Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer.

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.

Efficacy of thoracic endovascular aortic repair for aorto-esophageal fistula due to esophageal cancer: a systematic review and meta-analysis.

Aorto-esophageal fistula (AEF) due to esophageal cancer (EC) is a life-threatening condition characterized by sudden hemorrhage, which often causes sudden death. To evaluate the efficacy and safety of thoracic endovascular aortic repair (TEVAR) for AEF due to EC, we performed a systematic review and meta-analysis. We searched the MEDLINE (PubMed) databases, the Cochrane Library databases, Ichushi-Web (the databases of the Japan Medical Abstract Society), and CiNii (Academic information search service of the National Institute of Information from Japan) from January 2000 to November 2023 for articles about TEVAR for an emergent aortic hemorrhage (salvage TEVAR [S-TEVAR]), and the prophylactic procedure (P-TEVAR). Six studies (140 cases) were eligible for meta-analysis. The 90-day mortality of S-TEVAR and P-TEVAR was 40% (95% CI 23-60, I2 = 36%) and 8% (95% CI 3-17, I2 = 0%), respectively. Post-S-TEVAR hemorrhagic and infectious complications were 17% (95% CI 3-57, I2 = 71%) and 20% (95% CI 5-57, I2 = 66%), respectively. Post-P-TEVAR hemorrhagic and infectious complications were 2% (95% CI 0-10, I2 = 0%) and 3% (95% CI 1-12, I2 = 0%), respectively. TEVAR for AEF due to EC may be a useful therapeutic option to manage or prevent hemorrhagic oncological emergencies.

Effectiveness of Combination Chemotherapy With Docetaxel, Nedaplatin, and 5-Fluorouracil for Advanced and Recurrent Esophageal Cancer.

BACKGROUND/AIM: Chemotherapy and immunotherapy have been recently developed as potentially useful first-line treatments for unresectable, advanced, or recurrent esophageal cancer. We performed a retrospective study of the therapeutic effectiveness of triplet chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil therapy for advanced, recurrent, and unresectable advanced esophageal cancer at our hospital and compared the regimen's results with those of current and possible future treatment options. PATIENTS AND METHODS: The study cohort comprised 101 patients who received docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer at Gunma University from May 2008 to December 2017. We retrospectively evaluated the results of this combination chemotherapy and postulated future treatment strategies. RESULTS: The overall response and disease control rates, the latter including stable disease, for docetaxel, nedaplatin, and 5-fluorouracil were 33.6% and 61.4%, respectively. The median overall survival and progression-free survival were 12.26 months and 5.1 months, respectively. In patients with recurrence, the median overall and progression-free survivals were 14.97 months (449 days) and 5.1 months (152 days), respectively. No study patients developed acute kidney injury and there were no treatment-related deaths. However, leukopenia and neutropenia were frequent hematologic toxicities. CONCLUSION: Treatment with docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer is particularly useful for recurrent cases and has the advantage of not causing severe renal dysfunction.

Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring.

BACKGROUND: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma. METHODS: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours. Unbound concentrations were determined at 0.5 hours, 7.2 hours [at the 60% time point of the 12 hours administration interval (C7.2h)], and 11 hours (trough concentration) after the first infusion (rate: 2 g/h). The primary and secondary end points were the predictive performance of the area under the unbound concentration-time curve (AUC unbound ) and the effect of unbound cefepime pharmacokinetic parameters on clinical response, respectively. RESULTS: The mean (SD) AUC unbound was 689.7 (226.6) mcg h/mL, which correlated with C7.2h (R 2 = 0.90), and the Bayesian posterior AUC unbound using only the trough concentration (R 2 = 0.66). Although higher exposure was more likely to show a better clinical response, each parameter did not indicate a statistical significance between positive and negative clinical responses ( P = 0.0907 for creatinine clearance (Ccr), 0.2523 for C7.2h, 0.4079 for trough concentration, and 0.1142 for AUC unbound ). Cutoff values were calculated as 80.2 mL/min for Ccr (sensitivity: 0.889, specificity: 0.714), 18.6 mcg/mL for C7.2h (sensitivity: 0.571, specificity: 1.000), and 9.2 mcg/mL for trough concentration (sensitivity: 0.571, specificity: 1.000). When aiming for a time above 100% the minimum inhibitory concentration, both continuous infusion of 4 g/d and intermittent infusion of 2 g every 8 hours achieved a probability of approximately 100% at a minimum inhibitory concentration of 8 mcg/mL. CONCLUSIONS: Therapeutic drug monitoring by sampling at C7.2h or trough can facilitate rapid dose optimization. Continuous infusion of 4 g/d was recommended. Intermittent dosing of 2 g every 8 hours was alternatively suggested for patients with a Ccr of 60-90 mL/min.

