Prognostic significance of the Naples prognostic score in colorectal cancer patients undergoing curative resection: a propensity score matching analysis.

BACKGROUND: Systemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis. METHODS: A total of 533 CRC patients were enrolled in this study. Overall survival (OS) and disease-free survival (DFS) were compared between high-NPS and low-NPS groups. A time-dependent receiver operator characteristic (ROC) curve analysis was conducted to calculate the area under curve (AUC) of the NPS for OS. A multivariable Cox-proportional hazards regression analysis and PSM analysis were used to identify independent prognostic factors for OS and DFS. We compared the predictive value of the NPS to that of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Onodera prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) for OS. RESULTS: High-NPS was significantly associated with worse OS and DFS. After PSM, 123 patients were included in each group. A multivariate analysis revealed that Age ≥ 68, ASA-PS ≥ 3, high NPS and undifferentiated tumor type were independently associated with OS, while high NPS, advanced T and N stage were independently associated with DFS after PSM. The NPS had the greatest AUC for OS in comparison to the NLR, LMR, PNI and CONUT. CONCLUSIONS: We successfully validated the prognostic utility of the NPS for CRC patients after curative resection.

Predictive value of the Naples prognostic score on postoperative outcomes in patients with rectal cancer.

PURPOSE: The Naples prognostic score (NPS) is a prognostic index based on the nutritional and inflammatory status. However, its utility in predicting postoperative complications (POCs) has not been examined in rectal cancer (RC). We evaluated the predictive value of the preoperative NPS for POCs in RC. METHODS: We retrospectively analyzed 235 patients who underwent surgery for RC. The NPS was calculated based on serum albumin, serum total cholesterol, the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR). Severe POCs were defined as Clavien-Dindo classification grade ≥ III. The optimal cut-off value of the NPS was determined by a receiver operator characteristic (ROC) curve analysis. The NPS, NLR, LMR, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR), Glasgow prognostic score (GPS), Onodera prognostic nutritional index (PNI) and controlling nutritional status score (CONUT) were investigated as inflammation-based and/or nutritional markers. Predictors of severe POCs were analyzed by logistic regression modeling. RESULTS: Severe POCs were observed in 64 patients (27.2%). Male sex, operation time (> 257 min), blood loss (≥ 30 mL), albumin (< 4.0 g/dL), CRP (≥ 1.0 mg/dL), total cholesterol (≤ 180 mg/dL), NPS (≥ 2), LMR (≥ 3.48), PLR (≥ 103.6), CAR (> 0.025), GPS (≥ 1), PNI (< 48.1) and CONUT (≥ 2) were significantly associated with severe POCs. The multivariate analysis revealed that male sex, operation time (> 257 min), and a high NPS (≥ 2) were independent predictors of severe POCs. The ROC curve analysis revealed that the NPS had the greatest predictive value among the inflammation-based and/or nutritional markers. CONCLUSION: The NPS is a valuable predictor of severe POCs in RC.

Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation.

Foxp3-expressing regulatory T cells (Tregs) can be generated in vitro by antigenic stimulation of conventional T cells (Tconvs) in the presence of TGF-ß and IL-2. However, unlike Foxp3+ naturally occurring Tregs, such in vitro induced Tregs (iTregs) are functionally unstable mainly because of incomplete Treg-type epigenetic changes at Treg signature genes such as Foxp3 Here we show that deprivation of CD28 costimulatory signal at an early stage of iTreg generation is able to establish Treg-specific DNA hypomethylation at Treg signature genes. It was achieved, for example, by TCR/TGF-ß/IL-2 stimulation of CD28-deficient Tconvs or CD28-intact Tconvs without anti-CD28 agonistic mAb or with CD80/CD86-blocked or -deficient antigen-presenting cells. The signal abrogation could induce Treg-type hypomethylation in memory/effector as well as naive Tconvs, while hindering Tconv differentiation into effector T cells. Among various cytokines and signal activators/inhibitors, TNF-α and PKC agonists inhibited the hypomethylation. Furthermore, CD28 signal deprivation significantly reduced c-Rel expression in iTregs; and the specific genomic perturbation of a NF-κB binding motif at the Foxp3 CNS2 locus enhanced the locus-specific DNA hypomethylation even in CD28 signaling-intact iTregs. In addition, in vitro maintenance of such epigenome-installed iTregs with IL-2 alone, without additional TGF-ß or antigenic stimulation, enabled their expansion and stabilization of Treg-specific DNA hypomethylation. These iTregs indeed stably expressed Foxp3 after in vivo transfer and effectively suppressed antigen-specific immune responses. Taken together, inhibition of the CD28-PKC-NF-κB signaling pathway in iTreg generation enables de novo acquisition of Treg-specific DNA hypomethylation at Treg signature genes and abundant production of functionally stable antigen-specific iTregs for therapeutic purposes.

