Automated artificial intelligence-based phase-recognition system for esophageal endoscopic submucosal dissection (with video).

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.

Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

No difference in the incidence of postoperative pulmonary complications between abdominal laparoscopy and laparotomy for minimally invasive thoracoscopic esophagectomy: a retrospective cohort study using a nationwide Japanese database.

INTRODUCTION: There remains a lack of evidence regarding the optimal abdominal approach, including laparoscopy, hand-assisted, and open laparotomy for minimally invasive thoracoscopic esophagectomy. We aimed to compare the incidence of postoperative complications, particularly pulmonary complications, between laparoscopy and open laparotomy for minimally invasive thoracoscopic esophagectomy using nationwide Japanese databases. METHODS: Data from patients in the National Clinical Database (NCD) who underwent thoracoscopic esophagectomy for esophageal cancer were analyzed. The incidence of pulmonary complications was compared between abdominal laparoscopy and laparotomy after matching the propensity scores (PS) from preoperative factors to account for confounding bias. Laparoscopic-assisted surgery (LAS) was also compared to hand-assisted laparoscopic surgery (HALS). RESULTS: Of the 24,790 patients who underwent esophagectomy between 2018 and 2021, data from 12,633 underwent thoracoscopic procedure. The proportion of patients who experienced pulmonary complications did not significantly differ between the laparoscopy group and the laparotomy group after matching (664/3195 patients, 20.8% versus 702/3195 patients, 22.0%; P = 0.25). No difference in the incidence of pulmonary complications was observed among patients treated using the laparoscopic approach (508/2439 patients, 20.8% in the LAS group versus 498/2439 patients, 20.4% in the HALS group; P = 0.72). CONCLUSIONS: We observed no significant difference in the incidence of postoperative pulmonary complications between laparoscopy and laparotomy for thoracoscopic esophagectomy. Short-term outcomes were similar between the laparoscopic-assisted approach and the hand-assisted approach. This study provides valuable insights into the optimal abdominal approach for thoracoscopic esophagectomy using data from a nationwide database that reflect real-world clinical practice.

The Usability of Intensive Imaging Surveillance After Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

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

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

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

Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy. PATIENTS AND METHODS: Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy. Next-generation sequencing was performed to identify mutations from the plasma and the primary tumor. The relationships between changes in ctDNA and the pathological response and recurrence were assessed in patients with locally advanced ESCC. RESULTS: In pretreatment samples from 13 patients, multiple concordant mutations in ctDNA and primary tumors were observed in 11 patients (85%), who were classified as ctDNA positive before treatment. The ctDNA positive rate after NAC correlated with the pathological response (responders, 25%; nonresponders, 100%; p = 0.007). The risk of recurrence increased significantly in patients with positive ctDNA after surgery in analysis of 16 patients; the 1-year recurrence-free survival rates were 90 and 0% in ctDNA-negative and ctDNA-positive groups, respectively (p = 0.0008). In two patients with postoperative recurrence, ctDNA was detected approximately 5.5 months earlier than the diagnosis using radiographical imaging. CONCLUSIONS: ctDNA is a promising biomarker for predicting pathological response and postoperative recurrence in ESCC. To demonstrate the external validity, we are currently preparing a multicenter prospective study.

Updates of perioperative multidisciplinary treatment for surgically resectable esophageal cancer.

Esophageal cancer has one of the poorest prognoses among all cancer types, due to the propensity for an early spread through the lymphatics and the difficulty to perform surgical treatment. To improve the prognosis, the management of esophageal cancer has been developed through the conduct of several clinical trials worldwide. In western societies, neoadjuvant chemoradiotherapy has been established as the standard treatment approach, as indicated by the results of the CROSS trial. Recently, the Japanese JCOG1109 trial demonstrated the significant improvement of survival by neoadjuvant triplet chemotherapy. As an adjuvant treatment, an immune checkpoint inhibitor has shown promising results in the CheckMate-577 trial. Including adjuvant S-1 mono therapy as another option, a randomised control phase III study will determine the ideal treatment for surgically resectable esophageal cancer. Furthermore, the efficacy and safety of neoadjuvant cisplatin +5-fluorouracil or DCF plus nivolumab are examined in the JCOG1804E (FRONTiER) study. In addition to definitive chemoradiation therapy, the SANO trial is examining the safety and efficacy of active surveillance after neoadjuvant chemoradiotherapy, which might give us the choice to adopt organ preservation approach. The development of treatment has progressed dramatically with the advent of immunotherapy. Considering the biomarkers to predict the treatment response and prognosis, individualised multidisciplinary treatment strategies should be established for esophageal cancer patients.

