Significance of tumour regression in lymph node metastases of gastric and gastro-oesophageal junction adenocarcinomas.

The presence of lymph node (LN) metastases is one of the most important negative prognostic factors in upper gastrointestinal carcinomas. Tumour regression similar to that in primary tumours can be observed in LN metastases after neoadjuvant therapy. We evaluated the prognostic impact of histological regression in LNs in 480 adenocarcinomas of the stomach and gastro-oesophageal junction after neoadjuvant chemotherapy. Regressive changes in LNs (nodular and/or hyaline fibrosis, sheets of foamy histiocytes or acellular mucin) were assessed by histology. In total, regressive changes were observed in 128 of 480 patients. LNs were categorised according to the absence or presence of both residual tumour and regressive changes (LN-/+ and Reg-/+). 139 cases were LN-/Reg-, 28 cases without viable LN metastases revealed regressive changes (LN-/Reg+), 100 of 313 cases with LN metastases showed regressive changes (LN+/Reg+), and 213 of 313 metastatic LN had no signs of regression (LN+/Reg-). Overall, LN/Reg categorisation correlated with overall survival with the best prognosis for LN-/Reg- and the worst prognosis for LN+/Reg- (p < 0.001). LN-/Reg+ cases had a nearly significant better outcome than LN+/Reg+ (p = 0.054) and the latter had a significantly better prognosis than LN+/Reg- (p = 0.01). The LN/Reg categorisation was also an independent prognostic factor in multivariate analysis (HR = 1.23; 95% CI 1.1-1.38; p < 0.001). We conclude that the presence of regressive changes after neoadjuvant treatment in LNs and LN metastases of gastric and gastro-oesophageal junction cancers is a relevant prognostic factor

CT-Derived Quantitative Image Features Predict Neoadjuvant Treatment Response in Adenocarcinoma of the Gastroesophageal Junction with High Accuracy

BACKGROUND The purpose of this retrospective study was to evaluate the value of contrast-enhanced computed tomography (CE-CT) image features at baseline and after neoadjuvant chemotherapy in predicting histopathological response in patients with adenocarcinoma of the gastroesophageal junction (GEJ). METHODS A total of 105 patients with a diagnosis of adenocarcinoma of the GEJ were examined by CE-CT at baseline and preoperatively after neoadjuvant chemotherapy. All patients underwent surgical resection. Histopathological parameters and tumor regression grading according to Becker et al. were collected in 93 patients. Line profiles of the primary tumor area in baseline and preoperative CE-CT were generated using ImageJ. Maximum tumor density and tumor-to-wall density delta were calculated and correlated with the histopathological tumor response. In addition, tumor response was assessed according to standard RECIST measurements in all patients and by endoscopy in 72 patients. RESULTS Baseline and change in baseline to preoperative CE-CT parameters showed no significant differences between responders (Becker grade 1a, 1b) and non-responders (Becker grade 2, 3). After neoadjuvant therapy, responders and non-responders showed significant differences in maximum density and tumor-to-wall density delta values. Line profile measurements showed excellent inter-rater agreement. In comparison, neither RECIST nor endoscopy showed significant differences between these groups. CONCLUSIONS Posttreatment CE-CT can predict histopathological therapy response to neoadjuvant treatment in adenocarcinoma of GEJ patients with high accuracy and thus may improve patient management

Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [(18)F]Galacto-RGD

BACKGROUND: The integrin αvβ3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of αvβ3 expression. We developed [(18)F]Galacto-RGD, a (18)F-labeled glycosylated αvβ3 antagonist, allowing monitoring of αvβ3 expression with positron emission tomography (PET). METHODS AND FINDINGS: Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [(18)F]Galacto-RGD in the tumor correlates with αvβ3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize αvβ3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [(18)F]Galacto-RGD with PET enables noninvasive quantitative assessment of the αvβ3 expression pattern on tumor and endothelial cells in patients with malignant tumors. CONCLUSIONS: Molecular imaging with [(18)F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the αvβ3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases

Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development

Time-resolved transcriptome analysis of early pou5f1 mutant zebrafish embryos identified groups of developmental regulators, including SoxB1 genes, that depend on Pou5f1 activity, and a large cluster of differentiation genes which are prematurely expressed.Pou5f1 represses differentiation genes indirectly via activation of germlayer-specific transcriptional repressor genes, including her3, which may mediate in part Pou5f1-dependent repression of neural genes.A dynamic mathematical model is established for Pou5f1 and SoxB1 activity-dependent temporal behaviour of downstream transcriptional regulatory networks. The model predicts that Pou5f1-dependent increase in SoxB1 activity significantly contributes to developmental timing in the early gastrula.Comparison to mouse Pou5f1/Oct4 reveals evolutionary conserved targets. We show that Pou5f1 developmental function is also conserved by demonstrating rescue of Pou5f1 mutant zebrafish embryos by mouse POU5F1/OCT4

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA):long-term outcomes of a multicentre, double-blind, randomised controlled trial

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan–Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4–64.8), 24.7% (95% CI: 12.7–38.8), 29.8% (95% CI: 17.9–42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248–0.614, p &lt; 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309–0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.</p

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning

Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.</p

Prospective, observational, multicenter study on minimally invasive gastrectomy for gastric cancer: robotic, laparoscopic and open surgery compared on operative and follow-up outcomes - IMIGASTRIC II study protocol: IMIGASTRIC II

Background:Several meta-analyses have tried to defi ne the role of minimally invasive approaches.&nbsp;However, further evidence to get a wider spread of these methods is necessary. Current&nbsp;studies describe minimally invasive surgery as a possible alternative to open surgery&nbsp;but deserving further clarifi cation. However, despite the increasing interest, the&nbsp;difficulty of planning prospective studies of adequate size accounts for the low level of&nbsp;evidence, which is mostly based on retrospective experiences.A multi-institutional prospective study allows the collection of an impressive amount&nbsp;of data to investigate various aspects of minimally invasive procedures with the&nbsp;opportunity of developing several subgroup analyses.A prospective data collection with high methodological quality on minimally invasive&nbsp;and open gastrectomies can clarify the role of diff erent procedures with the aim to&nbsp;develop specifi c guidelines.Methods and analysis:a multi-institutional prospective database will be established including information on&nbsp;surgical, clinical and oncological features of patients treated for gastric cancer with&nbsp;robotic, laparoscopic or open approaches and subsequent follow-up.The study has been shared by the members of the International study group on&nbsp;Minimally Invasive surgery for GASTRIc Cancer (IMIGASTRIC)The database is designed to be an international electronic submission system and a&nbsp;HIPPA protected real time data repository from high volume gastric cancer centers.Ethics:This study is conducted in compliance with ethical principles originating from the&nbsp;Helsinki Declaration, within the guidelines of Good Clinical Practice and relevantlaws/regulations.Trial registration number:NCT0275108