Safety of robotic double-flap technique following proximal gastrectomy in the introductory phase compared with laparoscopic procedure: a propensity score-matched analysis.

BACKGROUND: Proximal gastrectomy (PG) is recommended for upper-third gastric cancer and esophagogastric junction (EGJ) cancer, preserving organ function while reducing postoperative symptoms. The double-flap technique (DFT) is one approach to minimize reflux after PG. However, laparoscopic PG with DFT (LPG-DFT) has drawbacks of increased complexity, such as hand sutures for anastomosis. Robotic surgery offers potential advantages for DFT reconstruction, but the safety of robotic DFT following PG (RPG-DFT) in the introductory phase is unknown. METHODS: This retrospective study compared the outcomes of RPG-DFT with LPG-DFT. Data from 402 patients (321 LPG-DFT, 81 RPG-DFT) between 2009 and 2023 were analyzed. Propensity score matching balanced patient demographics and tumor characteristics. Surgical parameters, complications, and long-term outcomes were assessed. RESULTS: The surgery time of LPG-DFT has stabilized in patients since 2016. Thus, LPG-DFT from 2016 was defined as a stable procedure. RPG-DFT was started in 2019, after minimally invasive DFT reconstruction had been mastered at our center. Therefore, we compared the surgical outcomes of introductory RPG-DFT with stable LPG-DFT. Matched analysis revealed that RPG-DFT in the introductory phase had significantly longer surgery times but less bleeding and shorter reconstruction times and hospital stays than stable LPG-DFT. Frequencies of short-term complications and reflux esophagitis were comparable in both groups. Although RPG-DFT in the introductory phase exhibited higher incidence of anastomotic stenosis than stable LPG-DFT, the incidence of anastomotic stenosis decreased over time. CONCLUSIONS: This study demonstrated the safety of RPG-DFT in the introductory phase for EGJ and upper-third stomach tumors, with outcomes comparable to stable LPG-DFT. RPG-DFT offers shorter reconstruction time and less blood loss compared with LPG-DFT. However, anastomotic stenosis is a complication to monitor in early robotic surgery.

Endoscopic Evaluation of Pathological Complete Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy-Multicenter Retrospective Study from Four Japanese Esophageal Centers.

BACKGROUND: Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. METHODS: This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. RESULTS: The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists' median of these was 43%, 90%, 85%, 65%, and 66%, respectively. CONCLUSIONS: This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.

Evaluation of Endoscopic Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy.

BACKGROUND: We previously reported that endoscopic response evaluation can preoperatively predict the prognosis and distribution of residual tumors after neoadjuvant chemotherapy (NAC). In this study, we developed artificial intelligence (AI)-guided endoscopic response evaluation using a deep neural network to discriminate endoscopic responders (ERs) in patients with esophageal squamous cell carcinoma (ESCC) after NAC. METHOD: Surgically resectable ESCC patients who underwent esophagectomy following NAC were retrospectively analyzed in this study. Endoscopic images of the tumors were analyzed using a deep neural network. The model was validated with a test data set using 10 newly collected ERs and 10 newly collected non-ER images. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the endoscopic response evaluation by AI and endoscopists were calculated and compared. RESULTS: Of 193 patients, 40 (21%) were diagnosed as ERs. The median sensitivity, specificity, PPV, and NPV values for ER detection in 10 models were 60%, 100%, 100%, and 71%, respectively. Similarly, the median values by the endoscopist were 80%, 80%, 81%, and 81%, respectively. CONCLUSION: This proof-of-concept study using a deep learning algorithm demonstrated that the constructed AI-guided endoscopic response evaluation after NAC could identify ER with high specificity and PPV. It would appropriately guide an individualized treatment strategy that includes an organ preservation approach in ESCC patients.

Comparison of hand-sewn and circular stapled esophagogastric anastomoses in the neck after esophagectomy for thoracic esophageal cancer: a propensity score-matched analysis.

