Minimally Invasive Esophagectomy Provides Better Short- and Long-Term Outcomes Than Open Esophagectomy in Locally Advanced Esophageal Cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) has been increasingly performed for locally advanced esophageal cancer in place of open transthoracic esophagectomy (OE). This study explored the significance of MIE for esophageal squamous cell carcinoma (ESCC), focusing mainly on the depth of primary esophageal tumors. METHODS: This study retrospectively assessed short- and long-term outcomes of patients who underwent esophagectomy for ESCC from 2005 through 2021. The inverse probability of the treatment-weighting (IPTW) method was used to compare the outcomes between OE and MIE. The outcomes also were evaluated in the subgroups stratified by cT category. RESULTS: Among 1117 patients, 447 (40%) underwent OE and 670 (60%) underwent MIE. After IPTW adjustment, the incidence of any postoperative complications was significantly higher in the OE group than in the MIE group (60.8% vs 53.7%; p = 0.032), whereas the R0 resection rate was significantly higher in the MIE group (98.6% vs 92.7%; p < 0.001). The MIE group showed better 3 year overall and cancer-specific survival than the OE group (p < 0.001). The incidence of locoregional recurrence within the surgical field was significantly more frequent in the OE group (p < 0.001). In the subgroup analysis stratified by cT category, the R0 resection rate was significantly higher and the incidence of locoregional recurrence was lower in the MIE group among the patients with cT3-4 tumors. In the patients with cT1-2 tumors, MIE showed no significant benefit over OE. CONCLUSIONS: For the patients with cT3-4 tumors, MIE showed fewer postoperative complications, better locoregional control, and better prognosis than OE. Compared with OE, MIE is beneficial, especially for locally advanced ESCC.

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.

Anatomical factor associated with thoracic procedural difficulty in robot-assisted minimally invasive esophagectomy.

BACKGROUND: Robotic surgical systems with full articulation of instruments, tremor filtering, and motion scaling can potentially overcome the procedural difficulties in endoscopic surgeries. However, whether robot-assisted minimally invasive esophagectomy (RAMIE) can overcome anatomical difficulties during thoracoscopic esophagectomy remains unclear. This study aimed to clarify the anatomical and clinical factors that influence the difficulty of RAMIE in the thoracic region. METHODS: Forty-five patients who underwent curative-intent RAMIE with upper mediastinal lymph node dissection for esophageal cancer were included. Using preoperative computed tomography images, we calculated previously reported anatomical indices to assess the upper mediastinal narrowness and vertebral body projections in the middle thoracic region. The factors influencing thoracic operative time were then investigated. RESULTS: During the thoracic procedure, the median operative time was 215 (124-367) min and the median blood loss was 20 (5-190) mL. Postoperatively, pneumonia, anastomotic leakage, and recurrent laryngeal nerve palsy occurred in 17.8%, 2.2%, and 6.7% of the patients, respectively. The multiple linear regression model revealed that a narrow upper mediastinum and greater blood loss during the thoracic procedure were significant factors associated with a prolonged thoracic operative time (P = 0.025 and P < 0.001, respectively). Upper mediastinal narrowing was not associated with postoperative complications. CONCLUSIONS: A narrow upper mediastinum was significantly associated with a prolonged thoracic operative time in patients with RAMIE.

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.

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.

Real-world Evaluation of the Efficacy of Neoadjuvant DCF Over CF in Esophageal Squamous Cell Carcinoma: Propensity Score-matched Analysis From 85 Authorized Institutes for Esophageal Cancer in Japan.

OBJECTIVE: We aimed to evaluate the efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy over cisplatin and 5-fluorouracil (CF) in patients with surgically resectable advanced esophageal squamous cell carcinoma (ESCC), using real-world data from 85 esophageal centers. BACKGROUND: JCOG1109 trial, which assessed the superiority of DCF over CF, and the superiority of chemoradiotherapy with CF over CF alone demonstrated the significant survival advantage of neoadjuvant DCF in overall survival (OS) over CF for ESCC. METHODS: The ESCC patients who received neoadjuvant CF or DCF at 85 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. After propensity score (PS) matching, the OS and recurrence-free survival were compared between CF and DCF. RESULTS: We initially enrolled 4781 patients. After data cleaning and PS matching using pretreatment variables, 1074 patients for each group were selected for subsequent analysis. There was no significant difference in the incidence of postoperative pneumonia and anastomotic leakage. In the survival analysis, OS was significantly longer in DCF group than CF group (hazard ratio, 0.868; 95% confidence interval, 0.770-0.978; P =0.02), as well as recurrence-free survival (hazard ratio, 0.850; 95% confidence interval, 0.761-0.949; P =0.004). The survival advantage of DCF was not observed in patients with 76 years old or older. CONCLUSIONS: Neoadjuvant DCF therapy showed a remarkable survival advantage in surgically resectable ESCC patients, especially in patients who were 75 years old or younger. The current real-world evidence will encourage recommendations for DCF as a standard regimen in neoadjuvant chemotherapy-based treatment strategy for ESCC.

