[Current surgical treatment options for liver metastasis]. / Lebermetastasen: aktueller Stand der chirurgischen Behandlungsmöglichkeiten.

Current surgical treatment options for liver metastasis Abstract. Metastasis are the most frequent hepatic tumors. Although current treatment regimens focus highly on interdisciplinarity and are individualized, surgical resection remains the only curative treatment and represents the current gold standard approach. Advances in surgical, systemic and interventional treatment within the last years have resulted in a multidisciplinary therapy, individualized for each patient depending on their disease stage and condition. With these advancements, initially non-resectable liver metastasis can now be candidates for a surgical approach. Neoadjuvant chemotherapy, minimal invasive ablation, two- or multi-staged resections of the liver with or without portal vein embolization have contributed to this development. Advances in surgical and perioperative treatment also account for significantly increased overall survival.

Resection or radiofrequency ablation for hepatocellular carcinoma? Assessment of validity of current studies, meta-analyses and their influence on guidelines.

BACKGROUND: Two Cochrane reviews compared overall survival following liver resection (LR) or radiofrequency ablation (RFA) for patients with hepatocellular carcinoma. The first from 2013, found moderate evidence for a survival advantage for LR over RFA when limiting the analysis to trials at low risk of bias. The second (2017), found no evidence for a difference in all-cause mortality for LR versus RFA. Aim was to assess the validity of the randomized controlled trials included in both Cochrane reviews and to investigate their impact on current guidelines. METHODS: The validity of the studies was analyzed using the CONSORT checklist. Two meta-analyses were then performed with all eligible studies from both meta-analyses. Finally, the impact of the result of the original meta-analyses on eight international guidelines was assessed. RESULTS: The four randomized controlled trials showed several inconsistencies (unclear or inadequate randomization, absence of sample-size calculation, missing blinded setup and/or conflicts of interest). All guidelines used recommendations based on the results of the meta-analyses or on studies included in the meta-analyses. CONCLUSION: The analyzed studies showed a substantial lack of overall validity. However the results of these studies and subsequent meta-analyses are used as the evidence base for the majority of current guidelines.

Can preoperative vitamin D deficiency predict postoperative hypoparathyroidism following thyroid surgery?

IMPORTANCE: Postoperative hypoparathyroidism remains a relevant problem after thyroid surgery. Although the roles of vitamin D deficiency and other risk factors have been discussed in previous studies, variable results have been reported. OBJECTIVE: Predicting the risk of postoperative hypocalcemia could be helpful for individual prognoses and medical treatment. PATIENTS AND METHODS: Documentation and analysis of bilateral thyroid operations performed between July 2011 and May 2014 were studied. Results involving age, gender, diagnosis, surgical techniques, pre- and postoperative calcium and parathyroid hormone (PTH) levels, and especially, the role of preoperative vitamin D levels were assessed in uni- and multivariate analyses. RESULTS: Bilateral thyroid surgery was performed in 361 patients with multinodular goiters (n = 224), Graves' disease (n = 40), or thyroid carcinoma (n = 97). In total, 124 patients (34%) with postoperative hypoparathyroidism, defined as having a PTH level ≤ 10 pg/mL, were treated with calcium and vitamin D regardless of their symptoms. The rate of permanent hypoparathyroidism was 3.6% and correlated with the extent of surgery; the highest risks were shown for total thyroidectomy and central lymph node dissection. In univariate analysis, the extent of surgery, parathyroid autotransplantation, and histopathology were the strongest predictors of hypoparathyroidism. Even severe vitamin D deficiency (< 10 ng/mL) showed a trend only towards a higher transient hypoparathyroidism risk (p = 0.0514) but failed to predict permanent hypoparathyroidism. CONCLUSION: Postoperative PTH levels accurately identified patients at risk for hypoparathyroidism. Decreased preoperative vitamin D levels could not predict hypocalcemia, and high vitamin D levels could not prevent permanent hypoparathyroidism.

Perioperative surgery- and anaesthesia-related risks of laparoscopic Roux-en-Y gastric bypass - a single centre, retrospective data analysis.

