Publications by authors named "Surasak Sangkhathat"

72 Publications

The attenuation effect of low piperine extract on doxorubicin-induced toxicity of blood chemical and immunological properties in mammary tumour rats.

Pharm Biol 2022 Dec;60(1):96-107

Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand.

Context: Many natural extracts have been shown to minimize the toxicity of doxorubicin (Dox). Low piperine L. (Piperaceae) extract (PFPE) is a natural extract containing many types of antioxidants that may reduce Dox toxicities.

Objective: To evaluate the effect of PFPE in attenuating the side effects of Dox.

Materials And Methods: Tumour-bearing Sprague Dawley rats were divided into five groups including normal, vehicle, 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P100 + Dox), 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P200 + Dox) and Dox. Rats were treated with Dox and/or PFPE three times/week for 4 weeks. Tumour burden, blood parameters, weight of internal organs and immunological data were investigated.

Results: The addition of 200 mg/kg PFPE significantly restored the levels of AST from 174.60 ± 45.67 U/L in the Dox group near to normal levels at 109.80 ± 4.99 U/L. The combination of PFPE and Dox also decreased the levels of CXCL7, TIMP-1, sICAM-1 and l-selectin about 1.4-1.6-fold compared to Dox group. Feeding rats with 200 mg/kg BW of PFPE combination with Dox slightly increased Th1 from 161.67 ± 14.28 cells in Dox group to 200.75 ± 5.8 cells meanwhile suppressed Treg from 3088 ± 78 cells in Dox to 2561 ± 71 cells.

Discussion And Conclusions: This study showed that PFPE ameliorated Dox toxicity in many aspects indicating the role of antioxidant and other substances in the extract on toxicity attenuation. This suggested the using of PFPE may be valuable for Dox treated patients.
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http://dx.doi.org/10.1080/13880209.2021.2018470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735876PMC
December 2022

Prognostic Impact of the Combination of Methylation and Promoter Mutation in Glioblastoma.

J Neurosci Rural Pract 2021 Oct 28;12(4):694-703. Epub 2021 Sep 28.

Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.

 The concept of combinational analysis between the methylation of ( ) and promoter ( ) mutation in glioblastoma (GBM) has been reported. The main study objective was to determine the prognosis of patients with GBM based on classification, while the secondary objective was to estimate the temozolomide effect on the survival time of GBM with classification.  A total of 50 GBM specimens were collected after tumor resection and were selected for investigating methylation and mutation. Clinical imaging and pathological characteristics were retrospectively analyzed. Patients with classification were analyzed using survival analysis to develop the nomogram for forecasting and individual prognosis.  All patients underwent resection (total resection: 28%, partial resection: 64%, biopsy: 8%). Thirty-two percent of all cases received adjuvant temozolomide with radiotherapy. Sixty-four percent of the case was found methylated , and 56% of the present cohort found mutation. Following combinational analysis of biomarkers, results showed that the GBMs with methylated and wild-type had a superior prognosis compared with other subtypes. Using Cox regression analysis with multivariable analysis, the extent of resection, postoperative chemoradiotherapy, classification were associated with a favorable prognosis. Hence, a web-based nomogram was developed for deploying individual prognostication.  The interaction of methylation and mutation was confirmed for predicting prognosis. The results from the present study could help physicians create treatment strategies for GBM patients in real-world situations.
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http://dx.doi.org/10.1055/s-0041-1735821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559075PMC
October 2021

Impact of immunohistochemistry-based subtyping of GATA3, CK20, CK5/6, and CK14 expression on survival after radical cystectomy for muscle-invasive bladder cancer.

Sci Rep 2021 10 27;11(1):21186. Epub 2021 Oct 27.

Division of Surgery, Prince of Songkla University, Hatyai, Songkhla, 90110, Thailand.

Molecular subtyping of muscle-invasive bladder cancer (MIBC) predicts disease progression and treatment response. However, standard subtyping based on transcriptomic analysis is relatively expensive. This study tried to use immunohistochemistry (IHC) to subtype MIBC based on GATA3, CK20, CK5/6, and CK14 protein expression. The IHC-based subtypes in MIBC subtypes were classified as luminal (GATA3 CK5/6, 38.6%), basal (GATA3CK5/6, 12.9%), mixed (GATA3 CK5/6, 37.9%), and double-negative (GATA3CK5/6, 10.6%) in 132 MIBC patients. All individual markers and clinicopathological parameters were analyzed against treatment outcomes after radical cystectomy. The mean patient age was 65.6 years, and the male to female ratio was 6.8:1. Positive IHC expression of GATA3, CK20, CK5/6, and CK14 were 80.3%, 50.8%, 42.4%, and 28.0%, respectively. Only GATA3 and CK5/6 were significantly associated with survival outcome (p values = 0.004 and 0.02). The mixed subtype was significantly better in 5-year OS at 42.8%, whereas the double-negative subtype had the worst prognosis (5-year OS 7.14%). The double-negative subtype had a hazard ratio of 3.29 (95% CI 1.71-6.32). Subtyping using GATA3 and CK5/6 was applicable in MIBCs, and patients with the double-negative subtype were at the highest risk and may require more intensive therapy.
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http://dx.doi.org/10.1038/s41598-021-00628-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551252PMC
October 2021

Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma.

Glob Med Genet 2021 Sep 22;8(3):116-122. Epub 2021 Jun 22.

Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

 Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA).  The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages.  Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT.  Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose-response relationship (Mann-Whitney's test,  = 0.02). Also, mutations of and were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test.  In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.
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http://dx.doi.org/10.1055/s-0041-1731069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378925PMC
September 2021

Fecal microbiome alterations in pediatric patients with short bowel syndrome receiving a rotating cycle of gastrointestinal prophylactic antibiotics.

Pediatr Surg Int 2021 Oct 22;37(10):1371-1381. Epub 2021 Jun 22.

Translational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Songkhla, Thailand.

Background: Pediatric patients with short bowel syndrome (SBS) are at risk of developing small intestinal bacterial overgrowth (SIBO). Prevention of SIBO using cyclic enteric antibiotics has been implemented to control the balance in microbial ecosystems, although its effectiveness has not been well studied.

Purpose: This study aimed to explore the change in the gut microbial composition in SBS patients during cyclic antibiotic phases and antibiotic-free period, and to compare the microbiota composition between healthy controls and SBS patients.

Method: SBS patients taking oral metronidazole alternating with trimethoprim-sulfamethoxazole (TMP-SMT) and antibiotic-free conditions as a '10-day cyclic protocol' were involved in fecal microbiome study using Illumina 16S sequencing.

Results: When healthy control possessed the majority of Bacteroidetes spp. (54%) and Firmicutes spp. (33%), the microbial composition in SBS patients especially Firmicutes spp. and Proteobacteria spp. was prominently changed in each phase of treatment. In antibiotic-free period, SBS patients displayed 49% Firmicutes and 36% Proteobacteria. However, higher Proteobacteria than Firmicutes were detected at the commencement of metronidazole (58% versus 33%). Similarly, 56% Proteobacteria and 27% Firmicutes were found during TMP-SMT. Escherichia coli increased prominently during the antibiotic periods.

Conclusion: Prophylactic antibiotics change the gut microbiota composition in an unfavorable direction, especially when repeatedly used for a long period. This practice should be reconsidered.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00383-021-04948-5DOI Listing
October 2021

Serum β-2 microglobulin levels are associated with distant metastasis in patients with breast cancer.

Mol Clin Oncol 2021 Jun 8;14(6):118. Epub 2021 Apr 8.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.

Serum β-2 microglobulin (β2-M) levels have been identified to be higher in patients with cancer than in healthy individuals. The aim of the present study was to evaluate the association between serum β2-M levels and clinicopathological characteristics of patients with breast cancer in a prospective cohort study, and to evaluate the effect of β2-M on cancer cell migration . Serum samples from 200 female patients with histologically confirmed invasive breast cancer were collected between 2017 and 2019. Their clinicopathological information was obtained and analyzed. The β2-M levels were identified to be associated with age, histologic subtype and metastatic status. When the diagnostic association of β2-M and metastatic status was analyzed, the area under the receiver operating characteristic curve was 0.78. Using a cut-off serum β2-M level of 1.9 µg/ml, the sensitivity for diagnosing metastatic status was 87.5%, the specificity was 65.0%, and the diagnostic odds ratio was 2.47. Upon age stratification, the association between the β2-M level and metastatic status was significant only in the group aged >55 years. In survival analysis, β2-M levels >1.9 µg/ml were associated with a poor survival outcome. , the MCF-7 breast cancer cell line exhibited increased cellular migration following treatment with 30 µg/ml β2-M. Serum β2-M may be a predictor of metastatic status in breast cancer.
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http://dx.doi.org/10.3892/mco.2021.2280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060845PMC
June 2021

Low Piperine Fractional Piper nigrum Extract Enhanced the Antitumor Immunity via Regulating the Th1/Th2/Treg Cell Subsets on NMU-Induced Tumorigenesis Rats.

Planta Med 2021 Apr 26. Epub 2021 Apr 26.

Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.

Cancer is one of the major causes of death worldwide. In addition to standard regimens, tumor suppression ability has been demonstrated in many types of natural products, including , or black pepper. In previous reports, we demonstrated the antitumor effect of low piperine fractional extract and . However, the effects of low piperine fractional extract in the aspect of antitumor immunity has not yet been investigated. In this study, tumor-bearing rats were fed with 100 mg/kg BW or 200 mg/kg BW of low piperine fractional extract 3 times per week for 4 weeks. Tumor burden and hematological data were then evaluated. Immunological data was investigated using a cytokine array and flow cytometry. The results showed that both doses of low piperine fractional extract significantly suppressed tumor progression in N-nitrosomethylurea-induced mammary tumor rats. There were no significant changes observed in the total white blood cells, red blood cells, and hemoglobin. Low piperine fractional extract suppressed some cytokine and chemokine levels including CXCL7, sICAM-1, and L-selectin 0.2- to 0.6-fold. Interestingly, 200 mg/kg BW of low piperine fractional extract significantly promoted type 1 T helper cell, and suppressed neutrophil, basophil, type 2 T helper cell, and regulatory T cell compared to the control group. In summary, these results indicate that low piperine fractional extract had a high efficacy in supporting antitumor activity at immunological levels via regulating Th1/Th2/Treg cells.
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http://dx.doi.org/10.1055/a-1458-5646DOI Listing
April 2021

Probiotic Properties of Lactobacillus Species Isolated from Fermented Palm Sap in Thailand.

