Yi-Ping Hung

Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients: A population‐based cohort study

Hepatocellular carcinoma (HCC) is a major complication of hepatitis B virus (HBV) infection. This study investigated the association between nucleos(t)ide analogue (NA) use and the risk of HCC and mortality in HBV carriers on the basis of the Taiwan National Health Insurance Database.

Clinical significance of circulating plasma DNA in gastric cancer

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5‐year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5‐year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.

Risk of Ischemic Stroke in Patients With Gastric Cancer: A Nationwide Population-Based Cohort Study.

Abstract Improvements in therapeutic modalities have prolonged the survival of gastric cancer patients. Comorbidities such as thromboembolic events that emerge as a result of disease complexities and/or treatments received have not been considered. The objectives of this study are to examine the relationship between gastric cancer and ischemic stroke, and to determine predictive risk factors. A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance database. A total of 45,060 gastric cancer patients and non-cancer counterparts without antecedent stroke were recruited. Hazard ratios (HRs) and the cumulative incidence of ischemic stroke were calculated, and risk factors for ischemic stroke were assessed. Gastric cancer patients were associated with higher risk of ischemic stroke (HR 1.11, 95% confidence interval [CI] 1.03–1.19, P = 0.007), especially in participants younger than 65 years (HR 1.61, 95% CI 1.39–1.86, P < 0.001) and in female participants (HR 1.30, 95% CI 1.14–1.49; P < 0.001) when compared with the matched cohort. Independent risk factors of ischemic stroke in gastric cancer patients included age, hypertension, atrial fibrillation, dyslipidemia, and having received major surgery for gastric cancer. Our findings suggest the importance of stroke surveillance and prevention strategies in high-risk patients. Having received major surgery for gastric cancer is a significant risk factor in these patients.

Evaluation of prognostic factors and implication of lymph node dissection in intrahepatic cholangiocarcinoma: 10-year experience at a tertiary referral center

Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy, and surgical resection remains the only potentially curative treatment. However, the existing literature indicates that those prognostic factors associated with outcome after surgery remain poorly defined. Methods Data were retrospectively collected from 103 patients with ICC who underwent surgical resection between 2005 and 2014. The patients were divided into two groups: one with (D1) and one without (D0) lymph node dissection of hepatic hilum according to the surgery performed. Thereafter, the prognostic values of clinicopathological characteristics were evaluated. Results The median overall survival (OS) after surgical resection of ICC was 43.9 months [95% confidence interval (CI), 11.6–76.2 months]. The 1‐, 3‐, and 5‐year OS rates were 85.5%, 52.8%, and 45.6%, respectively. Multivariable analysis showed that lymph node metastases [hazard ratio (HR), 6.70; 95% CI, 2.18–20.55], positive resection margins (HR, 2.67; 95% CI, 1.14–6.23), periductal infiltration (HR, 3.64; 95% CI, 1.27–10.44), and poor differentiation (HR, 2.90; 95% CI, 1.41–5.95) were independently associated with poor survival. There were no significant differences in clinicopathological characteristics between D1 and D0 groups, except for vascular invasion (p = 0.018) and perineural invasion (p = 0.008). In the D1 group, lymph node metastases were associated with late T stages, multiple tumors, and elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9) levels. Conclusion Regional lymph node metastasis, positive resection margin, periductal infiltration, and poor differentiation were poor prognostic factors in patients with ICC after curative surgery. Lymph node dissection did not show survival benefits, but was useful for nodal staging. However, lymph node metastases were strongly associated with late T stages, multiple tumors, and elevated serum CEA and CA19‐9 levels.

Incidence of and Risk Factors for Tuberculosis (TB) in Gastric Cancer Patients in an Area Endemic for TB: A Nationwide Population-based Matched Cohort Study

AbstractTo date, there have been few reports investigating the relationship between tuberculosis (TB) and gastric cancer.We conducted a nationwide population-based matched cohort study using data retrieved from Taiwans National Health Insurance Research Database to determine the incidence of and risk factors for TB in patients diagnosed with gastric cancer. From 2000 to 2011, we identified 36,972 gastric cancer patients and normal subjects from the general population matched for age, sex, and comorbidities at a 1:1 ratio. The data were analyzed using Cox proportional hazards models.Compared with the matched cohort, gastric cancer patients exhibited a higher risk for TB (adjusted hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.41–1.79, P < 0.001), and those with TB exhibited higher mortality (adjusted HR 2.29, 95% CI 2.03–2.29, P < 0.001). Old age (adjusted HR 2.40, 95% CI 1.92–2.99, P < 0.001), male sex (adjusted HR 2.13, 95% CI 1.76–2.57, P < 0.001), diabetes mellitus (adjusted HR 1.28, 95% CI 1.05–1.56, P = 0.013), and chronic obstructive pulmonary disease (COPD) (adjusted HR 1.44, 95% CI 1.19–1.75, P < 0.001) were identified as independent risk factors for TB in gastric cancer patients. Dyslipidemia was an independent protective factor for both TB (adjusted HR 2.13, 95% CI 1.73–2.62, P < 0.001) and mortality (adjusted HR 1.11, 95% CI 1.08–1.15, P < 0.001) in gastric cancer patients.Old age, male sex, diabetes mellitus, and COPD were independent risk factors for TB in gastric cancer. High-risk gastric cancer patients, especially those in TB-endemic areas, should be regularly screened for TB.

