Artifact suppression for breast specimen imaging in micro CBCT using deep learning.

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.

A Clinical Prediction Model for Breast Cancer in Women Having Their First Mammogram.

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.

Truncation effect reduction for fast iterative reconstruction in cone-beam CT.

BACKGROUND: Iterative reconstruction for cone-beam computed tomography (CBCT) has been applied to improve image quality and reduce radiation dose. In a case where an object's actual projection is larger than a flat panel detector, CBCT images contain truncated data or incomplete projections, which degrade image quality inside the field of view (FOV). In this work, we propose truncation effect reduction for fast iterative reconstruction in CBCT imaging. METHODS: The volume matrix size of the FOV and the height of projection images were extrapolated to a suitable size. These extended projections were reconstructed by fast iterative reconstruction. Moreover, a smoothing parameter for noise regularization in iterative reconstruction was modified to reduce the accumulated error while processing. The proposed work was evaluated by image quality measurements and compared with conventional filtered backprojection (FBP). To validate the proposed method, we used a head phantom for evaluation and preliminarily tested on a human dataset. RESULTS: In the experimental results, the reconstructed images from the head phantom showed enhanced image quality. In addition, fast iterative reconstruction can be run continuously while maintaining a consistent mean-percentage-error value for many iterations. The contrast-to-noise ratio of the soft-tissue images was improved. Visualization of low contrast in the ventricle and soft-tissue images was much improved compared to those from FBP using the same dose index of 5 mGy. CONCLUSIONS: Our proposed method showed satisfactory performance to reduce the truncation effect, especially inside the FOV with better image quality for soft-tissue imaging. The convergence of fast iterative reconstruction tends to be stable for many iterations.

Intraoperative Molecular Analysis of Total Tumor Load in Sentinel Lymph Node: A Predictor of Axillary Status in Early Breast Cancer.

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.

Real-life clinical pattern, management, and survival in Thai patients with early-stage or metastatic triple-negative breast cancer.

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.

The Pre-Treatment Neutrophil-Lymphocyte Ratio: a Useful Tool in Predicting Non-Sentinel Lymph Node Metastasis in Breast Cancer Cases

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.

Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and Clinicopathological Factors in Patients with Esophageal Squamous Cell Carcinoma.

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.

Mimicked cartilage scaffolds of silk fibroin/hyaluronic acid with stem cells for osteoarthritis surgery: Morphological, mechanical, and physical clues.

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.

Single nucleotide polymorphisms in the Gc gene for vitamin D binding protein in common cancers in Thailand.

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.

Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer.

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.

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.

BACKGROUND: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. METHODS: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. RESULTS: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. CONCLUSION: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

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.

Scaffold library for tissue engineering: a geometric evaluation.

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.

Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

Specific intronic p53 mutation in esophageal squamous cell carcinoma in Southern Thailand.

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_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.

Establishment the cost-effectiveness through set criteria of laparoscopic cholecystectomy.

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.

Correlation of epidermal growth factor receptor mutation, immunohistochemistry, and fluorescence in situ hybridization in esophageal squamous cell carcinoma.

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.

Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma.

PURPOSE: To assess the status of EGFR, HER-2, and CCND1 at the gene and protein levels in esophageal squamous cell carcinoma. METHODS: Dual-color FISH assays were performed using DNA probes for EGFR/CEP 7, HER-2/CEP 17, and CCND1/CEP 11. The respective proteins, furthermore, was assessed in IHC assays and correlated with patient and tumor characteristics. RESULTS: From 55 ESCCs, 8 (15%) tumors showed gene amplification and 20 (36%) had gene overrepresentation (balanced gene and chromosome 7 polysomy) for EGFR. High-level protein expression was frequent (49%), positively correlated with gene copy numbers (kappa=0.4), and associated with well-differentiated histology (p=0.02). For HER-2, gene amplification was detected in a single tumor (2%) and protein overexpression was rare (9%). CCND1 gene was amplified in 23 (42%) tumors; likewise, CCND1 protein overexpression was common (58%) and prevailed in gene overrepresentation or amplification. Only 1 patient showed gene amplification for both EGFR and CCND1. Survival was not associated with EGFR or CCND1 gene/protein status, whereas negative patients for HER-2 protein had a better survival than positive patients (p=0.04). CONCLUSIONS: Frequent overexpression and gene amplification of EGFR and CCND1 make these molecules and their pathways potential therapeutic targets for ESCC. In addition, EGFR and CCND1 appeared to be independently altered suggesting alternative mechanisms for pathway activation. Therapeutic agents targeting these molecules are urged to be tested in clinical trials and comprehensive biological analyses should be included to properly interpret the outcome.

Results of gastric pull-up reconstruction for pharyngolaryngo-oesophagectomy in advanced head and neck cancer and cervical oesophageal squamous cell carcinoma.

OBJECTIVE: To study long-term clinical swallowing function and survival outcome in head and neck and cervical oesophageal cancer patients who underwent pharyngolaryngo-oesophagectomy (PLE). METHODS: The clinical data of 48 patients who were treated with PLE were analysed. All patients had advanced disease, so the construction required a transposed stomach. Body weight and clinical swallowing function were evaluated postoperatively. The swallowing function was assessed at an interview concerning food ingestion and regurgitation. The survival group was studied using a Kaplan-Meier survival curve. RESULTS: Forty-one cases of hypopharyngeal cancer and four cases of cervical oesophageal cancer were studied. In three cases (6%), hypopharyngeal and thoracic oesophageal squamous cell carcinoma occurred together. Most cases had good-to-fair results. The average body weight gain was increased after surgery. There was one hospital death. The most common complications were pulmonary (4%). Median survival was 27 months. CONCLUSION: A pharyngogastric anastomosis after PLE can be performed with low morbidity and good swallowing function.

Mastectomy without drain at pectoral area: a randomized controlled trial.

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.