Outcome research on esophagectomy analyzed using nationwide databases in Japan: evidences generated from real-world data.

Esophagectomy for esophageal cancer is a highly invasive gastrointestinal surgical procedure. The National Clinical Database (NCD) of Japan, initiated in 2011, has compiled real-world data on esophagectomy, one of nine major gastroenterological surgeries. This review examines outcomes after esophagectomy analyzed using the Japanese big databases. Certification systems by the Japanese Society of Gastroenterological Surgery (JSGS) and the Japan Esophageal Society (JES) have shown that institutional certification has a greater impact on short-term surgical outcomes than surgeon certification. Minimally invasive esophagectomy has emerged as a viable alternative to open esophagectomy, although careful patient selection is crucial, especially for elderly patients with advanced tumors. The NCD has significantly contributed to the assessment and enhancement of surgical quality and short-term outcomes, while studies based on Comprehensive Registry of Esophageal Cancer in Japan (CRECJ) have provided data on patient characteristics, treatments, and long-term outcomes. The JES has conducted various questionnaire-based retrospective clinical reviews in collaboration with authorized institutions certified by JES. The Diagnosis Procedure Combination (DPC) database provides administrative claims data including itemized prices for surgical, pharmaceutical, laboratory, and other inpatient services. Analyzing these nationwide databases can offer precise insights into surgical quality for esophageal cancer, potentially leading to improved treatment outcomes.

Salivary metabolomic biomarkers for esophageal and gastric cancers by liquid chromatography-mass spectrometry.

Early detection of esophageal and gastric cancers is essential for patients' prognosis; however, optimal noninvasive screening tests are currently not available. Saliva is a biofluid that is readily available, allowing for frequent screening tests. Thus, we explored salivary diagnostic biomarkers for esophageal and gastric cancers using metabolomic analyses. Saliva samples were collected from patients with esophageal (n = 50) and gastric cancer (n = 63), and patients without cancer as controls (n = 20). Salivary metabolites were analyzed by liquid chromatography-mass spectrometry to identify salivary biomarkers. We also examined the metabolic profiles of gastric cancer tissues and compared them with the salivary biomarkers. The sensitivity of the diagnostic models based on salivary biomarkers was assessed by comparing it with that of serum tumor markers. Additionally, using postoperative saliva samples collected from patients with gastric cancer, we analyzed the changes in the biomarkers' concentrations before and after surgery. Cytosine was detected as a salivary biomarker for gastric cancer, and cytosine, 2-oxoglutarate, and arginine were detected as salivary biomarkers for esophageal cancer. Cytidine, a cytosine nucleotide, showed decreased concentrations in gastric cancer tissues. The sensitivity of the diagnostic models for esophageal and gastric cancers was 66.0% and 47.6%, respectively, while that of serum tumor markers was 40%. Salivary cytosine concentration increased significantly postoperatively relative to the preoperative value. In summary, we identified salivary biomarkers for esophageal and gastric cancers, which showed diagnostic sensitivity at least comparable to that of serum tumor markers. Salivary metabolomic tests could be promising screening tests for these types of cancer.

First case report of intestinal lymphangiectasia with refractory bleeding from the duodenum, successfully treated by intra-abdominal lymphaticovenous anastomosis with venous ligation.

Intestinal lymphangiectasia (IL) is a protein-losing enteropathy (PLE) that occasionally leads to gastrointestinal bleeding (GIB). We encountered a 41-year-old female with a 9-year history of duodenal IL with PLE and GIB that progressively worsened. Despite a diet, supplemented with medium-chain triglycerides, antiplasmin therapy, oral corticosteroids, octreotides, sirolimus, and repeated endoscopic hemostasis, her symptoms remained uncontrolled, leading to blood transfusion dependence. Lymphangiography revealed significant leakage from abnormal abdominal lymph vessels into the duodenal lumen. The patient subsequently underwent an abdominal-level lymphaticovenous anastomosis combined with local venous ligation. This approach resulted in a dramatic improvement and sustained resolution of both the PLE and GIB. More than 6 months after surgery, the patient remained free of symptoms and blood transfusion dependence.

