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Introduction: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. Results: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1–0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. Conclusion: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC. [ABSTRACT FROM AUTHOR]

Background: Induction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC.Methods: We retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34-82] years) treated at our hospital in 2007-2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test.Results: The optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0-1 or pN0-1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0-1, p < 0.001; TMTV pN0-1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011).Conclusions: The TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objectives: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A∗24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1. Summary of Background Data: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. Methods: This is a non-randomized prospective phase II clinical trial (UMIN000003557). ESCC patients curatively resected after preoperative therapy with pN(+) were allocated into the control and vaccine groups (CG and VG) according to the HLA-A status. One mg each of three epitope peptides was postoperatively injected 10 times weekly followed by 10 times biweekly to the VG. The primary and secondary endpoints were relapse-free survival (RFS) and esophageal cancer-specific survival (ECSS), respectively. Results: Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs 45.3%), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs 32.4%, P = 0.045) and this difference was more prominent in patients with CD8+ and programmed death-ligand 1 double negative tumor (68.0% vs 17.7%, P = 0.010). Conclusions: Our cancer peptide vaccine might improve the survival of ESCC patients, which is warranted to be verified in the phase III randomized controlled study. [ABSTRACT FROM AUTHOR]

Background The weakness for the circular stapler technique of esophagogastric anastomosis for esophageal cancer is anastomotic stricture. This study was performed to verify the superiority of a new 'non-tensioning method' for avoiding stricture of the cervical esophagogastric anastomosis by circular stapling compared with the conventional method. Methods In 461 patients who underwent McKeown esophagectomy with gastric conduit (GC) reconstruction were reviewed. A GC was pulled up at the cervical site through the retrosternal route. The esophagogastrostomy site of the GC was planned as far caudally as possible on the greater curvature side. In the conventional method, the stapler was fired while pulling the GC to avoid tissue slack. In the new method, the stapler was fired through the natural thickness of the stomach wall. The blind end length was changed from 4 to 2 cm. Anastomotic stricture was compared between the two techniques, and adjustment was performed using propensity score matching. Results The conventional group comprised 315 patients, and the non-tensioning group comprised 146 patients. Anastomotic leakage occurred in 22 (7%) and 6 (4%) patients, respectively (P = 0.211) [and in 9 (3%) and 3 (2%) patients, respectively, if leakage at the blind end was excluded]. Anastomotic stricture occurred in 92 (29%) and 7 (5%) patients, respectively (P < 0.001). The propensity score-matching analysis including 134 pairs of patients confirmed a lower stricture rate in the non-tensioning than conventional group (4% vs. 27%, P < 0.001). Conclusions The non-tensioning technique, the natural thickness of the stomach wall was fired with the stapler, significantly reduced the incidence of anastomotic stricture compared with the conventional technique. [ABSTRACT FROM AUTHOR]

Background In Japan, pre-operative5-FU and cisplatin (CDDP) (FP) combination therapy has been the standard neoadjuvant chemotherapy (NAC) for advanced resectable esophageal cancer (EC), whereas the efficacy of docetaxel (DTX)-containing triplet regimen, FP plus DTX has been reported (Yamasaki M, et al, Ann Oncol 2017). However, for frail patients, such as patients with old age, chronic renal failure, poor performance status, severe commodities or malnutrition, high dose CDDP is not generally recommended in terms of toxicity. We have been developing non-CDDP-containing triplet regimen, 5-FU, DTX, and nedaplatin (NED) (UDON) on a phase I/II trial basis. This retrospective study aimed to investigate the safety and efficacy of NAC with UDON combination for advanced EC. Methods Eleven patients with advanced resectable EC who were unsuitable for the administration of high dose CDDP were enrolled in this study. Patients received two cycles of NAC with UDON (5-FU, 640 or 800 mg/m2, day1–5, DTX, 28 or 35 mg/m2, day1 and 15 and NED, 72 or 90 mg/m2, day1, q28) followed by esophagectomy. Primary endpoint was response rate and secondary endpoint was adverse event (AE). Results The median age was 73 years (range: 58–80) with eight patients being aged 70 or older. ECOG PS was 1/2: 7/4. The main location of the tumor was Ce/Ut/Mt/Lt/Ae: 1/1/7/1/1 and cStage was IIA/IIB/IIIA/IIIB/IIIC/IV: 2/2/4/0/2/1. The RR (CR + PR) was 82% (CR/PR/SD/PD: 1/8/2/0). The pathological response was grade 0/1a/1b/2/3: 2/3/3/2/1. Major grade 3 or 4 adverse events included neutropenia (27%), febrile neutropenia (27%), diarrhea (18%), enteritis (9%) and hyponatremia (27%). The postoperative morbidity included recurrent nerve palsy (36%), aspiration (27%), pneumonia (18%), anastomotic leakage (9%) and delirium (36%). There was no treatment-related death and no reoperation. Conclusion NAC with UDON for advanced resectable EC unsuitable for the administration of high dose CDDP might be feasible and effective. We are planning a phase II clinical study based on the present results. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Unexpected dysphagia is an important problem affecting life prognosis in patients who have undergone an esophagectomy for esophageal cancer. For nutritional support in patients suffering from dysphagia after a previous esophagectomy, a simplified percutaneous endoscopic transgastric conduit feeding jejunostomy approach was developed that can be performed regardless of the patient's condition. The feasibility of this procedure in 25 patients with esophageal cancer who underwent three-stage esophagectomy with retrosternal gastric conduit reconstruction from April 2009 to December 2016 was evaluated retrospectively. Under fluoroscopy, a percutaneous endoscopic transgastric conduit feeding jejunostomy catheter (9 French) was introduced into the jejunum in the epigastric region using the Seldinger's technique. The following patient data were analyzed retrospectively: operating time, complications, reasons for oral intake difficulty, and clinical data describing patients' nutritional status before and 1 month after percutaneous endoscopic transgastric conduit jejunostomy treatment, such as serum albumin and clinical course. Median patients' age was 68 years (range 50–76 years). Indications for the procedure were late swallowing dysfunction (n  = 12), early swallowing dysfunction secondary to surgical complication (n  = 8), anastomotic leakage (n  = 3), and anorexia (n  = 2). Causes of late swallowing dysfunction were radiation injury (n  = 8), advanced age (n = 2), or cerebral infarction (n  = 2). The median operating time was 29 minutes (range 14–82 minutes). Four patients developed mild erosions at the stoma secondary to bile reflux along the side of the catheter. No patient experienced severe complications such as ileus and peritonitis. Patients were treated for a median of 160 days (range 18–3106 days) with percutaneous endoscopic transgastric conduit jejunostomy. Patient's serum albumin significantly increased from 2.8 to 3.3 g/dl in 1 month. Of the eight patients with early swallowing dysfunction, six successfully regained sufficient oral nutrition after receiving enteral feeding nutritional management. Although all except one late swallowing dysfunction patient could not discontinue tube feeding, five patients were long-term survivors at the time this report was written. This jejunostomy procedure is simple, safe, and useful for patients with unexpected dysphagia and accompanying malnutrition after esophagectomy. [ABSTRACT FROM AUTHOR]

