Management of Peritoneal Surface Malignancies in Saudi Arabia: An Update.

Peritoneal surface malignancies (PSM) are aggressive and associated with poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used to treat PSM since 1990. In Saudi Arabia, the first HIPEC and pressurized intraperitoneal aerosol chemotherapy (PIPAC) were performed in 2008 and 2019, respectively. With increasing incidences of PSM in Saudi Arabia, the demand for such procedures has grown. This article outlines the status of PSM management in Saudi Arabia and its prospects.

Robotic and Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, Multicenter Study From Saudi Arabia.

BACKGROUND: Peritoneal metastasis (PM) is a common evolution of abdominal tumors. Without aggressive multimodal treatment, it is associated with a poor prognosis. The aim of this study is to present a multicenter results from Saudi Arabia on minimally invasive CRS and HIIPEC. METHODS: A retrospective analysis of a prospective maintained multicenter database was queried for all patients treated with laparoscopic or robotic CRS and HIPEC between 2019 and 2024 in Saudi Arabia. Surgical and oncological outcome was analyzed. RESULTS: Eleven consecutive patients underwent minimally invasive CRS and HIPEC between 2019 and 2024. Eight patients (72.7%) were operated by laparoscopy, one of them by single port access and three patients (27.3%) were operated robotically. Six patients (54.5%) were female. Median age was 42 (29-64). Primary tumor was PMP from the appendix, colon, and MCM in 6 (54.5%), 4 (36.4%), and 1 (9.1%) respectively. The median duration to complete the surgical procedure for all patients was 330 (230-580) min and for robotic CRS the median docking time was 570 (330-580) min. Median PCI was 2 (1-7) and completeness Cytoreduction (CC score 0) was achieved in the all patients (100%). Median hospital stay was 8 days (3-20). Four patients had one night postoperative ICU stay. Major morbidity (CTCAE) 3 and 4 occurred in three patients (27.3%) (Port site hernia, bleeding, and wound infection). No readmission to the hospital and no 90 days mortalities. CONCLUSION: The minimally invasive approach by laparoscopy or robot is a feasible and promising option for CRS and HIPEC. It reduces the hospital stay, early return to intended oncological treatment (RIOT). Further prospective clinical studies are needed to evaluate this approach.

Appendiceal neoplasms in Saudi Arabia: prevalence and clinicopathological profile.

BACKGROUND: The appendix is a small organ with no particular known function. Primary appendiceal neoplasms (ANs) are rare. While the prevalence is increasing worldwide over the past two decades, no apparent increase in the prevalence of ANs has been reported in the Arabian Gulf States. Recently, a significant decline in the age at diagnosis of some types of ANs has been reported worldwide, with a female predominance. OBJECTIVES: Evaluate the prevalence and clinicopathological characteristics of ANs within our institution in Saudi Arabia and compare them to limited existing studies from different regions as well as the Arabian Gulf States. DESIGN: Retrospective cohort. SETTING: Tertiary care center in Riyadh. PATIENTS AND METHODS: All patients who underwent appendectomy and had the appendix submitted for histopathological evaluation between May 2015 and June 2020 were included to allow for a follow-up of 5 years or more at the time of data collection. MAIN OUTCOME MEASURES: Demographics, clinical presentations, surgical interventions, histopathological findings, complications, and recurrence rates. SAMPLE SIZE: 25 AN patients. RESULTS: Of 1110 patients, 25 had ANs (13 female and 12 male participants) with a mean (standard deviation) age of 54.6 (14.1) years. Only 40% presented with acute appendicitis, 64% had comorbidities, and less than 50% underwent laparoscopic appendectomy. Histopathologically, 72% were low-grade appendiceal mucinous neoplasms (LAMNs). Complications were minimal grades (Clavien-Dindo classification), with 80% experiencing none. The mean hospital stay was 9.96 days. Local recurrence occurred in 8% of cases, and distant metastasis was documented in one adenocarcinoma case. However, the 5-year overall and disease-free survival rates were 88% and 80%, respectively. CONCLUSIONS: The incidence of ANs is increasing in Saudi Arabia with the higher prevalence of LAMNs. The pathological examination of the resected appendix played a pivotal role in the diagnosis of ANs. LIMITATIONS: Data collected retrospectively, a single institution, and a small population.

