Does Neoadjuvant Chemoradiotherapy Have an Additional Effect to Lateral Pelvic Lymph Node Dissection for Rectal Cancer?

Objectives: A total mesenteric excision (TME) with lateral pelvic lymph node dissection (LLND) is the standard treatment for advanced low rectal cancer in Japan. Recently, neoadjuvant (chemo)radiotherapy (n(C)RT) has been used with LLND to improve outcomes at multiple Japanese institutes. This study evaluates the benefits of adding nCRT to TME with LLND. Methods: Seventy-two consecutive patients who underwent TME and LLND with or without nCRT between 2006-2019 to treat advanced low rectal cancer were retrospectively reviewed. The clinicopathological data were compared and the risk factors for local recurrence were evaluated. Results: Fifty-seven patients (79.1%) underwent TME and LLND with nCRT, and 15 patients (20.9%) without nCRT. There was no significant difference in the clinicopathological characteristics except the clinical T stage. The occurrence of postoperative complications was statistically insignificant. The 5-year local recurrence rate of patients with nCRT was significantly lower than those without (4.0% versus 26.6%, in all patients, p=0.002). Multivariate analysis revealed that the absence of nCRT was an independent risk factor for local recurrences in patients who underwent TME with LLND (hazard ratio: 6.04, p=0.04). Conclusions: The administration of nCRT prevented local recurrences more effectively in patients with advanced low rectal cancer who underwent TME with LLND.

Risk factors for liver dysfunction and their clinical importance after gastric cancer surgery.

Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Impact of hypoglycemia after gastrectomy on Global Leader Initiative on Malnutrition-defined malnutrition: a retrospective study.

PURPOSE: The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. METHODS: We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1 month and 1 year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). RESULTS: One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70 mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). CONCLUSIONS: Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1 year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.

Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer.

BACKGROUND: Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms. METHODS: From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1). RESULTS: Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice. CONCLUSIONS: Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.

Preoperative oral antibiotic administration in patients undergoing curative resection with stoma creation for colorectal cancer: effectiveness in preventing surgical site infection and the possibility of peristomal candidiasis induced by enterobacterial alteration.

AIM: There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract. METHOD: We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ. RESULTS: SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased. CONCLUSION: OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI.

Roles of miR-4442 in Colorectal Cancer: Predicting Early Recurrence and Regulating Epithelial-Mesenchymal Transition.

Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial-mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1.

Functional Analysis and Clinical Importance of ATP1A1 in Colon Cancer.

BACKGROUND: Na+/K+-ATPase α1 subunit (ATP1A1) exhibits aberrant expression in various types of cancer. Moreover, its levels in specific tissues are associated with the development of cancer. Nevertheless, the mechanism and signaling pathways underlying the effects of ATP1A1 in colon cancer (CC) have not been elucidated, and its prognostic impact remains unknown. METHODS: Knockdown of ATP1A1 expression was performed in human CC cell lines HT29 and Caco2 using small interfering RNA. The roles of ATP1A1 in various biological processes of cells (i.e., proliferation, cell cycle, apoptosis, migration, and invasion) were assessed. Microarray analysis was utilized for gene expression profiling. Samples obtained from 200 patients with CC who underwent curative colectomy were analyzed through immunohistochemistry. RESULTS: ATP1A1 knockdown suppressed cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that the upregulated or downregulated gene expression in ATP1A1-depleted cells was related to the extracellular signal-regulated kinase 5 (ERK5) signaling pathway [epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase 5 (MAP2K5), mitogen-activated protein kinase 7 (MAPK7), FOS, MYC, and BCL2 associated agonist of cell death (BAD)]. Immunohistochemical analysis demonstrated a correlation between ATP1A1 expression and pathological T stage (p = 0.0054), and multivariate analysis identified high ATP1A1 expression as an independent predictor of poor recurrence-free survival in patients with CC (p = 0.0040, hazard ratio: 2.807, 95% confidence interval 1.376-6.196). CONCLUSIONS: ATP1A1 regulates tumor progression through the ERK5 signaling pathway. High ATP1A1 expression is associated with poor long-term outcomes in patients with CC.

