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This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

IntroductionWe compare planned salvage surgery after definitive chemoradiotherapy (SALV) versus neoadjuvant chemoradiotherapy plus surgery (NCRS) for borderline resectable T4 esophageal squamous cell carcinoma.Patients and MethodsA total of 37 patients underwent planned SALV, and 20 underwent NCRS from 2004 to 2017. The short-term outcome measures were the R0 resection rate, complications, and treatment-related mortality. The long-term outcome measures were the 5-year overall survival rate and causes of death.ResultsR0 resection rate was similar between the SALV and NCRS groups (81% versus 85%). The incidence of postoperative pneumonia (35% versus 18%) and treatment-related mortality rate (9% versus 0%) tended to be higher in the SALV. ypT grade 2–3 (65% versus 30%, p = 0.012) and Clavien–Dindo grade ≥ IIIb complications (32% versus 0%, p = 0.008) were significantly more frequent in the SALV group. The groups had similar 5-year overall survival (26% versus 27%). The causes of death in the SALV and NCRS groups were primary esophageal cancer in 35% and 55% of patients, respectively, and pulmonary-related mortality in 24% and 5%, respectively. Multivariable Cox regression analysis revealed the following significant poor prognostic factors: stable disease as the clinical response, preoperative body mass index (BMI) of < 18.5 kg/m2, ypN stage 1–3, and R1–2 resection.ConclusionsSALV was associated with a higher incidence of late pulmonary-related mortality but had a stronger antitumor effect than NCRS. Consequently, the survival rate was similar between the groups. Surgery is recommended for patients with a partial response and preoperative BMI of ≥ 18.5 kg/m2.

Background This study was performed to verify the superiority of a new “non-tensioning method” for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method. Methods In total, 395 consecutive patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A 4 cm-wide GC was created and pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional technique, the stapler was fired while pulling the GC to avoid tissue slack. In the non-tensioning technique, the stapler was fired through the natural thickness of the stomach wall. The length of the blind end was changed from 4 to 2 cm in the non-tensioning technique. Anastomotic leakage and stricture formation were compared between the two techniques, and adjustment was performed using propensity score matching. Results The conventional group comprised 315 patients, and the non-tensioning group comprised 80 patients. Anastomotic leakage occurred in 22 (7%) and 2 (2.5%) patients, respectively ( P  = 0.134) [and in 9 (2.9%) and 2 (2.5%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29.2%) and 3 (3.8%) patients, respectively ( P  < 0.001). The propensity score-matching analysis including 79 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (2.5% vs. 29.1%, P  < 0.001). Conclusions The non-tensioning technique significantly reduced the incidence of anastomotic stricture compared with the conventional technique.

BackgroundThe impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection. MethodsIn this six-institution, matched-cohort study, 2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns. ResultsBased on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (p = 0.0078), 41.0% (p = 0.0297), and 55.3% (p = 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (p = 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (p = 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (p = 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (p = 0.0183). ConclusionsPerformance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.

BackgroundWhile a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC.MethodsWe enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival.ResultsThe median ITR was 21.07% (range −11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98–5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67–4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10–3.18), and ITR <10% (HR 2.48, 95% CI 1.42–4.32) were independent prognostic factors.ConclusionsTumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

PurposeWe retrospectively investigated the risk factors for mediastinal lymph node (MLN) metastasis in esophagogastric junction (EGJ) cancer with an epicenter within 2 cm above and below the anatomical cardia, including both adenocarcinoma (AC) and squamous cell carcinoma (SCC).MethodsFifty patients who underwent initial surgery for EGJ cancer from January 2002 to December 2013 were included in this study. We defined metastatic lymph nodes as pathological metastases in resected specimens and recurrence within 2 years postoperatively.ResultsThirty-four patients had AC and 16 had SCC; 24 patients underwent transhiatal resection and 26 underwent transthoracic resection. MLN metastasis was observed in 13 patients (26%) regardless of the histological type, 9 of whom had metastasis in the upper and middle mediastinum. Metastasis occurred when the esophageal invasion length (EIL) exceeded 20 mm. In addition, 10/13 patients had stage pN2–3 cancer. Multivariable analysis identified EIL ≥ 20 mm and stage pN2–3 as significant risk factors for MLN metastasis. The 5-year overall survival was 38% and 65% in the MLN-positive and -negative groups, respectively (p = 0.12). Multivariable Cox regression analysis showed that only stage pN2–3, and not the presence of MLN metastasis, was a significantly poor prognostic factor.ConclusionMLN metastasis in EGJ cancer may have a close association with the EIL of the tumor, but the presence of MLN metastasis itself was not a poor prognostic factor. The significance and indications for MLN dissection should be clarified in prospective clinical trials.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

BackgroundThe optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial.MethodsWe randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis.ResultsPatient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012–7.517).ConclusionsTwo courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC.Clinical trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).