BACKGROUND: Conservative obesity treatment often leads to limited results. Bariatric surgery is highly efficient, but the candidates are at risk of developing perioperative complications. Bariatric outcomes have been well described in the past, but there are only few reports of perioperative outcomes. The aim of this study was to evaluate the incidence of anaesthetic and surgical complications of Roux-en-Y bypass. METHODS: Data of all adult patients, who underwent primary Roux-en-Y gastric bypass surgery between 1/2006 and 12/2013 at the University Hospital Zurich were analysed. Using our clinical database, anaesthetic and surgical complications during the first 30 days after surgery were analysed and risk factors determined by multivariate analysis. RESULTS: Seven hundred eleven patients (72% female, median age 40 years) were analysed. Overall, surgical complications occurred in 34% patient, while complications attributable to anaesthesia occurred in 37%. Post-operative nausea and vomiting (PONV) were observed in 34%, intubation-related complications in 4%, and delayed extubation in 2% of our patients. Within the first 30 days after surgery, 22% of the patients presented with an infection. Gastrointestinal complications were found in 8%, and bleeding complications in 3%. Anaesthesia complications were less common in older patients and in patients anaesthetized with a volatile anaesthetic. Severe complications were more common in patients with a lower body mass index (BMI) and with longer surgery. The risk to develop a postoperative infection was higher in diabetic patients. CONCLUSION: Roux-en-Y bariatric surgery has few anaesthetic complications, the most common is PONV. PONV is more common in younger patients and not more common with volatile anaesthetics. Major complications are overall rare and occur in patients with lower BMI and longer surgery, likely reflecting more difficult procedures.

Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community.

Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.

Smad3 signaling in the regenerating liver: implications for the regulation of IL-6 expression.

Liver regeneration is vital for graft survival and adequate organ function. Smad activation regulates hepatocyte proliferation and macrophage function. The aim of the current study was to evaluate the impact of Smad3 signaling during liver regeneration in the mouse. Male C57Bl/6 wild-type (wt) mice or mice deficient in Smad3 (Smad3(-/-) ) were subjected to a 70% partial hepatectomy (pHx) or sham surgery and sacrificed 24, 42, or 48 h later. Tissue was analyzed for TGF-ß signaling, the mitogenic cytokine response [i.e., tumor necrosis factor alpha, TNF-α; interleukin (IL)-6], and liver regeneration. Partial hepatectomy stimulated a strong regenerative response measured by proliferating cell nuclear antigen-positive hepatocytes 42 and 48 h post-pHx in conjunction with an increased expression of IL-6, TNF-α, and Smad2/3 phosphorylation 24 h post-pHx in both hepatocytes and nonparenchymal cells. Surprisingly, Smad3 deficiency led to reduced hepatocyte proliferation 42 h post-pHx which recovered by 48 h, a process that correlated with and was preceded by significant reductions in IL-6 expression and signal transducer and activator of transcription 3 phosphorylation, and cyclin D1 induction 24 h post-pHx. Loss of Smad3 signaling suppresses the expression of key mitogenic cytokines and delays hepatocellular regeneration. Therapies directed at finely regulating Smad3 activation early within the regenerating liver may prove useful in promoting liver cell proliferation and restoration of liver mass.

Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315).

PURPOSE: First-line therapy options in advanced cholangiocarcinoma (CCA) are based on the ABC-02 trial regimen (gemcitabine/cisplatin [G/C]). The NIFE trial examined nanoliposomal irinotecan/fluorouracil/leucovorin (nal-IRI/FU/LV) as alternative first-line therapy in advanced CCA. METHODS: NIFE is a prospective, open-label, randomized, multicenter phase II study that aimed at detecting efficacy comparable with the standard treatment. Patients with advanced CCA were randomly assigned (1:1) to receive nal-IRI/FU/LV (arm A) or G/C (arm B). Stratification parameters were intrahepatic versus extrahepatic CCA, sex, and Eastern Cooperative Oncology Group (ECOG; 0/1). Arm A was designed as a Simon's optimal two-stage design and arm B served as a randomized control group. The primary goal was to exclude an inferior progression-free survival (PFS) at 4 months of only 40%, while assuming a rate of 60% on G/C population. RESULTS: Between 2018 and 2020, overall 91 patients were randomly assigned to receive nal-IRI/FU/LV (n = 49) or G/C (n = 42). The NIFE trial formally met its primary end point with a 4-month PFS rate of 51% in patients receiving nal-IRI/FU/LV. The median PFS was 6 months (2.4-9.6) in arm A and 6.9 months (2.5-7.9) in arm B. Median overall survival (OS) was 15.9 months (10.6-20.3) in arm A and 13.6 months (6.5-17.7) in arm B. The exploratory comparison of study arms suggested a numerical but statistically not significant advantage for nal-IRI/FU/LV (hazard ratio for PFS, 0.85 [95% CI, 0.53 to 1.38] and for OS, 0.94 [95% CI, 0.58 to 1.50]). Analysis for stratification parameters revealed no differences for sex and ECOG, but for tumor localization. The objective response rate was 24.5% with nal-IRI/FU/LV and 11.9% with G/C. No unexpected toxicities occurred. AEs related to nal-IRI/FU/LV were mainly GI and to G/C hematologic. CONCLUSION: Treatment of advanced CCA with nal-IRI/FU/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation.

Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature.

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.

Medical education during the COVID-19 pandemic: What students missed and what they did not. A questionnaire-based cross-sectional study.

Background: Medical education was and still is challenged by the COVID-19 pandemic, and several strategies were implemented by the universities worldwide in order to maintain a good level of education. The aim of this work is to point out how strategies adopted in a German university hospital reached students and how comfortable they felt with the proposed solutions in order to define future possibilities in modern teaching. Methods: A questionnaire was answered by medical students at the end of the 8th and 10th semester in a German university hospital asking them about their perception of medical education during the pandemic as well as about strategies adopted by the faculty. Results: A total of 92 out of 117 students answered the questionnaire (78.6% response rate). Students felt disadvantaged in their medical education because of the pandemic on a scale from 0 (not at all) to 10 (completely) (5.34±2.3, range 0-10 points), regardless of semester, gender, and whether they aimed at a surgical career or not. During the pandemic they missed practical exercises most (93.5%), followed by contact with other students (65.2%). Presence lessons were missed (28.3%) the least. Among the strategies offered to maintain education, recorded lessons were appreciated most, followed by skills labs. Live-stream lessons were considered less comfortable. Conclusions: Several aspects of medical education were replaced satisfactorily during the pandemic, others need to be adapted in the future in order to meet the students' needs and expectations. Theoretical online education but not live stream lessons could be an option beyond COVID-19 as they are highly appreciated by students.

Analysis of the CONKO-001 trial: Is the validity of the study sufficient to recommend adjuvant chemotherapy for pancreatic cancer?

BACKGROUND: Since randomized controlled trials have indicated that adjuvant chemotherapy prolongs survival and reduces recurrence rates after surgical resection of pancreatic adenocarcinoma, a gemcitabine based chemotherapy has become part of the interdisciplinary treatment concept for pancreatic cancer in accordance to current guidelines. OBJECTIVES: The aim of this project was to analyse the validity of the CONKO-001 trial as a basis for the recommendation of adjuvant chemotherapy in many international guidelines. METHODS: We analysed the validity of the CONKO-001 trial regarding study design, recruitment period, participating institutions, patient selection, randomisation, stratification, standardization of surgical treatment and histological examination, statistical methods and interpretation of results. We additionally analysed the study regarding the risk of bias using the RoB 2 Tool. Finally we reviewed the influence of the pharmaceutical industry and potential conflicts of interest. RESULTS: We identified several shortcomings of the study concerning the study protocol, the participating clinics, the patient recruitment, the randomization pattern, the standardization of surgical treatment and histological examination, the statistical methods, the evaluation of the results and the influence of the pharmaceutical industry. According to the Cochrane RoB 2 Tool the study was judged to raise some concerns in three of the five risk domains for the outcome "overall survival". CONCLUSIONS: Based on our review, the results of the CONKO-001-study should be revisited and critically reviewed. The recommendation to include adjuvant chemotherapy with gemcitabine deserves a critical appraisal.

Adjuvant gemcitabine after resection of pancreatic cancer without significant difference in overall survival: a retrospective cohort study.

