FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

Early Mobilization Using a Mobile Patient Lift in the ICU: A Randomized Controlled Trial.

OBJECTIVES: To ascertain whether a mobile patient lift facilitates early mobilization in ventilated ICU patients. DESIGN: A single-center, open-label, randomized controlled trial. SETTING: An academic ICU in Tokyo. PATIENTS: Eighty patients were admitted to ICU and expected ventilation for at least 48 hours. INTERVENTIONS: In the intervention group, in addition to the rehabilitation protocol received by the control group, patients were assisted in sitting, standing, transfers, and walking using the mobile patient lift. MEASUREMENTS AND MAIN RESULTS: The intervention group predominantly stood faster than the control group (1.0 vs. 3.0 d, p < 0.01). The Intervention group also had significantly higher Functional Status Score-ICU scores at ICU discharge. However, the Medical Research Council score and Barthel index at discharge, length of ICU stay, and number of ventilator-free days did not differ between the two groups. CONCLUSIONS: The use of mobile patient lifts facilitates the earlier standing of patients on ventilators. This may contribute to patients improved physical function in the ICU. TRIAL REGISTRATION: The study protocol was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000044965. Registered July 30, 2021.

Minimally Invasive Esophagectomy Provides Better Short- and Long-Term Outcomes Than Open Esophagectomy in Locally Advanced Esophageal Cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) has been increasingly performed for locally advanced esophageal cancer in place of open transthoracic esophagectomy (OE). This study explored the significance of MIE for esophageal squamous cell carcinoma (ESCC), focusing mainly on the depth of primary esophageal tumors. METHODS: This study retrospectively assessed short- and long-term outcomes of patients who underwent esophagectomy for ESCC from 2005 through 2021. The inverse probability of the treatment-weighting (IPTW) method was used to compare the outcomes between OE and MIE. The outcomes also were evaluated in the subgroups stratified by cT category. RESULTS: Among 1117 patients, 447 (40%) underwent OE and 670 (60%) underwent MIE. After IPTW adjustment, the incidence of any postoperative complications was significantly higher in the OE group than in the MIE group (60.8% vs 53.7%; p = 0.032), whereas the R0 resection rate was significantly higher in the MIE group (98.6% vs 92.7%; p < 0.001). The MIE group showed better 3 year overall and cancer-specific survival than the OE group (p < 0.001). The incidence of locoregional recurrence within the surgical field was significantly more frequent in the OE group (p < 0.001). In the subgroup analysis stratified by cT category, the R0 resection rate was significantly higher and the incidence of locoregional recurrence was lower in the MIE group among the patients with cT3-4 tumors. In the patients with cT1-2 tumors, MIE showed no significant benefit over OE. CONCLUSIONS: For the patients with cT3-4 tumors, MIE showed fewer postoperative complications, better locoregional control, and better prognosis than OE. Compared with OE, MIE is beneficial, especially for locally advanced ESCC.

Development and Validation Study of the Prognostic Impact of Deep Learning-Determined Myxoid Stroma After Neoadjuvant Chemotherapy in Patients with Esophageal Squamous Cell Carcinoma.

PURPOSE: This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital. METHODS: We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1. RESULTS: The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001). CONCLUSIONS: AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC.

Prognostic Impact of Thoracic Duct Resection in Patients Who Underwent Transthoracic Esophagectomy Following Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma: Exploratory Analysis of JCOG1109.

BACKGROUND: Although several studies have investigated whether thoracic duct (TD) resection improves prognosis, the conclusion remains controversial. JCOG1109 is a three-arm randomized phase III trial to confirm the survival advantage of docetaxel, cisplatin, 5-fluorouracil (DCF), and cisplatin plus 5-fluorouracil (CF) combined with radiotherapy (CF-RT) over CF as neoadjuvant treatment. The study aimed to evaluate the survival impact of TD resection and its association with neoadjuvant treatment and pathological response in patients enrolled in JCOG1109. PATIENTS AND METHODS: Clinicopathological factors, surgical results, and prognosis were compared between TD preserved and resected groups. The survival impact of TD resection was also evaluated in the subgroups on the basis of combinations of preoperative therapy and pathological response. RESULTS: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200) in JCOG1109. Of them, 541 patients underwent esophagectomy (183/181/177), and TD was resected in 265 patients (93/91/81). For the entire cohort, TD resection was not a significant prognostic factor for overall survival in the multivariable analysis (HR 1.20, 95% CI 0.91-1.57). In the subgroup analyses by combinations of neoadjuvant treatment and pathological response, TD resected group had a significantly better overall survival compared with TD preserved group in patients who received DCF and achieved pathological response (HR 0.20, 95% CI 0.07-0.61). CONCLUSIONS: The survival benefit of TD resection was not demonstrated in patients with surgically resectable esophageal squamous cell carcinoma enrolled in JCOG1109. The residual tumor burden after neoadjuvant treatment might be linked to the survival impact of TD resection.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Clinical characteristics of pulmonary Mycobacterium avium complex disease in patients with interstitial lung disease.

