Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers.

BACKGROUND: Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact. METHODS: Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model. RESULTS: In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare. CONCLUSIONS: F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.

Body Composition and Clinical Outcomes in Esophageal Cancer Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Obesity is associated with increased mortality in various cancers, but the relationship between obesity and clinical outcomes in unresectable or recurrent esophageal cancer who receive immune checkpoint inhibitors (ICIs) remains unknown. This study investigated the association between body composition and clinical outcomes in patients with unresectable or recurrent esophageal cancer who received ICIs. METHODS: Utilizing an unbiased database of 111 unresectable or recurrent esophageal cancers, we evaluated the relationships between body composition (body mass index, waist circumference, psoas major muscle volume, and subcutaneous and visceral fat areas) at the initiation of ICI treatment and clinical outcomes including the disease control rate and progression-free survival (PFS). RESULTS: Waist circumference was significantly associated with the disease control rate at the first assessment (P = 0.0008). A high waist circumference was significantly associated with favorable PFS in patients treated with nivolumab. In an univariable model, for 5-cm increase of waist circumference in the outcome category of PFS, univariable hazard ratio (HR) was 0.73 (95% confidence interval [CI], 0.61-0.87; P = 0.0002). A multivariable model controlling for potential confounders yielded a similar finding (multivariable HR, 0.56; 95% CI, 0.33-0.94; P = 0.027). We observed the similar finding in esophageal cancer patients treated with pembrolizumab+CDDP+5-FU (P = 0.048). In addition, waist circumference was significantly associated with the prognostic nutritional index (P = 0.0073). CONCLUSIONS: A high waist circumference was associated with favorable clinical outcomes in ICI-treated patients with unresectable or recurrent esophageal cancer, providing a platform for further investigations on the relationships among body composition, nutrition, and the immune status.

Laparoscopic versus open abdominal lymph node dissection for esophageal squamous cell carcinoma: a propensity score matching analysis.

PURPOSE: To compare the short- and long-term outcomes of laparoscopic and open abdominal lymph node dissection using propensity score matching (PSM) analysis. METHODS: The subjects of this retrospective analysis were 459 patients who underwent curative resection for esophageal squamous cell carcinoma (ESCC) between May, 2005 and December, 2019, at our hospital. Patients were divided into two groups: the Laparoscopic (Lap group) and the Open (Open group). Post-PSM, 139 patients from each group were selected for the analysis to compare the short- and long-term outcomes between the groups. RESULTS: The Lap group experienced fewer Clavien-Dindo (CD) Grade ≥ 2 complications (28.1% vs. 40.3%, P = 0.04) and lower rates of abdominal surgical site infections (SSI) (2.9% vs. 7.9%, P = 0.02) than the Open group. The number of lymph nodes harvested was similar in the Lap and Open groups (14.8 ± 7.5 vs. 15.7 ± 8.6, P = 0.34). There was no significant difference in 3-year overall survival rates (81.2% vs. 69.5%, P = 0.12) or relapse-free survival rates (61.1% vs. 58.2%, P = 0.54) between the groups. CONCLUSIONS: Laparoscopic abdominal lymph node dissection for ESCC can be performed safely and appears to be beneficial.

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.

C-Reactive Protein Levels After Esophagectomy are Associated with Increased Surgical Complications and Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear. METHOD: We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8. RESULTS: The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade >2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade >2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p < 0.001). Moreover, high day 7/8 CRP levels (>3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008). CONCLUSION: Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Frailty Assessed by the Clinical Frailty Scale is Associated with Prognosis After Esophagectomy.

BACKGROUND: The Clinical Frailty Scale (CFS) is a simple and validated tool for assessing frailty, and higher CFS scores are correlated with worse perioperative outcomes after cardiovascular surgery. However, the relationship between the CFS scores and postoperative outcomes after esophagectomy remain unclear. METHODS: We retrospectively analyzed data from 561 patients with esophageal cancer (EC) who underwent resection from August 2010 to August 2020. We defined a CFS score of ≥4 as indicative of frailty; thus, patients were classified into frail patients (CFS scores of ≥4) and non-frail patients (CFS scores of ≤3). The Kaplan-Meier method was used to describe the overall survival (OS) distributions with the log-rank test. RESULTS: Of the 561 patients, 90 (16%) had frailty and 471 (84%) did not. Frail patients had a significantly older age, lower body mass index, higher American Society of Anesthesiologists physical status classification, and greater cancer progression than non-frail patients. The 5-year survival rate was 68% in non-frail patients and 52% in frail patients. OS was significantly shorter in frail than non-frail patients (p = 0.017 by log-rank test). In particular, OS was significantly shorter in frail patients with clinical stage I-II EC (p = 0.0024 by log-rank test) but was not correlated with frailty in patients with clinical stage III-IV EC (p = 0.87 by log-rank test). CONCLUSIONS: Preoperative frailty was associated with shorter OS after resection of EC. The CFS score may be a prognostic biomarker for patients with EC, especially early-stage EC.

