Gastric conduit reconstruction after esophagectomy.

A high risk of complications still accompanies gastric conduit reconstruction after esophagectomy. In this narrative review, we summarize the technological progress and the problems of gastric conduit reconstruction after esophagectomy. Several types of gastric conduits exist, including the whole stomach and the narrow gastric tube. The clinical outcomes are similar between the two types of conduits. Sufficient blood supply to the conduit is mandatory for a successful esophageal reconstruction. Recently, due to the availability of equipment and its convenience, indocyanine green angiography has been rapidly spreading. When the blood perfusion of the planning anastomotic site is insufficient, several techniques, such as the Kocher maneuver, pedunculated gastric tube with duodenal transection, and additional microvascular anastomosis, exist to decrease the risk of anastomotic failure. There are two different anastomotic sites, cervical and thoracic, and mainly two reconstructive routes, retrosternal and posterior mediastinal routes. Meta-analyses showed no significant difference in outcomes between the anastomotic sites as well as the reconstructive routes. Anastomotic techniques include hand-sewn, circular, and linear stapling. Anastomoses using linear stapling is advantageous in decreasing anastomosis-related complications. Arteriosclerosis and poorly controlled diabetes are the risk factors for anastomotic leakage, while a narrow upper mediastinal space and a damaged stomach predict leakage. Although standardization among the institutional team members is essential to decrease anastomotic complications, surgeons should learn several technical options for predictable or unpredictable intraoperative situations.

Prognostic Impact of Serum SCC Antigen in the 566 Upfront Surgery Group of Esophageal Squamous Cell Carcinoma: A Multi-Institutional Study of the Japan Esophageal Society.

PURPOSE: This study aimed to determine the clinicopathologic and prognostic significance of squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal SCC who underwent radical surgery without neoadjuvant therapy. METHODS: This study included 566 patients with primary esophageal SCC who underwent radical resection without neoadjuvant therapy at 15 Japanese hospitals between 2008 and 2016. The cutoff value of SCC-Ag was 1.5 ng/mL based on the receiver operating characteristic curves. Preoperative SCC-Ag and postoperative SCC-Ag were analyzed to evaluate clinicopathological and prognostic significance. Survival curves were compared between the SCC-Ag-positive group and the SCC-Ag-negative group. The prognostic impact of SCC-Ag was evaluated using univariate and multivariate analyses. RESULTS: The preoperative SCC-Ag-positive rate was 23.5% (133/566). SCC-Ag-positive status was significantly associated with old age (p = 0.042), tumor depth (p <0.001), and tumor stages (p <0.001). The preoperative SCC-Ag-positive group had significantly poorer overall survival than the SCC-Ag-negative group (p = 0.030), but it was not an independent predictor of poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for poor overall survival (p = 0.034). CONCLUSION: Both pre- and postoperative SCC-Ag-positive statuses were significantly associated with poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for predicting overall survival.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Outcomes of patients with esophageal squamous cell carcinoma who achieved a pathological complete response in the primary lesion by neoadjuvant treatment: a Japanese nationwide cohort study.

BACKGROUND: Minimal data was reported regarding the characteristics, risks of lymph node metastasis, and prognostic factors in esophageal cancer patients who achieved remarkable response in the primary lesion to neoadjuvant treatment (NAT). METHODS: This study evaluated the nationwide data of esophageal squamous cell carcinoma (ESCC) patients who underwent surgery following NAT in Japan. Of 4484 patients, 300 (6.7%) had ypT0 following NAT and curative esophagectomy. Factors associated with lymph node metastasis and prognosis were analyzed. RESULTS: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) were administered in 260 (86.2%) and 40 (13.8%) patients, respectively. Pathologically, 72 (24.0%) had lymph node metastasis (residual nodal disease; RND), and pretherapeutic lymph node metastasis was the independent risk factor for RND (odd ratio [OR]: 3.21; 95% confidence interval [CI]: 1.44-8.20; P = 0.008). The 5-year overall and relapse-free survivals were significantly longer in patients with pathological complete response (pCR) than in those with RND (both P < 0.001). Pretherapeutic cT3 or T4a tumors (hazard ratio [HR]: 1.71; 95% CI: 1.02-2.88; P = 0.043), RND (HR: 3.30; 95% CI: 1.98-5.50; P < 0.001), and operative blood loss (Liter, HR: 1.53; 95% CI: 1.07-2.19; P = 0.021) were independent risk factors affecting relapse-free survival in multivariable analysis. CONCLUSIONS: Of patients with ypT0 after NAT, 24.0% had RND, and pretherapeutic lymph node metastasis was the risk factor. In addition, pretherapeutic cT3, or T4a tumors, RND, and operative blood loss were the poor prognosticators in patients with ypT0 after NAT.

