Published papers

The metastatic strategy of a cancer will be determined by the relative stiffness of the cancer tumor and the surrounding normal tissue, i.e. hard relative to the surrounding tissues push off, while those that are soft invade into the gaps. Therefore, it is necessary to detect differences in elastic properties from surrounding tissues specific to malignant tumors. This concept has been proposed and studied as Physical oncology [1]. We have been developed a novel method to estimate Young's modulus for soft tissue, agarose gel, by laser irradiation and induced-photoacoustic vibration analysis [2]. In this study, a novel elastography scheme for soft-tissue in vivo to replace the physician's palpation by applying the photoacoustic vibration generation by non-invasive laser irradiation. In this presentation, we report on the detection of cancer tumor onset by the audible frequency range for agarose gel phantoms of different Young's modulus and excised stomachs to detect differences in stiffness.

Background: Although several oesophageal squamous cell carcinoma (OSCC) studies have reported no definitive overall survival (OS) differences between neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC), the higher pCR rate with NACRT has been viewed as a potential advantage. Beyond ongoing concerns about the validity of pCR as a surrogate endpoint, it remains uncertain whether survival differs between these modalities among patients with OSCC who achieve pCR. Methods: An integrated analysis of individual patient data (IPD) from phase III trials evaluating perioperative therapies for resectable OSCC was conducted, emphasizing prognostic differences between NAC and NACRT, particularly among patients who achieved pCR. Results: IPD from seven phase III RCTs across six countries included data for 1044 patients with OSCC (83.5% male; mean age of 62.3 years). Of these patients, 605 (58.0%) received NAC and 439 (42.0%) received NACRT, with R0 resection rates of 89.6% versus 84.7% and pCR rates of 6.9% versus 34.2% respectively. Among patients who achieved pCR (192 patients), 5-year OS was 97.5% in the NAC group and 70.4% in the NACRT group, while 5-year recurrence-free survival was 80.8% and 63.7% respectively. Multivariable analysis demonstrated a significant survival advantage for NAC among patients who achieved pCR. Conclusion: Among patients who achieved pCR, postoperative outcomes varied considerably by neoadjuvant treatment modality. The markedly favourable prognosis associated with pCR after NAC suggests that these patients may represent an optimal candidate cohort for future evaluation of surgery-avoidance and watch-and-wait strategies.

Background: The anaesthesia regimen may affect the risk of postoperative respiratory complications. However, the optimal anaesthetic choice for oesophagectomy remains unclear. This retrospective study compared the effect of desflurane, sevoflurane, and propofol anaesthesia on short-term outcomes after oesophagectomy. Methods: Data of patients who underwent oesophagectomy for cancer during April 2012-March 2022 were extracted from a nationwide Japanese inpatient database. Propensity score matching weight analysis was conducted to compare respiratory complications, ventilatory failure, and in-hospital mortality between desflurane, sevoflurane, and propofol anaesthesia, adjusting for potential confounders. Sensitivity analyses were performed using multivariable logistic regression and instrumental variable analyses. Results: Among 21 080 included patients (desflurane group 7823, sevoflurane group 8932, and propofol group 4325 patients), respiratory complications and ventilatory failure occurred in 3399 (16.1%) and 960 (4.6%) patients respectively. Upon matching weight analysis, sevoflurane and propofol anaesthesia were significantly associated with higher incidences of respiratory complications (OR 1.13, 95% c.i. 1.03 to 1.24 and OR 1.43, 95% c.i. 1.28 to 1.58 respectively) and ventilatory failure (OR 1.21, 95% c.i. 1.02 to 1.43 and OR 1.29, 95% c.i. 1.06 to 1.56 respectively) compared with desflurane anaesthesia. In-hospital mortality after desflurane anaesthesia was the lowest of the three anaesthesia (1.6% and 1.8% versus 1.2%; OR 1.30, 95% c.i. 0.98 to 1.73 and OR 1.49, 95% c.i. 1.08 to 2.06 respectively). Multivariable logistic regression and instrumental variable analyses demonstrated similar results. Conclusions: Sevoflurane and propofol anaesthesia for oesophagectomy were associated with worse respiratory outcomes compared with desflurane anaesthesia.