Response to chemotherapy could predict the prognosis of esophageal squamous cell carcinoma treated with neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery: long-term results in a single institute.

BACKGROUND: Preoperative chemotherapy with 5-fluorouracil and cisplatin (FP) followed by surgery has been considered a standard treatment for patients with stage II/III esophageal squamous cell carcinoma (ESCC) based on the results of a phase III trial (JCOG9907) in Japan. Subsequently, the phase III NExT trial (JCOG1109) revealed the survival benefit of the neoadjuvant DCF regimen, which adds docetaxel to FP, and it became a standard treatment. However, the long-term results and prognostic factors of neoadjuvant DCF therapy in the real world are unknown. METHODS: We retrospectively investigated 50 patients with ESCC treated with neoadjuvant DCF therapy from July 2012 to December 2017 at The University of Tokyo Hospital. RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 32.3 [95% confidence interval (CI) 21.0-NA] and 10.0 months (95% CI 6.3-15.6), respectively. Median OS [not reached (95% CI 31.5-NA) vs. 21.4 months (95% CI 13.5-33.0); p = 0.028] and PFS [83.3 months (95% CI 6.4-NA) vs. 7.4 months (95% CI 6.0-12.8] were significantly longer in patients with an objective response than in non-responders. Of 44 surgical cases, median PFS tended to be longer in pathological lymph node metastasis-negative patients. Conversely, survival did not differ according to cStage (II/III vs. IV) or the average relative dose intensity (ARDI, ≥ 85% vs. < 85%). DISCUSSION: The response to neoadjuvant DCF therapy could predict patient prognosis. Additionally, pN+ tended to increase the recurrence risk, whereas cStage and ARDI did not influence survival.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

BACKGROUND: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. METHODS: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. RESULTS: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. CONCLUSION: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Ramucirumab Beyond Disease Progression After Paclitaxel Plus Ramucirumab in Gastric Cancer: A Phase II Trial.

BACKGROUND/AIM: Irinotecan monotherapy was the most widely used third-line chemotherapy for unresectable advanced or recurrent gastric cancer in Japan until the approval of nivolumab in September 2017 and trifluridine/tipiracil in August 2019. The benefit of continuing ramucirumab with irinotecan, an anti-VEGFR-2 monoclonal antibody, after the failure of paclitaxel plus ramucirumab (PTX+RAM) as second-line chemotherapy, has been under debate. PATIENTS AND METHODS: A single-center phase II study was conducted in patients with unresectable advanced or recurrent gastric cancer previously treated with fluoropyrimidines and platinum, who received PTX+RAM as second-line therapy and irinotecan plus ramucirumab (IRI+RAM) as third-line therapy after treatment failure (UMIN000022956). RESULTS: Eleven patients were enrolled from July 2016 to July 2018. Enrolment was discontinued due to difficulties in case ascertainment because of expanded third-line treatment options (originally planned for 53 patients). The median progression-free survival (the primary endpoint) of the IRI+RAM was 3.98 months [95% confidence interval (CI)=1.78-NA]. Among secondary endpoints, the transition rate to IRI+RAM was 45%, the rate of 8-week treatment continuation for IRI+RAM was 100%, the response rate for IRI+RAM was 0%, the median overall survival (OS) for PTX+RAM was 13.53 months (95%CI=1.61-24.36), and the median OS for IRI+RAM was 9.99 months (95CI=4.5-NA). CONCLUSION: The transition rate from PTX+RAM to IRI+RAM was reasonable. Ramucirumab beyond progressive disease may be beneficial for patients who are able to transition to IRI+RAM.

Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination.

BACKGROUND: Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS). METHODS: Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples. RESULTS: At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off. CONCLUSIONS: CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.

Janus kinase inhibitor overcomes resistance to immune checkpoint inhibitor treatment in peritoneal dissemination of gastric cancer in C57BL/6 J mice.

