Incidence and treatment of mediastinal leakage after esophagectomy: Insights from the multicenter study on mediastinal leaks

BACKGROUND Mediastinal leakage (ML) is one of the most feared complications of esophagectomy. A standard strategy for its diagnosis and treatment has been difficult to establish because of the great variability in their incidence and mortality rates reported in the existing series. AIM To assess the incidence, predictive factors, treatment, and associated mortality rate of mediastinal leakage using the standardized definition of mediastinal leaks recently proposed by the Esophagectomy Complications Consensus Group (ECCG). METHODS Seven Italian surgical centers (five high-volume, two low-volume) affiliated with the Italian Society for the Study of Esophageal Diseases designed and implemented a retrospective study including all esophagectomies (n = 501) with intrathoracic esophagogastric anastomosis performed from 2014 to 2017. Anastomotic MLs were defined according to the classification recently proposed by the ECCG. RESULTS Fifty-nine cases of ML were recorded, yielding an overall incidence of 11.8% (95%CI: 9.1%-14.9%). The surgical approach significantly influenced the occurrence of ML: the proportion of leakage was 10.5% and 9% after open and hybrid esophagectomy (HE), respectively, and doubled (20%) after totally minimally invasive esophagectomy (TMIE) (P = 0.016). No other predictive factors were found. The 30- and 90-d overall mortality rates were 1.4% and 3.2%, respectively; the 30- and 90-d leak-related mortality rates were 5.1% and 10.2%, respectively; the 90-d mortality rates for TMIE and HE were 5.9% and 1.8%, respectively. Endoscopy was the first-line treatment in 49% of ML cases, with the need for retreatment in 17.2% of cases. Surgery was needed in 44.1% of ML cases. Endoscopic treatment had the lowest mortality rate (6.9%). Removal of the gastric tube with stoma formation was necessary in 8 (13.6%) cases. CONCLUSION The incidence of ML after esophagectomy was high mainly in the TMIE group. However, the general and specific (leak-related) mortality rates were low. Early treatment (surgical or endoscopic) of severe leaks is mandatory to limit related mortality

Is there a role for palliative gastrectomy in asymptomatic metastatic gastric cancer?

Background: Surgery has an established role in gastric cancer for the palliation of major symptoms such as bleeding or obstruction. In other malignancies (like colorectal, kidney and breast cancer), resection of the primary tumor, even in presence of metastatic disease, appears to have a positive prognostic impact also in paucisymptomatic or asymptomatic patients and several randomized trials are ongoing Material and Methods: We retrospectively evaluated the data of patients treated from 2009 to 2014 at our Institution who fulfilled the following selection criteria: histologically confirmed gastric or gastroesophageal junction adenocarcinoma, locally advanced (unresectable) or metastatic disease and palliative treatment with at least one line of systemic chemotherapy. Primary end point of the analysis was overall survival (OS) from the start of first-line chemotherapy, estimated using the Kaplan–Meier method. Two-tailed log-rank test was used for survival comparison between groups and statistical significance was set at p < 0.05 Results: We identified 153 patients: five patients were excluded since they received palliative surgery because of symptoms referred to the primarytumor. Of the 148 patients analyzed, 62 (42%) underwent primary tumor resection in the absence of impending symptoms: tumor was located at the gastroesophageal junction in 26 patients and in the stomach in 122 patients. Median OS was 10.4 months for resected patients and 10.7 months for not resected ones (p = 0.523; HR 1.128, 95% CI 0.780–1.630). The difference was not significant even comparing resected patients with synchronous metastases (i.e. with metastatic disease ab initio or developing distant metastases within 3 months after an apparently radical surgery) with those who did not undergo any intervention (median OS: 12.3 and 10.7 months, respectively, p = 0.596; HR 0.874, 95% CI 0.532–1.437). Taking into account the 121 patients treated with homogeneous first-line chemotherapy (douplet or triplet regimes comprising a platinum derivative and a fluoropyrimidine), there was no significant difference in median OS between resected and not resected patients (11.9 and 10.7 months, respectively, p = 0.744; HR 0.931, 95% CI 0.608–1.426) and between resected patients with synchronous metastases and not resected patients (13.8 and 10.7 months, respectively; p = 0.458; HR 0.824, 95% CI 0.494–1.375) Conclusions: In pauci- or asymptomatic patients with metastatic gastroesophageal cancer treated with first-line chemotherapy, surgery on the primary tumor does not seem to play a role in improving OS comparing to systemic therapy alone