Background Elderly patients or those who have undergone surgery for head and neck cancer (HNC) have a potential risk of dysphagia, in addition, the latter has a considerable difficulty for surgery for the neck. Intrathoracic anastomosis is preferable to preserve swallowing function and reduce surgical risk, because the cervical procedure can be avoided. However, the stomach cannot be used as a substitute in gastrectomized patients; thus, securing graft blood supply is critical. Nevertheless, microvascular anastomosis cannot easily be added in procedures for intrathoracic posterior mediastinal reconstruction. We therefore designed a novel technique for esophageal reconstruction to enable both intrathoracic anastomosis and microvascular anastomosis simultaneously even in gastrectomized patients. The purpose of this study was to evaluate the usefulness and safety of this technique. Methods Esophagectomy with mediastinal lymphadenectomy is performed through a right thoracotomy in the left decubitus position, and temporary chest closure is done after the esophagus is divided at the upper mediastinum with safe margin. Next, the patient is placed in the left half side-lying position, and the jejunal or ileocolic graft for reconstruction is created after removal of the remnant stomach in the supine position. Then, after the patient's position is changed to the left decubitus one and rethoracotomy is performed, the graft is pulled up through the anterior mediastinum, and is then passed into the right thoracic cavity via a small hole made in the anterior mediastinal pleura. The graft is then finally anastomosed with the remnant esophagus in the upper posterior mediastinum. Thereafter, microvascular anastomosis is performed in the retrosternal space through the skin incision in the supine position. Finally, the continuity of alimentary tract is completed. Results This new reconstruction procedure was performed for 4 patients with no significant postoperative complications, good swallowing function postoperatively, and no retention of food in the graft. There was no in-hospital death. Conclusion This novel trans-mediastinal reconstruction technique is a possible option in terms of enabling intrathoracic anastomosis and addition of microvascular anastomosis for highly selected gastrectomized patients with advanced age or a past history of HNC surgery. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Most of esophageal squamous cell carcinoma (ESCC) develop in smoking males in Japan, but the genomic etiology and immunological characteristics of rare non-smoking female ECSS remain unclear. To elucidate the genomic and immunological features of ESCC in non-smoking females, we analyzed whole-genome or transcriptome sequencing data from 94 ESCCs, including 20 rare non-smoking female cases. In addition, 31,611 immune cells were extracted from four ESCC tissues and subject to single-cell RNA-seq. We compared their immuno-genomic and microbiome profiles between non-smoking female and smoking ESCCs. Non-smoking females showed much better prognosis. Whole-genome sequencing analysis showed no significant differences in driver genes or copy number alterations depending on smoking status. The mutational signatures specifically observed in non-smoking females ESCC could be attributed to aging. Immune profiling from RNA-seq revealed that ESCC in non-smoking females had high tumor microenvironment signatures and a high abundance of eosinophils with a favorable prognosis. Single-cell RNA-sequencing of intratumor immune cells revealed gender differences of eosinophils and their activation in female cases. ESCCs in non-smoking females have age-related mutational signatures and gender-specific tumor immune environment with eosinophils, which is likely to contribute to their favorable prognosis. • Risk factors for ESCC are often present in smoking males, but rare ESCCs in non-smoking females are recently present. • Immune-genomic analysis was performed on ESCC in non-smoking females, which show favorable prognosis. • Some mutational signatures specific to ESCCs in non-smoking females are likely to be age-related. • Single-cell analysis demonstrated that eosinophils and their activation in non-smoking female ESCCs. [ABSTRACT FROM AUTHOR]