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Hsin-Hsien Yu,1,2 Yutaka Yonemura,3,4 Mao-Chih Hsieh,2,5 Chang-Yun Lu,2 Szu-Yuan Wu,6,7 Yan-Shen Shan1,8 1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan; 4Department of Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan; 5Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Objectives: The prognosis of ovarian teratoma with malignant transformation and peritoneal dissemination (PD) is poor. This condition is rare but associated with a high recurrence rate even after aggressive debulking surgery and adjuvant chemotherapy. In the present paper, we describe our experience of using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for this condition. Methods: The data of ten female patients having ovarian teratoma with malignant transformation and PD between June 2007 and June 2017 were collected and reviewed retrospectively. CRS-HIPEC was performed according to the standard protocol. Patient characteristics, pathological reports, tumor markers, perioperative operative parameters, postoperative events, and disease status during the follow-up period were recorded. Results: The primary ovarian neoplasms were pure mature cystic teratoma with malignant transformation (n=6, including 5 of mucinous adenocarcinoma), mixed germ cell tumor with mature cystic teratoma and yolk sac tumor (YST) (n=1), pure immature teratoma (n=1), immature teratoma with growing teratoma syndrome (GTS) (n=1), and immature teratoma mixed YST with GTS (n=1). The mean levels of tumor markers, including carcinoembryonic antigen, cancer antigen 19-9 (CA19-9), and CA125, were markedly elevated. The recurrence rate was 10%. The median and mean disease-free survival (DFS) after CRS-HIPEC were 22.3 and 36.2 months, respectively, and the 5-year DFS rate is 88%. Conclusion: CRS-HIPEC is a safe therapeutic option for reducing the recurrence rate in selected patients with PD originating from ovarian teratoma with malignant transformation. Keywords: ovarian teratoma, malignant transformation, peritoneal dissemination, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy

Hsin-Hsien Yu,1,2 Yutaka Yonemura,3–5 Mao-Chih Hsieh,1,2 Akiyoshi Mizumoto,4 Satoshi Wakama,3 Chang-Yun Lu1,2 1Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka, Japan; 4Department of Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan; 5Nonprofit Organization to Support Peritoneal Surface Malignancy Treatment, Kyoto, Osaka, Japan Background: Goblet cell carcinomas (GCCs) of the appendix are rare and aggressive malignancies with early peritoneal dissemination. The aim of the present article is to describe our experience in the management of GCCs with peritoneal carcinomatosis (PC) through cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and to determine the impact of multiple clinical characteristics on the prognosis.Methods: From a prospectively maintained database of patients receiving CRS and HIPEC for peritoneal surface malignancy, the data of 15 patients with GCC and PC were collected. Neoadjuvant laparoscopic HIPEC was performed if indicated. CRS and HIPEC with mitomycin-C or 5-fluorouracil plus oxaliplatin were performed. Adjuvant chemotherapy was also arranged if suitable for the patient’s condition.Results: Nine males and six females with a mean age of 52.4 years were enrolled. The estimated median survival after the diagnosis of GCC with PC and after definitive CRS–HIPEC was 28 and 17 months, respectively. The 1-, 2-, 3-, 4-year survival rates were 86%, 69%, 57%, and 24%, respectively. Log-rank test revealed that the significant independent risk factors for more favorable outcomes were age >50 years, peritoneal cancer index (PCI)

Songcheng Yin,1,* Zhan Li,2,* Jinyu Huang,1 Zhifeng Miao,1 Junyan Zhang,1 Chunyang Lu,1 Hao Xu,1 Huimian Xu1 1Department of Surgical Oncology, 2Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Background: The prognostic significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer has long been assessed, yet results remain controversial. Therefore, we performed a meta-analysis to assess the prognostic value and clinicopathological significance of PCNA in gastric cancer. Methods: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases was conducted. Summary odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the correlations between PCNA expression and clinicopathological features, overall survival (OS), and disease-free survival (DFS). Results: A total of 19 studies involving 2,852 participants were included in our analysis. The pooled HR indicated that high PCNA expression was significantly associated with poor OS (HR 1.66, 95% CI 1.32–2.08) and DFS (HR 1.81, 95% CI 1.40–2.36). Subgroup analysis revealed that the association between PCNA and OS was also significant in Asian and European patients. In addition, the pooled ORs showed that high PCNA expression was significantly associated with deeper tumor invasion (OR 2.37, 95% CI 1.71–3.27), lymph node metastasis (OR 2.49, 95% CI 1.85–3.35), and advanced stage cancer (OR 1.89, 95% CI 1.36–2.63). Conclusion: Our meta-analysis indicates that high PCNA expression might be a prognosticator of poor survival and a promising therapeutic target for gastric cancer patients. Keywords: proliferating cell nuclear antigen, gastric cancer, prognosis, biomarker, meta-analysis

Chien-Yu Lu,1,2 Yung-Sung Yeh,3–5 Ching-Wen Huang,5,6, Cheng-Jen Ma,4,5 Fang-Jung Yu,1,2 Jaw-Yuan Wang4–10 1Division of Gastroenterology, Department of Internal Medicine, 2Department of Internal Medicine, Faculty of Medicine, College of Medicine, 3Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 4Graduate Institute of Clinical Medicine, College of Medicine, 5Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 6Graduate Institute of Medicine, College of Medicine, 7Cancer Center, Kaohsiung Medical University Hospital, 8Department of Genomic Medicine, 9Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI) combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT)1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being classified as stable disease and partial response, respectively. Moreover, the progression-free survival was over 6 months. FOLFIRI, with dose escalation of irinotecan according to UGT1A1 genotyping plus regorafenib appears to be a promising salvage therapy for patients with refractory metastatic colorectal cancer. Keywords: UGT1A1, irinotecan, dose escalation, metastatic colon cancer, regorafenib

Jing-Gao Li,1,* Miao-Rong She,2,* Ci-Yong Lu,3 Shan-Shan Wei,2 Ping-Fang Xia,2 Ze-Sheng Lu,2 Qi Peng2 1Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 2Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 3School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms.Materials and methods: The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting.Results: Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression.Conclusion: Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer.Keyword: Bcl-2, farnesyltransferase inhibitor, caspase-9, caspase-3, Bax

In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14-October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008-2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People's Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak. [ABSTRACT FROM AUTHOR]

Background: Hepatobiliary paragonimiasis (HP) is not commonly encountered and may be confused with hepatobiliary tumors; however, computed tomography (CT) and magnetic resonance imaging (MRI) features of HP allow this entity to be distinguished from other diseases. Purpose: To present the CT and MRI findings in patients with HP and to describe some specific imaging findings along with their pathological correlations. Material and Methods: Imaging and clinical findings of 21 patients (9 boys/men and 12 girls/women; age range 3-67 years; mean age 40 years) who were diagnosed with HP were retrospectively evaluated. Among these patients, 16 underwent CT examination only, two had MR examination only, and three underwent both CT and MR. All patients underwent surgery, and the HP diagnosis was confirmed by the surgical and histopathologic results. Results: Chronic abdominal pain or back pain was reported by 14 patients, severe abdominal pain with acute onset was reported by one patient, and six patients were asymptomatic and were discovered incidentally. Peripheral eosinophilia was present in 14 patients (14/21, 66.7%), and abnormal liver function tests were found in 16 patients (16/21, 76.2%). Of the 19 patients who underwent CT imaging, 17 patients showed multiple mixed hypodense lesions or multiple cysts with inlaying septation with separate irregular rims or circular enhancement on post-contrast CT images. Tunnel-shaped microabscesses and necrotic cavities were found in the lesions of 12 of those 17 patients. The other two patients showed smaller cystic masses. MRI showed faveolate T1 hypointense and T2 hyperintense areas in the liver parenchyma with rim or peripheral enhancement. Nodular or circular hyperintense materials were found scattered in the lesions on T1-weighted imaging. Conclusion: CT and MRI can reveal the radiological-pathological features of HP. Together with laboratory findings, MRI and CT findings may provide diagnostic clues, especially in endemic areas, that are very important for the selection of treatment methods. [ABSTRACT FROM AUTHOR]

During August-November 2009, to investigate disease transmission within households in Taiwan, we recruited 87 pandemic (H1N1) 2009 patients and their household members. Overall, pandemic (H1N1) 2009 virus was transmitted to 60 (27%) of 223 household contacts. Transmission was 4× higher to children than to adults (61% vs. 15%; p<0.001). [ABSTRACT FROM AUTHOR]

Objective: This study examined the association between a Medicaid prior-authorization policy for second-generation antipsychotic and anticonvulsant agents and medication discontinuation and health service use by patients with bipolar disorder.Methods: A pre-post design with a historical comparison group was used to analyze Maine Medicaid and Medicare claims data. A total of 946 newly treated patients were identified during the eight-month policy (July 2003-February 2004), and a comparison group of 1,014 was identified from the prepolicy period (July 2002-February 2003). Patients were stratified by number of visits to community mental health centers (CMHCs) before medication initiation (proxy for illness severity): CMHC attenders, at least two visits; nonattenders, fewer than two. Changes in rates of medication discontinuation and outpatient, emergency room, and hospital visits were estimated.Results: Compared with nonattenders, at baseline CMHC attenders had substantially higher rates of comorbid mental disorders and use of medications and health services. The policy was associated with increased medication discontinuation among attenders and nonattenders, reductions in mental health visits after discontinuation among attenders (-.64 per patient per month; p<.05), and increases in emergency room visits after discontinuation among nonattenders (.16 per patient per month; p<.05). During the eight-month policy period, the policy had no detectable impact on hospitalization risk.Conclusions: The prior-authorization policy was associated with increased medication discontinuation and subsequent changes in health service use. Although small, these unintended effects raise concerns about quality of care for a group of vulnerable patients. Long-term consequences of prior-authorization policies on patient outcomes warrant further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND: In response to rising pharmaceutical costs, many state Medicaid programs have implemented policies requiring prior authorization for high-cost medications, even for established users. However, little is known about the impact of these policies on the use of antihypertensive medicines in the United States. OBJECTIVE: The aim of this longitudinal, population-based study was to assess comprehensive prior-authorization programs for antihypertensives on drug use and costs in a vulnerable Medicaid population in Michigan and Indiana. METHODS: A prior-authorization policy for antihypertensives was implemented in Michigan in March 2002 and in Indiana in September 2002; Indiana also implemented an antihypertensive stepwise-therapy requirement in July 2003. Our study cohort included individuals aged >or=18 years in Michigan and Indiana who were continuously enrolled in both Medicaid and Medicare from July 2000 through September 2003. Claims data were obtained from the Centers for Medicare and Medicaid Services. We included all antihypertensive medications, including diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, alpha-blockers, and angiotcnsin II receptor blockers. We used interrupted time-series analysis to study policy-related changes in the total number and cost of antihypertensive prescriptions. RESULTS: Overall, 38,684 enrollees in Michigan and 29,463 in Indiana met our inclusion criteria. Slightly more than half of our cohort in both states was female (53.29%in Michigan and 56.32%in Indiana). In Michigan, 20.23% of patients were aged >or=65 years; 77.44% were white, 20.11% were black, and the remainder were Hispanic, Native American, Asian, or of other or unknown race. In Indiana, 20.07% were aged >or=65 years; 84.93% were white, 13.64% were black, and the remainder were Hispanic, Native American, Asian, or of other or unknown race. The implementation of both policies was associated with large and immediate reductions in the use of nonpreferred medications: 83.33% reduction in the use of such drugs in Michigan (-84.30 prescriptions per 1000 enrollees per month; P < 0.001) and 35.76% in Indiana (-64.45 prescriptions per 1000 enrollees per month; P < 0.001). As expected, use of preferred medications also increased substantially in both states (P < 0.001). Overall, antihypertensive therapy immediately dropped 0.16% in Michigan (P = 0.04) and 1.82% in Indiana (P = 0.02). Implementation of the policies was also associated with reductions in pharmacy reimbursement of $616,572.43 in Michigan and $868,265.97 in Indiana in the first postpolicy year. CONCLUSIONS: Prior authorization was associated with lower use of nonpreferred antihypertensive drugs that was largely offset by increases in the use of preferred drugs. The possible clinical consequences of policy-induced drug switching for individual patients remain unknown because the present study did not include access to medical record data. Further research is needed to establish whether large-scale switches in medicines following the inception of prior-authorization policies have any long-term health effects. [ABSTRACT FROM AUTHOR]

Using shared care to tackle the complexity of optimal patient management. [ABSTRACT FROM AUTHOR]