Hon-Yi Lin

A nationwide cohort study suggests that hepatitis C virus infection is associated with increased risk of chronic kidney disease.

The association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD) remains widely debated. Here we quantify this association by analysis of data from the Taiwan National Health Insurance Research Database and ICD-9 codes to identify 9430 adults with newly diagnosed HCV (years 1999-2006) and randomly selected 37,720 matched non-HCV control individuals. The incidence rate and risk of incident CKD were evaluated through the end of 2010. The frequency of CKD was 1.66-fold higher in the HCV than the non-HCV cohort (5.46 compared with 3.43 per 1000 person-years), and the adjusted hazard ratio remained significant at 1.28 (95% confidence interval, 1.12-1.46). A multivariate analysis was used to determine the influence of HCV on CKD risk with regard to age, gender, follow-up duration, and comorbidities. The risk for CKD in HCV-infected individuals was higher with diabetes, hyperlipidemia, and cirrhosis (8.44; 3.70-19.23), followed by men<50 years (2.32; 1.49-3.61), all individuals<50 years (1.90; 1.33-2.73), men overall (1.44; 1.22-1.71), and individuals followed for ≥6 years (1.35; 1.06-1.71); all with considerable significance. Thus, HCV infection is associated with an increased risk of CKD. Hence, high-risk HCV-infected individuals should be aggressively monitored for development of CKD.

Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo

PURPOSEnIncreasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization.nnnMETHODS AND MATERIALSnAn H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-kappaB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting.nnnRESULTSnConcurrent andrographolide treatment (10 microM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 +/- 2.5 days) compared with radiation alone (22 +/- 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-kappaB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-kappaB activity.nnnCONCLUSIONnAndrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-kappaB activity. These observations indicate that andrographolide is a novel radiosensitizing agent with potential application in cancer radiotherapy.

Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study.

BackgroundIncreased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients.MethodsThe study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke.ResultsThe 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51xa0years) than in older (age ≥51 years) cervical cancer patients (HRu2009=u20092.73, pu2009=u20090.04; HRu2009=u20091.37, pu2009=u20090.07) and in patients with more than two comorbid risk factors (5xa0years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%).ConclusionsThese study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed.

Infectious complications in head and neck cancer patients treated with cetuximab: propensity score and instrumental variable analysis.

Background To compare the infection rates between cetuximab-treated patients with head and neck cancers (HNC) and untreated patients. Methodology A national cohort of 1083 HNC patients identified in 2010 from the Taiwan National Health Insurance Research Database was established. After patients were followed for one year, propensity score analysis and instrumental variable analysis were performed to assess the association between cetuximab therapy and the infection rates. Results HNC patients receiving cetuximab (nu200a=u200a158) were older, had lower SES, and resided more frequently in rural areas as compared to those without cetuximab therapy. 125 patients, 32 (20.3%) in the group using cetuximab and 93 (10.1%) in the group not using it presented infections. The propensity score analysis revealed a 2.3-fold (adjusted odds ratio [OR]u200a=u200a2.27; 95% CI, 1.46–3.54; Pu200a=u200a0.001) increased risk for infection in HNC patients treated with cetuximab. However, using IVA, the average treatment effect of cetuximab was not statistically associated with increased risk of infection (OR, 0.87; 95% CI, 0.61–1.14). Conclusions Cetuximab therapy was not statistically associated with infection rate in HNC patients. However, older HNC patients using cetuximab may incur up to 33% infection rate during one year. Particular attention should be given to older HNC patients treated with cetuximab.

