Genomic alterations in two patients with esophageal carcinosarcoma identified by whole genome sequencing: a case report.

BACKGROUND: Esophageal carcinosarcoma (ECS) is a relatively rare malignancy, accounting for < 1% of all esophageal cancers. Its etiopathogenesis remains unknown. This study analyzed the genomic abnormalities in sarcomatous tumors from two patients undergoing subtotal esophagectomy using whole genome sequencing to elucidate the key characteristics of ECS. CASE PRESENTATION: We identified TP53 driver mutations, copy number gains in 11q13 (including CCND1), and Apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) signature enrichment in both ECS patients. Along with common genetic abnormalities, we identified CDKN2A driver mutations in case 1 and RAC1, NOTCH1, and TTC28 as novel fusion gene partners of MECOM in case 2. Notably, we detected germline pathogenic variant in Fanconi anemia (FA) complementation group I (FANCI) and group G (FANCG), which are involved in repairing DNA double-strand breaks by homologous recombination, for the first time, in ECS blood samples. These germline variants were truncating-type, Lys1221fs of FANCI (rs1567179036) for case 1 and Gln365Ter of FANCG (rs121434426) for case 2. We also identified somatic changes in cancer-associated pathways, such as PI3K/Akt/mTOR, cell cycle, and NOTCH signaling pathways, and structural chromosomal defects such as chromosome doubling. CONCLUSIONS: Our findings indicate that therapeutic drugs targeting the activation signal or FA pathway might be effective in treating ECS, however, their therapeutic significance should be elucidated in future studies.

Survival outcome of esophagectomy and chemoradiotherapy for resectable esophageal squamous cell carcinoma in patients >75 years of age.

BACKGROUND: The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC. METHODS: Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups. RESULTS: The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117). CONCLUSIONS: There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients.

Clinical Significance of Albumin-Bilirubin Grade in Thoracic Esophageal Squamous Cell Carcinoma.

INTRODUCTION: The albumin-bilirubin (ALBI) score evaluates liver dysfunction severity. However, this score had prognostic effects in patients with hepatocellular, pancreatic, and gastric carcinomas. We aimed to assess the predictive value of the ALBI score in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Data from 154 patients with ESCC who consecutively underwent neoadjuvant chemotherapy (NAC) and subtotal esophagectomy were retrospectively investigated. The ALBI score was calculated as pre-NAC ALBI and categorized into grades 1, 2a, 2b, and 3; low-ALBI group (n = 134) was assigned with ALBI grade 1 and the other grades were assigned to the high-ALBI group (n = 20). RESULTS: The pre-NAC ALBI was significantly associated with relapse-free survival (RFS) and overall survival (P = 0.003 and P = 0.014, respectively). Based on multivariate analysis, pre-NAC ALBI, pathological T factor, and N factor were identified as independent prognostic factors for poor RFS. Multivariate and univariate analyses limited to factors were obtained before treatment, indicating high pre-NAC ALBI as an independent prognostic factor of poor overall survival (P = 0.039) and RFS (P = 0.008). With respect to pathological response to NAC, patients in the high pre-NAC ALBI group had a significantly lower response than patients in the low pre-NAC ALBI group (P = 0.010). CONCLUSIONS: Our results suggested that the pre-NAC ALBI marker predicts the long-term outcome and pathological response to NAC in patients with ESCC consecutively undergoing NAC and a subtotal esophagectomy.

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.

Ramelteon and suvorexant for postoperative delirium in elderly patients with esophageal cancer.

BACKGROUND: There is no clear evidence on the prevention of postoperative delirium with pharmacotherapy in elderly patients with esophageal cancer. This retrospective study aimed to evaluate the efficacy of ramelteon and suvorexant in preventing postoperative delirium in this patient group. METHODS: Data on 251 patients who received radical esophagectomy for thoracic esophageal cancer were collected from January 2010 to September 2021. In total, 74 patients did not receive preventive intervention, and 177 received ramelteon and suvorexant. After propensity score matching, the rate of postoperative delirium was compared between the two groups. RESULTS: Seventy-two well-balanced patients in each group demonstrated similar clinical and pathological characteristics. The mean ages of the intervention and control groups were 70.8 and 70.3 years, respectively. All the patients underwent McKeown esophagectomy, and in the volume of intraoperative blood loss or operative time did not significantly differ between the two groups. The incidence rates of postoperative hyperactive delirium were 7% (5/72) in the intervention group and 32% (23/72) in the control group (p < 0.001). No severe adverse event potentially attributable to the intervention drug was observed. The multivariate analysis showed that the use of ramelteon and suvorexant was the only independent protective factor against postoperative delirium (hazard ratio 0.157, 95% CI 0.055-0.448, p < 0.001). CONCLUSIONS: Ramelteon and suvorexant may play an important role in reducing postoperative delirium in elderly patients with esophageal cancer.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