Significance of tumor heterogeneity of p-Smad2 and c-Met in HER2-positive gastric carcinoma with lymph node metastasis.

BACKGROUND: Tumor heterogeneity has frequently been observed in gastric cancer (GC), but the correlation between patients' clinico-pathologic features and the tumoral heterogeneity of GC-associated molecules is unclear. We investigated the correlation between lymph node metastasis and the intra-tumoral heterogeneity of driver molecules in GC. MATERIALS AND METHODS: We retrospectively analyzed the cases of 504 patients who underwent a gastrectomy at the Department of Gastroenterological Surgery, Osaka Metropolitan University and 389 cases drawn from The Cancer Genome Atlas (TCGA) data. We performed a clustering analysis based on eight cancer-associated molecules including HER2, c-Met, and p-Smad2 using the protein expression revealed by our immunohistochemical study of the patients' and TCGA cases. We determined the correlations between HER2 expression and the other molecules based on the degree of lymph node metastasis. RESULTS: Immunohistochemical staining data showed that a 43 of the 504 patients with GC (8.5%) were HER2-positive. In the HER2-positive cases, the expressions of c-Met and p-Smad2 were increased in accord with the lymph-node metastatic level. The overall survival of the HER2-positive GC patients with both p-Smad2 and c-Met expression was significantly (p = 0.030) poorer than that of the patients with p-Smad2-negative and/or c-Met-negative expression. The results of the TCGA data analysis revealed that 58 of the 389 GC cases (14.9%) were ERBB2-positive. MET expression was more frequent in the N1 metastasis group than the N0 group. In the high lymph-node metastasis (N2 and N3) group, SMAD2 expression was more frequent, as was ERBB2 and MET expression. CONCLUSION: p-Smad2 and c-Met signaling might play important roles in lymph node metastasis in HER2-positive GC.

Lipocalin-2 negatively regulates epithelial-mesenchymal transition through matrix metalloprotease-2 downregulation in gastric cancer.

BACKGROUND: Although the role of Lipocalin-2 (LCN2) in cancer development has been focused on recent studies, the molecular mechanisms and clinical relevance of LCN2 in gastric cancer (GC) still remain unclear. METHODS: Transcriptome analysis of GC samples from public human data was performed according to Lauren's classification and molecular classification. In vitro, Western blotting, RT-PCR, wound healing assay and invasion assay were performed to reveal the function and mechanisms of LCN2 in cell proliferation, migration and invasion using LCN2 knockdown cells. Gene set enrichment analysis (GSEA) of GC samples from public human data was analyzed according to LCN2 expression. The clinical significance of LCN2 expression was investigated in GC patients from public data and our hospital. RESULTS: LCN2 was downregulated in diffuse-type GC, as well as in Epithelial-Mesenchymal Transition (EMT) type GC. LCN2 downregulation significantly promoted proliferation, invasion and migration of GC cells. The molecular mechanisms of LCN2 downregulation contribute to Matrix Metalloproteinases-2 (MMP2) stimulation which enhances EMT signaling in GC cells. GSEA revealed that LCN2 downregulation in human samples was involved in EMT signaling. Low LCN2 protein and mRNA levels were significantly associated with poor prognosis in patients with GC. LCN2 mRNA level was an independent prognostic factor for overall survival in GC patients. CONCLUSIONS: LCN2 has a critical role in EMT signaling via MMP2 activity during GC progression. Thus, LCN2 might be a promising therapeutic target to revert EMT signaling in GC patients with poor outcomes.