OBJECTIVE: Mycobacterium avium complex pulmonary disease (MAC-PD) is occasionally complicated by interstitial lung disease (ILD) in clinical practice, but clinical studies are limited. This study aims to elucidate the clinical and imaging characteristics of MAC-PD in patients with ILD. METHODS: We retrospectively analyzed imaging and clinical data from medical records of 54 consecutive ILD patients diagnosed with MAC-PD from 2011 to 2021 at our institution. We compared the imaging and clinical data of these patients with 2218 ILD patients diagnosed at our institution. RESULTS: The mean age of the patients was 74 years, with 25 males and 29 females, and a mean body mass index (BMI) of 20.0 kg/m2. Compared to all ILD patients, ILD-associated MAC-PD had older ages, lower BMI. The most common underlying ILD diagnosis was unclassifiable interstitial pneumonia. MAC-PD imaging classification was nodular-bronchiectatic (NB) type in 17 patients, fibro-cavitary (FC) type in 15 patients, and unclassifiable (UC) type in 22 patients. Many UC types were difficult to diagnose due to the absence of clear findings indicative of MAC infection. Chronic pulmonary aspergillosis complication was 24.1 %. The mean survival of ILD-associated MAC-PD was 55.6 months, shorter than that of regular MAC-PD. The UC type had a shorter survival than the NB type, similar to the FC type. CONCLUSION: MAC-PD associated with ILD frequently complicates chronic pulmonary aspergillosis and has a poor prognosis. The most common imaging type, UC type, particularly has a shorter survival. Careful management is essential for MAC-PD associated with ILD.

Anatomical factor associated with thoracic procedural difficulty in robot-assisted minimally invasive esophagectomy.

BACKGROUND: Robotic surgical systems with full articulation of instruments, tremor filtering, and motion scaling can potentially overcome the procedural difficulties in endoscopic surgeries. However, whether robot-assisted minimally invasive esophagectomy (RAMIE) can overcome anatomical difficulties during thoracoscopic esophagectomy remains unclear. This study aimed to clarify the anatomical and clinical factors that influence the difficulty of RAMIE in the thoracic region. METHODS: Forty-five patients who underwent curative-intent RAMIE with upper mediastinal lymph node dissection for esophageal cancer were included. Using preoperative computed tomography images, we calculated previously reported anatomical indices to assess the upper mediastinal narrowness and vertebral body projections in the middle thoracic region. The factors influencing thoracic operative time were then investigated. RESULTS: During the thoracic procedure, the median operative time was 215 (124-367) min and the median blood loss was 20 (5-190) mL. Postoperatively, pneumonia, anastomotic leakage, and recurrent laryngeal nerve palsy occurred in 17.8%, 2.2%, and 6.7% of the patients, respectively. The multiple linear regression model revealed that a narrow upper mediastinum and greater blood loss during the thoracic procedure were significant factors associated with a prolonged thoracic operative time (P = 0.025 and P < 0.001, respectively). Upper mediastinal narrowing was not associated with postoperative complications. CONCLUSIONS: A narrow upper mediastinum was significantly associated with a prolonged thoracic operative time in patients with RAMIE.

Gastric conduit reconstruction after esophagectomy.