BACKGROUND: Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. METHODS: The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination was assessed using the YTN16 peritoneal dissemination tumor model. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A Janus kinase inhibitor (JAKi) was introduced based on the pathway analysis results. RESULTS: Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8 + T cells. However, in mice resistant to dual ICI treatment, even with CD8 + T cell infiltration, most of the T cells exhibited an exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8 + T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. CONCLUSION: Dual ICI treatment exerts its anti-tumor effects by increasing tumor-specific CD8 + T cell infiltration, and the addition of JAKi further improves ICI resistance by reshaping the immunosuppressive TME.

Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Genomic and Pathologic Profiling of Very Well-Differentiated Gastric Adenocarcinoma of Intestinal Type: A Study With Emphasis on Diffuse-Type Transformation.

Very well-differentiated adenocarcinoma of intestinal type is a distinct subtype of gastric cancer characterized by anastomosing glands with a hand-in-hand pattern and low-grade cytologic atypia resembling intestinal metaplasia. This is a slow-growing neoplasm with an indolent clinical course; however, a subset demonstrates transformation into adenocarcinoma with higher-grade histology, typically diffuse-type carcinoma, and behaves aggressively. This study aimed to better characterize the genomic and pathologic features, with a focus on factors associated with diffuse-type transformation. A total of 58 cases with (n=31) and without (n=27) diffuse-type transformation were analyzed for molecular and pathologic features. First, comprehensive deep DNA sequencing was conducted in 18 cases (discovery cohort), followed by a digital droplet polymerase chain reaction of hot spot RHOA mutations in 40 cases (validation cohort). In total, RHOA mutations were the most common alteration (34%), followed by loss of ARID1A (12%), p53 alterations (10%), and CLDN18 :: ARHGAP26/6 fusions (3.4%). FGFR2 amplification was identified in an advanced case with a p53 alteration. Altered p53 expression was recognized only in higher-grade components and was significantly associated with advanced disease ( P =0.0015) and diffuse-type transformation ( P =0.026). A mixed mucin phenotype was also strongly correlated with advanced disease ( P <0.001) and diffuse-type transformation ( P <0.001). Decreased E-cadherin expression was frequently observed (74%) in poorly cohesive components. This study demonstrated that a subset of RHOA -mutant diffuse-type gastric cancers develops through the transformation of very well-differentiated adenocarcinoma of intestinal type. Our observations suggest a mixed mucin phenotype as a risk factor and alterations in p53 and E-cadherin as drivers of diffuse-type transformation.

Preoperative NUn score serves as a robust predictor of overall and disease-specific survivals following radical surgery for gastric cancer.

PURPOSE: Methods to preoperatively stratify oncological risks associated with gastric cancer (GC) are limited. Host inflammatory parameters, i.e., serum C-reactive protein (CRP) and albumin levels, are known to be associated with outcomes. We examined the relationships between disease-specific mortality and four CRP-albumin-based indices (CRP-albumin ratio [CAR], modified Glasgow prognostic score [mGPS], Osaka prognostic score [OPS], and NUn score) preoperatively measured in cases with resectable GC. METHODS: Survival outcomes of 1290 consecutive GC patients with oncological gastrectomy were reviewed. Predictive significances of preoperative CAR, mGPS, OPS, and NUn scores were assessed with time-dependent receiver operating characteristic curves and Cox regression analyses. RESULTS: Median follow-up was 107 months. Area under the curve for predicting overall and disease-specific survivals (OS/DSS) for the preoperative NUn score was clearly superior to those of the other parameters. On univariate Cox regression analysis, preoperative CAR, mGPS, OPS, and the NUn score all correlated significantly with OS/DSS. On multivariate Cox regression analysis, the preoperative NUn score, as a continuous variable, showed an independent relationship with OS (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.16-1.50, per 1-unit increase, P < 0.001) and even DSS (HR 1.23, 95% CI 1.02-1.49, P = 0.032). The other three markers failed to maintain independence for DSS. CONCLUSIONS: Preoperative NUn scores are stably associated with outcomes, including disease-specific mortality, possibly serving as a simple measure to define the likelihood of progression to systemic disease after meticulous surgery for GC, which may contribute to identifying patients who would benefit from additional modalities.

Requirements for hospitals in Japan to have low operative mortality and failure-to-rescue rates.