The impact of the surgical Apgar score on oncological outcomes in patients with colorectal cancer: a propensity score-matched study.

BACKGROUND: The surgical Apgar score (SAS) predicts postoperative complications (POCs) following gastrointestinal surgery. Recently, the SAS was reported to be a predictor of not only POCs but also prognosis. However, the impact of the SAS on oncological outcomes in patients with colorectal cancer (CRC) has not been fully examined. The present study therefore explored the oncological significance of the SAS in patients with CRC, using a propensity score matching (PSM) method. METHODS: We retrospectively analyzed 639 patients who underwent radical surgery for CRC. The SAS was calculated based on three intraoperative parameters: estimated blood loss, lowest mean arterial pressure, and lowest heart rate. All patients were classified into 2 groups based on the SAS (≤6 and >6). The association of the SAS with the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) was analyzed. RESULTS: After PSM, each group included 156 patients. Univariate analyses revealed that a lower SAS (≤6) was significantly associated with a worse OS and CSS. A multivariate analysis revealed that the age ≥75 years old, ASA-Physical Status ≥3, SAS ≤6, histologically undifferentiated tumor type, and an advanced pStage were independent factors for the OS, and open surgery, a SAS ≤6, histologically undifferentiated tumor type and advanced pStage were independent factors for the CSS. CONCLUSIONS: A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.

Usefulness of the skeletal muscle index in postoperative ileus of colorectal cancer patients: a retrospective cohort study.

BACKGROUND: Postoperative complications of colorectal cancer mainly include infections (surgical site infection, remote infection, etc.), post-operative ileus (POI), and anastomosis leakage. POI reportedly prolongs the hospital stay and increases medical costs. Therefore, predicting POI is very important. There have been some reports on the relationships between sarcopenia and postoperative complications in colorectal cancer patients, but none have been limited to POI. We therefore conducted a retrospective clinical study with a logistic regression analysis to confirm the risk factors for ileus after colorectal cancer surgery. METHODS: We retrospectively analyzed 213 patients who underwent elective oncological colorectal surgery for colorectal cancer from November 2017 to July 2021. The skeletal muscle mass (SMM, kg) was estimated using a whole-body bioelectrical impedance analysis (BIA), and the skeletal muscle index (SMI) was calculated as the SMM/height2. We divided all patients into 2 groups based on a low SMI (male < 8.958 kg/m2, female < 8.443 kg/m2) or normal SMI. Preoperative and intraoperative factors as well as, postoperative outcomes were then compared between the two groups. RESULTS: The median (range) age of the 213 included patients was 72.0 (33-91) years old. Complications were noted in 96 patients (45.1%), including 21 (9.9%) with POI. There were 68 (31.9%) low SMI patients. POI occurred significantly more frequently in low SMI patients (19.1%) than in normal SMI patients (5.5%) (p = 0.005). In the multivariate analysis, bleeding (p = 0.039) and a low SMI (p = 0.031) were significantly associated with POI. In addition, a propensity score matching analysis was performed to further reduce the selection bias. As a result, a low SMI was the only independent POI predictor among the 78 matched cases. CONCLUSION: A preoperative low SMI in colorectal cancer patients was considered a risk factor for POI.

[A Case of Rectal Cancer and Multiple Lung Metastases That Had Complete Response Treated by XELOX plus Bevacizumab after Primary Lesion Resection].

A 54-year-old woman visited our hospital complaining of abdominal distension. Endoscopic examination revealed type 3 tumor in the rectum located 15 cm from the anal edge. Enhanced computed tomography showed multiple ground glass-like shadows in both lungs that were suspected of multiple metastases. We diagnosed as having rectal cancer with multiple lung metastases. After placing the stent transanally to release the intestinal obstruction, we performed laparoscopic high anterior resection. Then, the patient received chemotherapy with 10 courses of XELOX plus bevacizumab and 9 courses of the regimen without oxaliplatin. A whole-body CT revealed complete response. And while taking capecitabine the patient remains well and without recurrence. We describe the present case with reference to the literature.

