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BACKGROUND: Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. METHODS: This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3-4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m(2) days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) days 1-5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (250 mg/m(2) days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) days 1, 8, 22, and 29), followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin (100 mg/m(2) days 1 and 15), leucovorin (400 mg/m(2) days 1 and 15), and infusional fluorouracil (2400 mg/m(2) days 1-2 and 15-16; fluorouracil plus oxaliplatin group). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-4 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. DFS is the primary endpoint. Secondary endpoints, including toxicity, compliance, and histopathological response are reported here. Safety and compliance analyses included patients as treated, efficacy endpoints were analysed according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT00349076. FINDINGS: Of the 1265 patients initially enrolled, 1236 were evaluable (613 in the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group). Preoperative grade 3-4 toxic effects occurred in 140 (23%) of 606 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy. Grade 3-4 diarrhoea was more common in those who received fluorouracil and oxaliplatin during chemoradiotherapy than in those who received fluorouracil during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3-4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495 (79%) and 601 (96%) of 624 patients who received fluorouracil-based chemoradiotherapy, respectively. A pathological complete response was achieved in 103 (17%) of 591 patients who underwent surgery in the fluorouracil and oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the fluorouracil group (odds ratio 1·40, 95% CI 1·02-1·92; p=0·038). In the fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant chemotherapy completed all cycles (with or without dose reduction), as did 386 (83%) of 463 patients in the fluorouracil group. INTERPRETATION: Inclusion of oxaliplatin into modified fluorouracil-based combined modality treatment was feasible and led to more patients achieving a pathological complete response than did standard treatment. Longer follow-up is needed to assess DFS. FUNDING: German Cancer Aid (Deutsche Krebshilfe). [ABSTRACT FROM AUTHOR]

