Teeranut Boonpipattanapong

Somatic mutations of K-ras and BRAF in Thai colorectal cancer and their prognostic value.

BACKGROUND The study aimed to determine the incidence of K-ras and BRAF mutations in colorectal cancers (CRCs) in Thai patients and evaluate association with clinicopathological parameters including treatment outcomes in terms of event free survival (EFS). MATERIALS AND METHODS Two-hundred colorectal cancer specimens were collected for studies of K-Ras codon 12, 13 and 61, and BRAF codon 600 by polymerase chain reaction and direct nucleotide sequencing. RESULTS The overall incidence of K-Ras mutations in our patients was 23%. K-ras mutation frequencies in CRC stages (AJCC) I, II, III and IV were 6.7%, 16.1%, 23.3% and 26.6%, respectively (p-value>0.05). The three most common mutation forms were G12D, G12V and G13D. K-Ras mutation status was associated with poorer EFS in stage I-III CRCs (p-value 0.03). CONCLUSIONS The study found a lower mutation frequency of K-Ras and BRAF compared to reports involving other ethnic groups. However, K-Ras mutations did have a negative prognostic value in early-stage CRCs.

Impact of lymph node retrieval on surgical outcomes in colorectal cancers

Adequacy of lymph node sampling is fundamental to the accuracy of nodal status (N‐status) assessment in colorectal cancers (CRCs). This study aimed to determine the minimum sampling number to achieve reliable prognosis and to look for any association between the positive lymph node ratio (LNR) and overall survival (OS). Pathological reports of 533 stages I–III CRC patients who underwent curative resection during the period from January 1998 to December 2007 were retrospectively reviewed with regard to the number of lymph nodes obtained for pathological diagnosis (nLN) and number of positive nodes.

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.

WT1 expression as an independent marker of poor prognosis in colorectal cancers

WT1 has been proven to be a prognostic marker and molecular target in various human cancers. In this study, we aimed to investigate the prognostic role of WT1 in colorectal cancers (CRCs). Archival tissue samples from 157 CRC cases who underwent curative surgery in our institute from February 1999 to May 2004 were subjected to WT1 expression studies using an immunohistochemistry technique. Number of positive staining per 500 tumor cells and staining intensities were analyzed against overall survival. Of 157 CRCs, 83 were colonic and 74 were rectal cancers. The mean follow-up period was 116 (range 77-145) months. Five-year and seven-year OS rates were 60.9% and 52.8%, respectively. WT1 immunostaining was positive in 143 cases (91%). The median number of positive cells was 120 (range 0-420). Univariate analysis by Log-rank test showed that AJCC stage, tumor site (rectal cancer), number of positive cells > 120 and high staining intensity (score ++/+++) were significantly associated with poorer survival (p-value < 0.01). Five-year survival rates in cases with positive cells of ⩽ 120 cells and > 120 cells were 72.2% and 49.4%, respectively. Five-year survival in cases with staining intensity of ++ or more was 45.3%, compared with 69% in cases with intensity of less than ++. Multivariate regression analysis demonstrated that the staining intensity, high tumor stage and rectal site were independent factors indicating poorer survival. Our findings indicate that WT1 expression is a marker of poor prognosis in CRCs, independent of AJCC staging.

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.

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

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.

Expression of BMP6 is Associated with its Methylation Status in Colorectal Cancer Tissue but Lacks Prognostic Significance

BACKGROUND The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. MATERIALS AND METHODS Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allreds scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. RESULTS The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allreds scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). CONCLUSIONS CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.

Endoscopic obstruction is associated with higher risk of acute events requiring emergency operation in colorectal cancer patients

IntroductionUnplanned emergency operations in colorectal cancers (CRC) are generally associated with increased risk of operative complications. This study aimed to examine the association, if any, between an endoscopic finding of obstructing tumor and the subsequent need for an emergency operation, with the aim of determining if this finding could be useful in identifying CRC cases who are more likely to require an emergency operation.MethodsThe records of CRC cases operated on in our institute during the years 2002-2011 were retrospectively reviewed regarding an endoscopic obstruction (eOB), defined as a luminal obstruction of the colon or rectum severe enough to prevent the colonoscope from passing beyond the tumor. The eOBs were analyzed against outcomes in terms of need for emergency operation, surgical complications and overall survival (OS).ResultsA total of 329 CRCs which had been operated on during the study period had complete colonoscopic data. eOB was diagnosed in 209 cases (64%). Occurrence of eOB was not correlated with clinical symptoms. Colon cancer had a higher incidence of eOB (70%) than rectal cases (50%) (p-value < 0.01). eOB was significantly associated with higher tumor size and more advanced T-stage (p < 0.01). Twenty-two cases (7%) had required an emergency operation before their scheduled elective surgery. The cases with eOB had a significantly higher risk of requiring an emergency operation while waiting for their scheduled procedure (p-value < 0.01), and these emergency surgeries had more post-operative complications (36%) than elective procedures (13%) (p-value 0.01) and poorer OS (p-value < 0.01).ConclusionRegardless of the presenting symptom, luminal obstruction severe enough to prevent further passage of a colonoscope should prompt the physician to consider an urgent surgery.

Alteration of Leptin and Adiponectin in Multistep Colorectal Tumorigenesis.

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.

An Uncommon Cause of Small Bowel Bleeding from Appendiceal Carcinoma

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.