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.

Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.

BACKGROUND/AIM: Brain metastasis, a leading cause of cancer death, is a clinical challenge. Recently, genetic characterization of brain metastatic lesions based on next generation sequencing-based advanced technologies, such as single-cell RNA sequencing, has been performed to develop novel efficient therapies. The present study aimed to investigate brain-metastasis-specific biomarkers as well as relevant prognostic factors. PATIENTS AND METHODS: The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized. RESULTS: Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors. CONCLUSION: High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

A phase III randomized controlled trial comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer: ARMADILLO trial (JCOG1904).

Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).

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.

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.

BACKGROUND/AIM: Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. PATIENTS AND METHODS: Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. RESULTS: Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. CONCLUSION: These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.

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.

Whole-genome and Epigenomic Landscapes of Malignant Gastrointestinal Stromal Tumors Harboring KIT Exon 11 557-558 Deletion Mutations.

Gastrointestinal stromal tumors (GIST) with KIT exon 11 deletions involving in codons 557-558 (KIT Δ557-558) exhibit higher proliferation rates and shorter disease-free survival times compared with GISTs with other KIT exon 11 mutations. We analyzed 30 GIST cases and observed genomic instability and global DNA hypomethylation only in high-risk malignant GISTs with KIT Δ557-558. Whole-genome sequencing revealed that the high-risk malignant GISTs with KIT Δ557-558 (12 cases) had more structural variations (SV), single-nucleotide variants, and insertions and deletions compared with the low-risk, less malignant GISTs with KIT Δ557-558 (six cases) and the high-risk (six cases) or low-risk (6 cases) GISTs with other KIT exon 11 mutations. The malignant GISTs with KIT Δ557-558 showed higher frequency and significance in copy number (CN) reduction on chromosome arms 9p and 22q, and 50% of them had LOH or CN-dependent expression reduction in CDKN2A. In addition, SVs with driver potential were detected in 75% of them, in which AKT3 and MGMT were recurrently identified. Genome-wide DNA methylation and gene expression analyses showed global intergenic DNA hypomethylation, SNAI2 upregulation, and higher expression signatures, including p53 inactivation and chromosomal instability, as characteristics of malignant GISTs with KIT Δ557-558 that distinguished them from other GISTs. These genomic and epigenomic profiling results revealed that KIT Δ557-558 mutations are associated with increased genomic instability in malignant GISTs. Significance: We present genomic and epigenomic insights into the malignant progression of GISTs with KIT exon 11 deletions involving in 557-558, demonstrating their unique chromosomal instability and global intergenic DNA hypomethylation.

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.

Real-world management and outcomes of older patients with locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. METHODS: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. RESULTS: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10-11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10-3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717). CONCLUSIONS: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.

Early tumor shrinkage and depth of response in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil: an exploratory analysis of the JCOG0807.

BACKGROUND: We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer. METHODS: ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates. RESULTS: Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS < 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR < 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS. CONCLUSIONS: ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.

Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society.

BACKGROUND: Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). METHODS: Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. RESULTS: In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003). CONCLUSIONS: CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.

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.

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.

Effectiveness and safety of a newly introduced multidisciplinary perioperative enhanced recovery after surgery protocol for thoracic esophageal cancer surgery.

OBJECTIVE: Data are sparse regarding the multidisciplinary perioperative enhanced recovery after surgery protocol (E-P) for thoracic esophageal cancer surgery that was newly used at another institution. Therefore, this study aimed to retrospectively evaluate the effectiveness and safety of the protocol. METHODS: We enrolled 101 patients who underwent transthoracic esophagectomy for E-P at the Shizuoka Cancer Center Hospital (SCC). The outcomes obtained at the SCC were compared with the outcomes of 140 patients treated with E-P at the Saitama Medical University International Medical Center (SMU). At the SMU, we compared the results before and after the introduction of E-P. RESULTS: The rates of morbidity, pulmonary complications, and postoperative pneumonia were 44%, 31%, and 6.9% at the SCC and 44%, 27%, and 6.5% at the SMU (P = 0.91, 0.55, and 0.88, respectively). The mean time to walk was 1.1 and 1.5 days at the SCC and SMU, respectively (P < 0.001). The median length of hospital stay was longer at the SMU than at the SCC (24.0 versus 20.8 days; P = 0.004). In the comparative study before and after the introduction of E-P, the rate of postoperative pneumonia was 16% in the conventional management group and 6.5% in the E-P group (P = 0.02). CONCLUSION: Postoperative pneumonia was reduced before and after introduction of E-P. As similar short-term postoperative outcomes were promising (except for the time to walk and postoperative hospital stay), the same E-P that was safely performed at the SMU can be implemented as a standard practice.

Identification of tumor microenvironment-associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE.

Project High-tech Omics-based Patient Evaluation (HOPE), which used whole-exome sequencing and gene expression profiling, was launched in 2014. A total of ~2,000 patients were enrolled until March 2016, and the survival time was observed up to July 2019. In our previous study, a tumor microenvironment immune type classification based on the expression levels of the programmed death-ligand 1 (PD-L1) and CD8B genes was performed based on four types: A, adaptive immune resistance; B, intrinsic induction; C, immunological ignorance; and D, tolerance. Type A (PD-L1+ and CD8B+) exhibited upregulated features of T helper 1 antitumor responses. In the present study, survival time analysis at 5 years revealed that patients in type A had a better prognosis than those in other categories [5 year survival rate (%); A (80.5) vs. B (73.9), C (73.4) and D (72.6), P=0.0005]. Based on the expression data of 293 immune response-associated genes, 62 specific genes were upregulated in the type A group. Among these genes, 18 specific genes, such as activated effector T-cell markers (CD8/CD40LG/GZMB), effector memory T-cell markers (PD-1/CD27/ICOS), chemokine markers (CXCL9/CXCL10) and activated dendritic cell markers (CD80/CD274/SLAMF1), were significantly associated with a good prognosis using overall survival time analysis. Finally, multivariate Cox proportional hazard regression analyses of overall survival demonstrated that four genes (GZMB, HAVCR2, CXCL9 and CD40LG) were independent prognostic markers, and GZMB, CXCL9 and CD40LG may contribute to the survival benefit of patients in the immune type A group.