Sansanee Wongwaisayawan

Risk Factors of Breast Cancer: A Systematic Review and Meta-Analysis

The etiology of breast cancer might be explained by 2 mechanisms, namely, differentiation and proliferation of breast epithelial cells mediated by hormonal factors. We performed a systematic review and meta-analysis to update effects of risk factors for both mechanisms. MEDLINE and EMBASE were searched up to January 2011. Studies that assessed association between oral contraceptives (OC), hormonal replacement therapy (HRT), diabetes mellitus (DM), or breastfeeding and breast cancer were eligible. Relative risks with their confidence intervals (CIs) were extracted. A random-effects method was applied for pooling the effect size. The pooled odds ratios of OC, HRT, and DM were 1.10 (95% CI = 1.03-1.18), 1.23 (95% CI = 1.21-1.25), and 1.14 (95% CI = 1.09-1.19), respectively, whereas the pooled odds ratio of ever-breastfeeding was 0.72 (95% CI = 0.58-0.89). Our study suggests that OC, HRT, and DM might increase risks, whereas breastfeeding might lower risks of breast cancer.

Androgenic pathway in triple negative invasive ductal tumors: Its correlation with tumor cell proliferation

Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5α‐reductase type 1 (5αR1) and 17β‐hydroxysteroid dehydrogenase type 5 (17βHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5αR1, and 17βHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki‐67 labeling index, disease‐free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki‐67 labeling index than AR−/enzyme− samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki‐67 labeling index and AR status (P = 0.04) or 5αR1 (P < 0.001). Cox proportional hazards analysis showed that Ki‐67 labeling index and stage were the only factors predicting disease‐free and overall survival of the patients, although univariate Kaplan–Meier analysis revealed AR/5αR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation.

Dermabrasion: A Curative Treatment for Melasma

Abstract. Melasma is fairly common in Asian patients with a dark skin tone. It has long been known for its recalcitrance to any form of treatment. The objective of this article is to propose mechanical dermabrasion as a curative treatment for this entity. Five hundred and thirty-three patients with melasma were treated by mechanical dermabrasion using a rotatory diamond fraise. Four hundred and ten patients were available for long-term follow-up (mean follow-up time 5 years, range 1–9 years). Out of 410 patients, 398 (97%) achieved persistent clearance of melasma; in the remaining cases, there was partial recurrence after initial clearance. The common temporary sequelae were postoperative erythema or hyperpigmentation, pruritus, and milia formation. Two patients developed hypertrophic scars, one on the upper lip and one on the jawline, and one patient had permanent hypopigmentation on the forehead. In conclusion, mechanical dermabrasion is a relatively safe and highly effective means for curing melasma.

Ocular pythiosis: is it under-diagnosed?

PURPOSE To increase awareness of ocular pythiosis by presenting a typical case and summarizing clinical data of 11 ocular pythiosis cases in Ramathibodi Hospital. DESIGN Interventional case report. METHODS A 48-year-old healthy woman with a history of 3-week painful corneal ulcer of left eye was treated with enucleation. RESULTS The histopathology of enucleated eye revealed endophthalmitis and ulcerative keratitis with numerous hyphae in full-thickness of corneal stroma. The culture identification of the causative organism was Pythium insidiosum. The final diagnosis was ocular pythiosis. CONCLUSIONS Pythium insidiosum is a causative agent of pythiosis and is distributed worldwide. Ocular pythiosis may not be uncommon, as it may be underdiagnosed due to unfamiliarity among clinicians and microbiologists. Diagnosis of pythiosis is difficult. The disease has high morbidity, as evidenced by nearly evisceration or enucleation among all patients at Ramathibodi Hospital. Early detection and effective treatment are needed for possible cure.

Noninvasive treatment of bromidrosis by frequency-doubled Q-switched Nd:YAG laser

Abstract. Axillary bromidrosis (osmidrosis) is a common and disgusting disorder in Asian communities. Current treatments are basically invasive resulting in varying degrees of success and complications. The objective of this study was to investigate the efficacy of frequency-doubled Q-switched Nd:YAG laser as a possible noninvasive technique for treating axillary bromidrosis. Sixty-four axillae of 32 patients were lased by a single session of green light energy at the fluence of 3.5 joules at a 4-mm spot size. The follow-up time was 6–18 months (mean 15). Twenty-six patients (81.2%) showed good to excellent results, 4 patients (12.5%) had fair results, and 2 (6.2%) patients had poor results. The only side effect was a temporary hyperpigmentation at the periphery of the treated area in a few patients with dark skin color. In conclusion, frequency-doubled Q-switched Nd:YAG laser is an effective noninvasive treatment for axillary bromidrosis.

Correlation of UGT1A1*28 and *6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients

UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1(*)28 and (*)6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1(*)28 and (*)6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1(*)6 (AA). Neither UGT1A1(*)28 nor UGT1A1(*)6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1(*)28 and (*)6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1(*)28 and (*)6 polymorphisms may have an increased risk of irinotecan-induced neutropenia in Thai colorectal cancer patients.

Glioblastoma multiforme at the corpus callosum with spinal leptomeningeal metastasis

Glioblastoma multiforme (GBM) often occurs in the supratentorial white matter including corpus callosum. However, spinal leptomeningeal metastasis in cases of supratentorial GBM has been reported to be rare and there is usually a long interval between the cerebral lesion and the spinal seeding. We report here a case of GBM at the corpus callosum and other parts of the brain with simultaneous manifestation of spinal leptomeningeal seeding. The patient exhibited an abnormal motor behavior of the left hand as mirror movement when the right hand was performing a unimanual task (diagonistic dyspraxia) which is a sign of lesion of the posterior part and splenium of the corpus callosum. There were also signs of peripheral nerve or nerve root involvement suggestive of spinal metastasis without any sensory symptoms. He died 3 months after the onset of the symptoms confirming the poor prognosis and short survival time in cases with spinal leptomeningeal metastasis reported previously. The cerebral GBM with spinal seeding was disclosed at autopsy.

Development and Validation of a Breast Cancer Risk Prediction Model for Thai Women: A Cross-Sectional Study

BACKGROUND Breast cancer risk prediction models are widely used in clinical practice. They should be useful in identifying high risk women for screening in limited-resource countries. However, previous models showed poor performance in derived and validated settings. Therefore, we aimed to develop and validate a breast cancer risk prediction model for Thai women. MATERIALS AND METHODS This cross-sectional study consisted of derived and validation phases. Data collected at Ramathibodi and other two hospitals were used for deriving and externally validating models, respectively. Multiple logistic regression was applied to construct the model. Calibration and discrimination performances were assessed using the observed/expected ratio and concordance statistic (C-statistic), respectively. A bootstrap with 200 repetitions was applied for internal validation. RESULTS Age, menopausal status, body mass index, and use of oral contraceptives were significantly associated with breast cancer and were included in the model. Observed/expected ratio and C-statistic were 1.00 (95% CI: 0.82, 1.21) and 0.651 (95% CI: 0.595, 0.707), respectively. Internal validation showed good performance with a bias of 0.010 (95% CI: 0.002, 0.018) and C-statistic of 0.646(95% CI: 0.642, 0.650). The observed/expected ratio and C-statistic from external validation were 0.97 (95% CI: 0.68, 1.35) and 0.609 (95% CI: 0.511, 0.706), respectively. Risk scores were created and was stratified as low (0-0.86), low-intermediate (0.87-1.14), intermediate-high (1.15-1.52), and high-risk (1.53-3.40) groups. CONCLUSIONS A Thai breast cancer risk prediction model was created with good calibration and fair discrimination performance. Risk stratification should aid to prioritize high risk women to receive an organized breast cancer screening program in Thailand and other limited-resource countries.

Determination of irinotecan, SN-38 and SN-38 glucuronide using HPLC/MS/MS: Application in a clinical pharmacokinetic and personalized medicine in colorectal cancer patients

Irinotecan (CPT‐11) is chemotherapy used mainly in the metastatic colorectal cancer. The purpose of this study was to develop and validate the LC‐MS/MS for the simultaneous determination of CPT‐11, SN‐38, and SN‐38G.

HER2 expression in breast cancer with nonamplified HER2 and gains of chromosome 17 centromere.

Gains of chromosome 17 centromere (CEP17) may be accompanied by gains of chromosome 17q. To evaluate the effect of CEP17 gains (CEP17>3 copies per tumor nucleus) on the expression of the HER2 gene, which is located on chromosome 17q12-21.32, we analyzed HER2 amplification and expression in breast carcinomas with and without CEP17 gains. We isolated tumor nuclei from frozen tissues of 37 breast carcinomas for analysis of the HER2 gene and CEP17 by fluorescence in situ hybridization. HER2 expression was detected by immunohistochemistry (IHC) performed on formalin-fixed, paraffin-embedded sections of the corresponding tumors. Tumors with amplified HER2 as determined by both HER2 copy number and HER2/CEP17 ratio were detected in 29.7% (11/37). CEP17 gains were significantly associated with HER2 amplification (P=0.005) but not associated with estrogen receptor status, tumor grade, and lymph node status (P>0.05). In contrast, HER2 amplification was significantly associated with estrogen receptor negativity (P=0.020) but not with tumor grade and lymph node status (P>0.05). IHC analysis was performed in 7 HER2-amplified tumors and all of these were IHC 3+, which were used as positive controls. Among HER2–non-amplified tumors with CEP17 gains, only 1 tumor (1/8, 12.5%) was IHC 3+. However, none of the HER2–non-amplified tumors without CEP17 gains was IHC 3+. In HER2–non-amplified tumors, there was no significant association between HER2 protein expression as detected by IHC and CEP17 or HER2 copy number (P=0.999, P=0.785, respectively). These findings indicate that in the absence of HER2 amplification, CEP17 gains do not have a significant effect on HER2 protein expression.