Early postoperative hyperglycemia as a predictor of postoperative infectious complications and overall survival in non-diabetic patients with esophageal cancer.

BACKGROUND: Diabetes mellitus (DM) is known to be a risk factor for postoperative infectious complications (PICs). However, the significance of postoperative hyperglycemia in non-DM cases has not been well investigated. We sought to establish whether postoperative hyperglycemia is associated with PICs and survival among patients with esophageal cancer, with a focus on non-DM cases. METHODS: A total of 430 patients who underwent subtotal esophagectomy for esophageal cancer between 2014 and 2018 were enrolled. Postoperative blood glucose was measured by arterial blood gas test every 8 h from postoperative day (POD) 1 to POD4. The association between hyperglycemia (mean ≥ 200 mg/dl) and PICs or long-term outcomes on each POD was investigated. RESULTS: There were 53 DM and 377 non-DM cases. PICs occurred in 127 patients. In the multivariate analysis of all cases, PICs were associated with hyperglycemia on POD1 or -2 (odds ratio [OR] = 1.69, 95% CI, 1.05-2.73, P = 0.031 for POD1; OR = 2.55, 95% CI, 1.10-5.93, P = 0.029 for POD 2). Among non-DM cases, the association was more evident, and persisted until POD4 (OR = 1.94, 95% CI, 1.16-3.24, P = 0.012 for POD1; OR = 3.68, 95% CI, 1.28-10.6, P = 0.016 for POD2; OR = 3.07, 95% CI, 1.11-8.51, P = 0.031 for POD4). Survival analyses limited to R0 cases revealed hyperglycemia on POD2 as an independent prognostic factor in all cases (N = 412) [hazard ratio (HR) = 2.61, 95%CI, 1.21-5.63, P = 0.014], with the prognostic impact more evident among non-DM cases (N = 360) (HR = 4.38, 95% CI, 1.82-10.57, P = 0.0010). CONCLUSION: Postoperative hyperglycemia is associated with PICs and worse survival after esophagectomy, particularly in patients without DM.

Quantitative Evaluation of Periodontitis for Predicting the Occurrence of Postoperative Pneumonia After Oncologic Esophagectomy.

BACKGROUND: Periodontitis is a biofilm-associated inflammatory periodontal disease associated with postoperative complications after esophagectomy. However, few studies have evaluated the inflammatory burden posed by periodontitis quantitively for patients undergoing oncologic esophagectomy. This study aimed to clarify the relationship between periodontitis and postoperative pneumonia using periodontal inflammatory surface area (PISA). METHODS: The study analyzed 251 patients who underwent esophagectomy for esophageal cancer. The patients were classified into low-PISA and high-PISA groups according to preoperative PISA, and the relationship between the occurrence and severity of postoperative pneumonia was investigated. RESULTS: The high-PISA group (n = 69) included more males (P < 0.001) and patients with poor performance status (P < 0.024). Postoperative pneumonia occurred more frequently in the high-PISA group than in the low-PISA group (31.9 % vs. 15.9 %; P = 0.008), whereas the incidences of other complications did not differ significantly. In addition, the incidence of severe pneumonia was significantly higher in the high-PISA group (7.2 % vs. 1.6 %; P = 0.038). In the multivariable analysis for adjustment of preoperative confounders, age older than 70 years (odds ratio [OR], 2.62; P = 0.006), high PISA (OR, 2.45; P = 0.012), and smoking history (OR, 2.78; P = 0.006) were the independent variables predicting postoperative pneumonia. CONCLUSION: Preoperative higher PISA was significantly associated with the occurrence of overall and severe postoperative pneumonia. The quantitative evaluation of periodontitis using PISA is a useful measure for predicting postoperative pneumonia, and intensive periodontal intervention may contribute to decreasing postoperative pneumonia.

Endoscopic Evaluation of Pathological Complete Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy-Multicenter Retrospective Study from Four Japanese Esophageal Centers.

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.

McKeown Versus Ivor-Lewis Esophagectomy for Patients with a History of Total Pharyngolaryngectomy: A Comparison Study.

