Incidence and Risk Factors for Diaphragmatic Herniation Following Esophagectomy for Cancer.

OBJECTIVE: To evaluate the incidence and risk factors of diaphragmatic herniation following esophagectomy for cancer (DHEC), and assess the results of surgical repair. SUMMARY BACKGROUND DATA: The current incidence of DHEC is discussed with conflicting data regarding its treatment and natural course. METHODS: Monocentric retrospective cohort study (2009-2018). From 902 patients, 719 patients with a complete follow-up of CT scans after transthoracic esophagectomy for cancer were reexamined to identify the occurrence of a DHEC. The incidence of DHEC was estimated using Kalbfleisch and Prentice method and risk factors of DHEC were studied using the Fine and Gray competitive risk regression model by treating death as a competing event. Survival was analyzed. RESULTS: Five-year DHEC incidence was 10.3% [95% CI, 7.8%-13.2%] (n = 59), asymptomatic in 54.2% of cases. In the multivariable analysis, the risk factors for DHEC were: presence of hiatal hernia on preoperative CT scan (HR = 1.72 [1.01-2.94], P = 0.046), previous hiatus surgery (HR = 3.68 [1.61-8.45], P = 0.002), gastroesophageal junction tumor location (HR = 3.51 [1.91-6.45], P < 0.001), neoadjuvant chemoradiotherapy (HR = 4.27 [1.70-10.76], P < 0.001), and minimally invasive abdominal phase (HR = 2.98 [1.60-5.55], P < 0.001). A cure for DHEC was achieved in 55.9%. The postoperative mortality rate was nil, the overall morbidity rate was 12.1%, and the DHEC recurrence rate was 30.3%. Occurrence of DHEC was significantly associated with a lower hazard rate of death in a time-varying Cox's regression analysis (HR = 0.43[0.23-0.81], P = 0.010). CONCLUSIONS: The 5-year incidence of DHEC is 10.3% and is associated with a favorable prognosis. Surgical repair of symptomatic or progressive DHEC is associated with an acceptable morbidity. However, the optimal surgical repair technique remains to be determined in view of the large number of recurrences.

Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: implication of the Wnt/ß-catenin pathway.

Secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of ß-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/ß-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis.

Are Thoracotomy and/or Intrathoracic Anastomosis Still Predictors of Postoperative Mortality After Esophageal Cancer Surgery?: A Nationwide Study.

BACKGROUND: Intrathoracic (vs cervical) anastomosis and a thoracotomy (vs absence) have previously been associated with increasing postoperative mortality (POM). Recent improvements in surgical practices and perioperative management may have changed these dogmas. OBJECTIVES: The aim of this study was to evaluate the impact of performing intrathoracic anastomosis and/or thoracotomy on POM after esophageal cancer surgery in recent years. METHODS: All consecutive patients who underwent esophageal cancer surgery with reconstruction between 2010 and 2012 in France were included (n = 3286). Patients with a thoracoscopic approach were excluded (n = 4). We compared 30-day POM between patients having received intrathoracic (vs cervical) anastomosis and between those having received a thoracotomy or not. Multivariate analyses and propensity score matching were used to adjust for confounding factors. RESULTS: Patients had either cervical (n = 548) or intrathoracic (n = 2738) anastomosis. Thirty-day POM was higher after cervical anastomosis (8.8% vs 4.9%, P < 0.001). Having received a thoracotomy (n = 3061) was associated with a decreased risk of 30-day POM (5.3% vs 9.3%, P = 0.011). After adjustment for confounding factors, cervical anastomosis was associated with 30-day POM [odds ratio (OR) 1.71; 95% confidence interval (CI) 1.05-2.77); P = 0.032], whereas performing a thoracotomy was not associated with 30-day POM (OR 0.97; 95% CI 0.51-1.84; P = 0.926). CONCLUSIONS: Nowadays, intrathoracic anastomosis provides a lower 30-day POM rate compared to cervical anastomosis, and performing a thoracotomy is not associated with POM. Systematic anastomosis neck placement or thoracotomy avoidance is not a relevant argument anymore to decrease POM.

Is Centralization Needed for Esophageal and Gastric Cancer Patients With Low Operative Risk?: A Nationwide Study.

