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Conversion therapy, defined as curative‐intent surgery or chemoradiotherapy after induction therapy, is gaining attention in patients with initially unresectable esophageal squamous cell carcinoma due to adjacent organ invasion (cT4b) or distant metastasis (M1). This systematic review aimed to assess survival outcomes, treatment strategies, and the evolving role of immune checkpoint inhibitors in this context. PubMed, Embase, and the Cochrane Library were comprehensively searched to identify studies published between 2010 and 2025 that reported conversion therapy outcomes in patients with esophageal squamous cell carcinoma with cT4b or M1. This review included 15 studies. A 2019 systematic review established the foundation for current practice in cT4b. Subsequent retrospective and prospective studies have reported 5‐year overall survival rates of up to 51.6% in patients undergoing salvage or conversion surgery, with no residual tumor (R0) resection rates reaching 98.9% in extended procedures. The ongoing JCOG1510 phase III trial is expected to clarify the optimal strategy. Selected patients undergoing conversion surgery for M1 after induction therapy achieved a 5‐year overall survival of 31.7%, with an R0 resection rate of 87%. Survival was not significantly associated with the metastatic site or treatment modality, highlighting the importance of treatment response and multidisciplinary decision‐making. The incorporation of immune checkpoint inhibitors into induction regimens expands the pool of candidates eligible for curative‐intent local therapy. Conversion therapy may provide durable survival in carefully selected patients, and further prospective studies are warranted to refine patient selection and establish standardized treatment algorithms. We systematically reviewed conversion therapy for esophageal squamous cell carcinoma and propose a response‐based treatment strategy for cT4b and M1 disease. For cT4b, we emphasize definitive chemoradiotherapy with timed re‐evaluation and selective salvage or chemoselection to surgery; for M1, conversion is reserved for limited‐burden responders with sustained systemic control (ctDNA‐guided when available), targeting R0 resection or definitive local control.

Background Esophagectomy has a high risk of postoperative morbidity, and pulmonary complications are the most common causes of serious morbidity. Thoracoscopic esophagectomy has been reported to reduce postoperative pulmonary complications; however, it remains unclear whether laparoscopic gastric mobilization can reduce the occurrence of postoperative pulmonary complications after open thoracotomy or thoracoscopic esophagectomy. The present meta-analysis assessed the ability of laparoscopic gastric mobilization to prevent postoperative complications after open thoracotomy or thoracoscopic esophagectomy. Method Studies reported between January 2000 and April 2019 in the PubMed and the Cochrane Library databases that analyzed the impact of laparoscopy on postoperative complications were systematically reviewed. In the meta-analysis, data were pooled and the primary outcome was postoperative pulmonary complications. The secondary outcomes were other postoperative complications, operative details, length of hospital stay and postoperative mortality. Results A total of 13 studies (1915 patients; 1 randomized trial, 1 prospective study and 11 observational studies) were included. Laparoscopic gastric mobilization after open thoracotomy resulted in significantly reduced postoperative pulmonary complications (OR = 0.47, 95% confidence interval (CI): 0.27–0.82, p  = 0.008) and postoperative mortality (OR = 0.49, 95%CI: 0.25–0.94, p  = 0.03). Similarly, laparoscopic gastric mobilization after thoracoscopic esophagectomy resulted in significantly reduced postoperative pulmonary complications (OR = 0.56, 95%CI: 0.37–0.84, p  = 0.005) and anastomotic leakage (OR = 0.59, 95%CI: 0.39–0.91, p  = 0.02). Conclusions Laparoscopic gastric mobilization could be recommended for reducing postoperative pulmonary complications after esophagectomy irrespective of the thoracic approach.

