Moon phases and moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation.

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

[Pancreatic cancer in the elderly: guidelines and individualized therapy]. / Pankreaskarzinom im hohen Alter: Leitlinien und individualisierte Therapie.

The considerable increase of the aged population in western civilisation within the next years will result in a rising incidence of pancreatic cancer. Until the year 2020 an increment of 20  % of patients beyond 65 years old can be anticipated. Therefore, the focus will be on management of old and geriatric surgical patients leading to strategical re-evaluation of surgical indications under critical consideration of feasibility and purpose. Even under modern interdisciplinary therapy concepts the prognosis of ductal adenocarcinoma of the pancreas remains poor with an overall 5-year survival rate of less than 5  %. The surgical resection is still considered as the only potential curative treatment option with extended life expectancy; however, it is technically demanding and furthermore associated with significant morbidity. In particular, the quality of surgery of the now interdisciplinary therapy of pancreatic cancer is markedly improved when performed at a high-volume centres. Until now only a few retrospective data analyses evaluating the perioperative and long-term outcome after pancreatic tumor resections in geriatric patients exist. The available results, however, support radical surgical procedures even beyond the age of 75 years.

[Surgical quality of organ retrieval in Bavaria]. / Chirurgische Qualität der Organentnahme in Bayern.

Surgical problems during organ procurement may propagate complications in the transplant recipient. Ultimately, these problems may result in the complete loss of already scarce donor organs.Donor reports (Eurotransplant donor report) of 1,492 donor organs from January 2010 to August 2012 in the German Foundation of Organ Transplantation (DSO) region of Bavaria and corresponding organ quality forms were analyzed. Surgical problems were classified into 3 categories: (I) surgical problems recognized and reported by the donor surgeon, (II) surgical problems observed by the recipient surgeon but not reported by the donor surgeon and (III) surgical problems leading to organ loss. Surgical problems during this 20-month time period were reported for 17.6 % of organs; category I in 5.5 %, category II in 11.1 % and category III in 1 %. Damage of graft vasculature in 9.1 % was the most frequently reported problem. The mean error index for individual surgeons was 16 % and one out of the five Bavarian organ procurement centers had significantly more problems in all categories (30 %). Interestingly, surgeons who performed rapid retrieval procedures had more problems with quality than surgeons who took more time. Organ retrieval is prone to surgical problems. Especially in a system of organ transport, consistent reporting of surgical problems and quality assurance is needed to maintain and to improve surgical quality.

[Abdominal organ retrieval: strategies to improve quality]. / Viszerale Organexplantation: Maßnahmen zur Verbesserung der Qualität.

The blatant problem of organ shortage leads to an increasing acceptance of organs from extended criteria donors. This increases the importance of the process of organ donation and retrieval. A working group of representatives of Bavarian retrieval surgeons and the procurement organization German Foundation of Organ Transplantation (DSO) was initiated to develop consensus-based recommendations for quality improvements in the field of organ retrieval on the basis of regional data. The main aim was to professionalize retrieval teams by specified training standards and to define objective qualifications for retrieval surgeons. Initial measures of the working group included agreement on standardized retrieval techniques and improvement of documentation in terms of quality forms and the return rate of the forms. Quality data are being analyzed prospectively with a new categorization of complications. Communication among centers and teams and complication reporting has already been improved and initial structural changes have been set up.

[Chronic pancreatitis or pancreatic malignancy: clinical and radiological differential diagnosis of pancreas head space-occupying mass]. / Chronische Pankreatitis oder Pankreasmalignom : Klinische und radiologische Differenzialdiagnose der Pankreaskopfraumforderung.

Chronic pancreatitis can be complicated both by an inflammatory benign mass and by the development of pancreatic cancer. The distinction of these complications is not only difficult but also crucial as patients suffering from either of the two have significantly different prognoses. This article describes typical clinical and radiological findings, which may help the physician in differentiating these two maladies. Furthermore, we conducted a retrospective study where we evaluated the clinical patterns in patients with chronic pancreatitis who underwent resection for a pancreatic mass. Although certain findings may be indicative for benign tumors, none of the diagnostic tools available offers a sufficient degree of certainty. In cases of tumors secondary to autoimmune pancreatitis the diagnostic error is exceptionally high. Because of the poor prognosis related to untreated pancreatic cancer, the general recommendation is to perform resection of the tumor when technically possible and when carcinoma cannot be ruled out completely.