Clinical significance of measuring levels of tumor necrosis factor-alpha and soluble interleukin-2 receptor in nasopharyngeal carcinoma

Conclusion: Changes in tumor necrosis factor-alpha (TNF-α) and soluble interleukin-2 (sIL-2R) levels appear to be closely related to tumor progression and prognosis in nasopharyngeal carcinoma (NPC). Further investigation is suggested. Objectives: The study examined whether changes in TNF-α and sIL-2R in NPC can be used to predict tumor progression and prognosis. Patients and methods: The study was carried out in 58 patients with NPC newly diagnosed from December 2003 to December 2006 at a single institution and 60 control subjects of comparable age. Blood levels of TNF-α and sIL-2R were monitored before, during, and 3 months and 1 year after treatment. Results: Differences in TNF-α level between patients with NPC in all four stages and healthy controls and in sIL-2R level between patients with advanced stage NPC and healthy controls were significant (p <0.05). Furthermore, 1 year after completing radiotherapy, levels of TNF-α and sIL-2R in patients with recurrent tumors were significantly different from those in patients without recurrence and healthy control subjects.

Hyperbaric Oxygen Therapy for Late Radiation-Associated Tissue Necroses: Is It Safe in Patients With Locoregionally Recurrent and Then Successfully Salvaged Head-and-Neck Cancers?

PURPOSEnTo test, in a retrospective matched-pair study, whether necrosis-rescuing hyperbaric oxygen therapy (HBOT) increases the risk of cancer re-recurrence in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers.nnnMETHODS AND MATERIALSnBetween January 1995 and July 2004, we retrospectively identified 22 patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. We defined two groups: the HBOT group, 11 patients with HBOT for rescuing late radiation-associated tissue necroses; and the non-HBOT group, the other 11 matched-pair patients without HBOT. Between the two groups, the following four factors were matched for case pairing: primary cancer subsite, initial cancer stage, age, and gender.nnnRESULTSnThree findings indicate that HBOT increases the risk of cancer re-recurrence. First, we observed more cancer re-recurrences in the HBOT group than in the non-HBOT group: 9 of 11 vs. 4 of 11, with 5-year disease-free survival rates after salvage of 32.7% vs. 70.0% (hazard ratio 3.2; 95% confidence interval 1.03-10.7; p = 0.048). Second, re-recurrences developed rapidly after HBOT in 6 patients. Third, 3 patients had unusual cancer re-recurrences after HBOT. Remarkably, of 9 patients with cancer re-recurrences in the HBOT group, 4 patients had cancer disease-free intervals of 9 months or less before HBOT.nnnCONCLUSIONSnNecrosis-rescuing HBOT should be given with caution in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers; if it cannot be omitted entirely, deferring HBOT 9 months or longer after cancer re-treatment may be prudent.

Higher caseload improves cervical cancer survival in patients treated with brachytherapy

ObjectivesIncreased caseload has been associated with better patient outcomes in many areas of health care, including high-risk surgery and cancer treatment. However, such a positive volume vs. outcome relationship has not yet been validated for cervical cancer brachytherapy. The purpose of this study was to examine the relationship between physician caseload and survival rates in cervical cancer treated with brachytherapy using population-based data.MethodsBetween 2005 and 2010, a total of 818 patients were identified using the Taiwan National Health Insurance Research Database. Multivariate analysis using a Cox proportional hazards model and propensity scores was used to assess the relationship between 5-year survival rates and physician caseloads.ResultsAs the caseload of individual physicians increased, unadjusted 5-year survival rates increased (P = 0.005). Using a Cox proportional hazard model, patients treated by high-volume physicians had better survival rates (P = 0.03), after adjusting for comorbidities, hospital type, and treatment modality. When analyzed by propensity score, the adjusted 5-year survival rate differed significantly between patients treated by high/medium-volume physicians vs. patients treated by low/medium-volume physicians (60% vs. 54%, respectively; P = 0.04).ConclusionsProvider caseload affected survival rates in cervical cancer patients treated with brachytherapy. Both Cox proportional hazard model analysis and propensity scores showed association between high/medium volume physicians and improved survival.

