Advances in rectal cancer: Real-world evidence suggests limited gains in prognosis for elderly patients.

BACKGROUND: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

[The importance of microbiological results for the treatment of complicated appendicitis-a monocentric case-control study]. / Die Bedeutung mikrobiologischer Ergebnisse für die Therapie der komplizierten Appendizitis ­ eine monozentrische Fall-Kontroll-Studie.

BACKGROUND: Patients with complicated appendicitis frequently develop postoperative septic complications. There are no uniform standards for the choice of perioperative antibiotic prophylaxis and the duration of postoperative antibiotic treatment. The purpose of this study was to investigate associations between microbiological samples and postoperative complications. METHODS: Patients with appendectomy and positive intraoperative swabs during 2013-2018 were included in this case-control study. Pathogen classes and their resistance patterns were evaluated in initial and follow-up swabs and compared in each of the groups with and without complications. RESULTS: A total of 870 patients underwent surgery during the period studied. Pathogen detection succeeded in 102 of 210 cases (48.6%) with suspected bacterial peritoneal contamination. Conversion from laparoscopic to open intra-abdominal perforation and the presence of an abscess were independent risk factors for wound infections in the multivariate analysis. The combination of different classes of pathogens resulted in significantly increased overall resistance to ampicillin/sulbactam in both the initial swabs (57%) and the follow-up swabs (73%). Resistant E. coli strains combined with certain anaerobes were also regularly detected in postoperative intra-abdominal abscesses. Piperacillin/tazobactam was effective against 83% of positive swabs in our resistance tests. CONCLUSION: Surgical treatment for complicated appendicitis remains the central therapeutic column. A regular review of the existing resistance patterns in perforated appendicitis can help to adjust and improve antibiotic treatment. Piperacillin/tazobactam should be used cautiously as a reserve antibiotic. A valid alternative is second or third generation cephalosporins in combination with metronidazole.

[Clinical value of alternative technologies to standard laparoscopic cholecystectomy - single port, reduced port, robotics, NOTES]. / Klinischer Stellenwert alternativer Technologien zur standardmäßigen laparoskopischen Cholezystektomie ­ Single-Port, Reduced-Port, Roboter, NOTES.

Surgical interventions should ideally treat an existing disease curatively and achieve this with a low complication rate and minimal trauma. In this sense, laparoscopic cholecystectomy has become established as the recognized standard for the treatment of cholecystolithiasis. Newer procedures, such as single-port surgery or natural orifice transluminal endoscopic surgery (NOTES) have recently emerged to reduce the already low interventional trauma even further and to provide a better cosmetic outcome. With all new methods the main aim is the reduction of the transabdominal access points. Based on published results and diagnosis-related groups (DRG) data, this article examines whether this goal has been achieved, also with respect to the overall quality of treatment and the complication rates. In this context and in addition to the already mentioned approaches, robotic cholecystectomy and the reduced port approach are also considered.

Intestinal anastomotic healing models during experimental colitis.

BACKGROUND: Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease. METHODS: We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis. DISCUSSION: Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process. CONCLUSION: The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing.

Selective decontamination of the digestive tract in upper gastrointestinal surgery: systematic review with meta-analysis of randomized clinical trials.

BACKGROUND: Infectious complications are common after gastrointestinal surgery. Selective decontamination of the digestive tract (SDD) might reduce their incidence. SDD is used widely in colorectal resections, but its role in upper gastrointestinal resection is less clear. The aim of this study was to investigate the impact of SDD on postoperative outcome in upper gastrointestinal surgery. METHODS: Studies investigating SDD in upper gastrointestinal surgery were included after search of medical databases (PubMed, Ovid, Cochrane Library and Google Scholar). Results were analysed according to predefined criteria. The incidence of perioperative overall complications and death was pooled. Risk of bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: Some 1384 studies were identified, of which four RCTs were included in the final analysis. These studies included 415 patients, of whom 213 (51·3 per cent) received standard treatment/placebo and 202 (48·7 per cent) had SDD. The incidence of anastomotic leakage (odds ratio (OR) 0·39, 95 per cent c.i. 0·19 to 0·80; P = 0·010) and pneumonia (OR 0·42, 0·23 to 0·78; P = 0·006) was reduced in patients receiving SDD. Rates of surgical-site infection (P = 0·750) and mortality (P = 0·130) were not affected by SDD. CONCLUSION: SDD seems to be associated with reduction of anastomotic leakage and pneumonia following upper gastrointestinal resection, without affecting postoperative mortality.