Esophagectomy is a highly invasive surgical procedure; however, anastomotic leakage is one of the major surgical complications that should be prevented. Institutions have their own inherited or specialized anastomosis methods. The superior anastomosis procedure remains unknown despite the many studies to determine the optimal method. The present study enrolled 341 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2009 and January 2019. The anastomosis method was changed from circular stapled anastomosis to hand-sewn anastomosis in February 2014 to reduce the risk of anastomotic leakage. We retrospectively compared short-term results (anastomotic leakage and stricture) between hand-sewn and circular stapled anastomoses. Analysis of heterogeneity after propensity score matching between the 107 patients in the hand-sewn anastomosis group and 107 patients in the circular stapled anastomosis group revealed almost equal distributions. The incidence rate of anastomotic leakage was significantly lower in the hand-sewn anastomosis group than in the circular stapled anastomosis group (9 vs. 20%, hazard ratio: 2.521; 95% confidence interval: 1.112-5.716; P = 0.027). No significant difference was found in the incidence of anastomotic stricture (16 vs. 18%, P = 0.844). Furthermore, no significant difference was found in the incidence of anastomotic leakage in any of the tumor locations between the two anastomosis procedures. For esophagogastric anastomosis in the neck after esophagectomy, hand-sewn anastomosis is superior to circular stapled anastomosis with regard to reducing the risk of anastomotic leakage.

Effect of Postoperative Oral Intake Status on Sarcopenia Six Months After Esophageal Cancer Surgery.

PURPOSE: In patients with esophageal cancer, skeletal muscle mass has been reported to decrease progressively after surgery and be independently associated with a poor prognosis. The purpose of this study was to investigate perioperative changes in dysphagia, oral intake status, and nutritional status and identify factors related to sarcopenia 6 months after esophagectomy. METHODS: A total of 134 patients who underwent radical resection for thoracic esophageal cancer between March 2016 and July 2019 were analyzed retrospectively. The diagnosis of sarcopenia was made by CT taken 6 months postoperatively using the cut-off criteria of skeletal muscle index (SMI) < 52.4 cm2/m2 for male and SMI < 38.5 cm2/m2 for female patients. As factors related to postoperative sarcopenia, dysphagia, oral intake status, nutritional status, and physical function were extracted from the medical records. Multivariate logistic regression analysis was performed to identify perioperative risk factors related to sarcopenia 6 months after surgery. RESULTS: Of the 134 patients, 34.3% were judged to be unable to start oral intake on swallowing assessment. At discharge, 30.6% received tube feeding with or without oral intake. In the non-oral intake group on swallowing assessment, a significantly higher proportion of patients received tube feeding at discharge (p = 0.014). Preoperative BMI, postoperative handgrip strength, and tube feeding at discharge were independent risk factors for sarcopenia 6 months after esophagectomy in male patients. CONCLUSION: Tube feeding at discharge is significantly related to postoperative sarcopenia in patients with esophageal cancer. Identifying high-risk groups might allow early detection of malnutrition and provision of appropriate care.

Clinical predictors of early postoperative recurrence after radical esophagectomy for thoracic esophageal cancer.

PURPOSE: Esophagectomy for esophageal cancer has a high incidence rate of early postoperative recurrence and death. This study aimed to identify the clinical and pathological features in early recurrence cases and to confirm the usefulness of prediction using these factors for effective adjuvant therapy and postoperative surveillance. METHODS: One hundred and twenty five patients who developed postoperative recurrence after undergoing radical esophagectomy for thoracic esophageal cancer were classified into two groups as follows: those with early recurrence at ≤ 6 months and those with nonearly recurrence at > 6 months after surgery. After identifying related factors of early recurrence, usefulness of these factors for prediction were examined in all patients with and without recurrence. RESULTS: The analysis cohort consisted of 43 and 82 patients in the early and nonearly recurrence groups, respectively. In multivariate analysis, factors associated with early recurrence were higher initial levels of tumor markers (squamous cell carcinoma [SCC] ≥ 1.5 ng/ml in tumors, except for adenocarcinoma, and carcinoembryonic antigen [CEA] ≥ 5.0 ng/ml in adenocarcinoma) and higher venous invasion (v), i.e., ≥ 2 (p = 0.040 and p = 0.004, respectively). The usefulness of these two factors for recurrence prediction was confirmed in 378 patients, including 253 patients without recurrence. Patients with at least one of the two factors had significantly higher early recurrence rates than those without any factors in pStages II and III (odds ratio [OR], 6.333; p = 0016 and OR, 4.346; p = 0.008, respectively). CONCLUSIONS: Early recurrence of thoracic esophageal cancer (i.e., during ≤ 6 months after esophagectomy) was associated with higher initial tumor marker levels and pathological findings of v ≥ 2. The combination of these two factors is useful as a simple and critical predictor of early postoperative recurrence.

