Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.

Antimicrobial Prophylaxis With Ampicillin-sulbactam Compared With Cefazolin for Esophagectomy: Nationwide Inpatient Database Study in Japan.

OBJECTIVE: To assess the effect of antimicrobial prophylaxis with ampicillin-sulbactam (ABPC/SBT) compared with cefazolin (CEZ) on the short-term outcomes after esophagectomy. BACKGROUND: CEZ is widely used for antimicrobial prophylaxis in esophagectomy without procedure-specific evidence, whereas ABPC/SBT is preferred in some hospitals to target both aerobic and anaerobic oral bacteria. METHODS: Data of patients who underwent esophagectomy for cancer between July 2010 and March 2019 were extracted from a nationwide Japanese inpatient database. Overlap propensity score weighting was conducted to compare the short-term outcomes [including surgical site infection (SSI), anastomotic leakage, and respiratory failure] between antimicrobial prophylaxis with CEZ and ABPC/SBT after adjusting for potential confounders. Sensitivity analyses were also performed using propensity score matching and instrumental variable analyses. RESULTS: Among 17,772 eligible patients, 16,077 (90.5%) and 1695 (9.5%) patients were administered CEZ and ABPC/SBT, respectively. SSI, anastomotic leakage, and respiratory failure occurred in 2971 (16.7%), 2604 (14.7%), and 2754 patients (15.5%), respectively. After overlap weighting, ABPC/SBT was significantly associated with a reduction in SSI [odds ratio 0.51 (95% CI: 0.43-0.60)], anastomotic leakage [0.51 (0.43-0.61)], and respiratory failure [0.66 (0.57-0.77)]. ABPC/SBT was also associated with reduced respiratory complications, postoperative length of stay, and total hospitalization costs. The proportion of Clostridioides difficile colitis and noninfectious complications did not differ between the groups. Propensity score matching and instrumental variable analyses demonstrated equivalent results. CONCLUSIONS: The administration of ABPC/SBT as antimicrobial prophylaxis for esophagectomy was associated with better short-term postoperative outcomes compared with CEZ.

Significance of Surgery for Resectable M1 Lymph Node Metastases Without Organ Metastasis in Esophageal Carcinoma in the Era of Neoadjuvant Treatment.

BACKGROUND: M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma. PATIENTS AND METHODS: This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis. RESULTS: Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status. CONCLUSION: The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Neoadjuvant Chemotherapy Improves Feasibility of Larynx Preservation and Prognosis in Resectable Locally Advanced Cervical Esophageal Cancer.

BACKGROUND: The optimal strategy for cervical advanced esophageal cancer remains controversial in terms of oncologic outcome as well as vocal and swallowing function. Recently, in East Asian countries, neoadjuvant chemotherapy (NAC) has been a standard strategy for advanced esophageal cancer. METHODS: This study included 37 patients who underwent NAC, and 33 patients who underwent definitive chemoradiation therapy (dCRT) as larynx-preserving treatment for locally advanced cervical esophageal cancer from 2016 to 2021. This study retrospectively investigated outcomes, with comparison between NAC and dCRT for locally advanced cervical esophageal cancer. RESULTS: Larynx preservation was successful for all the patients with NAC and dCRT. After NAC, the rate of complete or partial response was 78.4%, and 30 patients underwent larynx-preserving surgery. On the other hand, after dCRT, the complete response rate was 71.9%, and 4 patients underwent larynx-preserving salvage surgery. Overall survival (OS) and progression free survival were similar between the two groups. However, for the patients with resectable cervical esophageal cancer (cT1/2/3), the 2-year OS rate was significantly higher with NAC (79.9%) than with dCRT (56.8%) (P = 0.022), and the multivariate analyses identified only NAC and cN0, one of the two as a significantly independent factor associated with a better OS (NAC: P = 0.041; cN0, 1: P = 0.036). CONCLUSION: The study showed that NAC as larynx-preserving surgery for resectable cervical esophageal cancer preserved function and had a better prognosis than dCRT. The authors suggest that NAC may be standard strategy for larynx preservation in patients with resectable cervical esophageal cancer.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

OBJECTIVE: The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. METHODS: We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. RESULTS: The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P = 0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P = 0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P = 0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P = 0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P < 0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P < 0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P = 0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P < 0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P = 0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P = 0.164). CONCLUSIONS: In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Robot-assisted transcervical esophagectomy with a bilateral cervical approach for thoracic esophagectomy.