International guidelines recommend adjuvant chemotherapy after resection of pancreatic adenocarcinoma. The administration of gemcitabine has become part of the interdisciplinary treatment concept. The authors aim to prove whether the benefit in overall survival (OS) reported in randomized controlled trials (RCTs) could be reached also for patients treated in their department. Materials and methods: The authors retrospectively analyzed the OS of all patients who underwent pancreatic resection at their clinic because of ductal adenocarcinoma between January 2013 and December 2020 in dependence on adjuvant treatment with gemcitabine. Results: Overall 133 pancreatic resections were performed between 2013 and 2020 due to malignant pancreatic pathology. Seventy-four patients had ductal adenocarcinoma. Forty patients received adjuvant gemcitabine chemotherapy postoperatively, 18 patients underwent only surgical resection, and 16 patients received other chemotherapy regimens. The authors compared the group receiving adjuvant gemcitabine (n=40) with the group undergoing surgery alone (n=18). The median age was 74 years (range: 45-85), and the median OS was 16.5 months [95% confidence interval (CI) 13-27]. Follow-up time was at least 23 months (range 23-99). No statistically significant difference in median OS was observed in the group who received adjuvant chemotherapy compared to the operation-only group [17.5 months (range: 5-99, 95% CI 14-27) versus 12.5 months (range: 1-94, 95% CI 5-66), P=0.75]. Conclusion: OS with and without adjuvant chemotherapy with gemcitabine was comparable to the results of those RCTs which serve as the basis of guideline recommendations. However, the analyzed patient cohort did not profit significantly from the adjuvant treatment.

[177Lu]Lu-PSMA-617 Therapy in a Patient with Chronic Kidney Disease.

We report the dosimetric evaluation of prostate-specific membrane antigen-based radioligand therapy (RLT) for metastatic prostate cancer in a patient with autosomal-dominant polycystic kidney disease. Methods: The patient received hemodialysis during each of 6 RLT cycles while staying as an inpatient. We used voxel dosimetry and blood sampling for the dose calculation. Results: The patient responded well to the RLT, as indicated by the prostate-specific antigen level decreasing from 298 to 7.1 ng/mL. The doses per cycle ranged from 0.19 to 0.4 Gy/GBq for the parotid gland, 0.14 to 0.28 Gy/GBq for the submandibular gland, 0.03 to 0.11 Gy/GBq per kidney, and 0.10 to 0.15 Gy/GBq for the red bone marrow. Conclusion: This case suggests that [177Lu]Lu-PSMA-based RLT can be applied successfully and safely to a patient with chronic kidney disease undergoing hemodialysis.

Viral Hepatitis and Hepatocellular Carcinoma: State of the Art.

Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation-fibrosis to cancer.

Diagnostic role of the 'white test' with lipidic solution in the early intraoperative identification of open bile ducts for the prevention of bile leakage after liver resection: study protocol for a randomised controlled multicentric superiority trial (BiLe-Trial).

INTRODUCTION: Bile leakage is a frequent complication after liver resection associated with the need of interventional drainage, endoscopic retrograde cholangio pancreatography (ERCP) or reoperation. The intraoperative application of the white test could be a promising strategy to reduce the occurrence of bile leakages. Therefore, we propose to conduct the first multicentric randomised controlled trial with rate of postoperative bile leakage as primary endpoint with and without the white test. METHODS AND ANALYSIS: The Bile-Leakage Trial trial is an investigator-initiated randomised controlled, parallel group, double-blinded, multicentric, superiority trial in four Swiss centres. A total of 210 patients undergoing a resection of at least 2 liver segments will be randomly allocated intraoperatively to either the intervention (identification of open bile ducts with administration of 20-40 mL SMOFlipid5% in the bile tract) or the control group (identification with a white gauze on the liver resection surface).Primary outcome will be the comparison of the postoperative bile leakage rate in both groups within 30 days after liver resection, defined according to the classification of the International Study Group of Liver Surgery. Secondary outcomes will be operative and postoperative complication, including severity grade of the bile leakage, rate of ERCP, interventional drainage, morbidity, intensive care unit stay, and mortality. ETHICS AND DISSEMINATION: The cantonal ethics committees of all participating centres and Swissmedic approved the study. SMOFlipid20% consists of a mixture of oils, no side effects resulting from the intraoperative application of 20-40 mL in the biliary tract with consecutive enteral absorption are expected nor are side effects described in the literature. SMOFlipid20% will be diluted intraoperatively with isotonic saline solution to a concentration of 5%. The results of the BiLe-Trial will be submitted to a peer-reviewed journal regardless of the outcome. As this is an investigator-initiated trial, data are property of the sponsor investigator and can be obtained on request. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID: NCT04523701. Registered on 25 August 2020.Swiss National Clinical Trials Portal (SNCTP), ID: SNCTP000004200. Registered on 20 January 2021. PROTOCOL VERSION: V3.2_14-12-2020_clean.pdf.