Postoperative respiratory morbidity can adversely affect prognosis in thoracoscopic esophagectomy for esophageal cancer: a retrospective study.

BACKGROUND: Esophagectomy for esophageal cancer is associated with frequent respiratory morbidities, which may deteriorate postoperative survival outcomes. Thoracoscopic esophagectomy (TE) is less invasive and is associated with fewer respiratory morbidities than open esophagectomy. However, the relationship between post-TE respiratory morbidity and prognosis has not been well established. METHODS: This study included 378 patients who underwent TE for esophageal cancer between May 2011 and November 2020. Patients were divided into two groups based on the presence of respiratory morbidity. Short-term and long-term outcomes of the groups were retrospectively compared. RESULTS: Respiratory morbidity was significantly associated with heavy past smoking habits (Brinkman index, p = 0.0039), short duration of smoking cessation (p = 0.0012), worse American Society of Anesthesiologists physical status (p = 0.016), frequent cardiovascular comorbidities (p = 0.0085), and long hospital stay (p < 0.001). Respiratory morbidity significantly deteriorated overall survival (OS) (p = 0.011) and relapse-free survival (p = 0.062) and could be an independent prognostic factor for OS (hazard ratio = 1.90, 95% confidence interval = 1.093-3.311, p = 0.023) along with clinical stage. CONCLUSION: Respiratory morbidity can adversely affect prognosis after TE. Various prophylaxes for respiratory morbidity are required to improve the short-term and long-term outcomes of TE for esophageal cancer.

Textbook outcome contributes to long-term prognosis in older adults with gastric cancer.

PURPOSE: Textbook outcome (TO) is a composite quality measurement of short-term outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative gastric cancer (GC) surgery in older adults. METHODS: We retrospectively analyzed 492 consecutive patients who underwent curative gastrectomy for GC from 2005 to 2017. Among these, 141 advanced-age patients were eligible. The patients were divided into two groups: those who achieved TO (a-TO group) and those who failed to achieve TO (f-TO group). In accordance with previous reports, TO consisted of eight metrics. We evaluated the association between TO and long-term survival. RESULTS: TO was achieved 73 (52%) patients. The patients in the f-TO group had a significantly higher body mass index (P = 0.01), longer surgery time (P = 0.03), and more blood loss (P = 0.001). The metric with the lowest achievement rate was "no postoperative severe complication." The patients in the f-TO group had significantly shorter overall survival than those in the a-TO group (P = 0.03). Multivariable Cox regression analyses of overall survival revealed that an American Society of Anesthesiologists physical status classification of 3 (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.79-5.98; P < 0.0001) and f-TO (HR, 1.92; 95% CI, 1.09-3.39; P = 0.02) were significantly associated with poor overall survival. CONCLUSION: TO can be used to predict outcomes after curative GC surgery in patients of advanced age.

Relationship between gut microbiome Fusobacterium nucleatum and LINE-1 methylation level in esophageal cancer.

BACKGROUND: We previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer. METHODS: We qualified the F. nucleatum DNA using a quantitative PCR assay and LINE-1 methylation via a pyrosequencing assay using formalin-fixed paraffin-embedded specimens from 306 esophageal cancer patients. RESULTS: Intratumoral F. nucleatum DNA was detected in 65 cases (21.2%). The LINE-1 methylation scores ranged from 26.9 to 91.8 (median = 64.8) in tumors. F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P < 0.0001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.71 for F. nucleatum positivity. Finally, we found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (P for interaction = 0.34). CONCLUSIONS: F. nucleatum alters genome-wide methylation levels in cancer cells, which may be one of the mechanisms by which F. nucleatum affects the malignant behavior of esophageal cancer.

PD-L1 and PD-L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma.

Immune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD-L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD-L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD-L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD-L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD-L1/L2 expression and PD-L1/L2-related pathways in vitro. We also examined PD-L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD-L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD-L2 expression showed no significant difference between patient groups. Cisplatin increased PD-L1 expression in cancer cell lines in vitro, but decreased PD-L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD-L1 and PD-L2 expression. PD-L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD-L1/L2 expression may be altered by preoperative chemotherapy, and PD-L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one-time evaluation is not sufficient to evaluate PD-L1/L2 expression as a biomarker in esophageal cancer.