Wnt/ß­catenin signaling is a novel therapeutic target for tumor suppressor CYLD­silenced glioblastoma cells.

Tumor suppressor cylindromatosis (CYLD) dysfunction by its downregulation is significantly associated with poor prognosis in patients with glioblastoma (GBM), the most aggressive and malignant type of glioma. However, no effective treatment is currently available for patients with CYLD­downregulated GBM. The aim of the present study was to identify the crucial cell signaling pathways and novel therapeutic targets for CYLD downregulation in GBM cells. CYLD knockdown in GBM cells induced GBM malignant characteristics, such as proliferation, metastasis, and GBM stem­like cell (GSC) formation. Comprehensive proteomic analysis and RNA sequencing data from the tissues of patients with GBM revealed that Wnt/ß­catenin signaling was significantly activated by CYLD knockdown in patients with GBM. Furthermore, a Wnt/ß­catenin signaling inhibitor suppressed all CYLD knockdown­induced malignant characteristics of GBM. Taken together, the results of the present study revealed that Wnt/ß­catenin signaling is responsible for CYLD silencing­induced GBM malignancy; therefore, targeting Wnt/ß­catenin may be effective for the treatment of CYLD­negative patients with GBM with poor prognosis.

Fibrolamellar hepatocellular carcinoma: a case report and gene analysis.

BACKGROUND: Fibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient. CASE PRESENTATION: A 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076-84, 2017). CONCLUSION: We encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis.

Subclonal accumulation of immune escape mechanisms in microsatellite instability-high colorectal cancers.

BACKGROUND: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH. METHODS: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed. RESULTS: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment. CONCLUSIONS: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.

High RRN3 expression is associated with malignant characteristics and poor prognosis in pancreatic cancer.

BACKGROUND: Pancreatic cancer has an extremely poor prognosis and is one of the most chemoresistant cancers. Targeting cancer cell transcriptional complexes may enhance chemotherapy effectiveness. RNA-polymerase I (Pol-I)-mediated transcription is an essential initial step for ribosome biogenesis and is related to cancer cell proliferation. RRN3 is a Pol-I-specific transcription initiation factor. In this study, we aimed to elucidate the function and clinical significance of RRN3 in pancreatic cancer. METHODS: We performed immunohistochemical staining to detect RRN3 protein expression in 96 pancreatic cancer tissues and analyzed the relationship between RRN3 protein expression, clinicopathological factors, and cancer patient prognosis. Moreover, we evaluated RRN3 function in vitro and in vivo using proliferation, invasion, and chemosensitivity assays in PANC-1 and SW1990 cell lines, with/without depleting RRN3 expression. RESULTS: RRN3 was mainly expressed in cancer cell nuclei. High levels of RRN3 expression were associated with Ki-67 expression and shorter overall survival. Additionally, proliferation and invasion ability were decreased when RRN3 was silenced with siRNA, compared to non-targeting siRNA-transfected cells. Chemosensitivity analysis showed that inhibition of RRN3 enhanced the sensitivity of pancreatic cancer cell lines to gemcitabine and paclitaxel. RRN3 siRNA-transfected PANC-1 tumors showed significantly reduced tumor volumes and high gemcitabine sensitivity compared to the control in a mouse xenograft model. CONCLUSION: High levels of RRN3 expression are associated with poor prognosis and cancer malignancy, such as proliferation, invasion ability, and chemosensitivity in pancreatic cancer. RRN3 targeting with anticancer drugs may be a promising therapeutic strategy to overcome refractory pancreatic cancer.

Gangrenous ischemic colitis localized to the cecum: a case report.

BACKGROUND: Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis. CASE PRESENTATION: A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications. CONCLUSION: It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed.

Relationship Between C-reactive Protein-to-albumin Ratio Before and After Bowel Decompression and Prognosis in Acute Malignant Large Bowel Obstruction.