A high risk of complications still accompanies gastric conduit reconstruction after esophagectomy. In this narrative review, we summarize the technological progress and the problems of gastric conduit reconstruction after esophagectomy. Several types of gastric conduits exist, including the whole stomach and the narrow gastric tube. The clinical outcomes are similar between the two types of conduits. Sufficient blood supply to the conduit is mandatory for a successful esophageal reconstruction. Recently, due to the availability of equipment and its convenience, indocyanine green angiography has been rapidly spreading. When the blood perfusion of the planning anastomotic site is insufficient, several techniques, such as the Kocher maneuver, pedunculated gastric tube with duodenal transection, and additional microvascular anastomosis, exist to decrease the risk of anastomotic failure. There are two different anastomotic sites, cervical and thoracic, and mainly two reconstructive routes, retrosternal and posterior mediastinal routes. Meta-analyses showed no significant difference in outcomes between the anastomotic sites as well as the reconstructive routes. Anastomotic techniques include hand-sewn, circular, and linear stapling. Anastomoses using linear stapling is advantageous in decreasing anastomosis-related complications. Arteriosclerosis and poorly controlled diabetes are the risk factors for anastomotic leakage, while a narrow upper mediastinal space and a damaged stomach predict leakage. Although standardization among the institutional team members is essential to decrease anastomotic complications, surgeons should learn several technical options for predictable or unpredictable intraoperative situations.

Impact of treatment guidelines and pivotal clinical trial results on a surgeon's decision regarding treatment for gastric cancer: a retrospective cohort study using the National Clinical Database.

PURPOSES: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan. METHODS: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes. RESULTS: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results. CONCLUSION: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials.

Validation of the cutoff values for the number of metastatic lymph nodes for esophageal cancer staging: a multi-institutional analysis of 655 patients in Japan.

BACKGROUND: The number of metastatic lymph nodes (LNs) is an important prognostic factor for esophageal cancer, and N staging is important for prognostic stratification. The optimal cutoff values for clinical (cN) and pathologic N (pN) staging should be reconsidered following advances in neoadjuvant therapy. METHODS: The study included 655 patients who underwent esophagectomy between January 2014 and December 2016 in four high-volume centers in Japan. Optimal cutoff values for the number of metastatic LNs in cN and pN staging were examined using X-tile, and their prognostic performance was validated using the Kaplan-Meier method. RESULTS: The cutoff values were 1, 2, and 3 for cN staging and 1, 3, and 7 for pN staging. Prognosis was significantly better in patients with cN0 than in those with modified (m)-cN1 (p = 0.0211). However, prognosis was not significantly different among the patients with m-cN1, m-cN2, and m-cN3 disease. Prognosis was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p < 0.0001; pN1 vs pN2, p < 0.0001; pN2 vs pN3, p < 0.0001). In patients who received preoperative neoadjuvant therapy, prognosis, which was not significantly different among the patients with cN0, m-cN1, m-cN2, and m-cN3 disease (cN0 vs m-cN1, p = 0.5675; m-cN1 vs m-cN2, p = 0.4425; m-cN2 vs m-cN3, p = 0.7111), was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p = 0.0025; pN1 vs pN2, p = 0.0046; pN2 vs pN3, p = 0.0104). CONCLUSIONS: cN has no prognostic impact in patients who underwent preoperative treatment followed by esophagectomy, despite the optimization of cN classification. The conventional TNM8th pN classification is useful for predicting prognosis even for patients who have undergone preoperative treatment. The conventional cutoffs for metastatic LNs in the International Union against Cancer tumor node metastasis staging system are valid and can be effectively used in clinical practice.

Outcomes of patients with esophageal squamous cell carcinoma who achieved a pathological complete response in the primary lesion by neoadjuvant treatment: a Japanese nationwide cohort study.

BACKGROUND: Minimal data was reported regarding the characteristics, risks of lymph node metastasis, and prognostic factors in esophageal cancer patients who achieved remarkable response in the primary lesion to neoadjuvant treatment (NAT). METHODS: This study evaluated the nationwide data of esophageal squamous cell carcinoma (ESCC) patients who underwent surgery following NAT in Japan. Of 4484 patients, 300 (6.7%) had ypT0 following NAT and curative esophagectomy. Factors associated with lymph node metastasis and prognosis were analyzed. RESULTS: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) were administered in 260 (86.2%) and 40 (13.8%) patients, respectively. Pathologically, 72 (24.0%) had lymph node metastasis (residual nodal disease; RND), and pretherapeutic lymph node metastasis was the independent risk factor for RND (odd ratio [OR]: 3.21; 95% confidence interval [CI]: 1.44-8.20; P = 0.008). The 5-year overall and relapse-free survivals were significantly longer in patients with pathological complete response (pCR) than in those with RND (both P < 0.001). Pretherapeutic cT3 or T4a tumors (hazard ratio [HR]: 1.71; 95% CI: 1.02-2.88; P = 0.043), RND (HR: 3.30; 95% CI: 1.98-5.50; P < 0.001), and operative blood loss (Liter, HR: 1.53; 95% CI: 1.07-2.19; P = 0.021) were independent risk factors affecting relapse-free survival in multivariable analysis. CONCLUSIONS: Of patients with ypT0 after NAT, 24.0% had RND, and pretherapeutic lymph node metastasis was the risk factor. In addition, pretherapeutic cT3, or T4a tumors, RND, and operative blood loss were the poor prognosticators in patients with ypT0 after NAT.

