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Although imaging surveillance after esophagectomy is required to achieve long-term survival for patients with esophageal cancer, the optimal surveillance timing and interval remain unclear. This study was designed to investigate the differences in oncological outcomes based on the detection method for recurrence and surveillance interval in patients with recurrence detected by routine imaging examination after esophagectomy.A total of 527 patients who underwent thoracic esophagectomy for esophageal cancer with R0 resection between 2003 and 2021 in our department were enrolled in this study. Postoperative, routine surveillance was conducted at an outpatient clinic every 3 months, thoracoabdominal computed tomography (CT) every 4-6 months, and esophagogastroduodenoscopy every 6 months. The detection method and optimal interval of imaging surveillance also were investigated.Of all patients, 161 patients developed recurrence during surveillance; 110 (68.3 %) by routine surveillance and 37 (23.0%) not detected by routine surveillance. Among patients who were diagnosed with recurrence following routine surveillance, patients with pStage IV disease on imaging surveillance by thoracoabdominal CT at an interval of ≤ 5 months had a better survival rate than those with an interval of 6 months (P = 0.004), whereas no significant difference among different intervals was observed in patients with pStage I-III disease.Recurrence may have been detectable by our routine surveillance in approximately 70% of patients who developed recurrence. These findings demonstrate the necessity of different imaging surveillance intervals for different pStages of esophageal cancer.

Background Previous studies have suggested that postoperative non-steroidal anti-inflammatory drug (NSAID) use may increase the risk of anastomotic leakage after colorectal surgery. However, the association between NSAIDs and anastomotic leakage after oesophagectomy is unclear. The aim of this retrospective study was to assess the effect of early postoperative NSAID use on anastomotic leakage after oesophagectomy. Methods The Data of patients who underwent oesophagectomy for cancer between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the association between NSAID use in the early postoperative period (defined as the day of and the day after surgery) and short-term outcomes, adjusting for potential confounders. The primary outcome was anastomotic leakage. The secondary outcomes were acute kidney injury, gastrointestinal bleeding, and mortality. Results Among 39 418 eligible patients, early postoperative NSAIDs were used by 16 211 individuals (41 per cent). Anastomotic leakage occurred in 5729 patients (15 per cent). In stabilized IPTW analyses, NSAIDs were not associated with anastomotic leakage (odds ratio 1.04, 95 per cent c.i. 0.97 to 1.10). The proportions of acute kidney injury and gastrointestinal bleeding, as well as 30-day mortality and in-hospital mortality, did not differ according to NSAID use. Propensity score matching and instrumental variable analyses demonstrated similar results. Conclusion Early postoperative NSAID use was not associated with anastomotic leakage or other complications in patients who underwent oesophagectomy.

Studies have shown that epidural analgesia (EDA) is associated with a decreased risk of pneumonia and anastomotic leakage after esophagectomy, and several guidelines strongly recommend EDA use after esophagectomy. However, the benefit of EDA use in minimally invasive esophagectomy (MIE) remains unclear.The aim of this retrospective study was to compare the short-term outcomes between patients with and without EDA undergoing MIE for esophageal cancer.Data of patients who underwent oncologic MIE (April 2014-March 2019) were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the associations between EDA use and short-term outcomes, adjusting for potential confounders.Among 12,688 eligible patients, EDA was used in 9954 (78.5%) patients. In-hospital mortality, respiratory complications, and anastomotic leakage occurred in 230 (1.8%), 2139 (16.9%), and 1557 (12.3%) patients, respectively. In stabilized IPTW, EDA use was significantly associated with decreased in-hospital mortality (odds ratio [OR] 0.46 [95% confidence interval 0.34-0.61]), respiratory complications (OR 0.74 [0.66-0.84]), and anastomotic leakage (OR 0.77 [0.67-0.88]). EDA use was also associated with decreased prolonged mechanical ventilation, unplanned intubation, nonsteroidal anti-inflammatory drug use, acetaminophen use, postoperative length of stay, and total hospitalization costs and increased vasopressor use. One-to-three propensity score matching and instrumental variable analyses demonstrated equivalent results.EDA use in oncologic MIE was associated with low in-hospital mortality as well as decreased respiratory complications, and anastomotic leakage, suggesting the potential advantage of EDA use in MIE.