Plasma miR-1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer.

This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR-323, 345, 409, and 1254) based on the microRNA microarray comparing pre-treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR-1254 was more highly elevated in pre-treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver-operating characteristic curve 0.7621). High plasma miR-1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR-1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR-1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR-1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR-1254 levels might improve chemosensitivity in ESCC.

Postoperative liver dysfunction is associated with poor long-term outcomes in patients with colorectal cancer: a retrospective cohort study.

BACKGROUND: Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. METHODS: We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I-IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. RESULTS: Forty-eight (13.3%) colorectal cancer patients (Stages I-IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox's proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54-4.73). CONCLUSIONS: Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction.

Value of the Tumor-Stroma Ratio and Structural Heterogeneity Measured by a Novel Semiautomatic Image Analysis Technique for Predicting Survival in Patients With Colon Cancer.

BACKGROUND: The tumor-stroma ratio and intratumor stromal heterogeneity have been identified as prognostic factors for several carcinomas. Recent advancements in image analysis technologies and their application to medicine have enabled detailed analysis of clinical data beyond human cognition. OBJECTIVE: This study aimed to investigate the tumor-stroma ratio and intratumor stromal heterogeneity measured using a novel objective and semiautomatic method with image analysis. DESIGN: A retrospective cohort design. SETTINGS: Single institution. PATIENTS: This study included patients who underwent curative colectomy for colon cancer. MAIN OUTCOME MEASURES: The survival analyses between tumor-stroma ratio or intratumor stromal heterogeneity high and low groups after colectomy were assessed in multivariate analyses. RESULTS: Two hundred patients were divided into 2 groups based on the median tumor-stroma ratio and intratumor stromal heterogeneity values. The 5-year overall survival and relapse-free survival rates after colectomy significantly differed between the high and low tumor-stroma ratio or intratumor stromal heterogeneity groups. Multivariate analysis identified low tumor-stroma ratio (HR: 1.90, p = 0.03) and high intratumor stromal heterogeneity (HR: 2.44, p = 0.002) as independent poor prognostic factors for relapse-free survival. The tumor-stroma ratio and intratumor stromal heterogeneity correlated with the duration from curative surgery to recurrence. Furthermore, postoperative recurrence within 2 years was predicted with higher accuracy by using the tumor-stroma ratio or intratumor stromal heterogeneity than by using the pathological stage. In a validation cohort, interobserver agreement was assessed by 2 observers, and Cohen's κ coefficient for the tumor-stroma ratio (κ value: 0.70) and intratumor stromal heterogeneity (κ value: 0.60) revealed a substantial interobserver agreement. LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: Tumor-stroma ratio and intratumor stromal heterogeneity calculated using image analysis software have potential as imaging biomarkers for predicting the survival of patients with colon cancer after colectomy. See Video Abstract at http://links.lww.com/DCR/C114 . VALOR DE LA PROPORCIN DE ESTROMA TUMORAL Y LA HETEROGENEIDAD ESTRUCTURAL MEDIDOS POR UNA NUEVA TCNICA DE ANLISIS DE IMGENES SEMIAUTOMTICA PARA PREDECIR LA SUPERVIVENCIA EN PACIENTES CON CNCER DE COLON: ANTECEDENTES:La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral han sido identificados como factores pronósticos para varios tipos de carcinomas. Los avances recientes en cuanto a las tecnologías de análisis de imágenes y sus aplicaciones en la medicina, han permitido un análisis detallado de los datos clínicos más allá del conocimiento humano.OBJETIVO:Investigar la relación del estroma tumoral y la heterogeneidad del estroma intratumoral calculados mediante un nuevo método objetivo y semiautomático para el análisis de imágenes.DISEÑO:Diseño de cohorte retrospectivo.AJUSTES:Institución única.PACIENTES:Pacientes sometidos a colectomía curativa por cáncer de colon.PRINCIPALES MEDIDAS DE RESULTADO:Los análisis de supervivencia entre la relación del estroma tumoral o la heterogeneidad del estroma intratumoral entre los grupos con valores altos y bajos tras la colectomía, fueron evaluados en análisis multivariados.RESULTADOS:Fueron divididos 200 pacientes en dos grupos basados en la mediana de la proporción con respecto a los valores del estroma tumoral y la heterogeneidad del estroma intratumoral. Las tasas de supervivencia general a los 5 años y de supervivencia libre de recaídas después de la colectomía, difirieron significativamente entre los grupos con índice de estroma tumoral o heterogeneidad del estroma intratumoral altos y bajos. El análisis multivariante identificó una proporción de estroma tumoral baja (cociente de riesgos instantáneos: 1.90, p = 0.03) y una heterogeneidad estromal intratumoral alta (cociente de riesgos instantáneos: 2.44, p = 0.002) como factores independientes de mal pronóstico para la supervivencia libre de recaídas. La proporción de estroma tumoral y la heterogeneidad del estroma intratumoral se correlacionaron con la duración de la recurrencia desde la cirugía.Además, la recurrencia posoperatoria dentro de los 2 años se predijo con mayor precisión mediante el uso del índice de estroma tumoral o la heterogeneidad del estroma intratumoral que mediante el uso del estadio patológico. En una cohorte de validación, la concordancia interobservador fue evaluada por dos observadores, y el coeficiente Kappa de Cohen para la proporción de estroma tumoral y la heterogeneidad estromal intratumoral reveló una concordancia interobservador sustancial (valor Kappa: 0.70, 0.60, respectivamente).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo de una sola institución.CONCLUSIONES:La proporción del estroma tumoral y la heterogeneidad del estroma intratumoral calculadas mediante software de análisis de imágenes tienen potencial como biomarcadores de imagen para predecir la supervivencia de los pacientes con cáncer de colon tras la colectomía. Consulte Video Resumen en http://links.lww.com/DCR/C114 . (Traducción-Dr. Osvaldo Gauto ).

