Published papers

Background: There are two methods of Roux-en-Y (RY) reconstruction after gastrectomy: the antecolic route (ACR) and retrocolic route (RCR). There is no evidence to support that the ACR achieves comparable long-term survival. Methods: This was a multi-center historical cohort study. Patients diagnosed with clinical T3/4a and any N stage who underwent open gastrectomy and R0 resection for gastric adenocarcinoma between January 2006 and December 2012 were enrolled. The primary outcome was the hazard ratio of ACR for overall survival, with adjustment for confounding factors by propensity score matching, and a Cox proportional hazards model. Results: A total of 1758 eligible patients were identified from the database. After matching, 410 patients in the ACR and RCR groups were included in the final analysis. The adjusted hazard ratio (95% CI) for ACR was 1.148 (0.870–1.492). The five-year survival rates in the ACR and RCR groups were 74.3% (69.5–78.4) and 77.3% (72.3–81.2), respectively. The short-term surgical outcomes of the two groups did not differ to a statistically significant extent. Conclusion: The route used to lift the jejunum in RY reconstruction did not affect the incidence of long-term survival or postoperative complications. The ACR and RCR are both acceptable options for RY reconstruction during gastric cancer surgery.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0–13%) than after photon-based RT (7.1–30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

As an optimal surgical procedure to accurately evaluate lymph node (LN) metastasis during surgery with minimal surgical resection, we have been developing sentinel node (SN) biopsy for early gastric cancer since the 1990s. Twelve institutions from the Japanese Society of Sentinel Node Navigation Surgery (SNNS), including Keio University Hospital, conducted a multicenter prospective trial to validate the SN concept using the dual-tracer method with blue dye and a radioisotope. According to the results, 397 patients were included in the final analysis, and the overall accuracy in detecting LN metastasis using SN biopsy was 99% (383 of 387). Based on the validation study, we are targeting cT1N0 with a primary tumor of ≤4 cm in diameter as an indication for SN biopsy for gastric cancer. We are currently running a multicenter nonrandomized phase III trial to assess the safety and efficacy of SN navigation surgery. The Korean group has reported the result of a multicenter randomized phase III trial. Since meticulous gastric cancer in the remnant stomach was rescued by subsequent gastrectomy, the disease-specific survival was comparable between the two techniques, implying that SN navigation surgery can be an alternative to standard gastrectomy. With the development of SN biopsy procedure and treatment modalities, the application of SN biopsy will be expanded to achieve an individualized minimally invasive surgery.

Introduction: The clinical importance of treatment approaches based on genomic sequencing has increased in esophageal cancer. This study aimed to clarify the current status and clinical usefulness of genomic panel testing using PleSSision-160 for resectable esophageal squamous cell carcinoma (ESCC). Materials and methods: Sixty-six tumor tissue samples from 61 patients with ESCC, including prospectively collected 46 surgical samples and retrospectively collected 20 biopsy samples before neoadjuvant chemotherapy, were tested using the PleSSision-160 panel. The associations of mutation profiles with long-term survival and chemotherapy resistance were investigated. Results: The top five mutations identified in surgical samples using PleSSision-160 were TP53 (80.4 %), KMT2D (13.0 %), NOTCH1 (13.0 %), EP300 (8.7 %), and AMER1 (8.7 %). Although individual mutations did not show significant associations with long-term survival, patients with high copy number alteration (CNA) status (≥30 counts) had poorer 5-year overall survival (OS) and recurrence-free survival (RFS) compared to those with low CNA status (p = 0.019 and 0.077 for OS and RFS, respectively). Multivariate analyses identified minimally invasive surgery, pStage ≥ III, and high CNA status as independent factors associated with both 5-year OS and RFS. Conclusion: This study is the first to investigate postoperative survival and chemotherapy resistance based on genomic panel testing using PleSSision-160 for resectable ESCC. The findings suggested that high CNA status was a risk factor for long-term survival. Compared to previous genomic sequencing studies in ESCC, further investigation using PleSSision-160 appears to be a promising approach.