[Non-curable tumours of the female genital tract: therapeutic options in bowel stenosis and bleeding]. / Inoperable Genitaltumoren der Frau: Therapeutische Optionen bei Darmstenose und -blutung.

BACKGROUND: Tumours of the female genital tract are often diagnosed at an advanced stage or re-lapse after initial curative therapy. Ovarian cancer is in particular associated with peritoneal carcinomatosis or local tumour progression entailing different intestinal complications. MATERIAL AND METHODS: Based on our own results and a systemic PubMed search, different intestinal complications in non-curable tumours of the female genital tract were defined and different surgical and non-surgical therapeutic options were analysed. RESULTS: Stenosis of the small bowel is often caused by direct infiltration of the tumour. Peritoneal carcinomatosis or postoperative abdominal adhesions may lead to an acute or even more often chronic recurrent obstruction. The rectum or sigmoid colon is in particular affected by stenosis caused by tumour masses within the pelvis, occurring fistulas or direct tumour infiltration which may lead to bleeding complications or a large bowel obstruction. Radiation-induced abdominal adhesions or stenosis of the small bowel as well as radiation-induced chronic proctocolitis are further common abdominal complications. Special attention with regard to a well balanced indication towards surgical, oncological or conservative management must be given in the palliative setting of the genital tract. CONCLUSION: In particular the dictum of "primum nihil nocere" has to be followed in consideration of the patient's declared intention, the patient's prognosis, general condition, psychological strain as well as the expected complications.

Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo.

PURPOSE: The close association of lymphatic and blood vessels and their coordinated development in vivo suggest that there are parallel mechanisms regulating hemangiogenesis and lymphangiogenesis. Here, we hypothesize that inhibition of the Src tyrosine kinase, apart from anti-hemangiogenic effects, results in a suppression of lymphangiogenesis. EXPERIMENTAL DESIGN: The ability of the Src kinase inhibitor PP2 to block Src in isolated lymphatic endothelial cells (LECs) was analyzed by Western Blot. The effects of PP2 on LEC proliferation, migration, and sprouting were assessed by MTT, Boyden chamber, and spheroid assays, respectively. The level of VEGF-C secreted by L3.6pl pancreatic carcinoma cells was measured by ELISA. For in vivo assessment of lymphangiogenesis, Src kinase inhibitor AZM475271 was used in mouse corneal micropocket and lymphangioma models. RESULTS: VEGF-C stimulation of isolated LECs led to an increased phosphorylation of Src kinase that was abrogated by PP2. Treatment with PP2 inhibited spheroid sprouting of LECs at even lower concentrations than suggested by the proliferation assay. Src inhibition significantly reduced the level of VEGF-C in L3.6pl supernatant. Treatment with PP2 also resulted in a significant reduction in the migratory activity of LECs. In vivo, Src inhibition reduced de novo formation of lymphangiomas and corneal neovascularization. CONCLUSIONS: Inhibition of Src kinase shows strong anti-lymphangiogenic activity in vitro and in vivo. Together with anti-angiogenic effects mediated by Src inhibition, this strategy may be attractive in the treatment of lymphatic and hematogeneous metastasis of cancer.

Blumgart anastomosis for pancreaticojejunostomy minimizes severe complications after pancreatic head resection.

