Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gen

Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.</p

Structured and shared CT radiological report of gastric cancer: a consensus proposal by the Italian Research Group for Gastric Cancer (GIRCG) and the Italian Society of Medical and Interventional Radiology (SIRM)

Objectives Written radiological report remains the most important means of communication between radiologist and referring medical/surgical doctor, even though CT reports are frequently just descriptive, unclear, and unstructured. The Italian Society of Medical and Interventional Radiology (SIRM) and the Italian Research Group for Gastric Cancer (GIRCG) promoted a critical shared discussion between 10 skilled radiologists and 10 surgical oncologists, by means of multi-round consensus-building Delphi survey, to develop a structured reporting template for CT of GC patients. Methods Twenty-four items were organized according to the broad categories of a structured report as suggested by the European Society of Radiology (clinical referral, technique, findings, conclusion, and advice) and grouped into three "CT report sections" depending on the diagnostic phase of the radiological assessment for the oncologic patient (staging, restaging, and follow-up). Results In the final round, 23 out of 24 items obtained agreement ( >= 8) and consensus ( 0.05). Conclusions The structured report obtained, shared by surgical and medical oncologists and radiologists, allows an appropriate, clearer, and focused CT report essential to high-quality patient care in GC, avoiding the exclusion of key radiological information useful for multidisciplinary decision-making

Textbook Neoadjuvant Outcome—Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the “All or None” method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the “ideal” and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.</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

Optimized EGFR blockade strategies in <i>EGFR</i> addicted gastroesophageal adenocarcinomas

Purpose: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.Experimental Design: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).Results: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition.Conclusions: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors

Updates on Robotic CME for Right Colon Cancer: A Qualitative Systematic Review

Background. Complete mesocolic excision (CME) is a surgical technique introduced with the aim of ameliorating the oncologic results of colectomy. Various experiences have demonstrated favorable oncologic results of CME in comparison with standard colectomy, in which the principles of CME are not respected. The majority of the literature refers to open or laparoscopic CME. This review analyses current evidence regarding robotic CME for right colectomy. Methods. An extensive Medline (Pub Med) search for relevant case series, restricted to papers published in English, was performed, censoring video vignettes and case reports. Results. Fourteen studies (ten retrospective, four comparative series of robotic versus laparoscopic CME) were included, with patient numbers ranging from 20 to 202. Four different approaches to CME are described, which also depend on the robotic platform utilized. Intraoperative and early clinical results were good, with a low conversion and anastomotic leak rate and a majority of Clavien–Dindo complications being Grades I and II. Oncologic adequacy of the surgical specimens was found to be good, although a homogeneous histopathologic evaluation was not provided. Conclusions. Further large studies are warranted to define long-term oncologic results of robotic right colectomy with CME and its eventual benefits in comparison to laparoscopy

Implementation of the ERAS program in gastric surgery: a nationwide survey in Italy

: Enhanced recovery after surgery (ERAS) programs have been developed by combining several evidence-based techniques for perioperative care, with the intention of reducing the stress response and organ dysfunction, thus allowing improved clinical results. ERAS programs have been widely adopted for colorectal surgery; however, their adoption for upper gastrointestinal surgery has been challenging even though good results have been reported in the literature. Our intent was to investigate the adoption of ERAS programs for resective gastric surgery in Italy. A survey was conducted among 20 departments of surgery belonging to the Italian Group for Research on Gastric Cancer (GC). Analysis of our survey showed that several evidence-based practices and many items of the ERAS guidelines for gastric surgery are not implemented in real practice in Italian centers dedicated to GC. This situation may be related to the hesitation of surgeons to introduce radical changes to the traditional postoperative management after gastrectomy. A multidisciplinary approach to the perioperative care of these patients is not routinely applied in many Italian centers. A strict collaboration of all clinicians involved in the perioperative care of patients undergoing gastrectomy for GC is key for the future implementation of ERAS in gastric surgery in our departments

Totally minimally invasive Ivor-Lewis esophagectomy: initial single center experience

Aim: Minimally invasive techniques for esophagectomy decrease cardiopulmonary complications and guarantee better quality of life (QoL) compared to open techniques, without compromising oncological radicality. This retrospective study compares the short-term and QoL outcomes of hybrid Ivor Lewis (HIL) and totally minimally invasive Ivor Lewis (TMIIL).Methods: Patients with cancer of the distal esophagus and esophagogastric junction were included into (HIL) and (TMIIL) groups in the period January 2017-July 2018. General features, intraoperative and postoperative results were analyzed. The surgical radicality and number of resected nodes were also evaluated. QoL was determined preoperatively and at 7 and 90 days postoperatively with EORTC QLQ-C30 questionnaire.Results: General features were similar in the TMIIL and HIL groups, which contained 13 and 14 patients, respectively. Median intervention duration was 360 min (range: 240-420) for TMIIL and 330 min (range: 240-400) for HIL (P = 0.0647). Median blood losses were similar for TMIIL and HIL at 100 mL (range: 50-400) and 175 mL (range: 50-350), respectively (P = 0.0831); pulmonary complications were 15% and 14% (P = 1) and leaks were 7% and 14% (P = 1) for TMIIL and HIL, respectively.Conclusion: Our experience suggests that TMIIL esophagectomy appears to give results similar to HIL and positively influences the QoL within 90 days after surgery. Duration of surgery and anastomotic leaks are the key elements influencing the learning curve. Randomized controlled trials are necessary to confirm the good results obtained and to give recommendations to avoid a high rate of complications during the learning curve for this difficult technique