Antitumor Effect of 5-Aminolevulinic Acid Through Ferroptosis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Due to its tumor-specific metabolic pathway characteristics, 5-aminolevulinic acid (5-ALA) is a natural amino acid widely used in cancer treatment. The current study, demonstrated that 5-ALA induced ferroptosis via glutathione peroxidase 4 (GPX4) and heme oxygenase 1 (HMOX1) and had an antitumor effect in esophageal squamous cell carcinoma (ESCC). METHODS: Expression of GPX4 and HMOX1 in pathologic specimens of 97 ESCC patients was examined, and prognostic analyses were performed. Real-time polymerase chain reaction (RT-PCR), RNA microarray, and Western blotting analyses were used to evaluate the role of 5-ALA in ferroptosis in vitro. In addition, this study used ferrostatin-1, a ferroptosis inhibitor, and a lipid peroxidation reagent against cell lines treated with 5-ALA. Finally, the role of 5-ALA was confirmed by its effect on an ESCC subcutaneous xenograft mouse model. RESULTS: The study showed that upregulation of GPX4 and downregulation of HMOX1 were poor prognostic factors in ESCC. In an RNA microarray analysis of KYSE30, ferroptosis was one of the most frequently induced pathways, with GPX4 suppressed and HMOX1 overexpressed by 5-ALA treatment. These findings were verified by RT-PCR and Western blotting. Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. In vivo, 5-ALA suppressed GPX4 and overexpressed HMOX1 in tumor tissues and led to a reduction in tumor size. CONCLUSIONS: Modulation of GPX4 and HMOX1 by 5-ALA induced ferroptosis in ESCC. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.

The prognostic significance of combined geriatric nutritional risk index and psoas muscle volume in older patients with pancreatic cancer.

BACKGROUND: The geriatric nutritional risk index (GNRI), originally developed as a nutritional assessment tool to evaluate mortality and morbidity in older hospitalized patients (i.e., those aged ≥65 years), is regarded as a prognostic factor in several cancers. Body composition is also an important consideration when predicting the prognosis of patients with cancer. This study aimed to investigate the relationship between the GNRI and psoas muscle volume (PMV) for survival outcomes in patients with pancreatic cancer. METHODS: This retrospective study evaluated the prognostic significance of the GNRI and PMV in 105 consecutive patients aged ≥65 years who underwent pancreatectomy for histologically confirmed pancreatic cancer. The patients were divided into high (GNRI > 98) and low GNRI groups (GNRI ≤98), and into high (PMV > 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) and low PMV (PMV ≤ 61.5 mm3/m3 for men and 44.1 mm3/m3 for women) groups. RESULTS: Both the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly greater among patients in the high GNRI group than among patients in the low GNRI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high PMV group than among patients in the low PMV group. Patients were stratified into three groups: those with both high GNRI and high PMV; those with either high GNRI or high PMV (but not both); and those with both low GNRI and low PMV. Patients with both low GNRI and low PMV had a worse 5-year OS rate, compared with patients in other groups (P <  0.001). The C-index of the combination of the GNRI and PMV for predicting 5-year OS was greater than the C-indices of either the GNRI or PMV alone. Multivariate analysis revealed that the combination of the GNRI and PMV was an independent prognostic factor in patients aged ≥65 years with pancreatic cancer (P = 0.003). CONCLUSIONS: The combination of the GNRI and PMV might be useful to predict prognosis in patients aged ≥65 years with pancreatic cancer.

Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer.

BACKGROUND: Decreased mean platelet volume (MPV) predicts poor prognosis in some cancers. However, its significance as a prognostic indicator in pancreatic cancer (PC) remains unclear. METHODS: A total of 91 PC patients who underwent pancreatectomy were included in this study. MPV and serum carbohydrate antigen 19-9 (CA19-9) were measured within 1 week before surgery. RESULTS: We divided patients into MPVhigh (≥ 8.65; n = 40), MPVlow (< 8.65; n = 51), CA19-9high (≥ 66.3; n = 47), and CA19-9low (< 66.3; n = 44) groups based on the optimal cut-off values determined from receiver operating characteristic curve analysis. The 5-year overall survival (OS) rates were significantly lower in the MPVlow than in the MPVhigh group (16.9% and 56.3%, respectively; P = 0.0038), and the 5-year disease-specific survival (DSS) rates in the MPVlow group and MPVhigh group were 20.5% and 62.2%, respectively (P = 0.0031). Multivariate analysis identified MPV as an independent prognostic indicator for both OS and DSS. The patients were then divided into groups A (MPVhigh and CA19-9low), B (MPVhigh and CA19-9high), C (MPVlow and CA19-9low), and D (MPVlow and CA19-9high), with 5-year OS rates of 73.2%, 40.4%, 25.8%, and 10.3%, respectively (P = 0.0002), and 5-year DSS rates of 80.8%, 44.9%, 27.3%, and 16.4%, respectively (P = 0.0003). CONCLUSIONS: Classification based on MPV and CA19-9 might be useful for predicting long-term outcomes in patients with PC.

