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

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

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

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

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor–Lewis esophagectomy: comparison of short-term outcomes

Purpose: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor–Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. Methods: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. Results: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. Conclusions: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture

End-to-side circular stapled versus side-to-side linear stapled intrathoracic esophagogastric anastomosis following minimally invasive Ivor–Lewis esophagectomy: comparison of short-term outcomes

Purpose: The search for the optimal procedure for creation of a safe gastroesophageal intrathoracic anastomosis with a lower risk of leakage in totally minimally invasive Ivor–Lewis esophagectomy (TMIIL) is ongoing. In the present study, we compared the outcomes of end-to-side (with circular stapler [CS]) and side-to-side (with linear stapler [LS]) techniques for intrathoracic anastomosis during TMIIL performed in 2 European high-volume centers for upper gastrointestinal surgery. A propensity score method was used to compare the CS and LS groups. Methods: We retrospectively evaluated patients with lower esophageal cancer or Siewert type 1 or 2 esophagogastric junction carcinoma who underwent a planned TMIIL esophagectomy, performed from January 2017 to September 2020. The anastomosis was created by a semi-mechanical technique using a LS in one center and by a mechanical technique using a CS in the other center. General features, operative techniques, pathology data, and short-term outcomes were analyzed. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. The primary endpoint of the study was the rate of anastomotic leakage in the two groups. Secondary endpoints included rates of anastomotic stricture and overall postoperative complications. Results: Considering the whole population, 256 patients were included; of those, 220 received the anastomosis with a circular stapler (CS group), and 36 received the anastomosis with a linear stapler (LS group). No significant differences by group in terms of sex, age, American Society of Anesthesiologists physical status classification, and type of neoplasm were showed. The rate of anastomotic leakage did not differ in the two groups (9.6% CS vs. 5.6% LS, p = 0.438), as well as the rate of anastomotic stricture in the 3-month follow-up (0.9% CS vs. 2.8% LS, p = 0.367). The rate of chyle leakage and of pulmonary, cardiac, and infective complications was not significantly different in the groups. After propensity score matching, 72 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. Conclusions: The results of our study suggest that both techniques for esophagogastric anastomosis during TMIIL are feasible, safe, and effective, with comparable rates of postoperative anastomotic leakage and stricture

MULTICENTER STUDY ON THE INCIDENCE AND TREATMENT OF MEDIASTINAL LEAKS AFTER ESOPHAGECTOMY (MUMELE 2)

Background: Management of mediastinal anastomotic leaks (MALs) after Ivor Lewis esophagectomy includes conservative, endoscopic, or surgical management. Endoscopic vacuum therapy (EVAC) is becoming a routine approach for MALs, although the outcomes have not been defined. Purpose: This study describes the incidence, treatment, and outcomes of MALs in patients who underwent esophagectomy in three Italian high-volume centers that routinely use EVAC for MAL. Methods: Patients who underwent Ivor Lewis esophagectomy between September 2018 and March 2023 were included. Results: A total of 681 patients underwent Ivor Lewis esophagectomy, of whom 88 had an MAL. MAL rates for open, minimally invasive, and robotic esophagectomy were 11.5%, 13.4%, and 14.8%, respectively. Global and specific 30- and 90-day mortality rates for MAL were 0.9% and 2.1% and 6.8% and 15.9%, respectively. Nonoperative management (NOM) as primary treatment was chosen for 62 patients. The most common NOM and OM was EVAC (62.9%) and anastomotic redo (53.8%), respectively. Diversion was the OM for seven patients, three of whom died. Primary treatment proved successful in 40 patients. Among them, EVAC alone was successful in 35.9% of patients. Globally, endoscopic treatment including EVAC was successful in 79% of NOM and 55.7% of MALs. NOM and OM were chosen as secondary treatment for 27 and 10 patients, respectively. Secondary treatment proved successful in 21 patients. Conclusions: The incidence of MAL after Ivor Lewis esophagectomy is approximately 13%. Endoscopic techniques have a success rate of almost 80%, with EVAC representing a significant part of this treatment process