Exploring animal protein sources against prevent age-related short-term memory decline in mice: Dietary fish (Alaska Pollock) protein exhibits superior protective effects.

Dietary factors, particularly proteins, have been extensively explored to combat cognitive impairment. We have previously reported that dietary fish (Alaska Pollock) protein (APP) is more effective than casein (CAS) or fish oil in maintaining short-term memory in senescence-accelerated mice prone 10 (SAMP10). To examine the specificity of the protective effect of APP intakes against short-term memory decline, we assessed the impact of various dietary animal proteins, including APP, CAS, chicken breast protein (CP), and whey protein (WP), against age-related cognitive function in SAMP10 mice. After feeding the experimental diets for 5 months, memory was assessed using the Y-maze. The APP group exhibited a significant increase in spontaneous alternation behavior as an indicator of working memory when group compared with groups fed with other protein source. Additionally, the APP group displayed significantly higher neurofilament heavy chain positivity than the CAS and CP groups, as evidenced immunohistochemical analysis. Gut microbiota analysis indicated that dietary APP significantly enhanced the relative abundance of Lactobacillus, which positively correlated with spontaneous alternation behavior. Collectively, these findings suggest that dietary APP is more effective than CAS, CP, or WP in preventing age-related short-term memory decline and morphological abnormalities in the hippocampal axons of SAMP10 mice. Moreover, APP-mediated improvements in cognitive deficits may be associated with changes in microbiota diversity. PRACTICAL APPLICATION: This research suggests that dietary fish protein from Alaska Pollock may be more efficient in prevention short-term memory decline in mice, compared to other animal proteins. This finding has practical implications for nutritional optimization, developing the new health food products, and elucidating the relationship between the impact of specific proteins on gut microbiota and prevention of age-related cognitive decline.

Proposal of an integrated staging system using albumin-bilirubin grade and serum alpha-fetoprotein values for predicting postoperative prognosis of recurrent hepatocellular carcinoma.

BACKGROUND: Because repeat hepatectomy for recurrent hepatocellular carcinoma is a potentially invasive procedure, it is necessary to identify patients who truly benefit from repeat hepatectomy. Albumin-bilirubin grading has been reported to predict survival in patients with hepatocellular carcinoma. However, as prognosis also depends on tumor factors, a staging system that adds tumor factors to albumin-bilirubin grading may lead to a more accurate prognostication in patients with recurrent hepatocellular carcinoma. METHODS: Albumin-bilirubin grading and serum alpha-fetoprotein levels were combined and the albumin-bilirubin-alpha-fetoprotein score was created ([albumin-bilirubin grading = 1; 1 point, 2 or 3; 2 points] + [alpha-fetoprotein<75 ng/mL, 0 points; ≥5, 1 point]). Patients were classified into three groups, and their characteristics and survival were evaluated. The predictive ability of the albumin-bilirubin-alpha-fetoprotein score was compared with that of the Cancer of the Liver Italian Program and the Japan Integrated Stage scores. RESULTS: Albumin-bilirubin-alpha-fetoprotein score significantly stratified postoperative survival (albumin-bilirubin-alpha-fetoprotein score = 1/2/3: 5-year recurrence-free survival [%]: 22.4/20.7/0.0, p < 0.001) and showed the highest predictive value for survival among the integrated systems (albumin-bilirubin-alpha-fetoprotein score/Japan Integrated Stage/Cancer of the Liver Italian Program: 0.785/0.708/0.750). CONCLUSIONS: Albumin-bilirubin-alpha-fetoprotein score is useful for predicting the survival of patients with recurrent hepatocellular carcinoma undergoing repeat hepatectomy.

Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.

A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.

Micro-hepatocellular carcinoma with bile duct tumor thrombus mimicking intrahepatic intraductal papillary neoplasm of the bile duct: a case report.

BACKGROUND: Microhepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult. CASE PRESENTATION: A 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located. CONCLUSIONS: Based on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery.

Dietary Alaska Pollock Protein Attenuates the Experimental Colitis Induced by Dextran Sulfate Sodium via Regulation of Gut Microbiota and Its Metabolites in Mice.