Appraisal of long-time outcomes after curative surgery in elderly patients with gastric cancer: a propensity score matching analysis.

BACKGROUND: This study was conducted to assess the long-term outcomes of elderly patients among propensity-score-matched gastric cancer patients after curative gastrectomy and to propose the proper management of elderly gastric cancer patients. METHODS: We enrolled 626 patients with gastric cancer who underwent curative gastrectomy at our institution between January 2004 and December 2015. To minimize selection bias among 2 groups, propensity score matching was performed. RESULTS: Patients were divided into an elderly group over 75 years old (EP group; n = 186) and a non-elderly group (NEP group; n = 440). After propensity score matching, patients were divided into EP group (n = 178) and NEP group (n = 175). Five-year overall survival was significantly lower in the EP group than in the NEP group, consistent with a subgroup analysis of each stage. However, the 5-year disease-specific survival among all enrolled patients and those with stage I and II disease did not differ significantly. Moreover, in the subgroup of stage III patients, 5 year disease-specific survival was significantly lower in the EP group (23.0%) than in the NEP group (59.4%; P = 0.004). Because elderly patients with stage III disease had an extremely poor prognosis, we decided to compare the two groups with stage III. The EP group contained significantly fewer patients with D2 lymphadectomy (P = 0.002) and adjuvant chemotherapy (P < 0.001) than the NEP group. C-reactive protein to albumin ratio was significantly higher in patients in the EP group than in the NEP group (P = 0.046), and the prognostic nutritional index was significantly lower in patients in the EP group than in the NEP group (P = 0.045).　Multivariate analysis revealed that the prognostic nutritional index and lymphatic invasion were independent prognostic factors. CONCLUSIONS: Elderly gastric cancer patients with stage III disease showed poorer disease-specific survival compared with non-elderly patients, which may be due to a poorer nutritional and inflammatory background, fewer D2 lymphadenectomies, and a lack of adjuvant chemotherapy. The safe induction of standard lymphadenectomy and adjuvant chemotherapy with perioperative aggressive nutritional support may improve the prognosis of elderly gastric cancer patients with stage III disease.

Estimation of Physiological Ability and Surgical Stress Score Is a Useful Prognostic Indicator for Elderly Patients with Colorectal Cancer.

BACKGROUND: The incidence of colorectal cancer (CRC) among the elderly has been increasing. Therefore, determining postoperative prognosis factors in elderly CRC patients has clinical importance. This study retrospectively investigated the prognostic significance of the estimation of physiological ability and surgical stress (E-PASS) in elderly CRC patients. METHODS: This study enrolled 166 elderly patients aged 75 or more with a histopathological diagnosis of colorectal adenocarcinoma who underwent curative surgery. RESULTS: According to the results of receiver operating characteristic analysis, the patients were divided into the following 2 groups based on the comprehensive risk score (CRS): CRS of ≥0.05 (CRSHigh) and CRS of < 0.05 (CRSLow). The 5-year overall survival rates of CRSHigh group and CRSLow group were 51.1 and 89.6%, respectively, and the difference was statistically significant (p < 0.001). Furthermore, 5-year disease-specific survival rates of CRSHigh group and CRSLow group were 81.4 and 96.3%, respectively, and the difference was statistically significant (p = 0.017). Also, multivariate analysis indicated that CRS was an independent prognostic indicator in elderly CRC patients. With regard to the cause of death, both recurrence and cancer-unrelated deaths were observed significantly more in the CRSHigh group than in the CRSLow group. CONCLUSIONS: E-PASS was a useful prognostic indicator in elderly CRC patients.

Disinfection with single or double usage of new antiseptic olanexidine gluconate in general surgery: a randomized study.

