Randomized multicenter phase II trial of prophylactic irradiation of para-aortic lymph nodes in advanced cervical cancer according to tumor hypoxia: Korean Radiation Oncology Group (KROG 07-01) study.

We conducted a prospective phase II study on whether extended-field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA-seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5-year para-aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease-free survival (DFS; 78% vs 70%, P = .066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)-only positive, CA9/hypoxia-inducible factor (HIF) double positive and CA9 negative. In the CA9-only positive, EFI successfully increased 5-year PARFS (100% vs 76.4%, P = .010), resulting in significantly improved long-term DFS (85.7% vs 54.7%, P = .023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA-seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = -.37, P < .01), which showed a higher 5-year DFS than the immunelow (P = .032). Hypoxia-related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P < .05). Only 17.4% of patients in CA9-negative group showed immunelow signatures, while 40.0% of patients in the double-positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9-only positive LAUCC, and not in CA9/HIFs double-positive subgroup. RNA-seq analysis suggested that hypoxia-induced immunosuppression may be related to treatment resistance in LAUCC.

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

Analysis of chemical constituents in the extract and rat serum from the chloroform extract of Oxytropis falcata Bunge by HPLC-MS.

Analysis of the constituents of the chloroform extract of Oxytropis falcata Bunge (CEOF), a traditional Tibetan medicine, in rat's serum after oral administration, has been performed by HPLC-MS. We have identified 10 compounds in CEOF and 11 bioactive ingredients from rat's serum after given CEOF. Six bioactive ingredients from rat's serum are matched with original form of the compounds of CEOF. Other five bioactive ingredients were seemed to be respectively metabolites. HPLC-MS is rapid, sensitive method and suitable for identification of bioactive components absorbed into blood of CEOF providing information for further research of pharmacological mechanism.

Loss of zinc-finger protein 143 contributes to tumour progression by interleukin-8-CXCR axis in colon cancer.

Several studies have shown that expression of zinc-finger protein 143 (ZNF143) is closely related to tumour progression including colon cancer. However, it remains unclear how ZNF143 expression is related to tumour progression within the tumour microenvironment. Here, we investigated whether ZNF143 expression affects the tumour microenvironment and tumour progression by screening molecules secreted by colon cancer cells stably expressing short-hairpin RNAs against ZNF143 or control RNAs. We observed that secretion of interleukin (IL)-8 was increased when ZNF143 expression was reduced in two colon cancer cell lines. The mRNA and protein levels of IL-8 were increased in cells following ZNF143 knockdown, and this effect was reversed when ZNF143 expression was restored. The Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) and extracellular signal-regulated kinase pathways were also shown to contribute to IL-8 expression in ZNF143-knockdown cells. The expression levels of ZNF143 and IL-8 were inversely correlated with three-dimensionally grown spheroids and colon cancer tissues. THP-1 cells were differentiated when cells were incubated with condition media from colon cancer cell with less ZNF143, drastically. Loss of ZNF143 may contribute to the development of colon cancer by regulating intracellular and intercellular signalling for cell plasticity and the tumour microenvironment respectively.

Cytopathological results of initial endoscopic ultrasound-guided fine needle aspiration for primary mass and prognosis in pancreatic cancer patients.

OBJECTIVES: Clinical outcomes remain unclear in patients suspected of having pancreatic cancer with indeterminate endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) results. This work aimed to investigate the prognosis of pancreatic cancer patients with indeterminate findings at initial EUS-FNA. METHODS: Findings in all patients who underwent EUS-FNA for suspected pancreatic cancer between 2008 and 2015 at the National Cancer Center, Korea, were retrospectively reviewed. A final diagnosis of pancreatic ductal adenocarcinoma was based on pathology reports. RESULTS: Of the 144 patients evaluated, 113 (78%) were diagnosed as being positive/suspicious for malignancy on cytological evaluation and 31 (22%) as having atypia/negative/non-diagnostic findings at initial EUS-FNA but subsequently diagnosed with pancreatic ductal adenocarcinoma. Tumour size, clinical stage and treatment modalities did not differ significantly between these two groups. Median overall survival was significantly shorter in patients diagnosed (11.3 ± 0.74 months; 95% confidence interval [CI], 9.4-12.8 months) than non-diagnosed (16.9 ± 2.34 months; 95% CI, 12.0-17.4 months) on initial EUS-FNA (P = .024). Multivariate Cox regression analysis showed that a non-diagnosis on initial EUS-FNA was independently associated with better overall survival (hazard ratio, 0.58; 95% CI, 0.38-0.88; P = .011). CONCLUSIONS: Non-diagnostic results on initial EUS-FNA of a primary mass may be associated with better prognosis in patients with pancreatic cancer.