Asporin Expression on Stromal Cells and/or Cancer Cells Might Be A Useful Prognostic Marker in Patients with Diffuse-Type Gastric Cancer.

BACKGROUND: Asporin (ASPN), a member of the proteoglycan family, has been shown to have a close correlation with cancer progression. It is not known whether ASPN is an oncogenic driver or a tumor suppressor in human gastric cancer. We sought herein to determine the relationship between ASPN expression and clinicopathological features of gastric cancer. PATIENTS AND METHODS: A total of 296 gastric cancer patients (diffuse type, n = 144; intestinal type, n = 152) were enrolled. The ASPN expression level in each case was analyzed by immunohistochemistry. RESULTS: ASPN was mainly found on stromal cells, especially on fibroblasts in tumor stroma, i.e., cancer-associated fibroblasts. The ASPN expression on either cancer cells or stromal cells was significantly high in macroscopic scirrhous-type tumors (p < 0.001) and histologically abundant stroma-type tumors (p < 0.001). Interestingly, a Kaplan-Meier survival curve of the 144 cases of diffuse-type gastric cancer revealed a significantly poorer prognosis in patients with ASPN-positive expression (p = 0.043; log rank) compared to those with ASPN-negative expression, but the prognoses were not significantly different in these subgroups of the 152 cases of intestinal-type gastric cancer. A multivariate analysis with respect to overall survival showed that ASPN expression on stromal cells and/or cancer cells was significantly correlated with overall survival in patients with diffuse-type gastric cancer (p = 0.041). CONCLUSION: In gastric cancer, ASPN was expressed mainly on stromal cells and partially on cancer cells. ASPN expression on stromal cells and/or cancer cells might be a useful prognostic marker in patients with diffuse-type gastric cancer.

Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study.

BACKGROUND: Postoperative anastomotic leakage (AL) is associated with not only prolonged hospital stay and increased medical costs, but also poor prognosis in esophageal cancer. Several studies have addressed the utility of various inflammation-based and/or nutritional markers as predictors for postoperative complications. However, none have been documented as specific predictors for AL in esophageal cancer. We aimed to identify predictors of AL after esophagectomy for thoracic esophageal cancer, focusing on preoperative inflammation-based and/or nutritional markers. METHODS: We retrospectively analyzed 295 patients who underwent radical esophagectomy for thoracic esophageal squamous cell carcinoma between June 2007 and July 2020. As inflammation-based and/or nutritional markers, Onodera prognostic nutritional index, C-reactive protein (CRP)-to-albumin ratio (CAR) and modified Glasgow prognostic score were investigated. Optimal cut-off values of inflammation-based and/or nutritional markers for AL were determined by receiver operating characteristic curves. Predictors for AL were analyzed by logistic regression modeling. RESULTS: AL was observed in 34 patients (11.5%). In univariate analyses, preoperative body mass index (≥ 22.1 kg/m2), serum albumin level (≤ 3.8 g/dL), serum CRP level (≥ 0.06 mg/dL), CAR (≥ 0.0139), operation time (> 565 min) and blood loss (≥ 480 mL) were identified as predictors of AL. Multivariate analyses revealed higher preoperative CAR (≥ 0.0139) as an independent predictor of AL (p = 0.048, odds ratio = 3.02, 95% confidence interval 1.01-9.06). CONCLUSION: Preoperative CAR may provide a useful predictor of AL after esophagectomy for thoracic esophageal squamous cell carcinoma.

[Effect of Upfront Dose Reduction in the First Cycle of Chemotherapy for Unresectable/Recurrent Gastric Cancers in Patients Aged Over 80 Years].

