year survival rates were 75.6%, 37.6% and 27.4%. Conclusion: The application of vascular replacement technique with allogenic blood vessel for pancreatic carcinoma has a great significance for improving the R0 resection rate and the prognosis of patients.

Autonomic and sensory nerve modulation of peristalsis in the upper urinary tract.

The primary function of the upper urinary tract is to propel urine and various water-soluble toxic compounds from the kidneys to the bladder for storage and evacuation to maintain body ionic balance and contribute to the regulation of blood volume and pressure. The mechanism by which the upper urinary tract propels urine has long been considered to be myogenic in origin as peristaltic contractions in vivo and in vitro (pyeloureteric peristalsis) propagate in a manner little affected by drugs that block nerve conduction or the sympathetic and parasympathetic transmission. However, it is now well established that the release of intrinsic prostaglandins and neuropeptides from primary sensory nerves (PSNs) helps to maintain pyeloureteric peristalsis. Electrical field stimulation of PSNs evokes species-specific positive inotropic and chronotropic effects that have been attributed to release of excitatory tachykinins superimposed on negative inotropic and chronotropic effects associated with the release of calcitonin gene related peptide (CGRP), a rise in cellular cyclic-adenosine monophosphate (cAMP) and a protein kinase A-dependent activation of glibenclamide-sensitive ATP-dependent K+ (KATP) channels. This review summarises the existing evidence of the nervous control of the upper urinary tract and recent evidence suggesting that the autonomic innervation may indirectly modulate pyeloureteric peristalsis via the activation of PSN nicotinic receptors and via the modulation of KV7 channels located on interstitial cells within the renal pelvis wall.

[Molecular diagnostics in melanoma]. / Molekulare Diagnostik beim Melanom.

The molecular landscape of melanoma is changing more rapidly than ever since new molecular technology approaches have made it possible to examine human melanoma for genetic alterations underlying the disease. In recent years, these approaches have identified new familial melanoma susceptibility genes, most of them also conferring risk to other cancers. This has implications for clinical testing and surveillance. Furthermore, molecular testing of melanoma to determine therapeutic eligibility for targeted therapies is now standard of care and should be familiar to the dermatologist.

Urinary expression of novel tissue markers of kidney injury after ureteroscopy, shockwave lithotripsy, and in normal healthy controls.

BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) and ureteroscopy (URS) are minimally invasive treatment alternatives for kidney stones. Although less invasive, SWL subjects the renal parenchyma to a high level of energy and the potential to cause renal injury. The ability to detect renal injury post-SWL in a reliable and noninvasive way would be clinically beneficial. Kidney injury molecule 1 (KIM-1) and N-acetyl-ß-D-glucosaminidase (NAG) are two proteins secreted by the kidney into the urine and have been found to be sensitive markers of acute kidney injury in transplant patients. The aim of this work was to measure urinary levels of KIM-1 and NAG in patients with kidney stone who were treated by SWL or URS and in nonstone volunteers. PATIENTS AND METHODS: Patients with kidney stones who were treated by SWL (n = 50) or URS (n = 10) were recruited. Voided urine samples were collected before and 2 to 3 hours after URS and SWL. In addition, further urinary specimens were collected 2 days and 2 weeks post-SWL treatment. Voided urine samples from healthy volunteers were also collected. RESULTS: Mean KIM-1 values were increased in patients with kidney stones when compared with volunteers. KIM-1 and NAG levels significantly increased post-SWL and returned to baseline within 2 weeks post-SWL. Poor kidney function was significantly associated with increased biomarker activity both in baseline and post-SWL measurements. There was no significant change in urinary KIM-1 and NAG concentrations before and after URS. CONCLUSIONS: Kim-1 and NAG levels significantly increased post-SWL treatment suggesting a potential role for these urinary markers in identifying patients at higher risk of tissue injury.

Nicotinic receptor activation on primary sensory afferents modulates autorhythmicity in the mouse renal pelvis.