Probiotics Antimicrob Proteins 2021 08 17;13(4):957-969. Epub 2021 Feb 17.

Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80161, Thailand.

Lactic acid bacteria (LAB), which are the most frequently used probiotics in foods, confer health benefits such as antimicrobial activity, immune stimulation, and anticancer activity. Fermented palm sap is a potential source of LAB. This study aimed to evaluate in vitro antimicrobial and probiotic properties of LAB isolated from traditional fermented palm sap in Thailand. Among 40 isolated LAB species, 10 were preliminarily selected for their antimicrobial activity. These 10 isolates were identified and confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing as Lactobacillus paracasei (8/10), Lactobacillus fermentum (1/10), and Lactobacillus brevis (1/10). They were evaluated for probiotic characteristics and antimicrobial activities against pathogens. These isolates were tolerant toward simulated gastrointestinal tract conditions, including low pH, pepsin, pancreatin, and bile salts. The 10 isolates retained strong auto-aggregation and cell surface hydrophobicity, and they adhered tightly to human intestinal epithelial cells. The isolates were susceptible to ampicillin, erythromycin, clindamycin, tetracycline, and chloramphenicol but resistant to vancomycin, kanamycin, and streptomycin. Moreover, all isolates exhibited no hemolytic activity. All isolates exhibited good antibacterial activity against nine pathogenic bacteria. Thus, these 10 Lactobacillus isolates from fermented palm sap are promising potential candidates for use as probiotics in functional fermented foods and pharmaceutical products.
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http://dx.doi.org/10.1007/s12602-021-09754-yDOI Listing
August 2021

Anti-cancer effect of engineered recombinant interleukin 18.

Adv Clin Exp Med 2020 10;29(10):1135-1143

Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.

Background: Interleukin 18 (IL-18) is an inflammatory cytokine belonging to the interleukin 1 (IL-1) superfamily, and is known for its role in anti-cancer activity by promoting type 1 immune response, and thus may be applied to cancer immunotherapy. Our previous report has showed 16 times higher activity of engineered E6K+T63A IL-18 than of native IL-18 in vitro. However, no data has been acquired for its anti-cancer effect in animal model.

Objectives: To investigate the anti-cancer effect of engineered E6K+T63A IL-18 as an immune stimulant in vivo.

Material And Methods: Tumor-bearing mice were treated with native IL-18 or E6K or E6K+T63A IL-18 once a day for 10 days after the tumor reached the volume of 100 mm3. Tumor volume and the number of certain immune cell type in the tumor microenvironment were investigated in this study.

Results: The results showed that tumor progression in mice treated with E6K+T63A was slower than in mice treated with E6K and native IL-18. The volume of the tumor was also smaller and the lifespan longer in the E6K+T63A IL-18-treated mice. The proportions of type 1 helper T cell (Th1) and cytotoxic T lymphocyte (CTL) were significantly higher in mice treated with E6K+T63A IL-18.

Conclusions: These results suggest that our engineered IL-18 conferred strong anti-tumor immunity in the animal model.
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http://dx.doi.org/10.17219/acem/126298DOI Listing
October 2020

Accuracy of high-resolution rectal magnetic resonance imaging re-staging with histopathology in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

Asian J Surg 2021 Jan 22;44(1):275-279. Epub 2020 Jul 22.

Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.

Background/objective: Re-staging of locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (NCRT) is a crucial step in surgical decision-making. Currently, MRI is the imaging of choice for evaluation of LARCs, however, the diagnostic accuracy of this modality is inconsistent. In this study, we evaluated the diagnostic accuracy of MRI in LARC and analyzed the factors that influenced the accuracy.

Methods: The records of 133 patients diagnosed with LARC who were operated on during 2011-2018 were retrospectively reviewed. All patients received NCRT followed by re-staging based on high-resolution rectal MRI. The MRI results were analyzed for their yT and yN accuracy and anal sphincter involvement and compared with the related histopathological studies after definitive surgery.

Results: Re-staging MRIs gave overall accuracy in both the yT stage and yN evaluation of 85% (K 0.45 and 0.21, respectively). The MRI tended to overstaging for tumor invasion and understaging for lymph node involvement (sign test p-values = 0.017 and 0.022, respectively.) The highest accuracy of the yT stage was yT4b (93%, K 0.71). The study found that larger tumors (>3 cm) were associated with significantly higher accuracy in the yT readings while lack of lymphovascular invasion was associated with higher accuracy in the yN readings. The negative predictive value for anal sphincter involvement was 100%.

Conclusion: MRI has limited accuracy in post-NCRT re-staging in LARC, tending to give overstaged yT readings and understaged yN readings. An MRI exclusion of sphincteric involvement is highly reliable.
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http://dx.doi.org/10.1016/j.asjsur.2020.07.001DOI Listing
January 2021

The clinical characteristics and prognostic factors of multiple lesions in glioblastomas.

Clin Neurol Neurosurg 2020 08 7;195:105891. Epub 2020 May 7.

Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. Electronic address:

Objective: Multiple glioblastomas (GBM) are the uncommon presentation of the disease. We aimed to identify the variables associated with the survival of patients with multiple GBMs according to the updated WHO classification.