Chemotherapy for elderly patients requires ingenuity in treatment to mitigate its high risk. Therefore, we investigated an upfront dose reduction in the first cycle of chemotherapy for unresectable/recurrent gastric cancers in patients over 80 years old. We examined 6 patients over 80 years old, who underwent S-1 plus L-OHP therapy(SOX)for unresectable/recurrent gastric cancer in our department between January 2020 and January 2021. There were no adverse events over Grade 3 in the upfront dose reduction group(U group), while 1 case(50.0%)in the normal dose group(N group)experienced an adverse event over Grade 3. Moreover, only the U group continued treatment for 4 or more courses, whereas none from the N group did. Partial response(PR)was achieved as a therapeutic effect in 3 patients of the U group. Only 2 cases of the U group advanced to the second-line regimen and both were able to transition to the third-line regimen. However, none were able to even transition to the second-line regimen in the N group. Therefore, it was suggested that by reducing the dose of chemotherapy from the first cycle for elderly patients over 80 years old, the incidence of adverse events can be kept low, which makes it possible to continue long-term chemotherapy.

Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells.

Scirrhous-type gastric carcinoma (SGC), which is characterized by the rapid proliferation of cancer cells accompanied by extensive fibrosis, shows extremely poor survival. A reason for the poor prognosis of SGC is that the driver gene responsible for SGC has not been identified. To identify the characteristic driver gene of SGC, we examined the genomic landscape of six human SGC cell lines of OCUM-1, OCUM-2M, OCUM-8, OCUM-9, OCUM-12 and OCUM-14, using multiplex gene panel testing by next-generation sequencing. In this study, the non-synonymous mutations of serine threonine kinase 11/liver kinase B1 (STK11/LKB1) gene were detected in OCUM-12, OCUM-2M and OCUM-14 among the six SGC cell lines. Capillary sequencing analysis confirmed the non-sense or missense mutation of STK11/LKB1 in the three cell lines. Western blot analysis showed that LKB1 expression was decreased in OCUM-12 cells and OCUM-14 cells harboring STK11/LKB1 mutation. The mammalian target of rapamycin (mTOR) inhibitor significantly inhibited the proliferation of OCUM-12 and OCUM-14 cells. The correlations between STK11/LKB1 expression and clinicopathologic features of gastric cancer were examined using 708 primary gastric carcinomas by immunochemical study. The low STK11/LKB1 expression group was significantly associated with SGC, high invasion depth and frequent nodal involvement, in compared with the high STK11/LKB1 expression group. Collectively, our study demonstrated that STK11/LKB1 mutation might be responsible for the progression of SGC, and suggested that mTOR signaling by STK11/LKB1 mutation might be one of therapeutic targets for patients with SGC.

Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor.

Fibroblast growth factor receptor (FGFR) is associated with proliferation, migration, and angiogenesis of carcinomas, and FGFR signaling inhibitors are considered a key drug for the treatment of solid tumors with FGFR overexpression. Amplification of FGFR2 is reportedly identified in 3%-10% of gastric cancers (GCs). The aim of this study is to clarify whether the identification of the circulating tumor cells (CTCs) with FGFR2 overexpression is useful to detect patients with FGFR2-overexpressing GC. One hundred GC patients who underwent gastrectomy were enrolled. A total volume of 8 mL of peripheral blood was collected from each patient just before gastrectomy, and mononuclear cells were enriched by Ficol density gradient centrifugation. These cells were immunostained with PI/CD45/EpCAM/FGFR2. The number of CTCs with FGFR2 expression in each sample was enumerated by FACScan. The FGFR2 expression level of the resected primary tumor was assessed by immunohistochemistry. The number of FGFR2-positive CTCs in the GC patients' peripheral blood was significantly correlated with the FGFR2 expression level of the primary GC. The relapse-free survival of the patients with FGFR2-positive CTCs (≥5 cells/10 mL blood) was significantly poorer (P = .018, log-rank) than that of the patients without FGFR2-positive CTCs (<5 cell/10 mL blood). These findings suggested that the determination of FGFR2-positive CTCs might help identify an existing tumor with FGFR2 overexpression.

[A Case of Malignant Lymphoma of the Jejunum That Developed Stenosis and Perforation after a Complete Response to Chemotherapy].

