Combined regression score predicts outcome after neoadjuvant treatment of oesophageal cancer.

BACKGROUND: Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS: Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS: Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS: Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.

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).

Predicting complicated appendicitis based on clinical findings: the role of Alvarado and Appendicitis Inflammatory Response scores.

PURPOSE: The pre-interventional differentiation between complicated and uncomplicated appendicitis is decisive for treatment. In the context of conservative therapy, the definitive diagnosis of uncomplicated appendicitis is mandatory. This study investigates the ability of clinical scoring systems and imaging to differentiate between the two entities. METHODS: This is a retrospective analysis of two cohorts from two tertiary referral centers in Switzerland and Germany. All consecutive patients underwent appendectomy between January 2008 and April 2013 (in the first cohort) or between January 2017 and June 2019 (the second cohort). Exclusion criteria did not apply as all patients found by the database search and received an appendectomy were included. Diagnostic testing and calculation of a receiver operating curve were performed to identify a cutoff for clinical scores that resulted in a minimum sensitivity of 90% to detect complicated appendicitis. The cutoff was combined with additional diagnostic imaging criteria to see if diagnostic properties could be improved. RESULTS: Nine hundred fifty-six patients were included in the analysis. Two hundred twenty patients (23%) had complicated appendicitis, and 736 patients (77%) had uncomplicated appendicitis or no inflammation. The complicated appendicitis cohort had a mean Alvarado score of 7.03 and a mean AIR of 5.21. This compared to a mean Alvarado of 6.53 and a mean AIR of 4.07 for the uncomplicated appendicitis cohort. The highest Alvarado score with a sensitivity of > 90% to detect complicated appendicitis was ≧ 5 (sensitivity = 95%, specificity 8.99%). The highest AIR score with a sensitivity of > 90% to detect complicated appendicitis was ≧ 3 (sensitivity 91.82%, specificity 18.53). The analysis showed that additional CT information did not improve the sensitivity of the proposed cut-offs. CONCLUSION: AIR and Alvarado scores showed limited capability to distinguish between complicated and uncomplicated appendicitis even with additional imaging in this retrospective cohort. As conservative management of appendicitis needs to exclude patients with complicated disease reliably, appendectomy seems until now to remain the safest option to prevent undertreatment of this mostly benign disease.

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial.

PURPOSE: Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. METHODS: One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. RESULTS: Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). CONCLUSION: Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial.

BACKGROUND: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer. METHODS: Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared. RESULTS: One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05). CONCLUSION: Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors. TRIAL REGISTRATION: EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).

Quantitative spleen and liver volume changes predict survival of patients with primary sclerosing cholangitis.

AIM: To assess the value of quantitative spleen and liver volume changes in predicting the survival of patients with primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: This institutional review board-approved single-centre study included 89 PSC patients with baseline and follow-up liver imaging studies and laboratory data between 2000 and 2018. Change in spleen, total and lobar liver volumes, and lobar-to-total liver volume ratio was compared between patients with and without adverse outcome (liver transplantation, transplant waiting list, and death). Receiver operating characteristic (ROC) and Kaplan-Meier analysis were performed to identify the volumetric threshold for prediction of outcome and show how these thresholds predict survival, respectively. A p-value of <0.05 was considered statistically significant. RESULTS: The present cohort included 53 men (60%), with mean age of 42 years at baseline. The only volumetric parameters with significant differences in change between patients with and without adverse outcome were spleen volume (p<0.001) and left-to-total liver volume ratio (L/T; p=0.025). The probability of transplant-free survival at 36 months was 59.1% versus 11.9% for patients with spleen volume change <50 ml versus ≥50 ml, respectively (AUC=0.731); and 61.3% versus 13.8% for patients with L/T change <0.04 versus ≥0.04, respectively (AUC=0.638). The patients with changes below the cut-off in both spleen volume and L/T, had a higher probability of transplant-free survival at 36 months (76.8%), compared to those with change at or below the cut-offs in one or both of these two parameters (36.7%, 15%, respectively; p=0.001). CONCLUSION: Spleen volume change and L/T change might be useful biomarkers for prediction of transplant-free survival in patients with PSC.

Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial.

Background: Surrogate end points in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase III trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase III trial. Patients and methods: Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. Results: After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS [75.9% (95% confidence interval [CI] 72.30% to 79.50%) versus 71.3% (95% CI 67.60% to 74.90%); P = 0.034; PC 1) and resulted in a shift toward lower NAR groups (P = 0.034, PC 2) compared with fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI 88.2% to 95.2%), 81.8% (95% CI 78.4% to 85.1%), and 58.1% (95% CI 52.4% to 63.9%) for low, intermediate, and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS [low versus high NAR: hazard ratio (HR) 4.670; 95% CI 3.106-7.020; P < 0.001; low versus intermediate NAR: HR 1.971; 95% CI 1.303-2.98; P = 0.001] in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC 4. Conclusion: Our study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase III trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase III trial data sets should aim to confirm trial-level surrogacy.

Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: a post hoc analysis of the CAO/ARO/AIO-04 phase III trial.

Background: The German rectal cancer trial CAO/ARO/AIO-04 has shown a significant benefit in 3-year disease-free survival (DFS) of adding oxaliplatin to a standard preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) and adjuvant chemotherapy in patients with locally advanced rectal cancer. The use of oxaliplatin as adjuvant treatment in elderly patients with colon cancer is controversial. We therefore investigated the impact of age on clinical outcome in the CAO/ARO/AIO-04 phase III trial. Patients and methods: We carried out a post hoc analysis of the CAO/ARO/AIO-04 phase III trial evaluating primary and secondary end points according to age. Patient and tumor characteristics, NCI CTC adverse events grades 3-4 (version 3.0), dose intensities as well as survival and recurrence data were analyzed in three specified age groups (<60, 60-70, and ≥70 years). The influence of age as a continuous variable on DFS was modeled using a subpopulation treatment effect pattern plot (STEPP) analysis. Results: A total of 1232 patients were assessable. With the exception of Eastern Cooperative Oncology Group status (P < 0.001), no differences in patient and tumor characteristics were noticed between age groups. Likewise, toxicity pattern, dose intensities of CRT and surgical results were similar in all age groups. After a median follow-up of 50 months, in patients aged <60 years a significant benefit of adding oxaliplatin to 5-FU-based CRT and adjuvant chemotherapy was observed for local (P = 0.013) and systemic recurrences (P = 0.023), DFS (P = 0.011), and even overall survival (OS; P = 0.044). The STEPP analysis revealed improved hazard ratios for DFS in patients aged 40-70 years compared with elderly patients treated with oxaliplatin. Conclusion: The addition of oxaliplatin significantly improved DFS and OS in younger patients aged <60 years with advanced rectal cancer. Patients aged ≥70 years had no benefit. Clinical Trials Number: NCT00349076.

Long-term prognostic impact of surgical complications in the German Rectal Cancer Trial CAO/ARO/AIO-94.

BACKGROUND: The influence of postoperative complications on survival in patients with locally advanced rectal cancer undergoing combined modality treatment is debatable. This study evaluated the impact of surgical complications on oncological outcomes in patients with locally advanced rectal cancer treated within the randomized CAO/ARO/AIO-94 (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society) trial. METHODS: Patients were assigned randomly to either preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) or postoperative CRT between 1995 and 2002. Anastomotic leakage and wound healing disorders were evaluated prospectively, and their associations with overall survival, and distant metastasis and local recurrence rates after a long-term follow-up of more than 10 years were determined. Medical complications (such as cardiopulmonary events) were not analysed in this study. RESULTS: A total of 799 patients were included in the analysis. Patients who had anterior or intersphincteric resection had better 10-year overall survival than those treated with abdominoperineal resection (63·1 versus 51·3 per cent; P < 0·001). Anastomotic leakage was associated with worse 10-year overall survival (51 versus 65·2 per cent; P = 0·020). Overall survival was reduced in patients with impaired wound healing (45·7 versus 62·2 per cent; P = 0·009). At 10 years after treatment, patients developing any surgical complication (anastomotic leakage and/or wound healing disorder) had impaired overall survival (46·6 versus 63·8 per cent; P < 0·001), a lower distant metastasis-free survival rate (63·2 versus 72·0 per cent; P = 0·030) and more local recurrences (15·5 versus 6·4 per cent; P < 0·001). In a multivariable Cox regression model, lymph node metastases (P < 0·001) and surgical complications (P = 0·008) were the only independent predictors of reduced overall survival. CONCLUSION: Surgical complications were associated with adverse oncological outcomes in this trial.

Tacrolimus interaction with oral oestrogen in kidney transplant recipients: A case-control study.

