André L. Mihaljevic

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies (PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial

BACKGROUNDnIncisional hernia is a frequent long-term complication after abdominal surgery, with a prevalence greater than 30% in high-risk groups. The aim of the PRIMA trial was to evaluate the effectiveness of mesh reinforcement in high-risk patients, to prevent incisional hernia.nnnMETHODSnWe did a multicentre, double-blind, randomised controlled trial at 11 hospitals in Austria, Germany, and the Netherlands. We included patients aged 18 years or older who were undergoing elective midline laparotomy and had either an abdominal aortic aneurysm or a body-mass index (BMI) of 27 kg/m2 or higher. We randomly assigned participants using a computer-generated randomisation sequence to one of three treatment groups: primary suture; onlay mesh reinforcement; or sublay mesh reinforcement. The primary endpoint was incidence of incisional hernia during 2 years of follow-up, analysed by intention to treat. Adjusted odds ratios (ORs) were estimated by logistic regression. This trial is registered at ClinicalTrials.gov, number NCT00761475.nnnFINDINGSnBetween March, 2009, and December, 2012, 498 patients were enrolled to the study, of whom 18 were excluded before randomisation. Therefore, we included 480 patients in the primary analysis: 107 were assigned primary suture only, 188 were allocated onlay mesh reinforcement, and 185 were assigned sublay mesh reinforcement. 92 patients were identified with an incisional hernia, 33 (30%) who were allocated primary suture only, 25 (13%) who were assigned onlay mesh reinforcement, and 34 (18%) who were assigned sublay mesh reinforcement (onlay mesh reinforcement vs primary suture, OR 0·37, 95% CI 0·20-0·69; p=0·0016; sublay mesh reinforcement vs primary suture, 0·55, 0·30-1·00; p=0·05). Seromas were more frequent in patients allocated onlay mesh reinforcement (34 of 188) than in those assigned primary suture (five of 107; p=0·002) or sublay mesh reinforcement (13 of 185; p=0·002). The incidence of wound infection did not differ between treatment groups (14 of 107 primary suture; 25 of 188 onlay mesh reinforcement; and 19 of 185 sublay mesh reinforcement).nnnINTERPRETATIONnA significant reduction in incidence of incisional hernia was achieved with onlay mesh reinforcement compared with sublay mesh reinforcement and primary suture only. Onlay mesh reinforcement has the potential to become the standard treatment for high-risk patients undergoing midline laparotomy.nnnFUNDINGnBaxter; B Braun Surgical SA.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial

BACKGROUNDnThere is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery.nnnMETHODSnThis randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013.nnnFINDINGSnBetween Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity.nnnINTERPRETATIONnNo differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting.nnnFUNDINGnGerman Research Foundation (DFG).

A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer

BackgroundPancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer.MethodsHere we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda ®) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin®) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cylce. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients.DiscussionPrimary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patients survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals.

Effectiveness of Tachosil® in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis

PurposePostoperative pancreatic fistula (POPF) is a frequent and clinically relevant problem after distal pancreatectomy. A variety of methods have been tested in the attempt to prevent POPF, most of them without convincing results.MethodsA systematic literature search was conducted in PubMed, Embase and the Cochrane Library to identify clinical studies comparing pancreatic stump closure with the addition of Tachosil® to conventional stump closure. The identified studies were critically appraised, and meta-analyses were performed using a random-effects model. Dichotomous data were pooled using odds ratios, and weighted mean differences were calculated for continuous outcomes, together with the corresponding 95xa0% confidence intervals.ResultsFour studies (two randomised controlled trials and two retrospective clinical studies) reporting data from 738 patients were included in the meta-analysis. Overall POPF, clinically-relevant POPF, mortality, reoperations, intraoperative blood loss and length of hospital stay did not differ significantly between conventional closure and additional covering of the pancreatic stump with Tachosil®. A sensitivity analysis of only randomised controlled trials confirmed the results.ConclusionsThe application of Tachosil® to the pancreatic stump after distal pancreatectomy is a safe procedure but provides no relevant benefit in terms of POPF, mortality, reoperation rate, blood loss or length of hospital stay. Future research should concentrate on novel methods of pancreatic stump closure to prevent POPF after distal pancreatectomy.

Outcome of gastric cancer in the elderly: a population-based evaluation of the Munich Cancer Registry

BackgroundGastric cancer accounts for 5xa0% of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting.MethodsAnalyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. ≥70xa0years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6xa0months.ResultsFifty-nine per cent of the cohort were ≥70xa0years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40xa0% for the youngest (<50xa0years) and 23xa0% for the oldest patients (≥80xa0years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50–59, 60–69 and 70–79xa0years was comparable (between 48 and 49.6xa0%) and slightly worse in the youngest and oldest (45xa0%), which may be explained by more aggressive tumours and effects of cellular senescence, respectively.ConclusionThe treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient’s general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups.

Surgical strategies in true adenocarcinoma of the esophagogastric junction (AEG II): thoracoabdominal or abdominal approach?