A 57-year-old woman was admitted owing to epigastric pain.Abdominal computed tomography demonstrated a tumor in the origin of the jejunum.After an endoscopic biopsy, we diagnosed diffuse large B-cell lymphoma.We treated her with CHOP chemotherapy because pancreaticoduodenectomy is highly invasive.After 1 course of chemotherapy, the tumor was reduced.However, she developed a jejunal stenosis; therefore, we performed laparoscopic gastrojejunostomy.Furthermore, she developed perforated peritonitis on the sixth day after the surgery, and therefore, an emergency partial jejunum resection was performed.Histopathologically, viable lymphoma cells were not found in the resected intestine.She had a complete response 10 months after the surgery.Chemotherapy may cause intestinal stenosis and perforation requiring surgery; therefore, decisions about surgical procedures must be made carefully.

The Efficacy of Chemical Bowel Preparation Against Incisional Surgical Site Infection in Colorectal Cancer Surgery: A Propensity Score Matching Study.

BACKGROUND/AIM: In colorectal cancer surgery, the risk of surgical site infection (SSI) is relatively high. The development of SSI is related to longer and costlier hospitalization and reduced quality of life; therefore, perioperative prevention of SSI is important. Chemical bowel preparation (CBP) combined with mechanical bowel preparation (MBP) may be more effective in preventing surgical site infection (SSI) compared to MBP alone. Since May 2021, we have been administering oral kanamycin and metronidazole as CBP, in addition to MBP, as a preoperative treatment for colorectal cancer surgery on the day before surgery. In this study, we investigated the clinical value of CBP in addition to MBP in colorectal cancer surgery using propensity score matching (PSM). PATIENTS AND METHODS: From January 2017 to December 2021, 136 consecutive patients underwent radical surgery for sigmoid colon and rectal cancer at the Osaka Metropolitan University Hospital. Patients were divided into two groups: CBP and N-CBP. In the N-CBP group, we performed only preoperative MBP, whereas in the CBP group, we performed preoperative CBP in addition to MBP. We retrospectively analyzed this relationship with PSM. RESULTS: Overall, 46 patients underwent preoperative CBP and MBP, 90 patients underwent preoperative MBP only. PSM was performed between the CBP and N-CBP groups based on the following ten factors: age, sex, diabetes mellitus, preoperative therapy, Glasgow Prognostic Score (GPS), operative time, blood loss, stoma, and pathological stage. After PSM, univariate and multivariate analyses of the relationship between SSI and clinicopathological factors were performed. Univariate analysis showed that age and CBP were correlated with the rate of SSI (p=0.039 and p=0.017, respectively), whereas sex was relatively correlated with the rate of SSI (p=0.066). The multivariate analysis of significant factors identified age of 75 or more and non-CBP as an independent risk factor for incisional SSI (HR=9.5; p=0.049 and HR=5.4×e-8; p=0.020). CONCLUSION: Preoperative CBP in addition to MBP was effective in preventing incisional SSI during colorectal cancer surgery.

Identification of novel lactic acid bacteria with enhanced protective effects against influenza virus.

Lactic acid bacteria (LAB) exert health-beneficial effects by regulating innate immunity in the intestinal tract. Due to growing health awareness, the demand for LAB and studies have focused on identifying beneficial LAB strains is increasing, especially those that stimulate innate immunity. In this study, the LAB strain D279 (NITE_BP-03645, Latilactobacillus sakei) was isolated from among 741 LAB strains that were analyzed for their ability to induce interleukin 12 (IL-12) production and was subsequently characterized. D279 induced the highest expression of IL-12 among the screened LABs. Furthermore, D279 significantly activated antiviral genes and preferentially induced interferon (IFN)λ expression in vitro, which plays a critical role in the epithelial tissue, thereby conferring strong anti-influenza potency without inflammation. However, it decreased the IFNα levels. The administration of pasteurized D279 to mice resulted in strong anti-influenza potency, with higher natural killer (NK) cell activity and a lower viral load in the lung than in the control. Importantly, none of the D279-administered mice were sacrificed during the viral infection tests. These results suggest that D279 administration confers beneficial effects by regulating innate immunity and that it may be relevant for commercial use in the future.

The Surgical Apgar Score Predicts Postoperative Complications in Elderly Patients After Surgery for Colorectal Cancer.