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) 2/m2 for male and SMI 2/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.

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.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.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).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.

The aim of this study was to evaluate clinical validity of the S-1 dosage formula based on body surface area (BSA) and creatinine clearance (CLcr) to achieve the target area under the concentration-time curve of 5-FU, which we had developed and refined in each prospective pharmacokinetic study.The recommended dose determined by the refined formula was assessed using data of the SPIRITS (S-1 vs. S-1 plus cisplatin [SP]) and the G-SOX (SP vs. S-1 plus oxaliplatin [SOX]) trials. Nine hundred and thirty-eight patients in these trials were classified into three groups according to their actual S-1 starting doses compared with the recommended doses (under-dosed, recommended dose; equal-dosed, =recommended dose; over-dosed, recommended dose).The patients in the under-dosed group in both trials showed similar tendencies: male, younger, higher BSA, and higher CLcr. The incidence of any grade neutropenia was significantly greater in the over-dosed group compared with the equal-dosed group in the S-1 and the SOX arms. The hazard ratios (HR) of overall survival (OS) (under-dosed vs. equal-dosed) were 1.361 (S-1 arm), 1.259 (SP arm) in the SPIRITS trial, and 1.381 (SOX arm), 0.999 (SP arm) in the G-SOX trial. Multivariate analysis in all the patients demonstrated that OS of the over-dosed group was equivalent (HR 1.002, 95% confidence interval [CI] 0.850-1.182, p = 0.980) and that of the under-dosed group was inferior (HR 1.267, 95% CI 1.005-1.597, p = 0.045) to the equal-dosed group.It is suggested that the refined S-1 dosage formula can recommend optimal dose in terms of safety and efficacy.

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.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.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).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.

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Despite advances in multidisciplinary treatment, esophagectomy remains the main curative treatment for esophageal cancer. The advantages and disadvantages of thoracic duct (TD) resection have been controversial for decades. We have herein reviewed relevant published literature regarding ‘thoracic duct,’ ‘esophageal cancer,’ and ‘esophagectomy’ describing the anatomy and function of the TD, and incidence of thoracic duct lymph nodes (TDLN) and TDLN metastases, as well as the oncological and physiological effects of TD resection. The presence of lymph nodes around the TD, referred to as TDLN, has been reported previously. The delineation of TDLNs is clearly defined by a thin fascial structure covering the TD and the surrounding adipose tissue. Previous studies have examined the number of TDLNs and the percentage of patients with TDLN metastasis and revealed that each patient had approximately two TDLNs. The percentage of patients with TDLN metastasis was reported to be 6–15%. Several studies have been conducted to compare the survival after TD resection with that after TD preservation. However, no consensus has been reached because all studies were retrospective, precluding firm conclusions. Although the issue of whether the risk of postoperative complications is affected by TD resection is still unclear, resecting the TD has been shown to have a long-term impact on nutritional status after surgery. In summary, TDLNs are quite common and present in most patients, while metastasis in the TDLNs occurs in a minority. However, the oncological value of TD resection in esophageal cancer surgery remains controversial due to varying findings and methodological limitations of previous comparative studies. Considering the potential but unproven oncological benefits and possible physiological drawbacks of TD resection, including postoperative fluid retention and disadvantages in the long-term nutritional outcome, clinical stage, and nutritional status should be considered before deciding whether to perform TD resection or not.

Systematic inflammation has been reported to contribute to cancer progression through various mechanisms; however, the exact mechanism is still the subject of research. In this study, we evaluated the influence of systematic inflammation on lung metastasis, using a murine abdominal sepsis model, and assessed its relationship with pneumonia after curative esophagectomy in patients with esophageal cancer.We used a murine abdominal sepsis model given highly metastatic osteosarcoma, to reveal the mechanism of systematic inflammation and its potential for lung metastasis. The therapeutic effect of aspirin (ASA) in preventing distant metastasis was also investigated. Subsequently, we analyzed, retrospectively, the relationship between pneumonia and lung metastasis after esophagectomy in patients who underwent esophagectomy at Keio University between January, 2007 and October, 2020.Abdominal sepsis provoked lung injury in the acute phase. ASA inhibited the recruitment of neutrophils triggered by the lung injury, and it also suppressed lung metastasis. Our retrospective study revealed that lung metastasis was more frequent in patients with postoperative pneumonia.Postoperative acute lung injury is associated with a higher risk of lung metastasis. ASA may be a potential preoperative treatment for inhibiting lung metastasis by preventing the recruitment of neutrophils.