Clinical and Pathologic Factors Affecting Lymph Node Yields in Colorectal Cancer

Objective Lymph node yield is recommended as a benchmark of quality care in colorectal cancer. The objective of this study was to evaluate the impact of various factors upon lymph node yield and to identify independent factors associated with lymph node harvest. Materials and Methods The records of 162 patients with Stage I to Stage III colorectal cancers seen in one institution were reviewed. These patients underwent radical surgery as definitive therapy; high-risk patients then received adjuvant treatment. Pathologic and demographic data were recorded and analyzed. The subgroup analysis of lymph node yields was determined using a t-test and analysis of variants. Linear regression model and multivariable analysis were used to perform potential confounding and predicting variables. Results Five variables had significant association with lymph node yield after adjustment for other factors in a multiple linear regression model. These variables were: tumor size, surgical method, specimen length, and individual surgeon and pathologist. The model with these five significant variables interpreted 44.4% of the variation. Conclusions Patients, tumor characteristics and surgical variables all influence the number of lymph nodes retrieved. Physicians are the main gatekeepers. Adequate training and optimized guidelines could greatly improve the quality of lymph node yields.

Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer.

BackgroundAberrant insulin-like growth factor-binding protein 7 (IGFBP-7) expression has been found in various cancers such as prostate, breast, and colon. IGFBP-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. This study investigates the causes and underlying mechanisms of aberrant IGFBP-7 expression in unravelling head and neck squamous cell carcinoma (HNSCC).MethodsA total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5′ region of IGFBP-7 by methylation-specific PCR (MS-PCR). Subsequently the invasion, overexpression, and knockdown of IGFBP-7 in the HNSCC A253 invasive subpopulation were employed to examine the effect of IGFBP-7. The epithelial–mesenchymal transition (EMT) marker genes and AKT/GSK3β/β-catenin signaling were further evaluated by Western blot for the understanding the role of aberrant IGFBP-7 expression and thereof putative mechanism.ResultsEMT expressed in the invasive subpopulation of HNSCC cell lines (A253 and RPMI 2650) was contemporary with the down-regulation of IGFBP-7. After treatment with 5-AZA-2′ deoxycytidine, the de-methylated CpG sites in the 5′ region of IGFBP-7 were observed and IGFBP-7 mRNA expression was also restored. Accordingly, re-expression IGFBP-7 in invasive subpopulation of A253 could induce the mesenchymal–epithelial transition (MET) and concurrently inhibited the cell invasion. Moreover, IGFBP-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor, loco-regional recurrence, and cancer sequence.ConclusionsIGFBP-7 can alter EMT relative marker genes and suppress cell invasion in A253 cell through AKT/GSK3β/β-catenin signaling. The epigenetic control of IGFBP-7 in the invasion and metastasis of HNSCC was reported, suggesting that IGFBP-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy.

Prognosticators and the relationship of depression and quality of life in head and neck cancer.

BACKGROUND AND PURPOSEnTo evaluate the relationship of emotional status and health-related quality of life (HRQOL) in disease-free head and neck cancer (HNC) patients post treatment and to explore their predictive factors.nnnMATERIALS AND METHODSnSeventy-three HNC patients, post treatment at least 1 year, were recruited to complete three questionnaires, EORTC QLQ-C30, EORTC-H&N35 cancer module, and the Beck Depression Inventory-II (BDI-II).nnnRESULTSnPatients with depression demonstrated significantly poor global health status/QoL (score 41.7 vs. 71.9, P<0.001) and almost all functioning, except for role functioning. Besides, depressive patients presented statistically significant worse symptoms in all QLQ-C30 items, except constipation and financial problems, and in all QLQ-H&N35 symptoms except for teeth and coughing problems. Depression was significantly negative correlated with all functional scales and global health status/QoL (r = -0.341 to -0.750, all P<0.05), and was significantly positive correlated with symptom scales (r = 0.348 to 0.793, all P<0.05), except for constipation. Stepwise multiple linear regression analyses showed that physical functioning and physical distressful symptoms play an important role in the perception of HRQOL (total 46% explained). Global health status and impaired social functioning could explain depression in addition to emotional functioning (total 64% explained).nnnCONCLUSIONSnHNC patients with depression were noted to have poorer HRQOL in almost every functioning symptom. HNC patients may get benefit from early interventions to improve HRQOL, emotional status, or both by a more rapid and friendly questionnaire to earlier identify patients with poor HRQOL or depressive status.