Patients And Methods: We retrospectively reviewed 173 patients with newly diagnosed GBM between January 2003 and December 2018 and analyzed patients with multiple lesions at the time of diagnosis. The clinical, radiographic, and biomarkers were evaluated for descriptive analysis. The median overall survival and the Kaplan-Meier curves of the multiple GBMs were estimated. Furthermore, the Cox proportional hazard regression was the estimated hazard ratio for death according to various factors. Moreover, Schoenfeld's global test was performed for estimating assumptions.

Results: Of these, 30 (17.3%) of all GBMs were multiple GBMs, and multifocal and multicentric GBMs were found in 27 (90%) and 3 (10%), respectively. The median survival of the multiple GBMs was significantly shorter than solitary GBM (6 vs. 12 months, p = 0.003). Using Cox proportional hazards regression, the independent prognostic factors of multiple GBMs were concomitant Temozolomide with radiotherapy, wild-type IDH1, methylated MGMT promoter methylation in univariate analysis. In multivariable analysis, concomitant Temozolomide (TMZ) with radiotherapy (RT) was the strongest predictor associated with prognosis in multiple GBMs (0.40, 95%CI 0.16-0.97).

Conclusions: Multiple lesions are uncommon findings in glioblastoma with poor prognostic features. Concomitant TMZ with RT was the strongest predictor of prognosis. In the future., IDH1 mutation and MGMT promoter methylation should be further explored as prognostic factors.
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http://dx.doi.org/10.1016/j.clineuro.2020.105891DOI Listing
August 2020

Temozolomide for patients with wild-type isocitrate dehydrogenase (IDH) 1 glioblastoma using propensity score matching.

Clin Neurol Neurosurg 2020 04 3;191:105712. Epub 2020 Feb 3.

Department of Surgery and Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. Electronic address:

Objective: The isocitrate dehydrogenase (IDH) 1 wild-type glioblastoma (GBM) is a major population of GBM that should be of concern in terms of the efficacy of using Temozolomide (TMZ) in adjuvant treatment. This study aimed to compare the effectiveness of TMZ with radiotherapy (RT) and RT alone in patients with IDH1wild-type GBM using a propensity score matching (PSM) approach.

Patients And Methods: Newly-diagnosed GBM patients were retrospectively analyzed. The clinical variables were collected from a hospital database. Multivariable analysis and propensity score matching (PSM) were used for adjusting the differences in characteristics among patients. The effect of TMZ on the survival of patients with GBM was evaluated by time-to-event analysis based on the multivariable model and PSM.

Results: One hundred and sixty-two patients were included in the unmatched analysis. Overall median survival time was 11 months (95 % CI 9.3-12.6). In the multivariable model, TMZ and RT were associated with significantly longer survival compared with RT alone (Hazard ratio [HR] 0.64, 95 %CI 0.43-0.93). After PSM, each of the 55 patients was assigned to TMZ with RT and RT alone groups. The overall median survival time of matched data was 12.0 months (95 %CI = 10.0-13.9). Additionally, the HR of TMZ with RT was 0.67 (95 %CI 0.46-0.99) in the PSM method.

Conclusions: The present study revealed that the effect of TMZ with RT in IDH1 wild-type GBM patients had advantages in terms of survival by using multivariable analysis and PS approaches. In real-world settings, confounders should be explored and controlled prior to statistical analysis. Also, an economic evaluation of the specific subgroups should be conducted in the future.
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http://dx.doi.org/10.1016/j.clineuro.2020.105712DOI Listing
April 2020

Decreasing Trend of Surgical Site Infections among Surgical Patients in a University Hospital in Thailand after an Active Surveillance Program.

Surg Infect (Larchmt) 2019 Jul 25;20(5):382-389. Epub 2019 Feb 25.

3 Infection Control Unit, Songklanagarind Hospital, Hat Yai, Songkhla, Thailand.

Reports from high-quality healthcare systems have shown that active surveillance and management of factors associated with surgical site infection (SSI) decreased the incidence and improved overall outcomes. This study aimed to appraise the incidence trend of SSIs during the 10-year period between 2007 and 2016 in a university hospital in a middle-income country, focusing on six high-risk and high-volume procedures. The study also examined factors associated with SSIs and their impact on surgical outcomes. A total of 10,139 procedures in 9,661 cases were reviewed. The overall incidence of SSI was 2.98%. The incidence increased substantially with increasing risk score according to the National Nosocomial Infection Surveillance (NNIS) system risk score. The incidence trend decreased over time during the 10-year period studied. The procedures with the highest SSI incidence were craniotomy, colonic surgery, and cholecystectomy, which were also the three procedures that had standardized infection ratios (SIR) higher than 1.0 in all risk score categories. Univariable analysis found that diabetes mellitus was the only risk factor associated with SSI (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.2-2.73). The majority of the positive cultures were gram-negative bacteria (45%) and 49% of all reported organisms were drug resistant. There were two important consequences of the infections: length of hospitalization increased substantially from 13 days to 24 days (p < 0.01) and patients with SSI had more than three times higher mortality rate (7% compared with 1.9%, p < 0.001). With active surveillance, the incidence of SSIs decreased to less than 2.0% over the 10-year study period. More intensive surveillance should implemented for operations with high SIR and cases with diabetes mellitus.
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http://dx.doi.org/10.1089/sur.2018.124DOI Listing
July 2019

Is "gallbladder length-to-width ratio" useful in diagnosing biliary atresia?

J Pediatr Surg 2019 Sep 23;54(9):1946-1952. Epub 2019 Jan 23.

Pediatric Surgery Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Thailand.