ANTECEDENTES: Las complicaciones infecciosas son frecuentes tras la cirugía gastrointestinal. La descontaminación selectiva del tracto digestivo (Selective Decontamination of the Digestive tract, SDD) podría reducir su incidencia. Mientras que la SDD es ampliamente utilizada en las resecciones colorrectales, su papel en las resecciones del tracto gastrointestinal superior está menos definido. El objetivo de este estudio fue investigar el impacto de la SDD en el resultado postoperatorio en cirugía del tracto gastrointestinal superior. MÉTODOS: Se incluyeron estudios que investigasen la SDD en cirugía del tracto gastrointestinal superior después de una búsqueda de bases de datos médicas (Pubmed, Ovid, Cochrane-Library y Google/Scholar). Los resultados se analizaron de acuerdo con criterios predefinidos. Se agrupó la incidencia de complicaciones perioperatorias globales y mortalidad. El riesgo de sesgo se analizó utilizando la herramienta de la colaboración Cochrane revisada para la evaluación del riesgo de sesgo. RESULTADOS: Se identificaron 1.380 estudios, de los cuales cuatro ensayos controlados aleatorizados fueron incluidos en el análisis final. Estos estudios incluían a 415 pacientes de los cuales 213 (51,3%) recibieron tratamiento estándar/placebo y 202 (48,7%) recibieron SDD. La incidencia de fugas anastomóticas (razón de oportunidades, odds ratio, OR: 0,39 (0,19-0,80); P = 0,010)) y neumonía (OR: 0,42 (0,23-0,78); P = 0,006)) se redujo en pacientes que recibieron SDD. Infecciones del sitio quirúrgico (P = 0,750) y la mortalidad (P = 0,130) no se relacionaron con la SDD. CONCLUSIÓN: SDD parece asociarse con reducción de fuga anastomótica y neumonía tras resecciones del tracto gastrointestinal superior, sin afectar a la mortalidad postoperatoria.

Association of bacteria in pancreatic fistula fluid with complications after pancreatic surgery.

BACKGROUND: Pancreatic fistula (PF) is a common complication after pancreatic surgery. It is unclear how microbes in PF fluid affect outcomes and which microbes are present after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). The aim of this study was to compare the microbiological spectrum of PF fluid after PD versus DP, and its association with postoperative complications. METHODS: Bacterial strains and antibiotic resistance rates of bacterial swabs obtained from the PF fluid of patients who underwent DP or PD were analysed. Cultured bacteria were classified as Enterobacterales and as 'other intestinal and non-intestinal microorganisms' based on whether they are typically part of the normal human intestinal flora. RESULTS: A total of 847 patients had a pancreatic resection (PD 600; DP 247) between July 2007 and December 2016. Clinically relevant PF was detected in 131 patients (15·5 per cent). Bacterial swabs were obtained from 108 patients (DP 47; PD 61), of which 19 (17·6 per cent) were sterile. Enterobacterales were detected in 74 per cent of PF fluid swabs after PD, and in 34 per cent after DP. Infected, polymicrobial or multidrug-resistant PF fluid was more common after PD (rates of 95, 50 and 48 per cent respectively) than after DP (66, 26 and 6 per cent respectively). Patients with higher grade complications (Clavien-Dindo grade IV-V) or grade C PF had more Enterobacterales and multidrug-resistant Enterobacterales in the PF fluid after DP. CONCLUSION: Enterobacterales and multidrug-resistant bacteria are detected frequently after PD and DP, and are associated with more severe complications and PF in patients undergoing DP.