Helicobacter pylori-Related Metabolic Parameters and Premalignant Gastric Mucosa Histological Lesions in Swiss Bariatric Patients.

Obesity, as a major risk factor of metabolic syndrome (MetS), represents a pandemic, especially in Western societies, and is considered a risk factor for malignancies. Helicobacter pylori (Hp), is a definite carcinogen with global distribution. We aimed to investigate, for the first time in Switzerland, the main gastric mucosa premalignant histological lesions of bariatric patients in correlation with MetS components and Hp Infection (Hp-I). By reviewing retrospectively 94304 patient cases, a total of 116 eligible patients having undergone bariatric surgery were identified. The mean patient age was 48.66 years. Hp(+) patients were 24% (28/116). Presence of gastric mucosa atrophy was documented in 8/28 Hp(+) patients (29%) and (2/88) Hp(-) ones (2%) (p = 0.006). Gastric mucosa intestinal metaplasia was observed in 14/28 (50%) Hp(+) patients versus 3/88 (3.4%) of Hp(-) group (p < 0.0001). Hp(+) patients exhibited statistically higher arterial hypertension (p = 0.033). The homeostatic model of assessment insulin resistance was also statistically significantly higher for the Hp(+) group (p < 0.001). In a multivariate analysis, including arterial hypertension, gastric mucosa atrophy, and intestinal metaplasia as variables, statistical significance remained only for intestinal metaplasia (p = 0.001). In conclusion, Hp-I is associated with premalignant gastric mucosa histologic lesions and MetS components, including arterial hypertension and IR. Further large-scale prospective studies are required to confirm these findings.

Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany.

BACKGROUND: Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients. AIM: To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age. METHODS: We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy. RESULTS: Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often. CONCLUSION: This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.

Validity of studies suggesting preoperative chemotherapy for resectable thoracic esophageal cancer: A critical appraisal of randomized trials.

BACKGROUND: In 2015, Kidane published a Cochrane review and meta-analysis to summarise the impact of preoperative chemotherapy versus surgery alone on survival for resectable thoracic esophageal cancer. The authors concluded that preoperative chemotherapy improved overall survival (OS). AIM: The aim of this article was to assess the validity of the three most powerful studies included in the Cochrane review and the meta-analysis supporting the advantage of preoperative chemotherapy and to investigate the impact of an exclusion of these three studies on the result of the meta-analysis. METHODS: OS was selected as the endpoint of interest. Among the ten included papers which analysed this endpoint, we identified the three publications with the highest weights influencing the final result. The validity of these papers was analysed using the CONSORT checklist for randomized controlled trials. We performed a new meta-analysis without the three studies to assess their impact on the general result of the original meta-analysis. RESULTS: The three analysed studies revealed several inconsistencies. Inappropriate answers were found in up to one third of the items of the CONSORT checklist. Missing information about sample-size calculation and power, unclear or inadequate randomisation, and missing blinded set-up were the most common findings. When the three criticized studies were excluded in the meta-analysis, preoperative chemotherapy showed no benefit in OS. CONCLUSION: The three most powerful publications in the Cochrane review show substantial deficits. After the exclusion of these studies from the meta-analysis, preoperative chemotherapy does not seem to result in an advantage in survival. We suggest a more critical appraisal regarding the validity of single studies.

Adjuvant chemotherapy in curatively resected rectal cancer: How valid are the data?