Background: The accurate assessment of gallbladder shape and wall abnormalities by ultrasound (US) in diagnosing biliary atresia (BA) remains a subjective determination. The objective of this study was to examine the reliability of gallbladder length-to-width ratio (LTWR) by US measurement for diagnosis of BA.

Methods: One hundred infants with conjugated hyperbilirubinemia and unknown cause of jaundice who underwent transabdominal US from February 2009 to February 2017 were enrolled. The gallbladder classification and other detailed US findings were reviewed.

Results: There were statistical differences in gallbladder lumen, classification, length, width and LTWR of gallbladder (all P < 0.05) between BA and non-BA groups. The gallbladder LTWR with a cutoff at 4.1 had the highest sensitivity of 71.7%, while the fibrotic cord thickness had the highest specificity of 95.9%. The combination of portal vein (PV) diameter > 4.4 mm, hepatic artery (HA) diameter > 1.2 mm, and gallbladder LTWR >4.1, provided much higher specificity (98%), odds ratio (11), and positive likelihood ratio (LR+) (10.6).

Conclusion: The gallbladder LTWR by US could be a suggestive US parameter for BA screening. The triad of PV diameter, HA diameter, and gallbladder LTWR yielded the highest specificity, odds ratio, and LR+ for diagnosing BA.

Level Of Evidence: Level III study of diagnostic test.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.01.008DOI Listing
September 2019

Molecular dynamic simulation of mutated β-catenin in solid pseudopapillary neoplasia of the pancreas.

Oncol Lett 2018 Jun 13;15(6):9167-9173. Epub 2018 Apr 13.

Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.

Solid pseudopapillary neoplasia of the pancreas (SPN) is a rare pancreatic neoplasm that frequently harbors mutations in catenin β1 (, encoding β-catenin) as a part of its molecular pathogenesis. Mutations to reported in SPN usually occur at the serine/threonine phosphorylation sites, including codons 33, 37 and 41, and the flanking residues of codon 33. On analysis of 3 cases of SPN, mutations to were detected in codon 32 (D32A and D32Y). As this residue, aspartic acid, is not a direct phosphorylation site of the protein, molecular modeling tools were used to predict the influence of these mutations on the protein structure of β-catenin. A total of three MD simulations (wild-type, D32A, and D32Y) were performed to visualize the conformations of β-catenin under , aqueous-phase conditions at 37°C. In the wild-type protein, the secondary structure of residues P16-H28 remained helical; we therefore hypothesized that the helical structure of this protein fragment (residues M11-G50) was necessary for phosphorylation of S33 phosphorylation. The loss of the secondary structure in P16-H28 was observed in D32A, losing its helical structure and becoming a turn; however, in the D32Y mutant, the helical structure remained. The present demonstrated that structural changes in the mutated β-catenin protein at D32 could potentially explain the mechanism behind its defective phosphorylation in the pathogenesis of SPN.
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http://dx.doi.org/10.3892/ol.2018.8490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958693PMC
June 2018

Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand.

J Pediatr Genet 2018 Jun 16;7(2):67-73. Epub 2018 Feb 16.

Pediatric Surgery Unit, Department of Surgery, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction-direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in (Alagille syndrome), 2 in (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in (Dubin-Johnson syndrome), (PFIC type 2), (Crigler-Najjar syndrome), (Kabuki syndrome), (Mitchell-Riley syndrome), (Fanconi anemia), and (Zimmermann-Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.
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http://dx.doi.org/10.1055/s-0038-1632395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916803PMC
June 2018

Single nucleotide polymorphisms within Adducin 3 and Adducin 3 antisense RNA1 genes are associated with biliary atresia in Thai infants.

Pediatr Surg Int 2018 May 5;34(5):515-520. Epub 2018 Mar 5.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.

Background: A genome-wide association study in East Asians suggested a genetic association between biliary atresia (BA) and a cluster of variants within the Adducin 3 (ADD3) and ADD3 antisense RNA1 (ADD3-AS1) genes. Another study in Thai neonates reported an association between BA and rs17095355. To validate those findings, this study aimed to analyze the BA association with single nucleotide polymorphisms (SNPs) and the additive influence of ADD3 and ADD3-AS1 in Thai neonates.

Methods: DNAs from 56 BA cases and 166 controls were genotyped for rs2501577, rs11194981, rs12268910 (ADD3) and rs17095355 (ADD3-AS1), using TaqMan PCR. Genotype distributions were compared between the groups, and SNP-SNP interactions were analyzed by combination of allelotypes.

Results: The risk allele frequencies of rs2501577, rs11194981, and rs17095355 in the BA group were significantly higher than in the controls. Univariate analysis showed that recessive variants in the three SNPs were associated with BA risk at ORs of 1.81 (95% CI 1.32-2.50), 1.58 (95% CI 1.14-2.20) and 1.92 (95% CI 1.39-2.66), respectively. SNP-SNP interaction analysis showed that the SNP combination of the two genes rs17095355 and rs2501577 provided an additive increase in BA risk.

Conclusion: ADD3 and ADD3-AS1 variants increased susceptibility to BA, suggesting that these genes may play an additive role in the pathogenesis of the disease. In addition, these interactions may give a clue to the overexpression of the ADD3 protein in the liver of BA patients.
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http://dx.doi.org/10.1007/s00383-018-4243-3DOI Listing
May 2018

Role of innate lymphoid cells in obesity and metabolic disease (Review).