WHAT IS KNOWN AND OBJECTIVE: Oestrogens could inhibit the metabolism of drugs, such as calcineurin inhibitors, that are substrates for cytochrome P-450 microsomal enzymes. This study assessed the potential tacrolimus interaction with oral conjugated oestrogen in kidney transplant recipients who received conjugated oestrogen as prophylaxis against bleeding, before kidney biopsy. METHODS: In this case-control study, 13 kidney transplant recipients who received oral conjugated oestrogen as prophylaxis against uraemic bleeding before allograft biopsy were considered as cases. Thirteen matched kidney transplant recipients with similar immunosuppressive regimen served as controls. In this study, comparisons were made between the groups regarding daily dose, blood trough concentrations and calculated concentration corrected for dose of tacrolimus at three time points of the study. RESULTS AND DISCUSSION: All patients in the case group received conjugated oestrogen at a dose of 3.75 mg/day for 4.78 ± 0.83 days. Without any change in tacrolimus dose, the blood concentration of tacrolimus increased during concomitant administration of conjugated oestrogen (from 8.10 ± 2.85 to 12.35 ± 4.62 ng/mL; P = .11) and decreased after cessation of conjugated oestrogen (6.07 ± 2.18 ng/mL; P = .015). The calculated concentration corrected for dose of tacrolimus increased from 127.04 ± 79.23 to 211.40 ± 146.38 ngmLmgkg/d after conjugated oestrogen administration (P = .036). Thereafter, it decreased to 108.55 ± 78.61 ngmLmgkg/d after cessation of oestrogen (P = .003). Only one patient experienced nausea while taking oestrogen without any change in her liver enzymes. WHAT IS NEW AND CONCLUSION: Concomitant administration of oral oestrogen increased tacrolimus blood concentration. Hence, it is necessary to monitor tacrolimus blood levels during concomitant oestrogen therapy and for several days after oestrogen withdrawal.

[Undergraduate Medical Students "On Call" to Assist in Theatre: Analysis of the Financial Aspects and a Mixed-Method Study Exploring Their Motives for Working]. / Studentische Hilfskräfte im "Operativen Rufdienst": Mixed-Method-Studie zur Analyse des finanziellen Aspekts und der Motive der Studierenden.

Background/Purpose: Surgical patient care has grown in complexity, as hospital workload has continuously increased. We therefore established a pool of "undergraduate medical students on call" to assist in the theatre outside working hours. We aimed to recruit talented students to reduce the burden on physicians and to motivate students into entering surgery. Methods: An exploratory mixed-method study was performed. In a qualitative study, guided interviews were conducted with five students about their reasons for working in the theatre and the results were used to construct an online questionnaire using EvaSys®. This was presented to 16 current and former students in a subsequent quantitative study. Furthermore, the cost of student employment was calculated and compared with physicians' salaries. Results: In 2013 and 2014, 8-9 students worked a total of 1063 and 1211 hours in the theatre, respectively. The difference in salaries between the students and surgical residents was € 28.37 per hour. We calculated that the annual savings were approximately € 60,000. When questioned on their motives during the interview, only a few students emphasised the financial aspects, whereas the majority emphasised the gain in experience. The analysis was based on comparison of the mean values (online survey) with a 4-point Likert scale (1 = high acceptance; 4 = no acceptance). We defined the motives with a mean ≤ 1.3 as primary. Based on this selection, gathering experience, fun/enjoyment, interest in surgery, and the change from studying were considered as distinct motives. In the interviews, students clearly pointed out that teaching and learning opportunities in the theatre were not commonly taken advantage of and that interaction with the surgeons should be improved. Conclusion: Students actively chose to work as assistants in the theatre, for a variety of motives. The financial aspects were subordinate. The concept of students assisting in the theatre is favourable for both employers and students. However, the results also reveal that there is room for improvement in the implementation of the concept.

[Recruiting and Personal Development in Surgical Departments of Large Referral Centers - Current Practice and Options for Improvement from Industry and Service Business]. / Personalgewinnung und -entwicklung in viszeralchirurgischen Kliniken von Großkrankenhäusern ­ derzeitiger Stand und Möglichkeiten der Optimierung aus Industrie und Dienstleistungsgewerbe.