BACKGROUND: Leakage from the pancreaticojejunostomy is the major cause of septic complications after partial pancreaticoduodenectomy. This study evaluated a new transpancreatic U-suture technique (Blumgart anastomosis, BA), which aims to avoid shear forces during knot-tying. METHODS: Using a before-after study design, BA was compared with a modified Cattell-Warren anastomosis (CWA). Two patient cohorts (CWA, 90; BA, 92), which were similar with respect to primary diagnosis, age, sex and American Society of Anesthesiologists score, were compared retrospectively. Dependent variables were surgical and overall morbidity and mortality after partial pancreaticoduodenectomy. RESULTS: Duration of operation (354 versus 328 min for CWA versus BA; P = 0.002), pancreatic leakage rate (13 versus 4 per cent; P = 0.032), postoperative haemorrhage (11 versus 3 per cent; P = 0.040), total surgical complications (31 versus 15 per cent; P = 0.011), general complications (36 versus 17 per cent; P = 0.005) and length of intensive care unit stay (median 5.4 versus 2.8 days; P = 0.015) were significantly reduced after BA. These effects were not related merely to an improvement over time. CONCLUSION: BA appears to be a fast, simple and safe technique for pancreaticojejunostomy. It might reduce leakage rates and surgical complications after partial pancreaticoduodenectomy.

Natural history, clinical pattern, and surgical considerations of pneumatosis intestinalis.

OBJECTIVE: Pneumatosis intestinalis has been increasingly detected in recent years with the more frequent use of computed tomography for abdominal imaging of the intestine. The underlying causes of the gas found during radiographic studies of the bowel wall can vary widely and different hypotheses regarding its pathophysiology have been postulated. Pneumatosis intestinalis often represents a benign condition and should not be considered an argument for surgery. However, it can also require life-threatening surgery in some cases, and this can be a difficult decision in some patients. METHODS: The spectrum of pneumatosis intestinalis is discussed here based on various computed tomographic and surgical findings in patients who presented at our University Medical Centre in 2003-2008. We have also systematically reviewed the literature to establish the current understanding of its aetiology and pathophysiology, and the possible clinical conditions associated with pneumatosis intestinalis and their management. RESULTS: Pneumatosis intestinalis is a primary radiographic finding. After its diagnosis, its specific pathogenesis should be ascertained because the appropriate therapy is related to the underlying cause of pneumatosis intestinalis, and this is sometimes difficult to define. Surgical treatment should be considered urgent in symptomatic patients presenting with an acute abdomen, signs of ischemia, or bowel obstruction. In asymptomatic patients with otherwise inconspicuous findings, the underlying disease should be treated first, rather than urgent exploratory surgery considered. Extensive and comprehensive information on the pathophysiology and clinical findings of pneumatosis intestinalis is provided here and is incorporated into a treatment algorithm. CONCLUSIONS: The information presented here allows a better understanding of the radiographic diagnosis and underlying aetiology of pneumatosis intestinalis, and may facilitate the decision-making process in this context, thus providing fast and adequate therapy to particular patients.

[Acute pancreatitis: is there a need for surgery?]. / Akute Pankreatitis: Wann ist der Chirurg gefragt?

The treatment of acute pancreatitis is primarily non-surgical. An interdisciplinary approach as well as timely and aggressive intensive care has led to a significant improvement of the prognosis in severe necrotising pancreatitis. Early surgical procedures were associated with high morbidity and mortality and therefore were abandoned and replaced with forceful conservative treatment. However, there are still specific indications for surgery during the course of acute pancreatitis. These include cholecystectomy for biliary pancreatitis, surgical debridement of infected necrosis in septic patients and emergency operations for gastrointestinal perforations or haemorrhage. The following article focuses on surgical indications, optimal timing of surgery and competing surgical and non-surgical concepts like laparoscopic or endoscopic management. All mentioned procedures demand the cooperation of an experienced team of gastroenterologists, surgeons, radiologists and intensive care specialists, who are able to manage the potentially life-threatening complications of this disease. All patients with severe necrotising pancreatitis should be transferred to a specialised centre for interdisciplinary therapy.

Inhibition of Src tyrosine kinase reverts chemoresistance toward 5-fluorouracil in human pancreatic carcinoma cells: an involvement of epidermal growth factor receptor signaling.