Alpha-lipoic acid reduces retinal cell death in diabetic mice.

Oxidative stress plays an important role in the development of diabetic retinopathy. Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice. The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes. We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death. Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose. Moreover, α-LA lowered the levels of O-linked ß-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells. Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells. Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas. Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.

Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial.

BACKGROUND: Weight loss in pancreatic cancer is associated with maldigestion due to pancreatic duct obstruction. Pancreatic exocrine replacement therapy (PERT) may significantly improve fat and protein absorption. OBJECTIVES: This prospective, double-blind, randomized, placebo-controlled phase II trial assessed whether PERT could reduce or prevent weight loss in patients with unresectable pancreatic cancer. METHODS: Sixty seven patients with unresectable pancreatic cancer were randomized to receive enteric coated PERT, consisting of 6-9 capsules of pancreatin (457.7 mg/capsule), or placebo. Patients took two capsules each three times daily during main meals and one capsule each up to three times daily when having between-meal snacks. The primary endpoint was the percentage change in body weight at eight weeks. RESULTS: The mean percentage change in body weight (1.49% [1.12 kg] vs. 2.99% [1.63 kg], P = 0.381) and the mean percent change in Patient-Generated Subjective Global Assessment (PG-SGA) score (8.85% vs. 15.69%, p = 0.18) did not differ significantly between the PERT and placebo groups. There was no improvement in quality of life and overall survival did not differ significantly between the PERT and placebo groups (5.84 months vs 8.13 months, p = 0.744). CONCLUSIONS: PERT did not reduce weight loss in patients with unresectable pancreatic cancer. Larger randomized trials are needed to identify those patients who may benefit from PERT. TRIAL REGISTRATION: ClinicalTrials.gov Number NCT01587534.

Cytidine Deaminase as a Molecular Predictor of Gemcitabine Response in Patients with Biliary Tract Cancer.

OBJECTIVE: Gemcitabine-based chemotherapy is regarded as the standard treatment for biliary tract cancer (BTC). Potential biomarkers for gemcitabine response include the activities of cytidine deaminase (CDA), human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (DCK), and ribonucleotide reductase M1 (RRM1). Here, we investigated whether single nucleotide polymorphisms (SNPs) in their encoding genes were associated with the efficacy of gemcitabine chemotherapy in treating BTC. METHODS: We retrospectively evaluated 11 SNPs in the CDA, hENT1, DCK, human concentrative nucleoside transporter 3 (hCNT3), and RRM1 genes in 80 patients with unresectable, metastatic, or recurrent BTC who were treated with gemcitabine plus cisplatin. RESULTS: After the results were adjusted for clinical predictors, the variant allele of rs1048977 in the CDA gene was associated with tumor response in a dominant model (OR, 0.23; 95% CI, 0.06-0.93; p = 0.039). No significant association was detected between the 11 SNPs and grade 3/4 toxicity. CONCLUSIONS: Our findings suggest that the polymorphism of CDA may be a potential predictive marker for the efficacy of gemcitabine-based chemotherapy in patients with BTC.

The prevalence and outcomes of pT0 disease after neoadjuvant hormonal therapy and radical prostatectomy in high-risk prostate cancer.