Background and Study Aims: Endoscopic laryngopharyngeal surgery is an effective treatment for superficial laryngopharyngeal cancer, particularly in cases with prior esophageal cancer treatment. Despite its frequent application, reports on the risk factors for postoperative complications are limited. This study aimed to identify the risk factors for pneumonia after endoscopic laryngopharyngeal surgery and to examine the variations in pneumonia incidence among the types of prior esophageal cancer treatment. Methods: Patients who had a history of esophageal cancer treatment and subsequently underwent endoscopic laryngopharyngeal surgery for superficial pharyngolaryngeal cancer were retrospectively analyzed. We examined the association between postoperative pneumonia and several factors, including number of lesions; diameter of the resected lesion; and type of previous esophageal cancer treatment, such as endoscopic submucosal dissection, chemoradiotherapy, and esophagectomy. Results: The study included 79 patients who had a mean age of 67.4 years. Postoperative pneumonia occurred in 16.4%. Multivariate analysis showed that the pneumonia incidence significantly increased in cases with multiple lesions (OR 4.794, 95% CI 1.133–20.288, p = 0.033) and larger diameter of the resected lesion (OR 7.047, 95% CI 1.791–27.730, p = 0.005). Importantly, compared with other treatments, prior esophagectomy for esophageal cancer did not increase the pneumonia incidence. Conclusions: Multiple lesions and larger lesion diameter were the significant predictors of postoperative pneumonia. Moreover, endoscopic laryngopharyngeal surgery can be safely performed even in patients who have previously undergone esophageal cancer surgery, although careful monitoring remains necessary.

Background: Although neoadjuvant treatment (NAT) has become the standard of care for patients with locally advanced esophageal cancer, the risk of recurrence remains high. The risk must be predicted accurately, so that appropriate adjuvant therapy can be planned. We aimed to develop a model predicting recurrence of esophageal squamous cell carcinoma (ESCC) in patients who received NAT before esophagectomy. Methods: This nationwide study included 3874 patients from 85 institutions. Patients who underwent NAT and then surgery for ESCC were eligible. We developed a Cox proportional hazards model and created a nomogram to predict disease recurrence after NAT and curative esophagectomy. Results: Of the patients, 268 (6.9%), 1280 (33.0%), 2006 (51.8%), and 320 (8.3%) had clinical stage I, II, III, and IV tumors, respectively. The 5-year recurrence rate was 45.1% (95% confidence interval 43.4%–46.7%). Multivariable analysis revealed that body mass index, type of neoadjuvant treatment, primary tumor location, operative blood loss, pathological tumor stage, pathological therapeutic effect, and leakage were independently associated with disease recurrence. Using 13 commonly measured perioperative variables, we created a predictive nomogram, and the area under the curve was 0.783 (95% confidence interval 0.766–0.800). This nomogram was also adequately validated internally and had excellent calibration capacity (calibration slope, 0.992). Conclusions: The model developed in this study adequately predicted ESCC recurrence in patients who underwent NAT and then esophagectomy. Further research with this nomogram is needed to assess the effect of adjuvant therapy in patients at high risk for recurrence.

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.

Background: Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC. Objective: We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases. Methods: Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates. Results: A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p = 0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS. Conclusions: Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis.

Background: Recent advances in multimodal treatments indicate that conversion therapy (CT) is a viable option for metastatic esophageal cancer (EC). JCOG1314 was a randomized phase III trial to confirm the survival benefit of docetaxel plus cisplatin plus 5-fluorouracil (DCF) versus cisplatin plus 5-fluorouracil (CF) for metastatic EC. The purpose of this analysis was to evaluate the safety and survival of CT in patients enrolled in JCOG1314. Methods: CT was defined as surgery or chemoradiotherapy (CRT) aimed at cure following initial treatment for tumors that were initially unresectable because of distant metastasis. Clinicopathological factors, surgical outcomes, toxicities during CRT, and survival were compared between the CT and non-CT groups. Results: Of 240 patients enrolled in JCOG1314, excluding patients with recurrent disease, 154 with initially unresectable EC because of distant metastasis were selected. Of these patients, 21 received CT, which included conversion surgery (n = 5) and conversion CRT (n = 16). There was no significant difference in the number of metastatic organs or chemotherapy regimen between the CT and non-CT groups. The most common M1 factor in the CT group was the thoracic lymph node. The 3-year overall survival (OS) for the CT and non-CT groups was 52.4 and 14.3%, respectively. Multivariable analysis revealed that CT patients showed significantly better OS compared with the non-CT group (HR 0.36, 95% CI 0.19–0.67, p < 0.01). Conclusion: CT may be safely performed with a favorable prognosis in EC. A prospective study is warranted to determine whether CT improves survival in metastatic EC.

