Published papers

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

Background: Precise recognition of anatomical structures such as the pancreas, transverse mesocolon, and right gastroepiploic vein (RGEV) is critical for the safety and effectiveness of infrapyloric lymph node dissection during robotic distal gastrectomy (RDG). Misrecognizing these structures can increase the risk of complications. However, even expert surgeons may encounter difficulties identifying these structures due to variations in patient anatomy and surgical technique. This study aims to validate the performance of an artificial intelligence (AI) model for automated anatomical recognition during RDG across multiple institutions and evaluate its clinical utility in supporting surgeons. Methods: Surgical videos from 90 patients who underwent RDG at multiple high-volume centers in Japan were analyzed. The AI model’s accuracy was evaluated using Intersection over Union (IoU) for the pancreas, transverse mesocolon, and RGEV across four high-volume institutions. The clinical utility of the AI model was assessed by comparing the accuracy of surgeons in identifying anatomical landmarks during infrapyloric lymph node dissection between procedures performed with and without AI assistance. Results: During this surgical procedure, the IoU of our AI model for the pancreas, transverse mesocolon, and RGEV were 0.624, 0.575, and 0.618, respectively. Furthermore, despite differences in accuracy across the four facilities, the AI model achieved consistent IoU values ranging from 0.5 to 0.7 across all institutions, demonstrating minimal variability. AI-assisted surgeons showed significantly higher accuracy in recognizing anatomical landmarks, particularly the transverse mesocolon’s edge, compared with those without AI assistance (91.7% vs. 80.6%, p = 0.043). These findings highlight the model’s ability to enhance the safety and precision of infrapyloric lymph node dissection. Conclusion: The AI model demonstrated strong external validity and improved surgeons’ recognition of anatomical structures during RDG. Its integration into clinical practice can potentially reduce the rate of surgical complications and improve patient outcomes.

Background: The purpose of the current study was to clarify the relationship between clinical features of dysphagia after esophagectomy and preoperative sarcopenia. Methods: A total of 187 cases were included in the current study. The psoas cross-sectional area on pre-treatment computed tomography was measured in thoracic esophageal cancer patients who underwent curative resection. The psoas muscle index (PMI) cut-off levels for sarcopenia were 6.36 cm2/m2 for men and 3.92 cm2/m2 for women. Swallowing function was evaluated using videofluoroscopic swallowing study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) at postoperative days 7-15, and classified according to the food intake level scale (FILS). Perioperative swallowing rehabilitation was performed in all cases. Results: In the 187 included patients, the median PMI was 5.42 cm2/m2 for men and 3.43 cm2/m2 for women, and 133 cases (71%) met the sarcopenia criteria. The FILS <4 (no oral intake) was 15% in the non-sarcopenia group, and 38% in the sarcopenia group (P = 0.003). There was no significant difference in the incidence of postoperative complications, including pneumonia and re-admission due to pneumonia, between the two groups. Preoperative sarcopenia and recurrent laryngeal nerve palsy were be independent risk factors for postoperative dysphagia. Conclusions: Sarcopenic patients with esophageal cancer develop postoperative dysphagia more often than non-sarcopenic patients. Prehabilitation and nutritional support for patients with preoperative sarcopenia could play an important role to mitigate postoperative dysphagia.

Background and Aims: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is a multistep treatment involving several endoscopic processes. Although analyzing each phase separately is worthwhile, it is not realistic in practice owing to the need for considerable manpower. To solve this problem, we aimed to establish a state-of-the-art artificial intelligence (AI)–based system, specifically, an automated phase-recognition system that can automatically identify each endoscopic phase based on video images. Methods: Ninety-four videos of ESD procedures for superficial esophageal cancer were evaluated in this single-center study. A deep neural network–based phase-recognition system was developed in an automated manner to recognize each of the endoscopic phases. The system was trained with the use of videos that were annotated and verified by 2 GI endoscopists. Results: The overall accuracy of the AI model for automated phase recognition was 90%, and the average precision, recall, and F value rates were 91%, 90%, and 90%, respectively. Two representative ESD videos predicted by the model indicated the usability of AI in clinical practice. Conclusions: We demonstrated that an AI-based automated phase-recognition system for esophageal ESD can be established with high accuracy. To the best of our knowledge, this is the first report on automated recognition of ESD treatment phases. Because this system enabled a detailed analysis of phases, collecting large volumes of data in the future may help to identify quality indicators for treatment techniques and uncover unmet medical needs that necessitate the creation of new treatment methods and devices.

Background: Although a number of robot-assisted minimally invasive esophagectomy (RAMIE) procedures have been performed due to three-dimensional field of view, image stabilization, and flexible joint function, both the surgeons and surgical teams require proficiency. This study aimed to establish an artificial intelligence (AI)-based automated surgical-phase recognition system for RAMIE by analyzing robotic surgical videos. Methods: This study enrolled 31 patients who underwent RAMIE. The videos were annotated into the following nine surgical phases: 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. An additional phase (“no step”) was used to indicate video sequences upon removal of the camera from the thoracic cavity. All the patients were divided into two groups, namely, early period (20 patients) and late period (11 patients), after which the relationship between the surgical-phase duration and the surgical periods was assessed. Results: Fourfold cross validation was applied to evaluate the performance of the current 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 < 0.001) phases predicted by the AI were significantly shorter in the late period than in the early period. Conclusions: A highly accurate automated surgical-phase recognition system for RAMIE was established using deep learning. Specific phase durations were significantly associated with the surgical period at the authors’ institution.