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.

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.

To examine the association of BMI with mortality and related outcomes after oncologic esophagectomy.Previous studies showed that high BMI was a risk factor for anastomotic leakage and low BMI was a risk factor for respiratory complications after esophagectomy. However, the association between BMI and in-hospital mortality after oncologic esophagectomy remains unclear.Data for patients who underwent esophagectomy for esophageal cancer between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Multivariate regression analyses and restricted cubic spline analyses were used to investigate the associations between BMI and short-term outcomes, adjusting for potential confounders.Among 39,406 eligible patients, in-hospital mortality, major complications, and multiple complications (≥2 major complications) occurred in 1069 (2.7%), 14,824 (37.6%), and 3621 (9.2%), respectively. Compared with normal weight (18.5-22.9 kg/m2), severe underweight (16.0 kg/m2), mild/moderate underweight (16.0-18.4 kg/m2), and obese (≥27.5 kg/m2) were significantly associated with higher in-hospital mortality [odds ratio 2.20 (95% confidence interval 1.65-2.94), 1.25 (1.01-1.49), and 1.48 (1.05-2.09), respectively]. BMI showed U-shaped dose-response associations with mortality, major complications, and multiple complications. BMI also showed a reverse J-shaped association with failure to rescue (death after major complications).Both high BMI and low BMI were associated with mortality, major complications, and multiple complications after esophagectomy for esophageal cancer. Patients with low BMI were more likely to die once a major complication occurred. The present results can assist with risk stratification in patients undergoing oncologic esophagectomy.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

BACKGROUND The safety and feasibility of robot-assisted minimally invasive esophagectomy (RAMIE) remain unclear. The aim of this study was to compare the short-term outcomes of RAMIE with extended lymphadenectomy and conventional minimally invasive esophagectomy (MIE) in order to investigate the safety and feasibility of RAMIE. METHODS A retrospective analysis of 87 patients who underwent minimally invasive esophagectomy at our institution between April 2018 and March 2020 was made, assigning 22 in the RAMIE group and 65 in the MIE group. Short-term clinical outcomes and clinical baseline data were compared. RESULTS The baseline characteristics were comparable. No significant difference in median thoracic phase blood loss and median number of dissected mediastinal lymph nodes were observed. The median operative time of thoracic approach was significantly longer in the RAMIE group than the MIE group (305 minutes [221-397] vs 227 minutes [133-365], P

This study aimed to validate the prognostic significance of stratification using pathological stage and response to neoadjuvant chemotherapy (NAC) with a nationwide database from an authorized institute by the Japan Esophageal Society.We proposed the combined criteria using pStage and pathological response. Conducting a validation study using an expanded cohort in the clinical setting would be valuable since it was developed using retrospective data collection.Patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed for esophageal cancer between 2010 and 2015. The prognostic value of the pathological response was evaluated within the same pStage. Moreover, risk stratification was developed to predict cancer-specific survival (CSS).The pathological response showed significant stratification of CSS in 3761 patients included in this analysis. We classified the patients into seven groups as survival was significantly different between responders and nonresponders under the stratification with pStage, excluding pStage I comprising pStage 0-I/II responder/II non-responder/III responder/III non-responder/IV responder/IV non-responder with the 5-year CSS of 83.7%/75.8%/68.9%/59.8%/44.4%/40.7%/23.1%, respectively. Furthermore, the area under the curve was significantly higher under the new classification than in the pStage alone (P0.001).The prognostic value of classification using pStage and the pathological response was successfully validated using real-world data in Japan. This result would guide appropriate treatment for patients with ESCC who received NAC followed by esophagectomy.

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.

SummaryEsophagectomy 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.