BACKGROUND: To identify the prevalence and clinical outcomes of pT0 disease following neoadjuvant hormonal therapy (NHT) and radical prostatectomy (RP) in high-risk prostate cancer. METHODS: We retrospectively included 111 patients who had received NHT and RP for the treatment of high-risk prostate cancer. We classified the patients into two groups, the pT0 group and the non-pT0 group, depending on whether a residual tumor was observed. RESULTS: We identified 6 cases (5.4%) with pT0 disease after reviewing the slides of all patients. There was no recurrence of disease in the pT0 group during a median follow-up of 59 months. Among the 105 patients in the non-pT0 group, biochemical recurrence (BCR) developed in 60 patients (57.1%), with the median time to BCR being 14 months. CONCLUSIONS: Among the 111 patients with high-risk prostate cancer, we found 6 cases that showed a complete pathological response after NHT and no recurrence of disease during the follow-up, meaning that the androgen deprivation therapy could potentially eradicate high-risk prostate cancer. This is one of the largest studies demonstrating the prevalence of pT0 disease and its outcomes after NHT among patients with high-risk prostate cancer.

Aralia elata prevents neuronal death by downregulating tonicity response element binding protein in diabetic retinopathy.

BACKGROUND/AIMS: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. CONCLUSIONS: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.

Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in a hepatitis B virus-endemic area.

BACKGROUND AND AIMS: To evaluate the clinical outcomes of patients with hepatocellular carcinoma (HCC) and compare the findings with that of a previous cohort. METHODS: Overall, 1972 HCC patients diagnosed and treated at the National Cancer Center, Korea between 2004 and 2009 were enrolled. The data of this cohort were compared with those of a previous cohort (2000-2003) from the same institution. RESULTS: In all (mean age, 56.4 years; 1642 men), 74.6% was hepatitis B virus (HBV) positive, 81.6% were Child-Pugh (CP) class A, and 64.4% was Barcelona Clinic Liver Cancer (BCLC) stage C. The modified Union for International Cancer Control (mUICC) stage I, II, III, IVa, and IVb was found in 8.9%, 29.6%, 24.8%, 23.1%, and 13.6% patients, respectively. The most common initial treatment was transarterial chemotherapy (58.3%), followed by resection (18.6%). The 5-year survival rate of BCLC stage 0, A, B, and C were 79.6%, 67.2%, 33.9%, and 17.1%, respectively. The performance status, BCLC stage, mUICC stage, CP class, model for end-stage liver disease score, tumor characteristics, portal vein tumor invasion, and serum alpha-fetoprotein level proved to be independent prognostic variables. Overall survival in the present cohort was better than that in the previous cohort (hazard ratio, 0.829; 95% confidence interval, 0.754-0.912), especially for advanced HCC patients with HBV-positive status. CONCLUSIONS: This cohort study provides valuable insights into the characteristics of HCC in Korean patients. Our findings may help develop clinical trials, treatment strategies, and prognosis systems for HCC patients in HBV-endemic areas.

Clinicopathological features and prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgery.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancer consisting of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of the rarity of this tumor, its feature is poorly understood. The present study aimed to evaluate the clinicopathological features and long-term prognosis of patients with cHCC-CC after surgery and to compare with those of the patients with stage-matched HCC and CC. METHODS: The clinicopathological features of the patients who underwent surgery for cHCC-CC at our center during the period of 2001-2010 were retrospectively analyzed and compared with those of stage-matched HCC and CC patients. Cancer staging was performed according to the AJCC Cancer Staging Manual (6th ed.). Overall survival and disease-free survival were compared among the groups and prognostic factors of cHCC-CC were evaluated. RESULTS: Significant differences were observed in clinicopathological features among 42 patients with cHCC-CC, 90 patients with HCC and 45 patients with CC. Similar to HCC patients, cHCC-CC patients had frequent hepatitis B virus antigen positivity, microscopic vessel invasion, cirrhosis and high level of serum alpha-fetoprotein. Similar to CC patients, cHCC-CC patients showed increased bile duct invasion and decreased capsule. The 1-, 3-, and 5-year overall survival and disease-free survival of patients with cHCC-CC were not significantly different from those with stage-matched patients with CC; but significantly poorer than those with HCC. In subanalysis of patients with stage II, the overall survival in patients with cHCC-CC or CC was significantly poorer than that in patients with HCC. We did not find the difference in patients with other stages. Univariate analysis of overall and disease-free survival of patients with cHCC-CC showed that the vascular invasion and intrahepatic metastasis were the significant predictive factors. CONCLUSION: Patients with cHCC-CC showed similar clinicopathological features as those with HCC or CC, and patients with cHCC-CC or CC had a poorer prognosis compared with those with HCC, especially at matched stage II.