Identification of 2-(N-aryl-1,2,3-triazol-4-yl) quinoline derivatives as antitubercular agents endowed with InhA inhibitory activity.

The spread of drug-resistant tuberculosis strains has become a significant economic burden globally. To tackle this challenge, there is a need to develop new drugs that target specific mycobacterial enzymes. Among these enzymes, InhA, which is crucial for the survival of Mycobacterium tuberculosis, is a key target for drug development. Herein, 24 compounds were synthesized by merging 4-carboxyquinoline with triazole motifs. These molecules were then tested for their effectiveness against different strains of tuberculosis, including M. bovis BCG, M. tuberculosis, and M. abscessus. Additionally, their ability to inhibit the InhA enzyme was also evaluated. Several molecules showed potential as inhibitors of M. tuberculosis. Compound 5n displayed the highest efficacy with a MIC value of 12.5 µg/mL. Compounds 5g, 5i, and 5n exhibited inhibitory effects on InhA. Notably, 5n showed significant activity compared to the reference drug Isoniazid. Molecular docking analysis revealed interactions between these molecules and their target enzyme. Additionally, the molecular dynamic simulations confirmed the stability of the complexes formed by quinoline-triazole conjugate 5n with the InhA. Finally, 5n underwent in silico analysis to predict its ADME characteristics. These findings provide promising insights for developing novel small compounds that are safe and effective for the global fight against tuberculosis.

Unveiling the potential of isatin-grafted phenyl-1,2,3-triazole derivatives as dual VEGFR-2/STAT-3 inhibitors: Design, synthesis and biological assessments.

The use of VEGFR-2 inhibitors as a stand-alone treatment has proven to be ineffective in clinical trials due to the robustness of cellular response loops that lead to treatment resistance when only targeting VEGFR-2. The over-activation of the signal transducer/activator of transcription 3 (STAT-3) is expected to significantly impact treatment failure and resistance to VEGFR-2 inhibitors. In this study, we propose the concept of combined inhibition of VEGFR-2 and STAT-3 to combat induced STAT-3-mediated resistance to VEGFR-2 inhibition therapy. To explore this, we synthesized new isatin-grafted phenyl-1,2,3-triazole derivatives "6a-n" and "9a-f". Screening on PANC1 and PC3 cancer cell lines revealed that compounds 6b, 6 k, 9c, and 9f exhibited sub-micromolar ranges. The most promising molecules, 6b, 6 k, 9c, and 9f, demonstrated the highest inhibition when tested as dual inhibitors on VEGFR-2 (with IC50 range 53-82 nM, respectively) and STAT-3 (with IC50 range 5.63-10.25 nM). In particular, triazole 9f showed the best results towards both targets. Inspired by these findings, we investigated whether 9f has the ability to trigger apoptosis in prostate cancer PC3 cells via the assessment of the expression levels of the apoptotic markers Caspase-8, Bcl-2, Bax, and Caspase-9. Treatment of the PC3 cells with compound 9f significantly inhibited the protein expression levels of VEGFR-2 and STAT-3 kinases compared to the control.

The relationship between baseline nutritional status with subsequent parenteral nutrition and clinical outcomes in cancer patients undergoing cytoreductive surgery: a retrospective study.

Introduction: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreductive Surgery (CRS) is the preferred treatment for peritoneal malignancies. This highly complex operation is associated with a high incidence of complications, particularly due to malnutrition. This study aimed to investigate the potential association between preoperative nutritional status and postoperative clinical outcomes in adult cancer patients who underwent CRS/HIPEC for peritoneal malignancy. Methods: A retrospective study with 140 adult cancer patients, on parenteral nutrition (PN) (n = 40) and not on PN (n = 100) who underwent CRS with or without HIPEC, was conducted. Results: Patients who received PN had significantly longer post-operative, hospital, and ICU LOS than those who did not (p = 0.001). ICU admission was significantly higher in the non-PN receiving group compared to the PN receiving group. When compared to the PN group, the majority of patients not receiving PN were at low risk of malnutrition (91% vs. 75%, p = 0.020), whereas 17.5% of PN patients were at risk of malnutrition during hospitalization. Multiple regression analyses revealed a strong positive relationship between patients with increased risk of malnutrition and ICU LOS (p = 0.047). Discussion: Routine preoperative nutrition assessment is essential to identify patients who are at higher nutritional risk, and nutrition support should be provided preoperatively.