Sentinel node (SN) mapping based on the SN concept has been applied to early gastric cancer. However, it is still controversial whether or not the oncological safety is ensured in case pathological stage was advanced in these patients. The aim of this study was to investigate the validity of SN mapping in patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors. We retrospectively analyzed 40 patients with a diagnosis of cT1N0 or cT2N0 single-lesion gastric cancer who were shown to have pT2 or deeper tumors after gastrectomy with SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs. The diagnostic accuracy and distribution of SNs at each tumor site were analyzed. Of the 40 patients, 24 (60%) were postoperatively diagnosed as pT2, and 16 (40%) as pT3 or T4. SNs were detected in all patients. The false negative rate was 9% (1/11), and in that patient, the non-SN metastasis was observed within the SN basin. Diagnostic accuracy was 98% (39/40). Overall distribution of SNs was similar to that for patients with early gastric cancer. No significant differences in overall and recurrence-free survival were observed between the patients who underwent standard gastrectomy and those who underwent function-preserving gastrectomy, based on the results of SN mapping. Our results confirmed validity of SN mapping for patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors after gastrectomy. Closed surveillance without additional surgical treatment is an option for these patients.

Background In Japan, the prevalence of synchronous multiple intramucosal gastric carcinoma is reported to be 5–15%. Here is a case of a synchronous small gastric carcinoma fulfilling the definite indication and curative criteria for endoscopic submucosal dissection with multiple lymph node metastases. Case presentation A Japanese woman in her fifties with a history of endoscopic resection for mucosal poorly differentiated adenocarcinoma was evaluated, with the UICC TNM classification stage being cT1aN0M0 cStageIA. She had undergone total gastrectomy with D1 + lymph node dissection. Histopathological examination revealed 16 individual sporadic lesions in the gastric body, with maximum diameter 3 mm and localization in the lamina propria. Twenty-seven nodes were resected, and metastasis of the carcinoma was revealed in 24 nodes. Conclusions Undifferentiated intramucosal gastric cancer has a relatively high probability of lymph node metastasis; however, synchronous early lesions are often overlooked. Frequent follow-up examinations may increase the detection of multiple gastric cancers.

Dynamic properties are derived from the structural flexibility of 2D polymers. Softening layered structures has the potential for tuning and enhancing the dynamic properties. In the present work, the flexibility of layered polydiacetylene (PDA) is tuned by the interlayer polymeric guests with different branching structures. PDA shows thermoresponsive color-change properties through shortening the effective conjugation length with molecular motion. Whereas the blue-to-red color transition is observed at certain threshold temperatures for the layered PDA without the interlayer guest, the intercalation of the bulky polymer guests lowers the starting temperature and widens the temperature range for the thermoresponsive color changes. The resultant layered composite of PDA and bulky polymer affords the homogeneous coating on substrates on the centimeter scale. The thermoresponsive color-change coating is applied to temperature-distribution imaging. The specific heat of liquids is colorimetrically estimated using the coating on the bottle. The coating on a silk cloth visualizes the temperature distribution on a simulated tissue during surgical operation using an ultrasonic coagulation cutting device. The coating can be applied to thermal imaging in a variety of fields. Moreover, the softening strategy contributes to explore dynamic properties of soft 2D materials.

More robot-assisted minimally invasive esophagectomy (RAMIE) procedures have been performed owing to three-dimensional field of view, image stabilization, and flexible joint function, however, both the surgeon, and surgical team require proficiency. Therefore, assessing the surgical learning curve and determining the surgical difficulty are essential for reducing complications. This study aimed to establish an artificial intelligence (AI)-based automated surgical phase recognition system for RAMIE by analyzing robotic surgical videos and evaluate the learning curve. This study enrolled 31 patients who underwent RAMIE. We annotated the videos into the following nine surgical phases, namely preparation, lower mediastinal dissection, upper mediastinal dissection, azygos vein division, subcarinal lymph node dissection (LND), right recurrent laryngeal nerve (RLN) LND, left RLN LND, esophageal transection, and post-dissection to completion of surgery to train the AI for automated phase recognition. We divided all patients into two groups, namely early period (20 patients) and late period (11 patients), after which the relationship between the surgical phase duration and learning curve was assessed. Frames were extracted from each video at a rate of one frame per second (fps), with an average of 14517 ± 4770 frames per video, which were used to train and test the AI model. Four-fold cross validation was applied to evaluate the performance of the present model. The AI had an accuracy of 84%. The preparation (p = 0.012), post-dissection to completion of surgery (p = 0.003), and ‘no step’ (p We established an automated surgical phase recognition system for RAMIE using deep learning. Specific phase durations were significantly associated with surgeons’ learning curve, and similar tendencies were observed on phase durations predicated by the AI. Our AI-based system can be useful for not only education or OR efficiency but also evaluating surgical skill.