ANTECEDENTES: La fístula pancreática (pancreatic fistula, PF) es una complicación frecuente de la cirugía pancreática. No está claro cómo los microorganismos que se encuentran en el líquido de la PF (pancreatic fistula fluid, PFF) afectan los resultados y qué microbios están presentes después de la duodenopancreatectomía (pancreaticoduodenectomy, PD) y de la pancreatectomía distal (distal pancreatectomy, DP). El objetivo de este estudio fue comparar el espectro microbiológico del PFF después de PD versus DP y su asociación con las complicaciones postoperatorias. MÉTODOS: Se analizaron las cepas bacterianas y las tasas de resistencia a los antibióticos de las muestras bacterianas obtenidas del PFF de pacientes de nuestra institución que se sometieron a DP o PD. Las bacterias identificadas en los cultivos se clasificaron en "enterobacterias" y "otros microorganismos intestinales y no intestinales" en función de si típicamente forman parte de la flora intestinal humana normal o no. RESULTADOS: Un total de 847 pacientes se sometieron a resección pancreática (PD: 600, DP: 247) entre julio de 2007 y diciembre de 2016, y se detectó FP clínicamente relevante en 131 pacientes (15,5%). Se obtuvieron muestras bacterianas de 108 pacientes (DP n = 47, PD N = 61), de los cuales 19 (18%) eran estériles. Se detectaron enterobacterias en el 74% del PFF después de PD y en el 34% después de DP. El PFF infectado, con flora polimicrobiana o flora multirresistente fue más frecuente después de la PD (95,1%, 50%, 47,5%, respectivamente) que después de la DP (66,0%, 25,8%, 6,4%, respectivamente). Los pacientes con complicaciones de grado superior (Clavien-Dindo 4/5) o PF grado C presentaron más enterobacterias y enterobacterias multirresistentes en el PFF después de DP. CONCLUSIÓN: Las enterobacterias y las bacterias multirresistentes se detectaron con frecuencia después de la PD y la DP, y se asociaron a complicaciones más graves y PF en pacientes sometidos a DP.

[Neoadjuvant treatment of primarily resectable and borderline resectable pancreatic cancer]. / Neoadjuvante Therapie beim primär resektablen und Borderline-resektablen Pankreaskarzinom.

Due to the increasing prevalence pancreatic cancer represents a severe tumor burden to the population and will be ranked second for cancer-related mortality by the year 2030. If a curative approach is pursued a radical R0 resection of the tumor with sufficient cancer-free resection margins (≥1 mm) should be performed. This has been shown to be associated with a clear benefit for survival. For treatment planning of pancreatic cancer the tumor stage plays a pivotal role. In cases of distant metastases a palliative concept is normally initiated. If no distant metastases are detected neoadjuvant treatment can be performed in cases of borderline resectability or locally advanced stages in order to downsize these tumors. In this situation a neoadjuvant treatment has been shown to significantly increase resectability rates and to improve the tumor stage (downstaging). The most recent randomized trials were able to show a significant survival advantage of neoadjuvant treatment for borderline resectable pancreatic cancer. In cases of primarily resectable pancreatic cancer the current standard of care is an upfront resection followed by adjuvant chemotherapy. Initial data are also available indicating a survival benefit even for resectable pancreatic cancer after neoadjuvant treatment; however, reliable randomized controlled trials showing a survival advantage of neoadjuvant treatment compared to the current standard treatment of adjuvant chemotherapy following resection are missing. Numerous randomized controlled trials investigating the efficacy of neoadjuvant chemotherapy for resectable pancreatic cancer are currently underway.

[Model-based treatment in surgery]. / Modellgestützte Therapie in der Chirurgie.

BACKGROUND: The "magic triangle" in surgery and other disciplines consists of the demand for increasingly gentler forms of treatment, simultaneous cost reduction and the fundamental primacy of improving the quality of results. The digitalization of medicine offers a promising opportunity to do justice to this, also in the sense of "Surgery 4.0". The aim is to create a cognitive, collaborative diagnostics and treatment environment to support the surgeon. METHODS: In the sense of a "theory building" for analysis and planning, process modeling is the cornerstone for modern treatment planning. The main distinction is made between the patient model and the treatment model. The course of the actual surgical treatment can also be modeled: in principle it is possible to describe the course of an operation in such fine detail that the surgical procedure can be mapped and reproduced down to each single step, such as a single implementation of forceps. Basically, this has already been achieved. So-called neural networks also open up completely new forms of knowledge acquisition, machine learning and flexible reaction to nearly all conceivable possibilities in highly complex processes. CONCLUSION: "Digitalization" is a necessary development in surgery. It offers not only countless possibilities to support the surgeon in the field of activity but also the chance of more precise data acquisition with respect to academic surgery. Modeling is an indispensable part of this and must be rigorously implemented and further developed.

Influence of the surgical technique on survival in the treatment of carcinomas of the true cardia (Siewert Type II) - Right thoracoabdominal vs. transhiatal-abdominal approach.