BACKGROUND: Oncologic esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. There are two different esophagectomy procedures: total esophagectomy with cervical anastomosis (McKeown) and subtotal esophagectomy with intrathoracic anastomosis (Ivor-Lewis). Differences in outcomes between McKeown and Ivor-Lewis esophagectomies for patients with this history remain unclear. METHODS: We retrospectively reviewed 36 patients with a history of TPL who underwent oncologic esophagectomy and compared the clinical outcomes between the procedures. RESULTS: Twelve (33.3%) and 24 (66.7%) patients underwent McKeown and Ivor-Lewis esophagectomies, respectively. McKeown esophagectomy was more frequently performed for the supracarinal tumors (P = 0.002). Other baseline characteristics, including the history of radiation therapy, were comparable between the groups. Postoperatively, the incidences of pneumonia and anastomotic leakage were higher in the McKeown group than in the Ivor-Lewis group (P = 0.029 and P < 0.001, respectively). Neither tracheal necrosis nor remnant esophageal necrosis was observed. The overall and recurrence-free survival rates were comparable between the groups (P = 0.494 and P = 0.813, respectively). CONCLUSIONS: When performing esophagectomy for patients with a history of TPL, if it is oncologically acceptable and technically available, Ivor-Lewis is preferable over McKeown esophagectomy for avoiding postoperative complications.

Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Real-World Data Comparison from A Japanese Nationwide Study.

BACKGROUND: Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. METHODS: Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. RESULTS: Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p < 0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. CONCLUSIONS: Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.

Prognostic significance of circulating basophil counts in patients who underwent esophagectomy for esophageal cancer.

PURPOSE: Recent reports have suggested that basophils influence allergic reactions and tumor immunity. In this study, we aimed to elucidate the association between preoperative circulating basophil (CB) counts and the outcomes of patients who underwent esophagectomy for esophageal cancer. METHODS: A total of 783 consecutive patients who underwent esophagectomy for esophageal cancer were eligible. The clinicopathological factors and prognoses were compared between the groups stratified by the preoperative counts of CB. RESULTS: There were more advanced clinical T and N stages in the low CB group than in the high CB group (P = 0.01 and = 0.04, respectively). The incidences of postoperative complications were comparable between the groups. The low CB count was associated with unfavorable overall and recurrence-free survivals (P = 0.04 and 0.01, respectively). In the multivariate analysis, low CB count was one of the independent prognostic factors for poor recurrence-free survival (HR 1.33; 95% CI 1.04-1.70; P = 0.02). In addition, hematogenous recurrence occurred more frequently in the low CB group than in the high CB group (57.6% vs. 41.4%, P = 0.04). CONCLUSION: A preoperative low CB count was an unfavorable prognosticator in patients who underwent esophagectomy for esophageal cancer.

Robotic-Assisted Esophagectomy: Current Situation and Future Perspectives.

Robotic-assisted minimally invasive esophagectomy (RAMIE) has been rapidly spreading worldwide as a novel minimally invasive approach for esophageal cancer. This narrative review aimed to elucidate the current situation and future perspectives of RAMIE for esophageal cancer. References were searched using PubMed and Embase for studies published up to 8 April 2023. Search terms included "esophagectomy" or "esophageal cancer" and "robot" or "robotic" or "robotic-assisted." There are several different uses for the robot in esophagectomy. Overall complications are equivalent or may be less in RAMIE than in open esophagectomy and conventional (thoracoscopic) minimally invasive esophagectomy. Several meta-analyses demonstrated the possibility of RAMIE in reducing pulmonary complications, although the equivalent incidence was observed in two randomized controlled trials. RAMIE may increase the number of dissected lymph nodes, especially in the left recurrent laryngeal nerve area. Long-term outcomes are comparable between the procedures, although further research is required. Further progress in robotic technology combined with artificial intelligence is expected.

Risk prediction of esophageal squamous cell carcinoma recurrence in patients who underwent esophagectomy after receiving neoadjuvant treatment: a nationwide retrospective study in Japan.

