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.

Effect of Perioperative Inhaled Tiotropium for patients with chronic Obstructive Pulmonary disease in Esophageal cancer surgery (EPITOPE): an open-label, randomized, parallel-group pilot study.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a risk factor for pneumonia following esophagectomy. This study aimed to investigate the efficacy of perioperative inhaled tiotropium in patients with COPD undergoing esophagectomy. METHODS: This open-label, randomized controlled trial randomly assigned 32 patients with COPD undergoing esophagectomy to conventional management or addition of tiotropium inhalation. The intervention group received tiotropium from two weeks before esophagectomy until the final evaluation one month after esophagectomy. The primary outcome was the incidence of pneumonia within 30 postoperative days. We also assessed the changes and the percentages from baseline in pulmonary function and walking distance of the incremental shuttle walking test to just before esophagectomy and final evaluation. RESULTS: Enrolled patients were randomly assigned to the control group (n = 18) and the intervention group (n = 14). Pneumonia was recorded in 4 (28.6%) and 5 (27.8%) patients in the intervention and control groups, respectively (risk difference: 0.8%, 95% confidence interval: - 30.6 to 32.2). The intervention group demonstrated a significant improvement in pulmonary function and walking distance preoperatively. Further, the pulmonary function test was significantly better preoperatively in the intervention group than in the control group. Postoperatively, pulmonary function deterioration was more significant in the control group than in the intervention group. CONCLUSIONS: Preoperative tiotropium inhalation significantly improved pulmonary function and exercise tolerance in patients with COPD undergoing esophagectomy. The perioperative tiotropium did not reduce pneumonia after esophagectomy, but it may contribute to patient recovery by reducing postoperative pulmonary function deterioration.

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.

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.

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.

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.

Identification of the factor affecting learning curves of laparoscopic gastrectomy through the experience at a Japanese high-volume center over the last decade.

Background: Though laparoscopic gastrectomy (LG) has become the gold standard for gastric cancer treatment according to the Japanese treatment guidelines, its learning curve remains steep. Decreasing numbers of surgeons and transitions in the work environment have changed LG training recently. We analyzed LG training over the last decade to identify factors affecting the learning curve. Study Design: Laparoscopic distal and pylorus-preserving gastrectomies conducted between 2010 and 2020 were included. We assessed learning curves based on the standard operation time (SOT) defined by analysis of covariance. Then we divided the trainees into two groups based on the length of the learning curve and examined the factors affecting the learning curve with linear regression analysis. Results: Among 2335 LGs, 960 cases treated by 27 trainees and 1301 cases treated by six attending surgeons were analyzed. The operation time was prolonged (p = 0.009) and postoperative morbidity rates were lower (p = 0.0003) for cases treated by trainees. Trainees experienced 38 (range, 9-81) cases as scopists and nine (range, 0-41) cases as first assistants to the first operator. The learning curve was approximately 30 cases. The SOT was calculated based on gender, body mass index, tumor location, reconstruction, and lymph node dissection. Trainees who had shorter learning curves had more experience (51-100 cases) with any laparoscopic surgery before LG training than the others (11-50 cases, p = 0.017). Conclusion: Sufficient experience with laparoscopic surgery before starting LG training might contribute to the efficiency of LG training and shorten the learning curve.

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.

Fully robotic side-to-side stapled anastomosis provides less anastomotic leakage than conventional minimally invasive approach in Ivor Lewis esophagectomy.

INTRODUCTION: This study evaluates surgical outcomes of minimally invasive Ivor Lewis esophagectomy (ILE) for esophageal and esophagogastric cancer, with the comparison of the robotic approach (RA) and the conventional minimally invasive approach (CA). METHODS: Selected patients who underwent minimally invasive ILE for esophageal cancer were included between January 2017 and December 2023. We retrospectively investigated the patients' background characteristics and the short-term surgical outcomes. RESULTS: In this period, among a total of 840 esophagectomies, 81 patients (9.6%) underwent minimally invasive ILE, consisting of 24 cases with RA and 57 with CA. The major indications for ILE were adenocarcinoma of the distal esophagus or esophagogastric junction and patients with prior head and neck cancer treatment. Among these thoracic approaches, there were no significant differences in the patients' indications and characteristics, including age, histology, tumor location, clinical TNM stage, and preoperative therapy. Compared with the CA group, no anastomotic leakage was observed in the RA group (17.5% vs. 0, p = .035). Rates of total postoperative complications and length of hospital stay also tended to be reduced in the RA group but did not reach significance. CONCLUSION: In the Ivor Lewis esophagectomy with a side-to-side linear-stapled anastomosis, the fully robotic approach has the potential to powerfully reduce anastomotic leakage compared to the conventional minimally invasive approach.

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.

Accelerated Iron Corrosion by Microbial Consortia Enriched from Slime-like Precipitates from a Corroded Metal Apparatus Deployed in a Deep-sea Hydrothermal System.

Microbiologically influenced corrosion refers to the corrosion of metal materials caused or promoted by microorganisms. Although some novel iron-corrosive microorganisms have been discovered in various manmade and natural freshwater and seawater environments, microbiologically influenced corrosion in the deep sea has not been investigated in detail. In the present study, we collected slime-like precipitates composed of corrosion products and microbial communities from a geochemical reactor set on an artificial hydrothermal vent for 14.5 months, and conducted culture-dependent and -independent microbial community ana-lyses with corrosive activity measurements. After enrichment cultivation at 37, 50, and 70°C with zero-valent iron particles, some of the microbial consortia showed accelerated iron dissolution, which was approximately 10- to 50-fold higher than that of the abiotic control. In a comparative ana-lysis based on the corrosion acceleration ratio and amplicon sequencing of the 16S rRNA gene, three types of corrosion were estimated: the methanogen-induced type, methanogen-sulfate-reducing bacteria cooperative type, and sulfate-reducing Firmicutes-induced type. The methanogen-induced and methanogen-sulfate-reducing bacteria cooperative types were observed at 50°C, while the sulfate-reducing Firmicutes-induced type was noted at 37°C. The present results suggest the microbial components associated with microbiologically influenced corrosion in deep-sea hydrothermal systems, providing important insights for the development of future deep-sea resources with metal infrastructures.

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.

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.

Hypersensitivity pneumonitis with Paecilomyces as suspected inciting antigen.

A 73-year-old man visited our hospital for persistent cough. Chest high-resolution CT (HRCT) showed infiltration shadows in lower lobes and diffuse ground glass opacities in the upper lobes. Blood tests showed elevated white blood cell, C-reactive protein, surfactant protein D, and Krebs von den Lungen-6 levels. After an antigen avoidance test, his HRCT and blood test findings improved; we diagnosed him with hypersensitivity pneumonitis (HP). A culture of the rotting interior walls within his home revealed Paecilomyces, which we believe caused his HP. Given the few patients with Paecilomyces-induced HP, systematic approach was important to identify the inciting antigen.

KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia.

Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRASG12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.

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.