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.

Exposure to a Postoperative Hypercoagulable State Predicts Poor Prognosis After Transthoracic Esophagectomy in Patients with Esophageal Cancer.

PURPOSE: The contribution of postoperative coagulation-fibrinolysis status to prognosis is yet to be fully investigated. Thus, in this study, we aimed to elucidate the relationship between postoperative hypercoagulable state (PHS) after transthoracic esophagectomy and long-term outcome in patients with esophageal cancer. METHODS: Patients with esophageal cancer who underwent transthoracic esophagectomy were selected from a prospectively maintained database. Based on the trend of postoperative plasma fibrin-fibrinogen degradation product (FDP) levels, patients with PHS were identified. The prognostic significance of PHS was evaluated via multivariate analysis using the Cox regression model. RESULTS: Based on the plasma FDP levels of 172 patients that reached a plateau between POD5 and POD7, we calculated the mean FDP value of POD5, 6, and 7, setting a median value as a cutoff. Consequently, 87 patients were classified as PHS. The overall survival (OS) in the PHS group was determined to be significantly lower than in the non-PHS group (5-year OS; 68% and 80%, p = 0.012). Recurrence-free survival (RFS) in the PHS group was significantly lower than in the non-PHS group (5-year RFS; 60% and 79%, p = 0.017). Using the pathological stage as a covariate in the multivariate analysis, PHS was an independent prognostic factor of OS [hazard ratio (HR) 2.517, p = 0.009] and RFS (HR 1.905, p = 0.041). CONCLUSIONS: PHS was found to be an independent negative prognostic factor in patients with esophageal cancer. Possible improvement of the oncological outcome by early postoperative intervention with anticoagulants should be explored in clinical trials.

Elevation of the Prognostic Factor Plasma Fibrinogen Reflects the Immunosuppressive Tumor Microenvironment in Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Despite previous reports on the clinical significance of plasma fibrinogen (FNG) levels as a prognostic indicator of ESCC, its underlying mechanism remains unclear. This study aimed to validate the prognostic impact of plasma FNG levels and clarify its relationship with primary tumors in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The prognostic impact of FNG was evaluated in patients with ESCC who underwent esophagectomy between 2000 and 2019. The RNA sequencing of the primary ESCC site, which was from pre-operative biopsy, was performed, followed by immune profile characterization using an immunogram. Those profiles were assessed via the immunohistochemical staining of tumor-associated macrophages (TAMs) and clinical response to nivolumab. RESULTS: Multivariate analysis identified FNG as a significant prognostic factor in ESCC. The immunogram suggested an immunosuppressive tumor environment in the high-FNG group. Immunostaining with the TAM markers CD163 and CD204, revealed that the high-FNG group had significantly higher number of TAMs compared with the low-FNG group. The immunosuppressive characteristics were clinically validated in patients with metastatic ESCC; those who had elevated FNG levels showed poor response to nivolumab. CONCLUSION: This study successfully validated the prognostic impact of plasma FNG levels in an expanded cohort with ESCC. Accordingly, our findings showed that increased plasma FNG reflects an immunosuppressive tumor microenvironment that facilitates tumor progression and poor responses to nivolumab.

Clinical Significance of Endoscopic Response Evaluation to Predict the Distribution of Residual Tumor after Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

PURPOSE: To appropriately adopt the organ preservation approach, including subsequent chemoradiotherapy (CRT) in patients who respond to neoadjuvant chemotherapy (NAC), the distribution of residual disease, including pathological lymph nodes (LNs) and recurrence site, needs to be recognized preoperatively. This study was designed to evaluate whether endoscopic response evaluation can predict residual tumor distribution. METHODS: Patients with esophageal squamous cell carcinoma who underwent transthoracic esophagectomy (TTE) were retrospectively reviewed. Endoscopic responder (ER) to NAC was defined according to primary tumor endoscopic findings. Recurrence-free survival (RFS), overall survival (OS), and residual tumor patterns were compared between groups. RESULTS: Of 193 patients, 40 (20%) were classified as ER. ERs showed significantly better RFS and OS. The pN location was found within the primary tumor and cN field in 88% of ERs, which was significantly higher than non-ERs at 63% (p = 0.004). Furthermore, the postoperative recurrence incidence in the distant organ was significantly lower in the ERs than the non-ERs (8%, 32%, respectively, p = 0.002). Residual disease, including postoperative initial recurrence, existed within the same field as the primary tumor and cN in 88% of ERs, significantly higher than 42% in the non-ERs (p < 0.001). CONCLUSIONS: Endoscopic response evaluation can preoperatively predict distribution of residual tumors after NAC, which could help radiation field selection in subsequent definitive CRT when patients prefer to omit TTE. Along with improvements in NAC response rate, this could facilitate organ preservation in patients who respond to NAC.

Effects of let-7a microRNA and C-C chemokine receptor type 7 expression on cellular function and prognosis in esophageal squamous cell carcinoma.

BACKGROUND: C-C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression. METHODS: The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis. RESULTS: A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups. CONCLUSIONS: The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients. TRIAL REGISTRATION: Retrospectively registered.

A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001-2013).

BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

Role sharing between minimally invasive oesophagectomy and organ preservation approach for surgically resectable advanced oesophageal cancer.

Oesophageal cancer is a dismal disease since it metastasizes widely even from an early stage. In order to improve treatment outcomes, multidisciplinary treatments including surgery, chemotherapy and radiotherapy have been developed. While oesophagectomy is the mainstay in the treatment strategy, it is highly invasive since it requires two to three field approaches. To reduce surgical stress and morbidity, minimally invasive oesophagectomy including thoracoscopy, robotic assisted surgery and mediastinoscopy were introduced. Various clinical trials proved that these techniques decrease the post-operative morbidity rate. Furthermore, with the advancement of multidisciplinary treatment with a higher response rate, the possibility arose for omission of surgical resection in remarkable responders to neoadjuvant therapy. However, in order to safely provide organ preservation without increasing the risk of post-treatment recurrence, an accurate tumour monitoring system is required. Although endoscopy and computed tomography imaging have been a standard, the detection rate of residual tumours after treatment is still unsatisfactory. Utilizing liquid biopsy which could evaluate tumour derivative and host response, an appropriate monitoring system of tumour burden during multidisciplinary treatment can be developed. With the advancement of minimally invasive surgery and multidisciplinary treatment, the treatment strategy needs to be highly individualized based on the tumour biology, patients' condition and their preferences. Along with the improvement of the tumour monitoring system, appropriate role sharing can be achieved between a minimally invasive surgery and the organ preservation approach.

Clinical Features of Recurrence Pattern with Lung Metastasis After Radical Esophagectomy for Thoracic Esophageal Cancer.

BACKGROUND: One of the difficulties in the treatment of esophageal cancer surgery is the high rate of postoperative recurrence. After esophagectomy, distant metastatic recurrence frequently occurs in the lung. This study aimed to determine the clinical features of a recurrence pattern with lung metastasis. METHODS: The current study analyzed data from 138 patients who had postoperative recurrence of esophageal cancer after a radical esophagectomy. According to the recurrence pattern at the time of initial diagnosis, the patients were classified into two groups as follows: those with lung metastasis and those without. RESULTS: Twenty-three of the 138 investigated patients had a recurrence pattern with lung metastasis. Salvage surgery and postoperative pneumonia (p = 0.041 and 0.030, respectively) were identified as risk factors for recurrence pattern with lung metastasis in multivariate analysis. When we compared the sites of primary esophageal tumors, we found that the frequencies of distant metastases, such as lung and liver metastases, as well as pleural/peritoneal dissemination, were higher in the mid and distal esophageal tumors. Patients with a recurrence pattern showing lung metastasis alone had a better overall and post-recurrence survival than those with other recurrence patterns (p < 0.001 and p < 0.001). CONCLUSIONS: In patients who had postoperative recurrence after esophagectomy for thoracic esophageal cancer, salvage surgery, and postoperative pneumonia were significantly related to recurrence pattern with lung metastasis. Postoperative recurrence with lung metastasis alone had a better prognosis than other recurrence patterns; therefore, when pulmonary recurrence is suspected, performing intensive examinations for early diagnosis is critical.