BACKGROUND: Thoracic esophageal cancer resection through the neck approach has recently been reported as mediastinoscopic surgery. We present the first report of a new minimally invasive technique for thoracic esophageal cancer: robot-assisted transcervical esophagectomy with a bilateral cervical approach. METHODS: Ten cases of robot-assisted bilateral transcervical esophagectomy performed at the National Cancer Center Hospital East, Japan, from February 2023 to August 2023 were reviewed. The short-term surgical outcomes were presented, and the feasibility and efficacy of this procedure were discussed. RESULTS: The mean operation time for the cervical procedure was 184.2 ± 23.6 min. The total time for the whole procedure was 472.7 ± 28.4 min, and total intraoperative blood loss was 162.2 ± 40.0 ml. Among the 10 cases, one patient developed recurrent nerve paralysis, one patient developed pulmonary complications, and no patients developed postoperative pneumonia. The median postoperative hospital stay was 22 (range: 12-43) days. No patients developed severe postoperative surgical complications, which were graded as Clavien-Dindo ≥ III. The total number of surgically harvested mediastinal lymph nodes was 37.2 ± 11.2. CONCLUSIONS: Robot-assisted bilateral transcervical esophagectomy, a novel procedure for thoracic esophageal cancer, was safe and feasible. Using this procedure, the incidence of recurrent nerve palsy, which is a problem with transcervical esophagectomy and mediastinoscopic esophagectomy, is expected to decrease.

Total RAMIE with three-field lymph node dissection by a simultaneous two-team approach using a new docking method for esophageal cancer.

BACKGROUND: Thoracic esophageal cancer surgery using robotic approaches for the thoracic and abdominal parts has recently been reported as total robot-assisted minimally invasive esophagectomy (RAMIE). We herein present the first report of a new technique for esophageal cancer: total RAMIE with three-field lymph node dissection (3FLND) by a simultaneous two-team approach using a new docking method. METHODS: We reviewed 20 patients who underwent total RAMIE with 3FLND by a simultaneous two-team approach at the National Cancer Center East Hospital from March 2023 to September 2023. Short-term surgical outcomes and the safety and efficacy of this technique were analyzed. RESULTS: The mean operative time for abdominal surgery with this new docking technique was 135 ± 19.6 min. The total operative time was 488 ± 42.9 min, and the time from the end of abdominal manipulation to the end of surgery was 80.1 ± 15.6 min. The intraoperative blood loss was 116.7 ± 64.4 mL. The incidence of anastomotic leakage, postoperative vocal cord paralysis, and postoperative pneumonia was 10%, 5%, and 10%, respectively. The median postoperative hospital stay was 14 days (range 11-63 days). No in-hospital deaths occurred, and R0 resection was possible in all cases. The average number of lymph nodes dissected was 87.7. CONCLUSION: These results demonstrate that total RAMIE with a simultaneous two-team approach using the new docking method can be safely introduced. The simultaneous cervical and abdominal manipulation with the new docking method allowed total RAMIE without prolonging the operating time, suggesting that it may be a valuable approach for esophageal cancer surgery.

Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

BACKGROUND: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. METHODS: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. RESULTS: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. CONCLUSION: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

Long-term outcomes after non-curative endoscopic resection for esophageal squamous cell carcinoma followed by additional chemoradiotherapy.

Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is evaluated pathologically, and additional treatment is recommended for cases resulting in non-curative resection, defined as pMM with lymphovascular invasion (LVI), pSM, or positive vertical margin. This study aimed to assess long-term outcomes and risk factors for recurrence in patients with ESCC treated with non-curative ER followed by additional chemoradiotherapy (CRT). We retrospectively reviewed the clinical courses of patients who underwent non-curative ER followed by additional CRT for ESCCs between August 2007 and December 2017. Recurrence rates and risk factors for recurrence were analyzed. Among 97 patients with non-curative ER, 73 underwent additional CRT. With a median follow-up period of 71 months, recurrences were observed in 10 (14%) of 73 patients, with a median interval of 24.5 (1-59 months). The 3- and 5-year recurrence-free survival were 89 and 85%, respectively, and the 3- and 5-year overall survival rates were 96 and 91%, respectively. Multivariate analysis showed that lymphatic invasion was an independent risk factor for recurrence in patients with non-curative ESCC receiving additional CRT. Among the 10 patients with recurrence, 4, 3, 2, and 1 underwent surgery, chemotherapy, supportive care, and CRT, respectively. Notably, all four patients who underwent surgery survived, regardless of regional and/or distant lymph node metastasis. Lymphatic invasion is an independent risk factor for the recurrence of non-curative ESCCs. Careful follow-up is required for at least 5 years after ER with additional CRT.

Efficiency of conversion surgery for esophageal squamous cell carcinoma with solitary abdominal para-aortic lymph node metastasis.

PURPOSE: Abdominal para-aortic lymph nodes (PANs) are sites of distant metastasis in esophageal squamous cell cancer (ESCC). The prognosis of patients with Stage IVB ESCC and abdominal PAN metastasis is extremely poor. However, chemotherapy for ESCC has recently been developed, and the effectiveness of combined induction therapy and conversion surgery remains unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of conversion surgery for ESCC and solitary abdominal PAN metastases after induction therapy. METHODS: Thirteen patients who underwent conversion esophagectomy for cStage IVB ESCC with solitary abdominal PAN metastasis after induction therapy between January 2017 and October 2022 at our institution were enrolled. The short- and long-term outcomes of conversion surgery were retrospectively evaluated. RESULTS: Three patients (23.1%) had pathological abdominal PAN metastasis, and six patients (46.2%) without pathological abdominal PAN metastasis showed that chemotherapy eliminated the tumors in the abdominal PAN. Three patients (23.1%) had postoperative complications of Clavien-Dindo grade II or higher. The 3-year overall and recurrence-free survival rates were 83.1% and 51.3%, respectively. CONCLUSIONS: Our findings showed that conversion surgery for ESCC and solitary abdominal PAN metastasis led to a good prognosis when induction therapy was successful.

Pectoralis Major Muscle Flap Utilization in Salvage Esophagectomy Including Great Vessel Resection Reconstructed by Prosthetic Grafts.

BACKGROUND: Salvage surgery is a therapeutic option for recurrent or residual esophageal cancer after definitive chemoradiation therapy. This report aimed to describe the procedure of reconstruction after salvage esophagectomy involving great vessel resection using prosthetic grafts, a pectoralis major muscle (PM) flap, and free jejunal transfer, if required. To the best of our knowledge, no previous report has described the reconstruction of the defect after combined esophageal and great vessel resection. PATIENTS AND METHODS: From January 2017 to December 2022, 4 patients underwent salvage esophagectomy with excision of the great vessels and reconstruction with prosthetic grafts, as well as a PM flap placement in a single center. We retrospectively investigated the patients' clinical data. The patients were all men, with a median age of 70 (range, 67-77) years. Regarding neoadjuvant therapy, 2 patients received chemoradiation therapy, 1 patient received radiotherapy only due to drug-induced pneumonia, and 1 patient received chemotherapy with adjuvant radiotherapy. RESULTS: Alimentary tract reconstruction was performed by free jejunal transfer in 2 cases, direct suture in 1 case, and stomach roll in 1 case. In all cases, a vascular bypass was established before tumor resection. We created mediastinal tracheostoma in 2 cases. A PM flap was inserted to cover the prosthetic grafts and approximate the tracheal mucosa. With regard to major complications, leakage from the jejunal esophageal anastomotic site was observed in 2 cases. The leakage improved with conservative treatment without graft removal or replacement in both cases. CONCLUSIONS: In cases of locally recurrent or residual tumors after definitive chemoradiation therapy, salvage esophagectomy along with great vessel resection, followed by reconstruction using prosthetic grafts, PM flaps, and free jejunal transfer, if necessary, is a useful option.

A novel device to assess the oxygen saturation and congestion status of the gastric conduit in thoracic esophagectomy.