Impact of COVID-19 outbreak on esophageal cancer surgery in Northern Italy: lessons learned from a multicentric snapshot

Coronavirus Disease-19 (COVID-19) outbreak has significantly burdened healthcare systems worldwide, leading to reorganization of healthcare services and reallocation of resources. The Italian Society for Study of Esophageal Diseases (SISME) conducted a national survey to evaluate changes in esophageal cancer management in a region severely struck by COVID-19 pandemic. A web-based questionnaire (26 items) was sent to 12 SISME units. Short-term outcomes of esophageal resections performed during the lockdown were compared with those achieved in the same period of 2019. Six (50%) centers had significant restrictions in their activity. However, overall number of resections did not decrease compared to 2019, while a higher rate of open esophageal resections was observed (40 vs. 21.7%; P=0.034). Surgery was delayed in 24 (36.9%) patients in 6 (50%) centers, mostly due to shortage of anesthesiologists, and occupation of intensive care unit beds from intubated COVID-19 patients. Indications for neoadjuvant chemo (radio) therapy were extended in 14% of patients. Separate COVID-19 hospital pathways were active in 11 (91.7%) units. COVID-19 screening protocols included nasopharyngeal swab in 91.7%, chest computed tomography scan in 8.3% and selective use of lung ultrasound in 75% of units. Postoperative interstitial pneumonia occurred in 1 (1.5%) patient. Recovery from COVID-19 pandemic was characterized by screening of patients in all units, and follow-up outpatient visits in only 33% of units. This survey shows that clinical strategies differed considerably among the 12 SISME centers. Evidence-based guidelines are needed to support the surgical esophageal community and to standardize clinical practice in case of further pandemics

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.

Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer. More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted. Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment. Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples

Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV) positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples

EAES recommendations for the management of gastroesophageal reflux disease

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most frequent benign disorders of the upper gastrointestinal tract. Management of GERD has always been controversial since modern medical therapy is very effective, but laparoscopic fundoplication is one of the few procedures that were quickly adapted to the minimal access technique. The purpose of this project was to analyze the current knowledge on GERD in regard to its pathophysiology, diagnostic assessment, medical therapy, and surgical therapy, and special circumstances such as GERD in children, Barrett's esophagus, and enteroesophageal and duodenogastroesophageal reflux. METHODS: The European Association of Endoscopic Surgery (EAES) has tasked a group of experts, based on their clinical and scientific expertise in the field of GERD, to establish current guidelines in a consensus development conference. The expert panel was constituted in May 2012 and met in September 2012 and January 2013, followed by a Delphi process. Critical appraisal of the literature was accomplished. All articles were reviewed and classified according to the hierarchy of level of evidence and summarized in statements and recommendations, which were presented to the scientific community during the EAES yearly conference in a plenary session in Vienna 2013. A second Delphi process followed discussion in the plenary session. RESULTS: Recommendations for pathophysiologic and epidemiologic considerations, symptom evaluation, diagnostic workup, medical therapy, and surgical therapy are presented. Diagnostic evaluation and adequate selection of patients are the most important features for success of the current management of GERD. Laparoscopic fundoplication is the most important therapeutic technique for the success of surgical therapy of GERD. CONCLUSIONS: Since the background of GERD is multifactorial, the management of this disease requires a complex approach in diagnostic workup as well as for medical and surgical treatment. Laparoscopic fundoplication in well-selected patients is a successful therapeutic option