BackgroundThe optimal surgical approach for adenocarcinoma directly at the esophagogastric junction (AEG II) is still under debate. This study aims to evaluate the differences between right thoracoabdominal esophagectomy (TAE) (Ivor–Lewis operation) and transhiatal extended gastrectomy (THG) for AEG II.MethodsFrom a prospective database, 242 patients with AEG II (TAE, nxa0=xa056; THG, nxa0=xa0186) were included and analyzed according to characteristics and perioperative morbidity and mortality and overall survival (chi-square, Mann–Whitney U, log-rank, Cox regression).ResultsGroups were comparable at baseline with exception of age. Patients older than 70xa0years were more frequently resected by THG (pxa0=xa00.003). No differences in perioperative morbidity (pxa0=xa00.197) and mortality (pxa0=xa00.711) were observed, including anastomotic leakages (pxa0=xa00.625) and pulmonary complications (pxa0=xa00.494). There was no significant difference in R0 resection (pxa0=xa00.719) and number of resected lymph nodes (pxa0=xa00.202). Overall median survival was 38.4xa0months. Survival after TAE was significantly longer than after THG (median OS not reached versus 33.6xa0months, pxa0=xa00.02). Multivariate analysis revealed pN-category (pxa0<xa00.001) and type of surgery (pxa0=xa00.017) as independent prognostic factors. The type of surgery was confirmed as prognostic factor in locally advanced AEG II (cT 3/4 or cN1), but not in cT1/2 and cN0 patients.ConclusionsOur single-center experience suggests that patients with (locally advanced) AEG II tumors may benefit from TAE compared to THG. For further evaluation, a randomized trial would be necessary.

Optimal literature search for systematic reviews in surgery

BackgroundThe aim of the present study was to determine empirically which electronic databases contribute best to a literature search in surgical systematic reviews.MethodsFor ten published systematic reviews, the systematic literature searches were repeated in the databases MEDLINE, Web of Science, CENTRAL, and EMBASE. On the basis of these reviews, a gold standard set of eligible articles was created. Recall (%), precision (%), unique contribution (%), and numbers needed to read (NNR) were calculated for each database, as well as for searches of citing references and of the reference lists of related systematic reviews (hand search).ResultsCENTRAL yielded the highest recall (88.4%) and precision (8.3%) for randomized controlled trials (RCT), MEDLINE for non-randomized studies (NRS; recall 92.6%, precision 5.2%). The most effective combination of two databases plus hand searching for RCT was MEDLINE/CENTRAL (98.6% recall, NNR 97). Adding EMBASE marginally increased the recall to 99.3%, but with an NNR of 152. For NRS, the most effective combination was MEDLINE/Web of Science (99.5% recall, NNR 60).ConclusionsFor surgical systematic reviews, the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical systematic reviews of NRS, Web of Science instead of CENTRAL should be searched. EMBASE does not contribute substantially to reviews with a surgical intervention.

The TRIANGLE operation – radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single arm observational study

BACKGROUNDnNeoadjuvant therapy is an important strategy for locally advanced pancreatic cancer (PDAC) as resection rates increase with modern chemotherapy regimens even in patients with arterial tumor encasement. The aim of this study is the description of technique and initial outcomes of a new type of radical and arterial-sparing resection after neoadjuvant treatment for locally advanced PDAC.nnnMETHODSnThe surgical technique and perioperative results of a new type of operation are described, comprising radical tumor removal by sharp dissection along the celiac axis and the superior mesenteric artery with complete dissection of all soft tissue between both - arteries and superior mesenteric/portal vein (TRIANGLE operation).nnnRESULTSn15 patients underwent artery-preserving tumor removal without mortality, 7/15 patients showed postoperative complications and an R0 resection was achieved in 6/15 patients. Functional outcome was good in 11/15 patients despite the extended approach of dissection.nnnCONCLUSIONnAfter neoadjuvant therapy for locally advanced PDAC, surgical exploration should be attempted in patients with stable disease or remission to clarify true vascular infiltration. In case of absent viable tumor, the described technique allows to perform radical surgery without arterial resection in this subgroup of patients.

Prophylaxis of lymphocele formation after kidney transplantation via peritoneal fenestration: a systematic review

Lymphocele formation after kidney transplantation is a frequent complication which causes pain, secondary graft loss, rehospitalizations and reoperations. Therefore, prophylaxis of lymphocele formation is of utmost importance. To assess the effectiveness of peritoneal fenestration in renal transplantation to prevent lymphocele development. A systematic literature search was conducted combined with hand‐searches on lymphocele prevention following renal transplantation using peritoneal fenestration. A qualitative and quantitative analysis of included trials was conducted. We identified three trials including 414 patients and 437 transplantations which studied peritoneal fenestration. Only one randomized controlled trial was identified. Critical appraisal uncovered a number of methodological flaws, predominantly in the nonrandomized studies. Most importantly endpoint definitions varied among trials, selection bias was high and interventions and follow‐up were not standardized. Meta‐analysis of the included trials showed a significant reduction of clinically symptomatic lymphoceles (OR: 0.23, 95% CI: 0.09–0.64, P = 0.005) and overall postoperative fluid collections (OR: 0.49, 95% CI: 0.28–0.88, P = 0.02) without a significant increase in other surgical complications. Although peritoneal fenestration is a promising technique to reduce lymphocele formation, only few studies have investigated this technique so far. Given the low methodological quality of included trials, more studies are necessary to evaluate the effectiveness and the risks and benefits of this technique.

Influence of neoadjuvant chemotherapy on resection of primary colorectal liver metastases: A propensity score analysis

There is ongoing debate about whether patients planned for liver resection of colorectal liver metastases (CRLM) benefit from neoadjuvant chemotherapy (NC). Therefore, we performed a retrospective survival analysis of patients with and without NC prior to surgery.