Discovery and Mechanistic Studies of Dual-Target Hits for Carbonic Anhydrase IX and VEGFR-2 as Potential Agents for Solid Tumors: X-ray, In Vitro, In Vivo, and In Silico Investigations of Coumarin-Based Thiazoles.

A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a-h, 6, and 7a-e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5e can effectively inhibit both targets. 5a, 5d, and 5e cytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5e to interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivo efficacy of compound 5e as an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5e and CA IX and VEGFR-2 binding pockets.

Surveillance Compliance and Quality of Life Assessment Among Surgical Patients with Familial Adenomatous Polyposis Syndrome.

BACKGROUND: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. We aimed to explore surveillance compliance in our population, as well as the disease impact on their quality of life (QoL). METHODS: All patients with FAP who underwent surgical resection at King Saud University Medical City between 2016 and 2022 were included. Demographic data, clinical features, family history, and compliance with surveillance were collected and analyzed. QoL questionnaires: Short-form health survey (SF-36) and European Organization for Research and Treatment (EORTC) were conducted by phone interview. RESULTS: A total of 14 patients were included with an average age of 25 years. Three patients (21.4%) were the first of their family members to develop FAP. Nine patients (64%) were untested for genetic mutation due to lack of referral to geneticists. The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. QoL scores varied among patients, with a mean score above 60 across all SF-36 domains. CONCLUSION: An overall poor compliance was observed among our participants, particularly toward thyroid ultrasound. Increased health awareness and patient education are essential. In addition, the importance of surveillance and genetic counseling should be emphasized among physicians treating these patients.

Clinical outcomes of lower gastrointestinal bleeding in patients managed with lower endoscopy: A tertiary center results.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is an urgent presentation with increasing prevalence and remains a common cause of hospitalization. The clinical outcome can vary based on several factors, including the cause of bleeding, its severity, and the effectiveness of management strategies. The aim of this study is to provide a comprehensive report on the clinical outcomes observed in patients with LGIB who underwent lower endoscopy. METHODS: All patients who underwent emergency lower endoscopy for fresh bleeding per rectum, from May 2015 to December 2021, were included. The primary outcome was to identify the rate of rebleeding after initial control of bleeding. The second was to measure the clinical outcomes and the potential predictors leading to intervention and readmission. RESULTS: A total of 84 patients were included. Active bleeding was found in 20% at the time of endoscopy. Rebleeding within 90 days occurred in 6% of the total patients; two of which (2.38%) were within the same admission. Ninety-day readmission was reported in 19% of the cases. Upper endoscopy was performed in 32.5% of the total cases and was found to be a significant predictor for intervention (OR 4.1, P = 0.013). Personal history of inflammatory bowel disease (IBD) and initial use of sigmoidoscopy were found to be significant predictors of readmission [(OR 5.09, P = 0.008) and (OR 5.08, P = 0.019)]. CONCLUSIONS: LGIB is an emergency that must be identified and managed using an agreed protocol between all associated services to determine who needs upper GI endoscopy, ICU admission, or emergency endoscopy within 12 hours.

Surgical outcomes and stoma-related complications in inflammatory bowel disease in Saudi Arabia: a retrospective study.