INTRODUCTION: It is still a matter of debate whether subtotal esophagectomy via a right thoracoabdominal approach (RTA) or extended gastrectomy using a transhiatal-abdominal approach (TH) is the favorable technique in the treatment of Siewert type II esophago-gastric junction adenocarcinoma (EJA). MATERIALS AND METHODS: Patients undergoing RTA or TH for EJA at our institution between 2000 and 2013 were extracted from a prospective database. Of 270 patients 91 (33.7%) underwent RTA and 179 (66.3%) were treated by TH. Differences in baseline characteristics, 30d mortality and complications were investigated using the χ2-test or exact testing. Survival analysis was performed using the Kaplan-Meier method and log rank testing. Median survival and hazard ratios were calculated and multivariable analysis of predictors was performed using a Cox model. Confounders were balanced using propensity score matching (PSM). RESULTS: No significant difference between the two procedures was detected regarding overall-survival (OS) and disease-free survival (DFS). 30d mortality rates were 1.1% in the RTA group and 4.5% in the TH group (p = 0.134). Morbidity was 34.1% in the RTA and 24.6% in the TH group (p = 0.006). Cox regression analysis identified age, ASA class and UICC stage as independent prognostic factors for OS. After PSM survival curves (OS + PFS) showed no significant difference. CONCLUSION: The present study could not detect a difference between RTA and TH from the oncologic point of view; RTA was not associated with higher 30d mortality. RTA for Siewert Type II EJA is justified whenever the oral tumor margin cannot be safely reached via a transhiatal approach.

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma.

BACKGROUND: Neoadjuvant therapy may increase the rate of radical tumour resection in patients with pancreatic cancer. Its impact on tumour recurrence has not been investigated fully. This study aimed to assess the impact of neoadjuvant therapy on patterns of recurrence. METHODS: A systematic review was performed of articles identified through the PubMed, Scopus, Embase, Ovid and Google Scholar databases that analysed the relationship between neoadjuvant therapy and recurrence published to January 2016. The main endpoint was overall tumour recurrence. Other endpoints included local recurrence, any kind of distant, hepatic, pulmonary or peritoneal metastasis. RESULTS: A total of 4257 citations were reviewed. Twelve observational studies comprising 1365 patients were analysed. Neoadjuvant therapy significantly reduced the risk of overall (risk ratio (RR) 0·82, 95 per cent c.i. 0·74 to 0·90; P < 0·001) and local (RR 0·42, 0·32 to 0·55; P < 0·001) recurrence. Neoadjuvant therapy did not reduce the risk of any kind of distant (RR 1·02, 0·91 to 1·14; P = 0·78), hepatic (RR 0·86, 0·68 to 1·10; P = 0·23), pulmonary (RR 0·99, 0·37 to 2·66; P = 0·98) or peritoneal (RR 0·88, 0·57 to 1·38; P = 0·58) metastasis. CONCLUSION: Neoadjuvant therapy reduced the risk of local recurrence but not that of distant metastasis.

Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer.

BACKGROUND: It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS: A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS: Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION: Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.

[Resection of main duct and mixed type IPMN ≥5 mm]. / Resektion von Hauptgang- und Mischtyp-IPMN ≥5 mm.

The incidence of cystic pancreatic lesions is steadily increasing due to the technical advances in imaging. Within the group of cystic pancreatic lesions intraductal papillary mucinous neoplasms (IPMNs) depict an important entity. Due to a possible progression to malignancy the clinical strategy has to be well chosen. For primary diagnostic work-up imaging by magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) and computed tomography (CT) scanning is recommended. Additional information can be gained by endosonography and a biopsy of the cystic lesion, allowing analysis of biomarkers, such as GNAS and KRAS mutation as wells as NLR. These can help to differentiate between IPMN and other cystic lesions although the clinical importance for the diagnosis of main duct (MD) and mixed IPMN is limited. The current guidelines (Fukuoka and EU guidelines) recommend resection of MD and mixed IPMN following oncological standards. For the definition of MD-IPMN, a duct dilatation between 5-10 mm is needed when following the current guidelines; however, current publications claim an even lower cut-off of ≥5 mm due to the risk of malignant progression. Intraoperative frozen sections are recommended to evaluate the margins status and extended resection is recommended for residual high-grade dysplasia. Surveillance of potentially at risk patients is recommended at regular intervals of 6-12 months while patients with malignant IPMN should be followed according to pancreatic cancer protocols. A screening for extrapancreatic malignancy is not indicated.

The clinical picture of cachexia: a mosaic of different parameters (experience of 503 patients).