Protein derived from fish has not only nutritional properties but also health-promoting properties. Few studies have examined the effect of dietary Alaska pollock protein (APP) on the anticolitis effect reported to be associated with metabolic syndrome (MetS). This study investigated the effect of APP intake on colitis symptoms, gut microbiota, and its metabolites in the experimental colitis mouse model induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were divided into three groups: (1) DSS-untreated mice fed an American Institute of Nutrition (AIN) 93G diet (protein source is casein), (2) DSS-treated mice fed an AIN93G diet, and (3) DSS-treated mice fed an APP diet. After the mice were fed the diets for 21 days, experimental colitis was induced by three cycles of 2% DSS administration for 5 days followed by washouts over the course of 5 days. APP-reduced body weight loss increased the disease activity index, and elevated spleen weight and alleviated colon length shortening and colonic tissue damage. Furthermore, APP altered the structure and composition of the microbiota and short-chain fatty acids in feces. Since APP intake alleviates experimental colitis induced by DSS administration through alterations in the gut microbiota and its metabolites, we deduced that APP would inhibit MetS progression via colitis suppression.

Is left-sided involvement of hepatocellular carcinoma an important preoperative predictive factor of poor outcome?

BACKGROUND: The tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models. METHODS: Patients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors. RESULTS: There were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size. CONCLUSION: The left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma.

Features of Hepatocellular Carcinoma With Micro Hepatic Vein Invasion and their Correlation With Hepatitis B and C Virus.

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.

Microsatellite Analysis of Recurrent Lesions Confirms Merit of Anatomical Liver Resection for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.

Dramatic decreases of all haemorrhagic coagulation factors by acquired inhibitors after extended left lobectomy.

INTRODUCTION: Acquired inhibition of coagulation factors is a rare disease, and the diagnosis is often difficult and delayed. We experienced a deficiency in all coagulation factors after hepatobiliary surgery. CASE PRESENTATION: Extended left liver resection was undertaken and hepaticojejunostomy was performed in a 70-year-old man. He had suffered from a high fever caused by cholangitis for 35 days. The major cause was a narrowing of the hepaticojejunostomy, and reconstruction was carried out. Twenty-four days later, there was a sudden massive bleed from his nose and the surgical site. Steroid pulse therapy was used as a treatment because cross mixing and some blood tests revealed the patient was experiencing an inhibition of all coagulation factors, and consequently the levels of coagulation factors dramatically recovered. DISCUSSION: We considered malignancy and surgical damages to be the underlying cause. The reported treatment and examination will help clinicians explore additional reasons for massive bleeding after a severe physical injury. CONCLUSION: We have described the first case of acquired inhibition of all coagulation factors associated with extended left lobectomy.

A case of obstructive jaundice due to early carcinoma of the cystic duct protruding into the common bile duct.

INTRODUCTION: Cystic duct carcinoma is a rare disease, and only 33 cases reported worldwide have completely fulfilled the criteria first established by Farrar in 1951. Here we describe an extremely rare case of early cystic duct carcinoma that fulfilled the Farrar criteria, the papillary tumour protruding into the common bile duct, leading to obstructive jaundice. CASE PRESENTATION: A 76-year-old man visited a clinic with icteric conjunctivae, and was referred to our hospital for investigation of suspected obstructive jaundice. He was initially diagnosed as having a distal bile duct carcinoma on the basis of ultrasonography (US), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiography (MRC), and underwent pancreatoduodenectomy with regional lymphadenectomy. Macroscopic examination showed that the stalk of the papillary tumour originated from the cystic duct, and that the protruding lesion was 50 mm in size. Histopathological examination revealed the tumour to be a papillary adenocarcinoma confined within the fibromuscular layer, with no evidence of lymph node metastasis. Therefore, the final diagnosis was early cystic duct carcinoma. CONCLUSION: To our knowledge, this is the first case report of obstructive jaundice due to early carcinoma of the cystic duct protruding into the bile duct, with characteristics fulfilling the Farrar criteria.

Preoperative globulin-to-albumin ratio predicts outcome after curative resection in patients with gastric cancer.

AIM: The globulin-to-albumin ratio (GAR) is useful for prognostication of patients with various cancers. However, the significance of GAR in gastric cancer (GC) remains unclear. Our purpose was to investigate the relationship between the GAR and outcome after curative resection in GC patients. METHODS: Three-hundred and seventy-six patients who had undergone curative resection for GC were retrospectively reviewed. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS), and their cut-off values were identified using receiver operating characteristic (ROC) curve analyses. Kaplan-Meier analysis and log-rank test were used for comparison of OS and relapse-free survival (RFS). RESULTS: Multivariate analysis using 17 clinical characteristics selected by univariate analyses revealed that GAR (>0.80/≤0.80) was significantly associated with OS (hazard ratio [HR], 2.305; 95% CI, 1.122-4.735; P = 0.023), as well as lymph node metastasis (presence/absence) (HR, 2.417; 95% CI, 1.077-5.426; P = 0.032), neutrophil-to-lymphocyte ratio (>2.7/≤2.7) (HR, 2.368; 95% CI, 1.138-4.930; P = 0.002), and serosal invasion (presence/absence) (HR, 3.443; 95% CI, 1.048-11.31; P = 0.042). Kaplan-Meier analysis and log-rank test demonstrated that the OS and RFS of patients with a high GAR (>0.80) were significantly poorer than those with low GAR (≤0.80). CONCLUSIONS: The GAR is a useful predictor of postoperative outcome among GC patients undergoing curative resection.