Prognostic impact of perioperative change in serum p53 antibody titers in esophageal squamous cell carcinoma.

BACKGROUND: The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC. METHODS: From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3 months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups. RESULTS: There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2 months vs. 36.7 months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS. CONCLUSIONS: Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

The clinical impacts of postoperative complications after colon cancer surgery for the clinical course of adjuvant treatment and survival.

AIM: We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan PATIENTS AND METHODS: The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). RESULTS: A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). CONCLUSION: POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

Effect of Postoperative Oral Intake Status on Sarcopenia Six Months After Esophageal Cancer Surgery.

PURPOSE: In patients with esophageal cancer, skeletal muscle mass has been reported to decrease progressively after surgery and be independently associated with a poor prognosis. The purpose of this study was to investigate perioperative changes in dysphagia, oral intake status, and nutritional status and identify factors related to sarcopenia 6 months after esophagectomy. METHODS: A total of 134 patients who underwent radical resection for thoracic esophageal cancer between March 2016 and July 2019 were analyzed retrospectively. The diagnosis of sarcopenia was made by CT taken 6 months postoperatively using the cut-off criteria of skeletal muscle index (SMI) < 52.4 cm2/m2 for male and SMI < 38.5 cm2/m2 for female patients. As factors related to postoperative sarcopenia, dysphagia, oral intake status, nutritional status, and physical function were extracted from the medical records. Multivariate logistic regression analysis was performed to identify perioperative risk factors related to sarcopenia 6 months after surgery. RESULTS: Of the 134 patients, 34.3% were judged to be unable to start oral intake on swallowing assessment. At discharge, 30.6% received tube feeding with or without oral intake. In the non-oral intake group on swallowing assessment, a significantly higher proportion of patients received tube feeding at discharge (p = 0.014). Preoperative BMI, postoperative handgrip strength, and tube feeding at discharge were independent risk factors for sarcopenia 6 months after esophagectomy in male patients. CONCLUSION: Tube feeding at discharge is significantly related to postoperative sarcopenia in patients with esophageal cancer. Identifying high-risk groups might allow early detection of malnutrition and provision of appropriate care.

Selective Lymphadenectomy for Salvage Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Extensive lymph node dissection increases the risk of postoperative complications, especially in salvage surgery, after definitive chemoradiotherapy (≥ 50 Gy) in patients with esophageal squamous cell carcinoma. The purpose of this retrospective study is to compare the outcomes of salvage esophagectomy with selective lymphadenectomy of only clinically positive lymph nodes. METHODS: Clinically positive lymph nodes, diagnosed as metastases using computed and positron emission tomography performed before chemoradiotherapy or salvage surgery, were targeted for dissection in selective lymphadenectomy. We compared postoperative complications between 52 patients who underwent salvage esophagectomy with selective lymphadenectomy and 207 controls who underwent nonsalvage esophagectomy with 3-field lymphadenectomy. We also analyzed postoperative recurrence pattern and survival in salvage group. RESULTS: The mean number of dissected lymph nodes was 12.9 in the salvage esophagectomy group compared with 48.1 in the 3-field lymphadenectomy group (p < 0.001). Differences in the number of postoperative complications, comparing Clavien-Dindo all-grade and ≥ grade 3, were not significant between the groups. Both 30- and 90-day mortality were 0% (0/52) in the salvage group. Five cases had recurrence only in the locoregional area without distant metastasis. Of these five cases, only one had recurrence in the subcarinal lymph node without prophylactic mediastinal lymphadenectomy. A 3-year recurrence-free survival and 3-year overall survival from salvage esophagectomy were 43.3% and 46.3%, respectively. CONCLUSIONS: It may contribute to obtaining good short- and long-term outcomes by dissecting only clinically positive lymph nodes in salvage esophagectomy.