BACKGROUND: Despite our growing knowledge about the pathomechanisms of cancer cachexia, a whole clinical picture of the cachectic patient is still missing. Our objective was to evaluate the clinical characteristics in cancer patients with and without cachexia to get the whole picture of a cachectic patient. METHODS: Cancer patients of the University Clinic "Klinikum rechts der Isar" with gastrointestinal, gynecological, hematopoietic, lung and some other tumors were offered the possibility to take part in the treatment concept including a nutrition intervention and an individual training program according to their capability. We now report on the first 503 patients at the time of inclusion in the program between March 2011 and October 2015. We described clinical characteristics such as physical activity, quality of life, clinical dates and food intake. RESULTS: Of 503 patients with cancer, 131 patients (26.0%) were identified as cachectic, 369 (73.4%) as non-cachectic. The change in cachexia were 23% reduced capacity performance (108 Watt for non-cachectic-patients and 83 Watt for cachectic patients) and 12% reduced relative performance (1.53 Watt/kg for non-cachectic and 1.34 Watt/kg for cachectic patients) in ergometry test. 75.6% of non-cachectic and 54.3% of cachectic patients still received curative treatment. CONCLUSION: Cancer cachectic patients have multiple symptoms such as anemia, impaired kidney function and impaired liver function with elements of mild cholestasis, lower performance and a poorer quality of life in the EORTC questionnaire. Our study reveals biochemical and clinical specific features of cancer cachectic patients.

[Surgical treatment of esophageal diverticula : Endoscopic or open approach?] / Operative Therapie von Divertikeln der Speiseröhre : Endoskopisch oder offen?

Esophageal diverticula are comparatively rare. The majority are Zenker's diverticula but parabronchial and epiphrenic diverticula can also occur. Parabronchial diverticula are of low clinical relevance, whereas Zenker's and epiphrenic diverticula both belong to the group of pulsion diverticula and can become clinically apparent by dysphagia and regurgitation. Approximately 100 years after the first surgical treatment, peroral approaches (e.g. stapler dissection and flexible endoscopic diverticulotomy) have now achieved a certain level of importance. Both approaches are less invasive than the open approach but are evidently more prone to recurrences. Accordingly, traditional open diverticulectomy with cervical myotomy should be recommended to patients with a reasonable life expectancy and an acceptable operative risk. This holds particularly true for Brombart stages I-III of the disease, as complete myotomy cannot be achieved via the peroral access. The classical surgical treatment of epiphrenic diverticula is open or laparoscopic/thoracoscopic diverticulectomy with distal myotomy, mostly combined with an anterior partial fundoplication; however, the leakage rate is high and several alternative options are currently being evaluated.

Effect of preoperative biliary drainage on bacterial flora in bile of patients with periampullary cancer.

BACKGROUND: Patients with obstructive jaundice due to periampullary tumours may undergo preoperative biliary drainage (PBD). The effect of PBD on the microbiome of the biliary system and on postoperative outcome remains unclear. METHODS: A single-centre retrospective study of patients with obstructive jaundice due to periampullary cancer, treated between July 2007 and July 2015, was undertaken. Intraoperative bile samples were obtained for microbiological analysis after transection of the common bile duct. Postoperative complications were registered. RESULTS: Of 290 patients treated, intraoperative bile samples were present for 172 patients (59·3 per cent) who had PBD and 118 (40·7 per cent) who did not. Contamination of bile was increased significantly in patients who underwent stenting (97·1 per cent versus 18·6 per cent in those without stenting; P < 0·001). PBD resulted in a shift in the biliary microbiome from Escherichia coli in non-stented patients (45 per cent versus 19·2 per cent in stented patients; P = 0·009) towards increased contamination with Enterococcus faecalis (9 versus 37·7 per cent respectively; P = 0·008) and Enterobacter cloacae (0 versus 20·4 per cent; P = 0·033). This shift was associated with a high incidence of bacterial resistance against ampicillin-sulbactam (63·6 per cent versus 18 per cent in patients with no PBD; P < 0·001), piperacillin-tazobactam (30·1 versus 0 per cent respectively; P = 0·003), ciprofloxacin (28·5 versus 5 per cent; P = 0·047) and imipenem (26·6 versus 0 per cent; P = 0·011). The rate of wound infection was higher in patients with a positive bile culture (21·0 per cent versus 6 per cent in patients with sterile bile; P = 0·002). Regression analysis revealed the presence of Enterococcus faecium (odds ratio 2·83, 95 per cent c.i. 1·17 to 6·84; P = 0·021) and Citrobacter species (odds ratio 5·09, 1·65 to 15·71; P = 0·005) as independent risk factors for postoperative wound infection. CONCLUSION: There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.