BACKGROUND AND PURPOSE: The modulation of the spontaneous electrical and Ca(2+) signals underlying pyeloureteric peristalsis upon nicotinic receptor activation located on primary sensory afferents (PSAs) was investigated in the mouse renal pelvis. EXPERIMENTAL APPROACH: Contractile activity was followed using video microscopy, electrical and Ca(2+) signals in typical and atypical smooth muscle cells (TSMCs and ASMCs) within the renal pelvis were recorded separately using intracellular microelectrodes and Fluo-4 Ca(2+) imaging. KEY RESULTS: Nicotine and carbachol (CCh; 1-100 µM) transiently reduced the frequency and increased the amplitude of spontaneous phasic contractions in a manner unaffected by muscarininc antagonists, 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide) and pirenzipine (10 nM) or L-NAME (L-Nω-nitroarginine methyl ester; 200 µM), inhibitor of NO synthesis, but blocked by the nicotinic antagonist, hexamethonium or capsaicin, depletor of PSA neuropeptides. These negative chronotropic and delayed positive inotropic effects of CCh on TSMC contractions, action potentials and Ca(2+) transients were inhibited by glibenclamide (Glib; 1 µM), blocker of ATP-dependent K (KATP) channels. Nicotinic receptor-evoked inhibition of the spontaneous Ca(2+) transients in ASMCs was prevented by capsaicin but not Glib. In contrast, the negative inotropic and chronotropic effects of the non-selective COX inhibitor indomethacin were not prevented by Glib. CONCLUSIONS AND IMPLICATIONS: The negative chronotropic effect of nicotinic receptor activation results from the release of calcitonin gene-related peptide (CGRP) from PSAs, which suppresses Ca(2+) signalling in ASMCs. PSA-released CGRP also evokes a transient hyperpolarization in TSMCs upon the opening of KATP channels, which reduces contraction propagation but promotes the recruitment of TSMC Ca(2+) channels that underlie the delayed positive inotropic effects of CCh.

Changes in body weight, glucose homeostasis, lipid profiles, and metabolic syndrome after restrictive bariatric surgery.

OBJECTIVE: Bariatric surgery is an established therapy for morbid obesity. We evaluated the effects of sleeve-gastrectomy on weight, glucose and lipid metabolism and prevalence of metabolic-syndrome for up to 2 years. METHODS: In 52 morbidly obese patients weight, BMI, total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, Lipoprotein(a), glucose, HbA1c, insulin, and criteria defining the metabolic-syndrome were determined preoperatively and 6 (n=52), 12 (n=41) and 24 (n=5) months after surgery. RESULTS: BMI decreased from 51±8 kg/m² to 40±7, 39±8, and 38±9 kg/m² at 6, 12, and 24 months postoperatively. Glucose and HbA1c changed from 116±44 to 93±21 and 94±18 mg/dl and 6.0±1.3 to 5.4±0.8 and 5.4±0.8% at 6 and 12 months postoperatively. Triglycerides decreased from 159±87 to 116±41 and 116±62 mg/dl, while HDL--cholesterol increased from 46±12 to 50±12 and 56±13 mg/dl at 6 and 12 months. None of the changes correlated with changes in weight. Prevalence of metabolic syndrome decreased from 81% to 36% and 34% at 6 and 12 months, with individual criteria (central obesity, triglycerides, HDL-cholesterol, hypertension, and fasting glucose) being reduced by 8/12%, 31/28%, 12/37%, 27/30%, and 38/31% at 6/12 months, respectively. The decrease in triglycerides and HbA1c was more pronounced in hypertriglyceridemic patients compared to normo-triglyceridemic patients, while there was no significant difference between diabetic and non-diabetic patients. CONCLUSIONS: This is the first study evaluating sleeve-gastrectomy in German patients. Our data indicate that sleeve-gastrectomy induces a similar metabolic improvement as malabsorptive surgery. Although metabolic improvement did not correlate with weight reduction, improvement almost exclusively occurred within the first 6 months, when significant weight reduction occurred. It is unclear whether this relates to the operative techniques or to the selection of patients.

The impact of local anesthetic distribution on block onset in ultrasound-guided interscalene block.

