Adjuvant and/or neoadjuvant therapy for gastric cancer? A perspective review

Surgery is still the only curative therapy for locoregional gastric cancer. Hereby it is important to achieve negative margins (R0 resection) and to perform an adequate lymph-node dissection (D2 lymphadenectomy). Unfortunately most cases of gastric cancer are diagnosed in a locally advanced tumor stage. The poor prognosis of patients with these tumors is due to the frequent recurrences after primary resection in curative intent. This observation led to the development of (neo)adjuvant treatment concepts. Beginning with the end of the 1980s, more and more patients with locally advanced tumors were subjected to a preoperative, perioperative, or postoperative treatment in order to improve the prognosis after curative resection. However, in different regions of the world, different regiments are preferred. While adjuvant chemotherapy is the established treatment in Asia, adjuvant chemoradiotherapy is favored in the USA and perioperative chemotherapy is considered the treatment of choice in Europe. However, recently a certain convergence of the different philosophies is to be observed. This article covers the relevant studies dealing with neoadjuvant and adjuvant treatment concepts and gives an overview on the latest developments in this field

Novel Histologic Categorization Based on Lauren Histotypes Conveys Prognostic Information for Gastroesophageal Junction Cancers—Analysis from a Large Single Center Cohort in Germany

Adenocarcinoma of the gastroesophageal junction (AEG) ranks among the most common cancers in the Western world with increasing incidence. However, the prognostic influence and applicability of the Lauren classification was not examined in detail before. The purpose of this analysis was to analyze the oncologic outcomes of GE-junction cancer related to the Lauren histotype in a large single center cohort. Data from the prospectively documented database of the Klinikum Rechts der Isar (TUM School of Medicine) for patients undergoing curatively intended oncologic resection for GE-junction cancer between 1984 and 2018 were extracted. Univariate and multivariate regression analyses were performed to identify predictors for overall survival. Kaplan-Meier analyses were done to investigate the survival rates according to the Lauren histotype. After identification of two distinct histologic categories with prognostic implications, propensity score matching (PSM) was performed to balance for confounders and evaluate its oncologic outcomes retrospectively. In the time period indicated, 1710 patients were treated for GE-junction cancer. Exclusion criteria were: R2-resections (n = 134), metastatic disease (n = 296), 30-day mortality (n = 45), Siewert type I (n = 21), and missing/incomplete data (n = 61). Finally, 1153 patients were analyzed. In a multiple variable analysis, age, UICC-stage, all Lauren histotypes, R-stage, and postoperative complications were significant predictors of overall survival. Kaplan Meier analysis demonstrated significant survival differences between intestinal, diffuse, and mixed Lauren-histotypes (p = 0.001 and p = 0.029). Survival rates were comparable between non-classifiable and intestinal Lauren-types (p = 0.16) and between diffuse and mixed types (p = 0.56). When combining non-classifiable, well, and moderately differentiated Lauren-types and combining poorly differentiated intestinal, diffuse, and mixed types, two highly prognostic groups were identified (p < 0.0001). This was confirmed after PSM for possible confounders. The Lauren histotypes demonstrate highly prognostic value after oncologic resection of GE-junction cancer (Siewert type II and type III) in a single center Western patient cohort. A simplified histotype classification based on Lauren subtypes revealed a clear distinction of prognostic groups and should be considered for further evaluation

Additional file 1: of Parenteral nutrition during neoadjuvant chemotherapy for patients with non-metastatic gastric or esophago-gastric cancer to reduce postoperative morbidity (PERCOG): study protocol for a randomized controlled trial

SPIRIT 2013 checklist. (PDF 104 kb

Additional file 2: of Intraoperative wound irrigation to prevent surgical site infection after laparotomy (IOWISI): study protocol for a randomized controlled trial

List of local ethical committees that approved the IOWISI study protocol. (DOCX 60 kb

Intraoperative wound irrigation to prevent surgical site infection after laparotomy (IOWISI): study protocol for a randomized controlled trial

Abstract Background Postoperative surgical site infection (SSI) is one of the most common hospital infections and contributes substantially to postoperative morbidity and mortality. In addition, SSIs dramatically increase the treatment cost and length of hospital stay. Following visceral surgery by laparotomy, SSI rates are especially high (14–25%). Therefore, measures to prevent SSI in this field are urgently needed. Prophylactic intraoperative wound irrigation (IOWI) of the subcutaneous soft tissue before skin closure hypothetically represents an easy and economical option to reduce SSI rates and is already frequently used in clinical practice. However, there are currently no definite recommendations on the use of IOWI since high-level evidence supporting its use is lacking. Consequently, clinical practice varies widely. Antiseptic polyhexanide (PHX)-based solutions are approved for soft-tissue wound irrigation in surgery but have not been specifically evaluated in randomized clinical trials for the prevention of SSI following laparotomy for visceral surgery. Methods/design The IOWISI trial is a multicentre, randomized, observer- and patient-blinded clinical trial with three parallel treatment groups, comparing IOWI with a 0.04% PHX solution to no irrigation (test 1) or saline (test 2) before skin closure after laparotomy for visceral surgery (contamination level II–IV). The primary endpoint of the trial is the SSI rate within 30 days postoperatively. Statistical analysis of the primary endpoint measure will be based on the intention-to-treat population. The global level of significance is set at 2.5% for test 1 and 5% for test 2 and the sample size (n = 540) is determined to assure a power of 94% (test 1) and 85% (test 2). Discussion The IOWISI trial will provide high-level evidence as a basis for clinical recommendations regarding the use of IOWI with PHX or saline and will potentially impact on future clinical guidelines and practice. The pragmatic trial design guarantees high external validity. Trial registration Registered at the German Clinical Trials Register, DRKS00012251 . Registered on 3 July 2017