Analyzing the structure-activity relationship of raspberry polysaccharides using interpretable artificial neural network model.

The structure-activity relationship has been a hot topic in the field of polysaccharide research. Six polysaccharides and three polysaccharide fragments were obtained from raspberry pulp. Based on their structural information and immune-enhancing activity data, an artificial neural network (ANN) model was used for prediction, and Gradient-weighted class activation mapping (Grad-CAM) algorithm was exploited for explanation structure-activity relationship of these raspberry polysaccharides in the present study. The structural information and immune activity data of raspberry polysaccharides were respectively used as input and output in the ANN model. The training and testing losses of ANN model was no longer decreased after trained for 200 epochs. The mean-square error (MSE) of training set and test set stabilized around 0.003 and 0.013, and the mean absolute percentage error (MAPE) of training set and test set were 0.21 % and 0.98 %, indicating the trained ANN model converged well and exhibited strong robustness. The interpretability analysis showed that molecular weight, content of arabinose, galactose or galacturonic acid, and glycosyl linkage patterns of →3)-Arap-(1→, Araf-(1→, →4)-Galp-(1 â†’ were the main structural factors greatly affecting the immune-enhancing activity of raspberry polysaccharides. This work may provide a new perspective for the study of structure-activity relationship of polysaccharides.

Appropriate indications of initial endoscopic ultrasound evaluation for detecting mural nodules in branch duct intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: The presence of mural nodules is a strong predictor of malignancy in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). Endoscopic ultrasound (EUS) is the most sensitive imaging for the detection of mural nodules. The aim was to evaluate whether initial EUS evaluation is necessary to detect mural nodules in all patients with BD-IPMNs. MATERIAL AND METHODS: We reviewed retrospectively the medical records of all 104 patients with BD-IPMNs diagnosed by EUS from January 2008 to December 2011. Of the 104 patients, 13 (12.5%) had mural nodules (MN-positive group) and 91 (87.5%) did not (MN-negative group). RESULTS: Patients in the MN-positive group were significantly older (69 years vs. 61 years, p = 0.013), had larger-sized cysts on EUS (24.1 ± 8.3 mm vs. 16.2 ± 8.0 mm, p = 0.001), a higher rate of main pancreatic duct dilatation (30.8% vs. 3.3%, p = 0.004), and higher serum CA 19-9 concentrations (67.8 ± 109.4 U/mL vs. 17.5 ± 27.0 U/mL, p = 0.012), than patients in the MN-negative group. Cyst sizes measured by EUS, CT, and MRCP did not differ significantly. Multivariate logistic regression analysis showed that cysts ≥16 mm in size on CT (odds ratio [OR], 9.84; 95% confidential interval [CI], 1.08-89.93; p = 0.043) and main pancreatic duct dilatation (OR, 12.65; 95% CI, 1.62-98.99; p = 0.016) were independent predictors of mural nodules. CONCLUSIONS: Patients with BD-IPMNs, cyst size ≥16 mm, and main pancreatic duct dilatation should be further evaluated by EUS for the presence of mural nodules.

Comparison of uncovered and covered stents for the treatment of malignant duodenal obstruction caused by pancreaticobiliary cancer.