Exploratory prospective study of the influence of radical esophagectomy on perioperative physical activity in patients with thoracic esophageal cancer.

Sarcopenia, which involves two important aspects, namely skeletal muscle loss and decreased physical function, was suggested as a poor prognostic factor in esophageal cancer surgery. The purpose of this study was to clarify the perioperative change in daily physical activity and propose effective preventive strategies. We prospectively enrolled patients with esophageal cancer who were scheduled to undergo radical esophagectomy. Their daily physical activities were recorded using an accelerometer before surgery, immediately after discharge, and 6 months after surgery. The relationships of physical activity level and the perioperative factors, especially skeletal muscle change, with the risk factors of low daily activity level were investigated. The data of 20/28 enrolled patients were analyzed. The mean activity level of the 20 patients decreased after discharge and subsequently recovered on postoperative month 6. The percentage of activity levels >1.5 metabolic equivalents/day after discharge significantly correlated to the change rate in total muscle cross-sectional area from baseline to POM 6 (r = 0.452, P = 0.045). In a stepwise multiple regression analysis, age, neoadjuvant chemotherapy, and anastomotic leakage were identified as negative associated factors of activity time at >1.5 metabolic equivalents at postoperative month 6. Activity level immediately after discharge was significantly associated with skeletal muscle loss at postoperative month 6 in patients with esophageal cancer who underwent esophagectomy. Elderly patients and patients who received neoadjuvant chemotherapy and had an anastomotic leakage might require intensive prevention. Prospective interventions aimed at increasing daily activity can prevent sarcopenia.

Preoperative maximum phonation time as a predictor of pneumonia in patients undergoing esophagectomy.

PURPOSE: Esophagectomy is a highly invasive procedure, associated with several postoperative complications including pneumonia, anastomotic leakage, and sepsis, which may result in multiorgan failure. Pneumonia is considered a major predictor of poor long-term prognosis, so its prevention is important for patients undergoing surgery for esophageal cancer. METHODS: The subjects of this study were 137 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January, 2012 and December, 2016. Patients who underwent R0 or R1 resection or esophagectomy with organ excision were included. Patients who underwent salvage surgery or resection of recurrent laryngeal nerve, and those with preoperative recurrent laryngeal nerve palsy, were excluded. We investigated the effect of the maximum phonation time on the development of postoperative pneumonia. RESULTS: Pneumonia developed more frequently in patients with a long operative time, clinically left recurrent nerve lymph node metastasis, and a short preoperative maximum phonation time (p = 0.074, 0.046, and 0.080, respectively). Pneumonia was also more common in men with an abnormal maximum phonation time (p = 0.010). CONCLUSIONS: The maximum phonation time is a significant predictor of postoperative pneumonia after esophagectomy in men.

Neutrophil-to-lymphocyte ratio change predicts histological response to and oncological outcome of neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Evaluating tumor response to neoadjuvant chemotherapy (NAC) is important to predict survival and to select the optimal strategy for patients with esophageal cancer. The aim of this study is to investigate the relation between neutrophil-to-lymphocyte ratio (NLR) change after NAC and histological response and oncological outcomes in patients with esophageal cancer. METHODS: This study enrolled 209 patients who underwent NAC and thoracic esophagectomy for esophageal cancer as the primary treatment between 2000 and 2019 in our department. Several predictors of survival including NLR change, which was calculated as post-NAC NLR/pre-NAC NLR, were investigated. We used classification and regression tree (CART) analysis to determine the optimal cutoff values of NLR change for the prediction of histological response. RESULTS: The best cutoff value of NLR change was 0.55 using the CART analysis. Then we divided all patients into two groups; the patients with NLR change below the cutoff were allocated to the NLR reduction group (n = 53), whereas the patients with NLR change above the cutoff were allocated to the no-NLR reduction group (n = 156). NLR change was identified as a significant predictor for histological responder (odds ratio 3.80; 95% confidence interval (CI) 1.69-8.58; p = 0.001) and recurrence-free survival (hazard ratio 0.55; 95% CI 0.33-0.89; p = 0.015) in multivariable analysis. CONCLUSION: The present study demonstrated that NLR change is associated with both histological response to and oncological outcomes of NAC for patients with esophageal cancer. NLR change can help not only to predict survival, but also to facilitate personalized multidisciplinary treatment.