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

AIM: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. METHOD: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. RESULTS: Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04). CONCLUSION: Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

The Role of Inflammation-associated microRNA-4257 as a Promoter of Malignancy in Colorectal Cancer.

BACKGROUND/AIM: The clinical significance ofmiR-4257 in patients with colorectal cancer (CRC) remains unclear. Here, we investigated the usefulness of measuring miR-4257 levels in the plasma and cancer tissues of patients with CRC, and the function of miR-4257 in CRC cell lines. MATERIALS AND METHODS: miR-4257 levels were measured in the plasma and cancer tissues of patients with CRC using quantitative polymerase chain reaction. The relationships between miR-4257 level and clinicopathological features were examined. Proliferation, transwell, wound healing, and adhesion assays were performed using a miR-4257 mimic and inflammatory cytokines. RESULTS: Relapse-free survival was significantly lower in patients with high miR-4257 levels in the plasma and cancer tissue (p<0.001 andp=0.016, respectively). High miR-4257 expression was an independent predictive factor for recurrence (p=0.017 and p=0.028). Addition of inflammatory cytokines to CRC and normal cell lines increased the expression of miR-4257 in the cell lines and cell culture medium. Over-expression of miR-4257 in CRC cells increased malignancy, while over-expression in normal cells increased adhesion to CRC cells. The addition of inflammatory cytokines to normal cell lines enhanced adhesion to CRC cell lines. CONCLUSION: miR-4257 level in plasma and cancer tissues is a biomarker of disease recurrence in patients with CRC. Moreover, miR-4257 promoted tumour growth and was associated with cancer-induced inflammation.

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy.

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.

Calcifying fibrous tumor of the ileum resected by single-port laparoscopic surgery: a case report.