PURPOSE: Olanexidine gluconate is a newly developed solution for skin disinfection that was recently approved in Japan. We aimed to compare single and double application of the solution in preventing surgical site infection (SSI) in patients undergoing general surgery. METHODS: This randomized study was conducted at the Tottori University Hospital. Patients scheduled to undergo gastrointestinal or hernia surgery were randomly assigned to one of two groups using either one or two Olanedine applicators for skin disinfection. The primary endpoint was the difference in SSI incidence between the two groups. The secondary endpoint was all adverse events related to olanexidine gluconate. RESULTS: A total of 393 patients qualified for the study protocol: 193 received a single application, and 200 received a double application of Olanedine. SSI occurred in 10 patients (2.5%) overall; nine were superficial incisional SSIs, and one patient had a deep incisional SSI. Of the 10 patients who developed SSI, six (3.1%) were in the group receiving a single application, and four (2.0%) were in the group receiving a double application; there was no statistically significant difference between the two groups (P = 0.537). Allergic reactions or skin disorders related to olanexidine gluconate were not observed. CONCLUSION: There was no difference in the SSI incidence between the use of one or two Olanedine applicators for skin preparation in elective general surgery. Therefore, a single application of Olanedine is sufficient and is recommended for general surgery as a standard disinfection precaution. TRIAL REGISTRATION NUMBER: UMIN000027319; 5/12/2017.

Sarcopenia as a prognostic factor in patients with recurrent pancreatic cancer: a retrospective study.

BACKGROUND: Sarcopenia is a prognostic factor in various cancers. However, the impact of sarcopenia in patients with recurrent pancreatic cancer remains unclear. This study evaluated the prognostic significance of sarcopenia in patients with recurrent pancreatic cancer. METHODS: Seventy-four patients who developed postoperative recurrence of pancreatic cancer after undergoing pancreatectomies were enrolled. Sarcopenia in these patients was defined according to the psoas muscle index (PMI) measured via computed tomography at the third vertebra. RESULTS: The mean PMIs at the time of recurrence were 4.47 ± 1.27 cm2/m2 for men and 3.26 ± 0.70 cm2/m2 for women. Of the 74 patients, 65 (87.8%) were diagnosed with sarcopenia with low PMI. The 2-year post-recurrence survival curve in the sarcopenia group was significantly worse than that in the non-sarcopenia group (P = 0.034). Multivariate analysis revealed that sarcopenia at the time of recurrence was an independent prognostic factor (P = 0.043) along with a high neutrophil-to-lymphocyte ratio (P = 0.004), early recurrence (P = 0.001), and chemotherapy after recurrence (P = 0.005) in patients with recurrent pancreatic cancer. Furthermore, the area under the curve (AUC) of the combination of sarcopenia and time to recurrence for predicting 2-year survival was 0.763, which was much higher than that of sarcopenia alone (AUC = 0.622). CONCLUSIONS: Sarcopenia is a useful prognostic factor in patients with recurrent pancreatic cancer. The combination of sarcopenia and time of recurrence may more accurately predict post-recurrence survival than can sarcopenia alone.

Prognostic significance of platelet × C-reactive protein multiplier in patients with esophageal squamous cell carcinoma.

PURPOSE: The prognostic significance of the peripheral platelet count × serum C-reactive protein level multiplier (P-CRP) has not been widely studied in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed data from 116 thoracic ESCC patients who underwent curative esophagectomy. RESULTS: The patients were divided into the P-CRPHigh ( > 1.674) and P-CRPLow ( ≤ 1.674) groups, according to a cut-off value determined by a receiver operator curve. The 5-year overall survival (OS) rates significantly differed between the groups (P-CRPHigh: 46.4% and P-CRPLow: 77.3%; P = 0.0056). In the multivariate analysis, the P-CRP was an independent prognostic factor. We also evaluated the survival in the subgroup of patients who received neoadjuvant chemotherapy (NAC; n = 49). Among 28 patients who were P-CRPHigh before NAC, 20 remained. P-CRPHigh after NAC, while eight became post-P-CRPLow. Among 21 patients who were P-CRPLow before NAC, 16 remained post-P-CRPLow after NAC, while five became post-P-CRPHigh. The 5-year OS rate for patients who were P-CRPLow both before and after NAC was 92.9%, compared with 30.2% in other patients (P = 0.0034). In the multivariate analysis, the combination of P-CRP + post-P-CRP was an independent prognostic factor in ESCC patients who underwent NAC. CONCLUSIONS: The P-CRP is useful for predicting the prognosis in ESCC patients.