OBJECTIVE: To investigate the impact of center volume on postoperative mortality (POM) according to patient condition. BACKGROUND: Centralization has been shown to improve POM in esophageal and, to a lesser extent, gastric cancer surgery; however, the benefit of centralization for patients with low operative risk is questionable. METHODS: All consecutive patients who underwent esophageal or gastric cancer surgery between 2010 and 2012 in France were included (N = 11,196). The 30-day POM was compared in terms of the center volume (low: <20 cases per year, intermediate: 20-39, high: 40-59, and very high: ≥60) and stratified according to the Charlson score (0, 1-2, ≥3). The consistency across the esophageal (n = 3286) and gastric (n = 7910) subgroups, and variations between 30-day and 90-day POM were analyzed. RESULTS: Low-volume centers treated 64.2% of patients. A linear decrease in 30-day and 90-day POM was observed with increasing center volume, with rates of 5.7% and 10.2%, 4.3% and 7.9%, 3.3% and 6.7%, and 1.7% and 3.6% in low, intermediate, high, and very high-volume centers, respectively (P < 0.001). Comparing low and very high-volume centers, 30-day POM was 4.0% versus 1.1% for Charlson 0 (P = 0.001), 7.5% versus 3.4% for Charlson 1 to 2 (P < 0.001), and 14.7% versus 3.7% for Charlson ≥3 (P = 0.003) patients. A similar linear decrease was observed in the esophageal and gastric cancer subgroups. Between the low and very high-volume centers, an almost 70% reduction in the relative risk of POM was systematically observed, independent of Charlson score or tumor location. CONCLUSIONS: To improve POM, esophageal and gastric cancer surgery should be centralized, irrespective of the patient's comorbidity or tumor location.

Esophageal Adenocarcinoma: Impact of a Large Hiatal Hernia on Outcomes After Surgery.

OBJECTIVE: To evaluate complete tumor resection rate (primary objective), 30-day postoperative outcomes, and survival (secondary objectives) in patients with a hiatal hernia (HH) ≥5 cm (HH group) compared with those who did not have a HH or presented with a HH <5 cm (control group). BACKGROUND: HH is a risk factor for esophageal and junctional adenocarcinoma (EGJA). Its impact on the outcomes after EGJA surgery is unknown. METHODS: Among 367 patients who underwent surgery for EGJA, a HH was searched for on computerized tomography scan and barium swallow, with comparison between the HH (n = 42) and control (n = 325) groups. RESULTS: In the HH group, EGJAs exhibited higher rates of incomplete resection (50.0% vs 4.0%; P < 0.001), of pN3 stages (28.5% vs 10.1%; P = 0.002), and lower median survival (20.9 vs 41.0 mos; P = 0.001). After adjustment, a HH ≥5 cm was a predictor of incomplete resection (odds ratio 21.0, 95% confidence interval 9.4-46.8, P < 0.001) and a poor prognostic factor (hazard ratio 1.6, 95% confidence interval 1.1-2.5, P = 0.025). In the HH group, 30-day mortality was significantly higher in patients who received neoadjuvant radiotherapy (20.0% vs 0%; P = 0.040), which was related to greater cardiac and pulmonary toxicity. CONCLUSIONS: For the first time, we showed that a HH ≥5 cm is associated with a poor prognosis in patients who had surgery for EGJA, linked to greater incomplete resection and lymph node involvement. Neoadjuvant radiotherapy was associated with a significant toxicity in patients with a HH ≥5 cm.

Anatomic patterns of anastomotic leaks after Ivor Lewis esophagectomy for cancer: Impact on management and outcomes.

BACKGROUND: Anastomotic leakage presentation after Ivor Lewis esophagectomy may vary on imaging. Such variations may influence anastomotic leakage management and outcomes. METHODS: All consecutive patients who underwent Ivor Lewis esophagectomy for cancer between 2012 and 2019 in 2 referral centers were included. Anatomical patterns of anastomotic leakage were defined on imaging as follows: eso-mediastinal anastomotic leakage was a leak contained in the posterior mediastinum, eso-pleural anastomotic leakage was a leak involving the pleural cavity, and eso-bronchial anastomotic leakage was a leak communicating with the tracheobronchial tract. According to the Esophageal Complications Consensus Group definition, management and 90-day mortality were evaluated according to these patterns. RESULTS: Among 731 patients, 111 (15%) developed anastomotic leakage consisting of eso-mediastinal anastomotic leakage (n = 87, 79%), eso-pleural anastomotic leakage (n = 16, 14%) and eso-bronchial anastomotic leakage (n = 8, 7%). There was no difference among these groups regarding preoperative characteristics or time to anastomotic leakage diagnosis. There was a significant difference in initial management according to anastomotic leakage anatomic patterns (P = .001). More than half of patients who experienced eso-mediastinal anastomotic leakage (n = 46, 53%) were initially treated conservatively without requiring intervention (Esophageal Complications Consensus Group type I), whereas most patients with eso-pleural anastomotic leakage (n = 14, 87.5%) and all with eso-bronchial anastomotic leakage (n = 8, 100%) initially required interventional or surgical treatment (Esophageal Complications Consensus Group type II-III). Anastomotic leakage anatomic patterns had a statistically significant impact on 90-day mortality, intensive care unit stay, and total hospital stay (P < .001). CONCLUSION: Anastomotic leakage anatomic patterns after Ivor Lewis esophagectomy influence outcomes. Further studies are warranted to validate it in a prospective setting. Anastomotic leakage anatomic patterns may help in guiding anastomotic leakage management.