Mol Med Rep 2018 Jan 13;17(1):1403-1412. Epub 2017 Nov 13.

Tumor Biology Research Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.

The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti‑obese immune regulators by secreting anti‑inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon‑γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity‑associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions.
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http://dx.doi.org/10.3892/mmr.2017.8038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780078PMC
January 2018

An Uncommon Cause of Small Bowel Bleeding from Appendiceal Carcinoma.

Case Rep Gastroenterol 2017 Jan-Apr;11(1):250-255. Epub 2017 Apr 28.

NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Massive hematochezia caused by a small bowel lesion is a rare entity. Currently, video capsule endoscopy and balloon-assisted enteroscopy are effective in identifying the source of small intestine bleeding. Herein, we report a case of small bowel bleeding caused by a nonmucinous appendiceal adenocarcinoma with ileal invasion which was detected by video capsule endoscopy and single-balloon endoscopy. Despite the advanced disease stage with hepatic and peritoneal metastases, as of September 2016 the patient has had 8 years' disease-free survival after surgical resection and chemotherapy.
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http://dx.doi.org/10.1159/000468512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437429PMC
April 2017

The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts.

Biomed Res Int 2017 12;2017:7604861. Epub 2017 Mar 12.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET. Therefore, genetic screening before phototherapy treatment may be required.
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http://dx.doi.org/10.1155/2017/7604861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366218PMC
April 2017

Diets link metabolic syndrome and colorectal cancer development (Review).

Oncol Rep 2017 Mar 18;37(3):1312-1320. Epub 2017 Jan 18.

Tumor Biology Research Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.

Diets have been believed to be an important factor in the development of metabolic syndrome and colorectal cancer (CRC). In recent years, many studies have shown an intimate relationship between mucosal immunity, metabolism and diets, which has led to a greater understanding of the pathophysiology of metabolic syndrome and CRC development. Although the precise effects of diets on oncogenesis have not been compl-etely elucidated, microbiota changes and inflammation are believed to be important factors that influence the development of CRC. Moreover, increased release of pro-inflammatory cytokines and alteration of adipokine levels have been observed in patients with colorectal adenoma and/or CRC, and these all have been considered as the important mechanisms that link diets to the development of metabolic syndrome and CRC. Importantly, a high-fat, low-fiber diet is associated with dysbiosis, and as the gut signature becomes more important in metabolic syndrome and CRC, an increased understanding of diets on bacterial activity in the pathogenesis of metabolic syndrome and CRC will lead to new preventive and therapeutic strategies.
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http://dx.doi.org/10.3892/or.2017.5385DOI Listing
March 2017

Senescence Process in Primary Wilms' Tumor Cell Culture Induced by p53 Independent p21 Expression.

J Cancer 2016 2;7(13):1867-1876. Epub 2016 Sep 2.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand 90110.

Wilms tumor (WT) is an embryonal tumor occurring in developing kidney tissue. WT cells showing invasive cancer characteristics, also retain renal stem cell behaviours. In-vitro culture of WT is hampered by limited replicative potential. This study aimed to establish a longterm culture of WT cells to enable the study of molecular events to attempt to explain its cellular senescence.

Methods: Primary cell cultures from fresh WT tumor specimen were established. Of 5 cultures tried, only 1 could be propagated for more than 7 passages. One culture, identified as PSU-SK-1, could be maintained > 35 passages and was then subjected to molecular characterization and evaluation for cancer characteristics. The cells consistently harbored concomitant mutations of CTNNB1 (Ser45Pro) and WT1 (Arg413Stop) thorough the cultivation. On Transwell invasion assays, the cells exhibited migration and invasion at 55% and 27% capability of the lung cancer cells, A549. On gelatin zymography, PSU-SK-1 showed high expression of the matrix metaloproteinase. The cells exhibited continuous proliferation with 24-hour doubling time until passages 28-30 when the growth slowed, showing increased cell size, retention of cells in G1/S proportion and positive β-galactosidase staining. As with those evidence of senescence in advanced cell passages, expression of p21 and cyclin D1 increased when the expression of β-catenin and its downstream protein, TCF, declined. There was also loss-of-expression of p53 in this cell line. In conclusion, cellular senescence was responsible for limited proliferation in the primary culture of WT, which was also associated with increased expression of p21 and was independent of p53 expression. Decreased activation of the Wnt signalling might explain the induction of p21 expression.
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http://dx.doi.org/10.7150/jca.16316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039371PMC
September 2016

Digital camera image analysis of faeces in detection of cholestatic jaundice in infants.

Afr J Paediatr Surg 2016 Jul-Sep;13(3):131-5

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.

Background: Stool colour assessment is a screening method for biliary tract obstruction in infants. This study is aimed to be a proof of concept work of digital photograph image analysis of stool colour compared to colour grading by a colour card, and the stool bilirubin level test.

Materials And Methods: The total bilirubin (TB) level contents in stool samples from 17 infants aged less than 1 year, seven with confirmed cholestatic jaundice and ten healthy subjects was measured, and outcome correlated with the physical colour of the stool.

