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.

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.

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

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.

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.

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.

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

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 (WT1) 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 WT1 gene with the occurrence of CRC, using an age-matched case-control study design. In addition, the correlation between genotype and WT1 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 WT1 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.

Influence of payer source on treatment and outcomes in colorectal cancer patients in a university hospital in Thailand.

The study aimed to compare the 2 main types of insurance used by colorectal cancer (CRC) patients in a university hospital in Thailand: universal coverage (UC) and 'Civil Servant Medical Benefit Scheme' (CSMBS) in terms of hospital expenditure and survival outcomes. CRC cases in stages I-IV who were operated on and had completed their adjuvant therapy in Songklanagarind Hospital from 2004 through 2013 were retrospectively reviewed regarding their hospital expenditure, focusing on surgical and chemotherapy costs. Of 1,013 cases analyzed, 524 (51.7%) were in the UC group while 489 (48.3%) belonged to the CSMBS group. Cases with stage IV disease were significantly more frequent in the UC group. Average total treatment expenditure (TTE) was 143,780 Thai Baht (THB) (1 US$=~30 THB). The TTE increased with tumor stage and the chemotherapy cost contributed the most to the TTE increment. TTE in the CSMBS group was significantly higher than in the UC group for stage II-III CRCs. The majority of cases in the UC group (65.5%) used deGramont or Mayo as their first line regimen, and the proportion of cases who started with a capecitabine-based regimen (XELOX or Xeloda®) was significantly higher in the CSMBS group (61.0% compared to 24.5% in the UC group, p-value<0.01). On survival analysis, overall survival (OS) and progress free survival in the CSMBS group were significantly better than in the UC group. The 5-year OS in the CSMBS and UC groups were 84.3% and 74.6%, respectively (p-value<0.01). In conclusion, the study indicates that in Thailand, the type of insurance influences resource utilization, especially the choice of chemotherapy, in CRC cases. This disparity in treatment, in turn, results in a gap in treatment outcomes.

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 Allred's 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. Allred's 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.

Predicting the occurrence of cancer-associated colorectal polyp using a metabolic risk score.

This study was conducted with the aim of developing a metabolic risk score to help identify patients who are likely to have a cancer-associated polyp (CAP) on colonoscopy, based on a metabolic syndrome-related clinical profile. The clinical history and anthropometric and metabolic profiles of patients who came for a screening colonoscopy at our institute between June, 2010 and December, 2012 were prospectively collected. The data were analyzed for their association with the occurrence of CAP. Subsequently, six parameters were selected in order to construct a metabolic risk score that correlated with the presence of CAP. A total of 286 subjects (132 males and 154 females), with an age range of 19-85 years, were included in this study. The colonoscopy detected polyps in 56 cases (19.6%). Anthropometric parameters that were significantly associated with CAP included a body mass index (BMI) of >23.4 kg/m2 and a waist circumference of >32 inches in females. Laboratory profiles that were significantly associated with CAP were fasting blood sugar (FBS) >110 mg%, hemoglobin A1C (HbA1C) >7%, aspartate transaminase (SGOT) >40 IU/l, alanine transaminase (SGPT) >50 IU/l and uric acid >7 mg%. When a metabolic risk score was constructed, it was observed that moderate (2-3) and high risk (4-6) was significantly associated with CAP [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.0-12.0 and OR=13.7, 95% CI: 4.4-43.0, respectively]. The association between the risk score and CAP was stronger in the subgroup of patients aged <65 years, in whom the moderate and high metabolic risk groups exhibited ORs of 5.6 (95% CI: 1.8-17.9) and 39.0 (95% CI: 8.2-186.6), respectively. In conclusion, this study demonstrated that it is possible to use a metabolic profile to construct a reliable scoring method to identify patients at higher risk of having CAP who should be fast-tracked for a colonoscopy.

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

INTRODUCTION: Unplanned 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. METHODS: The 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). RESULTS: A 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). CONCLUSION: Regardless of the presenting symptom, luminal obstruction severe enough to prevent further passage of a colonoscope should prompt the physician to consider an urgent surgery.

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.

BACKGROUND: 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: The median nLN was 10 nodes and the mean number of positive nodes was 1.7 nodes. On the N-status attribution plot, the cut-off point where the converging curves turned parallel was at 12 nodes. This cut-off was supported by the significant difference in OS between cases with nLN ≥ 12 (5-year OS 73.0%) and those with nLN < 12 (5-year OS 62.7%), (P-value < 0.01). Multivariate analysis showed that both nLN-12 and LNR were independent factors predicting survival probability. CONCLUSION: Our data emphasize the importance of lymph node harvesting during the surgical resection of CRCs. In addition, LNR is a strong independent factor associated with CRC survival.

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.

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers.

AIM: To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters. METHODS: Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model. RESULTS: Beta-catenin immunoreactivity was detected in 161 samples (98.8%), of which 131 cases had nuclear staining. High OSD (> or = 75%), detected in 123 cases (75.5%), was significantly associated with earlier clinical staging (P < 0.01), lower nodal status (P = 0.02), non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51, 95% confidence interval (CI) 0.31-0.83]. Although high NSD (> or = 75%) was correlated with high pre-operative serum CEA (P = 0.03), well differentiation (P < 0.01), and increased staining intensity (P < 0.01), the parameter was not significantly associated with survival. CONCLUSION: Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.

Preoperative carcinoembryonic antigen and albumin in predicting survival in patients with colon and rectal carcinomas.

OBJECTIVE: To examine the relationship between postoperative outcomes of colorectal carcinoma patients and preoperative serum carcinoembryonic antigen (CEA) and albumin (ALB) levels and evaluate if these levels can accurately predict outcomes and/or be factor indicating adjuvant chemotherapy. BACKGROUND: CEA is a marker for colorectal carcinoma and its level usually increases before a distant metastasis is detected. Also, a low level of serum ALB is usually found in metastatic colorectal carcinoma patients. STUDY: A retrospective cohort study of patients with colorectal carcinomas who were treated with curative surgery in Songklanagarind Hospital between 1998 and 2002. RESULTS: One hundred seventy patients were identified with a median survival of 1131 days (range 71 to 2293 d) and with an overall 5-year survival rate of 54%. Patients were stratified using CEA at 5 ng/mL and an ALB level at 3.5 g/dL into 4 groups: (1) low CEA, high ALB; (2) low CEA, low ALB; (3) high CEA, high ALB; and (4) high CEA, low ALB. The 5-year survival rates for groups 1 to 4 were 66%, 63%, 46%, and 34%, respectively. There was statistically significant difference in 5-year survival between the well-differentiated tumor with low CEA and the poorly differentiated tumor with high CEA (P=0.0115). The high CEA patients who had the well-differentiated tumor had longer survival than those with a poorly differentiated tumor (P=0.0412). CONCLUSIONS: A preoperative CEA level greater than or equal to 5 ng/mL and ALB level less than 3.5 g/dL predict a poor survival chance for colorectal carcinoma patients. In high CEA patients, tumor differentiated is an independent factor affecting survival.

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.