Resistance to chemotherapy is believed to be a major cause of treatment failure in pancreatic cancer. Thus, it is necessary to explore alternative therapeutic modalities to overcome drug resistance in pancreatic cancer treatment. We tested the hypothesis that Src tyrosine kinase inhibition could augment the chemosensitivity of 5-fluorouracil (5-FU)-resistant human pancreatic cancer cells to 5-FU. As detected by MTT proliferation assay, propidium iodide and annexin V staining, a combination of 5-FU+Src kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) reflected the chemotherapeutic sensitivity and restored the 5-FU-induced apoptosis in 5-FU-resistant cells. Furthermore, when small-interfering RNA approach to silence Src gene expression was applied, the degree of 5-FU-induced apoptosis was increased in all cell lines independently of the chemoresistance status. Western blotting and RT-PCR analysis revealed that the expression of thymidylate synthase (TS) was higher in 5-FU-resistant cells, however, decreased significantly after pretreatment with PP2. Furthermore, the combination of 5-FU+PP2 decreased the 5-FU-induced activation of epidermal growth factor receptor (EGFR)-AKT pathway. Finally, PP2 in combination with 5-FU substantially decreased the in vivo tumor growth and inhibited distant metastases. Taken together, 5-FU chemoresistance can be reversed through indirect TS regulation by inhibiting Src tyrosine kinase. A potential mechanism of action of Src kinase inhibitors on 5-FU chemosensitivity might be linked to the inhibition of 5-FU-induced EGFR-AKT activation.

Contrast enhanced MRI and intravital fluorescence microscopy indicate improved tumor microcirculation in highly vascularized melanomas upon short-term anti-VEGFR treatment.

Anti-angiogenic therapy by blocking VEGF signalling combined with standard chemotherapy is a novel strategy for clinical cancer treatment. The mechanisms for enhanced antitumoral effects are still a matter of controversial debate. Tumor vessel "normalization" upon anti-angiogenic therapy leading to improved drug delivery has been proposed as possible mechanism. Therefore, aim of the study was to investigate tumor microvascular function upon anti-VEGFR treatment in highly vascularized melanomas. A detailed intravital-microscopic analysis of tumor microcirculation including the distribution pattern of vessel diameters and blood flow velocities was performed in melanomas grown in dorsal skinfold chambers of hamsters. Animals with highly vascularized established tumors were treated by a VEGFR tyrosin kinase inhibitor (SU5416) on 3 repetitive days. Tumor tissue oxygenation was measured by phosphorescence quenching technique. Overall tumor microcirculation of subcutaneous tumors was investigated by contrast enhanced MRI (CE-MRI). Vessel density was significantly decreased in treated animals. A significant shift in the distribution patterns towards increased vessel diameters and faster red blood cell velocities in remaining tumor vessels was observed upon anti-VEGF treatment, compensating reduced vascular density. Moreover, a trend towards elevated pO(2) levels in treated tumors was observed. Compared to controls, inflow kinetics of tumors quantified by CE-MRI as well as overall uptake of contrast agent in tumor tissue were significantly increased following short-term SU5416 treatment. In conclusion the results confirm temporarily improved tumor microvascular function in highly vascularized melanomas upon short term anti-VEGFR treatment leading to enhanced tumor blood supply and oxygenation potentially improving the efficacy of simultaneous chemo- or radiotherapy.

Angiogenesis in cancer: molecular mechanisms, clinical impact.

BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, is fundamental in tumor growth, progression, and metastasis. Inhibiting tumor angiogenesis is a promising strategy for treatment of cancer and has been successfully transferred from preclinical to clinical application in recent years. Whereas conventional therapeutic approaches, e.g. chemotherapy and radiation, are focussing on tumor cells, antiangiogenic therapy is directed against the tumor supplying blood vessels. MATERIALS AND METHODS: This review will summarize important molecular mechanisms of tumor angiogenesis and advances in the design of antiangiogenic drugs. Furthermore, clinical implications of antiangiogenic therapy in surgical oncology will be discussed. RESULTS: First antiangiogenic drugs have been approved for treatment of advanced solid tumors in several countries. Leading antiangiogenic drugs are designed to inhibit vascular endothelial growth factor-mediated tumor angiogenesis. Combining antiangiogenic agents with conventional chemotherapy or radiation is currently investigated clinically with great emphasis to realize a multimodal tumor therapy, targeting both the tumor cell and tumor vascular compartment. CONCLUSION: Antiangiogenic tumor therapy represents a promising strategy for treatment of cancer and will most likely exhibit its clinical potential in combination with established standard tumor therapies in the future.