Results: The seven infants with cholestasis included 6 cases of biliary atresia and 1 case of pancreatic mass. All pre-operative stool samples in these cases were indicated as grade 1 on the stool card (stool colour in healthy infants ranges from 4 to 6). The average stool TB in the pale stool group was 43.07 μg/g compared to 101.78 μg/g in the non-pale stool group. Of the 3 colour channels assessed in the digital photographs, the blue and green light were best able to discriminate accurately between the pre-operative stool samples from infants with cholestasis and the samples from the healthy controls. With red, green, and blue (RGB) image analysis using wave level as the ANN input, the system predicts the stool TB with a relationship coefficient of 0.96, compared to 0.61 when stool colour card grading was used.

Conclusion: Input from digital camera images of stool had a higher predictive capability compared to the standard stool colour card, indicating using digital photographs may be a useful tool for detection of cholestasis in infants.
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http://dx.doi.org/10.4103/0189-6725.187810DOI Listing
October 2017

Immunologic Function and Molecular Insight of Recombinant Interleukin-18.

PLoS One 2016 2;11(8):e0160321. Epub 2016 Aug 2.

Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand.

In recent years, cytokine-mediated therapy has emerged as further advance alternative in cancer therapy. Interleukin-18 (IL-18) has exhibited interesting anti-cancer properties especially when combined with IL-12. We engineered IL-18 in order to improve its activity using single point mutagenesis. IL-18 mutants were constructed according to binding residues and polarity which we tried to increase polarity in M33Q and M60Q, enhanced cationicity in E6K, and flexibility in T63A. All IL-18 proteins were expressed in Pichia pastoris, purified, and then measured the activity by treating with the NK-92MI cell line to evaluate interferon-γ (IFN-γ) stimulation. The E6K and T63A mutant forms showed higher activity with respect to native proteins at the concentration of 200 ng mL-1 by inducing the expression of IFN-γ, about factors of 9 and 4, respectively. Meanwhile, M33Q and M60Q had no significant activity to induce IFN-γ. Interestingly, the combination of E6K and T63A mutations could synergize the induction activity of IL-18 to be 16 times at 200 ng mL-1. Furthermore, molecular dynamics studies have elucidated the effect due to mutation on conformation of the binding site of IL-18. The results turn out that E6K provides structural perseverance against mutation, while M33Q and M60Q promote vivid overall change in protein conformation, especially at the binding site. For T63A, mutation yields small difference in structure but clearly increases structural flexibility. However, a small structural change was observed when T63A was combined with E6K. Our research resulted in a novel version of IL-18 which could be a new key candidate for cytokine-mediated therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970725PMC
July 2017

Alteration of Leptin and Adiponectin in Multistep Colorectal Tumorigenesis.

Asian Pac J Cancer Prev 2016 ;17(4):Page

Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand E-mail :

Background: There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin.

Objectives: To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score.

Results: In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group.

Conclusions: The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.
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http://dx.doi.org/10.7314/apjcp.2016.17.4.2119DOI Listing
January 2017

Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

Mol Clin Oncol 2015 Nov 16;3(6):1401-1405. Epub 2015 Sep 16.

Central Research Laboratory, Faculty of Medicine, Prince of Songkhla University, Songkhla 90110, Thailand.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Our recent study demonstrated that the expression of Wilms' tumor 1 gene () is associated with surgical outcome in CRC patients. The present study aimed to investigate the genetic association of the single-nucleotide polymorphism rs16754 in the gene with the occurrence of CRC, using an age-matched case-control study design. In addition, the correlation between genotype and expression was investigated. Genomic DNA samples from 104 CRC cases, aged 15-65 years, and 208 healthy controls, were genotyped for rs16754 using the TaqMan genotyping method. The genotype distribution conformed to the Hardy-Weinberg equilibrium (P=0.80). The overall minor allele frequency (MAF) of rs16754 (allele A) was 0.33. The MAF among CRC cases was significantly higher compared with that in controls (0.39 vs. 0.31, respectively; P=0.03). The AA genotype was significantly associated with the disease (odds ratio = 2.51, 95% confidence interval: 1.24-5.07, P=0.01). Cases with the AA genotype exhibited a significantly poorer 3-year overall survival (60%), compared with those with the GG or GA genotypes (80%) (log-rank test, P<0.01). Reverse transcription quantitative polymerase chain reaction analysis demonstrated that the expression of in tumor tissues was higher compared with that in normal tissue; however, there were no significant differences in its expression among different genotypes. Therefore, rs16754 was found to be associated with the occurrence and prognosis of CRC in our subjects.
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http://dx.doi.org/10.3892/mco.2015.647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665320PMC
November 2015

Primary synovial sarcoma of the abdominal wall: a case report and literature review.

J Radiol Case Rep 2015 Jul 31;9(7):47-52. Epub 2015 Jul 31.

Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Thailand.

Synovial sarcoma (SS) is the fourth most common type of soft tissue sarcoma, following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma. It usually occurs in the extremities near the large joints of middle-aged patients. We describe a case of synovial sarcoma of the anterior abdominal wall (SSAW) in an adolescent girl and undertake a review of the literature.
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http://dx.doi.org/10.3941/jrcr.v9i7.1977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638410PMC
July 2015

Current management of pediatric soft tissue sarcomas.

World J Clin Pediatr 2015 Nov 8;4(4):94-105. Epub 2015 Nov 8.

Surasak Sangkhathat, Department of Surgery and Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.