Distribution of Residual Disease and Recurrence Patterns in Pathological Responders After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to elucidate the residual disease distribution and recurrence patterns in patients with ESCC responding to NAC. SUMMARY BACKGROUND DATA: To appropriately plan a prospective trial for the organ preservation approach which includes additional chemoradiotherapy in patients who responded to NAC, the distribution of residual disease needs to be elucidated. Given that the residual tumor is located in the regional field, chemoradiotherapy can be safely added to eliminate the residual disease. METHODS: Overall, 483 patients with resectable ESCC who received NAC followed by transthoracic esophagectomy at 2 high-volume centers were reviewed. The recurrence-free survival, overall survival (OS), and residual and recurrent tumor patterns were compared among the pathological responses. RESULTS: Compared with nonpathological responders, pathological responders exhibited significantly longer recurrence-free survival [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.25 ( P < 0.001)/0.17 ( P < 0.001)/0.16 ( P = 0.003)] and OS [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.26 ( P < 0.001)/0.12 ( P < 0.001)/0.11 ( P = 0.003)]. In terms of the distribution of recurrence, the percentages of solitary recurrence in the regional field out of all recurrence was significantly higher in patients with Grade 1b (60%)/2 (67%)/3 (67%) whereas less than 25% in Grade 0 or 1a. CONCLUSIONS: It was found that postoperative recurrence in responders occurred in the regional field mostly as a solitary lesion without the distant failure, indicating that the residual tumor cells can be eliminated by additional chemoradiotherapy.

Clinical Significance of Pretreatment Red Blood Cell Distribution Width as a Predictive Marker for Postoperative Morbidity After Esophagectomy for Esophageal Cancer: A Retrospective Study.

BACKGROUND: Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. METHODS: This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. RESULTS: Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien-Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707-8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552-12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). CONCLUSIONS: Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.

Treatment strategies and outcomes for elderly patients with locally advanced squamous cell carcinoma of the esophagus.

PURPOSE: A multidisciplinary treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) is required to achieve prolonged survival. We aimed to clarify the differences in treatment strategies for locally advanced ESCC and the outcomes of elderly (aged ≥ 75 years) vs. younger patients (aged < 75 years). METHODS: We compared the treatment strategy selection and the outcomes of 40 elderly and 160 younger patients with cStage II/III ESCC diagnosed between January, 2014 and December, 2016. RESULTS: Nineteen (47.5%) of the elderly patients and 144 (90.0%) of the younger patients underwent esophagectomy and 9 (22.5%) of the elderly patients and 131 (81.9%) of the younger patients received neoadjuvant chemotherapy. Ivor-Lewis or transhiatal esophagectomy was performed more frequently in the elderly group than in the younger group (P = 0.0096). The survival rate after esophagectomy was higher in the younger group than in the elderly group. The overall survival rate of the elderly patients who underwent esophagectomy was significantly higher than that in those who did not. CONCLUSIONS: Esophagectomy is a practical choice for elderly patients with locally advanced ESCC, although reduced treatment intensity may impact long-term survival.

Immunogenic characteristics of microsatellite instability-low esophagogastric junction adenocarcinoma based on clinicopathological, molecular, immunological and survival analyses.

Microsatellite instability (MSI) is categorized by mutation frequency: high MSI (MSI-H), low MSI (MSI-L) and microsatellite stable (MSS). MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-PCR assays (BAT25, BAT26, BAT40, D2S123, D5S346 and D17S250) were performed on 363 Epstein-Barr virus-negative, surgically resected esophagogastric junction (EGJ) adenocarcinoma samples. Tumors were characterized as MSI-H (≥2 markers), MSI-L (1 marker) or MSS (0 markers). CD8+ cell counts, PD-L1 and HER2 expression levels, TP53 mutations, epigenetic alterations and prognostic significance were also examined. All pathological and molecular experiments were conducted using serial, whole-tumor sections of chemo-naïve surgical specimens. MSI-H and MSI-L were assigned to 28 (7.7%) and 24 (6.6%) cases, respectively. Compared to MSS cases, MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82; P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.