Clinical Significance of Pretherapeutic Serum Squamous Cell Carcinoma Antigen Level in Patients with Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although squamous cell carcinoma antigen (SCC-Ag) is a tumor marker widely used to estimate the progression of esophageal SCC (ESCC), only a few studies have focused on the relationship between serum SCC-Ag levels and the therapeutic effect of neoadjuvant chemotherapy (NAC). OBJECTIVE: This study aimed to elucidate the clinical significance of pretherapeutic serum SCC-Ag levels in patients who underwent NAC followed by esophagectomy. METHODS: Data of 453 patients who underwent NAC followed by esophagectomy were collected from the esophageal cancer database of two high-volume Japanese centers. Serum SCC-Ag levels were measured prior to NAC, and the pathological therapeutic effect of NAC and patient survival were evaluated. Patients were classified according to the tertiles of the serum SCC-Ag value (low, middle, and high groups), and the outcomes among the groups were compared. RESULTS: The levels of serum SCC-Ag were significantly associated with tumor stage (p < 0.01). With regard to the pathological therapeutic effect, the levels of serum SCC-Ag were negatively correlated with the therapeutic effect (p = 0.02). Moreover, increased levels of serum SCC-Ag negatively influenced relapse-free survival (p < 0.01). Multivariate analyses revealed the 'high' group as the independent factor for both the unfavorable therapeutic effect (p = 0.01) and the increased risk of disease recurrence (p < 0.01) when compared with the 'low' group. CONCLUSION: Elevated levels of pretherapeutic serum SCC-Ag are significantly associated with advanced tumor stage, poor response to NAC, and increased risk of disease recurrence.

Relationship Between Early Postoperative Change in Total Psoas Muscle Area and Long-term Prognosis in Esophagectomy for Patients with Esophageal Cancer.

PURPOSE: Postoperative sarcopenia following esophagectomy for esophageal cancer has become a severe problem due to the increasing number of elderly patients undergoing surgery. This study aimed to clarify the relationship between early postoperative skeletal muscle change and cancer prognosis, and propose effective interventions to prevent sarcopenia. METHODS: This study retrospectively analyzed 152 patients who underwent esophagectomy for esophageal cancer. Total psoas muscle area (TPA) was measured before surgery as baseline and on postoperative day 7 (± 2). The effect of early postoperative skeletal muscle loss on 5-year survival was investigated. Moreover, 5-year survival in patients with postoperative complications and a high inflammatory status, which were previously reported as poor prognostic factors of esophageal cancer, was also investigated. RESULTS: Among the 152 patients, 52 (34.2%) showed a decrease in TPA, while 100 (65.8%) maintained their TPA. The TPA decreasing group exhibited poor 5-year overall survival (OS) (p = 0.003) and 5-year recurrence-free survival (RFS) (p < 0.001). The TPA decreasing group also showed a poor 5-year OS in patients who developed severe postoperative complications (p = 0.015). Multivariate analyses showed that decreased TPA was found to be independently associated with OS (p = 0.017) as well as RFS (p = 0.002). CONCLUSIONS: Our findings suggested a relationship between decreased TPA within 1 week after esophagectomy and long-term prognosis among patients with esophageal cancer. If TPA can be maintained, the prognosis was better even in cases with serious complications.

Usefulness of Neutrophil to Lymphocyte Ratio at Recurrence for Predicting Long-Term Outcomes in Patients with Recurrent Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed. PATIENTS AND METHODS: We conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated. RESULTS: Among all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002-1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374. CONCLUSIONS: NLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.