BACKGROUND: Recent investigations of local anesthetic distribution in the lower extremity have revealed that completely surrounding the sciatic nerve with local anesthetic provides the advantage of more rapid and complete anesthesia in the territory served by the nerve. We hypothesized that a pattern of distribution that entirely envelops the targeted nerve roots during interscalene block would provide similar benefits of more rapid anesthesia onset. METHODS: During interscalene block guided by ultrasound with nerve stimulator confirmation, the pattern of local anesthetic distribution was recorded and later classified as complete or incomplete envelopment of the visible nerve elements in 50 patients undergoing ambulatory shoulder arthroscopic surgery. The pattern was then compared with the extent of block setup at pre-determined intervals, as well as to post-operative pain levels and block duration. RESULTS: Twenty-two patients (44%) had complete envelopment of the nerves in the plane of injection during ultrasound imaging of the interscalene block. There was no difference in the fraction of blocks that were fully set-up at 10 min with regards to complete or incomplete envelopment of the nerves by local anesthetic. All of the patients had complete setup of the block by 20 min. In addition, the post-operative pain levels and duration of block did not vary among the two groups with complete vs. incomplete local anesthetic distribution around the nerves. CONCLUSION: The presence or absence of complete envelopment of the nerve elements in the interscalene groove by local anesthetic did not determine the likelihood of complete block effect at pre-determined time intervals after the procedure.

Anesthetic management in upper extremity transplantation: the Pittsburgh experience.

BACKGROUND: Hand/forearm/arm transplants are vascularized composite allografts, which, unlike solid organs, are composed of multiple tissues including skin, muscle, tendons, vessels, nerves, lymph nodes, bone, and bone marrow. Over the past decade, 26 upper extremity transplantations were performed in the United States. The University of Pittsburgh Medical Center has the largest single center experience with 8 hand/forearm transplantations performed in 5 recipients between January 2008 and September 2010. Anesthetic management in the emerging field of upper extremity transplants must address protocol and procedure-specific considerations related to the role of regional blocks, effects of immunosuppressive drugs during transplant surgery, fluid and hemodynamic management in the microsurgical setting, and rigorous intraoperative monitoring during these often protracted procedures. METHODS: For the first time, we outline salient aspects of upper extremity transplant anesthesia based on our experience with 5 patients. We highlight the importance of minimizing intraoperative vasopressors and improving fluid management and blood product use. RESULTS: Our approach reduced the incidence of perioperative bleeding requiring re-exploration or hemostasis and shortened in-hospital and intensive care unit stay. Functional, immunologic and graft survival outcomes have been highly encouraging in all patients. CONCLUSIONS: Further experience is required for validation or standardization of specific anesthetic protocols. Meanwhile, our recommendations are intended as pertinent guidelines for centers performing these novel procedures.

Identification of coffee components that stimulate dopamine release from pheochromocytoma cells (PC-12).

Coffee and caffeine are known to affect the limbic system, but data on the influence of coffee and coffee constituents on neurotransmitter release is limited. We investigated dopamine release and Ca(2+)-mobilization in pheochromocytoma cells (PC-12 cells) after stimulation with two lyophilized coffee beverages prepared from either Coffea arabica (AR) or Coffea canephora var. robusta (RB) beans and constituents thereof. Both coffee lyophilizates showed effects in dilutions between 1:100 and 1:10,000. To identify the active coffee compound, coffee constituents were tested in beverage and plasma representative concentrations. Caffeine, trigonelline, N-methylpyridinium, chlorogenic acid, catechol, pyrogallol and 5-hydroxytryptamides increased calcium signaling and dopamine release, although with different efficacies. While N-methylpyridinium stimulated the Ca(2+)-mobilization most potently (EC(200): 0.14±0.29µM), treatment of the cells with pyrogallol (EC(200): 48±14nM) or 5-hydroxytryptamides (EC(200): 10±3nM) lead to the most pronounced effect on dopamine release. In contrast, no effect was seen for the reconstituted biomimetic mixture. We therefore conclude that each of the coffee constituents tested stimulated the dopamine release in PC-12 cells. Since no effect was found for their biomimetic mixture, we hypothesize other coffee constituents being responsible for the dopamine release demonstrated for AR and RB coffee brews.

Transcriptome profiling of female alates and egg-laying queens of the Formosan subterranean termite.