The postoperative platelet distribution width is useful for predicting the prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: The platelet distribution width (PDW) is reportedly useful as a prognostic indicator for some cancers. However, its prognostic significance in esophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We enrolled 104 patients with thoracic ESCC, who underwent curative esophagectomy. RESULTS: Receiver operating curve analyses indicated that the optimal cut-off values of pre- and postoperative PDW were 16.9 and 17.0, respectively. The 5-year overall survival (OS) rate was significantly lower in patients with a high-preoperative PDW (≥ 16.9; 52.6%) than in those with a low-preoperative PDW (< 16.9; 61.0% P = 0.045). The 5-year disease-specific survival (DSS) rates were 64.3% in patients with a high-preoperative PDW and 69.3% in those with a low-preoperative PDW (P = 0.13). Regarding the postoperative PDW, the 5-year OS rate was significantly lower in patients with a high-postoperative PDW (≥ 17.0; 35.7%) than in those with a low-postoperative PDW (< 17.0; 66.8% P = 0.0017). The 5-year DSS rates were 52.2% in patients with a high-postoperative PDW and 73.2% in those with a low-postoperative PDW (P = 0.037). Finally, a multivariate analysis revealed that the postoperative PDW but not the preoperative PDW was an independent prognostic factor. CONCLUSIONS: The postoperative PDW was useful for predicting the prognosis of patients with ESCC.

Combined prognostic nutritional index ratio and serum amylase level during the early postoperative period predicts pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to investigate the usefulness of the range of change in prognostic nutritional index (PNI) during the early postoperative period as a predictor of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. METHODS: Data were retrospectively analyzed for 192 patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were used to evaluate perioperative variables. PNIP3-Pre ratio represented the range of change in PNI from before surgery to postoperative day (POD) 3, PNIP1-Pre ratio represented the range of change in PNI from before surgery to POD 1, and PNIP3-P1 ratio represented the range of change in PNI from POD 1 to POD 3. RESULTS: The area under the curve (AUC) for PNIP3-P1 for prediction of POPF following pancreaticoduodenectomy was 0.683 (P <  0.001), which was highest among PNI ratios and higher than PNI on POD 3. The AUC for serum amylase level on POD 1 was 0.704 (P <  0.001), which was superior to the corresponding AUC on POD 3. The AUC for the combination of PNIP3-P1 ratio and serum amylase level on POD 1 for prediction of POPF was higher than the AUC of either indicator alone (0.743, P <  0.001). The combination of PNIP3-P1 ratio and serum amylase level on POD 1 was an independent predictor of POPF following pancreaticoduodenectomy (P = 0.018). CONCLUSIONS: The combination of the range of change in PNI from POD 1 to POD 3 and serum amylase levels on POD 1 may be useful for prediction of POPF following pancreaticoduodenectomy.

NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44.

CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the NEAT1 gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner.

[A Case of Solitary Metastasis to the Small Intestine with Lymph Node Metastasis after Surgery in Rectal Cancer].

The patient was a 63-year-old man. He underwent laparoscopic anterior resection of a rectal cancer when he was 60 years. The tumor was diagnosed as T3N0M0, Stage Ⅱ, and he was followed up without adjuvant chemotherapy. Two years and 9 months after surgery, anemia and increased levels of tumor markers were observed. CT scan revealed a mass in the mesentery. We suspected rectal cancer recurrence and performed partial resection of the jejunum with regional lymph node dissection. As the tumor appearance and histological findings were similar to those of the previous rectal cancer, the tumor was diagnosed as hematogenous metastasis of rectal cancer with lymph nodes metastasis. The hematogenous metastasis of rectal cancer to the small intestine is rare; however, it may cause metastasis to regional lymph nodes. Therefore, lymph node dissection may be necessaryin surgical interventions for metastatic tumors of the small intestine.

Bacterial smear test of drainage fluid after pancreaticoduodenectomy can predict postoperative pancreatic fistula.

OBJECTIVES: It is widely accepted that postoperative pancreatic fistula (POPF) accompanied by bacterial infection results in a worse outcome than POPF alone. However, few studies evaluating predictive indicators of POPF have focused on bacterial infection. METHODS: A consecutive 100 patients who underwent pancreaticoduodenectomy at our institute for periampullary disease were enrolled. POPF was assessed according to the International Study Group of Pancreatic Fistula consensus guidelines; grades B and C were defined as clinically relevant POPF (CR-POPF). The patients' characteristics, perioperative surgical factors, and laboratory data including the results of culture and smear testing performed using drainage fluid on postoperative days (PODs) 1 and 3 were analyzed. RESULTS: The overall incidence of CR-POPF was 25%. Univariate analyses revealed that the factors associated with CR-POPF were male sex, soft pancreas, MPD diameter, higher serum C-reactive protein concentration and white blood cell count on POD 3, higher amylase concentration in drainage fluid, and culture and/or smear positivity of drainage fluid. Multivariate analysis newly revealed that the smear positivity of drainage fluid on POD 3 was the independent risk factors for CR-POPF (p = 0.027). CONCLUSIONS: Smear positivity of drainage fluid on POD 3 after pancreaticoduodenectomy may be a new predictor of CR-POPF.