Pediatric soft tissue sarcomas are a group of malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia and fat. The tumors have a biphasic peak for age of incidence. Rhabdomyosarcoma (RMS) is diagnosed more frequently in younger children, whereas adult-type non-RMS soft tissue sarcoma is predominately observed in adolescents. The latter group comprises a variety of rare tumors for which diagnosis can be difficult and typically requires special studies, including immunohistochemistry and molecular genetic analysis. Current management for the majority of pediatric sarcomas is based on the data from large multi-institutional trials, which has led to great improvements in outcomes over recent decades. Although surgery remains the mainstay of treatment, the curative aim cannot be achieved without adjuvant treatment. Pre-treatment staging and risk classification are of prime importance in selecting an effective treatment protocol. Tumor resectability, the response to induction chemotherapy, and radiation generally determine the risk-group, and these factors are functions of tumor site, size and biology. Surgery provides the best choice of local control of small resectable tumors in a favorable site. Radiation therapy is added when surgery leaves residual disease or there is evidence of regional spread. Chemotherapy aims to reduce the risk of relapse and improve overall survival. In addition, upfront chemotherapy reduces the aggressiveness of the required surgery and helps preserve organ function in a number of cases. Long-term survival in low-risk sarcomas is feasible, and the intensity of treatment can be reduced. In high-risk sarcoma, current research is allowing more effective disease control.
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http://dx.doi.org/10.5409/wjcp.v4.i4.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637813PMC
November 2015

Rotational thromboelastometry in the diagnosis of coagulopathy in major pediatric surgical operations.

J Pediatr Surg 2015 Nov 15;50(11):2001-4. Epub 2015 Aug 15.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.

Objectives: To examine the correlation between rotational thromboelastometry (ROTEM) and coagulopathy after major pediatric surgical operations.

Methods: From November 2013 until April 2015, pediatric cases who underwent major noncardiac surgeries and met the coagulopathy-risk criteria were reviewed for postoperative clinically significant coagulopathy (CSC). Two ROTEM studies, EXTEM and INTEM, were performed at the immediately postoperatively without the results being taken into any clinical decision making.

Results: Seventy-seven operations on 73 patients were included in this analysis. CSC occurred following 24 operations (32%) with a significantly higher incidence when a patient had a higher coagulopathy risk. On univariate analysis, evidence of diffuse bleeding in the operative field and massive bleeding were the 2 parameters with the strongest association with CSC. INTEM and EXTEM had specificities in diagnosing CSC of 75.5% and 94.3%, respectively. When each individual EXTEM and INTEM item was analyzed against CSC using ROC analysis, clot forming time (CFT) gave the largest under the curve area. The cut-off CFTs that gave the highest sensitivity and specificity in this study were 120seconds for EXTEM and 100seconds for INTEM.

Conclusion: Postoperative coagulopathy is a risk that should always be considered in pediatric surgical operations. Thromboelastometry can be a hemostatic test providing high predictive value for this condition.
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http://dx.doi.org/10.1016/j.jpedsurg.2015.08.007DOI Listing
November 2015

Factors determining low anterior resection syndrome after rectal cancer resection: A study in Thai patients.

Asian J Surg 2016 Oct 2;39(4):225-31. Epub 2015 Sep 2.

Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand; Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. Electronic address:

Background/objective: Defective defecation function, also known as low anterior resection syndrome (LARS), is a common problem after surgical treatment of rectal cancer that has a detrimental effect on quality of life. This study aimed to look for the incidence of LARS in patients whose native rectum could not be kept and determine factors influencing major LARS.

Methods: Rectal cancer patients who underwent tumor removal with mesorectal excision and colorectal anastomosis by a colorectal surgeon during the years 2004-2013 were asked to participate a structured interview using the verified version of the Low Anterior Resection Score questionnaire. Clinical parameters were analyzed against the incidence of major LARS. The cut-off anastomotic level that corresponded to the risk of major LARS was calculated by using a receiver operating characteristic curve. Anorectal physiology was compared between those with major LARS and those without LARS by anorectal manometry.

Results: This study included 129 patients (67 men and 62 women). Incidences of minor LARS (LAR score 21-29) and major LARS (LARS score ≥ 30) score 21een those with major LARS and those univariate analysis, factors associated with major LARS were extent of operation, presence of temporary ostomy, and chemoradiation therapy. Major LARS was found at 28.2% in those who underwent low anterior resection, which was significantly higher than the incidence of 5.2% in the anterior resection group (p < 0.01). Radiation therapy was the only factor independently associated with major LARS at an odds ratio of 6.55 (95% confidence interval: 2.37-18.15). The receiver operating characteristic curve plot between sensitivity and specificity of the anastomotic level in determining major LARS showed an area under the curve of 0.73. The cut-off anastomotic level that best predicted major LARS was at 5 cm, which gave a negative predictive value of 89%. Individual defecation symptoms that were significantly associated with major LARS included pain on defecation, difficulty holding stool, and needing to use a pad. Anorectal manometry showed a significant difference in the resting anal pressure and squeeze pressure, which suggests that derangement in sphincteric function caused by surgery and postoperative adjuvant treatment may contribute to the LARS.

Conclusion: LARS is a significant problem found in about one third of rectal cancer patients after colorectal anastomosis. Symptoms of concern include pain on defecation and decreased ability to hold. Risk of having major LARS increases with adjuvant treatment and lower anastomotic level.
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http://dx.doi.org/10.1016/j.asjsur.2015.07.003DOI Listing
October 2016
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