BACKGROUND: The prevalence of inflammatory bowel diseases (IBD), Crohn's (C) and ulcerative colitis (UC) has increased in Saudi Arabia during the past decade. Even though medical treatment is first-line therapy, most patients require surgery during the course of the disease. Stoma creation complications in IBD are underreported in the literature of the Middle East and especially in Saudi Arabia. OBJECTIVES: Report the postoperative, stoma and peristomal complications following stoma creation in (C) versus UC. DESIGN: Retrospective cohort study. SETTINGS: Tertiary care center. PATIENTS AND METHODS: Patients with IBD who underwent stoma creation for either UC or CD between August 2015 and July 2020 were included. The diseases were compared to assess their characteristics and association to postoperative, stoma and peristomal complications. All complications were reported over a 90-day duration from the surgery. Patients younger than 14 years of age were excluded. MAIN OUTCOME MEASURES: Postoperative complications, stoma and peristomal complications in IBD patients who underwent stoma creation. SAMPLE SIZE: 50. RESULTS: Of 50 IBD patients underwent stoma creation, 32 patients (64%) were diagnosed with CD and 18 patients (36%) with UC. Most of the procedures in both groups were laparoscopic and elective. Low BMI and serum albumin were more prevalent in the CD group. Postoperative complications were higher in the CD patients compared to the UC patients (CD 40.6% vs UC 11.1%, P=.028) with the most common complication being abdominal collection[a]. Stoma complications were comparable between the two groups (UC 16.7% vs CD 15.6%). However, peristomal complications were higher clinically in UC patients in comparison with the CD patients (UC 61.1% vs CD 37.5% P=.095) with the most common complication being skin excoriation (UC 44.4% vs CD 37.5%). CONCLUSIONS: CD has significantly higher postoperative complications compared to UC. Peristomal complications were high in both groups and had a negative impact on quality of life. Therefore, comprehensive stoma education and regular outpatient follow ups are recommended to improve the overall outcomes. LIMITATIONS: Retrospective and conducted in one academic institution with a small sample size.

The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-ß-SMAD pathway in colorectal cancer.

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-ß) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-ß and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines. Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-ß demonstrated that PT-complex significantly regulated the TGF-ß-mediated altered expressions of EMT markers. Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-ß-regulated EMT markers. These findings provide new insight into TGF-ß/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex.

Colorectal cancer-related resource utilization and healthcare costs in Saudi Arabia.

Background: Recently, there has been an increase in the incidence of colorectal cancer in Saudi Arabia. Although numerous studies worldwide have investigated the economic burden of colorectal cancer the information specific to Saudi Arabia remains limited. While advanced cancer treatments offer substantial benefits, they they also come with substantial financial challenges. Objective: This study aimed to estimate the economic burden of colorectal cancer and identify the primary cost drivers. Method: This retrospective, single-center cost of illness study examined all patients with colorectal cancer from January 2017 to December 2020. This study used a micro-costing, bottom-up approach to estimate healthcare resource utilization and direct medical costs associated with colorectal cancer. Result: The study included 326 patients with colorectal cancer. The total direct medical cost for all patients were $19 million, with an annual cost per patient of $58,384. Medication costs were the primary driver of healthcare spending (45%) of the total cost, followed by surgical costs (27%). This study explained cost associated with colorectal cancer, which represents a significant cost to the Saudi healthcare budget. The expected growth and aging of the population and availability of costly treatments may lead to an increase in costs. These findings are valuable for healthcare policymakers seeking to comprehend the economic challenges posed by colorectal cancer.

5-year oncological outcomes in left-sided malignant colonic obstruction: stent as bridge to surgery.

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.

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (-658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between -658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.

Oncological outcomes of elective versus emergency surgery for colon cancer: A tertiary academic center experience.

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 impact of preoperative total parenteral nutrition on the surgical complications of Crohn's disease: A retrospective cohort study.

Background: Crohn's disease (CD) is associated with malnutrition, an independent risk factor for surgical morbidity and mortality in more than 65% of patients, with a significant impact on disease outcomes. In this single-center retrospective cohort study, we aimed to investigate the impact of total parenteral nutrition (TPN) on the surgical outcomes of patients with CD. Methods: This study included patients with CD who underwent abdominal surgery. We compared patients who received preoperative total parenteral nutrition (TPN group) to those who did not (non-TPN group). Prolonged oral intolerance, albumin level <30 g/L, and body mass index <18.5 were the main indications for TPN. We evaluated postoperative surgical complications in both groups. Results: Between January 2010 and October 2018, 169 eligible patients underwent abdominal surgery. The TPN and non-TPN groups included 40 and 129 patients, respectively. The mean albumin level was significantly lower in the TPN group (P = 0.013). Laparoscopic surgery was performed in 76.9% of the patients, with a conversion rate of 11.6%. Infectious and non-infectious complications developed in 8.9% and 16% of patients, respectively. Surgical complications were comparable between the groups (P >0.05). Conclusions: Despite oral intake intolerance and severe disease in the TPN group, the surgical complications were comparable between the groups.

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating ß­catenin and increases irinotecan sensitivity in colorectal cancer.