In vivo functional dissection of a context-dependent role for Hif1α in pancreatic tumorigenesis.

Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection. Cells were transplanted into wild-type mice through orthotopic or portal vein injection in order to test the in vivo function of Hif1α in two major tumour-associated biological scenarios: primary tumour growth and remote colonization/metastasis. Although Hif1α protects PDAC cells from stress-induced cell deaths in both scenarios-in line with the general function Hif1α-its depletion leads to different oncogenic consequences. Hif1α depletion results in rapid tumour growth with marked hypoxia-induced cell death, which potentially leads to a persistent tumour-sustaining inflammatory response. However, it simultaneously reduces tumour colonization and hepatic metastases by increasing the susceptibility to anoikis induced by anchorage-independent conditions. Taken together, the role of Hif1α in pancreatic tumorigenesis is context-dependent. Clinical trials of Hif1α inhibitors need to take this into account, targeting the appropriate scenario, for example palliative vs adjuvant therapy.

[Curriculum for Practical Surgical Education during Internships - with a Strategy for New Perspectives]. / Curriculum der chirurgisch-praktischen Ausbildung im PJ - mit Strategie zu neuen Perspektiven.

BACKGROUND: It seems that the experience gained in the courses of surgical training in medical education does not really motivate students for surgery in Germany. Inspired by this problem the Department of Surgery of the Klinikum rechts der Isar, Technical University of Munich has developed a substantial reform for the internship since 2009 with the aim of not only improving the quality of education significantly, but also the attractiveness and thus the fascination for the subject. METHODS: Based on the slogan "We want to awaken your fascination for surgery" a structured and standardised training of all students in their internship regardless of the ward or section and local conditions was developed. For this purpose a completely new curriculum was steadily implemented into clinical practice, based on the following four basic principles: (i) integration and perception in the clinic, (ii) central and peripheral maintenance, (iii) systematic and individual training, (iv) evaluation and feedback at all levels. To analyse the effectiveness of the reform, standardised evaluations by students and faculty were carried out regularly. RESULTS: To date, since the beginning of the reform in 2009, there has been an approximately linear increase in the number of students in the PJ surgery. The daily systematic courses showed a good to excellent rating in all formats. The comparison showed a clear increasing trend in all the values, in particular, the "integration into the overall hospital" significantly improved (mean, 4.7 vs. 5.5, p = 0.003). However, the point "motivating for surgery" (mean, 3.3) remains at a low level. But also medical educators were satisfied with the new curriculum for the internship students (mean, 4.5). CONCLUSION: The reform was adopted universally in a very positive manner and the current data support the need for such a reform. Overall, the reform showed a positive development of the internship training in the surgical department of the faculty. The satisfaction of the students and teachers could be increased by gradual implementation of the reform. Even if a lot of individual aspects gain a higher acceptance, the main concern, the inspiration of the "fascination" of the central surgical field, the training in the operating room, seems to succeed only partially.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

Treating ischaemia-reperfusion injury with prostaglandin E1 reduces the risk of early hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Surgical stress by hepatic ischaemia-reperfusion (I/R) is supposed to promote intra- and extrahepatic tumour recurrence. Treatment with prostaglandin E1 (PGE1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti-cancer effects have not been analysed. AIM: To evaluate the impact of PGE1 therapy on risk of hepatocellular carcinoma (HCC) recurrence in liver transplant patients. METHODS: A retrospective review of 106 liver transplant patients with HCC was conducted. Fifty-nine patients underwent early post-liver transplantation (LT) treatment with the stable PGE1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni- and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging. RESULTS: Three- and 5-year recurrence-free survival rates were 87.9% and 85.7% in the PGE1-group, but only 65.3% and 63.1% in the non-PGE1-population (P = 0.003). Multivariate Cox regression analysis identified absence of PGE1-treatment (HR = 11.42), along with presence of poor tumour grading (HR = 2.69) and microvascular tumour invasion (HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out-patients, only therapy with PGE1 (HR = 5.09) and well/moderate tumour differentiation (HR = 6.51) were independent promoters of recurrence-free survival. CONCLUSIONS: Treating hepatic ischaemia-reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT. In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE1-treatment. The molecular mechanisms of the anti-tumour effects need to be further assessed.