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

PURPOSE: Risk stratification to select appropriate candidates for adjuvant therapy is required for esophageal cancer patients based on adjuvant therapy advancement including immunotherapy. The current study aims to develop a novel staging system using pathological stage (pStage) and response to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC). METHODS: ESCC patients who received NAC and underwent transthoracic esophagectomy at two Japanese high-volume esophageal centers were retrospectively reviewed. The prognostic value of NAC response was evaluated within the same pStage, and a novel risk stratification to predict cancer-specific survival (CSS) was developed. RESULTS: The HR (95% CI) of pathological responders in pStage 0-I, II, III, and IV was 0.29 (0.07-1.17), 0.37 (0.12-1.10), 0.37 (0.15-0.92), and 0.24 (0.06-0.98), respectively. Responders in pStage 0-II were classified to be in the same class and those in pStage III/IV in another group, because the 5-year CSS (5y-CSS) rate of responders in pStage 0-I, II, III, and IV was 94%, 92%, 76%, and 71%, respectively. Combining nonresponders in pStage 0-II as the same group, all patients were subdivided into five groups. Intriguingly, the 5y-CSS in pStage III-IV responders was 75%, almost identical to that of nonresponders in pStage 0-II (78%). CONCLUSIONS: The histological response influenced the long-term outcomes of patients who underwent esophagectomy after NAC, even within groups stratified by pathologic stage. The current risk stratification system will contribute to selecting appropriate candidates for adjuvant therapy.

Successful transition from open to minimally invasive approach in Ivor Lewis esophagectomy: a single-center experience in Japan.

PURPOSE: This study evaluates surgical outcomes of Ivor Lewis esophagectomy (ILE) in our institution, with the transition from open ILE to hybrid or totally minimally invasive ILE (MI-ILE). METHODS: Selected patients who underwent ILE for esophageal cancer between 2013 and 2020 were included. We retrospectively investigated the patients' background characteristics and the short-term surgical outcomes. RESULTS: In this period, among a total of 858 esophagectomies, selected seventy-one patients (8.3%) underwent ILE, consisted of 17 cases with completely open procedures, 27 with hybrid MI-ILE, and 27 with total MI-ILE. The major indications for ILE were adenocarcinoma of the distal esophagus or esophagogastric junction (33.8%) and patients with prior treatment of head and neck cancer (31.0%). Among these approaches, there were no significant differences in the characteristics including age, body mass index (BMI), tumor location, preoperative therapy, and clinical TNM stage, except for histology. Compared to the completely open and hybrid groups, incidences of both total and severe complications in the total MI-ILE group were significantly lower (total 70.6 vs. 66.6 vs. 37.0%, p=0.036; severe 35.3 vs. 44.4 vs. 11.1%, p=0.023), and also, those of pneumonia (41.2 vs. 29.6 vs. 7.4%, p=0.026) and postoperative stricture (11.8 vs. 18.5 vs. 0%, p=0.001) were significantly fewer in the total MI-ILE group. CONCLUSIONS: We have been able to achieve the transition from completely open to total MI-ILE with better short-term outcomes. Total MI-ILE with linear-stapled anastomosis can be a good alternative to open procedures for the selected patients with reducing the incidence of postoperative pneumonia and anastomotic stricture.

Significance of D-dimer-based screening for detecting pre-operative venous thromboembolism in patients with esophageal cancer after neoadjuvant chemotherapy.

BACKGROUND: A limited number of studies have evaluated the risk of developing venous thromboembolism (VTE) during neoadjuvant chemotherapy (NAC) for esophageal cancer and the efficacy of a D-dimer (DD)-based VTE screening (DBS). In the present study, we aimed to clarify the changes in DD levels and the effectiveness of DBS. METHODS: We included 234 patients who underwent esophagectomy between August 2017 and July 2019 and evaluated the changes in DD levels before and after NAC. We had introduced the DBS strategy in August 2018, in which we recommended ultrasound (US) of the leg or computed tomography (CT) with the deep vein thrombosis (DVT) protocol. We then evaluated the incidence of VTE detected by DBS compared with that in the clinical practice as a control. RESULTS: The DD levels were significantly increased after NAC. After the introduction of DBS, the proportion of patients who underwent US and CT after NAC was significantly increased. VTE was more frequently detected in the DBS group than in the control group (16.7% vs. 3.0%, p < 0.02) among patients who underwent NAC. Pulmonary embolism (PE) during NAC was also more frequent in the DBS than in the control group (7.6% vs. 1.5%, p = 0.06). The DD levels after NAC were significantly higher in patients with VTE than in those without. CONCLUSIONS: NAC for patients with esophageal cancer increases the risk of developing VTE. DBS is useful in identifying asymptomatic DVT and may contribute to improving patient safety.

Comparison of the outcomes between total eversion and conventional triangulating stapling technique in cervical esophagogastric anastomosis after esophagectomy: a propensity score-matched analysis.