Estimating the esophageal endoscopic submucosal dissection (ESD) technical difficulty is important to reduce complications. Endoscopic duration is one of the related factors to a technical difficulty. The relationship between the esophageal ESD technical difficulty and its intraoperative process was analyzed as a first step toward automatic technical difficulty recognition using artificial intelligence.This study enrolled 75 patients with superficial esophageal cancer who underwent esophageal ESD. The technical difficulty score was established, which consisted of three factors, including total procedure duration, en bloc resection, and complications. Additionally, technical difficulty-related factors, which were perioperative factors that included the intraoperative process, were investigated.Eight (11%) patients were allocated to high difficulty, whereas 67 patients (89%) were allocated to low difficulty. The intraoperative process, which was shown as the extension of each endoscopic phase, was significantly related to a technical difficulty. The area under the curve (AUC) values were higher at all the phase duration than at the clinical characteristics. Submucosal dissection phase (AUC 0.902; 95% confidence intervals (CI) 0.752-1.000), marking phase (AUC 0.827; 95% CI 0.703-0.951), and early phase which was defined as the duration from the start of marking to the end of submucosal injection (AUC 0.847; 95% CI 0.701-0.992) were significantly related to technical difficulty.The intraoperative process, particularly early phase, was strongly associated with esophageal ESD technical difficulty. This study demonstrated the potential for automatic evaluation of esophageal ESD technical difficulty when combined with an AI-based automatic phase evaluation system.

Background and Aim Percutaneous endoscopic gastrostomy (PEG) has been used in patients with dysphagia and inadequate food intake via an oral route. Despite being a procedure with a high success rate, complications and death have been reported. The aim was to identify the factors related to major complications and mortality, as well as PEG removal prognostic factors due to improvement of their general condition. Methods Patient characteristics, comorbidities, laboratory data, concomitant medication, sedation, and indication for PEG placement were collected. Major complications, mortality, and PEG removal factors were assessed. Results A total of 388 patients were enrolled. There were 15 (3.9%) cases of major complications, with major bleeding being the most frequent in 6 (1.5%) patients. Corticosteroids were the independent variable associated with major complications (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.71–20; P =, Chronic corticosteroid users potentially a risk factor for major complications after percutaneous endoscopic gastrostomy (PEG) placement. Previous history of aspiration pneumonia was a factor associated with permanent use of PEG. Prophylactic PEG tube feeding in patients with oncological indication was the most benefited in achieving recovery.

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. 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. 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. 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.

Because cancers of hollow organs such as the esophagus are hard to detect even by the expert physician, it is important to establish diagnostic systems to support physicians and increase the accuracy of diagnosis. In recent years, deep learning-based artificial intelligence (AI) technology has been employed for medical image recognition. However, no optimal CT diagnostic system employing deep learning technology has been attempted and established for esophageal cancer so far. To establish an AI-based diagnostic system for esophageal cancer from CT images. In this single-center, retrospective cohort study, 457 patients with primary esophageal cancer referred to our division between 2005 and 2018 were enrolled. We fine-tuned VGG16, an image recognition model of deep learning convolutional neural network (CNN), for the detection of esophageal cancer. We evaluated the diagnostic accuracy of the CNN using a test data set including 46 cancerous CT images and 100 non-cancerous images and compared it to that of two radiologists. Pre-treatment esophageal cancer stages of the patients included in the test data set were clinical T1 (12 patients), clinical T2 (9 patients), clinical T3 (20 patients), and clinical T4 (5 patients). The CNN-based system showed a diagnostic accuracy of 84.2%, F value of 0.742, sensitivity of 71.7%, and specificity of 90.0%. Our AI-based diagnostic system succeeded in detecting esophageal cancer with high accuracy. More training with vast datasets collected from multiples centers would lead to even higher diagnostic accuracy and aid better decision making.