BACKGROUND/AIM: We investigated the relationship between prognosis and the necessity of decompression of large bowel obstruction (LBO) among patients with colorectal cancer admitted to the hospital in an emergency, as well as the correlation between prognosis and improvement in the C-reactive protein-to-albumin ratio (CAR) after decompression. PATIENTS AND METHODS: Seventy-four patients admitted to the hospital between 2013 and 2021 in an emergency due to LBO were included. We examined perioperative clinicopathological factors, bowel decompression type, and prognosis. RESULTS: Of the 74 patients, 24 (32.4%) required bowel decompression. A higher percentage of patients who required bowel decompression had a colorectal obstruction scoring system (CROSS) score 0 (p<0.001) with higher frequency of nutritional disorders (p=0.063) than that in no bowel decompression-requiring patients. The 3-year-disease-free survival was 70.8% in the no decompression-requiring group and 26.9% in the bowel decompression group (p=0.007), while the 3-year-overall survival was 90.8% and 76.5%, respectively (p=0.001). The 3-year-disease-free survival was 49.2% in the improved CAR group and 0.0% in the non-improved CAR group (p=0.024), while the 3-year-overall survival was 91.7% and 56.3%, respectively (p=0.061). CONCLUSION: The necessity of emergency decompression was associated with a poorer prognosis, compared to the no decompression-requiring group. Similarly, a CROSS score of 0 was an independent poor prognostic factor. Among patients who required emergency bowel decompression, those who showed improvement in CAR before and after decompression treatment had a better prognosis than those who did not.

Preoperative evaluation of oral hygiene may predict the overall survival of patients with esophageal cancer.

BACKGROUND: Previously, the association between tooth loss and prognosis after esophagectomy was reported; however, the presence of periodontal disease has not been assessed. This study investigated the association between the degree of oral hygiene, as evaluated by tooth loss and periodontal disease, and the prognosis of patients with esophageal cancer. METHODS: A total of 163 esophageal cancer patients who underwent surgery with perioperative oral care and examination were enrolled. We assessed the periodontal pocket depth for the presence of periodontal disease and established a periodontal pocket index, defined as the sum of the periodontal pocket depth of the remaining tooth divided by the total count of the remaining teeth. Patients were divided into three groups: Group A (tooth loss < 13 and periodontal pocket index < 3.67); Group B (tooth loss < 13 and periodontal pocket index ≥ 3.67); and Group C (tooth loss ≥ 13). Overall survival and cancer-specific survival were analyzed, and a multivariate analysis was performed. RESULTS: There was a significant difference in the 5-year overall survival rates between the groups (A:B:C = 74.8%:62.8%:50.5%; p = 0.0098), but not in the 5-year cancer-specific survival rates (A:B:C = 80.2%:64.2%:62.2%; p = 0.0849). In multivariate analysis, oral hygiene (tooth loss < 13 and periodontal pocket index ≥ 3.67 + tooth loss ≥ 13; p = 0.041) was a significant independent poor prognostic factor for overall survival. CONCLUSIONS: Oral evaluation, focusing on tooth loss and periodontal disease, is meaningful in predicting the long-term prognosis of postoperative esophageal cancer patients.

Persistent epigenetic alterations in transcription factors after a sustained virological response in hepatocellular carcinoma.

Background and Aim: The risk of hepatocellular carcinoma (HCC) persists in a condition of sustained virologic response (SVR) after hepatitis C virus (HCV) eradication. Comprehensive molecular analyses were performed to test the hypothesis that epigenetic abnormalities present after an SVR play a role in hepatocarcinogenesis. Methods: Whole-genome methylome and RNA sequencing were performed on HCV, SVR, and healthy liver tissue. Integrated analysis of the sequencing data focused on expression changes in transcription factors and their target genes, commonly found in HCV and SVR. Identified expression changes were validated in demethylated cultured HCC cell lines and an independent validation cohort. Results: The coincidence rates of the differentially methylated regions between the HCV and SVR groups were 91% in the hypomethylated and 71% in the hypermethylated regions in tumorous tissues, and 37% in the hypomethylated and 36% in the hypermethylated regions in non-tumorous tissues. These results indicate that many epigenomic abnormalities persist even after an SVR was achieved. Integrated analysis identified 61 transcription factors and 379 other genes that had methylation abnormalities and gene expression changes in both groups. Validation cohort specified gene expression changes for 14 genes, and gene ontology pathway analysis revealed apoptotic signaling and inflammatory response were associated with these genes. Conclusion: This study demonstrates that DNA methylation abnormalities, retained after HCV eradication, affect the expression of transcription factors and their target genes. These findings suggest that DNA methylation in SVR patients may be functionally important in carcinogenesis, and could serve as biomarkers to predict HCC occurrence.