OBJECTIVE: The surgical Apgar score (SAS) has been validated as a risk assessment tool for postoperative complications. However, the utility of the SAS in elderly patients with colorectal cancer remains unclear. In this study, we evaluated the utility of the SAS for predicting the severe complications in elderly patients with colorectal cancer. METHODS: We retrospectively analyzed 295 patients underwent radical surgery for colorectal cancer in elderly patients ≥75 years old. The SAS was calculated based on 3 intraoperative parameters: estimated blood loss (EBL), lowest mean arterial pressure, and lowest heart rate. Severe complications were defined as Clavien-Dindo classification grade ≥ IIIa. We divided all patients into 2 groups according to with or without severe complications. The optimal cut-off value of SAS for severe complications has been determined by receiver operator characteristic curve. Predictors for severe complications were analyzed by logistic regression modeling. RESULTS: Severe complications were observed in 57 patients (19.3%). Male, rectal cancer, operation time (>240 minutes), EBL (≥120 mL), and a low SAS (≤6) were significantly associated with severe complications in univariate analysis. A multivariate analysis revealed that male, rectal cancer, and a low SAS (≤6) were independent predictors for severe complications. CONCLUSIONS: A low SAS (≤6) was associated with severe complications after colorectal cancer surgery in elderly patients. The SAS is a valuable predictor for severe complications in elderly patients with colorectal cancer.

Usefulness of intraoperative ultrasound examination for laparoscopic right-side colon cancer surgery: a propensity score-matched study.

Complete mesocolic excision (CME) with central vascular ligation (CVL) in laparoscopic surgery for right-sided colon cancer (RSCC) requires a precise understanding of the vascular anatomy. The efficacy of intraoperative ultrasound (IUS) in the identification of blood vessels for RSCC surgery was not evaluated. The aim of this study was to compare the intraoperative and short-term outcomes of CME with CVL with or without IUS by laparoscopic surgery for RSCC. We performed IUS on 26 patients of RSCC and compared with a total of 124 patients who underwent the surgery for RSCC at our institution. Propensity score matching (PSM) was performed to reduce the confounding effects to imbalances in the use of IUS. The IUS identified the main feeding artery and the accompanying vein in all 26 cases. After PSM, the amount of intraoperative blood loss in the IUS group was significantly lower than that in the conventional group (5 ml vs. 30 ml, p = 0.035) and no significant difference of the postoperative complications was observed. The IUS reduced the risk of bleeding in the surgery for RSCC. The IUS is a safe and feasible technique that help the surgeons for anatomical understandings under real-time condition in the laparoscopic surgery of RSCC.

Establishment of a gastric cancer cell line with high microsatellite instability, OCUM-13, derived from Borrmann type-2 primary tumor.

Gastric cancer (GC) with microsatellite instability (MSI) has been reported to be sensitive to immunotherapy, however some of GC cases with MSI remain resistant to immunotherapy. Cancer cell lines showing MSI might be useful for the analysis of mechanisms of immunotherapy, while only a few GC cell lines with MSI are available so far. In this study, we established a unique GC cell line with MSI, OCUM-13, from a primary GC with abundant tumor-infiltrating lymphocytes. MSI assay indicated that OCUM-13 cells as well as the primary tumor showed a band shift in more than 3 of 5 microsatellite loci, suggesting that OCUM-13 did have high MSI. The subcutaneous inoculation of OCUM-13 cells into mice performed tumor formation. Insulin-like growth factor 1 receptor inhibitor decreased the growth of OCUM-13 cells. The newly established cell line with MSI, OCUM-13, might be useful for the analysis of cancer therapy for GC with MSI.

Hard Palate Metastasis from Rectal Adenocarcinoma.

The most common sites of metastasis from colorectal cancer are liver, lungs, and peritoneum. Oral cavity metastasis is extremely rare, accounting for only 1-2% of all oral cancers. We report the case of a 71-year-old male who presented with hard palate metastasis 20 months after his initial diagnosis for T4N1M1 rectal adenocarcinoma according to the UICC TNM classification. To the best of our knowledge, hard palate metastasis from colorectal cancer has never been previously reported in the literature. The hard palate metastasis deteriorates oral function, resulted in unfavorable prognosis. Early detection of oral cavity metastasis could lead to the opportunities for additional treatment and improve outcomes following treatment.