BACKGROUND: Although neoadjuvant treatment (NAT) has become the standard of care for patients with locally advanced esophageal cancer, the risk of recurrence remains high. The risk must be predicted accurately, so that appropriate adjuvant therapy can be planned. We aimed to develop a model predicting recurrence of esophageal squamous cell carcinoma (ESCC) in patients who received NAT before esophagectomy. METHODS: This nationwide study included 3874 patients from 85 institutions. Patients who underwent NAT and then surgery for ESCC were eligible. We developed a Cox proportional hazards model and created a nomogram to predict disease recurrence after NAT and curative esophagectomy. RESULTS: Of the patients, 268 (6.9%), 1280 (33.0%), 2006 (51.8%), and 320 (8.3%) had clinical stage I, II, III, and IV tumors, respectively. The 5-year recurrence rate was 45.1% (95% confidence interval 43.4%-46.7%). Multivariable analysis revealed that body mass index, type of neoadjuvant treatment, primary tumor location, operative blood loss, pathological tumor stage, pathological therapeutic effect, and leakage were independently associated with disease recurrence. Using 13 commonly measured perioperative variables, we created a predictive nomogram, and the area under the curve was 0.783 (95% confidence interval 0.766-0.800). This nomogram was also adequately validated internally and had excellent calibration capacity (calibration slope, 0.992). CONCLUSIONS: The model developed in this study adequately predicted ESCC recurrence in patients who underwent NAT and then esophagectomy. Further research with this nomogram is needed to assess the effect of adjuvant therapy in patients at high risk for recurrence.

Prognostic impact of endoscopic response evaluation after neoadjuvant chemotherapy for esophageal squamous cell carcinoma: a nationwide validation study.

BACKGROUND: Our previous study reported the prognostic significance of endoscopic response (ER) evaluation, defined ER, and revealed ER as an independent prognostic factor of overall survival (OS) and recurrence-free survival (RFS) for esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemotherapy (NAC) and surgery. The present study aimed to validate the prognostic impact of ER using a nationwide database from the authorized institute for board-certified esophageal surgeons by the Japan Esophageal Society. METHODS: This study retrospectively reviewed patients with ESCC who underwent subtotal esophagectomy at 85 authorized institutes for esophageal cancer from 2010 to 2015. Patients were classified as ER when the tumor size was markedly reduced post-NAC compared to pre-NAC. The correlation between OS and RFS was investigated. RESULTS: Of 4781 patients initially enrolled, 3636 were selected for subsequent analysis. Of them, 642 (17.7%) patients were classified as the ER group. Patients with ER showed significantly better OS and RFS. Subgroup analysis revealed the statistical difference in OS and RFS in cStage II and III, while the magnitude of survival difference between ER and non-ER was not evident in cStage I and IV. The percentage of ER varied from 46 to 87% among groups when institutions were classified into 3 subgroups based on the hospital volume, which would indicate the interinstitutional inconsistency. CONCLUSIONS: The prognostic impact of ER was validated using a nationwide database. Standardization of ER evaluation is required to improve the interinstitutional consistency and clinical validity of the ER evaluation.

Old age and intense chemotherapy exacerbate negative prognostic impact of postoperative complication on survival in patients with esophageal cancer who received neoadjuvant therapy: a nationwide study from 85 Japanese esophageal centers.

BACKGROUND: The prognostic impact of docetaxel, cisplatin, and 5-FU (DCF) reported in JCOG1109 was successfully validated using real-world data in patients < 75 years old. However, DCF was not reported to be beneficial in elderly patients with a relatively higher postoperative complication incidence. This study aimed to clarify the impact of postoperative complications on the prognosis of ESCC and the difference in the magnitude of the impact by age and regimen. METHODS: Patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed from 2010 to 2015. The prognostic impact of postoperative anastomotic leakage (AL) and pneumonia on survival was evaluated. The prognostic value of the postoperative complications was assessed by stratifying patients according to age and neoadjuvant chemotherapy regimen. RESULTS: Patients with AL, pneumonia, and infectious complications (ICs: a combination of pneumonia and AL) showed significantly worse overall survival (OS). IC served as a negative prognostic factor of OS and recurrence-free survival, and its negative prognostic impact was more evident in patients aged > 75 years. When the patients were further stratified by chemotherapeutic regimens, using the CF/IC(-) group as a reference, the DCF/IC (+) group showed significantly shorter OS in patients aged > 75 years with a hazard ratio (HR) of 2.551. The HR of the CF/IC (+) group was 1.503. CONCLUSIONS: The negative impact of postoperative complications on survival was confirmed in this nationwide study. Furthermore, its magnitude was higher in elderly patients who received triplet chemotherapy.