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients

Background: Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19–9 (CA 19–9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR‐70 and evaluated its performance in screening and response monitoring. Methods: The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR‐70, CEA, and CA 19–9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed‐up the patients every 3 months; DR‐70 levels and abdominal computed tomography scans were re‐evaluated and repeated, respectively, at each follow‐up. The correlation between treatment response and DR‐70 level after chemotherapy was analyzed. The overall survival and progression‐free survival rates were also evaluated. Results: A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR‐70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19–9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR‐70 level after chemotherapy. No difference in either overall survival or progression‐free survival was observed between the DR‐70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR‐70 group, although this was not statistically significant. Conclusion: DR‐70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation.

Comparative study of the 7th and 8th AJCC editions for gastric cancer patients after curative surgery

Objectives The classification of pathological tumor-node-metastasis (pTNM) staging of gastric cancer was revised in the 8th American Joint Committee on Cancer (AJCC) edition. The major revision was the separation of pN3a and pN3b in the pTNM staging. The current study evaluated the prognostic impact of this change. Methods A total of 1,517 patients who underwent curative surgery for gastric cancer with a retrieved lymph node number ≥15 at our institution from January 1995 to December 2011 were enrolled. Survival was compared for the disease classified according to both the 7th and 8th editions. Results After separation of pN3a and pN3b in the pTNM stage definition, the 8th edition still provides significant survival differences between each stage. The multivariate analysis demonstrated that the pTNM stage in both the 7th and 8th editions was an independent prognostic factors of overall survival and disease-free survival. The 8th edition has a better homogeneity than the 7th edition with a significantly higher likelihood ratio chi-square test. Regarding the OS and DFS, the time-dependent receiver operating characteristic (ROC) curves of the two staging systems are almost overlapping, indicating that the prognostic performance is comparable between the two staging systems. Conclusions Both the 7th and 8th edition-based stages are independent prognostic factors for gastric cancer. The 8th edition has a better homogeneity than the 7th edition; the 8th edition provides discriminant survival differences among each pTNM stage that are comparable to those in the 7th edition.

Toxicities, safeties and clinical response of dacarbazine-based chemotherapy on neuroendocrine tumors in Taiwan population

Background: Currently, the role of dacarbazine (DTIC) based chemotherapy in neuroendocrine tumors (NETs) in Asia is unclear. Here, we report the outcomes of dacarbazine (DTIC)‐based chemotherapy in Taiwan population. Methods: DTIC alone (250 mg/m2/day), or 5‐fluorouracil (5‐FU, 500 mg/m2/day) and DTIC (200 mg/m2/day) with or without epirubicin (200 mg/m2/day), for 3 days, every 3–4 weeks. Subgroups were analyzed by grading, and by Ki‐67 index. Results: 48 patients were reviewed in this study, including 3 had grade 1 tumors, 23 had grade 2, while 22 were grade 3. In grade 3 NEC patients, the tumor Ki‐67 index of 21–55% were noted in 8 patients, and >55% in 14 patients. Progression‐free survival (PFS) was 5.1 months, and overall survival (OS) was 31.6 months. The PFS (in months) were 12.5 and 1.8 for patients with NETs and neuroendocrine carcinomas (NECs), respectively (p < 0.001). The OS were not reached and 5.9 months for patients with NETs and NECs, respectively (p = 0.001). Patients with NECs were divided into two groups, according to their Ki‐67 index. In patients with a tumor Ki‐67 index of 21–55%, PFS was 4.1 months, and OS was not reached; in those with a tumor Ki‐67 index of >55%, they were 1.5 and 1.8 months, respectively (p < 0.001 and p = 0.013). Conclusion: NETs, and grade 3 NECs, with Ki‐67 indices of 20–55% had good responses to DTIC‐based chemotherapy, with acceptable side effects. Ki‐67 index could predict prognosis for grade 3 NEC patients, and guide further chemotherapy choices.