Outcome research on esophagectomy analyzed using nationwide databases in Japan: evidences generated from real-world data.

Esophagectomy for esophageal cancer is a highly invasive gastrointestinal surgical procedure. The National Clinical Database (NCD) of Japan, initiated in 2011, has compiled real-world data on esophagectomy, one of nine major gastroenterological surgeries. This review examines outcomes after esophagectomy analyzed using the Japanese big databases. Certification systems by the Japanese Society of Gastroenterological Surgery (JSGS) and the Japan Esophageal Society (JES) have shown that institutional certification has a greater impact on short-term surgical outcomes than surgeon certification. Minimally invasive esophagectomy has emerged as a viable alternative to open esophagectomy, although careful patient selection is crucial, especially for elderly patients with advanced tumors. The NCD has significantly contributed to the assessment and enhancement of surgical quality and short-term outcomes, while studies based on Comprehensive Registry of Esophageal Cancer in Japan (CRECJ) have provided data on patient characteristics, treatments, and long-term outcomes. The JES has conducted various questionnaire-based retrospective clinical reviews in collaboration with authorized institutions certified by JES. The Diagnosis Procedure Combination (DPC) database provides administrative claims data including itemized prices for surgical, pharmaceutical, laboratory, and other inpatient services. Analyzing these nationwide databases can offer precise insights into surgical quality for esophageal cancer, potentially leading to improved treatment outcomes.

No difference in the incidence of postoperative pulmonary complications between abdominal laparoscopy and laparotomy for minimally invasive thoracoscopic esophagectomy: a retrospective cohort study using a nationwide Japanese database.

INTRODUCTION: There remains a lack of evidence regarding the optimal abdominal approach, including laparoscopy, hand-assisted, and open laparotomy for minimally invasive thoracoscopic esophagectomy. We aimed to compare the incidence of postoperative complications, particularly pulmonary complications, between laparoscopy and open laparotomy for minimally invasive thoracoscopic esophagectomy using nationwide Japanese databases. METHODS: Data from patients in the National Clinical Database (NCD) who underwent thoracoscopic esophagectomy for esophageal cancer were analyzed. The incidence of pulmonary complications was compared between abdominal laparoscopy and laparotomy after matching the propensity scores (PS) from preoperative factors to account for confounding bias. Laparoscopic-assisted surgery (LAS) was also compared to hand-assisted laparoscopic surgery (HALS). RESULTS: Of the 24,790 patients who underwent esophagectomy between 2018 and 2021, data from 12,633 underwent thoracoscopic procedure. The proportion of patients who experienced pulmonary complications did not significantly differ between the laparoscopy group and the laparotomy group after matching (664/3195 patients, 20.8% versus 702/3195 patients, 22.0%; P = 0.25). No difference in the incidence of pulmonary complications was observed among patients treated using the laparoscopic approach (508/2439 patients, 20.8% in the LAS group versus 498/2439 patients, 20.4% in the HALS group; P = 0.72). CONCLUSIONS: We observed no significant difference in the incidence of postoperative pulmonary complications between laparoscopy and laparotomy for thoracoscopic esophagectomy. Short-term outcomes were similar between the laparoscopic-assisted approach and the hand-assisted approach. This study provides valuable insights into the optimal abdominal approach for thoracoscopic esophagectomy using data from a nationwide database that reflect real-world clinical practice.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Esophagectomy for esophageal cancer in patients with a history of total pharyngolaryngectomy: a Japanese nationwide retrospective cohort study.

BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.

Intratumour Fusobacterium nucleatum and immune response to oesophageal cancer.