A prognostic index for colorectal cancer based on preoperative absolute lymphocyte, monocyte, and neutrophil counts.

PURPOSE: Associations between the preoperative absolute neutrophil count (NC), lymphocyte count (LC), and monocyte count (MC) in the peripheral blood and the prognosis of colorectal cancer (CRC) patients have not been widely studied. METHODS: We enrolled 361 patients who underwent surgery for CRC between January 2007 and December 2013 to analyze correlations among the LC, MC, and NC and prognosis. RESULTS: Based on cut-off values determined by a receiver operating characteristic analysis, patients were subgrouped as LymphHigh or LymphLow (cut-off: LC = 1460 cells/µL); as MonoHigh or MonoLow (cut-off: MC = 421 cells/µL); and as NeutHigh or NeutLow (cut-off: NC = 3247 cells/µL). Patients were then given lymphocyte-monocyte-neutrophil (LMN) scores by adding the points of their different subgroups (1 point each for LymphLow, MonoHigh and NeutHigh; 0 points for LymphHigh, MonoLow and NeutLow). The 5-year overall survival rates significantly differed by the LMN score (0: 89.7%, 1: 80.6%, 2: 68.8%, and 3: 57.4%; P < 0.0001). In the multivariate analysis, the LMN score was found to be an independent prognostic indicator. CONCLUSIONS: The combination of the preoperative absolute number of lymphocytes, monocytes, and neutrophils is a useful prognostic indicator in CRC patients.

Impact of postoperative mean arterial pressure on the incidence of postoperative complications after hepatic resection for primary liver malignancy.

PURPOSE: We conducted this study to evaluate the impact of the postoperative mean arterial pressure (MAP) on surgical complications after hepatic resection. METHODS: The subjects of this study were 199 patients who underwent hepatic resection for primary liver malignancy between 2004 and 2013. A clinically relevant postoperative complication was defined as a Clavien-Dindo grade ≥ III complication. RESULTS: Based on an MAP cut-off value of 81.1 mmHg, the patients were grouped as follows: low MAP on both postoperative days (PODs) 1 and 2 (continuously low MAP), normal MAP on both PODs 1 and 2 (normal MAP), and others (transiently low MAP). The continuously low MAP group had the highest incidence of complications and the normal MAP group had the lowest incidence of complications compared with the expected incidence for this cohort (p < 0.01 and p = 0.01, respectively). Multivariate analysis revealed that both a continuously and transiently low MAP were independent predictors of postoperative complications (p = 0.03 and p < 0.01, respectively). Among the subtypes of complications, a low MAP had a significant relationship with ascites/pleural effusion and respiratory complications (p < 0.01 and p = 0.03, respectively). CONCLUSIONS: A low MAP on POD 1 and/or 2 is an independent predictor of postoperative complications.

Combined preoperative platelet-to-lymphocyte ratio and serum carbohydrate antigen 19-9 level as a prognostic factor in patients with resected pancreatic cancer.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the most frequently used tumor marker and serves as a prognostic indicator in patients with pancreatic cancer (PC). The platelet-to-lymphocyte ratio (PLR) is thought to be an inflammation-related serum marker. An elevated PLR represents increased inflammatory status and is associated with poor prognosis in patients with various cancers including PC. METHODS: This study involved 103 patients with a histopathological diagnosis of pancreatic ductal adenocarcinoma who underwent pancreatectomy. The patients were assessed to determine the prognostic significance of the combination of the PLR and CA19-9 level. RESULTS: Based on the receiver operating characteristic analysis results, the patients were divided into PLRHigh (PLR ≥ 129.1) and PLRLow (PLR < 129.1) groups and into CA19-9High (CA19-9 ≥ 74.0 U/mL) and CA19-9Low (CA19-9 < 74.0 U/mL) groups. The cumulative 5-year overall survival (OS) and disease-specific survival (DSS) rates significantly differed by both the PLR (PLRHigh group: 19.5% and 22.9%; PLRLow group: 39.1% and 45.9%) and CA19-9 (CA19-9High group: 19.1% and 25.6%; CA19-9Low group: 41.0% and 41.0%). We then divided the patients into Groups A (PLRLow/CA19-9Low), B (PLRLow/CA19-9High or PLRHigh/CA19-9Low), and C (PLRHigh/CA19-9High). The cumulative 5-year OS rates in Groups A, B, and C were 44.0%, 31.9%, and 11.9%, respectively (P = 0.002). The cumulative 5-year DSS rates in Groups A, B, and C were 47.7%, 36.4%, and 16.8%, respectively (P = 0.002). Multivariate analysis revealed that the combination of the PLR and CA19-9 was an independent prognostic factor in patients with resected PC. CONCLUSIONS: The combination of the PLR and CA19-9 is useful for predicting the prognosis of patients with resected PC.