Background: 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. Objective: The aim of this retrospective study was to compare the short-term outcomes between patients with and without EDA undergoing MIE for esophageal cancer. Methods: 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. Results: 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. Conclusions: 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.

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 <.0001). With respect to postoperative complications such as recurrent laryngeal nerve paralysis (Clavien–Dindo ≥ grade II) (RAMIE 4.6% vs MIE 17%, P =.11) and postoperative pneumonia (Clavien–Dindo ≥ grade III) (RAMIE 9% vs MIE 23%, P =.13), no significant difference was observed. The patients in the RAMIE group had a better postoperative swallowing function (P =.023) and were able to start oral food intake significantly earlier (P =.007). The median hospital stay was significantly shorter in the RAMIE group than in the MIE (23 days vs 35 days, P =.009). Conclusions: RAMIE with extended lymphadenectomy was safe and feasible for esophageal cancer and resulted in improved postoperative swallowing function and shorter postoperative hospital stay.

Background: Precision medicine for esophageal squamous cell carcinoma (ESCC) has not been implemented owing to a lack of site-specific therapeutic markers and biomarkers. We hypothesized that the genomic background of each subsite of the esophagus might be different, allowing us to develop site-specific treatment strategies (cervical, upper thoracic, middle thoracic and lower thoracic). Methods: This was a single-center retrospective cohort study. Patients diagnosed with ESCC who underwent comprehensive genomic profiling (CGP) at Keio University Hospital between April 2017 and March 2024 were recruited. Genomic profiles were analyzed and compared across esophageal subsites. Results: Among the 107 patients with ESCC who underwent CGP, 6 were cervical, 16 were upper thoracic, 54 were middle thoracic, and 31 were lower thoracic. The most frequently altered genes were TP53, followed by CDKN2A and NFE2L2. The frequency of NFE2L2 mutations was significantly higher in the middle thoracic region (P = 0.041). The mutation rate increased from Stage I to IV (P = 0.0046). NFE2L2 mutations were rarely observed in early-stage cancers, suggesting that they may subsequently be acquired during growth and metastasis. Furthermore, a significant association was observed between a history of heavy alcohol consumption and NFE2L2 mutations. The overall survival of patients with unresectable or metastatic ESCC harboring NFE2L2 mutations was 12.0 months, compared to 29.7 months in patients without the mutations (HR: 2.37, P = 0.047). Conclusion: NFE2L2 mutations were more common in the middle thoracic esophagus, appeared to be associated with tumor progression, and were linked to poor prognosis.

Background: The immunogenic cell death induced by radiotherapy (RT) has been demonstrated to enhance the systemic antitumor effect of immune checkpoint inhibitors (ICIs). The incorporation of RT into ICIs has the potential to mitigate the occurrence of early treatment failure, particularly with dual ICI combination, in patients with advanced or recurrent esophageal cancer. Methods: This randomized phase II trial, initiated in November 2024, aims to explore the superiority of the combination of RT with nivolumab plus ipilimumab over nivolumab plus ipilimumab alone in patients with advanced or recurrent esophageal squamous cell carcinoma. The primary endpoint is progression-free survival, while the secondary endpoints include overall survival, response rate, duration of response, and adverse events. We assumed a 6-month PFS of 35% in the nivolumab plus ipilimumab alone arm and expected a 15% increase in the 6-month PFS for the RT with nivolumab plus ipilimumab arm (HR, 0.66). The total required sample size was calculated to be 70 (35 per arm) to achieve a desired power of 80% with an overall one-sided alpha of 20%, an accrual period of 2.5 years, and a follow-up period of 1 year. A total of 74 patients will be enrolled from 41 institutions in Japan. An ancillary study analyzes cytokine profiles and phenotypic characteristics in peripheral blood mononuclear cells during treatment with the protocol. Discussion: The objective of this trial is to assess the safety and efficacy of RT in combination with dual ICIs in reducing early treatment failure and improving outcomes with translational research. Findings from this trial will inform a future phase III trial in this patient population. Trial registration: This trial has been registered on November 5th, 2024, in the Japan Registry of Clinical Trials as jRCT1031240461 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT1031240461).

