Current status of the surgical training system in Japan: results of a nationwide questionnaire survey of graduating surgical trainees.

PURPOSE: To identify the problems trainees face during surgical training in Japan. METHODS: A nationwide online questionnaire survey was conducted targeting newly certified surgical trainees. RESULTS: The response rate was 53.8% (758/1410). Among those respondents, 25.6% were women, 71.4% were either married or had a partner, 41.3% had children, 72.7% had performed over 200 surgeries under general anesthesia, and 54.1% had chosen, before graduating from medical school, to become a surgeon. While 88.8% were interested in learning surgical techniques, 63.8% were hesitant to become a surgeon for fear of a compromised quality of private life (QOL). Conversely, only 1.4% chose their surgical training programs based on QOL. Overall, 84.6% of the trainees were satisfied with their training and this correlated with the number of surgeries performed. Only 29.9% received non-technical skill training. The average number of night shifts per month was 5.6, and 10.6% worked over 80 h per week. Harassment was reported by 41.5% of the respondents. Moreover, 33.0% had considered dropping out at some time, primarily because of their QOL (51.1%) or the harassment they had encountered (50.4%). CONCLUSION: This survey revealed that while trainees were satisfied with the overall training system, issues such as long working hours and harassment are prevalent. Working to improve these issues could make surgery more attractive for young trainees.

Effects of povidone-iodine wound irrigation on surgical site infection in gastroenterological surgery: A randomized controlled trial.

BACKGROUND: The irrigation efficacy of a povidone-iodine solution to prevent surgical site infection is still controversial. We assessed the irrigation effect with a povidone-iodine solution on the incidence of surgical site infection after gastroenterological surgery. METHODS: This study is a single-center, prospective, randomized, blinded-end point superiority trial for surgical wound irrigation. Patients undergoing gastroenterological surgery were randomly assigned in a 1:1 replacement ratio using computer-generated randomization. Patients were grouped according to their surgical wound treatment into the control group using the normal sterile saline and the povidone-iodine group using 10% povidone-iodine solution after the NS solution. The main finding was 30-day surgical site infections assessed in the full analysis set. RESULTS: From November 2020 to December 2022, 697 of 894 patients were eligible for the study, among which 347 were in the povidone-iodine group and 350 in the control group. Thirty-day surgical site infections occurred in 100 (14%) patients-54 (16%) in the povidone-iodine group and 46 (13%) in the control group (odds ratio, 1.229; 95% CI, 0.800-1.889; P = .406). Superficial incisional surgical site infections occurred in 30 (9%) and 15 (4%) patients, respectively (odds ratio, 2.154; 95% CI, 1.134-4.090; P = .026). Only 3 patients (1%) in the control group developed adverse skin reactions. CONCLUSION: This study examined the irrigation efficacy of povidone-iodine for surgical site infection prevention compared to control in gastroenterological surgery. Povidone-iodine wound irrigation has shown no additional beneficial effect on the occurrence of surgical site infections.

A silicone disc for liver retraction in laparoscopic gastrectomy reduces the postoperative increase in the liver enzyme level.

PURPOSE: To compare changes in liver enzyme levels on postoperative day 1 between patients with and without silicone disc (SD) use during liver retraction in laparoscopic gastrectomy for gastric cancer and laparoscopic gastric mobilization for esophageal cancer. METHODS: This prospective randomized controlled phase II trial was conducted between June 30, 2020, and November 30, 2022, to investigate the benefits of using an SD with a Nathanson liver retractor (NLR) compared with those using an NLR in laparoscopic gastrectomy and gastric mobilization. The primary endpoint was the change in transaminase level on postoperative day 1. RESULTS: A total of 86 patients received randomized assignments and were included in the analysis, with 44 assigned to the SD (-) group and 42 to the SD (+) group. On postoperative day 1, the SD (+) group showed a significantly lower increase in the aspartate aminotransferase levels than the SD (-) group (SD [+], 94.4% vs. SD [-], 179.8%; p = 0.012). Similarly, the SD (+) group showed a significantly lower increase in alanine aminotransferase levels than the SD (-) group (SD [+], 71.6% vs. SD [-], 201.5%; p = 0.014). CONCLUSION: In laparoscopic gastrectomy, the use of an SD combined with an NLR appears to mitigate postoperative liver dysfunction.

Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma.

The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan-Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, p = 0.007; HR = 0.54, p = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1's contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.

Protocol digest of a randomized controlled adaptive Phase II/III trial of neoadjuvant chemotherapy for Japanese patients with oesophagogastric junction adenocarcinoma: Japan Clinical Oncology Group Study JCOG2203 (NEO-JPEG).

Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182).

Clinical impact of diarrhea during enteral feeding after esophagectomy.

BACKGROUND: Enteral feeding (EF) is recommended to enhance nutritional status after esophagectomy; however, diarrhea is a common complication of EF. We investigated the clinical and prognostic impact of diarrhea during EF after esophagectomy. METHODS: One hundred and fifty-two patients who underwent transthoracic esophagectomy were enrolled. The King's stool chart was used for stool characterization. The short- and long-term outcomes were compared between a non-diarrhea (Group N) and diarrhea group (Group D). RESULTS: A higher dysphagia score (≥ 1) was observed more frequently in Group D than in Group N (45.7% vs. 19.8%, p = 0.002). Deterioration of serum total protein, serum albumin, serum cholinesterase, and the prognostic nutritional index after esophagectomy was greater in Group D than in Group N (p = 0.003, 0.004, 0.014, and 0.001, respectively). Patients in Group D had significantly worse overall survival (OS) and recurrence-free survival (RFS) than those in Group N (median survival time (MST): OS, 21.9 vs. 30.6 months, p = 0.001; RFS, 12.4 vs. 27.7 months, p < 0.001). In stratified analysis due to age, although there was no difference in OS with or without diarrhea in young patients (MST: 24.1 months in a diarrhea group vs. 33.6 months in a non-diarrhea group, p = 0.218), patients in a diarrhea group had significantly worse OS than those in a non-diarrhea group in elderly patients (MST: 17.8 months vs. 27.9 months, p < 0.001). CONCLUSIONS: Diarrhea during EF can put elderly patients at risk of postoperative malnutrition and a poor prognosis after esophagectomy.

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.

What is the best reconstruction procedure after esophagectomy? A meta-analysis comparing posterior mediastinal and retrosternal approaches.

Thoracic esophagectomy is a particularly invasive and complicated surgical procedure, with a reconstruction of the gastrointestinal tract, such as the stomach, jejunum, or colon. The posterior mediastinal, retrosternal, and subcutaneous routes are the three possible esophageal reconstruction routes. Each route has advantages and disadvantages, and the optimal reconstruction route after esophagectomy remains controversial. Additionally, the best anastomotic techniques after esophagectomy in terms of location (Ivor Lewis or McKeown) and suturing (manual or mechanical) are debatable. Our meta-analysis investigating postoperative complications after esophagectomy between the posterior mediastinal and retrosternal routes revealed that the posterior mediastinal route was associated with a significantly lower anastomotic leakage rate than the retrosternal route (odds ratio = 0.78, 95% confidence interval: 0.70-0.87, p < 0.0001). Conversely, pulmonary complications (odds ratio = 0.80, 95% confidence interval: 0.58-1.11, p = 0.19) and mortality between the posterior mediastinal and retrosternal routes (odds ratio = 0.79, 95% confidence interval: 0.56-1.12, p = 0.19) were not significantly different. However, the incidence of pneumonia may be lower when using the retrosternal route rather than the posterior mediastinal route for performing minimally invasive esophagectomy. The McKeown procedure is oncologically necessary for tumors located above the carina to dissect upper mediastinal and cervical lymph nodes; however, the Ivor Lewis procedure offers perioperative and oncological safety for tumors located under the carina. An individualized treatment strategy for selecting the optimal reconstruction procedure can be proposed in future studies based on oncological and patient risk factors considering mid- to long-term quality of life.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

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.

Recent Advances in Sentinel Node Navigation Surgery for Early Gastric Cancer.

Maintaining the postoperative quality of life (QOL) while ensuring curability without overtreatment is important in the treatment of early gastric cancer. Postoperative QOL is anticipated to be maintained through minimally invasive function-preserving gastrectomy in early gastric cancer. The concept of the sentinel lymph node (SN) basin is essential to maintain the curability of early gastric cancer using minimally invasive function-preserving gastrectomy. However, additional resection after surgery is difficult to perform in gastric cancer. Thus, the SN basin theory is important. Recently, a multicenter randomized phase III trial in South Korea (SENORITA trial) proved that laparoscopic sentinel node navigation surgery (LSNNS) for stomach preservation results in better postoperative QOL compared with standard gastrectomy in patients with early gastric cancer. LSNNS contributes to patients' QOL based on the concept that curability is not impaired. A multicenter nonrandomized phase III trial is ongoing in Japan, and oncologic safety is expected to be demonstrated. LSNNS has been established as a treatment option for selected patients with early gastric cancer, and its application will become widespread in the future.