Potential use of EGFR-targeted molecular therapies for tumor suppressor CYLD-negative and poor prognosis oral squamous cell carcinoma with chemoresistance.

BACKGROUND: Tumor suppressor CYLD dysfunction by loss of its expression, triggers malignant transformation, especially drug resistance and tumor invasion/metastasis. Although loss of CYLD expression is significantly associated with poor prognosis in a large variety of tumors, no clinically-effective treatment for CYLD-negative cancer patients is available. METHODS: We focused on oral squamous cell carcinoma (OSCC), and sought to develop novel therapeutic agents for CYLD-negative cancer patients with poor prognosis. CYLD-knockdown OSCC cells by using CYLD-specific siRNA, were used to elucidate and determine the efficacy of novel drug candidates by evaluating cell viability and epithelial-mesenchymal transition (EMT)-like change. Therapeutic effects of candidate drug on cell line-derived xenograft (CDX) model and usefulness of CYLD as a novel biomarker using patient-derived xenograft (PDX) model were further investigated. RESULTS: CYLD-knockdown OSCC cells were resistant for all currently-available cytotoxic chemotherapeutic agents for OSCC, such as, cisplatin, 5-FU, carboplatin, docetaxel, and paclitaxel. By using comprehensive proteome analysis approach, we identified epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, played key roles in CYLD-knockdown OSCC cells. Indeed, cell survival rate in the cisplatin-resistant CYLD-knockdown OSCC cells was markedly inhibited by treatment with clinically available EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib. In addition, gefitinib was significantly effective for not only cell survival, but also EMT-like changes through inhibiting transforming growth factor-ß (TGF-ß) signaling in CYLD-knockdown OSCC cells. Thereby, overall survival of CYLD-knockdown CDX models was significantly prolonged by gefitinib treatment. Moreover, we found that CYLD expression was significantly associated with gefitinib response by using PDX models. CONCLUSIONS: Our results first revealed that EGFR-targeted molecular therapies, such as EGFR-TKIs, could have potential to be novel therapeutic agents for the CYLD-negative OSCC patients with poor prognosis.

Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-RT) for Patients With Potentially Resectable Esophageal Cancer.

BACKGROUND/AIM: We evaluated the long-term outcome of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for patients with potentially resectable esophageal cancer (EC) in clinical settings. PATIENTS AND METHODS: Twenty-eight patients with potentially resectable thoracic EC were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m2 (day 1), CDDP at 60 mg/m2 (day 1), and 5-FU at 600 mg/m2 (days 1 to 4), repeated every four weeks for two cycles along with radiotherapy (60 Gy in 30 fractions). Potentially resectable esophageal cancer was defined as clinical stage (cStage) I, II, III, and IV with supraclavicular lymph node metastasis [M1(Lym)]. RESULTS: The overall complete response (CR) rate was 88.5%. The 5-year overall survival (OS) rates for cStage I, cStage II-III, and IV [M1(lym)] patients were 79.5%, 76.2%, and 50.0%, respectively. The most frequent grade 3 or 4 acute toxicities were leucopenia (85.7%), neutropenia (78.5%), and febrile neutropenia (FN) (21.4%). The rate of any grade 3 or 4 late toxicity was 7.7%. CONCLUSION: DCF-RT demonstrated a satisfactory CR rate and OS with a higher rate of FN for potentially resectable thoracic EC patients. Prophylactic treatment with granulocyte-colony-stimulating factor and antibiotics may be appropriate supportive care for patients undergoing DCF-RT.

Preoperative Risk Factors and Prognostic Impact of Postoperative Complications Associated with Total Gastrectomy.

INTRODUCTION: We evaluated the risk factors for patients with gastric cancer (GC) undergoing total gastrectomy (TG) that predict postoperative complications, including anastomotic leakage, postoperative pneumonia, and heart disease. METHODS: We collected 106 patients who received TG for GC between May 2009 and May 2017 at Gunma University Graduate School of Medicine, including clinicopathologic, surgical, postoperative complication, laboratory test, and physiologic test data. RESULTS: Of 106 patients, 92 (86.8%) had no complications, and 14 (13.2%) had complications. Univariate analyses revealed that a high American Society of Anaesthesiologists physical status (ASA-PS) and neutrophil-lymphocyte ratio (NLR) of ≥3.5 significantly correlated with postoperative complications. Multivariate analyses showed that high ASA-PS was an independent prognostic factor of postoperative complications. The cancer recurrence rate was 34.8% in the noncomplication group and 71.4% in the complication group. CONCLUSION: Patients with postoperative complications are prone to recurrence and poor prognosis. For patients with high-risk GC with poor ASA-PS and high NLR, more thorough perioperative management is essential.