BACKGROUND: In thoracic esophagectomy, anastomotic leakage is one of the most important surgical complications. Indocyanine green (ICG) is the most widely used method to assess tissue blood flow; however, this technique has been pointed out to have disadvantages such as difficulty in evaluating the degree of congestion, lack of objectivity in evaluating the degree of staining, and bias easily caused by ICG injection, camera distance, and other factors. Evaluating tissue oxygen saturation (StO2) overcomes these disadvantages and can be performed easily and repeatedly. It is also possible to measure objective values including the degree of congestion. We evaluate novel imaging technology to assess tissue oxygen saturation (StO2) in the gastric conduit during thoracic esophagectomy. METHODS: Fifty patients were enrolled, with seven excluded due to intraoperative findings, leaving 43 for analysis. These patients underwent thoracic esophagectomy for esophageal cancer. The device was used intraoperatively to evaluate tissue oxygen saturation (StO2) and total hemoglobin index (T-HbI), which guided the optimal site for gastric tube anastomosis. The efficacies of StO2 and T-HbI in relation to short-term outcomes were analyzed. RESULTS: StO2, indicating blood supply to the gastric tube, remained stable beyond the right gastroepiploic artery (RGEA) end but significantly decreased distally to the demarcation line (p <  0.05). T-HbI, indicative of congestion, significantly decreased past the RGEA (p <  0.05). Three patients experienced anastomotic leakage. These patients exhibited significantly lower StO2 (p <  0.01) and higher T-HbI (p <  0.01) at both the RGEA end and the demarcation line. Furthermore, the anastomotic site, usually within 3 cm of the RGEA's anorectal side, also showed significantly lower StO2 (p <  0.01) and higher T-HbI (p <  0.01) in patients with anastomotic leakage. CONCLUSIONS: The novel device provides real-time, objective evaluations of blood flow and congestion in the gastric tube. It proves useful for safer reconstruction during thoracic esophagectomy, particularly by identifying optimal anastomosis sites and predicting potential anastomotic leakage.

Refining postoperative monitoring of recurrent laryngeal nerve injury in esophagectomy patients through transcutaneous laryngeal ultrasonography.

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) leading to vocal cord paralysis (VCP) is a significant complication following minimally invasive esophagectomy (MIE) with upper mediastinal lymphadenectomy. Transcutaneous laryngeal ultrasonography (TLUSG) has emerged as a non-invasive alternative to endoscopic examination for evaluating vocal cord function. Our study aimed to assess the diagnostic value of TLUSG in detecting RLNI by evaluating vocal cord movement after MIE. METHODS: This retrospective study examined 96 patients with esophageal cancer who underwent MIE between January 2021 and December 2022, using both TLUSG and endoscopy. RESULTS: VCP was observed in 36 out of 96 patients (37.5%). The incidence of RLNI was significantly higher on the left side than the right (29.2% vs. 5.2%, P < 0.001). Postoperative TLUSG showed a sensitivity and specificity of 88.5% (31/35) and 86.5% (45/52), respectively, with an AUC of 0.869 (P < 0.001, 95% CI 0.787-0.952). The percentage agreement between TLUSG and endoscopy in assessing VCP was 87.4% (κ = 0.743). CONCLUSIONS: TLUSG is a highly effective screening tool for VCP, given its high sensitivity and specificity. This can potentially eliminate the need for unnecessary endoscopies in about 80% of patients who have undergone MIE.

Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND: Chemotherapy consisting of 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel is the standard perioperative treatment for resectable esophageal adenocarcinoma and esophagogastric junctional adenocarcinoma (EGJ-AC) in Western countries. Meanwhile, preoperative chemotherapy consisting of docetaxel, cisplatin, and 5-fluorouracil (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there are few reports on the safety and efficacy of preoperative DCF for resectable EGJ-AC in the Japanese population. METHODS: Patients with histologically confirmed resectable EGJ-AC who received preoperative DCF (docetaxel 70 mg/m2 and cisplatin 70 mg/m2 on day 1 and continuous infusion of 5-fluorouracil 750 mg/m2/day on days 1-5 every 3 weeks with a maximum of three cycles) between January 2015 and April 2020 were retrospectively evaluated. We assessed the rates of completion of ≥ 2 courses of DCF and R0 resection, histopathological response, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Thirty-two patients were included. Median follow-up was 28.7 (range, 5.2-70.8) months and median age was 63 (range, 42-80) years. Twenty-one patients (66%) had a performance status of 0. The proportions of clinical stage IIA/IIB/III/IVA/IVB disease were 3%/0%/44%/44%/9%, respectively. The treatment completion rate was 84%. A histopathological response of grade 1a/1b/2/3 was obtained in 58%/26%/13%/3% of cases. Median PFS was 40.7 months (95% confidence interval 11.8-NA). Median OS was not reached (80.8% at 3 years). Grade ≥ 3 adverse events were observed in 63% of cases (neutropenia, 44%; febrile neutropenia, 13%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative DCF for resectable EGJ-AC was well tolerated and has promising efficacy.

Impact of Prophylactic Corticosteroid Use on In-hospital Mortality and Respiratory Failure After Esophagectomy for Esophageal Cancer: Nationwide Inpatient Data Study in Japan.

OBJECTIVE: To assess the effect of preoperative prophylactic corticosteroid use on short-term outcomes after oncologic esophagectomy. BACKGROUND: Previous studies have shown that prophylactic corticosteroid use may decrease the risk of respiratory failure following esophagectomy by attenuating the perioperative systemic inflammation response. However, its effectiveness has been controversial, and its impact on mortality remains unknown. METHODS: Data of patients who underwent oncologic esophagectomy between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting, propensity score matching, and instrumental variable analyses were performed to investigate the associations between prophylactic corticosteroid use and short-term outcomes, such as in-hospital mortality and respiratory failure, adjusting for potential confounders. RESULTS: Among 35,501 eligible patients, prophylactic corticosteroids were used in 22,620 (63.7%) patients. In-hospital mortality, respiratory failure, and severe respiratory failure occurred in 924 (2.6%), 5440 (15.3%), and 2861 (8.1%) patients, respectively. In stabilized inverse probability of treatment weighting analyses, corticosteroids were significantly associated with decreased in-hospital mortality [odds ratio (OR)=0.80; 95% confidence interval (CI): 0.69-0.93], respiratory failure (OR=0.84; 95% CI: 0.79-0.90), and severe respiratory failure (OR=0.87; 95% CI: 0.80-0.95). Corticosteroids were also associated with decreased postoperative length of stay and total hospitalization costs. The proportion of anastomotic leakage did not differ with the use of Propensity score matching and instrumental variable analysis demonstrated similar results. CONCLUSIONS: Prophylactic corticosteroid use in oncologic esophagectomy was associated with lower in-hospital mortality as well as decreased respiratory failure and severe respiratory failure, suggesting a potential benefit for preoperative corticosteroid use in esophagectomy.

Early postoperative non-steroidal anti-inflammatory drugs and anastomotic leakage after oesophagectomy.

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.

Non-curative resection for surgical T4b esophageal cancer: esophagectomy or non-esophagectomy?

BACKGROUND: Recently, with the development of multidisciplinary treatment, the treatment outcomes of esophageal cancer (EC) have improved. However, despite advances in diagnostic imaging modalities, preoperative diagnosis of T4 EC is still difficult, and the prognosis of T4 EC remains very poor. In addition, the prognosis of surgical T4b EC (sT4b EC) after surgery remains unclear. In this study, we retrospectively reviewed sT4b EC. METHODS: We evaluated the clinical course of sT4b EC and compared palliative esophagectomy with R2 resection (PE group) with other procedures without esophagectomy (NE group) (e.g., only esophagostomy) for sT4b EC. RESULTS: Forty-seven patients with thoracic EC underwent R2 resection at our institution between January 2009 and December 2020. Thirty-four patients were in the PE group, and 13 patients were in the NE group. The 2-year overall survival rate was 0% in the PE group and 20.2% in the NE group (p = 0.882). There was one case of long-term survival in the NE group that underwent surgery followed by definitive chemoradiation. Postoperative complications (Clavien-Dindo grade ≥ 3) were observed in 25 patients (73.5%) in the PE group and in three patients (23.1%) in the NE group (p = 0.031). The median time to the initiation of postoperative treatment was 68.1 days in the PE group and 18.6 days in the NE group (p = 0191). CONCLUSIONS: If EC is diagnosed as sT4b, palliative esophagectomy should be avoided because of the high complication rate and the lack of long-term survival.

Perioperative Decrease in Tongue Pressure is an Intervenable Predictor of Aspiration After Esophagectomy.

Despite the increasing use of minimally invasive esophagectomies, aspiration pneumonia remains the most serious complication. This study clarified the association between perioperative tongue pressure and postoperative aspiration after thoracoscopic-laparoscopic esophagectomy in patients with esophageal cancer. This retrospective, single-center, observational study evaluated data of 216 patients scheduled for thoracoscopic-laparoscopic esophagectomy. Tongue pressure was measured before the procedure and on postoperative day 6; perioperative changes were assessed. Patients were divided into non-aspiration and aspiration groups according to penetration-aspiration scale scores. Hierarchical and stratified logistic regression analyses were performed to identify factors associated with aspiration. Receiver operating characteristic curves were used to assess the cut-off value of perioperative changes in tongue pressure for aspiration. Perioperative changes in tongue pressure (odds ratio 0.92; 95% confidence interval 0.88-0.96, P < 0.001), age (odds ratio 1.07; 95% confidence interval 1.01-1.13, P = 0.013), and postoperative recurrent laryngeal nerve palsy (odds ratio 3.04; 95% confidence interval 1.15-8.03, P = 0.025) were significantly associated with aspiration. The cut-off value of perioperative changes in tongue pressure for postoperative aspiration was - 6.58%. In addition, decreases in tongue pressure were associated with aspiration regardless of recurrent laryngeal nerve palsy and age. The perioperative decrease in tongue pressure, higher age, and postoperative recurrent laryngeal nerve palsy were significant factors strongly associated with aspiration in the acute phase post-esophagectomy. Decreased tongue pressure is the only intervenable predictor of aspiration. Rehabilitation for preventing decreases in tongue pressure may reduce the risk of aspiration.

The evaluation of the association between preoperative sarcopenia and postoperative pneumonia and factors for preoperative sarcopenia in patients undergoing thoracoscopic-laparoscopic esophagectomy for esophageal cancer.

PURPOSE: This study identified the relationship between postoperative pneumonia and preoperative sarcopenia as well as the factors for preoperative sarcopenia in patients with esophageal cancer. METHODS: In this retrospective, single-center, observational study, we evaluated the data of 274 patients who were scheduled for thoracoscopic-laparoscopic esophagectomy. Sarcopenia was defined using the skeletal muscle index, handgrip strength, and gait speed. The physical activity and nutritional status were evaluated. A multivariate logistic regression analysis was performed to confirm the association between sarcopenia and postoperative pneumonia and identify sarcopenia-related factors. A Spearman's correlation analysis was used to identify the relationship between physical activity and nutritional status. RESULTS: Age, male sex, sarcopenia, and postoperative recurrent laryngeal nerve palsy were significantly associated with postoperative pneumonia. Age, male sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. There was a significant correlation between physical activity and nutritional status. CONCLUSIONS: Preoperative sarcopenia was confirmed to be a predictor of postoperative pneumonia. Furthermore, age, sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. Physical activity and nutritional status are closely associated with each other in patients with esophageal cancer. A multidisciplinary approach to preoperative sarcopenia, taking exercise and nutrition into account, is recommended.

[Management of Postoperative Infectious Complications After Thoracic Esophagectomy].

Although minimally invasive procedures such as thoracoscopic surgery and robot-assisted surgery have become increasingly popular in esophageal cancer in recent years, perioperative management remains a very important topic. However, perioperative management is still an extremely important issue, as esophagectomy is still a highly invasive procedure. Especially in recent years, as the patient population ages, it is expected that we will have more and more opportunities to deal with patients with various pre-existing medical conditions in addition to the original decline in physical function. In this article, we discuss the management of infectious complications in the perioperative management of esophageal surgery, with a particular focus on esophagectomy and reconstruction.