Background Cut-throat competition, cost pressure, generation Y, shortage of qualified staff and feminisation influence human resources management in visceral surgery. The assessment of the current situation by chief surgeons (CS) as well as proof of transferability of strategies from industry and service business (ISB) have not yet been investigated. Material and Methods The CS of university hospitals and large referral centres (> 800 beds) were interviewed (n = 100) on the basis of a standardised questionnaire including 43 items. Closed questions were designed with a 5-point Likert scale and their analysis was presented as means (MW) and standard deviations (±). Ten human resources manager (HMR) of ISB were invited to participate in 45-minute telephone interviews. Results Thirty-seven CS participated in the survey, 15 of whom were full professors. Unsolicited applications (100%), job advertisements (78%) and direct approaches to final year students (78%) were the most common ways of recruitment. Only 17% of CS used a standardised form for preparation. Professional expertise (MW 2.2 ± 0.9), social skills (MW 1.9 ± 0.6) and excellent German language skills (MW 1.8 ± 0.8) were named as important qualifications for employment, while references and certificates were regarded as being less important (MW 3.2 ± 0.9). Personal development was regarded as important (MW 1.1 ± 0.2), but a defined period for residency was not guaranteed (MW 3.0 ± 1.5). Transparent selection criteria for career opportunities (MW 2.5 ± 1.1) and different career models (MW 2.7 ± 1.2) were only rarely available. Six HRM participated in the interviews. Active head-hunting (75%), Internet platforms (75%), presentations at conferences (75%), as well as hiring trainees (50%), job advertisements (50%) and social media (50%) were established options to find qualified employees. Professional and management careers were often separate career paths, while social expertise was regarded as being crucial for filling management positions. Conclusion In visceral surgery, unsolicited applications, job advertisements and direct approaches to final year students are the most common ways for recruitment. Diversified professional and management careers are not yet established. Recruiting strategies that are successful in ISB - such as active scouting and use of social media - should be evaluated for visceral surgery, as well as diversified career models.

[Implementation of Robot-Assisted Surgery]. / Aufbau eines Roboterprogramms.

The implementation of robot-assisted surgery requires a multi disciplinary approach with appropriate training and cooperation of surgical, anesthetic and technical staff. Besides acquiring the technical skills and getting used to complex technique, patient selection and an appropriate frequency of procedures are required to avoid complications.

[General principles of tumour biology in visceral surgery]. / Allgemeine Grundlagen der Tumorbiologie in der Viszeralchirurgie.

Within the last decade, there has been a tremendous progress in understanding the molecular basis of cancer. In particular, the development and the characteristic features of cancer cells are being increasingly understood. The understanding of these molecular characteristics is mandatory for the development of novel, targeted therapeutic strategies and their integration into clinical practice. In addition, tumour genetics play a critically important role for hereditary cancer syndromes, with respect to both diagnostics and clinical decision-making. The aim of this review is to highlight general principles of tumour genetics from a visceral surgeon's point of view, although a comprehensive summary of all aspects would be beyond the scope of this article due to the complexity of the topic.

[Advance Directives - Not a Lot of Margin for Error - The Surgeon's View of a Complex Medical-Legal Topic]. / Patientenverfügungen - welchen Spielraum erlauben sie? - Chirurgische Sicht auf ein komplexes medizinjuristisches Thema.

Since September 1st, 2009, the most recent version of the German "Betreuungsrechtsänderungsgesetz" has been validated by the legislators. It precisely sets out how physicians and nursing staff have to deal with a written declaration of a patient's will. This new law focuses in a special way on advance directives, describes the precise rules for the authors of an advance directive and shows both its sphere of action and its limitations. This article aims to give an overview on the legal scope of advance directives, and to illustrate potential limitations and conflicts. Furthermore, it shows the commitments and rights of the medical team against the background of an existing advance directive.

Discrepancies between medical oncologists and surgeons in assessment of resectability and indication for chemotherapy in patients with colorectal liver metastases.

BACKGROUND: Multidisciplinary discussion of the treatment of patients with colorectal liver metastases (CRLM) is advocated currently. The aim of this study was to investigate medical oncologists' and surgeons' assessment of resectability and indication for chemotherapy, and the effect of an educational intervention on such assessment. METHODS: Medical histories of 30 patients with CRLM were presented to ten experienced medical oncologists and 11 surgeons at an initial virtual tumour board meeting (TB1). Treatment recommendations were obtained from each participant by voting for standardized answers. Following lectures on the potential of chemotherapy and surgery, assessment was repeated at a second virtual tumour board meeting (TB2), using the same patients and participants. RESULTS: Overall, 630 answers (21 × 30) were obtained per tumour board meeting. At TB1, resectability was expected more frequently by surgeons. Participants changed 56·8 per cent of their individual answers at TB2. Assessment shifted from potentially resectable to resectable CRLM in 81 of 161 and from unresectable to (potentially) resectable CRLM in 29 of 36 answers. Preoperative chemotherapy was indicated more often by medical oncologists, and overall was included in 260 answers (41·3 per cent) at TB1, compared with only 171 answers (27·1 per cent) at TB2. Medical oncologists more often changed their decision to primary resection in resectable patients (P = 0·006). Postoperative chemotherapy was included in 51·9 and 52·4 per cent of all answers at TB1 and TB2 respectively, with no difference in changes between medical oncologists and surgeons (P = 0·980). CONCLUSION: Resectability and indication for preoperative chemotherapy were assessed differently by medical oncologists and surgeons. The educational intervention resulted in more patients deemed resectable by both oncologists and surgeons, and less frequent indication for chemotherapy.

mFOLFOX6 versus mFOLFOX6 + aflibercept as neoadjuvant treatment in MRI-defined T3-rectal cancer: a randomized phase-II-trial of the German Rectal Cancer Study Group (CAO/ARO/AIO 0214).