BACKGROUND/AIM The inflammatory cytokine IL-8 and its receptor CXCR2 are key signalling pathway molecules in cancer development. We hypothesized that IL-8/CXCR2 signalling promotes tumour progression in oesophageal squamous cell carcinoma (ESCC) patients. MATERIALS AND METHODS We examined the relationship between IL-8/CXCR2 expression and clinicopathological factors by immunohistochemistry in samples from 63 patients with resectable ESCC. The effects of IL-8/CXCR2 signalling on cell proliferation and gene expression were examined in vitro and in vivo using ESCC cell lines. RESULTS Increased IL-8/CXCR2 signalling was associated with shorter overall survival (p

In patients with impaired renal function, S‐1–related toxicities increase due to higher exposure of 5‐fluorouracil (5‐FU). Our previous pharmacokinetic study in 16 cancer patients with various renal functions developed an S‐1 dosage formula based on individual creatinine clearance (CLcr) and body surface area (BSA). To evaluate and refine the formula, this prospective study was conducted. Thirty‐three patients with various renal functions received S‐1 for 4 weeks at doses determined by the nomogram derived from the previously developed formula. A series of blood samples were collected after the first dose to calculate the area under the concentration‐time curve (AUC) of 5‐FU. Thirty patients with BSA of 1.14‐1.84 m2 and CLcr of 23.8‐96.4 mL/min were assessable for pharmacokinetics. The observed daily AUC ranged from 712.6 to 2868.7 ng·h/mL, and 18 patients achieved the target AUC (1447.8 ± 545.4 ng·h/mL). Three patients experienced S‐1–related grade 3 adverse events during the first course. In the population pharmacokinetic analysis from the combined data of 46 patients in this study and the previous study, sex was identified as a statistically significant covariate for 5‐FU clearance. Hence, the refined formula includes sex as an additional factor: Recommended daily dose = target AUC × (14.5 + 8.23 × SEX [0 for female and 1 for male] + 0.301 × CLcr) × BSA. Revised nomograms for recommended daily doses derived from the refined formula can be used in clinical practice to achieve the target AUC ensuring efficacy and safety of S‐1., Our previously developed S‐1 dosage formula based on renal function was prospectively evaluated. Revised nomograms for recommended daily doses derived from the refined formula can be used in clinical practice to achieve the target AUC ensuring efficacy and safety of S‐1.

Aim We have previously reported the existence of lymph nodes surrounding the thoracic duct ( TDLN) and transthoracic esophagectomy (TTE) with thoracic duct (TD) resection increased the number of lymph nodes (LNs) retrieved. The current study aims to evaluate the prognostic impact of TDLN metastasis in esophageal cancer patients subdivided by its location and comparing the patients’ survival with those with extra‐regional LN metastasis. Methods Patients who underwent TTE with TD resection for esophageal squamous cell carcinoma (ESCC) were reviewed. Patients were classified into those with or without TDLN metastasis, and clinicopathological factors were compared between groups. TDLN was further divided into TDLN‐Ut/Mt/Lt based on the location in the mediastinum. The relapse‐free survival (RFS) and overall survival (OS) were compared between groups. Results Of 232 patients, TDLN metastasis was observed in 17 (7%). RFS and OS were significantly worse in the TDLN metastasis group. TDLN metastasis was shown to be an independent prognostic factor for RFS and OS in the multivariate analysis. The negative prognostic impact of TDLN metastasis was evident in TDLN‐Mt/Lt. The RFS and OS of patients with TDLN metastasis were almost identical to those with positive LN metastasis in extra‐regional LNs. Conclusion TDLN metastasis was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be independently classified from the current regional LNs. Given that neoadjuvant therapy has been a standard, we might need to introduce adjuvant therapy when TDLN metastasis is observed., Metastasis at the lymph node surrounding the thoracic duct (TDLN) was proven to be a strong prognostic indicator. Although the TDLN has been included in the classification of regional LN in the current staging systems, it could be separately classified and dealt with as distant metastasis.