Background: Esophageal squamous cell carcinoma(ESCC) often develops resistance to standard chemotherapy regimens ofdocetaxel/cisplatin/5-fluorouracil(DCF) therapy. Strategies to overcome chemoresistance remain a significant clinical challenge. Methods: DCF-resistant ESCC cell lines were established in the beginning through long-term exposure to chemotherapeutic agents.Gene expression profiles were analyzed via RNA sequencing, and functional assays were conducted to evaluate the impact ofvarious calcium channel blockers(CCBs) on cell viability. Results: Transcriptomic analysis revealed enrichment of endoplasmic reticulum(ER) stress pathways in DCF-resistant ESCC cells.Among CCBs tested, combined therapy DCF with CCBs restored chemosensitivity. Conclusion: DCF-resistant ESCC cells were resensitized with combined therapy with DCF and CCBs by enhacing ER stressresponse. This may provide a potential rationale for repurposing CCBs as adjuvant agents in chemotherapy of ESCC.

Background: The concept of oligometastatic disease (OMD) is an intermediate state in which local treatment may offer long-term disease control. While definitions and treatment strategies have been established for esophagogastric adenocarcinoma, they cannot be extrapolated to esophageal squamous cell carcinoma (ESCC) due to distinct biological behaviors and treatment strategies. Currently, no standardized global definition or treatment algorithm for oligometastatic ESCC (OMESQ) exists, which impedes the design of high-quality prospective trials. The OMESQ project aims to develop a global multidisciplinary consensus on the definition, diagnosis, and treatment of OMESQ. Methods: The OMESQ project is an international initiative led by the Japan Esophageal Oncology Group (JEOG) involving 58 centers across 14 countries or regions. The project consists of sequential sub-studies. OMESQ-1 is a systematic review that identifies current definitions and evaluates the survival impact of local treatment. The OMESQ-2 involves multidisciplinary tumor board discussions of real-life clinical cases to assess variability in diagnosis and treatment. The OMESQ-3 is a large-scale, multicenter, retrospective study evaluating the clinical outcomes and efficacy of conversion therapy in patients with five or fewer distant metastases. Integrating the findings from these three steps, the OMESQ-4 will establish a global consensus using a modified Delphi method with international experts, utilizing a 7-point Likert scale to evaluate statements. Finally, the OMESQ-5 is planned as a prospective international multicenter clinical trial based on the established consensus. Discussion: This comprehensive project will generate the first standardized consensus statement for the OMESQ. By harmonizing the definition, diagnosis, and treatment strategies, the OMESQ consensus will improve consistency in clinical practice and serve as the foundation for future prospective trials aimed at improving patient survival rates.

The metastatic strategy of cancer depends on the stiffness of the tumor relative to surrounding tissue: harder tumors displace adjacent tissue, while softer ones infiltrate gaps. Detecting elasticity differences is therefore essential, forming the basis of physical oncology. We developed a novel method to estimate Young's modulus of soft tissue, using photoacoustic vibration induced by non-invasive laser irradiation. This elastography approach aims to replace subjective palpation with objective measurements. In this study, we investigated cancer detection through audible-frequency photoacoustic vibration analysis of agarose gel phantoms with varying stiffness and excised stomach tissues. Our system used a 405 nm diode laser (impact laser) modulated at 1 kHz with 50% duty cycle, delivering ~10 mW average power. Vibrations generated in tissue were measured by a Laser Doppler Vibrometer (LDV). Experimental results showed that samples with low Young's modulus (normal tissue) exhibited clear vibration peaks at 1 kHz, corresponding to the excitation frequency. In contrast, high modulus samples (tumors) demonstrated diminished vibration peaks, lower signal-to-noise ratios, and weaker harmonic responses. These differences reflect the mechanical contrast between normal and malignant tissues. The proposed laser-induced photoacoustic vibration method provides a non-invasive diagnostic modality capable of distinguishing stomach tumors from surrounding tissue based on stiffness. This approach suggests a promising new axis for early cancer detection and real-time in vivo evaluation of tissue elasticity, supporting reliable diagnosis beyond conventional palpation.

