Usage of dried blood spots for molecular diagnosis and monitoring HIV-1 infection

The usage of dried blood spots as specimens for diagnosis and monitoring of HIV-1 infection in Thailand was evaluated. EDTA blood samples, which were collected from 100 HIV seronegative and 109 HIV seropositive individuals, were tested on dried blood spots; Whatman, Schleicher and Schuell (S&S) No. 903 and S&S IsoCode filter paper. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by an "in-house" multiplex PCR and a commercial Amplicor HIV-1 PCR test (Roche, version 1.0). HIV-1 RNA qualitative (QL) and quantitative (QT) detection was determined by Nucleic Acid Sequence Based Amplification (NASBA). The average DNA per blood spot recovered from Whatman and S&S IsoCode was not statistically different (p = 0.512) with a range of 218.9+/-46.84 and 225.63+/-88.33 microg, respectively. The concordance of HIV-1 proviral DNA detection by PCR from dried blood spots Whatman and S&S IsoCode was 94% versus 89.4% for sensitivity and 100% versus 100% for specificity. The sensitivity and specificity of HIV-1 RNA QL detection in dried blood spots was 89.7 and 97.5%, respectively. The HIV-1 RNA QT from dried blood spots showed a good correlation in paired dried blood spots and plasma with Pearson correlation, r = 0.817 (R2 = 0.667, P < 0.05). The data showed that dried blood spots could be used for the diagnosis and monitoring of HIV-1 infection.     

Cost-utility analysis of treatments for stage IB cervical cancer

Objective

To analyze the cost-utility of two common clinical practices for stage IB cervical cancer patients from provider and societal viewpoints.

Methods

A decision tree model was conducted to examine value for expenditure between the following: (1) radical hysterectomy with pelvic lymph node dissection (RHPLND) with or without postoperative adjuvant therapy according to the risk of recurrence and (2) concurrent chemoradiotherapy (CCRT). The relevant studies were identified to extract the probability data, and meta-analysis was performed. Direct medical costs were estimated from hospital database and medical records review. Direct non-medical costs and utility parameters were obtained through interviews with patients to estimate quality-adjusted life years (QALYs) outcome. The time horizon was according to the life expectancy of Thai women.

Results

From provider viewpoint, RHPLND and CCRT resulted in approximate costs of US $5,281 and US $5,218, respectively. The corresponding costs from societal viewpoint were US $6,533 and US $6,335, respectively. QALYs were 16.40 years for RHPLND and 15.94 years for CCRT. The estimated incremental cost effectiveness ratio of RHPLND in comparison to CCRT from provider and societal viewpoints were US $100/QALY and US $430/QALY, respectively. RHPLND had more cost-effectiveness than CCRT if patients did not need adjuvant therapy. The most effective parameter in model was a direct medical cost of CCRT. At the current ceiling ratio in Thailand, RHPLND provides better value for money than CCRT, with a probability of 75%.

Conclusion

RHPLND is an efficient treatment for stage IB cervical cancer. This advantage is only for patients who require no adjuvant treatment.     

Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer

Objective

To compare the treatment outcomes between squamous cell carcinoma (SCC) and adenocarcinoma (ACA) in locally advanced cervical cancer patients.

Methods

All medical records of stages IIB-IVA of cervical cancer patients who had completed treatment between 1995 and 2008 were reviewed. ACA 1 case was matched for SCC 2 cases with clinical stage, tumor size, treatment modalities (radiation therapy (RT) vs concurrent chemoradiation (CCRT)). Treatment outcomes including response to RT/CCRT, time to complete response (CR), patterns of treatment failure and survival outcomes were analyzed.

Results

A total of 423 patients with stages IIB-IVA (141 ACA: 282 SCC) were included. Most of the patients (about 60%) had stage IIB. The overall complete responses (CR) between ACA and SCC were 86.5% and 94.7%, respectively (p = 0.004). Median time to clinical CR from RT/CCRT of ACA were 2 months (0-5 months) compared with 1 month (0-4 months) for SCC (p = 0.001). Pelvic recurrence and distant failure were found in 2.1% and 14.9% in ACA, and corresponding with 3.9% and 15.6% in SCC. The 5-year overall survival rates of ACA compared to SCC were 59.9% and 61.7% (p = 0.191), respectively. When all prognostic factors are adjusted, clinical staging was the only factor that influenced overall survival.

Conclusion

ACA in locally advanced cervical cancer had poorer response rate from treatment and also used longer time to achieve CR than SCC. However, these effects were not determinants of survival outcomes.     

Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer

Objective

To determine whether preoperative platelets to lymphocyte ratio (PLR) could predict disease stage, surgical outcome, and survival in patients with epithelial ovarian cancer (EOC).

Methods

Medical records of EOC patients who had surgery between January 2004 and December 2010 were reviewed. Clinicopathological and complete blood count data were collected. The optimal predictive value of PLR to predict advanced stage, suboptimal surgery, and survival was determined and compared with those of thrombocytosis (≥400,000 cells/mm³) and neutrophil to lymphocyte ratio (NLR) ≥2.6.

Results

A total of 166 EOC patients were included in the study. PLR of 200 yielded better predictive values than those of thrombocytosis and NLR ≥2.6. The area under curve (AUC), sensitivity, specificity, positive and negative predictive values, and accuracy of PLR to predict advanced stage were: 0.66, 59.0%, 72.7%, 65.7%, 66.7%, and 66.3%, respectively. The corresponding values to predict suboptimal surgery were: 0.70, 70.0%, 69.8%, 50.0%, 84.4%, and 69.9%. The patients who had PLR≥200 had significantly shorter progression-free and overall survivals than those with PLR<200. Stage, grade, surgical outcome, thrombocytosis, and PLR were significant prognostic factors for survivals by univariable analyses while only stage remained significant by multivariable analysis.

Conclusion

PLR had potential clinical value in predicting advanced stage disease or suboptimal surgery. PLR was a better prognostic indicator for survivals of EOC patients compared to thrombocytosis or NLR>2.6.     

Paclitaxel and carboplatin for large cell neuroendocrine carcinoma of the uterine cervix

The prognosis of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is generally poor despite multimodality of treatments. We report a case of advanced stage cervical LCNEC that showed definite response to paclitaxel/carboplatin, resulting in years of survival. The patient was referred to our institution after undergoing a simple hysterectomy with bilateral salpingo-oophorectomy in her local hospital because of a ruptured metastatic ovarian mass. She declined pelvic radiation treatment, so adjuvant chemotherapy (six cycles of paclitaxel/carboplatin) was given for the residual pelvic nodal diseases. Clinical complete remission was obtained, with a disease-free period of 19 months. Systemic recurrent diseases also showed partial response to the same drug regimen for months with only minimal toxicity. However, she subsequently had progressive diseases in the liver and brain and finally died at 44 months after primary diagnosis and 19 months after recurrent diseases.     

Prognostic Value of p53 Expression in Early Stage Cervical Carcinoma Treated by Surgery.

Objective: To evaluate the prognostic significance of p53 protein expression in patients with early stage cervical carcinoma treated by surgery alone in a well-controlled study. Methods: A matched case-control study was performed in patients with stage Ib-IIa cervical carcinoma who underwent radical hysterectomy with pelvic lymphadenectomy. Patients had neither lymph node metastasis nor involvement of the parametrium and surgical margins, and did not receive any adjuvant treatment. Cases included 30 patients who had tumor recurrence within 5 years after surgery; controls included 60 patients who were disease-free for at least 5 years after surgery. Cases and controls were within 10 years of age, had the same stage and tumor type, and underwent surgery on as close to the same date as possible. The tumor sizes of cases and controls were within 1 cm of each other. Expression of p53 protein was studied by immunohistochemistry. Expression was considered positive when at least 10% of tumor cells showed nuclear staining. Results: No significant difference of p53 expression was observed between the case group and the control group (33% versus 40%). High histologic grade of tumors and lymphovascular space invasion were significantly associated with tumor recurrence in multivariable analysis (p=0.012 and 0.014, respectively). Conclusion: In this study, expression of p53 did not correlate with tumor recurrence. Immunohistochemistry for p53 protein appears to provide no prognostic information in the patients with early stage cervical cancer treated by surgery.     

A risk score for selective screening for gestational diabetes mellitus

Objective

To develop a risk score to predict women who are likely to have an abnormal glucose challenge test (GCT) for gestational diabetes mellitus (GDM) screening.

Study design

A cohort of 1876 pregnant women who underwent a GCT between March 2005 and December 2005 at our institution were studied. A multivariable analysis was performed to determine the clinical features that were significantly associated with an abnormal GCT. These factors were incorporated into the equation which was subsequently transformed to the risk score. The validity of this risk score was then tested in a different cohort of 1900 women who underwent a GCT between October 2006 and July 2007.

Results

Of 1876 women in the derivation cohort, 586 (31.2%) had positive GDM screening. In a multivariable analysis, age, body mass index, family history of diabetes, prior macrosomia, and history of ≥2 spontaneous abortions were significantly associated with an abnormal GCT. These five variables were added into the equation to determine the risk score. At a cutoff score of ≥380, the sensitivity, specificity, positive predictive value, and negative predictive value to predict an abnormal GCT were 86.9%, 45.0%, 41.8%, and 88.3%, respectively. When the equation with the same cutoff score was tested in the validation cohort, a similar diagnostic performance was obtained. By adopting this risk scoring approach to GDM screening, 41.3% of women could avoid GCT.

Conclusion

Our risk score based on clinical data is simple, noninvasive, costless, and reliable to identify women who are likely to have an abnormal GCT.