Chen My

Detection of hematogenous bone metastasis in cervical cancer: 18F-fluorodeoxyglucose-positron emission tomography versus computed tomography and magnetic resonance imaging.

In this large‐scale, retrospective study, the authors evaluated the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and 18F‐fluorodeoxyglucose‐positron emission tomography (18F‐FDG–PET) in detecting hematogenous bone metastasis in patients with cervical cancer. The associated risk factors also were analyzed.

Outcomes and prognosis of patients with recurrent cervical cancer after radical hysterectomy

OBJECTIVE Our aim was to investigate the clinical features and outcomes following recurrence after primary radical hysterectomy for cervical cancer. METHODS Clinical data of 121 documented recurrent cervical cancer patients who received primary radical hysterectomy and bilateral pelvic lymphadenectomy between 1993 and 2000 at Chang Gung Memorial Hospital were retrospectively reviewed. Clinicopathological variables, primary treatment, failure pattern, salvage treatment and outcomes were analyzed. Outcomes of the current study were compared to those treated between 1982 and 1992 (1982-1992 cohort). RESULTS Cancer recurrence was documented at a median time to recurrence (TTR) of 28.4 months (1.2-129.9 months). Assessable failure patterns (n=106) included loco-regional in 46.3%, distant in 47.2% and combined pelvic-distant in 6.6%. 5-year survival of the 121 patients was 22.3% after cancer recurrence. The median survival after recurrence (SAR) was 16.4 months (range 0-144.2 months). By multivariate analysis, extravaginal sites of recurrence (HR 2.56, 1.28-5.12; p=0.008) and HPV16-positive (HR 0.60, 0.38-0.96; p=0.033) were significant prognostic factors for SAR. Non-squamous histology or pelvic node metastasis at primary surgery were not significant (5-year SAR of 16.4% and 20.0%, respectively), though they were (0% and 0%) in the 1993-2000 cohort. Salvage surgery and concurrent chemoradiation were more frequently used in the 1993-2000 cohort (48.3% versus 12.4%). CONCLUSION HPV16-negativity and extravaginal relapse were significant poor prognostic factors. Future randomized controlled trials for recurrent cervical cancer could be stratified for these two factors if further studies using external validation confirm these results.

Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma

BACKGROUND Our aims were to evaluate the genotype distribution of human papillomavirus (HPV) and the correlation between HPV parameters and clinicopathological/treatment variables with prognosis in cervical adeno-adenosquamous carcinoma (AD/ASC). PATIENTS AND METHODS Consecutive patients who received primary treatment for cervical AD/ASC International Federation of Gynecology and Obstetrics (FIGO) stages I-IV between 1993 and 2008 were retrospectively reviewed. Prognostic models were constructed and followed by internal validation with bootstrap resampling. RESULTS A total of 456 AD/ASC patients were eligible for HPV genotyping, while 452 were eligible for survival analysis. HPV18 was detected in 51.5% and HPV16 in 36.2% of the samples. Age >50 years old, FIGO stages III-IV and HPV16-negativity were significantly related to cancer relapse, and age >50, FIGO stages III-IV, HPV16-negativity and HPV58-positivity were significant predictors for cancer-specific survival (CSS) by multivariate analyses. HPV16-positivity was also significantly associated with good prognosis in those receiving primary radiotherapy or concurrent chemoradiation (RT/CCRT) (CSS: hazard ratio 0.41, 95% confidence interval 0.21-0.78). Patients with FIGO stages I-II and HPV16-negative AD/ASC treated with primary RH-PLND had significantly better CSS (p<0.0001) than those treated with RT/CCRT. CONCLUSIONS Age >50 years old, FIGO stages III-IV and HPV16-negativity were significant poor prognostic factors in cervical AD/ASC. Patients with HPV16-negative tumour might better be treated with primary surgery (e.g. radical hysterectomy for stages I-II and pelvic exenteration for stage IVA). Those with unresectable HPV16-negative tumour (stage IIIB) should undergo CCRT in combination with novel drugs. The inferences of a single-institutional retrospective study require prospective studies to confirm.

