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Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer-related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, out of which 53,200 individuals would succumb to the disease in the USA alone in 2020. CRC-related mortality ranks third among both males and females in the USA. CRC arises from 3 major pathways: i) The adenoma-carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer. With widespread CRC screening, the incidence and mortality from CRC have decreased in developed countries. However, over the past few decades, CRC cases and mortality have been on the rise in young adults (age, <50 years). In addition, CRC cases are increasing in developing countries with a low gross domestic product (GDP) due to lifestyle changes. CRC is an etiologically heterogeneous disease classified by tumor location and alterations in global gene expression. Accumulating genetic and epigenetic perturbations and aberrations over time in tumor suppressor genes, oncogenes and DNA mismatch repair genes could be a precursor to the onset of colorectal cancer. CRC can be divided as sporadic, familial, and inherited depending on the origin of the mutation. Germline mutations in APC and MLH1 have been proven to play an etiological role, resulting in the predisposition of individuals to CRC. Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis. Timely detection and effective precision therapies based on the present knowledge of CRC is essential for successful treatment and patient survival. The present review presents the CRC incidence, risk factors, dysregulated signaling pathways and targeted therapies.

Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the 'C' allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population.

Background: Obesity is a major global public health problem. Observational studies have shown an increasing incidence of syncope and pre-syncope following bariatric surgery in obese patients. However, there is paucity of the true incidence of syncope following bariatrics sugary in the literature. Methods: We have randomly surveyed 200 patients who underwent bariatric surgery between 2016-2018 using Calgary Syncope Score (CSS). Results: Of the 200 patients enrolled, 107 (53.5%) were female with 167 patients (83.5%) between 18 and 50 years of age. The most-reported comorbidities were diabetes mellitus 26 (13%) hypertension 25 (12.5%) and pulmonary disease 18 (9%). The majority 98 (49%) of the patients had pre-operative body mass index (BMI) of 40-50 kg/m 2, and most of them had laparoscopic sleeve gastrectomy (LSG). Sixty-two (31%) patients had vasovagal syncope (VVS), 52 (26%) patients had non-VVS and 86 (43%) had no syncope. Conclusion: Vasovagal syncope in patients following bariatric sugary is quite common and affects 15% of bariatric patients in our series in the first year postoperatively. Further randomized controlled trials are required to prove our results.

Abstract Background: In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection. Methods: All patients who underwent curative resection for colon cancer between July 2015 and December 2019 were retrospectively reviewed and analyzed. Patients were divided into two groups based on the presentation into elective and emergency groups. Results: A total of 215 patients with colon cancer were admitted and underwent curative surgical resection. Of those, 145 patients (67.4%) were elective cases, and 70 (32.5%) were emergency cases. Family history of malignancy was positive in 44 patients (20.5%) and significantly more common in the emergency group (P = 0.016). The emergency group had higher T and TNM stages (P = 0.001). The 3-year survival rate was 60.9% and significantly less in the emergency group (P = 0.026). The mean duration from surgery to recurrence, 3-year disease-free survival, and overall survival were 1.19, 2.81, and 3.11, respectively. Conclusion: Elective group was associated with better 3-year survival, longer overall, and 3-year disease-free survival compared to the emergency group. The disease recurrence rate was comparable in both groups, mainly in the first two years after curative resection.

The heterogenous nature of colorectal cancer (CRC) highlights the need for a better understanding of the growth factors that affect tumour growth and cancer progression. The aim of the present study was to evaluate the role of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the early (I and II) and late (III and IV) stages of CRC. The serum levels and mRNA expression (n=30) of the aforementioned growth factors were measured and immunohistochemistry (n=20) was performed in patients with CRC. Histological examination revealed comparable distribution of early-stage [I: 8 (26.7%) and II: 7 (23.3%)] and late-stage [III: 8 (26.7%) and IV: 7 (23.3%)] CRC. The mean serum concentrations of VEGF during the early (152.9±14.5 vs. 88.39±3.99 pg/ml; P=0.001) and late (182.7±25.8 vs. 88.39±3.99 pg/ml; P=0.002) stages were significantly higher compared with those in controls. Similarly, the mean serum concentrations of EGF in the early (409.4±7.96 vs. 153.7±13.8 pg/ml; P=0.05) and HGF in the late (90.4±17.4 vs. 56.9±4.97 pg/ml; P=0.05) stages were significantly higher compared with those in controls. The serum concentrations of VEGF, EGF and HGF were comparable between the early and late stages of CRC. Compared to normal tissues, the mRNA expression of both VEGF (P<0.001) and HGF (P<0.01) was upregulated in early-stage and downregulated in late-stage CRC. The expression of EGF remained significantly elevated during both the early and late stages of CRC (P<0.01). Histopathological analyses confirmed increased expression of VEGF in cancerous tissues compared with that in normal tissues. The present study emphasized the need for monitoring the serum levels and tissue expression of growth factors to fully elucidate their role in patients with CRC.