Background: Detecting pathological complete response (pCR) preoperatively facilitated a non-surgical approach after neoadjuvant chemotherapy (NAC). We previously developed a deep neural network-based endoscopic evaluation to determine pCR preoperatively. Its quality warrants improvement with a larger data series for clinical application. Methods: This study retrospectively reviewed patients with esophageal squamous cell carcinoma (ESCC) receiving NAC at 46 Japanese esophageal centers certified by the Japan Esophageal Society. Endoscopic images after NAC were collected with clinicopathological factors and long-term outcomes. We randomly selected the same number of patients with Grades 0–1a and Grades 1b–2 based on those with pCR (Grade 3). A deep neural network was used for endoscopic image analyses. A test data set, consisting of 100 photos, was utilized for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the deep neural network-based model and experienced physicians were calculated. Results: The study enrolled 1041 patients, including 354 (33%) patients with pCR, the same number of histological non-responders (Grade 0–1a/1b–2, 352 [33%]/368 [34%]). The median values of sensitivity, specificity, PPV, NPV, and accuracy for pCR detection were 80%, 90%, 89%, 82%, and 85%, respectively. The patients with pCR preoperatively demonstrated significantly better overall survival and recurrence-free survival. Conclusions: This large-scale study revealed that the deep neural network-based endoscopic evaluation after NAC identified pCR with feasible accuracy. The current artificial intelligence technology may guide an individualized treatment strategy, including a non-surgical approach, in patients with ESCC through prospective studies with careful external validation.

Background: Neoadjuvant treatment has become the standard of care for patients with advanced esophageal cancer. However, few studies have elucidated the clinical factors that predict response to neoadjuvant therapy in a large multicenter cohort. We aimed to develop a predictive model of therapeutic effect in patients with esophageal squamous cell carcinoma (SCC) who received neoadjuvant treatment. Methods: This nationwide study included 4078 patients from 85 institutions. Patients who received neoadjuvant treatment followed by surgery for esophageal SCC were eligible. We developed a logistic regression model to predict good pathological therapeutic effects, and a predictive nomogram was generated by applying the logistic regression formula. Results: Among neoadjuvant regimens, cisplatin plus 5-fluorouracil (CF) was the most frequently used (60.2%), followed by docetaxel plus CF (DCF, 27.4%), CF with radiotherapy (CF-RT, 4.5%), adriamycin plus CF (3.6%), nedaplatin plus 5-fluorouracil (0.9%), and DCF-RT (0.5%). Multivariable analysis revealed that male sex, advanced cT category, and increased pretherapeutic SCC antigen level were independently associated with not achieving a good therapeutic effect. Moreover, intensified neoadjuvant regimens were independently associated with favorable therapeutic effects; DCF-RT elicited the best therapeutic effect, followed by CF-RT and DCF. A predictive model including nine commonly measured preoperative variables was generated, and the area under the curve was 0.679 (95% confidence interval: 0.658–0.700). This nomogram was also adequately validated internally. Conclusions: The model developed in this study was validated and predicts the therapeutic effect in patients with esophageal SCC who received neoadjuvant treatment. This model might contribute to individualized treatment strategies.

Despite advancements in multidisciplinary treatment, esophagectomy remains the primary curative treatment for esophageal cancer. Given that lymph node metastases can spread from the cervical to abdominal regions, three-field lymph node dissection has been established as a standard approach. However, this highly invasive procedure involves multiple anatomical regions—thoracic, abdominal, and cervical—leading to significant surgical burden. To reduce surgical invasiveness, minimally invasive esophagectomy (MIE) has become increasingly common worldwide. With its adoption and advancements in multidisciplinary therapy, discussions have emerged regarding the potential omission of lymph node dissection in selected cases. Since the introduction of robot-assisted minimally invasive esophagectomy (RAMIE) in 2004, this technique has progressively replaced conventional MIE. Robotic systems—equipped with a magnified 3D camera, articulated instruments, and tremor filtering—allow surgeons to perform complex procedures with greater precision than manual techniques. One randomized controlled trial (RCT) has demonstrated fewer postoperative complications with RAMIE compared to open esophagectomy. Additionally, RAMIE has been shown to enable more extensive lymph node dissection around the left recurrent laryngeal nerve than conventional MIE. However, the long-term oncological benefits of RAMIE remain unproven, as no RCTs have definitely confirmed its impact on long-term survival in esophageal cancer patients. Ongoing randomized trials are expected to provide further insights into its prognostic benefits.