Nationwide Validation Study of the Prognostic Significance of Stratification Using Pathological Stage and Response to Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to validate the prognostic significance of stratification using pathological stage and response to neoadjuvant chemotherapy with a nationwide database from an authorized institute by the Japan Esophageal Society. BACKGROUND: We proposed the combined criteria using pStage and pathological response. Conducting a validation study using an expanded cohort in the clinical setting would be valuable since it was developed using retrospective data collection. METHODS: Patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy at 85 authorized institutes were retrospectively reviewed for esophageal cancer between 2010 and 2015. The prognostic value of the pathological response was evaluated within the same pStage. Moreover, risk stratification was developed to predict cancer-specific survival (CSS). RESULTS: The pathological response showed significant stratification of CSS in 3761 patients included in this analysis. We classified the patients into 7 groups as survival was significantly different between responders and nonresponders under the stratification with pStage, excluding pStage I comprising pStage 0-I/II responder/II nonresponder/III responder/III nonresponder/IV responder/IV nonresponder with the 5-year CSS of 83.7%/75.8%/68.9%/59.8%/44.4%/40.7%/23.1%, respectively. Furthermore, the area under the curve was significantly higher under the new classification than in the pStage alone ( P <0.001). CONCLUSIONS: The prognostic value of classification using pStage and the pathological response was successfully validated using real-world data in Japan. This result would guide appropriate treatment for patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy followed by esophagectomy.

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.

Development and Validation of a Predictive Model of Therapeutic Effect in Patients with Esophageal Squamous Cell Carcinoma Who Received Neoadjuvant Treatment: A Nationwide Retrospective Study in Japan.

BACKGROUND: Neoadjuvant treatment has become the standard of care for patients with advanced esophageal cancer. However, few studies have elucidated the clinical factors that predict response to neoadjuvant therapy in a large multicenter cohort. We aimed to develop a predictive model of therapeutic effect in patients with esophageal squamous cell carcinoma (SCC) who received neoadjuvant treatment. METHODS: This nationwide study included 4078 patients from 85 institutions. Patients who received neoadjuvant treatment followed by surgery for esophageal SCC were eligible. We developed a logistic regression model to predict good pathological therapeutic effects, and a predictive nomogram was generated by applying the logistic regression formula. RESULTS: Among neoadjuvant regimens, cisplatin plus 5-fluorouracil (CF) was the most frequently used (60.2%), followed by docetaxel plus CF (DCF, 27.4%), CF with radiotherapy (CF-RT, 4.5%), adriamycin plus CF (3.6%), nedaplatin plus 5-fluorouracil (0.9%), and DCF-RT (0.5%). Multivariable analysis revealed that male sex, advanced cT category, and increased pretherapeutic SCC antigen level were independently associated with not achieving a good therapeutic effect. Moreover, intensified neoadjuvant regimens were independently associated with favorable therapeutic effects; DCF-RT elicited the best therapeutic effect, followed by CF-RT and DCF. A predictive model including nine commonly measured preoperative variables was generated, and the area under the curve was 0.679 (95% confidence interval: 0.658-0.700). This nomogram was also adequately validated internally. CONCLUSIONS: The model developed in this study was validated and predicts the therapeutic effect in patients with esophageal SCC who received neoadjuvant treatment. This model might contribute to individualized treatment strategies.

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.

Can Extracellular Vesicles as Drug Delivery Systems Be a Game Changer in Cardiac Disease?

Cardiac diseases such as myocardial infarction and heart failure have been the leading cause of death worldwide for more than 20 years, and new treatments continue to be investigated. Heart transplantation, a curative treatment for severe cardiac dysfunction, is available to only a small number of patients due to the rarity of donors and high costs. Cardiac regenerative medicine using embryonic stem cells and induced pluripotent stem cells is expected to be a new alternative to heart transplantation, but it has problems such as induction of immune response, tumor formation, and low survival rate of transplanted cells. On the other hand, there has been a focus on cell-free therapy using extracellular vesicles (EVs) due to their high biocompatibility and target specificity. Exosomes, one type of EV, play a role in the molecular transport system in vivo and can be considered a drug delivery system (DDS) innate to all living things. Exosomes contain nucleic acids and proteins, which are transported from secretory cells to recipient cells. Molecules in exosomes are encapsulated in a lipid bilayer, which allows them to exist stably in body fluids without being affected by nuclease degradation enzymes. Therefore, the therapeutic use of exosomes as DDSs has been widely explored and is being used in clinical trials and other clinical settings. This review summarizes the current topics of EVs as DDSs in cardiac disease.

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.

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.