Effects of correcting missing daily feed intake values on the genetic parameters and estimated breeding values for feeding traits in pigs.

Daily feed intake (DFI) is an important consideration for improving feed efficiency, but measurements using electronic feeder systems contain many missing and incorrect values. Therefore, we evaluated three methods for correcting missing DFI data (quadratic, orthogonal polynomial, and locally weighted (Loess) regression equations) and assessed the effects of these missing values on the genetic parameters and the estimated breeding values (EBV) for feeding traits. DFI records were obtained from 1622 Duroc pigs, comprising 902 individuals without missing DFI and 720 individuals with missing DFI. The Loess equation was the most suitable method for correcting the missing DFI values in 5-50% randomly deleted datasets among the three equations. Both variance components and heritability for the average DFI (ADFI) did not change because of the missing DFI proportion and Loess correction. In terms of rank correlation and information criteria, Loess correction improved the accuracy of EBV for ADFI compared to randomly deleted cases. These findings indicate that the Loess equation is useful for correcting missing DFI values for individual pigs and that the correction of missing DFI values could be effective for the estimation of breeding values and genetic improvement using EBV for feeding traits.

The Value of the C-Reactive Protein-to-Albumin Ratio is Useful for Predicting Survival of Patients with Child-Pugh Class A Undergoing Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: Although a recent study has shown that the C-reactive protein-to-albumin ratio (CAR) can predict the survival in patients with hepatocellular carcinoma (HCC), it is unclear whether CAR can predict the survival after surgery. OBJECTIVE: To investigate the utility of CAR for prediction of postoperative survival among HCC patients with Child-Pugh class A. METHODS: We retrospectively reviewed 239 patients with Child-Pugh class A who were newly diagnosed with HCC and received initial liver resection. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS), and their cutoff values were identified using receiver operating characteristic curve analyses. The cutoff value of CAR was 0.028. Kaplan-Meier analysis and the log-rank test were used for the comparison of OS and disease-free survival (DFS) between two CAR groups (>0.028/≤0.028). RESULTS: Multivariate analysis using 16 clinical characteristics selected by univariate analyses revealed that CAR (>0.028/≤0.028) (HR, 3.211; 95% CI 1.065-9.680; P = 0.038) was significantly associated with OS, as well as anatomical resection (presence/absence) (HR, 0.275; 95% CI 0.119-0.635; P = 0.275). A significant difference in OS and DFS was observed between patients with low CAR (≤0.028) and patients with high CAR (>0.028). CONCLUSIONS: CAR is a useful predictor of postoperative survival among HCC patients with Child-Pugh class A.

The preoperative globulin-to-albumin ratio, a novel inflammation-based prognostic system, predicts survival after potentially curative liver resection for patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Although the globulin-to-albumin ratio (GAR) is useful for prognostication of patients with various cancers, its relationship with hepatocellular carcinoma (HCC) remains unclear. The study aims to investigate the relationship between GAR and postoperative survival among patients with HCC undergoing potentially curative liver resection (LR). METHODS: We retrospectively reviewed 368 patients with newly diagnosed HCC who underwent initial and potentially curative LR. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with overall survival (OS). Kaplan-Meier analysis and log-rank test were used to compare OS and disease-free survival (DFS). RESULTS: The result of multivariate analysis using 25 clinical characteristics selected by univariate analysis revealed that the GAR (≥0.918/<0.918) was significantly associated with OS (hazard ratio [HR], 2.398; 95% confidence interval [CI], 1.012-5.683; P = 0.047), as well as platelet count (<14/≥14, ×104 /mm3 ) and portal vein invasion (presence/absence). Kaplan-Meier analysis and log-rank test demonstrated that the OS and DFS of patients with a high GAR (>0.918) were significantly worse than that of patients with a low GAR (≤0.918). CONCLUSIONS: The GAR is a useful predictor of postoperative survival among patients with HCC undergoing potentially curative LR.

Dual pharmacological inhibition of glutathione and thioredoxin systems synergizes to kill colorectal carcinoma stem cells.