BACKGROUND: Anastomotic leakage and stenosis remain major problems after esophageal reconstruction. This study evaluated the clinical outcomes between the total eversion (TE) triangulating stapling technique (TST) and conventional (C) TST. METHODS: The study included 404 consecutive patients with esophageal cancer who underwent cervical esophagogastrostomy by TST between January 2013 and December 2018. The postoperative outcomes were compared between TE-TST and C-TST using propensity score-matched analysis. RESULTS: Before matching, the cT stage and the cTNM stage were different between the groups. After matching, each group consisted of 128 patients. The patients' background characteristics were similar between the groups. Although the incidence of anastomotic leakage was similar between the groups (p = 0.216), anastomotic stricture occurred in 19 (14.8%) and 7 (5.5%) patients in the C-TST and the TE-TST groups, respectively (p = 0.021). CONCLUSIONS: The incidence of anastomotic stenosis was significantly lower in the TE-TST group than in the C-TST group. TE-TST decreases the incidence of anastomotic stricture and can improve the quality of life in patients undergoing esophagectomy.

Efficacy of postoperative radiotherapy in esophageal squamous cell carcinoma patients with positive circumferential resection margin.

BACKGROUND: The significance of postoperative radiotherapy for residual disease after esophageal cancer surgery remains controversial. The purpose of this study was to elucidate the efficacy of postoperative radiotherapy in esophageal squamous cell carcinoma (ESCC) patients with positive circumferential resection margin (CRM). METHODS: We retrospectively analyzed data from 1190 patients who underwent esophagectomy for ESCC at our hospital from 2005 to 2018, of whom 61 (5.1%) patients were diagnosed with positive CRM of ESCC. Overall survival (OS), progression-specific survival (PSS), local progression-specific survival (LPSS), and clinicopathological factors were compared between patients with and without postoperative radiotherapy. The efficacy of additional radiotherapy on patient outcomes was evaluated. RESULTS: Among the 61 patients analyzed, 29 (47.5%) underwent radiotherapy (RT group) and 32 (52.5%) did not (NRT group). In the RT group, 22 patients (75.9%) received radiotherapy and 7 patients (24.1%) received chemoradiotherapy. The RT group included younger patients, a greater number of upper-esophageal tumors, and a greater rate of R2 resections than the NRT group. The LPSS and PSS of the RT group were significantly better than those of the NRT group (P = 0.007, P < 0.001, respectively). In multivariate analysis, postoperative radiotherapy was an independent factor for LPSS [P < 0.001; hazard ratio (HR) 0.17; 95% confidence interval (CI) 0.06-0.46] and PSS (P < 0.001; HR 0.31; 95% CI 0.16-0.60). CONCLUSIONS: Postoperative radiotherapy contributed to the control of residual tumor and was significantly associated with better LPSS and PSS among patients with positive CRM after esophagectomy for ESCC.

Influence of Preoperative Oropharyngeal Microflora on the Occurrence of Postoperative Pneumonia and Survival in Patients Undergoing Esophagectomy for Esophageal Cancer.

OBJECTIVE: The aim of this study was to clarify the correlation between oropharyngeal microflora and postoperative complications as well as long-term survival after esophagectomy. BACKGROUND: Although the oral cavity is known to be a potential reservoir for pathogens, the influence of abnormal oropharyngeal microflora on the outcomes of patients undergoing esophagectomy remains unknown. METHODS: This study included 675 patients who underwent esophagectomy between 2007 and 2014. Saliva samples from the oropharynx were collected 2 days before the operation. There were 442 patients with indigenous flora (Ind group) and 233 with allopatric flora. Among the patients with allopatric flora, 140 had antibiotic-sensitive microbes only (Allo-S group) while 93 had different types of antibiotic-resistant microbes (Allo-R group). We investigated the correlation between the types of oropharyngeal microflora and the incidence of postoperative complications as well as long-term outcomes. RESULTS: Sixteen microbes could be cultivated from the saliva samples. The incidence of postoperative pneumonia in the Allo-S and Allo-R groups was significantly higher than in the Ind group (P < 0.001). In addition, acute respiratory distress syndrome was more often observed in the Allo-R group than in the other groups (P = 0.002). A significantly higher rate of antibiotic use and longer hospital stays were observed in the Allo-R group compared with the Ind group. Multivariate logistic regression analysis revealed that the presence of allopatric antibiotic-resistant microbes in the oropharynx was an independent risk factor for postoperative pneumonia (odds ratio, 3.93; 95% confidence interval, 2.41-6.42). The overall survival was significantly poorer in the Allo-R group than in the other groups. CONCLUSIONS: Preoperative oropharyngeal culture is a simple and low-cost method that can predict both the occurrence of postoperative pneumonia and poor prognosis after esophagectomy.