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Background: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy., Methods: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated., Results: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005)., Conclusions: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status., (© 2024. Society of Surgical Oncology.)

Background: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer., Methods: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated., Results: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts., Conclusions: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer., (© 2023. Society of Surgical Oncology.)

Background: Pretreatment metastatic lymph node (LN) size has been reported to be associated with prognosis in esophageal squamous cell carcinoma (ESCC). However, its relationship with response to preoperative chemotherapy or prognosis has not been clarified. We investigated the relationship between metastatic LN size and response to preoperative treatment, and prognosis in patients with metastatic esophageal cancer who underwent surgery., Patients and Methods: A total of 212 clinically node-positive patients who underwent preoperative chemotherapy followed by esophagectomy for ESCC were enrolled. Patients were stratified into three groups on the basis of the length of the short axis of the largest LN in pretreatment computed tomography images: < 10 mm (group A), 10-19 mm (group B), and ≥ 20 mm (group C)., Results: Group A had 90 patients (42%), group B had 103 patients (49%), and group C had 19 patients (9%). Group C had significantly lower percent reduction in total metastatic LN size than groups A and B (22.5% versus 35.7%, P = 0.037). Group C had significantly more metastatic LNs based on histological examination than groups A and B (10.1 versus 2.4, P < 0.001). Group C patients whose LNs responded had significantly fewer metastatic LNs than nonresponders (5.1 versus 11.9, P = 0.042). Group C had significantly poorer overall survival than groups A and B (3-year survival, 25.4% versus 67.3%, P < 0.001). However, group C patients whose LNs responded had better survival than nonresponders (3-year survival, 57.1% versus 0%, P = 0.008)., Conclusions: Patients with large metastatic LNs have poor response and poor prognosis. However, if a response is obtained, long-term survival can be expected., (© 2023. Society of Surgical Oncology.)

Background: Outcomes of salvage surgery after failed definitive chemoradiation (CRT) for esophageal cancer have been well defined. However, only a few studies have focused on salvage esophagectomy for recurrent disease after CRT., Methods: In 227 patients with esophageal cancer who underwent salvage esophagectomy after definitive CRT, consisting of 116 patients who underwent esophagectomy for persistent disease (the persistent group) and 111 patients who underwent esophagectomy for recurrent disease (the recurrent group), the short- and long-term outcomes were investigated., Results: The rates of any postoperative complication were similar between the groups (49.1% in the persistent group vs. 49.5% in the recurrent group, p = 0.951), although there was a higher rate of anastomotic leakage in the recurrent group (p = 0.027). Thirty-day mortality was also similar between the groups (1.7% in the persistent group vs. 0.9% in the recurrent group, p = 0.587). The 3-year and 5-year overall survival rates were 33.7% and 28.0% in the persistent group and 48.7% and 41.7% in the recurrent group, respectively (p = 0.0175). In the recurrent group, clinically nodal status before CRT as well as pathologically nodal status and time to relapse were identified as independent prognostic factors. In the persistent group, pT and resection margin were identified as independent factors associated with survival., Conclusions: The present study showed that salvage surgery for recurrent disease can provide acceptable short- and long-term outcomes. Considering clinically and pathologically nodal status and time to relapse, adjuvant therapy might be offered for patients who underwent salvage esophagectomy for recurrent disease after definitive CRT., (© 2022. Society of Surgical Oncology.)