Termites are known to have an extraordinary reproductive plasticity and capacity, but the underlying genetic patterns of termite reproductive biology are relatively understudied. The goal of this study was to identify genes for which expression levels differ between dealated precopulatory females (virgins) and egg-laying queens of the Formosan subterranean termite, Coptotermes formosanus Shiraki. We constructed a normalized polyphenic expressed sequence tag (EST) library that represents genomic material from most of the castes and life stages of the Formosan subterranean termite. Microarrays were designed using probes from this EST library and public genomic resources. Virgin females and queens were competitively hybridized to these microarrays and differentially expressed candidate genes were identified. Differential expression of eight genes was subsequently confirmed via reverse transcriptase quantitative PCR (RT-QPCR). When compared to virgins, queens had higher expression of genes coding for proteins related to immunity (gram negative binding protein), nutrition (e.g., termite-derived endo-beta-1,4-glucanase), protein storage, regulation of caste differentiation and reproduction (hexamerin, juvenile hormone binding protein). Queens also had higher transcript levels for genes involved in metabolism of xenobiotics, fat, and juvenile hormone (glutathione-S-transferase-like proteins, and cytochrome P450), among others. In particular, hexamerin, juvenile hormone binding protein, and a cytochrome P450 from the 4C subfamily are likely to be involved in initiating the inactive period during the reproductive cycle of the queen. Vice versa, virgins had higher expression than queens of genes related to respiration, probably due to recent flight activity, and several genes of unknown function.

[Bariatric surgery and associated complications: radiological imaging]. / Adipositaschirurgie und ihre Komplikationen : Radiologische Bildgebung.

Obesity is an increasing problem faced by the healthcare system. In managing obesity, bariatric surgery is becoming more important with evidence showing a reduction in long-term morbidity and mortality. There are special challenges faced by the radiology department in providing an imaging service for this population of patients, from technical requirements through to the interpretation of post-surgical images. This article provides an overview of the most frequently performed procedures, normal postoperative imaging findings and the appearance of common complications.

The Eyes Absent phosphatase-transactivator proteins promote proliferation, transformation, migration, and invasion of tumor cells.

The Eyes Absent (EYA) proteins combine transactivation, tyrosine phosphatase, and threonine phosphatase activities in their function as part of a conserved regulatory cascade involved in embryonic organ development. EYA tyrosine phosphatase activity contributes to fly eye development, and vertebrate EYA is involved in promoting DNA damage repair subsequent to genotoxic stress. EYAs are known to be expressed at elevated levels in ovarian and breast cancers. Here, we show that the tyrosine phosphatase activity of the EYAs promotes tumor cell migration, invasion, and transformation. These cellular effects are accompanied by alterations of the actin cytoskeleton and increased levels of active Rac and Cdc42. The invasiveness conferred by EYA is reflected in vivo by inhibition of metastasis seen when EYA3 expression is silenced in the invasive breast cancer cell line MDA-MB-231. Together, our data directly associate the tyrosine phosphatase activity of the EYAs with the oncogenesis-associated cellular properties of motility and invasiveness.

[Tracheal stents for esophagotracheal fistula in laryngectomy patients. Safe fixation to the tracheostoma]. / Trachealstents wegen ösophagotrachealer Fistel beim Laryngektomierten. Sichere Fixierung am Tracheostoma.

BACKGROUND: Postradiotherapy or malignant esophagotracheal fistulas still represent a dilemma. In the absence of surgical options attempts are made to close the fistula endoscopically by means of esophageal and/or tracheal stents. Tracheal stent placement in laryngectomy patients with terminal stomas is particularly problematic due to the risk of stent dislocation during cannula replacement PATIENTS AND METHODS: Six laryngectomy patients with high esophagotracheal fistulas were each fitted with a coated Ultraflex stent (Boston Scientific, Watertown/MA, US). Following skin undermining, the stents were fixed to the tracheostoma with interrupted sutures and the skin flaps attached to the stent with a second row of sutures. RESULTS: Fistulas could be completely closed in all patients and there were no cases of stent dislocation. Cannula replacement was unproblematic. CONCLUSIONS: Suture fixation of tracheal stents is a viable procedure even for patients with esophagotracheal fistulas and terminal tracheostomy following laryngectomy.

[Management of cholecysto- and choledocholithiasis--survey and analysis of 16 615 cholecystectomies and common bile duct explorations in bavaria]. / Aktuelle Therapie der Cholezysto- und Choledocholithiasis - Umfrageergebnisse mit Analyse von 16 615 Eingriffen in Bayern.