BACKGROUND: Experimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour immunity. We investigated the relationship between intratumour F. nucleatum and immune response to oesophageal cancer. METHODS: Utilising an unbiased database of 300 resected oesophageal cancers, we measured F. nucleatum DNA in tumour tissue using a quantitative polymerase chain reaction assay, and evaluated the relationship between the abundance of F. nucleatum and the densities of T cells (CD8 + , FOXP3 + and PDCD1 + ), as well as lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoural lymphocytic reaction, stromal lymphocytic reaction and tumour-infiltrating lymphocytes) in oesophageal carcinoma tissue. RESULTS: F. nucleatum was significantly and inversely associated only with the peritumoural lymphocytic reaction (P = 0.0002). Compared with the F. nucleatum-absent group, the F. nucleatum-high group showed a much lower level of the peritumoural lymphocytic reaction (univariable odds ratio, 0.33; 95% confidence interval, 0.16-0.65; P = 0.0004). A multivariable model yielded a similar finding (multivariable odds ratio, 0.34; 95% confidence interval 0.16-0.69; P = 0.002). CONCLUSIONS: Intratumour F. nucleatum is associated with a diminished peritumoural lymphocytic reaction, providing a platform for further investigations on the potential interactive roles between intratumour F. nucleatum and host immunity.

Prognosis of Patients with Esophageal Carcinoma After Routine Thoracic Duct Resection: A Propensity-matched Analysis of 12,237 Patients Based on the Comprehensive Registry of Esophageal Cancer in Japan.

OBJECTIVE: To clarify whether routine thoracic duct (TD) resection improves the prognosis of patients with esophageal cancer after radical esophagectomy. SUMMARY OF BACKGROUND DATA: Although TD resection can cause nutritional disadvantage and immune suppression, it has been performed for the resection of surrounding lymph nodes. METHODS: We analyzed 12,237 patients from the Comprehensive Registry of Esophageal Cancer in Japan who underwent esophagectomy between 2007 and 2012. TD resection and preservation groups were compared in terms of prognosis, perioperative outcomes, and initial recurrent patterns using strict propensity score matching. Particularly, the year of esophagectomy and history of primary cancer of other organs were added as covariates. RESULTS: After propensity score matching, 1638 c-Stage I-IV patients participated in each group. The 5 year overall survival and cause-specific survival rates were 57.5% and 65.6% in the TD-resected group and 55.2% and 63.4% in the TD-preserved group, respectively, without significant differences. The TD-resected group had significantly more retrieved mediastinal nodes (30 vs 21, P < 0.0001) and significantly fewer lymph node recurrence (376 vs 450, P = 0.0029) compared with the TD-preserved group. However, the total number of distant metastatic organs was significantly greater in TD-resected group than in the TD-preserved group (499 vs 421, P = 0.0024). CONCLUSIONS: TD resection did not improve survival in patients with esoph-ageal cancer. Despite having retrieved more lymph nodes, TD resection caused distant metastases in more organs compared to TD preservation. Hence, prophylactic TD resection should not be recommended in patients with esophageal cancer.

Nationwide Validation Study of the Prognostic Significance of Stratification Using Pathological Stage and Response to Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to validate the prognostic significance of stratification using pathological stage and response to neoadjuvant chemotherapy with a nationwide database from an authorized institute by the Japan Esophageal Society. BACKGROUND: We proposed the combined criteria using pStage and pathological response. Conducting a validation study using an expanded cohort in the clinical setting would be valuable since it was developed using retrospective data collection. METHODS: Patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed for esophageal cancer between 2010 and 2015. The prognostic value of the pathological response was evaluated within the same pStage. Moreover, risk stratification was developed to predict cancer-specific survival (CSS). RESULTS: The pathological response showed significant stratification of CSS in 3761 patients included in this analysis. We classified the patients into 7 groups as survival was significantly different between responders and nonresponders under the stratification with pStage, excluding pStage I comprising pStage 0-I/II responder/II nonresponder/III responder/III nonresponder/IV responder/IV nonresponder with the 5-year CSS of 83.7%/75.8%/68.9%/59.8%/44.4%/40.7%/23.1%, respectively. Furthermore, the area under the curve was significantly higher under the new classification than in the pStage alone ( P <0.001). CONCLUSIONS: The prognostic value of classification using pStage and the pathological response was successfully validated using real-world data in Japan. This result would guide appropriate treatment for patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy followed by esophagectomy.