With >1.85 million cases and 850,000 deaths annually, colorectal cancer (CRC) is the third most common cancer detected globally. CRC is an aggressive malignancy with metastasis and, in spite of advances in improved treatment regimen, distant disease failure rates remain disappointingly high. Mucin­like 1 (MUCL1) is a small glycoprotein highly expressed mainly in breast cancer. The involvement of the MUCL1 protein in CRC progression and the underlying mechanism have been largely unknown. The aim of the present study was to investigate the MUCL1 expression profile and its functional significance in CRC. The Cancer Genome Atlas dataset revealed that MUCL1 expression was higher in colorectal tumor compared with normal tissues. MUCL1 was also revealed to be expressed in human CRC cell lines. The results demonstrated that MUCL1 promoted cell proliferation and colony formation, confirming its oncogenic potential. Silencing MUCL1 with short interfering RNA inhibited the protein expression of Bcl2 family proteins, such as Bcl2 and BclxL. Targeting MUCL1 resulted in significant inhibition in cell invasive and migratory behavior of HT­29 and SW620 cells. In addition, the expression of E­cadherin increased whereas the expression of vimentin decreased in MUCL1­silenced cells, confirming inhibition of epithelial­mesenchymal transition (EMT) process. Thus, it was revealed that MUCL1 plays a notable role in cell invasion and migration by inhibiting EMT in CRC. Mechanistically, MUCL1 drives ß­catenin activation by Ser­552 phosphorylation, nuclear accumulation and transcriptional activation. Targeting MUCL1 increases the drug sensitivity of CRC cells towards irinotecan. These findings thus demonstrated that MUCL1 acts as a modifier of other pathways that play an important role in CRC progression and MUCL1 was identified as a potential target for CRC therapeutics.

Hemorrhagic Necrotizing Cholecystitis With Cholecystocolonic Fistula: A Case Report.

Cholecystocolonic fistula (CCF) and hemorrhagic cholecystitis are rare complications of gallstones that have a wide range of non-specific symptoms and clinical severity. We present a case of a 74-year-old woman on warfarin who presented to the emergency department with a 10-day history of abdominal pain, vomiting, and watery diarrhea. Her abdomen was distended with generalized tenderness and palpable mass in the right lower quadrant. Laboratory tests revealed leukocytosis and an elevated international normalized ratio (INR). After admission and imaging, exploratory laparotomy showed hemorrhagic cholecystitis with CCF in the cecum. There was no pus or stool contamination. A cholecystectomy followed by right hemicolectomy with primary ileocolic anastomosis was performed. The postoperative course was uneventful, and the patient was discharged in stable condition. The presence of hemorrhagic cholecystitis in conjunction with CCF could lead to significant consequences such as hemorrhagic and septic shock in older patients with comorbidities. It is crucial to identify and intervene early before clinical deterioration.

Community knowledge and awareness of colorectal cancer and screening tools: Community-based survey of 1,912 residents of Riyadh.

BACKGROUND: Participation in Colorectal cancer (CRC) screening programs is low in Saudi Arabia. Public awareness of CRC and knowledge of available screening tools are crucial for improving screening uptake. This study aimed to examine the level of awareness and knowledge of CRC among the Saudi population. MATERIALS AND METHODS: A survey-based study was conducted on 1912 residents of Riyadh, Saudi Arabia. The survey comprised 20 questions; these concerned the definition of the colon and rectum; the function of the colon; the incidence, risk factors, symptoms, screening methods, prevention methods, and treatment methods for CRC; and the value of early detection of CRC. RESULTS: Of the 1912 participants who completed the survey, only 51.7% knew that the colon was the large intestine, while 57% knew that the rectum was the end of the large intestine. Colonoscopy was the preferred screening tool (72.8%). Most respondents believed early detection of CRC through colonoscopy is associated with high survival rates. However, 65.7% of the participants reported that they would not like to undergo a CRC screening. Higher education level was also associated with knowledge that CRC can develop asymptomatically, with postgraduates most likely to know this (P = 0.032). CONCLUSIONS: There is a lack of knowledge regarding CRC among certain demographic groups in Saudi Arabia, and education and screening programs should target populations with the most limited knowledge.

Expression of VEGF, EGF and HGF in early- and late-stage colorectal cancer.

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.