BACKGROUND: Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer. PATIENTS AND METHODS: Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI. Patients were randomized 1 : 2 to six cycles mFOLFOX6 ± aflibercept. Surgery was scheduled 4 weeks after chemotherapy. Primary endpoint was the rate of centrally confirmed pCR. The study was designed to detect an improvement of pCR from 10% to 27% (power 80%, type I error 20%). RESULTS: A total of 119 randomized patients started treatment (39 patients mFOLFOX6, arm A, and 80 mFOLFOX + aflibercept, arm B). The incidence of all grade adverse events was similar in both arms, however, adverse events grade ≥3 were more than twice as high in the experimental arm due to hypertension. Surgical complications were comparable. Aflibercept did not improve the pCR rate (arm A 26% versus arm B 19%, P = 0.47) and more patients in arm B had node positivity. With a median follow-up of 40.1 months, the 4-year disease-free survival was 83% in arm A and 85% in arm B (P = 0.82). Only two patients in arm A and one patient in arm B developed local recurrence. CONCLUSIONS: In patients with locally advanced rectal cancer and MRI-defined low risk of local recurrence, neoadjuvant mFOLFOX6 + aflibercept was feasible and did not compromise surgery. Survival data were favorable in both arms, but pCR rates were not increased by the addition of aflibercept.

[Value of one-stage surgical treatment of diffuse peritonitis (relaparotomy on demand): a single-center analysis]. / Stellenwert der einzeitigen chirurgischen Therapie bei diffuser Peritonitis (Relaparotomie "on demand"): eine unizentrische Analyse.

BACKGROUND: Despite modern surgical and intensive-care concepts, diffuse peritonitis remains a major source of high morbidity and mortality. The aim of this study was to critically evaluate the value of relaparotomy on demand (ROD) for patients with diffuse peritonitis. PATIENTS AND RESULTS: In a retrospective analysis, the clinical course of 231 patients with diffuse peritonitis was analysed. The mean Mannheim Peritonitis Index (MPI) was 25.3. Overall lethality in this cohort was 14.3 %. In 214 patients, source control was successful during the index operation, and these patients were treated according to an on-demand strategy. For 178 of these patients, there was no demand for a relaparotomy, whereas 36 of these patients required further surgical interventions. Lethality for these subgroups was 9 % (no relaparotomy) and 27 % (relaparotomy), respectively. CONCLUSIONS: This retrospective analysis confirms that an on-demand strategy is reasonable and feasible after successful source control and lavage. However, it still remains of clinical importance to identify parameters that may assist in selecting those patients who require a relaparotomy.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.

Randomized comparative long-term survival study of endoscopic and thoracoscopic esophageal wall repair after NOTES mediastinoscopy in healthy and compromised animals.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) has not yet been widely adopted because of lack of suitable equipment and fear of possible serious complications, especially in the mediastinum. We compared endoscopic with thoracoscopic esophageal wall repair after full-thickness esophageal wall incision (FTEI) and NOTES mediastinoscopy in healthy versus compromised animals. METHODS: After FTEI for mediastinoscopy, 24 pigs (12 healthy, 12 compromised) were randomly allocated to endoscopic or thoracoscopic repair (each arm of each group, n = 6). They were kept alive for 3 months after endoscopic closure with prototype T-anchor suturing or thoracoscopic repair. RESULTS: FTEI and mediastinoscopy were uneventful in all as was the initial repair of the incision (mean repair times: thoracoscopic 65 +/- 3.2 minutes, endoscopic 52 +/- 5.1 minutes; P < 0.0005). Post procedure, all 12 healthy pigs thrived with no complications or deaths. Two compromised animals died during the preparation period, and had to be replaced. In the compromised group, during endoscopic repair, 2 / 6 pigs suffered from gastric reflux into esophagus and mediastinum; the repair was completed and the pigs kept alive; one subsequently died of mediastinitis, and in the other, autopsy showed a gastric abscess in the lower mediastinum. Regarding the compromised thoracoscopic subgroup, one animal died from mediastinitis and all had abscesses at or near the incision sites. CONCLUSION: Transesophageal mediastinoscopy could be performed equally well as the transthoracic procedure, both in healthy and compromised animals. However, on follow-up, the compromised animals had worse outcomes, with more complications and two deaths (17 %), one in each arm.