Usefulness of Procalcitonin as a Predictor of Long-Term Prognosis in the Early Postoperative Period after Esophagectomy for Esophageal Cancer.

The aim of this study was to investigate the relationship between serum procalcitonin (PCT) levels after esophagectomy and infectious complications and long-term prognosis. A total of 105 patients who underwent esophagectomy between 2012 and 2019 were stratified into two groups: PCT-High group of ≥1 ng/mL and PCT-Low group of <1 ng/mL. The clinical outcomes and prognostic factors were compared between the two groups 2 postoperative days (POD), 4 POD, and 7 POD after esophagectomy. As the postoperative days passed, the association between PCT and infectious complications became stronger, and the positive predictive value was 100% at 7 POD. At 2 POD, there was no significant association between PCT elevation and infectious complications. Patients in the PCT-Low group had significantly worse overall survival (OS) and recurrence-free survival (RFS) than those in the PCT-High group at 2 POD (p = 0.026 and p = 0.011, respectively). In multivariate analysis, advanced pathological stage (hazard ratio (HR), 5.348; 95% confidence interval (CI), 2.299−12.500; p < 0.001) and PCT-Low group at 2 POD (HR, 3.673; 95% CI, 1.116−12.092; p = 0.032) were also independent predictors of worse OS. PCT in the early postoperative period after esophagectomy could be a good predictor of prognosis.

Neutrophil-to-Lymphocyte Ratio to Predict the Efficacy of Immune Checkpoint Inhibitor in Upper Gastrointestinal Cancer.

BACKGROUND/AIM: Although the effectiveness of immune checkpoint inhibitors (ICIs) in upper gastrointestinal (UGI) cancer including esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal adenocarcinoma (GEA) has been proven, prediction of their efficacy remains unknown. This study aimed to develop optimal serum nutritional indicators or a combination of blood cell components to predict the efficacy of ICI before beginning UGI cancer treatment. PATIENTS AND METHODS: We retrospectively reviewed the data of 61 UGI cancers (31 ESCC and 30 GEA) patients treated with nivolumab or pembrolizumab. We investigated the impact of serum albumin level, total lymphocyte count (TLC), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) on the efficacy of ICIs and long-term survival. The median cutoff value was adopted separately in ESCC and GEA. RESULTS: NLR-Low was significantly correlated with better overall survival (p=0.014), and PLR-Low was significantly correlated with improved disease control rate and better progression-free survival in UGI cancer patients. Both results indicate that a better prognosis is correlated to a greater number of lymphocytes. Multivariate analysis revealed that NLR-High [hazard ratio (HR)=2.865; 95% confidence interval (CI)=1.030-7.937; p=0.044] was the only independent poor prognostic factor. CONCLUSION: NLR-Low has the potential to predict the good efficacy of ICIs and survival outcomes in patients with UGI cancer. NLR could be useful in determining the optimal treatment strategies for these patients.

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

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.

Development and Validation of the Optimal Circumferential Resection Margin in Pathological T3 Esophageal Cancer: A Multicenter, Retrospective Study.

BACKGROUND: The clinical significance of circumferential resection margin (CRM) in esophageal squamous cell carcinoma (ESCC) remains unclear. Optimal CRM for predicting the recurrence of pathological T3 ESCC was investigated. METHODS: Seventy-three patients were retrospectively investigated in the development cohort. Patients were divided into CRM-negative and CRM-positive groups, and clinicopathological factors and survival outcomes were compared between the groups. The cutoff value was validated in another validation cohort (n = 99). RESULTS: Receiver operating characteristic analysis in the development cohort showed the cutoff value of CRM was 600 µm. In the validation cohort, patients in the CRM-positive group showed a significantly higher rate of locoregional recurrence (p = 0.006) and worse recurrence-free survival (RFS) (p < 0.001) than those in the CRM-negative group. Multivariate analysis identified positive CRM as an independent predictive factor for poor RFS (hazard ratio, 2.695; 95% confidence interval, 1.492-4.867; p = 0.001). The predictive value of our criteria of positive CRM for RFS was higher than that of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) criteria. Stratified analysis in the neoadjuvant chemotherapy groups also revealed that the rate of locoregional recurrence was higher in the CRM-positive group than in the CRM-negative group both in the pathological N0 and N1-3 subgroups. CONCLUSIONS: CRM of 600 µm can be the optimal cutoff value rather than the RCP and CAP criteria for predicting locoregional recurrence after esophagectomy. These results may support the impact of perioperative locoregional control of locally advanced ESCC.

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.