Background and Purpose: This systematic review summarised and critically appraised evidence on the efficacy and safety of interventions for anal cancer to support the panel of experts developing the national evidence-based anal cancer guideline in Germany., Materials and Methods: We conducted a systematic review and meta-analyses of interventions for the treatment of stage I to III anal squamous cell carcinoma (SCCA). We systematically searched several databases and included any randomised controlled trial (RCT) assessing the pre-specified patient populations, regardless of the interventions studied. Non-randomised controlled studies of selected, pre-specified interventions were included if RCTs were not available or contained insufficient information. Where possible, we conducted meta-analyses and critically assessed confidence in the effect estimates using the GRADE approach., Results: Our searches yielded 10,325 (25 October 2018) and 889 hits (update search on 18 July 2019). Among the 41 studies (47 publications) included, we identified 19 comparisons of interventions for SCCA, and confidence in the effect estimates ranged from very low to high. Most RCTs compared various chemoradiation regimes. For other treatment options, such as local excision in early stages or different radiotherapies, we mostly identified comparative cohort studies., Conclusion: Our findings indicate that, in most clinical situations, primary chemoradiation based on 5-FU and MMC is still the gold standard. However, treatment options for stage I anal cancer, particularly of the anal margin, as well as newer treatment approaches should be investigated in future RCTs. Overall, our findings may help health care professionals and patients make informed decisions about treatment choices., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers., Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with stage II/III rectal cancers were evaluated. LR-rates and OS were stratified by hospital recruitment volume (≤20 vs. 21-90 vs. >90 patients) and by surgeon volume (≤10 vs. 11-50 vs. >50 procedures)., Results: Patients treated in high-volume hospitals had a longer OS than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was adversely associated with LR (p = 0.01) but had no influence on overall survival. The positive effect of neoadjuvant chemoradiation (CRT) on local control was the strongest in patients being operated by medium-volume surgeons, less in patients being operated by high-volume surgeons and missing in those being operated by low-volume surgeons., Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on long-term local tumour control. The effect of neoadjuvant CRT on local tumour control may likewise depend on the surgeon volume., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aim: miRNA expression patterns vary within primary rectal cancers and play a pivotal role in carcinogenesis. It is unknown, however, if these regulatory changes also play a role in local recurrent rectal cancers. In this study, the expression of various angiogenetic small non-coding ribonucleic acids, namely miRNA-21, miRNA-215, miRNA-221, and miRNA-222 were analysed in cancerous and healthy rectal tissues., Patients and Methods: miRNA expression was analyzed via quantitative polymerase chain reaction (qPCR). Samples were obtained from 20 patients who were treated for local recurrent rectal cancer at the Department for general and visceral surgery, Klinikum Oldenburg, Germany., Results: No significant differences in the expression of miRNA-221, miRNA-222 and miRNA-215 were observed between cancerous and healthy rectal tissues. However, a significant differential expression was detected for miRNA-21., Conclusion: miRNA-21 is differentially expressed in recurrent rectal cancer tissue and healthy tissues. However, miRNA-215, miRNA-221 and miRNA-222 are not significantly differentially expressed., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Importance: Previous retrospective studies have shown that surgical quality affects local control in rectal cancer.., Objective: In this secondary end point analysis, we evaluated the prognostic effect of the total mesorectal excision (TME) plane in the CAO/ARO/AIO-04 phase 3 randomized clinical trial., Design, Setting, and Participants: The CAO/ARO/AIO-04 trial enrolled 1236 patients with cT3-4 and/or node-positive rectal adenocarcinoma from 88 centers in Germany between July 25, 2006, and February 26, 2010., Interventions: Patients were randomized to receive treatment with standard fluorouracil-based preoperative chemoradiotherapy (CRT) alone (control arm) or oxaliplatin (experimental arm) followed by TME and adjuvant chemotherapy., Main Outcomes and Measures: The TME quality (mesorectal, intramesorectal, and muscularis propria plane) was prospectively assessed in 1152 operation specimens. An assessment was performed independently by pathologists and surgeons. The results were correlated with clinicopathologic data and the clinical outcome was tested, including multivariable analysis with the Cox regression model., Results: Of 1152 German Caucasian participants, 332 (28.8) were women and the mean age was 63 years. The plane of TME was mesorectal in 930 patients (80.7%), intramesorectal in 169 (14.7%), and muscularis propria in 53 (4.6%). In a univariable analysis, the TME plane was significantly associated with 3-year disease-free survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 73.1-78.8 vs 61.6-76.0 vs 55.6-81.3, respectively; P = .01), cumulative incidence of local and distant recurrences (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 2.0-4.5 vs 1.2-8.1 vs 2.5-20.5, respectively; P < .001; and mesorectal vs intramesorectal vs muscularis propria, 95% CI, 17.0-22.4 vs 18.3-32.0 vs 14.2-39.0, respectively; P = .03, respectively), and overall survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 88.3-92.3 vs 79.7-91.0 vs 81.6-98.7, respectively; P = .02). In contrast to the pathologist-based evaluation, the assessment of TME plane by the operating surgeon failed to demonstrate prognostic significance for any of these clinical end points. In a multivariable analysis, the plane of surgery (mesorectal vs muscularis propria TME) constituted an independent factor for local recurrence (P = .002)., Conclusions and Relevance: This phase 3 randomized clinical trial confirms the long-term clinical effect of TME plane quality on local recurrence, as initially reported in the MRC CR07 study. The data highlight the key role of pathologists and surgeons in the multidisciplinary management of rectal cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT00349076.

Objective: Retroperitoneal sarcomas (RPSs) are rare cancers with some variability in clinical and histopathological presentation. In Germany, general treatment strategies of retroperitoneal sarcoma are unknown since centralized registries do not exist. The objective of this survey was to access the medical care of RPS patients in Germany., Methods: In cooperation with the German Society of General and Visceral surgery, the German Interdisciplinary Sarcoma Study Group and the patient advocacy group Das Lebenshaus we designed an online survey assessing diagnostic and treatment strategies (e. g. performance of tumor biopsies, administration of multimodal therapies and surgical strategy). All departments for general and visceral surgery in Germany were addressed (n = 976)., Results: Responses were received from 191 of 976 departments. Only 11 surgical departments treat more than 10 RPS patients per year. A multidisciplinary sarcoma board exists in 19 hospitals. Staging is generally performed by cross-sectional imaging. In 54% of the departments pretreatment tumor biopsy is a standard procedure. Surgery is performed as compartment resection in 85% of the departments. A systematic lymph node dissection is done in 40%. Adjuvant radio- or chemotherapy is performed as a standard treatment in 27% and 22% departments, respectively., Conclusion: The survey demonstrates a large heterogeneity in RPS diagnostic and treatment strategies. Dedicated education programs and centralized treatment strategies are warranted to improve the standard of care.