Development and Validation of the Optimal Circumferential Resection Margin in Pathological T3 Esophageal Cancer: A Multicenter, Retrospective Study.

BACKGROUND: The clinical significance of circumferential resection margin (CRM) in esophageal squamous cell carcinoma (ESCC) remains unclear. Optimal CRM for predicting the recurrence of pathological T3 ESCC was investigated. METHODS: Seventy-three patients were retrospectively investigated in the development cohort. Patients were divided into CRM-negative and CRM-positive groups, and clinicopathological factors and survival outcomes were compared between the groups. The cutoff value was validated in another validation cohort (n = 99). RESULTS: Receiver operating characteristic analysis in the development cohort showed the cutoff value of CRM was 600 µm. In the validation cohort, patients in the CRM-positive group showed a significantly higher rate of locoregional recurrence (p = 0.006) and worse recurrence-free survival (RFS) (p < 0.001) than those in the CRM-negative group. Multivariate analysis identified positive CRM as an independent predictive factor for poor RFS (hazard ratio, 2.695; 95% confidence interval, 1.492-4.867; p = 0.001). The predictive value of our criteria of positive CRM for RFS was higher than that of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) criteria. Stratified analysis in the neoadjuvant chemotherapy groups also revealed that the rate of locoregional recurrence was higher in the CRM-positive group than in the CRM-negative group both in the pathological N0 and N1-3 subgroups. CONCLUSIONS: CRM of 600 µm can be the optimal cutoff value rather than the RCP and CAP criteria for predicting locoregional recurrence after esophagectomy. These results may support the impact of perioperative locoregional control of locally advanced ESCC.

Association of anastomotic leakage with long-term oncologic outcomes of patients with esophagogastric junction cancer.

BACKGROUND: Despite improvements in surgical procedures and peri-operative patients management, the postoperative complications in esophagogastric junction (EGJ) cancer remain high because of technical aspects. Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery. However, no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer. AIM: To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer. METHODS: A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study. We examined the association between complications and long-term oncologic outcomes. RESULTS: In all patients, the 3-year overall survival (OS) rate was 71.9%, and the recurrence-free survival (RFS) rate was 67.5%. Compared with patients without anastomotic leakage, those with anastomotic leakage had poor median OS (8 mo vs not reached, P = 0.028) and median RFS (5 mo vs not reached, P = 0.055). Among patients with cervical anastomosis, there were not significant differences between patients with and without anastomotic leakage. However, among patients who underwent intrathoracic anastomosis, patients with anastomotic leakage had significantly worse OS (P = 0.002) and RFS (P = 0.005). CONCLUSION: Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer, especially those who underwent intrathoracic anastomosis. Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.

Preoperative maximum phonation time as a predictor of pneumonia in patients undergoing esophagectomy.

PURPOSE: Esophagectomy is a highly invasive procedure, associated with several postoperative complications including pneumonia, anastomotic leakage, and sepsis, which may result in multiorgan failure. Pneumonia is considered a major predictor of poor long-term prognosis, so its prevention is important for patients undergoing surgery for esophageal cancer. METHODS: The subjects of this study were 137 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January, 2012 and December, 2016. Patients who underwent R0 or R1 resection or esophagectomy with organ excision were included. Patients who underwent salvage surgery or resection of recurrent laryngeal nerve, and those with preoperative recurrent laryngeal nerve palsy, were excluded. We investigated the effect of the maximum phonation time on the development of postoperative pneumonia. RESULTS: Pneumonia developed more frequently in patients with a long operative time, clinically left recurrent nerve lymph node metastasis, and a short preoperative maximum phonation time (p = 0.074, 0.046, and 0.080, respectively). Pneumonia was also more common in men with an abnormal maximum phonation time (p = 0.010). CONCLUSIONS: The maximum phonation time is a significant predictor of postoperative pneumonia after esophagectomy in men.

Difficult to treat esophageal perforation after endoscopic balloon dilation for stenosis due to endoscopic submucosal dissection followed by chemoradiotherapy: A case report.