BACKGROUND: Few clinical studies to date have compared different types of self-expandable metallic stents (SEMS) and their outcomes in patients with pure duodenal obstruction caused by pancreaticobiliary cancer. The aim of this study was to compare the clinical effectiveness and side effects of uncovered and covered SEMS for the palliation of duodenal obstruction caused by pancreaticobiliary cancer. METHODS: We retrospectively analyzed all patients with pancreaticobiliary cancer who underwent upper endoscopy with SEMS placement for malignant duodenal obstruction at the National Cancer Center of Korea between April 2003 and December 2010. The technical and clinical success rates of the procedure, complications, and durations of stent patency and overall survival were evaluated. RESULTS: We identified 70 patients with a mean age of 51.2 years (range = 39-81 years); of these, 46 (65.7 %) had pancreatic cancer, 9 (12.9 %) had bile duct cancer, 11 (15.7 %) had gallbladder cancer, and 4 (5.7 %) had cancer of the ampulla of Vater. Twenty-four patients (34.3 %) received covered SEMSs and 46 (65.7 %) received uncovered SEMSs. Technical and clinical success rates were similar for the covered and uncovered stent groups. The complication rate was higher in the covered than in the uncovered group (62.5 vs. 34.8 %, P = 0.025), due primarily to a significantly higher stent migration rate (20.8 vs. 0 %, P = 0.004). Perforation as a late complication occurred in four patients, two in each group (8.3 vs. 4.3 %, P = 0.425). Stent patency tended to be shorter for covered than for uncovered duodenal stents (13.7 ± 8.6 weeks vs. not reached, P = 0.069). CONCLUSIONS: The use of uncovered stents may be a preferred option for duodenal obstruction secondary to pancreaticobiliary malignancies, since they were effective in preventing stent migration and tended to have longer patency than covered stents. Careful attention should be paid to signs and symptoms of perforation during follow-up.

Gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective cohort study.

BACKGROUND AND AIM: Gemcitabine plus cisplatin (GP) is a standard chemotherapy option for patients with advanced biliary tract cancer (BTC). We compared the efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced BTC. METHODS: The records of all patients treated with GP or XP chemotherapy for unresectable, metastatic, or recurrent BTC at the National Cancer Center between December 2001 and August 2012 were reviewed retrospectively. Patients with histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or extrahepatic cholangiocarcinoma were enrolled. RESULTS: Of the 344 patients enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9 months, the median time to progression was longer in the GP group than in the XP group (5.6 vs. 4.7 months), but the difference was not statistically significant (p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with statistical significance retained following multivariate analysis (HR 0.72; 95% CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). CONCLUSIONS: GP was superior to XP in prolonging OS, despite increasing the rate of grade 3/4 adverse events.

Risk of pancreatic cancer in relation to ABO blood group and hepatitis C virus infection in Korea: a case-control study.

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.

Patterns of initial disease recurrence after resection of biliary tract cancer.

OBJECTIVES: This study aimed to provide further insights into the indications for adjuvant therapeutic strategies via analysis of the sites of initial recurrence after resection of gallbladder cancer (GBC) and intrahepatic (IHC) and extrahepatic cholangiocarcinoma (EHC). METHODS: Patients with biliary tract cancer who underwent potentially curative resection were identified from the database. Sites of initial disease recurrence were categorized as locoregional or distant. RESULTS: Between March 2001 and April 2009, 231 patients underwent curative resection. Initial GBC and IHC recurrence involving a distant site occurred in 70.8 and 86.8% patients, respectively, compared to 56.9% patients with EHC (p = 0.002). The median time to disease recurrence (TTR) was shorter among the GBC and IHC groups compared with that in EHC patients (6.3 and 6.7 vs. 13.1 months, respectively; p = 0.003). Moreover, median times to distant recurrence in GBC and IHC groups were shorter than that in EHC (5.8 and 6.5 vs. 14.1 months, respectively; p = 0.002). CONCLUSIONS: After resection, recurrent GBC and IHC are more likely to involve a distant site and are associated with significantly shorter TTR than recurrent EHC. These findings suggest that an adjuvant therapeutic strategy targeting distant disease is likely to have a significant impact on the overall management of GBC and IHC.

Central nervous system aquaporin-4 autoimmunity presenting with an isolated cerebral abnormality.

Advances in the understanding of central nervous system aquarporin-4 autoimmunity have promoted the recognition of diverse clinical presentations beyond the traditional view of neuromyelitis optica. We describe a patient who developed hemiparesis caused by an extensive cerebral lesion as an initial manifestation of central nervous system aquarporin-4 autoimmunity. Although the patient had no history of optic neuritis or myelitis, not only was serum anti-aquarporin-4 antibody positive, but an imaging, treatment response and histopathological features also revealed characteristic findings suggestive of central nervous system aquarporin-4 autoimmunity. The present case highlights the importance of a comprehensive evaluation for anti-aquarporin-4 antibody even in patients presenting with isolated cerebral lesions.