Background: We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial., Methods: TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided., Results: With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4., Conclusions: Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

R1 resections in rectal cancer particularly affect the circumferential resection margin (CRM) and lead to increased local recurrence rates, more distant metastases and a poorer prognosis. The proximity of the tumor to the CRM is already sufficient to increases these risks; therefore, according to the guidelines, it is now necessary to distinguish between R0 wide (≥1 mm distance), R0 close (<1 mm) and R1. The surgical technique is decisive for avoiding R1 situations. The preparation follows the boundary layers and envelope fascia in a standardized radical way and if necessary deviates away from these structures and the tumor under en bloc resection of neighboring structures. Neoadjuvant therapy also contributes to the reduction of R1 situations but cannot compensate for inadequate surgical procedures.

Background: After gastrectomy or esophagectomy, esophagogastrostomy and esophagojejunostomy are commonly used for reconstruction. Water-soluble contrast swallow is often used as a routine screening to exclude anastomotic leakage during the first postoperative week. In this retrospective study, the sensitivity and specificity of oral water-soluble contrast swallow for the detection of anastomotic leakage and its clinical symptoms were analysed., Material/methods: Records of 104 consecutive total gastrectomies and distal esophagectomies were analysed. In all cases, upper gastrointestinal contrast swallow with the use of a water-soluble contrast agent was performed on the 5 th postoperative day. Extravasation of the contrast agent was defined as anastomotic leakage. When anastomotic insufficiency was suspected but no extravasation was present, a computed tomography (CT) scan and upper endoscopy were performed., Results: Oral contrast swallow detected 7 anastomotic leaks. Based on CT-scans and upper endoscopy, the true number of anastomotic leakage was 15. The findings of the oral contrast swallow were falsely positive in 4 and falsely negative in 12 patients, respectively. The sensitivity and specificity of the oral contrast swallow was 20% and 96%, respectively., Conclusions: Routine radiological contrast swallow following total gastrectomy or distal esophagectomy cannot be recommended. When symptoms of anastomotic leakage are present, a CT-scan and endoscopy are currently the methods of choice., Competing Interests: Statement There is no conflict of interest. There was no funding of this original research. An ethical approval was not required.

Background: Tumor response after neoadjuvant radiochemotherapy (NRC) prior to surgery and other parameters are likely to have an influence on the survival rate of patients suffering from T3 rectal cancer., Methods: 51 patients (17 female, 34 male; 59.0 years; Apache < 9 points: 95.1%; ASA I-II 88.3% and ASA III 11.8%) were treated with NRC (50.4 Gy; 5-fluorouracil/folinic acid) 4-6 weeks prior to surgery because of uT3 rectal cancer (G2: 96%; adenocarcinoma 86.3%; cUICC II 62.7%). NRC led to a tumor response (TR) (ypT0-ypT2) in 45.1% (ypT0N0M0 7.8%)., Results: Neither the age of patients nor Apache/ASA score, histology, UICC staging, ypTNM, Dukes staging, infiltration of vessels, surgical procedure, local recurrence nor TR had a significant influence on the patients' survival time. Patients with metachronous distant metastasis (MDM) during the follow-up period (mean: 8.2 years; 1 month to 14.5 years) and patients with ypN1-ypN2 had a significantly shorter survival time., Conclusions: NRC prior to surgery leads to a remarkable TR rate but has no significant impact of TR on the patients' survival time. Occurrence of MDM during the follow-up period and ypN1/N2 status do have a greater influence. It is necessary to investigate larger cohorts of patients in the future to obtain more conclusive results and to define factors with influence on survival.

Introduction: Pelvic floor defects following pelvic exenteration constitute a challenge to the reconstructive surgeon. Whenever the common reconstruction options such as the gluteus maximus myocutaneous flap (GLM) and the vertical rectus abdominis myocutaneous flap (VRAM) are not feasible, free tissue transfer will be the only remaining option. Being one of the most reliable and versatile flaps used for microsurgical reconstruction, the free latissimus dorsi (LD) muscle flap provides an adequate solution to this problem., Patients and Methods: We describe our experience with 12 consecutive patients who underwent the free transfer of LD free flap for secondary reconstruction of the pelvic floor and perineum following pelvic exenteration for management of locally advanced pelvic malignancies in Klinikum Oldenburg from 2007 to 2014., Results: Recurrent cancer of the anal canal was the most common pathology necessitating the performance of pelvic exenteration. Thrombosis of the vascular anastomosis was reported in two cases and ended with total flap loss in one of them. Functional limitations arose in two patients postoperatively. The mean hospital stay was 25 days., Conclusion: Free LD myocutaneous flap provides an adequate solution for reconstruction of pelvic defects resulting from radical oncological resections in cases where the use of locoregional flaps, such as the gluteus maximus flap and the vertical rectus abdominis flap, is not feasible because of an extensive defect, disruption of the vascular pedicle, or due to planning for bilateral stomas placement.

Background . After pancreaticoduodenectomy (PD), pancreatic fistulas (PF) are a frequent complication. Infusions may compromise anastomotic integrity. This retrospective analysis evaluated associations between intraoperative fluid excess and PF. Methods . Data on perioperative parameters including age, sex, laboratory findings, histology, infusions, surgery time, and occurrence of grade B/C PF was collected from all PD with pancreaticojejunostomy (PJ) performed in our department from 12/2011 till 02/2015. The glomerular filtration rate (GFR), infusion rate, and the ratio of both and its association with PF were calculated. ROC analysis was employed to identify a threshold. Results . Complete datasets were available for 83 of 86 consecutive cases. Median age was 66 years (34-84; 60% male), GFR was 93 mL/min (IQR 78-113), and surgery time was 259 min (IQR 217-307). Intraoperatively, 13.6 mL/min (7-31) was infused. In total, n = 18 (21%) PF occurred. When the infusion : GFR ratio exceeded 0.15, PF increased from 11% to 34% ( p = 0.0157). No significant association was detected for any of the other parameters. Conclusions . This analysis demonstrates for the first time an association between intraoperative fluid excess and PF after PD with PJ even in patients with normal renal function. A carefully patient-adopted fluid management with due regard to renal function may help to prevent postoperative PF., Competing Interests: The authors declare that they have no competing interests.

Transsphincteric resection of rectal tumors was first described about 120 years ago. Nowadays, this approach faded into obscurity due to standardized guidelines and practice in surgical oncology including lymphadenectomy, mesorectal excision and radical dissection of veins. However, transsphincteric resection seems reasonable in some cases, especially if an abdominal approach can be avoided. In the following, we will present and describe the technique of the transsphincteric approach with its variations in rectal surgery in the case of a rare pararectal tumor., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Locally recurrent rectal tumours in the pelvis are found in about 6% following treatment for rectal cancer. This type of tumour can cause serious local complications and symptoms. The aim of modern surgical oncology is to offer a curative treatment option embedded in an interdisciplinary network of specialities to the patient. Due to advancements in surgical techniques and procedures, especially regarding surgical reconstruction, the possibilities of a curative treatment regarding recurrent cancers have been expanded and established. To aim for a curative treatment one must introduce a multimodal therapy including radio- and chemotherapy, and a radical oncological surgery with en bloc resection of the tumour and affected surrounding organs to achieve a R0-resection.

Background and Aims: Esophageal perforation is a rare diagnosis, which is associated with a high morbidity and mortality. There is only small scientific background regarding the best choice of treatment. Parameters indicating a good clinical outcome seem to be localization, depth of the defect, pre-existing risk factors, and time interval between the event and start of treatment., Material and Methods: We evaluate retrospective data from 39 patients who were treated with a esophageal perforation in our hospital between 2004 and 2012., Results and Conclusions: Our collected data agree with the available published literature. Endoscopic treatment seems to be favorable in early diagnosis., (© The Finnish Surgical Society 2014.)

Background: Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy., Methods: In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3-4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m(2) on days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) on days 1-5 and 29); or to an investigational group receiving preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m(2) on days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m(2) on days 1 and 15), leucovorin (400 mg/m(2) on days 1 and 15), and infusional fluorouracil (2400 mg/m(2) on days 1-2 and 15-16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-3 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of patients in this trial is completed and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00349076., Findings: Of the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38-61), disease-free survival at 3 years was 75·9% (95% CI 72·4-79·5) in the investigational group and 71·2% (95% CI 67·6-74·9) in the control group (hazard ratio [HR] 0·79, 95% CI 0·64-0·98; p=0·03). Preoperative grade 3-4 toxic effects occurred in 144 (24%) of 607 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorouracil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (36%) had grade 3-4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late grade 3-4 adverse events in patients who received protocol-specified preoperative and postoperative treatment occurred in 112 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group., Interpretation: Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy (at the doses and intensities used in this trial) significantly improved disease-free survival of patients with clinically staged cT3-4 or cN1-2 rectal cancer compared with our former fluorouracil-based combined modality regimen (based on CAO/ARO/AIO-94). The regimen established by CAO/ARO/AIO-04 can be deemed a new treatment option for patients with locally advanced rectal cancer., Funding: German Cancer Aid (Deutsche Krebshilfe)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Extended resections of pelvic malignancies, especially in cases of recurrent malignancies, result in the formation of large tissue defects in the region of the pelvic floor and perineum, which are difficult to deal with. Both after extra levator rectal excision and pelvic exenteration, wound healing deficiencies and local infections of the perineal wound are frequent. Primary closure is often impossible due to a lack of tissue substance after resection and an additional previous radiotherapy in most cases. This can result in poor or non-healing wounds, a consecutive need of complex care and an increased risk of secondary problems including tumour recurrences. A permanent wound closure of good quality can therefore only be achieved by plastic surgery. This can be done by local or distant muscle flaps with or without skin, for example, the gluteus maximus flap, the vertical rectus abdominis muscle flap (VRAM) or free flaps such as the latissimus dorsi flap., (Georg Thieme Verlag KG Stuttgart · New York.)

The higher incidence of gallstone formation after gastrectomy for cancer has been reported as a common complication in many studies but the management strategies are still controversial and need further evaluation. We retrospectivaly analysed between 2007 and 2013, 206 patients who underwent gastric and or oesophageal resection. In 29/93 patients receiving an oesophagectomy a simultaneous cholecystectomy was performed, respectively 31 from 111 patients who underwent a gastrectomy received an incidental cholecystectomy. In 2 patients with an extended gastrectomy, the gallblader removing was performed simultaneously in one case. A subsequent cholecystectomy was performed in 11 cases. The increased surgical mortality was significant higher correlated with an intervention at a later stage point. That suggest that the prohylactic cholecystectomy can be safely performed during a major intervention in order to reduce complication and a reoperation., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

The incidence of malnutrition in oncological and visceral surgical units can be high. The screening of malnourished patients is very important, especially in the preoperative setting. The available published literature provides crucial knowledge about the risks inherent to malnutrition and subsequent perioperative morbidity and mortality. The preoperative screening of malnourished patients followed by a subsequent renutrition is the key to decreasing rates of postoperative morbidity and mortality. The data and guidelines given by the European Society of Parenteral and Enteral Nutrition (ESPEN) in 2006 for the preoperative nutritional conditioning are clear and give no doubt regarding the necessity of preparation of malnourished patients for elective abdominal surgery. Despite this fact, the observance and application of these guidelines among German surgical units remain low. To fill this void a model of systematic screening and treatment of malnutrition in the preoperative setting for elective abdominal surgery was created and implemented at the university hospital of Oldenburg. A practical treatment regimen was designed to prepare malnourished patients within 2-3 weeks before elective surgery. Initial results regarding the feasibility of preoperative home renutrition therapy were moderate but encouraging. The success of such a conditioning process depends on cooperation between the surgical unit, the general practitioner (GP) and the homecare environment. In the German healthcare system the prescription of home nutrition (i.e. enteral feeding) can lead to the prescription limits of a GP being exceeded and has to be justified to the medical insurance company in each case. This article presents a simple yet applicable way of screening and preparing malnourished patients a few weeks prior to elective surgery. Therefore, simple tools which can be promptly used in daily clinical life, especially in the outpatient surgical consultations prior to elective visceral surgery are proposed.

Purpose: We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months., Patients and Methods: TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS)., Results: Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026)., Conclusion: Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting., (© 2014 by American Society of Clinical Oncology.)

Background: Initially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation., Patients and Methods: Patients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012., Results: Between December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI 28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2-15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%)., Conclusions: This study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion' treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional 'line of therapy' in those patients who are not cured., Clinical Trial Number: NCT00153998, www.clinicaltrials.gov.

This article presents and summarizes different treatment options for rectal cancer. The aim of this article is an historical review of treating primary and recurrent rectal cancer, highlighting the development and advancement in surgical and multimodal therapy. Limitations, specifically regarding recurrent rectal cancer are discussed and reviewed. A R0 resection can almost always be achieved in primary rectal cancer. In recurrent rectal cancer a R0 resection with extended surgical resection can be achieved in up to 70 % of the cases. In addition, surgical therapy plays a crucial role in the case of metastatic disease but should be incorporated into a multimodal network. The analysis of tumor genetics and predictive parameters will lead to the emergence of new treatment concepts shifting the limits of the current gold standard. Oncological long-term survival and improving the quality of life are the main focal points.

Background: The combination of right sided portal vein ligation and hepatic parenchymal transection thus inducing a hypertrophy of the left or left lateral sector is an innovative treatment option in treating locally advanced hepatic tumors or hepatic metastases. The available published data regarding this procedure is weak. We analyzed our own data regarding tumor recurrence and complications. The data was then used to be critically analyzed using the available published literature., Methods: We treated n = 5 patients with an ALPPS (associating liver partition and portal vein ligation for staged hepatectomy). The follow-up was 3 years. We analyzed the perioperative period, complications, mortality and oncological survival rate., Results: In all patients (n = 5) a R0-resection was achieved. N = 1 patient died postoperatively. N = 1 patient died 6 month later due to a pulmonary embolism. N = 3 patients had a tumor recurrence within 6 months., Conclusion: Selected patients can be successfully treated by ALPPS in terms of an R0-resection. However, risk of tumor recurrence and rate of complications are high., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Rectovaginal fistulas constitute a serious burden for the affected patient and a major challenge for the attending surgeon. Definitive surgical treatment of the fistula depends on the size and location of the fistula, the underlying disease, and any previous therapies. In regards to complicated recurrent rectovaginal fistulas, transposition of the gracilis muscle is one of the well-established therapeutic options with a success rate of up to 70%., Material and Methods: Between 01/2004 and 06/2010, ten patients diagnosed with a recurrent rectovaginal fistula were treated in the surgical department of Klinikum Oldenburg by gracilis muscle transposition; their data were collected and analyzed. Post-operative evaluation was performed using a standardized telephone interview. All patients had a protective stoma. The primary endpoint of assessment was the long-term healing of the fistula following stoma reversal, and the comparison between those who were treated successfully versus those who were not., Results: Over a time span of 6years, ten women with a complicated rectovaginal fistula underwent fistula repair with the gracilis muscle transposition. Patient age ranged from 29 and 64years. There were five rectovaginal fistulas, four pouch-vaginal fistulas, and one anovaginal fistula. The underlying disease was rectal cancer in seven patients, Crohn's disease in one patient, previous complicated gynecologic surgery in one patient, and idiopathic anal fistula in one patient. All seven patients with rectal cancer underwent radiochemotherapy with 50.4Gy (n=6 neo-adjuvant, n=1 adjuvant). All ten patients had previously undergone repair by a different surgical approach while five presented with a second or third recurrence. Post-operative complications were noted in two patients (perineal wound defect, thigh hematoma). Follow-up of the patients ranged from 8 to 60months. Recurrent rectovaginal fistula occurred in four patients. Evaluation of the data failed to identify statistically significant criteria for treatment failure of rectovaginal fistula repair., Conclusion: Our results are similar to previous studies in this area. For the majority of the patients, the gracilis muscle transposition was a long-term effective treatment of recurrent rectovaginal fistulas, however recurrences were noted in 40% of cases. Predictive criteria for treatment failure could not be established., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: The CAO/ARO/AIO-94 phase-III-trial demonstrated a significant improvement of preoperative chemoradiotherapy (CRT) versus postoperative CRT on local control for UICC stage II/III rectal cancer patients, but no effect on long-term survival. In this add-on evaluation, we investigated the association of gender and age with acute toxicity and outcome., Patients and Methods: According to actual treatment analyses, 654 of 799 patients had received pre- (n=406) or postoperative CRT (n=248); in 145 patients postoperative CRT was not applied. Gender, age and clinicopathological parameters were correlated with CRT-associated acute toxicity and survival., Results: The 10-year survival was higher in women than in men, with 72.4% versus 65.6% for time to recurrence (p=0.088) and 62.7% versus 58.4% for overall-survival (OS) (p=0.066), as expected. For patients receiving CRT, women showed higher hematologic (p<0.001) and acute organ toxicity (p<0.001) in the entire cohort as well as in subgroup analyses according to pre- (p=0.016) and postoperative CRT (p<0.001). Lowest OS was seen in patients without acute toxicity (p=0.0271). Multivariate analyses for OS showed that acute organ toxicity (p=0.034) was beneficial while age (p<0.001) was associated with worse OS., Discussion: Female gender is significantly associated with CRT-induced acute toxicity in rectal cancer. Acute toxicity during CRT may be associated with improved long-term outcome., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Castleman's disease is presented in the following article in more detail using the case report of a 55-year-old patient with abdominal pain without any significant pre-existing medical conditions. A computer tomography of the abdomen demonstrated a retroperitoneal tumor in the lower abdomen below the aortic bifurcation. Because malignancy of the tumor could not be excluded, surgical extirpation was performed without complications. Histopathological examination revealed the diagnosis of a localized castleman's tumor. Castleman's disease is a rare disease of the lymph nodes of unknown etiology. In the prognosis, benign forms can be distinguished from malignant forms.

Over the last decades the therapy of rectal carcinoma has shown continuous improvement. Due to improvements in operative techniques, such as the establishment of total mesorectal excision (TME) and the combination of surgery and (neo-) adjuvant radiochemotherapy, the incidence of locally recurrent rectal cancer could be improved from nearly 50% to less then 10%. Nevertheless recurrent rectal carcinoma remains a severe problem. Predictive factors relating to locally recurrent rectal cancer are surgical experience, localization of the tumor, circumferential resection margins, stage-oriented multimodal therapy and a suitable oncological procedure for the primary tumor. In addition the tumor-specific biology also seems to be a relevant risk factor for recurrence. Operative treatment of locally recurrent rectal cancer was seen for a long time as a palliative procedure. Newer data show that resection of locally recurrent rectal cancer can be carried out with a curative intention in experienced institutions with a long-term 5 year survival of about 30% and mortality around 5%. The composite sacropelvic resection technique is a reasonable option in the curative treatment of locally recurrent rectal cancer. For the future the focus must be on improvements in the primary therapy of rectal carcinoma to avoid local recurrence. In addition early diagnosis of local recurrence and multimodal therapies will be of decisive importance.

Background: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting., Methods: Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or > or =5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4-6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998., Findings: 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI -8 to 30; odds ratio [OR] 1.62, 0.74-3.59; p=0.23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35-8.66; p=0.0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p<0.0001)., Interpretation: Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability., Funding: Merck-Serono, Sanofi-Aventis, and Pfizer., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The basic principle in the treatment of rectal cancer is the complete surgical removal of the tumor together with the lymphatic drainage region, i.e. the mesorectum encased by the mesorectal 'fascia pelvis visceralis' according to Westhues. It was shown in the 1990s that the results of surgery alone could be improved by additional adjuvant and neoadjuvant therapy. Because of less toxicity and a lower rate of local recurrence, neoadjuvant therapies in International Union Against Cancer (UICC) stage II and III disease are now preferred over adjuvant strategies. The German Rectal Cancer study CAO/ARO/AIO-94 showed a full remission rate of 8% after a 5-fluorouracil (5-FU)based chemotherapy added to a conventional fractional radiation therapy (50.4 Gy). This figure, together with similar results of others, leads to the question whether surgical radicality in rectal cancer treatment could be limited in case of a good remission after neoadjuvant therapy. There are several promising possibilities under investigation, e.g. local excision instead of radical resection, or even no resection at all. Nevertheless, up to now these strategies did not prove to give comparable results to standard surgical procedures. Therefore, reduction of radicality in curable rectal cancer should be limited to accurately designed randomized clinical trials., (Copyright (c) 2009 S. Karger AG, Basel.)

During the last decade no gastrointestinal tumor underwent such profound modifications in diagnostics and therapy as rectal cancer (total mesorectal excision, multimodal therapy). Despite all efforts and continuous improvements in the results of oncological treatment, local recurrence of rectal carcinoma is still a considerable problem. Optimized surgery methods and multimodal therapies allow a local recurrence rate lowered to about 6%. Without surgical intervention the 5-year survival rate after local recurrence is approximately 4%, and the median survival time in a palliative situation is about 13 months and often associated with considerable restriction of quality of life. Morbidity after complex pelvic surgery is still high, but its mortality rate in highly professional surgical centers has reached an acceptable level of about 6%. Surgical oncology today has the ability for remarkable improvement in the prognosis of locally recurrent rectal cancer. After R0 resection the 5-year survival rate is nearly 30%.

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.