Borderline-resectable pancreatic adenocarcinoma: Contour irregularity of the venous confluence in pre-operative computed tomography predicts histopathological infiltration.

PurposeThe purpose of the current study was to compare CT-signs of portal venous confluence infiltration for actual histopathological infiltration of the vein or the tumor/vein interface (TVI) in borderline resectable pancreatic ductal adenocarcinoma (PDAC).Methods and materials101 patients with therapy-naïve, primarily resected PDAC of the pancreatic head without arterial involvement were evaluated. The portal venous confluence was assessed for contour irregularity (defined as infiltration) and degree of contact. The sensitivity and specificity of contour irregularity versus tumor to vein contact >180° as well as the combination of the signs for tumor cell infiltration of the vessel wall or TVI was calculated. Overall survival (OS) was compared between groups.ResultsSensitivity and specificity of contour irregularity for identification of tumor infiltration of the portal venous confluence or the TVI was higher compared to tumor to vessel contact >180° for tumor cell infiltration (96%/79% vs. 91%/38% respectively, p180°/ both signs had significantly worse overall survival (16.2 vs. 26.5 months/ 17.9 vs. 37.4 months/ 18.5 vs. 26.5 months respectively, all pConclusionPortal venous confluence contour irregularity is a strong predictor of actual tumor cell infiltration of the vessel wall or the TVI and should be noted as such in radiological reports

Pancreatic stump closure techniques and pancreatic fistula formation after distal pancreatectomy: Meta-analysis and single-center experience

<div><p>Background</p><p>Pancreatic fistula/PF is the most frequent and feared complication after distal pancreatectomy/DP. However, the safest technique of pancreatic stump closure remains an ongoing debate. Here, we aimed to compare the safety of different pancreatic stump closure techniques for preventing PF during DP.</p><p>Methods</p><p>We performed a PRISMA-based meta-analysis of all relevant studies that compared at least two techniques of stump closure during DP with regard to PF rates/PFR. We further performed a retrospective analysis of our institutional PFR in correlation with stump closure techniques.</p><p>Results</p><p>8301 studies were initially identified. From these, ten randomized controlled trials/RCTs, eleven prospective and 59 retrospective studies were eligible. Stapler closure (26%vs.31%, OR:0.73, <i>p</i> = 0.02), combination of stapler and suture (30%vs.33%, OR:0.70, <i>p</i> = 0.05), or stump anastomosis (14%vs.28%, OR:0.51, <i>p</i> = 0.02) were associated with lower PFR than suture closure alone. Spleen preservation/splenectomy, or laparoscopic/open DP, TachoSil^®, fibrin-like glue-application, or bioabsorbable-stapler-reinforcements (Seamguard^®) did not influence PFR after DP. In contrast, autologous patches (falciform ligament/seromuscular patches) resulted in lower PFR than no patch application (21.9%vs.25,8%, OR:0.60, <i>p</i> = 0.006). In our institution, the major three techniques of stump closure resulted in comparable PFR (suture:27%, stapler:29%, or combination:24%). However, selective suturing/clipping of the main pancreatic duct during pancreatic stump closure prevented severe PF (<i>p</i> = 0.02).</p><p>Conclusion</p><p>After DP, stapler closure, pancreatic anastomosis, or falciform/seromuscular patches lead to lower PFR than suture closure alone. However, the differences are rather small, and further RCTs are needed to test these effects. Selective closure of the main pancreatic duct during stump closure may prevent severe PF.</p></div

Anastomosis of the pancreatic stump during DP is superior to suture, but not to stapling, for reducing fistula rates.

<p><b>A.</b> Forrest plot of studies that compared anastomosis (i.e. pancreatico-gastrostomy or–enterostomy) of the pancreatic stump to stapler closure with regard to overall (upper plot) and clinically relevant (grade B/C, lower plot) postoperative PF rates after DP. RCTs: randomized controlled trials. <b>B.</b> The Forrest plot of studies that compared anastomosis to suture closure of the pancreatic stump show a beneficial effect of anastomosis for reducing overall (upper plot) and clinically relevant (grade B/C, lower plot) postoperative PF rates after DP. Bottom: funnel plot of included studies in the comparison of anastomosis vs. suture with regard to PF rates after DP.</p