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

BackgroundStandard treatment for unresectable locally advanced esophageal cancer is definitive chemoradiotherapy (dCRT). Although salvage esophagectomy is the only curative treatment available following dCRT failure, the appropriate candidates for salvage esophagectomy remain unclear.Patients and MethodsThree hundred seventeen patients who underwent dCRT from April 2004 to December 2016 were stratified into three study groups—a complete response (CR) group, chemotherapy or best supportive care (BSC) group, and salvage esophagectomy group—and compared. We also investigated the clinical outcomes and prognostic factors of salvage esophagectomy.ResultsSeventy-one patients (22.4%) achieved CR after dCRT, 18 patients (5.7%) underwent salvage esophagectomy, and 228 patients (71.9%) underwent palliative chemotherapy or BSC. The 5-year overall survival (OS) rates of the CR group, salvage esophagectomy group, and chemotherapy or BSC group were 83.0%, 51.6%, and 1.3%, respectively. Salvage esophagectomy recipients had a worse OS rate than CR patients (p < 0.001) but a better OS rate than those in the chemotherapy or BSC group (p < 0.001). Incomplete resection was the only significant variable associated with poor OS on univariate Cox proportional-hazards analysis (hazard ratio: 7.633, 95% confidence interval: 1.692–34.482; p = 0.008). Patients with tumors in the upper thoracic esophagus were more likely to undergo incomplete resection (p = 0.011).ConclusionsPatients who achieve R0 resection are good candidates for salvage esophagectomy regardless of their response to dCRT. Those with upper thoracic esophageal tumors are at risk of incomplete resection; careful attention is required when considering these patients for salvage esophagectomy.

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

In the era of minimally invasive surgery, esophagectomy remains a highly invasive procedure with a high rate of postoperative complications. Preoperative risk assessment is essential for planning esophagectomy in patients with esophageal cancer, and it is crucial to implement evidence‐based perioperative management to mitigate these risks. Perioperative support from multidisciplinary teams has recently been reported to improve the perioperative nutritional status and long‐term survival of patients undergoing esophagectomy. Intraoperative management of anesthesia and fluid therapy also significantly affects short‐term outcomes after esophagectomy. In this narrative review, we outline the recent updates in the perioperative management of esophagectomy, focusing on preoperative risk assessment, intraoperative management, and perioperative support by multidisciplinary teams to improve operative outcomes. In this review we outline the recent updates in the perioperative management of esophagectomy, especially in McKeown esophagectomy, focusing on preoperative risk assessment, intraoperative management, and perioperative support by multidisciplinary teams to improve operative outcomes.

BackgroundThe standard treatment for patients 75 years of age or younger with cStage 2 or 3 esophageal cancer is preoperative chemotherapy followed by esophagectomy. The optimal treatment for elderly patients, especially those considered vulnerable, remains unclear.MethodsThis study retrospectively reviewed the data for 42 patients ages 75–80 years with cStage 2 or 3 esophageal cancer who underwent esophagectomy between October 2002 and February 2019. The patients who received preoperative chemotherapy were compared with those who did not. The study also examined short- and long-term outcomes and the impact of preoperative chemotherapy on overall survival (OS) stratified by performance status (PS).ResultsOf the 42 patients, 18 underwent esophagectomy without preoperative chemotherapy and 24 underwent esophagectomy after preoperative chemotherapy. A significantly greater proportion of the patients with PS 0 received preoperative chemotherapy than the patients with PS 1 (P =0.007). The multivariate analysis showed preoperative chemotherapy to be an independent negative prognostic factor for OS (hazard ratio [HR], 5.025; 95% confidence interval [CI] 1.136–22.222; P = 0.033). Subgroup analysis showed that preoperative chemotherapy had a significant negative impact on the OS of the patients with PS 1 (P < 0.001).ConclusionPreoperative chemotherapy was ineffective for the patients with PS 0 and had a significantly negative impact on the OS of the patients with PS 1. Preoperative chemotherapy should not be administered to patients 75 years of age or older with cStage 2 or 3 esophageal cancer.

Background Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. Methods This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. Results The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists’ median of these was 43%, 90%, 85%, 65%, and 66%, respectively. Conclusions This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.