Background: In patients with locally advanced T4 esophageal cancer, surgery is typically considered if curative resection appears feasible after chemotherapy or chemoradiotherapy. Many institutions do not perform surgery in cases with persistent T4 diseases, while some challenge combined organ resection to achieve curative resection. However, this approach may be inappropriate for patients at high risk of developing early postoperative distant metastases. Methods: We retrospectively analyzed 445 patients with esophageal squamous cell carcinoma who were unable to undergo curative esophagectomy due to cancer invasion into surrounding organs. Survival outcomes, progression patterns, and predictive factors for distant progression as the initial site of failure were evaluated. Results: During follow-up, 242 patients (54.8%) developed distant metastases as the initial site of progression. Multivariable analysis revealed pN2–3 (hazard ratio [HR] 2.14; 95% confidence interval [95% CI] 1.45–3.17), pM1 (HR 2.11; 95% CI 1.22–3.64), and preoperative chemotherapy (HR 1.52; 95% CI 1.09–2.11) as significant predictors of distant progression. The 2-year distant progression rates were 76.3% (95% CI 67.2%-82.9%) for pN2–3, 78.3% (95% CI 55.5%–88.4%) for pM1, and 46.3% (95% CI 32.5%–57.3%) for pN0. Conclusions: In patients with T4 esophageal cancer and extensive lymph node metastasis, the decision to perform combined organ resection should be made with caution. Conversely, T4 patients without lymph node metastasis may benefit from extended surgery with combined organ resection.

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

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

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.

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

Background: Postoperative pneumonia is a serious prognostic problem that can appear after esophagectomy in patients with esophageal cancer. The past reports have considered the usefulness of perioperative culture examinations for predicting postoperative pneumonia; however, the direct relationship between these examinations and postoperative complications remains unclear. Methods: This study retrospectively analyzed esophageal cancer patients who underwent esophagectomy followed by sputum culture on the first postoperative day. The bacterial species that frequently cause hospital-acquired pneumonia were chosen as the target species in this study. The relationship between culture examination and postoperative pneumonia within one week (7 days) after esophagectomy was investigated. Results: Sputum cultures on the first postoperative day were investigated in 238 patients who underwent esophagectomy for esophageal cancer. Forty-one patients developed pneumonia within one week after surgery. The target bacterial species were detected in 26 of 238 sputum cultures (10.9%). In the univariate analysis, a Brinkman index, detection of target bacterial species, detection of Gram-positive cocci, and Gram-negative rods were significantly associated with postoperative pneumonia. In the three independent multivariate analyses, the target bacterial species, Gram-positive cocci, and Gram-negative rods (p = 0.001, 0.042, and < 0.001) were individually identified as independent risk factors of postoperative pneumonia in addition to a Brinkman index. Conclusions: Detection of target bacterial species by sputum culture on the first postoperative day after esophagectomy was an independent risk factor of postoperative pneumonia within 7 days after surgery. Prospective studies for the prevention of early postoperative pneumonia using sputum culture on the first postoperative day can be considered.

Introduction: A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. Materials and methods: Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relationship between ctDNA alterations and recurrence in patients with locally advanced ESCC. Results: Pretreatment samples from 25 patients (100 %) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92 % for ctDNA-negative patients and 8 % for ctDNA-positive patients (p < 0.001). Conclusions: Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.

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.

Background: Although proximal gastrectomy (PG) is a function-preserving surgical option, it remains unclear as to which reconstruction method can prevent reflux and maintain body composition. Methods: Patients who underwent PG at Keio University between April 2011 and November 2018 were analyzed. Changes in the subcutaneous and visceral adipose tissues were comparatively assessed before and after a year of surgery for three common reconstruction methods. We also compared the endoscopic findings of reflux esophagitis and the number of patients prescribed with proton-pump inhibitor after a year of surgery. Results: This study included 76 patients, of which 33 patients underwent esophagogastrostomy with a circular stapler (CS), 35 under double flap (DF) reconstruction, and 8 underwent double tract (DT) reconstruction. Comparing esophagogastrostomy (CS and DF) and DT showed that esophagogastrostomy could significantly preserve both subcutaneous and visceral adipose tissues (P < 0.001 and P = 0.04, respectively). However, the change in the subcutaneous and visceral adipose tissues was comparable between CS and DF. As for reflux esophagitis, DF showed the lowest incidence rate for esophagitis and the least number of patients who were prescribed a proton-pump inhibitor. Conclusion: DF is a relatively better reconstruction method for preserving fat mass and preventing reflux among the three common reconstruction methods.

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