Background: Optimal timing for surgery after neoadjuvant chemoradiotherapy (NCRT) remains controversial, necessitating reliable preoperative indicators. This study examines how sarcopenia and surgical timing affect prognosis in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Patients and Methods: This retrospective study analyzed patients with LA-ESCC who underwent NCRT and surgery at three institutions in China from 2014 to 2023. The skeletal muscle area at the third lumbar vertebra was measured to calculate the skeletal muscle index (SMI). Prognostic analysis was performed using Cox proportional hazards models and propensity score matching (PSM), with survival curves generated using the Kaplan-Meier method and statistical significance set at p<0.05., Results: A total of 415 patients were analyzed, with a median follow-up of 39.1 months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 59.3% and 53.1%, respectively. Malnutrition and time to surgery (TTS) were independent prognostic factors for both OS and PFS (p < 0.05). Patients with long TTS showed better OS [hazard ratio (HR) = 0.62, p = 0.01] and PFS (HR = 0.68, p = 0.02) compared with those with short TTS. Among patients with sarcopenia, long TTS significantly improved OS (HR = 0.56; p = 0.01) and PFS (HR = 0.62; p = 0.02), while no survival benefit was observed for TTS in patients who were nonsarcopenic (p > 0.05)., Conclusions: Sarcopenia does not independently impact OS or PFS. Patients with sarcopenia benefit from a longer surgical time interval after NCRT. In addition, preoperative evaluation of muscle quality may aid in optimizing surgical timing to improve outcomes., Competing Interests: Disclosure: The authors declare that they have no conflicts of interest. Ethical Approval: The TIMES study was approved by the Ethics Committee for Medical Research and NEW Medical Technology of Sichuan Cancer Hospital (SCCHEC-02-2023-134) and performed in accordance with the principles of the Declaration of Helsinki., (© 2025. Society of Surgical Oncology.)

Background: Lymphovascular invasion (LVI) is reported to correlate with postoperative prognosis in esophageal squamous cell carcinoma (ESCC). However, reports analyzing lymphatic and venous invasion separately are rare, and no studies have examined the correlation in resected specimens after neoadjuvant chemotherapy (NAC). This study evaluated the postoperative prognosis and distant metastatic recurrence patterns in ESCC patients who underwent esophagectomy after NAC., Methods: This retrospective study analyzed 427 ESCC patients who underwent radical esophagectomy after NAC. The study examined the association of LVI patterns with postoperative overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). The study also evaluated the correlation with postoperative distant metastasis patterns., Results: Multivariate analyses showed that patients with venous invasion (VI) alone had significantly worse OS (HR, 2.99; p < 0.001), RFS (HR, 2.92; p < 0.001), and DMFS (HR, 3.63; p < 0.001) than patients without LVI. Patients with both lymphatic invasion (LI) and VI had the worst OS (HR, 4.23; p < 0.001), RFS (HR, 3.38; p < 0.001), and DMFS (HR, 4.59; p < 0.001) among all groups. For the ypN0 patients, VI positivity was the only independent risk factor for DMFS (HR, 5.33; p < 0.001). Regarding distant organ metastasis, liver, brain, and bone metastasis were more frequently detected in patients with both LI and VI than in patients with other LVI patterns., Conclusions: The study showed that ESCC patients treated with NAC who have resected specimens positive for VI, especially those also with positive lymphatic invasion, have a worse postoperative prognosis and a higher risk for postoperative distant metastases than those without LVI. More aggressive postoperative adjuvant therapy may be suitable for improving the prognosis of such patients., Competing Interests: Disclosure: Daisuke Kajiyama, Naoto Fujiwara, Takashi Shigeno, Kazuma Sato, Masayuki Yamaguchi, Shingo Sakashita, Hiroyuki Daiko, and Takeo Fujita have no conflicts of interest to declare in relation to this work., (© 2024. Society of Surgical Oncology.)