NRF2 stabilizes redox potential through genes for glutathione and thioredoxin antioxidant systems. Whether blockade of glutathione and thioredoxin is useful in eliminating cancer stem cells remain unknown. We used xenografts derived from colorectal carcinoma patients to investigate the pharmacological inhibition of glutathione and thioredoxin systems. Higher expression of five glutathione S-transferase isoforms (GSTA1, A2, M4, O2, and P1) was observed in xenograft-derived spheroids than in fibroblasts. Piperlongumine (2.5-10 µmol/L) and auranofin (0.25-4 µmol/L) were used to inhibit glutathione S-transferase π and thioredoxin reductase, respectively. Piperlongumine or auranofin alone up-regulated the expression of NRF2 target genes, but not TP53 targets. While piperlongumine showed modest cancer-specific cell killing (IC50 difference between cancer spheroids and fibroblasts: P = 0.052), auranofin appeared more toxic to fibroblasts (IC50 difference between cancer spheroids and fibroblasts: P = 0.002). The synergism of dual inhibition was evaluated by determining the Combination Index, based on the number of surviving cells with combination treatments. Molar ratios indicated synergism in cancer spheroids, but not in fibroblasts: (auranofin:piperlongumine) = 2:5, 1:5, 1:10, and 1:20. Cancer-specific cell killing was achieved at the following drug concentrations (auranofin:piperlongumine): 0.25:2.5 µmol/L, 0.5:2.5 µmol/L, or 0.25:5 µmol/L. The dual inhibition successfully decreased CD44v9 surface presentation and delayed tumor emergence in nude mouse. However, a small subpopulation persistently survived and accumulated phosphorylated histone H2A. Such "persisters" still retained lesser but significant tumorigenicity. Thus, dual inhibition of glutathione S-transferase π and thioredoxin reductase could be a feasible option for decreasing the tumor mass and CD44v9-positive fraction by disrupting redox regulation.

Usefulness of intraoperative observation using a fluorescence imaging instrument for patients with nonocclusive mesenteric ischemia.

The authors evaluated the usefulness of intraoperative photodynamic eye (PDE) observation in patients with nonocclusive mesenteric ischemia (NOMI). Between February 2012 and July 2013, 6 patients who had undergone emergency surgery for NOMI were enrolled. Intraoperative PDE observation was performed to decide the adequate length of bowel resection including all skipped dark spots, which could not be detected as ongoing mucosal ischemic changes under visible light observation. All ongoing mucosal ischemic changes were easily detected as dark spots using PDE observation in all 6 patients. The mean length of adequate ileal resection (92 ± 48 cm) was significantly longer than that of ischemic ileum (85 ± 50 cm) (mean ± SD) (P = 0.043). After resection of an adequate length of bowel, all the patients had a good course until discharge without incidents due to residual bowel ischemia, except for 1patient who died. PDE observation is useful for deciding the adequate length of bowel to resect, including ongoing mucosal ischemic changes that cannot be detected under visible light observation. In patients with NOMI, resection of an adequate length of bowel is necessary to prevent postoperative incidents due to residual bowel ischemia.

Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas.

Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 µM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP(+) ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs.

Clinical significance of an inflammation-based prognostic system for gastric cancer patients with a preoperative normal serum level of carcinoembryonic antigen.

AIM: To investigate the significance of the Glasgow Prognostic Score (GPS) for predicting the postoperative survival of gastric cancer (GC) patients with a normal preoperative serum level of carcinoembryonic antigen (CEA). Because CEA is a useful marker for prognostication of several types of cancer, some patients with GC have a normal CEA level. On the other hand, the GPS has been established as a valuable inflammation-based prognostic system for cancer patients. PATIENTS AND METHODS: Among 650 patients who had undergone elective surgery for GC, 425 with a normal preoperative serum CEA level (≤5.0 ng/ml) were enrolled. Uni- and multivariate analyses were performed to evaluate the relationship of the GPS to overall survival. The Kaplan-Meier analysis and log rank test were used to compare the survival curves among patients with GPS 0, 1 and 2. RESULTS: Multivariate analysis using clinical characteristics selected from univariate analyses revealed that the GPS (0, 1/2) was associated with overall survival (hazard ratio=2.048; 95% C.I. (confidence interval)=1.002-4.185; p=0.049) along with age (≤70/>70) (years), sex, tumor type (3, 4, 5/0, 1, 2), lymph node metastasis (presence/absence) and platelet count (≤35/>35) (×10(4)/mm(3)). The Kaplan-Meier analysis and log rank test demonstrated that there were significant differences in overall survival among patients with GPS 0, 1 and 2 (p<0.001). CONCLUSION: Even if GC patients have a normal serum level of CEA, the GPS is able to predict their postoperative survival and classify such patients into three independent groups before surgery.

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

AIM: To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). PATIENTS AND METHODS: One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. RESULTS: Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). CONCLUSION: PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery.