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.

Association between preoperative serum zinc level and prognosis in patients with advanced esophageal cancer in the neoadjuvant treatment era.

Background: Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear. Methods: This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients' outcomes. Results: The patients were divided into a low Zn group (<64 µg/dL) and a high Zn group (≤64 µg/dL) according to the mean preoperative serum Zn level. Low Zn had significantly worse overall survival (OS) (2-year OS rate: 76.2% vs. 83.3% in low vs. high Zn; p = 0.044). A low Zn in pathological non-responders (Grade ≤ 1a) was significantly associated with a shorter 2-year recurrence-free survival (RFS) rate (39.6% vs. 64.1% in low vs. high Zn; p = 0.032). The multivariate analysis identified low BMI and Zn level among preoperative nutritional status indices as an independent risk factor for worse RFS in non-responders. Compared with responders, pathological non-responders comprised significantly more males and a performance status of ≥1, and there was no difference in Zn level according to pathological response. Conclusion: A preoperative low Zn level had a negative impact on early recurrence in esophageal cancer patients who underwent neoadjuvant chemotherapy. This suggests the need to administer Zn supplementation to patients with esophageal cancer who have preoperative Zn deficiency.

Efficacy and Safety of Salvage-line Nivolumab Monotherapy for Advanced Esophageal Squamous Cell Carcinoma: Comparison of 240 mg Versus 480 mg Doses.

BACKGROUND: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. METHODS: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. RESULTS: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. CONCLUSIONS: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of esophageal squamous cell carcinoma after neoadjuvant triplet chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy followed by esophagectomy is the standard treatment for resectable advanced esophageal squamous cell carcinoma (ESCC) in Japan. Triplet chemotherapy is the standard neoadjuvant regimen. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) are well-known prognostic factors for esophageal cancer. However, their usefulness in patients with resectable advanced disease undergoing esophagectomy after neoadjuvant triplet chemotherapy is unknown. METHOD: We examined 144 ESCC patients who underwent neoadjuvant triplet chemotherapy followed by esophagectomy between January 2015 and December 2020 to investigate the relationship between inflammatory markers and recurrence-free survival (RFS). Optimal marker cutoff values for RFS were determined using receiver operating characteristic curve analysis. Patients were divided into high and low NLR groups (NLR cutoff, 3.0). RESULTS: NLR was high in 61 patients and low in 83. Univariate analyses demonstrated that low NLR was significantly associated with worse RFS (p = 0.049). Multivariate analyses demonstrated that high NLR was an independent predictor of RFS (odds ratio, 1.911; 95% confidence interval, 1.098-3.327; p = 0.022). RFS significantly differed between the low and high NLR groups. RFS did not significantly differ between the patients when stratified according to the other inflammatory markers. CONCLUSION: Preoperative NLR is an easily obtained and useful predictor of RFS in patients with resectable advanced ESCC treated with neoadjuvant triplet chemotherapy followed by esophagectomy.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Prognostic impact of extramural venous invasion detected by contrast-enhanced CT colonography in colon cancer.

BACKGROUND: The impact of computed tomography (CT)-detected extramural venous invasion on the recurrence of colon cancer is not fully understood. The aim of this study was to investigate the clinical significance of extramural venous invasion diagnosed before surgery by contrast-enhanced CT colonography using three-dimensional multiplanar reconstruction images. METHODS: Patients with colon cancer staged greater than or equal to T2 and/or stage I-III who underwent contrast-enhanced CT colonography between 2013 and 2018 at the National Cancer Center Hospital in Japan were retrospectively investigated for CT-detected extramural venous invasion. Inter-observer agreement for the detection of CT-detected extramural venous invasion was evaluated and Kaplan-Meier survival curves were plotted for recurrence-free survival using CT-TNM staging and CT-detected extramural venous invasion. Preoperative clinical variables were analysed using Cox regression for recurrence-free survival. RESULTS: Out of 922 eligible patients, 544 cases were analysed (50 (9.2 per cent) were diagnosed as positive for CT-detected extramural venous invasion and 494 (90.8 per cent) were diagnosed as negative for CT-detected extramural venous invasion). The inter-observer agreement for CT-detected extramural venous invasion had a κ coefficient of 0.830. The group positive for CT-detected extramural venous invasion had a median follow-up of 62.1 months, whereas the group negative for CT-detected extramural venous invasion had a median follow-up of 60.7 months. When CT-TNM stage was stratified according to CT-detected extramural venous invasion status, CT-T3 N(-)extramural venous invasion(+) had a poor prognosis compared with CT-T3 N(-)extramural venous invasion(-) and CT-stage I (5-year recurrence-free survival of 50.6 versus 89.3 and 90.1 per cent respectively; P < 0.001). In CT-stage III, the group positive for CT-detected extramural venous invasion also had a poor prognosis compared with the group negative for CT-detected extramural venous invasion (5-year recurrence-free survival of 52.0 versus 78.5 per cent respectively; P = 0.003). Multivariable analysis revealed that recurrence was associated with CT-T4 (HR 3.10, 95 per cent c.i. 1.85 to 5.20; P < 0.001) and CT-detected extramural venous invasion (HR 3.08, 95 per cent c.i. 1.90 to 5.00; P < 0.001). CONCLUSION: CT-detected extramural venous invasion was found to be an independent predictor of recurrence and could be used in combination with preoperative TNM staging to identify patients at high risk of recurrence.

Preoperative physical activity is associated with prognosis in patients with esophageal cancer undergoing thoracoscopic-laparoscopic esophagectomy after neoadjuvant chemotherapy.

OBJECTIVE: This study examined the association between a single preoperative physiotherapy session during neoadjuvant chemotherapy and physical function and that between preoperative physical activity and prognosis. METHODS: In this retrospective, single-center, observational study, we evaluated data from 234 patients scheduled for neoadjuvant chemotherapy and thoracoscopic-laparoscopic esophagectomy who underwent a single preoperative physiotherapy session. The five-repetition sit-to-stand test was performed before and after neoadjuvant chemotherapy. After neoadjuvant chemotherapy, patients were classified into high- and low-physical activity groups based on preoperative physical activity. To examine the association between preoperative physiotherapy and changes in physical function, a multivariate regression analysis was performed. The Cox proportional hazards model was used to investigate the association between preoperative physical activity and overall survival. RESULTS: The median percentage change in the five-repetition sit-to-stand test score was - 3.36%. In the multivariate regression analysis, the regression coefficient of the constant term was - 23.93 (95% confidence interval - 45.31 to - 2.56; P = 0.028). Low physical activity was significantly associated with overall survival after adjustment for confounding factors (P = 0.040). CONCLUSIONS: This study demonstrated that a single preoperative physiotherapy session during neoadjuvant chemotherapy improves physical function, and preoperative physical activity is significantly associated with prognosis.

A novel imaging technology to assess tissue oxygen saturation and its correlation with indocyanine green in the gastric conduit during thoracic esophagectomy.

BACKGROUND: Anastomotic leakage in esophagectomy is a serious complication, and assessing blood perfusion in the conduit can help minimize this risk. Indocyanine green is the most widely used method to assess tissue blood flow; however, this technique has disadvantages. Evaluating tissue oxygen saturation in the gastric conduit during thoracic esophagectomy compared with indocyanine green blood perfusion assessment addresses these disadvantages and can be performed easily and repeatedly. METHODS: This was a prospective study of patients with esophageal cancer who underwent thoracic esophagectomy. Intraoperative tissue oxygen saturation and indocyanine green measurements were obtained to determine the anastomotic site and to compare the correlation between the 2 methods. Tissue oxygen saturation and indocyanine green values were obtained at the tip of the gastric conduit, the demarcation line indicating visible perfusion, and the end of the right gastroepiploic artery. RESULTS: Fifty-seven patients were enrolled in this study; 3 developed anastomotic leakage, and all 3 underwent robotic thoracic surgery. The tissue oxygen saturation value decreased gradually toward the tip of the conduit, as did congestion, and was significantly decreased at the tip compared with the value at the demarcation line (P = .001). Mean tissue oxygen saturation differed significantly between the leakage and no-leakage groups at the anastomosis site (P = .04). We found a negative correlation between tissue oxygen saturation and indocyanine green values at the end of the right gastroepiploic artery (r = -0.361; P = .03). CONCLUSION: Tissue oxygen saturation imaging was useful in determining the anastomotic site and addressed the disadvantages associated with indocyanine green.