IL-17 expressed by Th17 cells play a crucial role in tissue inflammation by induction of proinflammatory and neutrophil mobilizing cytokines, and IL-17 polymorphisms are associated with colorectal cancer (CRC). We investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population. The study included 117 diagnosed CRC patients and 100 age- and gender-matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C) single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were assessed. We observed significant association between rs2275913 in IL-17A and susceptibility to CRC ( = 0.016228). The AG and AA genotypes conferred 2-fold and 2.8-fold, respectively, higher risk of developing CRC compared with individuals having GG genotype. Stratification of the data based on gender and age revealed very strong association of CRC with IL17A rs2275913 only in males and \"AG\" genotype in patients ≤57 years of age at the time of disease diagnosis. The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL-17A mRNA expression in CRCs was significantly elevated compared to adjacent normal tissues, particularly in early stages of disease ( = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors. The IL-17A G197A variant may be utilized as a genetic screening marker in assessing CRC risk, and its expression can be used as a biomarker for early detection of CRC in the Saudi population.

Background A considerable number of patients with colon cancer present with a colonic obstruction. The use of self-expanding metallic stents (SEMS) as a bridge to surgery (BTS) in potential curative patients with left-sided colonic cancer obstruction remains debatable. Therefore, this study aimed to investigate the 5-year oncological outcomes of using a SEMS as a BTS. Methods All patients with left-sided malignant colon obstruction who underwent curative surgery with no metastasis upon presentation between March 2009 and May 2013 were retrospectively reviewed and analyzed. Results A total of 45 patients were included, 28 patients underwent upfront surgery, and 17 patients had a stent as a bridge to surgery. T4 stage was statistically significantly higher in patients who had a SEMS as a BTS (35.3% vs. 10.7%) (p-value 0.043) . The mean duration in days of the SEMS to surgery was 13.76 (SD 10.08). TNM stage 3 was a prognostic factor toward distant metastasis (HR 5.05). When comparing patients who had upfront surgery to those who had a SEMS as a BTS, higher 5-year disease-free survival (75% vs. 72%) and 5-year overall survival (89% vs. 82%) were seen in patients who had upfront surgery. However, both were statistically insignificant. Conclusion Using self-expanding metallic stents as a bridge to surgery yields comparable 5-year survival and disease-free survival rates to upfront emergency surgery. The decision to use SEMS versus opting for emergency surgery should be made after careful patient selection and with the assistance of experienced endoscopists. Trial registration N/A.

We are presenting the case of a 62-year-old woman who developed a pneumomediastinum as a complication of anastomotic leakage (AL) following laparoscopic sigmoid resection due to diverticulitis. The patient presented with retroperitoneal air, pneumomediastinum, emphysematous gall bladder, air in the wall of stomach, and proximal small bowel. There were a few tiny air bubbles around the anastomosis. We discuss this unusual clinical presentation of intraperitoneal and extraperitoneal air as a presenting sign of AL.

Lymphangiomas are rare tumors affecting the gastrointestinal tract, and may be seen in the bowel, gall bladder, and pancreas. They resemble hemangiomas, but consist of spaces of variable sizes containing lymph. In this report, we describe the case of a 53-year-old male who presented with abdominal pain and constipation. Computerized tomography (CT) scan showed a polypoidal lesion at the ileocecal valve which was thought to be a gastrointestinal stromal tumor. Resected specimen did, however, show a lymphangioma. We also describe the clinicopathologic features of gastrointestinal lymphangiomas with a literature review.

Background Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history. Aim The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data. Methods Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation. Results Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06–1.60) as shown by multivariable analysis. Conclusions Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients. Graphical Abstract