Background: Patients with esophageal squamous cell carcinoma (ESCC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy a viable option for patients with incurable ESCC., Objective: We aimed to assess the safety and efficacy of conversion therapy for ESCC with distant metastases., Methods: Conversion therapy was defined as surgery or chemoradiotherapy (CRT) used to cure tumors that were previously considered incurable because of distant metastasis. We conducted a retrospective review of patients who underwent ESCC conversion therapy and assessed the treatment outcomes, including adverse events and survival rates., Results: A total of 147 patients from 22 institutions were included. Systemic chemotherapy was initially administered to all patients. The most common M1 factor was the para-aortic lymph node, accounting for 55% of cases. Following the initial treatment, 116 patients underwent surgery, with 31 receiving CRT as conversion therapy. Postoperative complications in surgery patients included pneumonia (16%), anastomotic leakage (7%), and recurrent laryngeal nerve palsy (6%). During CRT, 18% of patients developed grade 3 or higher non-hematological toxicities. The 5-year overall survival (OS) rate was 31.7%. Pathological responders had significantly longer OS than non-responders (hazard ratio 0.493, p = 0.012). The distribution of distant metastasis, regimen type, clinical response, and conversion therapy modality did not have a significant impact on OS., Conclusions: Conversion therapy can be safely performed for ESCC with distant metastasis and has a favorable prognosis., Competing Interests: Disclosure: Motoo Nomura has received honoraria from ONO, BMS, and MSD, and advisory board fees from ONO. Shun Yamamoto has received honoraria from ONO, BMS, MSD, and Taiho; advisory board fees from ONO; and expert testimony fees from Hokuto. Katsuyuki Sakanaka has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Novartis Pharma, and support for attending meetings and/or travel from MSD. Ken Kato reports funding, paid to the institution, from MSD, Ono Pharmaceuticals, BMS, Beigene, Shionogi, Merck Biopharma, Oncolys BioPharma, Daiichi Sankyo, Novartis, Taiho Pharmaceutical, Janssen, AstraZeneca, and Chugai. Takayuki Tsuji, Satoru Matsuda, Yuta Sato, Koji Tanaka, Ken Sasaki, Masaya Watanabe, Yoichi Hamai, Motomi Nasu, Zenichiro Saze, Yuichiro Nakashima, Eisuke Booka, Koshiro Ishiyama, Takeo Bamba, Takahiro Tsushima, Hiroya Takeuchi, and Hirofumi Kawakubo have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Background: The association between tumor-infiltrating lymphocytes and tumor immunity has long been recognized. Among T-cell types, CD45RO-positive memory T cells (CD45RO + ) are reported to correlate with survival in several cancer types, but clinical evidence is lacking in esophageal squamous cell carcinoma (ESCC)., Methods: In surgical specimens from 162 preoperatively untreated patients, immunohistochemistry for CD45RO was performed to evaluate the density of CD45RO + in the tumor core (CT) and invasive margin (IM) using an auto-count method. Patients were classified into high- versus low-CD45RO + groups based on CD45RO + density in CT and IM separately and combined. The relationship between CD45RO + density and clinicopathological factors, including prognosis, was evaluated., Results: Average CD45RO + density was 133/mm 2 in CT and 372/mm 2 in IM. No significant differences in clinicopathological factors according to high- versus low-CD45RO + scores were identified. Using CT scores, the CD45RO + -high group had a better 5-year overall survival (OS) rate (77.2% vs. 54.7% CD45RO + -low, P = 0.0433), but OS rates did not differ statistically between the two groups by IM scores (75.7% vs. 50.3%, P = 0.0576). Using immunohistochemical scores for CT+IM, the survival difference was significant, with a 5-year OS rate of 73.7% for the CD45RO + -high group versus 46.3% for the CD45RO + -low group (P = 0.0141). Multivariate analysis identified CD45RO + CT+IM density as an independent prognostic variable in OS (hazard ratio 2.27, 95% confidence interval 1.43-3.62, P = 0.0006)., Conclusions: Density of CD45RO + expression in the CT and IM might be a predictor of long-term survival in ESCC., Competing Interests: Disclosures: There are no conflicts of interest., (© 2024. The Author(s).)

Background: In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases., Methods: The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n = 56) and those who received an open-close (OC) procedure (n = 12)., Results: Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p = 0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p = 0.549) and in-hospital mortality (0% vs. 5.4%; p = 0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p = 0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31-0.87; p = 0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15-0.49; p = 0.010) were independently associated with a more favorable OS., Conclusion: PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT., (© 2024. Society of Surgical Oncology.)

Background: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate., Objectives: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN)., Methods: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated., Results: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences., Conclusions: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed., (© 2021. Society of Surgical Oncology.)