BACKGROUND: According to the result of the Cochrane review published in 2012, postoperative adjuvant chemotherapy (CTx) is associated with a survival benefit for rectal cancer patients operated for cure in comparison to patients who underwent only the surgical resection. AIM: To analyze the quality of the data supporting the advantage of adjuvant CTx after surgery for rectal cancer. In the times of increasing health care costs, it is imperative to offer the patient an evidence-based therapy that justifies potential side effects as well as costs. METHODS: Overall survival was selected as endpoint of interest. Among the 21 included papers which analyzed this endpoint, we identified those three publications which have the highest weights to influence the final result. The validity of these papers was analyzed using the CONSORT checklist for randomized controlled trials. We performed a second meta-analysis excluding the three analyzed studies (n = 18) in order to assess their impact on the overall result of the original meta-analysis. Finally, we performed a third meta-analysis excluding all studies (n = 16) which showed a statistically improved overall survival. RESULTS: The detailed analysis of the three most relevant RCTs according to the items of the CONSORT checklist showed several pitfalls. In up to 47% of the items, inappropriate answers were found. Generally, a lack of information regarding the randomization procedure as well as the absence of allocation concealment, blinded set-up, of intention-to-treat analysis and omission of sample size calculation were common problems of the analyzed studies. The exclusion of these three studies from the meta-analysis did not affect the general result of the meta-analysis, still confirming a survival advantage after adjuvant chemotherapy. After exclusion of single studies with a statistically significant outcome improvement, the meta-analysis of the remaining 16 studies again shows a statistically significant result due in part to a large remaining sample size. CONCLUSION: The three most powerful publications show substantial deficits. We suggest a more critical appraisal regarding the validity of single studies because a meta-analysis cannot overcome the limitations of individual trials by pooling treatment effect estimates to generate a single best estimate.

Severe complications after mesh migration following abdominal hernial repair: report of two cases and review of literature.

Background: Migration of mesh after ventral and incisional hernia repair is a rare but well described complication. The aim of our work is to present two cases of mesh migration after incisional hernia repair and to review the current literature. Methods: We describe the two cases of mesh migration that occurred at our department. Additionally, we performed a systematic literature search. Results: In both cases we observed a mesh migration with formation of an entero-cutaneous fistula that required surgical therapy. In the literature search we found a total of 16 publications dealing with mesh migration after incisional (n=14) and ventral hernia (n=2) repair in adult patients (15 case reports and one retrospective study). In 9 out of 15 patients (54%) who presented with mesh migration or erosion, a polypropylene mesh was responsible for this complication. Conclusions: Mesh migration after abdominal hernia repair is rare, the only available retrospective study reports a rate of 2.7%. The ability of polypropylene mesh to migrate into hollow viscera is well known and confirmed both by our data and the results of the literature review. As the incidence of mesh erosion/migration is significantly lower than the recurrence rate after hernia repair without mesh, up to now, no better alternative exists for the treatment of abdominal wall hernia than mesh augmentation.

Validity of studies suggesting postsurgical chemotherapy for resectable gastric cancer: critical appraisal of randomised trials.

BACKGROUND AND AIM: In 2013, Diaz-Nieto et al published a Cochrane review to summarise the impact of postsurgical chemotherapy versus surgery alone on survival for resectable gastric cancer. The authors concluded that postsurgical chemotherapy showed an improvement in overall survival. The aim of this article was to assess the validity of four studies included in the Cochrane review and to investigate the impact of an exclusion of these four studies on the result of the meta-analysis. METHODS: Overall survival was selected as endpoint of interest. Among the 34 included papers which analysed this endpoint, we identified the four publications which have the highest weights to influence the final result. The validity of these papers was analysed using the CONSORT (Consolidated Standards of Reporting Trials) checklist for randomised controlled trials. We performed a new meta-analysis without the four studies in order to assess their impact on the general result of the original meta-analysis. RESULTS: The analysed four studies revealed several inconsistencies: inappropriate answers were found in up to 77% of the items of the CONSORT checklist. Unclear or inadequate randomisation, missing blinded set-up, conflict of interest and lacking intention-to-treat analysis were the most common findings. When performing a meta-analysis excluding the four criticised studies, postsurgical chemotherapy still showed a significant improvement in overall survival. Even when excluding all single studies with a statistically significant outcome by themselves and performing a meta-analysis on the remaining 26 studies, the result remains statistically significant. CONCLUSION: The four most powerful publications in the Cochrane review show substantial deficits. We suggest a more critical appraisal regarding the validity of single studies. However, after the exclusion of these four studies, the result of the meta-analysis did not change.