INTRODUCTION AND IMPORTANCE: There is no clear consensus on a specific treatment for esophageal perforation. The surgical approach is deemed necessary for local severe infection and pleural contamination requiring debridement. PRESENTATIONS OF CASE: We have reported herein the case of a patient with esophageal perforation with severe mediastinal and thoracic abscess after endoscopic balloon dilation for stenosis due to endoscopic submucosal dissection and chemoradiotherapy. A surgical approach with primary closure was performed, but not found effective; while conservative treatment with mediastinal drainage via posterior neck and recovery of nutritional status was found to be effective. For the recovery of nutritional status, enteral nutrition was assessed using a polymeric formula through a percutaneous endoscopic gastrojejunostomy tube. DISCUSSION: Esophageal perforation is a life-threatening condition. Iatrogenic injuries are the frequent cause of esophageal perforation. For esophageal perforation, not only surgical interventions but also conservative treatments including various endoscopic approaches have been performed. If the inflammation is not localized, surgical intervention is often needed; however, if the patient's general condition is stable, conservative treatment with drainage, antibiotics, and nutritional management may be considered, even in cases of esophageal perforation. CONCLUSIONS: Esophageal perforation with a large perforation site with widespread inflammation can be improved with proper thoracic and mediastinal drainage and adequate nutrition support if the patient's condition is mild.

Tissue Oxygen Saturation during Gastric Tube Reconstruction with Cervical Anastomosis for Esophagectomy: A Case Series.

BACKGROUND: One cause of anastomotic leakage after radical esophagectomy is blood flow insufficiency at the cervical anastomosis site. . METHODS: Eighteen patients, who underwent radical esophagectomy with gastric tube reconstruction, were studied. The regional tissue oxygen saturation (rSO2) was measured at the tip (point pre 0) and 2, 4, and 6 cm on the distal side of the tip (point pre 1, pre 2, and pre 3, respectively) before the gastric tube was raised to the cervical site through the retrosternal route. After that, rSO2 was measured at the tip, 2 and 4 cm on the distal side of the tip (points post 0, post 1, and post 2), the actual anastomotic site (point AN), and the chest skin as an indicator of whole-body oxygenation. The relationship between rSO2 scores and the rate of anastomotic leakage was determined. RESULTS: The mean rSO2 at pre 0, pre 1, pre 2, and pre 3 were 48.9%, 52.3%, 54.8%, and 56.9%, respectively (p < 0.05). The mean rSO2 at post 0, post 1, and post 2 were 47.8%, 50.5%, and 52.3%, respectively, and the rSO2 at point AN was 52.1%.Anastomotic leakage was found in 6 patients. The rSO2 at points pre 0, pre 1, and pre 2, post 0 and point AN were significantly lower in patients with anastomosis leakage than those without (p < 0.05). CONCLUSION: Tissue oxygen saturation monitoring was a useful indicator of blood flow insufficiency in the gastric tube during radical esophagectomy.

Distribution of Residual Disease and Recurrence Patterns in Pathological Responders After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to elucidate the residual disease distribution and recurrence patterns in patients with ESCC responding to NAC. SUMMARY BACKGROUND DATA: To appropriately plan a prospective trial for the organ preservation approach which includes additional chemoradiotherapy in patients who responded to NAC, the distribution of residual disease needs to be elucidated. Given that the residual tumor is located in the regional field, chemoradiotherapy can be safely added to eliminate the residual disease. METHODS: Overall, 483 patients with resectable ESCC who received NAC followed by transthoracic esophagectomy at 2 high-volume centers were reviewed. The recurrence-free survival, overall survival (OS), and residual and recurrent tumor patterns were compared among the pathological responses. RESULTS: Compared with nonpathological responders, pathological responders exhibited significantly longer recurrence-free survival [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.25 ( P < 0.001)/0.17 ( P < 0.001)/0.16 ( P = 0.003)] and OS [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.26 ( P < 0.001)/0.12 ( P < 0.001)/0.11 ( P = 0.003)]. In terms of the distribution of recurrence, the percentages of solitary recurrence in the regional field out of all recurrence was significantly higher in patients with Grade 1b (60%)/2 (67%)/3 (67%) whereas less than 25% in Grade 0 or 1a. CONCLUSIONS: It was found that postoperative recurrence in responders occurred in the regional field mostly as a solitary lesion without the distant failure, indicating that the residual tumor cells can be eliminated by additional chemoradiotherapy.