Evaluation of surgical complexity by automated surgical process recognition in robotic distal gastrectomy using artificial intelligence.

BACKGROUND: Although radical gastrectomy with lymph node dissection is the standard treatment for gastric cancer, the complication rate remains high. Thus, estimation of surgical complexity is required for safety. We aim to investigate the association between the surgical process and complexity, such as a risk of complications in robotic distal gastrectomy (RDG), to establish an artificial intelligence (AI)-based automated surgical phase recognition by analyzing robotic surgical videos, and to investigate the predictability of surgical complexity by AI. METHOD: This study assessed clinical data and robotic surgical videos for 56 patients who underwent RDG for gastric cancer. We investigated (1) the relationship between surgical complexity and perioperative factors (patient characteristics, surgical process); (2) AI training for automated phase recognition and model performance was assessed by comparing predictions to the surgeon-annotated reference; (3) AI model predictability for surgical complexity was calculated by the area under the curve. RESULT: Surgical complexity score comprised extended total surgical duration, bleeding, and complications and was strongly associated with the intraoperative surgical process, especially in the beginning phases (area under the curve 0.913). We established an AI model that can recognize surgical phases from video with 87% accuracy; AI can determine intraoperative surgical complexity by calculating the duration of beginning phases from phases 1-3 (area under the curve 0.859). CONCLUSION: Surgical complexity, as a surrogate of short-term outcomes, can be predicted by the surgical process, especially in the extended duration of beginning phases. Surgical complexity can also be evaluated with automation using our artificial intelligence-based model.

Towards automatic verification of the critical view of the myopectineal orifice with artificial intelligence.

BACKGROUND: Visualization of key anatomical landmarks is required during surgical Trans Abdominal Pre Peritoneal repair (TAPP) of inguinal hernia. The Critical View of the MyoPectineal Orifice (CVMPO) was proposed to ensure correct dissection. An artificial intelligence (AI) system that automatically validates the presence of key and marks during the procedure is a critical step towards automatic dissection quality assessment and video-based competency evaluation. The aim of this study was to develop an AI system that automatically recognizes the TAPP key CVMPO landmarks in hernia repair videos. METHODS: Surgical videos of 160 TAPP procedures were used in this single-center study. A deep neural network-based object detector was developed to automatically recognize the pubic symphysis, direct hernia orifice, Cooper's ligament, the iliac vein, triangle of Doom, deep inguinal ring, and iliopsoas muscle. The system was trained using 130 videos, annotated and verified by two board-certified surgeons. Performance was evaluated in 30 videos of new patients excluded from the training data. RESULTS: Performance was validated in 2 ways: first, single-image validation where the AI model detected landmarks in a single laparoscopic image (mean average precision (MAP) of 51.2%). The second validation is video evaluation where the model detected landmarks throughout the myopectineal orifice visual inspection phase (mean accuracy and F-score of 77.1 and 75.4% respectively). Annotation objectivity was assessed between 2 surgeons in video evaluation, showing a high agreement of 88.3%. CONCLUSION: This study establishes the first AI-based automated recognition of critical structures in TAPP surgical videos, and a major step towards automatic CVMPO validation with AI. Strong performance was achieved in the video evaluation. The high inter-rater agreement confirms annotation quality and task objectivity.

Lymph node metastatic patterns and the development of multidisciplinary treatment for esophageal cancer.

Abundant lymphatic flow and the anatomical location of the esophagus can result in the widespread distribution of lymph node metastasis of esophageal cancer from the cervical to the abdominal field. Historically, the Japan Esophageal Society and American Joint Committee on Cancer offer two different classifications of lymph node group location surrounding the esophagus. The location of sentinel lymph nodes in midthoracic esophageal cancer reflects the variety of lymphatic drainage routes. In fact, in cT1N0 esophageal cancer, pathological lymph node metastasis has been observed from the cervical to the abdominal field, and the locations were shown to be closely linked to the primary tumor location in advanced stages. While the impact of histology on the distribution of LN metastasis has been extensively debated, a recent prospective study on esophagogastric junction cancer found that metastatic patterns did not differ by histology. Thoracic duct lymph nodes were defined as one of the regional lymph node stations in the mediastinum. Although lymph node metastasis around the thoracic duct has occasionally been observed, the oncologic impact of thoracic duct lymph node dissection has not been fully elucidated. To eradicate tumors locoregionally, three-field lymph node dissection, a strategy for extended lymph node clearance, has been established. In esophagectomy, three-field lymph node dissection is defined as a procedure for complete regional cervico-thoraco-abdominal lymph node dissection. However, its therapeutic efficacy must be evaluated based on the balance between oncological outcomes and possible added surgical risk. To further improve survival, multidisciplinary treatment consisting of surgery, chemotherapy, and radiotherapy has been established worldwide as a standard treatment for esophageal cancer. Now that neoadjuvant therapy followed by esophagectomy is the standard, adding adjuvant therapy including immunotherapy could be a promising treatment option. The ideal combination of various multidisciplinary treatment approaches and extensive LN dissection need to be established to improve the oncological outcomes for EC patients.

Oncological and physiological impact of thoracic duct resection in esophageal cancer.

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.

The impact of thoracic duct resection on the long-term body composition of patients who underwent esophagectomy for esophageal cancer and survived without recurrence.

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.

Inhibitory effect of aspirin on inflammation-induced lung metastasis of cancer cells associated with neutrophil infiltration.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The relationship between the esophageal endoscopic submucosal dissection technical difficulty and its intraoperative process.

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.

Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

Automated Surgical-Phase Recognition for Robot-Assisted Minimally Invasive Esophagectomy Using Artificial Intelligence.

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.

Evaluation of clinical validity of an S-1 dosage formula based on renal function using data of the SPIRITS and the G-SOX trials.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: It is suggested that the refined S-1 dosage formula can recommend optimal dose in terms of safety and efficacy.

Robotic endoscopic cooperative surgery for colorectal tumors: a feasibility study (with video).

BACKGROUND: Laparoscopic endoscopic cooperative colorectal surgery (LECS-CR) is a promising technique to achieve full-thickness resection of colorectal tumors. This approach has shown good rates of complete resection and low local recurrence, especially for large laterally spreading tumors, which are difficult to remove via endoscopy alone. However, it is often difficult to prevent peritoneal leakage of intestinal content, causing infections and risks of cancer spreading. It was hypothesized that a robotic assistance could make the procedure easier and decrease intestinal fluid leakage. This preclinical trial aims to assess the feasibility of robotic and endoscopic cooperative colorectal surgery (RECS-CR). METHODS: LECS-CR was performed in five female pigs and RECS-CR was also performed in five female pigs. With the animal under general anesthesia, pseudotumors were created on the colonic mucosa at a distance comprised between 20 and 25 cm from the anal verge. Desired resection margins were marked endoscopically and two stay sutures were placed either robotically or laparoscopically. A mucosa-to-submucosa dissection was performed endoscopically along the markings. Complete full-thickness dissection was performed cooperatively. The specimen was withdrawn endoscopically. The colon was closed using a self-fixating running suture. Abdominal contaminations, operating times, complications, and complete resections were evaluated and compared between LECS-CR and RECS-CR. RESULTS: The mean number of colonies of Escherichia coli in the RECS group was significantly lower than in the LECS group (36.7 ± 30.2 vs. 142.2 ± 78.4, respectively, p < 0.05). Operating time was comparable (118 ± 11.2 vs. 98.6 ± 25.7, respectively, p = 0.22). Two stenoses occurred in the LECS group. R0 resection was achieved in all cases. CONCLUSION: This study suggests that RECS-CR is feasible and has the potential to reduce intestinal content leakage, potentially preventing postoperative infections.

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

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