Background: An aortoenteric fistula (AEF) is a rare and lethal complication of esophagectomy. Fistulas frequently result from problems regarding acute infections or leaks, which are typically evident weeks after the treatment. However, some cases exhibit AEF years after the initial operation. Here, we describe a rare case of AEF caused by chronic friction of the stapler toward the aortic arch, in which stent graft repair and surgery were successful. Case presentation: A 71-year-old man had undergone esophagectomy for esophageal carcinoma and reconstruction with a gastric conduit through the posterior mediastinal route 11 years previously. He visited our outpatient clinic with the chief complaint of hematemesis. However, after arrival, he experienced massive hematemesis and severe shock due to bleeding from an AEF. Endoscopic hemostasis using a Sengstaken-Blakemore tube followed by stent graft repair controlled the bleeding. We performed a partial resection of the gastric conduit, including the fistula, followed by digestive reconstruction using a jejunal interposition graft. The patient recovered gradually after receiving intensive care and was discharged 115 days after hospitalization. Conclusions: We present a rare case of bleeding due to AEF long after esophagectomy, which was successfully treated with endovascular stent graft repair and surgery. Endoscopic hemostasis using a Sengstaken-Blakemore tube followed by stent graft repair was effective.

Successful treatment of esophageal cancer requires a multidisciplinary approach consisting of surgery, chemotherapy, and radiotherapy. Esophagectomy is highly invasive with substantial morbidity and mortality. In order to reduce surgical invasiveness and improve outcomes, minimally invasive esophagectomy (MIE) and robot-assisted MIE were introduced. MIE reduces the incidence of postoperative complications, including pneumonia, when compared to open esophagectomy. In the last decade, several studies demonstrated that the modification of neoadjuvant and perioperative therapy could further improve outcomes. However, overall survival was still unsatisfactory: 5-year overall survival rate was 45% in the FLOT4 trial, 47% in the CROSS trial, and 55% in the JCOG9907 trial. Adjuvant therapy in combination with neoadjuvant chemotherapy may be a strategy to improve oncological outcomes. However, tolerability for adjuvant treatment is a concern as postoperative complications may delay recovery and hamper the application of adjuvant treatment. Secondly, not all patients likely benefit form adjuvant treatment. Individualization of treatment based on risk stratification of recurrent disease by new technologies is the future. Although further validation and interventional studies are required, liquid biopsies may be promising indicators to guide multidisciplinary treatment for esophageal cancer.

TGF-β induces senescence in embryonic tissues. Whether TGF-β in the hypoxic tumor microenvironment (TME) induces senescence in cancer and how the ensuing senescence-associated secretory phenotype (SASP) remodels the cellular TME to influence immune checkpoint inhibitor (ICI) responses are unknown. We show that TGF-β induces a deeper senescent state under hypoxia than under normoxia; deep senescence correlates with the degree of E2F suppression and is marked by multinucleation, reduced reentry into proliferation, and a distinct 14-gene SASP. Suppressing TGF-β signaling in tumors in an immunocompetent mouse lung cancer model abrogates endogenous senescent cells and suppresses the 14-gene SASP and immune infiltration. Untreated human lung cancers with a high 14-gene SASP display immunosuppressive immune infiltration. In a lung cancer clinical trial of ICIs, elevated 14-gene SASP is associated with increased senescence, TGF-β and hypoxia signaling, and poor progression-free survival. Thus, TME-induced senescence may represent a naturally occurring state in cancer, contributing to an immune-suppressive phenotype associated with immune therapy resistance.

310Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.

Background: We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear. Methods: Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5. Results: This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group. Conclusions: The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term.

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: 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. Methods: 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. Results: 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. Conclusions: 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: 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. Methods: 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. Results: 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. Conclusions: 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.