Aim: We explored institutional factors in Japan associated with lower operative mortality and failure-to-rescue (FTR) rates for eight major gastrointestinal procedures. Methods: A 22-item online questionnaire was sent to 2119 institutional departments (IDs) to examine the association between institutional factors and operative mortality and FTR rates. IDs were classified according to the number of annual surgeries, board certification status, and locality. In addition, the top 20% and bottom 20% of IDs were identified based on FTR rates and matched with the results of the questionnaire survey. Factors associated with operative mortality were selected by multivariate analysis. Results: Of the 1083 IDs that responded to the questionnaire, 568 (213 382 patients) were included in the analysis. Operative morbidity, operative mortality, and FTR rates in the top 20% and bottom 20% of IDs were 13.1% and 8.4% (p < 0.001), 0.52% and 4.3% (p < 0.001), and 4.0% and 51.2% (p < 0.001), respectively. Based on the patients' background characteristics, the top 20% of IDs handled more advanced cases. No significant difference in locality was seen between better or worse hospital FTR rates, but fewer esophagectomies, hepatectomies, and pancreatoduodenectomies were performed in depopulated areas. Six items were found to be associated with operative mortality by multivariate logistic analysis. Only 50 (8.8%) IDs met all five factors related to better FTR rates. Conclusions: The present findings indicate that several hospital factors surrounding surgical treatment, characterized by abundant human resources, are closely related to better postoperative recovery from severe complications.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Association between Care-need Level after Discharge and Long-term Outcomes in 7491 Patients Requiring Rehabilitation for Stroke.

Introduction: Stroke is a major cause of disability and mortality worldwide and requires long-term care, including rehabilitation. This study aims to elucidate the association between care-need levels after discharge and long-term outcomes in patients with stroke. Methods: We used a Japanese administrative database that covers both medical and long-term care insurance systems to retrospectively identify 7491 patients who underwent acute-phase in-hospital rehabilitation for stroke between June 2014 and February 2019. We investigated the association between nationally standardized care-need levels (support levels 1-2 and care-need levels 1-3) 6 months after discharge and long-term outcomes. Using the Fine-Gray model, we conducted multivariable survival analysis with adjustment for patient backgrounds and treatment courses to estimate hazard ratios (HR) for mortality and the incidence of being bedridden. Results: The median age was 82 (interquartile range [IQR], 76-87) years, 5418 patients (72%) had cerebral infarction, and 4009 patients (54%) had partial dependence after discharge. During a median follow-up of 580 (IQR, 189-925) days, 1668 patients (22%) became bedridden, and 2174 patients (29%) died. Compared with patients with support level 1, those with higher care-need levels showed significantly higher proportions of being bedridden-the subdistribution HR [95% confidence interval] were 1.52 [1.10-2.12], 2.85 [2.09-3.88], and 3.79 [2.79-5.15] in those with care-need levels 1, 2, and 3, respectively. Higher care-need levels were also significantly associated with higher mortality. Conclusions: This large-scale observational study demonstrated that a higher level of care-need after discharge was significantly associated with poorer functional outcomes and higher mortality.

Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

Patient survey on cancer genomic medicine in Japan under the national health insurance system.

In Japan, comprehensive genomic profiling (CGP) tests have been reimbursed under the national health care system for solid cancer patients who have finished standard treatment. More than 50,000 patients have taken the test since June 2019. We performed a nation-wide questionnaire survey between March 2021 and July 2022. Questionnaires were sent to 80 designated Cancer Genomic Medicine Hospitals. Of the 933 responses received, 370 (39.7%) were web based and 563 (60.3%) were paper based. Most patients (784, 84%) first learned about CGP tests from healthcare professionals, and 775 (83.1%) gave informed consent to their treating physician. At the time of informed consent, they were most worried about test results not leading to novel treatment (536, 57.4%). On a scale of 0-10, 702 respondents (75.2%) felt that the explanations of the test result were easy to understand (7 or higher). Ninety-one patients (9.8%) started their recommended treatment. Many patients could not receive recommended treatment because no approved drugs or clinical trials were available (102/177, 57.6%). Ninety-eight patients (10.5%) did not wish their findings to be disclosed. Overall satisfaction with the CGP test process was high, with 602 respondents (64.5%) giving a score of 7-10. The major reason for choosing 0-6 was that the CGP test result did not lead to new treatment (217/277, 78.3%). In conclusion, satisfaction with the CGP test process was high. Patients and family members need better access to information. More patients need to be treated with genomically matched therapy.