HBx and c-MYC Cooperate to Induce URI1 Expression in HBV-Related Hepatocellular Carcinoma.

Unconventional prefoldin RNA polymerase II subunit 5 interactor (URI1) has emerged as an oncogenic driver in hepatocellular carcinoma (HCC). Although the hepatitis B virus (HBV) represents the most common etiology of HCC worldwide, it is unknown whether URI1 plays a role in HBV-related HCC (HCC-B). In the present study, we investigated URI1 expression and its underlying mechanism in HCC-B tissues and cell lines. URI1 gene-promoter activity was determined by a luciferase assay. Human HCC-B samples were used for a chromatin immunoprecipitation assay. We found that c-MYC induced URI1 expression and activated the URI1 promoter through the E-box in the promoter region while the HBx protein significantly enhanced it. The positivity of URI1 expression was significantly higher in HCC-B tumor tissues than in non-HBV-related HCC tumor tissues, suggesting that a specific mechanism underlies URI1 expression in HCC-B. In tumor tissues from HCC-B patients, a significantly higher level of c-MYC was recruited to the E-box than in non-tumor tissues. These results suggest that HBx and c-MYC are involved in URI1 expression in HCC-B. URI1 expression may play important roles in the development and progression of HCC-B because HBx and c-MYC are well-known oncogenic factors in the virus and host, respectively.

The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy.

PURPOSE: Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management. METHODS: Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HUmin, HUmax, and HUmean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HUSD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria. RESULTS: The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HUSD (odds ratio 3.092; 95% CI 1.018-9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001-1.00022) as significant risk factors for PF. CONCLUSIONS: The HUSD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients.

PURPOSE: Inflammation is closely related to cancer development and progression. This retrospective study investigated the prognostic value of the combination of pre- and postoperative C-reactive protein (CRP) levels in patients with colorectal cancer (CRC). METHODS: The subjects of this study were 406 patients who underwent surgery for CRC. RESULTS: Based on receiver-operating characteristic analysis, patients were divided into the following groups: those with a preoperative CRP of ≥ 0.5 mg/dL (pre-CRPHigh), those with a preoperative CRP of < 0.5 mg/dL (pre-CRPLow), those with a postoperative CRP of ≥ 17.0 mg/dL (post-CRPHigh), and those with a postoperative CRP of < 17.0 mg/dL (post-CRPLow). They were then allocated to one of the following three groups: Group A, comprised of those in the pre-CRPHigh and post-CRPHigh groups; Group B, comprised of those in either the pre-CRPHigh and post-CRPLow or pre-CRPLow and post-CRPHigh groups; and Group C, comprised of those in the pre-CRPLow and post-CRPLow groups. The disease-specific 5-year survival rates were 53.8%, 72.8%, and 87.2% in Groups A, B, and C, respectively, and these differences were significant. Finally, multivariate analysis revealed that the combination of pre- and postoperative CRP levels was an independent prognostic indicator. CONCLUSIONS: The combination of pre- and postoperative CRP was predictive of the prognosis of CRC patients.

Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma.

BACKGROUND: Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma (HCC). METHODS: We included 145 HCC patients who underwent initial and curative resection between January 2004 and December 2013. Postoperative complications of grade III or higher based on Clavien-Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase recurrence. RESULTS: Thirty-eight patients (26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration (P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications (P = 0.015). Early-phase recurrence was observed in 20/38 (53%) patients who suffered postoperative complications and 36/107 (34%) patients with no complications, which was statistically significant (P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level (P = 0.042), multiple tumors (P < 0.001), poor differentiation (P = 0.036) and presence of postoperative complication (P = 0.039). CONCLUSIONS: Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC.