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BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655.

Background: Giant fibrovascular polyps of the esophagus are rare tumors. They are usually located in the upper third of the esophagus. Symptoms include dysphagia and regurgitation of the mass into the oral cavity, which can cause airway obstruction, secondary to mechanical pressure on the larynx. We present a 34-year-old male patient with a 10-month history of gradually intermittent dysphagia and regurgitating mass into the mouth without syncope, airway obstruction, weight loss, melena and hematemesis. After diagnosis of a giant fibrovascular polyp of the esophagus, endoscopic polypectomy was performed. Histopathological examination revealed a fibrovascular polyp. Esophagoscopy at 2 years after excision showed no mass or symptom recurrence. The literatures regarding giant esophageal polyp were reviewed. [ABSTRACT FROM AUTHOR]

Background: The multidisciplinary approach for the improvement of the accuracy of sentinel lymph node (SN) examination is beneficial as it is a less invasive procedure for breast cancer patients . The trend in avoiding axillary dissection will decrease the operative morbidity. The intraoperative technique for the detection of tumor cells in SN by imprint immunocytochemistry (ICC) was studied to avoid axillary dissection. Objective: The aim of this study was to compare the results of intraoperative scrape imprint ICC with the results of serial section stained by combined hematoxylin-eosin (H&E) and subsequent immunohistochemistry (IHC). The accuracy, sensitivity and specificity of both methods were analysed. Material and Methods: From April 2005 to March 2006, 33 patients with breast cancer were enrolled. The sentinel lymph nodes were removed and sent to pathologists for scrape imprint cytology. The anticytokeratin ICC was used to detect metastatic cancer cells. The sentinel lymph nodes were then routinely examined by H&E staining. If the cancer cells were not detected by the routine H&E study, the negative nodes were then serially sectioned at 20 μm and stained by anticytokeratin IHC to rule out the false negative results. The axillary contents of all cases were removed following the SN dissection for complete pathologic examination to confirm the SN node examination results. Results: Seventy-two sentinel lymph nodes were removed from 33 patients with operable breast cancer. The results of imprint cytology were compared with those of the serial section of SN stained using the combined H&E and IHC methods. The sensitivity of intraoperative SN imprint ICC was 33%, the specificity 94% and the accuracy 66%. The positive predictive value of the imprint ICC was 83% and the negative predictive value 63%. Conclusions: The intraoperative SN imprint ICC in this study was found to have 33% sensitivity, 66% accuracy and low negative predictive value when compared with serial section with combined H&E and IHC. The intraoperative SN imprint ICC alone is not sufficient to be used as a guide to avoid axillary lymph node dissection in operable breast cancer. [ABSTRACT FROM AUTHOR]

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64-0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24-0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis.

Background: Cone-beam computed tomography (CBCT) has been introduced for breast-specimen imaging to identify a free resection margin of abnormal tissues in breast conservation. As well-known, typical micro CT consumes long acquisition and computation times. One simple solution to reduce the acquisition scan time is to decrease of the number of projections, but this method generates streak artifacts on breast specimen images. Furthermore, the presence of a metallic-needle marker on a breast specimen causes metal artifacts that are prominently visible in the images. In this work, we propose a deep learning-based approach for suppressing both streak and metal artifacts in CBCT., Methods: In this work, sinogram datasets acquired from CBCT and a small number of projections containing metal objects were used. The sinogram was first modified by removing metal objects and up sampling in the angular direction. Then, the modified sinogram was initialized by linear interpolation and synthesized by a modified neural network model based on a U-Net structure. To obtain the reconstructed images, the synthesized sinogram was reconstructed using the traditional filtered backprojection (FBP) approach. The remaining residual artifacts on the images were further handled by another neural network model, ResU-Net. The corresponding denoised image was combined with the extracted metal objects in the same data positions to produce the final results., Results: The image quality of the reconstructed images from the proposed method was improved better than the images from the conventional FBP, iterative reconstruction (IR), sinogram with linear interpolation, denoise with ResU-Net, sinogram with U-Net. The proposed method yielded 3.6 times higher contrast-to-noise ratio, 1.3 times higher peak signal-to-noise ratio, and 1.4 times higher structural similarity index (SSIM) than the traditional technique. Soft tissues around the marker on the images showed good improvement, and the mainly severe artifacts on the images were significantly reduced and regulated by the proposed., Conclusions: Our proposed method performs well reducing streak and metal artifacts in the CBCT reconstructed images, thus improving the overall breast specimen images. This would be beneficial for clinical use., (© 2024. The Author(s).)

Background: Digital mammography is the most efficient screening and diagnostic modality for breast cancer (BC). However, the technology is not widely available in rural areas. This study aimed to construct a prediction model for BC in women scheduled for their first mammography at a breast center to prioritize patients on waiting lists., Methods: This retrospective cohort study analyzed breast clinic data from January 2013 to December 2017. Clinical parameters that were significantly associated with a BC diagnosis were used to construct predictive models using stepwise multiple logistic regression. The models' discriminative capabilities were compared using receiver operating characteristic curves (AUCs)., Results: Data from 822 women were selected for analysis using an inverse probability weighting method. Significant risk factors were age, body mass index (BMI), family history of BC, and indicated symptoms (mass and/or nipple discharge). When these factors were used to construct a model, the model performance according to the Akaike criterion was 1387.9, and the AUC was 0.82 (95% confidence interval: 0.76-0.87)., Conclusion: In a resource-limited setting, the priority for a first mammogram should be patients with mass and/or nipple discharge, asymptomatic patients who are older or have high BMI, and women with a family history of BC.

Background: Axillary lymph node dissection (ALND) remains the standard of care in breast cancer patients with positive sentinel lymph node (SLN). However, approximately 40-60% of patients with positive SLNs have not developed to non-SLN metastasis and ALND seems to be an overtreatment. The purpose of this study was to analyze predictors and define a specific cut-off of total tumor load (TTL) of CK19 that can be used as a predictive factor of non-SLN metastasis in early breast cancer patients., Materials and Methods: The records of 238 patients with cT1-3N0 breast cancer who had an intraoperative SLN evaluation performed through One-Step nucleic acid (OSNA) assay at Songklanagarind Hospital between 1 January 2015 and 31 December 2019 were examined. Univariate and Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict metastasis to non-SLNs. Finally, receiver operative characteristics (ROC) curves were used to choose an optimal TTL cut-off value., Results: Of a total of 110 patients who had a positive SLN, only 48 (43.64%) were found to have positive nodes in non-SLN. Multivariate analysis revealed that lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/μL) were independent predictors of positive non-SLNs.  TTL cut-off value was 19,000 copies/μL, with an AUC of 0.838 with 72.7% sensitivity and 84.7% specificity to predict non-SLN metastasis., Conclusions: The likelihood of positive non-SLNs in patients who showed a positive SLN correlates with lymphovascular invasion, type of SLN metastasis and SLN TTL (copies/μL). Our result revealed that the patients with a SLN TTL ≥19,000 copies/µl continue to attract the recommendation to proceed with ALND. This cut-off value can then help clinicians to assess which patients would benefit from ALND.

Objectives: To characterize the clinical pattern and evaluate real-life practices in the management of patients with triple-negative breast cancer (TNBC) in Thailand., Methods: In this multicenter, prospective, observational cohort, females (aged ≥18 years) with histologically and immunohistochemically confirmed TNBC were enrolled. Patient data was collected at four study visits-an inclusion visit (for enrollment), and three subsequent follow-up visits at 12±1, 24±1, and 36±1 months after completion of first day of any planned chemotherapy., Results: Of the 293 enrolled patients, 262 (89.4%) had early-stage TNBC (Stage I: 46 patients, Stage II: 151 patients, and Stage III: 65 patients) and 31 (10.6%) had metastatic TNBC (mTNBC). Chemotherapy was prescribed to 95.4% of the early-stage patients and to 100.0% of the mTNBC patients; most commonly as anthracycline-based in combination with cyclophosphamide and other agents. Patients' performance status and consensus guidelines were the major factors affecting choice of treatment. In early-stage patients, median disease-free survival (DFS) and overall survival (OS) had not been reached for Stage I and II patients, and were calculated to be 37.0 months and 40.0 months, respectively, in Stage III patients. In mTNBC patients, progression-free survival (PFS) and OS were found to be 10.0 months and 14.0 months, respectively. In Stage III patients, anthracycline-based regimens were found to be associated with increase in DFS (p = 0.0181) and OS (p = 0.0027) compared to non-anthracycline-based regimens. In mTNBC patients, non-taxane-based regimens were associated with an increase in PFS (p = 0.0025). The 3-year survival rates in early-stage and mTNBC patients were 85.0% and 21.0%, respectively., Conclusion: Clinical management of TNBC in Thailand follows the general guidelines for treatment of TNBC. However, prognosis and survival outcomes are suboptimal, especially in progressive disease. This study is the first assessment in the existing practices in which the results could pave to way to improve the treatment outcome of TNBC in Thailand., Competing Interests: This study was funded by Sanofi Aventis (Thailand) Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The sentinel lymph node (SLN) biopsy is a highly accurate predictor of overall axillary nodal status in early breast cancer patients. There is however, still a debate on which patients with a positive SLN can benefit from axillary lymph node dissection (ALND). Numerous studies have been designed to identify variables that are predictive of non-SLN metastasis to avoid a complete ALND. The aim of this study was to determine whether the pre-treatment neutrophil-lymphocyte ratio (NLR) can be a predictive factor of non-SLN metastasis in early breast cancer patients. Materials and Methods: The records of 214 consecutive patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation at Songklanagarind Hospital between the 1stof March 2011 and the 30thof May 2016 were examined. Data on patient demographics, tumor variables and NLR were collected and factors for non-SLN metastasis were analyzed using multivariate logistic regression. The power of the NLR was quantified with receiver operating characteristics (ROC) curves as measured by the areas under curves (AUC). Results: Multivariate analysis established presence of lymphovascular invasion (OR 8.4, 95%CI 2.3-31.3, p=0.002), macrometastasis (OR 6.6, 95%CI 1.8-24.7, p=0.005), and NLR (OR 2.3, 95%CI 1.1-4.8, p=0.033) as predictive factors of non-SLN metastasis with statistical significance. The AUC for NLR was 0.7 (95%CI 0.6-0.8) with an optimal cut-off of 2.6 giving a sensitivity of 62%, a specificity of 83.8%, a positive predictive value of 77.3% and a negative predictive value of 70.5%. Conclusion: Pre-treatment NLR is a useful diagnostic aid for predicting additional non-SLN metastasis., (Creative Commons Attribution License)

Osteoarthritis is a critical disease that comes from degeneration of cartilage tissue. In severe cases surgery is generally required. Tissue engineering using scaffolds with stem cell transplantation is an attractive approach and a challenge for orthopedic surgery. For sample preparation, silk fibroin (SF)/hyaluronic acid (HA) scaffolds in different ratios of SF/HA (w/w) (i.e., 100:0, 90:10, 80:20, and 70:30) were formed by freeze-drying. The morphological, mechanical, and physical clues were considered in this research. The morphological structure of the scaffolds was observed by scanning electron microscope. The mechanical and physical properties of the scaffolds were analyzed by compressive and swelling ratio testing, respectively. For the cell experiments, scaffolds were seeded and cultured with human umbilical cord-derived mesenchymal stem cells (HUMSCs). The cultured scaffolds were tested for cell viability, histochemistry, immunohistochemistry, and gene expression. The SF with HA scaffolds showed regular porous structures. Those scaffolds had a soft and elastic characteristic with a high swelling ratio and water uptake. The SF/HA scaffolds showed a spheroid structure of the cells in the porous structure particularly in the SF80 and SF70 scaffolds. Cells could express Col2a, Agg, and Sox9 which are markers for chondrogenesis. It could be deduced that SF/HA scaffolds showed significant clues for suitability in cartilage tissue engineering and in surgery for osteoarthritis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67) in ESCC patients., Objective: To study the correlation between SCCA, CYFRA 21-1, Ki-67, and clinicopathological factors in ESCC patients., Material and Method: Pretreatment SCCA and CYFRA 21-1 serum levels were measured, while the expression of Ki-67 was assessed on tumor tissue. The associations between these biomarkers, clinicopathological factors, and overall survival were analyzed., Results: One hundred sixty six patients participated in this study. Elevated SCCA and CYFRA 21-1 were found in 78.9% and 50.0% of the patients, respectively, while 42.8% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p = 0.128) to each other nor to age, sex, T N, M location, grade, or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p = 0.010), M1 (p = 0.010), and poor grade (p = 0.015) but not to age, sex, N, or location. Levels of SCCA, CYFRA 21-1, and Ki-67, alone or in any combination, were not correlated to survival of patients., Conclusion: The authors showed that Ki-67 in tumor tissue is probably a more reliable marker than serum SCCA and CYFRA 21-1 in predicting the clinical course of ESCC.

Purpose: To evaluate the correlation between cosmetic outcome (CO), body image, and quality of life in post breast-conserving therapy (BCT) women., Materials and Methods: This cross-sectional study concerned one-year post-completed BCT Thai women. The data included subjective and objective CO with a questionnaire covering demographic and clinical data, anti-hormonal treatment status, Eastern Cooperative Oncology Group (ECOG) performance status, Self-Reported Cosmetic Outcomes (SRCO), Self-Reported Breast Symmetry (SRBS), Body Image Scale (BIS), and the Functional Assessment of Cancer Therapy with Breast Cancer subscale (FACT-B). Participants had breast photographs taken for the evaluation of objective cosmetic outcome (OCO) after breast cancer conservation treatment. The relationship between CO and FACT-B was tested using Spearman's rank correlation Results: A total 127 participants volunteered for the study. The participant characteristics were age 52(±9), Buddhist 87%, married 65%, body mass index 25.0(±4.6), breast cup size A-C 91%, college educated 60%, employed 66%, ECOG 0-1 95%, tumor size less than or equal to 2 cm 55%, no lymph node metastasis 98%, and taking tamoxifen 57%. Two percent of the participants regretted their decision to undergo BCT. The SRCO was excellent in 2%, good in 68%, fair in 30%, and poor in 0%. For SRBS, rates were 17%, 58%, 24% and 1% for excellent, good, fair and poor cosmetic outcomes, respectively. The BCCT scores were excellent 24%, good 39%, fair 32%, and poor 6%. The median total QOL score of the participants was 130 (93-144). There was no significant correlation between CO and FACT-B scores., Conclusions: The significance of CO for FACT-B in Thai women with breast cancer could not be assessed in detail because of a very low level of correlation. The results may be due to the effects of cultural background.

Background: This case-control study aimed to determine if there were any associations between the two single nucleotide polymorphisms (SNPs) in Gc, rs7041 (Asp416Glu) and rs4588 (Thr420Lys) and 3 common cancers (breast, lung and colorectal) in Thai patients., Materials and Methods: Two hundred and eighty two colorectal, 101 breast and 113 lung cancer patients were recruited from one institute during 2011-2013. The controls were age-matched volunteers who had a negative history of index cancers. In addition, vitamin D levels were compared among different genotypes in the 2 SNPs., Results: The minor allele frequencies of rs7041 (G) and rs4588 (A) were 0.32 and 0.24, respectively. Under the dominant model, the study found significant associations between minor-allele genotypes of the SNP rs7041 (TG/GG) and lung cancer (odds ratio [OR] 1.78, 95% CI 1.05-3.03). When subgroup analysis was performed according to sex and age at diagnosis, the study found that the minor- allele genotypes of rs7041 (TG/GG) were significantly associated with colorectal cancer in patients whose age at diagnosis was more than 60 years (OR 1.67, 95%CI 1.06-2.61) and the minor-allele genotypes of rs4588 (CA/AA) were significantly associated with colorectal cancer in males aged 60 years or less (OR 2.34, 95%CI 1.25-4.37). When SNP combinations (rs7041-rs4588) were examined, the TT-CA combination had a significant protective association with lung cancer (OR 0.44, 95% CI 0.22-0.85). On evaluation of serum 25(OH)D levels in 205 individuals without cancer (males 144, females 61), the proportion of subjects with low serum vitamin D (< 20 ng/ml) in those harboring CA or AA genotypes of rs4588 (41.7%) was significantly higher than the CC genotype (15.5%, p-value < 0.01)., Conclusions: Genetic polymorphisms in Gc were associated with lung and colorectal cancers in Thai patients. Lower serum 25(OH)D in minor variants of rs4588 may explain this association.

Concurrent chemoradiotherapy (CCRT) induces toxicities from inflammation and immunological suppression. Omega-3 fatty acids, glutamine, and arginine are therapeutic factors that can attenuate such inflammation and promote cellular immunity. The question is whether immunonutrition (IN) during CCRT reduces inflammation and improves the immune function in patients with esophageal squamous cell carcinoma (ESCC). Seventy-one locally advanced ESCC patients being treated with CCRT (5-FU and cisplatin) were randomized into 2 groups. The IN group received a combination of omega-3 fatty acids, glutamine, and arginine, whereas the control group received standard formula. The levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interferon-gamma (IFN), interleukin (IL-6, IL-10), CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes were measured before and during treatment. The levels of CRP (P = 0.001) and TNF (P = 0.014) increased more during treatment in the control group than the treatment group, whereas IFN, IL-6, and IL-10 were similar but not significantly. CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes decreased more in the control group than in the treatment group, but not significantly. Enteral IN during CCRT reduced the increase of inflammatory cytokine levels.

Background: Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest., Patients and Methods: BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up., Results: Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths., Conclusion: Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P ≤ 3 × 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 × 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype., (© 2012 Wiley Periodicals, Inc.)

The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 × 10(-13)]. Thus, 19p13.1 is the first triple-negative-specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways., (©2012 AACR.)

Tissue engineering scaffold is a biological substitute that aims to restore, to maintain, or to improve tissue functions. Currently available manufacturing technology, that is, additive manufacturing is essentially applied to fabricate the scaffold according to the predefined computer aided design (CAD) model. To develop scaffold CAD libraries, the polyhedrons could be used in the scaffold libraries development. In this present study, one hundred and nineteen polyhedron models were evaluated according to the established criteria. The proposed criteria included considerations on geometry, manufacturing feasibility, and mechanical strength of these polyhedrons. CAD and finite element (FE) method were employed as tools in evaluation. The result of evaluation revealed that the close-cellular scaffold included truncated octahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. In addition, the suitable polyhedrons for using as open-cellular scaffold libraries included hexahedron, truncated octahedron, truncated hexahedron, cuboctahedron, rhombicuboctahedron, and rhombitruncated cuboctahedron. However, not all pore size to beam thickness ratios (PO:BT) were good for making the open-cellular scaffold. The PO:BT ratio of each library, generating the enclosed pore inside the scaffold, was excluded to avoid the impossibility of material removal after the fabrication. The close-cellular libraries presented the constant porosity which is irrespective to the different pore sizes. The relationship between PO:BT ratio and porosity of open-cellular scaffold libraries was displayed in the form of Logistic Power function. The possibility of merging two different types of libraries to produce the composite structure was geometrically evaluated in terms of the intersection index and was mechanically evaluated by means of FE analysis to observe the stress level. The couples of polyhedrons presenting low intersection index and high stress level were excluded. Good couples for producing the reinforced scaffold were hexahedron-truncated hexahedron and cuboctahedron-rhombitruncated cuboctahedron.

Aim: To investigate p53 mutations in esophageal cancer in a high-risk population, and correlate them with smoking, alcohol consumption and betel chewing., Methods: One hundred and sixty-five tumor samples of esophageal squamous cell carcinoma (ESCC) obtained from a university hospital in Songkhla province, Southern Thailand were investigated for p53 mutations in exons 5-8, using polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. A polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay was additionally used to confirm possible germline mutation in intron 6. A history of risk habits was obtained by interviews. The association between risk habits and mutation frequency was evaluated using the χ(2) test., Results: The studied specimens were from 139 male and 26 female patients with ESCC, treated at Songklanagarind Hospital. Most of the patients were smokers (86.7%) and alcohol consumers (72.73%), and 38.3% were betel chewers. Forty-three mutations of the p53 gene were detected in 25.5% (42/165) of tumor samples. Mutations were most commonly found in exon 5 (25.6%) and exon 8 (25.6%). Mutations in the hot-spot codon 248 were found in four cases (9.3% of all mutations). G:C→C:G (30.23%), G:C→A:T (27.90%) and G:C→T:A (16.28%) were the prevalent spectra of mutations. Unexpectedly, among 10 intronic mutations, eight cases harbored a similar mutation: G→C substitution in intron 6 (nucleotide 12759, GenBank NC&#95;000017). These were additionally confirmed by the RFLP technique. Similar mutations were also detected in their matched blood samples using RFLP and direct sequencing, which suggested germline mutations. There was no significant correlation between risk habits and p53 mutation frequency., Conclusion: A proportion of Thai ESCC patients harbored specific intronic p53 mutations, which might be germline mutations. Further studies are needed to explore this novel finding.

Objective: To assess the set criteria of laparoscopic cholecystectomy (LC) in reducing the length of hospital stay (LOHS), and total treatment expenditure., Material and Method: The measurement outcomes were prospectively analyzed through the medical record, and self questionnaire of the patients., Results: During the 1-year trial, a total of 122 patients were scheduled for LC. Among these, 85 cases had met the set criteria of low risk clients of both preoperative indicator of a) American Society of Anesthesiologists (ASA) class 1 or 2, and postoperative indicators of b) no surgical drainage, and c) no immediate complication, while 37 cases were excluded due to ASA class 3 or 4, and various reasons. Distributed by the duration of hospital stay, the patients were classified in to three groups; group A was overnight hospital stay, 15 of 85 subjects (17.6%), group B was short hospital stay (within 3 days), 51 of 85 subjects (60.0%), and group C was long hospital stay (more than 3 days), 19 of 85 subjects (22.4%). The mean length of hospital stay (LOHS) was 24 +/- 1.61 hours in group A, 55 +/- 11.16 in group B, and 108 +/- 21.59 in group C, while the average total expenditure was 531.22 +/- 111.09, 665.5 +/- 133.35 and 812.33 +/- 158.62, respectively. For the overnight hospital stay group, the LOHS and the total treatment expenditure was significantly lower the other groups (p < 0.001). The majority of the overnight hospital stay group had rated the patient satisfaction as excellent., Conclusion: The set criteria of laparoscopic cholecystectomy (LC) are helpful and establish the cost-effectiveness in terms of reduction of LOHS and total treatment expenditure.

Background: The epidermal growth factor receptor (EGFR) has become a promising target for novel anticancer therapy Evaluation of its biological profiles including gene mutation, amplification, and protein expression in esophageal squamous cell carcinoma (ESCC) is essential to establish the EGFR molecular feature(s) suitable to select patients in anti-EGFR therapy., Material and Method: The subjects' specimens of ESCC at Songklanagarind Hospital were obtained and investigated for EGFR protein expression and gene amplification. Polymerase chain reaction (PCR) was performed to amplify the EGFR DNA product. The mutational status of EGFR exons 19 and 21 was analyzed using direct sequencing. The entire biological profiles of the EGFR were then correlated., Results: There were 48 eligible ESCC specimens. No somatic mutation in the tyrosine kinase domain of EGFR was detected A high level of EGFR protein was exhibited in 22 patients (46%). Twenty-three patients (48%) had shown a high gene copy numbers. However, no direct correlation between EGFR protein and gene status was observed., Conclusion: EGFR mutations in the tyrosine kinase domain of exons 19 and 21 were absent in ESCC, whereas, protein overexpression and gene amplification was prevalent. Therefore, selection of ESCC patients for studies with anti-EGFR agents based on protein expression or gene copy number, not gene mutation, is rational.

Objectives: Mastectomy is still one of the standard alternative procedures for the management of female breast cancer. Axillary node dissection is also performed to establish the accurate staging. After operation, the axilla must be drained because of lymphatic leakage. Whether the raw surface at the pectoral area should be drained or not is an interesting controversial point. The authors conducted a randomized controlled trial to compare outcomes after modified radical mastectomy (MRM) with and without drainage at the pectoral area., Methods: Sixty patients who agreed to be treated with MRM and had given their consent were enrolled. Mastectomy was performed to remove the breast tissue proper by scalpel in order to minimize tissue injury. The axillary contents were removed by sharp instrument. After bleeding had stopped, patients were randomly allocated to one or other of 2 groups: group I (n = 30): only 1 drain was inserted at the axilla area; group II (n = 30): 2 conventional drains were inserted into the pectoral area and axilla area. The size of tube drain and negative suction pressure were constant in all cases. Volume of contents was recorded daily. Subcutaneous seroma or hematoma were carefully observed and confirmed by ultrasonography 3-5 days after operation. Overall drainage contents and complications were compared., Results: The mean weight of breast tissue of group I was 632.1 g and group II 654.0 g (p = 0.81). Total drainage contents (median) from the two groups were 250 cm3 and 231 cm3 respectively (p = 0.796). Complications occurred in 1 case in group I and 2 cases in group II (p = 0.35). None of the above differences were statistically significant., Conclusion: Mastectomy by scalpel can be performed without drainage at the pectoral area. Overall complications in the conventional group and the group without drain did not differ significantly.

The association of lifestyle habits and polymorphism of ADH2 and ALDH2 genes with the risk of esophageal cancer in Thai population was investigated in a hospital-based case-control study: 202 cases and 261 controls. The results of multivariate logistic analysis showed that alcohol consumption >60g/day, smoking >10 cigarettes/day and chewing betel >or=10 quids/day significantly increased risk (odds ratio (OR) 5.84, 95% confidence interval (CI) 3.15-10.83; 4.65, 95% CI 1.99-10.84; and 4.68, 95% CI 2.05-10.72, respectively). ADH2*1/*1 also increased the risk significantly (OR 1.56, 95% CI 1.01-2.39) while ALDH2 did not (OR of ALDH2*1/*2 1.57, 95% CI 0.89-2.76). However, the combined at risk genotypes, ADH2*1/*1 and ALDH2*1/*2 increased risk to four-fold. In addition, significant gene-environment interaction was found. Heavy drinkers >60g/d harboring ADH2*1/*1 or ALDH2*1/*2 had about an 11-fold increased risk.

Background: Southern Thailand is an area with a high frequency of esophageal carcinoma. This paper presents basic data regarding esophageal carcinoma patients from this region., Methods: Patients with histopathological confirmed esophageal carcinoma were retrospectively reviewed. The age, sex, location of tumor and resectability were studied., Results: A total of 813 cases of esophageal carcinoma were reviewed, male:female ratio was 3.54:1 (634:179). Average age in males was 64.62 years and 64.30 years in females. The peak age-incidence was 51-70 years. Squamous cell carcinoma was most commonly found in the mid thoracic portion of the esophagus with 369 cases (45.39%), 70 cases (8.61%) were found in the cervical portion of the esophagus. Adenocarcinoma cancer was found at the esophagogastric junction in 47 cases (5.78%). Only 293 cases (36.04%) were operable. Respiratory tract involvement was noted in 49 cases., Conclusion: The most common type of esophageal cancer in Southern Thailand is squamous cell carcinoma, as in other countries in Asia. The status of the patients, advanced age and locally advanced tumor were major factors of our low operable rate.

Squamous-cell carcinoma of the esophagus (SCCE) shows geographic variations in incidence that are thought to reflect the etiological involvement of environmental or dietary risk factors. Mutations of TP53 are frequent in SCCE, and there is evidence that both the frequency and type of these mutations may differ from one geographic area to the other. Although SCCE is relatively rare in most parts of Thailand, the province of Songkhla (south Thailand) has been described as a high-risk area for SCCE. We have analyzed 56 SCCE cases from this area for TP53 mutations by denaturing gradient gel electrophoresis (DGGE, exons 5-8) and direct DNA sequencing. The same tumors were also analyzed for MDM2 gene amplification by differential PCR. TP53 mutations were detected in 23 cases (41%). In contrast, clear amplification of MDM2 was detected in only 2 cases (4%), both of which contained wild-type TP53. Comparison with published results from other geographic areas of high SCCE incidence revealed that the spectrum of TP53 mutations in south Thailand is similar to that observed in central China (Henan Province) but clearly differs from that of SCCE from western Europe (Normandy, France; northern Italy), with more G:T transversions and fewer mutations affecting A and T base pairs. These results suggest that SCCE from south Thailand and from central China may involve similar risk factors., (Copyright 2000 Wiley-Liss, Inc.)

The gallstones from 55 patients in Southern Thailand were analyzed to disclose the chemical components using infrared grating spectrophotometry. The main components were calcium bilirubinate, calcium phosphate, calcium carbonate, choleterol and protein inproportions 52.6, 5.5, 5.5, 30.9 and 5.5 per cent of stones, respectively. These proportions are not different from those of gallstones in the northern or central regions of Thailand.

Clinical data from 175 patients with squamous cell carcinoma of the oesophagus or cardia admitted to Songklanagarind Hospital between 1982 and 1988 were analysed to evaluate the effects on survival of various tumour and treatment variables. Most tumours (greater than = 86%) were in stage III or IV. Forty-seven percent of stage-IV tumours and 99 per cent of those in stages I, II or III were resectable. One-year and 3-year survival rates of resected stage-III patients (57.3% and 27.5%) were significantly higher than those of resected stage-IV patients (33.3% and 0%). Resection conferred no benefit over radiotherapy chemotherapy or no treatment on the survival of stage-IV cases beyond one year. Combined chemotherapy/radiotherapy/resection of stage-III and stage-IV patients gave no statistically significant improvement in survival. Among resected patients, only lymph node involvement was associated with significantly lower survival (relative risk compared to no involvement = 2.3, 95% CL: 1.2, 4.6), while the fungating type of tumour was possibly associated with improved survival (relative risk compared with all other types = 0.24, 95% CL: 0.05, 1.1).