MATERIALS AND METHODS: Paraffin blocks of 133 CRCs were retrieved from the Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia. Immunostaining was done using antibody to clusterin. Staining expression in 10% of malignant cells was used as a cut-off to determine low immunostaining and high immunostaining. Statistical tests were used to evaluate the association of clusterin immunostaining with clinicopathological parameters.
RESULTS: Immunohistochemical results showed clusterin low immunostaining in CRC and nodal metastases. No association was found between clusterin immunostaining and tumour grade, age, tumour invasiveness, distant metastases, vascular invasion, nodal metastases, relapse, and survival.
CONCLUSION: Our study showed low clusterin immunostaining in CRC with lack of association with prognostic indicators in CRC. These results raise the controversy of understanding the role of clusterin in CRC. Further molecular studies are required to explore more about possible mechanisms of clusterin association with tumorigenicity, apoptosis, tumour growth progression, local and vascular invasion, and metastasis of CRC.
CONCLUSIONS: HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.
METHODS: ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus process with additional experts for one round of formal ratings.
RESULTS: Existing sets of guidelines from 12 guideline developers were identified and reviewed; adapted recommendations from six guidelines form the evidence base and provide evidence to inform the formal consensus process, which resulted in agreement of 75% or more on all recommendations.
RECOMMENDATIONS: For nonmaximal settings, the recommended treatments for colon cancer stages nonobstructing, I-IIA: in basic and limited, open resection; in enhanced, adequately trained surgeons and laparoscopic or minimally invasive surgery, unless contraindicated. Treatments for IIB-IIC: in basic and limited, open en bloc resection following standard oncologic principles, if not possible, transfer to higher-level facility; in emergency, limit to life-saving procedures; in enhanced, laparoscopic en bloc resection, if not possible, then open. Treatments for obstructing, IIB-IIC: in basic, resection and/or diversion; in limited or enhanced, emergency surgical resection. Treatment for IIB-IIC with left-sided: in enhanced, may place colonic stent. Treatment for T4N0/T3N0 high-risk features or stage II high-risk obstructing: in enhanced, may offer adjuvant chemotherapy. Treatment for rectal cancer cT1N0 and cT2n0: in basic, limited, or enhanced, total mesorectal excision principles. Treatment for cT3n0: in basic and limited, total mesorectal excision, if not, diversion. Treatment for high-risk patients who did not receive neoadjuvant chemotherapy: in basic, limited, or enhanced, may offer adjuvant therapy. Treatment for resectable cT3N0 rectal cancer: in enhanced, base neoadjuvant chemotherapy on preoperative factors. For post-treatment surveillance, a combination of medical history, physical examination, carcinoembryonic antigen testing, imaging, and endoscopy is performed. Frequency depends on setting. Maximal setting recommendations are in the guideline. Additional information can be found at www.asco.org/resource-stratified-guidelines .
NOTICE: It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guidelines are intended to complement but not replace local guidelines.
METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.
RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.
CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.
METHODS: Histopathological reports of all patients diagnosed with colorectal carcinoma from January 2012 to December 2016 from public hospitals in Sabah were retrieved from the central computerized database of the Pathology Department of Queen Elizabeth Hospital in Kota Kinabalu, Sabah. Supplementary data was obtained from patients' case files from each hospital. Clinico-pathological data were analysed using the IBM SPSS Statistical Software Version 23 for Windows for descriptive statistics (mean, median, ASR, AR, relative risk) and inferential statistics (Chi square test).
RESULTS: A total of 696 patients met the inclusion criteria. The median age for colorectal cancer in Sabah was 62 years (95% CI 60.3 to 62.3), with an age specific incidence rate of 21.4 per 100 000 population. The age specific incidence rate in the indigenous populations was 26.6 per 100 000, much lower than the Chinese, at 65.0 per 100 000. The risk of colorectal cancer occurring before the age of 50 was three times higher in the indigenous population compared to the Chinese. The tumours were mainly left-sided (56.5%), adenocarcinoma in histology (98.4%) and moderately differentiated (88.7%). Approximately 79.2% of patients received curative treatment.
CONCLUSION: Indigenous populations in Sabah develop colorectal cancer at an earlier age, and present at more advanced stages. This has implications for screening and therapeutic strategic planning.
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METHODS: Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).
RESULTS: In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.
CONCLUSION: Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.
METHODS: This study enrolled 100 patients in a single-center tertiary teaching hospital. Patients presented for screening colonoscopy, and those with suspicious colorectal lesions were included in this study. During colonoscopy, the most suspicious lesion in each patient was analyzed using the NBI system based on Sano's classification. Each lesion was biopsied for histopathological analysis, the gold standard. Endoscopic images were captured electronically. The sensitivity, specificity, and diagnostic accuracy of NBI colonoscopy were assessed. Other associated factors related to neoplastic and non-neoplastic lesions were analyzed accordingly.
RESULTS: The sensitivity and specificity of the NBI were 88.2% and 71.9%, respectively. The area under the receiver-operator curve was 0.801, indicating that NBI has a good ability to differentiate between disease and non-disease. There are significant associations between histopathological examination outcomes and both presenting symptoms, especially weight loss, and lesion site, even after other variables were controlled (P
METHODS: Colonic EMRs performed for polypoid and nonpolypoid lesions at a tertiary institution were prospectively collected and analyzed for efficacy, and short and long-term complications.
RESULTS: 224 colonic neoplasms (143 flat, 65 sessile and 16 subpedunculated) were excised by the standard inject-and-cut method, with standard accessories. The median size of all lesions was 10 mm (range 2-50 mm) and 110 (49.2%) lesions were located in the proximal colon. Histological completeness of resection was achieved in 87% of cases. Of the lesions 77.2% were dysplastic, with 5 cases of carcinoma in situ and 18 severely dysplastic adenomas. Complications included bleeding in five cases (2.2 %) and a single case of perforation (0.4%). All complications were managed endoscopically. Median follow up at 24 +/- 16 months (range 12-84 months) revealed a 7.2% local recurrence rate, all of which were subsequently eradicated by repeat EMR.
CONCLUSIONS: Standard inject-and-cut colonic EMR is practical and effective in the eradication of superficial colonic neoplasia.
MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.
RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.
CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.
METHODS: Eighteen pairs of colorectal cancerous tissues in addition to tissues from normal mucosa were analysed. Hydrophobic proteins were extracted from the tissues, separated using 2-D gel electrophoresis and analysed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Statistical analysis of the proteins was carried out in order to determine the significance of each protein to colorectal cancer (CRC) and also their relation to CRC stages, grades and patients' gender.
RESULTS: Thirteen differentially expressed proteins which were expressed abundantly in either cancerous or normal tissues were identified. A number of these proteins were found to relate strongly with a particular stage or grade of CRC. In addition, the association of these proteins with patient gender also appeared to be significant.
CONCLUSION: Stomatin-like protein 2 was found to be a promising biomarker for CRC, especially in female patients. The differentially expressed proteins identified were associated with CRC and may act as drug target candidates.