BACKGROUND: Calcifying fibrous tumors (CFTs) are rare benign tumors. Because CFTs sometimes relapse, radical resection with adequate margins is necessary. We report a case of ileal CFT resected using single-port laparoscopic surgery. CASE PRESENTATION: A 33-year-old man presented with chief complaints of abdominal pain and vomiting. Computed tomography demonstrated a 45-mm-sized pelvic mass with partial calcification in the ileum. The patient was diagnosed with an ileal tumor, and partial resection of the ileum was performed using the single-port laparoscopic technique. Pathologic findings revealed hypocellular spindle cells with dense hyalinized collagen, interspersed calcification, and infiltration of lymphoplasmacytic cells. Immunohistochemical analysis showed that the factor XIIIa was positive and other tumor-specific markers were negative. Based on these findings, the tumor was finally diagnosed as a CFT. CONCLUSIONS: Although CFT is benign, multifocal and recurrent CFTs have been reported. Therefore, careful intraperitoneal observation and curative resection are necessary. Single-port laparoscopic surgery is acceptable, both in terms of curability and minimal invasiveness.

Removal of small extracellular vesicles inhibits the progression of peritoneal dissemination in gastric cancer.

BACKGROUND: The prognosis of gastric cancer patients with peritoneal dissemination is extremely poor and effective treatment for peritoneal dissemination has not been established. Gastric cancer-derived small extracellular vesicles play an important role in the development of a favorable microenvironment for peritoneal metastasis and progression of peritoneal dissemination. Here, we aimed to investigate the transformation of gastric cancer cells by removing gastric cancer-derived small extracellular vesicles and to develop a novel therapy for inhibiting peritoneal dissemination. METHODS: Gastric cancer cells were cultured in medium containing gastric cancer- and peritoneal mesothelium-derived small extracellular vesicles and in medium from which small extracellular vesicles were removed by ultracentrifugation. Cell function assays were performed in vitro, and the alternations in gene expression in gastric cancer cells were analyzed. The inhibitory effect of intraperitoneal lavage on peritoneal dissemination was investigated in vivo as a method to remove gastric cancer-derived small extracellular vesicles. RESULTS: Removal of gastric cancer-derived small extracellular vesicles suppressed the proliferative and migrative abilities of gastric cancer cells and the adhesion of gastric cancer cells to peritoneal mesothelial cells. It altered the expression of several genes related to the cell cycle and epithelial-mesenchymal transition pathways of gastric cancer cells, leading to the inhibition of gastric cancer cell growth and peritoneal dissemination in vivo. CONCLUSIONS: Our study provides novel insights into a novel therapy for inhibiting the peritoneal dissemination of gastric cancer by targeting gastric cancer-derived small extracellular vesicles to improve the prognosis of gastric cancer patients with peritoneal metastasis.

Overexpression of Tetraspanin31 contributes to malignant potential and poor outcomes in gastric cancer.

Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer-promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition of GC cells through the PI3K-Akt pathway and increased cell apoptosis in a TP53 mutation-independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor-malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC.

Is Preoperative Spirometry Necessary for Gastrointestinal Cancer Surgery?

BACKGROUND/AIM: The significance of spirometry as preoperative risk assessment for gastrointestinal surgery has been controversial. At the beginning of the COVID-19 pandemic, preoperative spirometry was temporarily suspended in our institute. This study was aimed to investigate the necessity of spirometry for gastrointestinal cancer surgery. PATIENTS AND METHODS: We compared short-term postoperative outcomes between 318 patients who underwent surgery for colorectal or gastric cancer with (Spirometry group; n=272) or without spirometry (Non-spirometry group; n=46). RESULTS: Respiratory functional disorders were detected in 77 (28.3%) patients in the Spirometry group. No significant differences were noted in complications, including pneumonia, or the length of hospital stay between the two groups. An advanced age, male sex, comorbidities with respiratory diseases, and a smoking history significantly correlated with abnormal results in spirometry. CONCLUSION: Preoperative spirometry may be substituted with other clinical factors in patients with gastrointestinal cancer.