Days of the week and 90-day mortality after esophagectomy: analysis of 33,980 patients from the National Clinical Database.

PURPOSE: The effect of the days of the week on the short-term outcomes after elective surgeries has been suggested; however, such data on esophagectomies remain limited. This study aimed to investigate the association between the day of the week and mortality rates after elective esophagectomy using a large-scale clinical database in Japan. METHODS: The data of elective esophagectomies, registered in the National Clinical Database in Japan, for esophageal cancer treatment between 2012 and 2017 were analyzed. We hypothesized that the later days of the week could have higher odds ratios of death after elective esophagectomy. With 22 relevant clinical variables and days of surgery, 90-day mortality was evaluated using hierarchical logistic regression modeling. RESULTS: Ninety-day mortality rates among 33,980 patients undergoing elective esophagectomy were 1.8% (range, 1.5-2.1%). Surgeries were largely concentrated on earlier days of the week, whereas esophagectomies performed on Fridays accounted for only 11.1% of all cases. Before risk adjustment, lower odds ratios of 90-day mortality were found on Tuesday and a tendency towards lower odds ratios on Thursday. In the hierarchical logistic regression model, 21 independent factors of 90-day mortality were identified. However, the adjusted odds ratios of 90-day mortality for Tuesday, Wednesday, Thursday, and Friday were 0.87, 1.09, 0.85, and 0.88, respectively, revealing no significant difference. CONCLUSION: The results imply that the variation in 90-day mortality rates after esophagectomy on different days of the week may be attributed to differing preoperative risk factors of the patient group rather than the disparity in medical care provided.

Percent vital capacity predicts postoperative sarcopenia after esophagectomy in initially nonsarcopenic esophageal cancer patients: a retrospective cohort study.

PURPOSE: The development of sarcopenia after esophagectomy is reported to affect the outcomes of patients with esophageal cancer (EC); however, the characteristics of patients likely to be predisposed to postoperative sarcopenia have not been defined. This study explores the associations between preoperative respiratory function and surgery-induced sarcopenia in EC patients confirmed as nonsarcopenic preoperatively. METHODS: The subjects of this retrospective review were 128 nonsarcopenic patients who underwent esophagectomy for EC. We took body composition measurements and performed physical function tests 3 and 6 months postoperatively, to establish whether sarcopenia was present, according to the 2019 Asian Working Group for Sarcopenia guideline. We defined patients with surgery-induced sarcopenia as those with evidence of the development of sarcopenia within 6 months postoperatively or those with documented sarcopenia at 3 months but who could not be evaluated at 6 months. RESULTS: Surgery-induced sarcopenia developed in 19 of the 128 patients (14.8%), which correlated significantly with the preoperative %VC value (p < 0.01), but not with the preoperative FEV1.0% value. We set the lower quartile %VC value (91%) as the cut-off for predicting surgery-induced sarcopenia. A low %VC was independently associated with surgery-induced sarcopenia (odds ratio: 5.74; 95% confidence interval: 1.99-16.57; p < 0.01). CONCLUSIONS: Based on the findings of this study, %VC was a simple but valuable factor for predicting sarcopenia induced by esophagectomy.

Impact of COVID-19 pandemic on short-term outcomes after low anterior resection in patients with rectal cancer: Analysis of data from the Japanese National Clinical Database.

Aim: The Coronavirus Disease 2019 (COVID-19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short-term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. Methods: Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID-19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). Results: This study included 74 181 patients, including 43 663 (58.9%) from COVID-19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30-day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. Conclusion: Although the pandemic temporarily decreased the ICU admission rate, its impact on short-term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.

Immuno-genomic analysis reveals eosinophilic feature and favorable prognosis of female non-smoking esophageal squamous cell carcinomas.

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.