A nationwide validation of the prognostic impact of pathological response and the distribution of recurrence patterns in responders after neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

BACKGROUND: We previously reported that postoperative recurrence in responders occurred in the regional field mostly as a solitary lesion without distant failure. However, further validation is necessary due to the low percentage of pathological responders, especially those with pCR. This study aimed to validate the prognostic impact of pathological response and the distribution of residual tumors in pathological responders using a nationwide database from 85 Japanese esophageal centers. METHODS: We retrospectively reviewed patients with esophageal squamous cell carcinoma (ESCC) who underwent subtotal esophagectomy at 85 authorized institutes for esophageal cancer between 2010 and 2015. The recurrence free survival (RFS), overall survival (OS), and recurrent tumor patterns were compared among the pathological responses. RESULTS: Of 4781 patients initially enrolled, 3840 were selected for subsequent analysis, including 237 patients with pathological complete response (pCR, 6%). The RFS and OS were significantly correlated with pathological response. When the recurrence pattern was classified into regional or distant recurrence, the incidence of distant failure was significantly lower in patients with pCR in cT1/2. Three percent of all patients with pCR in cT1/2 encountered postoperative recurrence in distant organs. CONCLUSION: The prognostic impact of pathological response was reproduced in the nationwide data. pCR in ESCC patients with cT1/2 provides a favorable prognosis with less incidence of distant failure. This finding may contribute to selecting appropriate candidates for an organ preservation approach based on the response to induction therapy.

Influence of patient position in thoracoscopic esophagectomy on postoperative pneumonia: a comparative analysis from the National Clinical Database in Japan.

BACKGROUND: Two prominent patient positions during thoracoscopic esophagectomy are the left lateral decubitus position (LP) and the prone position (PP). However, whether the patient position during thoracoscopic esophagectomy influences short-term outcomes, especially postoperative pneumonia, remains unclear. We aimed to elucidate the impact of patient position on the occurrence of postoperative pneumonia. METHODS: We analyzed 9850 patients who underwent oncologic thoracoscopic esophagectomies between 2016 and 2019 from the National Clinical Database. We compared the short-term outcomes between the LP and PP groups, and the primary outcome measure was the incidence of postoperative pneumonia. RESULTS: This study included 2637 (26.8%) and 7213 (73.2%) patients in the LP and the PP groups, respectively. The baseline characteristics of the two groups were well-balanced. Compared with the LP group, the PP group had a longer operative time and less blood loss. There were no significant differences in the incidences of postoperative pneumonia, recurrent laryngeal nerve palsy, anastomotic leakage, severe complications, and reoperation between the groups. Meanwhile, prolonged ventilation and surgery-related mortality occurred more frequently in the LP than in the PP group (P < 0.001 and 0.046, respectively). After multivariable adjustment, the patient position did not significantly influence the incidence of postoperative pneumonia (odds ratio 0.91, 95% confidence interval 0.80-1.04). CONCLUSIONS: Although prolonged ventilation and surgery-related mortality occurred more frequently in the LP group than in the PP group, the patient position did not significantly influence the occurrence of postoperative pneumonia.

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.

Association Between Preoperative HbA1c Levels and Complications after Esophagectomy: Analysis of 15,801 Esophagectomies From the National Clinical Database in Japan.

OBJECTIVE: To elucidate the association between preoperative hemoglobin A1c (HbAlc) levels and short-term outcomes after oncologic esophagectomy. SUMMARY BACKGROUND DATA: Although diabetes mellitus is associated with an increased risk of postoperative morbidity in several types of surgery, the association of diabetes mellitus with short-term outcomes after esophagectomy has shown conflicting results. METHODS: We analyzed 15,801 patients who underwent oncologic esophagectomy between 2015 and 2017 from the National Clinical Database. We evaluated the associations between preoperative HbA1c levels and short-term outcomes, using multivariable logistic regression and restricted cubic spline models. RESULTS: The cohort included 12,074, 1361, 1097, 909, and 360 patients with HbA1c levels of ≤5.9%, 6.0% to 6.4%, 6.5% to 6.9%, 7.0% to 7.9%, and ≥8.0%, respectively. There were value-dependent associations between HbA1c values and odds ratios for anastomotic leakage, surgical site infections, pneumonia, and composite outcomes. Compared with the HbA1c category of ≤5.9%, the categories of 7.0% to 7.9% and ≥8.0% were at higher risk for anastomotic leakage ( P < 0.001 and 0.031, respectively), the category of ≥8.0% was at higher risk for surgical site infections ( P = 0.001), the categories of 6.5% to 6.9% and 7.0% to 7.9% were at higher risk for pneumonia ( P = 0.016 and 0.002, respectively), and the categories of 7.0 to 7.9 and > 8.0% were at higher risk for composite outcomes (P < 0.001 and 0.001, respectively). CONCLUSIONS: Preoperative HbA1c levels are associated with the risk of postoperative complications after esophagectomy, and the threshold values differed among the outcomes. Preoperative HbA1c is useful in predicting the risk of postoperative complications.