Serum microRNAs in clear cell carcinoma of the ovary

OBJECTIVE To identify candidate microRNAs (miRNAs) in the serum of patients with clear cell carcinomas in monitoring disease progression. MATERIALS AND METHODS The sera of patients with diagnosed ovarian clear cell carcinoma were collected from 2009 to 2012. Real-time quantitative polymerase chain reaction (PCR) analysis for 270 miRNAs was performed. To offset the potential extraction bias, an equal amount of Caenorhabditis elegans cel-miR-238 was added to each serum specimen before miRNA isolation. miRNA expression was analyzed using the ΔCt method, with cel-miR-238 as controls. RESULTS Twenty-one patients with clear cell carcinoma were included. In the discovery phase on four pairs of pre- and postoperative sera, 18 differentially expressed miRNAs were selected from 270 miRNAs. In the validation phase on an independent set of 11 pairs of pre- and postoperative sera, 4 miRNAs (hsa-miR-130a, hsa-miR-138, hsa-miR-187, and hsa-miR-202) were confirmed to be higher in the preoperative sera. In the application phase, hsa-miR-130a remained consistent with the different time points in seven of the 10 patients during clinical follow-up periods. More importantly, in three patients, hsa-miR-130a levels were elevated in early disease recurrences before CA125 was found to be elevated. CONCLUSION Hsa-miR-130a may be a useful serum biomarker for detecting recurrence of ovarian clear cell cancer, and warrants further studies.

Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan.

Summary Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (Pis). Whether the HIV-1 from these patients with virological failure to first-generation Pls remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation Pls in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 Pls. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation Pls.

Outcomes and prognoses of patients with ovarian cancer using bevacizumab: 6-year experience in a tertiary care hospital of northern Taiwan

Purpose Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data related to outcome is scant. This retrospective study reviewed patients with OC treated with BEV and analyzed their results. Patients and methods All patients with OC treated with BEV from 2009 to 2015 in the Linkou branch of Chang Gung Memorial Hospital in Northern Taiwan were included. According to the means of administration, the patients were classified into 6 groups as follows: A—BEV plus chemotherapy (C/T) for initial platinum-resistant (PR) recurrent OC, B—BEV plus C/T for initial platinum-sensitive (PS) recurrent OC, C—BEV alone for recurrent OC, D—BEV plus 1st adjuvant C/T, E—BEV plus neoadjuvant C/T, and F—intraperitoneal (IP) BEV. Progression-free survival (PFS), overall survival (OS), hazard ratios (HRs), overall response rate (ORR), and mean number of BEV cycles were analyzed for groups A to E. Clinical improvement of ascites was assessed for group F. Results A comparison of early use (only one round of prior C/T) versus late use (multiple rounds of prior C/T) in patients of groups A and B showed a superior PFS (8.27 vs. 3.67, p = 0.037) in the early use group. No significant differences were found between groups A and B (PFS: 4.24 vs. 4.17 months, p = 0.690; OS: 10.06 vs. 9.93 months, p = 0.819; mean BEV cycles: 4.63 vs. 5.0 p = 0.992; ORR: 48.1% vs. 53.5%, p = 0.425). Comparing the response and non-response subgroups of patients in groups A and B, a better outcome was associated with endometrioid type cell (HR = 0.28, p = 0.008), good ECOG performance status (HR = 0.51, p = 0.005), and lack of ascites (HR = 0.67, p = 0.004). Comparing group C with groups A plus B, the BEV alone group had a poorer PFS (1.02 VS. 4.19, p = 0.04) and OS (1.42 VS. 9.99 p = 0.001) than the BEV plus C/T group. In group F, a good clinical benefit rate (85.6%) of ascites improvement was noted. Two patients had grade 5 gastrointestinal bleeding and venous/arterial thromboembolic events after administration of BEV. Grade 3 neutropenia and thrombocytopenia occurred more frequently in our study. Conclusion Early use of BEV combined with chemotherapy had a significant benefit in PFS for patients with recurrent OC. BEV plus chemotherapy was better than BEV alone for recurrent OC. In addition, IP BEV was helpful for improving clinical ascites.

Phase I Dose-escalation Study of Weekly Paclitaxel and Cisplatin Followed by Radical Hysterectomy in Stages Ib2 and Iia2 Cervical Cancer

Purpose: To define the optimal dose of paclitaxel combining cisplatin, as weekly neoadjuvant chemotherapy (NAC) for early-stage bulky squamous cell carcinoma of the uterine cervix. Methods: A prospective trial was conducted for International Federation of Gynecology and Obstetrics stages IB2 and IIA2 cervical squamous cell carcinoma patients with magnetic resonance imaging or positron emission tomography-defined lymph node negative. Weekly fixed-dose cisplatin (40 mg/m2) and 4-level dose escalation of paclitaxel (50, 60, 70, 80 mg/m2) for 3 courses was given and followed by radical hysterectomy and pelvic lymph node dissection (RH-PLND) 14 to 28 days later. Postoperative adjuvant therapy was tailored according to pathologic response. Results: No dose-limiting toxicity occurred. Twelve subjects were enrolled without reaching maximum tolerated dose, nor was any RH-PLND procedure delayed for >2 weeks. Pathologic response rate was 50% (complete in 2 and partial in 4). Paclitaxel dose level seemed unrelated to pathologic response. No subjects had grade ≥3 acute adverse events. Seven patients (58.3%) received postoperative radiotherapy or chemoradiation. Patients with human papillomavirus 16-negative tumor and aged 55 years and older had marginally higher risk (100%) of adjuvant radiotherapy or chemoradiation after NAC than those with human papillomavirus 16-positive or age less than 55 (P=0.081). With a median follow-up of 45.5 months, all 12 patients remained alive without disease. Conclusions: Weekly paclitaxel and cisplatin NAC for 3 courses can be tolerated with excellent short-term outcome. With the caveat of small number of patients, this study supports future phase II trials of weekly paclitaxel and cisplatin NAC for 4 to 5 cycles.

Positron emission tomography in the management of documented or suspected recurrent ovarian cancer

BACKGROUND To prospectively evaluate the value of positron emission tomography (PET) or integrated computed tomography (CT) and PET (PET/CT) in the management of documented or suspected recurrent ovarian cancer. METHODS Patients with ovarian cancer who had completed primary cytoreductive surgery and standard adjuvant chemotherapy were studied to evaluate the following indications: (1) CA125 elevation after complete remission with negative CT or magnetic resonance imaging (MRI) result; (2) post-therapy surveillance CT/MRI-detected suspicious lesions that guided biopsy was not feasible; (3) documented relapse for restaging prior to or after curative salvage therapy. The clinical impact of PET, as compared with those of CT/MRI, was determined on a per scan basis. RESULTS From 2002 to 2009, 73 patients were recruited, and 92 PET scans were performed. Up to June 2015, 53 patients had died of disease, four were alive with disease, and the remaining 16 were alive without disease. Among the 92 scans, PET had positive impacts in 72.8%, no clinical impacts in 21.7%, and negative impacts in 5.4%. For indication 1, the sensitivity and positive predictive value of PET in detecting recurrence were 80.0% and 92.3%, respectively. For indication 2, the sensitivity, specificity, positive predictive value, and negative predictive value of PET were 91.2%, 62.5%, 91.2%, and 62.5%, respectively. For indication 3, PET provided positive impact in 85.3% and negative impact in 2.9% of the 34 scans. CONCLUSION PET has value in the management of suspected or documented recurrent ovarian cancer, with positive impacts on confirming recurrent status and offering a better treatment plan.

Self-sampling HPV test in women not undergoing Pap smear for more than 5 years and factors associated with under-screening in Taiwan

BACKGROUND/PURPOSE Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. METHODS Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. RESULTS Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT

BACTEREMIA AND FUNGEMIA IN PATIENTS WITH ADVANCED HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION IN TAIWAN

434,866 to NT