Jakob R. Izbicki

C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1 polymorphisms as prognostic factors in NSCLC

The progress of non-small cell lung cancer (NSCLC) is dependent on sufficient angiogenesis. Thrombin induced activation of proteinase-activated receptor 1 (PAR-1) on platelets leads to platelet secretion and aggregation. This influences cell survival, apoptosis and angiogenesis by the release of VEGF and Endostatin (ES), a potent angiogenesis inhibitor. Interleukin-8 (IL-8) induces tumor angiogenesis independent of the VEGF pathway through the chemokine C-X-C motif receptor 2 (CXCR-2). Our purpose was to evaluate germline polymorphisms of these potential therapy targets as prognostic markers for disease free survival (DFS) and overall survival (OS) in surgically treated NSCLC patients. In total 209 Caucasian patients, treated between 1996 and 2011, were included in this study. Genomic DNA was extracted from peripheral blood leucocytes. Genotyping of CXCR-2 +1208 C > T and +785 C > T, PAR-1 -506 Ins/del and -14 Ivs A > T and ES +4349 G > A was performed by TaqMan(®) genotyping assays or by polymerase chain reaction (PCR) followed by capillary electrophoresis. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of selected polymorphisms. The PAR-1 -14 Ivs A/A genotype was associated with advanced tumor stages (p = 0.024) and, in univariate analysis, with shorter median OS in squamous cell lung carcinoma (SqCC, p = 0.035). The CXCR-2 + 1208T/T genotype was associated with aggressive tumor biology (p = 0.038), and shorter DFS and OS (p = 0.018, p = 0.021) in NSCLC and especially in SqCC a negative predictor for DFS and OS (p = 0.045, p = 0.041). Genotyping of the CXCR-2 +1208 C >T polymorphism could be a useful tool to identify high-risk SqCC subgroups.

Evaluation of the robotic approach concerning pitfalls in rectal surgery

INTRODUCTIONnThe feasibility and advantages of robotic rectal surgery (RRS) in comparison to conventional open or laparoscopic rectal resections have been postulated in several reports. But well-known challenges and pitfalls of minimal invasive rectal surgery have not been evaluated by a prospective, multicenter setting so far. Aim of this study was to analyze the perioperative outcome of patients following RRS especially in regard to the pitfalls such as obesity, male patients and low tumors by a European multicenter setting.nnnMETHODSnThis prospective study included 348 patients undergoing robotic surgery due to rectal cancer in six major European centers. Clinicopathological parameters, morbidity, perioperative recovery and short-term outcome were analyzed.nnnRESULTSnA total of 283 restorative surgeries and 65 abdominoperineal resections were carried out. The conversion rate was 4.3%, mean blood loss was 191xa0ml, and mean operative time was 315xa0min. Postoperative complications with a Clavien-Dindo score >2 were observed in 13.5%. Obesity and low rectal tumors showed no significant higher rates of major complications or impaired oncological parameters. Male patients had significant higher rates of major complications and anastomotic leakage (pxa0=xa00.048 and pxa0=xa00.007, respectively).nnnDISCUSSIONnRRS is a promising tool for improvement of rectal resections. The well-known pitfalls of minimal-invasive rectal surgery like obesity and low tumors were sufficiently managed by RRS. However, RRS showed significantly higher rates of major complications and anastomotic leakage in male patients, which has to be evaluated by future randomized trials.

Blood fibrinogen levels discriminate low- and high-risk intraductal papillary mucinous neoplasms (IPMNs)

BACKROUNDnThe risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection.nnnMETHODSnPatients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured.nnnRESULTSnA total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62xa0g/L (SDxa0±xa01.14); group 2: mean 4.49xa0g/L (SDxa0±xa01.57); pxa0=xa00.027). A ROC-curve analysis calculated cut-off value of 4.71xa0g/L separated groups 1 and 2 (pxa0=xa00.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant.nnnCONCLUSIONnBlood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.

Non-trauma Emergency Pancreatoduodenectomies: A Single-Center Retrospective Analysis

ObjectiveTo retrospectively assess the frequency and indications for emergency pancreatoduodenctomies in a tertiary referral center.MethodsPancreatoduodenectomies between January 2005 and January 2014 were retrospectively assessed for emergency indications defined as surgery following unplanned hospital admission in less than 24xa0h. Data on indications and on the intraoperative as well as the post-operative course were collected.ResultsOut of 583 pancreatoduodenectomies during the interval, a total of 10 (1.7xa0%) were performed as an emergency surgery. Indications included uncontrollable bleeding, duodenal and proximal jejunal perforations, and endoscopic retrograde cholangiopancreatography-related complications. Three of the 10 (30.0xa0%) patients died during the hospital course. In one patient, an intraoperative mass transfusion was necessary. No intraoperative death occurred. All but one patient were American Society of Anesthesiologists class three or higher. In two cases, the pancreatic remnant was left without anastomosis for second-stage pancreatojejunostomy. Median operation time was 326.5xa0min (SD 100.3xa0min). Hospital stay of the surviving patients was prolonged (median 43.0xa0days; SD 24.0xa0days).ConclusionEmergency pancreatoduodenectomies are non-frequent, have a diverse range of indications and serve as an ultima ratio to cope with severe injuries and complications around the pancreatic head area.

Solid-pseudopapilläre Neoplasien: OP-Verfahren und Evidenz der operativen Therapie

Solide pseudopapillare Neoplasien (SPN) sind seltene Tumoren des Pankreas und treten mit einem homogenen Verteilungsmuster innerhalb des gesamten Pankreas auf. Betroffen sind vorwiegend Frauen (Verhaltnis Manner/Frauen 1 : 9,5) im jungen Erwachsenenalter, das mediane Erkrankungsalter liegt bei 29 Jahren. Das Auftreten von Metastasen ist extrem selten, jedoch in Einzelfallberichten beschrieben. Die Resektion ist die Therapie der Wahl, haufig gelingt eine definitive Diagnosestellung erst durch eine Resektion und nachfolgende histologische Aufarbeitung, bildgebende Verfahren sind in einer Diagnosestellung haufig unzureichend. Das Evidenzniveau bei SPN ist insgesamt als niedrig zu bewerten, randomisierte Studien liegen nicht vor, samtliche vorhandenen Daten beruhen auf kleinen Fallserien oder Einzelfallberichten. Der Stellenwert der Metastasenchirurgie ist umstritten und ohne nachweisliche Evidenz.

Langzeitverlauf nach Beobachtung und chirurgischer Therapie zystischer Pankreasneoplasien

Die Langzeitprognose ist in der Regel bei zystischen Pankreaslasionen (inklusive der malignen Tumoren) deutlich besser als bei duktalen Adenokarzinomen einzustufen. Dennoch unterscheidet sich die individuelle Prognose stark – abhangig von dem jeweilig zugrundeliegenden histologischen Subtyp. Aufgrund der hoheren Entartungsrate der Hauptgang-IPMN finden sich die Rezidive auch uberwiegend bei diesem Subtyp (ca. 60–80 %). Die Langzeituberlebensraten korrelieren eng mit dem Nachweis invasiver Areale und sind in diesem Falle deutlich kurzer als bei Patienten ohne Malignitatsnachweis. Bei den muzinosen Zystadenomen hangt die Prognose direkt von einem evtl. Nachweis invasiver Areale ab. Serose Zystadenome haben eine exzellente Prognose, ein Rezidiv ist bei einer vollstandigen Tumorresektion in der Regel nicht zu erwarten. Durch eine operative Therapie konnen bei den solid-pseudopapillaren Neoplasien exzellente Langzeitverlaufe mit Heilungsraten > 95 % erreicht werden.

Seröse Zystadenome des Pankreas: OP-Verfahren und Evidenz der operativen Therapie

Aufgrund gesunkener perioperativer Morbiditats- und Mortalitatsraten sollte die Indikation zur operativen Resektion von SCA heute groszugiger gestellt werden als noch vor einigen Jahren. Das jeweilige Operationsverfahren hangt unmittelbar von der jeweiligen Tumorlokalisation ab. Bei Tumoren im Bereich des Pankreasschwanzes ist die distale Pankreasresektion als Option der Wahl anzusehen; hier sollte wann immer moglich eine milzerhaltende Variante bevorzugt werden, wobei besonderes Augenmerk auf eine sichere Versorgung der V. lienalis zu richten ist. Bei Tumoren im Bereich des Pankreaskopfes ist die Grose des Tumors entscheidend fur die Wahl des Resektionsverfahrens. Bei sehr grosen Tumoren lasst sich haufig eine Whipple-Resektion nicht vermeiden. Bei kleineren Tumoren sollten auch hier organsparende Verfahren (Nakao- oder Beger-Verfahren) angewendet werden. Bei zentral, d. h. im Pankreaskorpus lokalisierten Tumoren bietet sich eine zentrale Pankreassegmentresektion an.

Abdominothoracic Subtotal en bloc Esophagectomy and Reconstruction with Gastric Tube Transposition

Mid thoracic esophageal carcinoma n n nEsophageal squamous-cell carcinoma in the lower third of the esophagus n n nLong peptic stricture, if transhiatal resection is not possible.

Conventional Resection of Esophageal Diverticula

Esophageal diverticula are rare. They can be either local or generalized, with local circumscript diverticula being the most common types. According to their location they are divided into: Cervical/pharyngoesophageal, parabronchial/ mid-thoracic, and epiphrenic diverticula.

Post-operative Complications of the Esophagus and Esophagus Bridge Graft

Due to the grave risk of insufficiency of the esophageal anastomosis and considering the severe operative trauma that is involved, surgery of the esophagus is one of the most dreaded operations in visceral surgery even today.