Background: The optimal surgical procedure for primary duodenal cancer has not been established because of its low incidence. The purpose of this study was to examine the distribution of lymph node (LN) metastasis in duodenal bulb tumors. Specifically, in tumors with submucosal invasion, we aimed to evaluate the feasibility of distal gastrectomy with duodenal bulb resection combined with lymphadenectomy of regional gastric LNs. Methods: Data from patients who underwent surgery for either adenocarcinoma or neuroendocrine tumors located in the duodenal bulb between 2000 and 2020 were retrospectively analyzed from five high-volume centers in Japan. Patient background, clinicopathological factors, type of surgery, distribution of LN metastasis, and long-term outcomes were evaluated. Results: The frequency of LN metastasis in tumors with submucosal invasion was 18%. Metastatic LNs were identified in T1b adenocarcinomas for #6, #8a, #8p, with similar results for neuroendocrine tumors. The 3-year overall survival rate for adenocarcinoma in stages T1a, T1b, and T2–4 was 100%, 81%, and 56%, respectively. Neuroendocrine tumors were 100% at all depths of invasion. Regarding LN tumors with submucosal invasion, while three patients had a recurrence, two cases were observed in distant organs without regional LNs, and one patient who underwent pancreaticoduodenectomy had metastasis in the gastric regional LNs. Conclusion: For duodenal bulb tumors, based on the distribution of LN metastasis with tumors with submucosal invasion, distal gastrectomy with duodenal bulb resection and regional LN dissection is considered a curative treatment. Conversely, pancreaticoduodenectomy is recommended for tumors invading the muscularis propria and beyond.

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.

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.

Background: Despite improvements in surgical techniques and perioperative management, the incidence of postoperative surgical site infection after pancreatoduodenectomy remains high. This study aim to assess whether broad-spectrum antibiotic prophylaxis can reduce complications after pancreatoduodenectomy compared with standard care antibiotics. Methods: Data of patients who underwent pancreatoduodenectomy between July 2010 and March 2022 were extracted from a nationwide Japanese inpatient database. First- and second-generation cephalosporins were designated as narrow-spectrum, and third- and fourth-generation cephalosporins and piperacillin–tazobactam as broad-spectrum antibiotics. Patients who received either narrow- or broad-spectrum antibiotics on the day of surgery were included in the analysis. Using propensity-score stabilized inverse probability of treatment weighting, the postoperative complications were compared between patients who received antimicrobial prophylaxis with narrow-spectrum antibiotics versus broad-spectrum antibiotics. Results: From among 45 099 eligible patients, 36 742 (81.5%) and 8357 (18.5%) patients received narrow- and broad-spectrum antibiotics, respectively. After stabilized inverse probability of treatment weighting, the use of broad-spectrum antibiotics bore a significant association with the reduction in intra-abdominal infections [risk difference (RD), −7.4; 95% confidence interval (CI), −8.7 to −6.0], postoperative pancreatic fistula (RD, −3.0; 95% CI, −4.0 to −1.9), post-pancreatectomy hemorrhage (RD, −1.5; 95% CI, −1.9 to −1.1). The use of broad-spectrum antibiotics was also associated with a shorter postoperative length of hospital stay and lower total hospitalization costs. The proportion of Clostridioides difficile infection did not differ between the groups. Conclusions: The administration of broad-spectrum antibiotics as antimicrobial prophylaxis was associated with better in-hospital postoperative outcomes compared with narrow-spectrum in patients undergoing pancreatoduodenectomy.

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.

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.

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.

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.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.