BACKGROUND AND METHODS: The aim of this study was the evaluation of the management of cholecysto- and choledocholithiasis and outcome of -laparoscopic as well as open cholecystectomy (CHE) and common bile duct (CBD) exploration in Bavaria, Germany. A written questionnaire -in-cluding 201 structured items was sent to all 180 hospitals and departments performing gen-eral or abdominal surgery in Bavaria. RESULTS: The response rate was 60 %. A total of 16 615 operations for gallstone disease including 16 051 cholecystectomies and 453 CBD explo-ra-tions with or without cholecystectomy were -reported. 88 % of all cholcystectomies started -laparoscopically, the conversion rate was 5.6 %. The Veres needle (69 %), 4 trocar techniques and electrosurgical hook knife were reported as standard procedures. A retrieval bag was used by 53 % of all surgeons. The overall complication rate for cholecystectomy was 5.46 % including 0.15 % -major bile duct injuries. Relaparoscopy was performed in 0.35 %, relaparotomy in 0.44 % and postoperative treatment by ERC in 1.45 %. The overall hospital mortality rate was 0.13 %. When choledocholithiasis was suspected, a two-stage management ("therapeutic splitting") with preoperative ERC was preferred (99 %). The conversion rate of simultaneous laparoscopic CHE+CBD exploration was 43 %. CONCLUSION: These results allow an estimation of the frequency and overall risks in surgical therapy for gallstones. At present, new techniques like combined laparoscopic and endoscopic proce-dures, microinstruments or N.O.T.E.S do not play a significant role in Germany.

Transcriptome profiling of selectively bred Pacific oyster Crassostrea gigas families that differ in tolerance of heat shock.

Sessile inhabitants of marine intertidal environments commonly face heat stress, an important component of summer mortality syndrome in the Pacific oyster Crassostrea gigas. Marker-aided selection programs would be useful for developing oyster strains that resist summer mortality; however, there is currently a need to identify candidate genes associated with stress tolerance and to develop molecular markers associated with those genes. To identify candidate genes for further study, we used cDNA microarrays to test the hypothesis that oyster families that had high (>64%) or low (<29%) survival of heat shock (43 degrees C, 1 h) differ in their transcriptional responses to stress. Based upon data generated by the microarray and by real-time quantitative PCR, we found that transcription after heat shock increased for genes putatively encoding heat shock proteins and genes for proteins that synthesize lipids, protect against bacterial infection, and regulate spawning, whereas transcription decreased for genes for proteins that mobilize lipids and detoxify reactive oxygen species. RNAs putatively identified as heat shock protein 27, collagen, peroxinectin, S-crystallin, and two genes with no match in Genbank had higher transcript concentrations in low-surviving families than in high-surviving families, whereas concentration of putative cystatin B mRNA was greater in high-surviving families. These ESTs should be studied further for use in marker-aided selection programs. Low survival of heat shock could result from a complex interaction of cell damage, opportunistic infection, and metabolic exhaustion.

[Operative techniques and outcomes in metabolic surgery: sleeve gastrectomy]. / Operative Techniken und deren Outcome in der metabolischen Chirurgie: Sleeve-Gastrektomie.

Laparoscopic sleeve gastrectomy (LSG) was initially introduced for super-obese patients in a two-step concept in order to reduce the perioperative risk. Many years before a very similar technique - the Magenstrasse and Mill (M & M) operation - was developed by Johnston in Leeds / UK as a "more physiological" bariatric procedure with acceptable weight loss, while preserving gastric emptying mechanisms and thus minimising possible side-effects such as vomiting, dumping and diarrhoea, which are common complications of gastric bypass procedures. The following manuscript analyses the current literature and our own preliminary results and parallels publications of the M & M procedure. Until now numerous modifications (e. g., bougie size and residual volume, stapler technique, use of buttress mate-rial) have been reported. However, reported -morbidity and mortality rates were equal to those of gastric banding and gastric bypass (RYGB). In conclusion, laparoscopic sleeve gastrectomy (LSG) has now proven to be as effective as the RYGB for weight loss over a three-year period. Control of hunger and feeling of fullness are -reported to be superior compared to gastric band-ing. Laparoscopic sleeve gastrectomy is no longer an experimental procedure. It should be accepted as one of the effective standard procedures for surgical treatment of morbid obesity.