ASO Author Reflections: Impact of the Ratio of the Visceral Fat Area (VFA) to Psoas Muscle Area (PMA) (V/P Ratio) on Survival for Patients with Surgically Resected Esophageal Cancer.

PAST: The true impact of co-occurring muscle mass reduction and fat accumulation on patients with surgically resected esophageal cancer (EC) remains controversial. PRESENT: The current study defined reduction in muscle mass and excess body adiposity as the ratio of the visceral fat area (VFA) to the psoas muscle area (V/P ratio) on the same axial computed tomography slice at the third lumbar vertebra (L3). A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), larger VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis showed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) of EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio still was significant for EC patients with a BMI lower than 25 kg/m2. FUTURE: A high V/P ratio was an independent prognostic factor for OS of EC patients who underwent surgery, even BMI-defined non-obese EC patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value for EC patients regardless of body composition differences.

Impact of the Ratio of Visceral Fat Area (VFA) to Psoas Muscle Area (PMA) (V/P Ratio) on Survival for Surgically Resected Esophageal Cancer.

BACKGROUND: The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. METHODS: One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). RESULTS: A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), higher VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI < 25. CONCLUSIONS: A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

A case of spontaneous esophageal submucosal hematoma.

A 78-year-old man visited a nearby hospital owing to chest pain triggered by vomiting. As computed tomography revealed suspected esophageal perforation, he was referred to our hospital. Upper gastrointestinal endoscopy showed blood coagula extending from the middle intra-thoracic to the esophago-cardiac junction (ECJ), and it was diagnosed as an esophageal submucosal hematoma. Conservative therapy was initiated by fasting and discontinuing oral anticoagulants. The lesion was monitored by upper gastrointestinal endoscopy. On day 12 of the symptom appearance, the hematoma had completely disappeared and on day 22, the patient was discharged from the hospital. In most cases, esophageal submucosal hematoma has a favorable course with preservative treatment. Esophageal submucosal hematoma should be considered as one of the differential diagnoses for chest pain triggered by vomiting.

Salvage thoracoscopic esophagectomy after carbon-ion radiotherapy in a patient with esophageal squamous cell carcinoma: a case report.

BACKGROUND: Carbon-ion radiotherapy (CIRT) for esophageal cancer has been receiving significant attention given its high local control rates and minimal damage to normal tissues. However, the efficacy and safety of salvage surgery after CIRT for esophageal cancer remain unclear. We report the case of a patient who underwent salvage thoracoscopic surgery after CIRT. CASE PRESENTATION: A 51-year-old woman underwent upper gastrointestinal endoscopy and a type 0-IIa + 0-IIc esophageal squamous cell carcinoma located 27-29 cm from the patient's incisors, classified as clinical stage I (T1bN0M0), was detected. She received CIRT (50.4 Gy [relative biological effectiveness, RBE]/12 fr) for localized esophageal cancer and achieved complete remission after 4 months. Six years after CIRT, follow-up endoscopic examination demonstrated a type 0-IIa + 0-IIc tumor in the previously treated area. In addition, a type 0-IIa lesion located 20-22 cm from the incisors was found. We diagnosed localized ESCC, classified as clinical stage I (T1bN0M0). Salvage thoracoscopic surgery was performed in the prone position with five access ports. Although the esophagus tightly adhered to the thoracic descending aorta and left main bronchus with severe fibrosis, the esophagus could be separated from the surrounding organs with careful forceps manipulation. The operation time and blood loss were 8 h 45 min and 253 mL, respectively. The patient was discharged from our hospital 17 days after the salvage surgery without any complications. Pathological findings revealed two squamous cell carcinomas. Both tumors were localized in the lamina propria mucosa, and lymph node metastasis was not detected. The tumors were diagnosed as pathological stage IA (pT1aN0M0) according to the TNM criteria. Moreover, pathological examinations showed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field. Following the surgery, the patient had no recurrence for 1 year and 6 months. CONCLUSIONS: Thoracoscopic radical esophagectomy can be performed as salvage surgery. Careful and discreet surgery is integral to perform salvage surgery after CIRT since CIRT may cause severe adhesions and fibrosis in the irradiated field.