Unveiling the anticancer potential of novel spirooxindole-tethered pyrazolopyridine derivatives.

In the current medical era, human health is confronted with various challenges, with cancer being a prominent concern. Therefore, enhancing the therapeutic arsenal for cancer with a constant influx of novel molecules that selectively target tumor cells while displaying minimal toxicity toward normal cells is imperative. This study delves into the antiproliferative and EGFR kinase inhibitory activities of newly reported spirooxindole-pyrazolo[3,4-b]pyridine derivatives 8a-h and 10a-h. The inhibitory effects on the growth of human cancer cell lines A-549 (lung carcinoma), Panc-1 (pancreatic carcinoma), and A-431 (skin epidermoid carcinoma) were evaluated, and the SAR has been clarified through analysis. With IC50 values in the single-digit micromolar range, compounds 8b, 8d, 10a-b, and 10d were shown to be the most effective antiproliferative candidates against the studied cancer cell lines. They also exerted negligible cytotoxicity (with selectivity scores between 8.63 and 30.02) against the human lung MRC5 cell line. Additionally, we investigated the potential inhibitory action of compounds 8b, 8d, 10a-b, and 10d on EGFR and VEGFR-2. 10a was this investigation's most effective EGFR inhibitor, with an IC50 value of 0.54 µM. Ultimately, the molecular docking analysis of congener 10a highlighted its effective suppression of EGFR by examining its binding mode and docking score compared to Erlotinib. These findings underscore the potential of spirooxindole-pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents targeting EGFR kinase.

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.

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.

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.

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.

Outcomes of Sinus Laser Therapy in Sacrococcygeal Pilonidal Sinus Disease: A Single-Center Experience.

Sacrococcygeal pilonidal sinus disease (SPND) is an acquired chronic disease with no precise etiopathogenesis. The morbidity associated with the disease necessitates the implementation of new techniques, such as sinus laser therapy (SiLaT), to improve disease management. However, surgical techniques as of now are preferred as the mainstay mode of treatment. A retrospective study was conducted to evaluate and report the healing outcome of the application of SiLaT on patients with SPND at a tertiary center. All patients who underwent SiLaT for primary or recurrent pilonidal sinus from February 2012 to December 2019 were included in the study and followed up for at least six months. Forty-one participants (37 males (90.2%) and four females (9.8%)) were included. Of the participants, 58.5% presented with chief complaints of painful swelling with mucopurulent discharge. Most of the participants were students (43.9%). SiLaT was the primary intervention for 82.9% of the participants. The mean duration of hospital stays, resumption of regular activity, and complete wound healing by secondary intention were 30±21.5 hours, 18.4±14.3 days, and 6.5±6.6 weeks, respectively. Around 95.1% of wounds healed without complications. The overall recurrence rate was 24.4%, while the recurrence rate with SiLaT being the primary intervention was 11.8%. Only three (7.32%) patients experienced wound infections as postoperative complications. The visual analog scale (VAS) score decreased postoperatively in the first and second weeks to 3.9±3.2 and 1.9±1.9, respectively, and 78.1% of the total patients showed satisfaction post-surgical interventions. The current study showed that the SiLaT technique is a feasible technology with promising results to evolve. Further studies are encouraged.

Multiple primary gastrointestinal tumors of gastric, pancreatic and rectal origin; a case report.

INTRODUCTION: The occurrence of multiple primary synchronous or metachronous malignancies is a described phenomenon. Such cases may have genetic predisposition or could be related to environmental risk factors but may also be sporadic. We are reporting a unique combination of triple primary synchronous malignancies in the same patient. CASE PRESENTATION: A 71 year old man presented with constipation and per rectal bleeding with a palpable mass 5-6 cm from the anal verge on physical examination. Colonoscopy with biopsy confirmed adenocarcinoma of rectal origin. After multi-disciplinary tumor board meeting, the patient received neoadjuvant chemoradiation therapy followed by single-stage surgery. Re-staging work up showed the presence of pancreatic lesion. Incidental finding of a gastric nodule upon surgical exploration which was confirmed to be a gastrointestinal stromal tumor. The patient had an uneventful postoperative course. DISCUSSION: Multiple primary malignancies of the gastrointestinal system has previously been reported in the literature; whether in the form of double, triple, quadruple or even quintuple primaries. Furthermore, gastrointestinal malignancies have been reported to be combined with extra-intestinal malignancies. However, this unique combination of pancreatic adenocarcinoma, rectal adenocarcinoma and gastric gastrointestinal stromal tumor has not been previously reported in the literature. Single-stage multiple resections was successful. CONCLUSION: We are reporting a unique case of three primary malignancies involving the rectum, pancreas and stomach. For such patients, there is no clear guidelines regarding management or surveillance, but rather should be individualized.

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.

Short-term outcomes after self-expandable metal stent insertion for obstructing colon cancer: a retrospective cohort study.

BACKGROUND: Self-expanding metal stents (SEMS) are used as a bridge to surgery for colon cancer patients as an alternative to emergency surgery. Currently, there is a paucity of literature from Saudi Arabia on the preoperative usage of SEMS. OBJECTIVE: Determine whether SEMS are associated with a higher rate of complications. DESIGN: Retrospective cohort study SETTINGS: Tertiary care hospital in Saudi Arabia. PATIENTS AND METHODS: In patients diagnosed with obstructing colon cancer, up-front surgical resection was compared with insertion of SEMS followed by surgical resection between the years 2009 and 2013. MAIN OUTCOME MEASURES: Rate of stent-related short-term complications. Secondary endpoint, postoperative complications. SAMPLE SIZE: 65. RESULTS: Twenty-four (36.9%) patients underwent SEMS placement; 41 (63.1%) underwent primary surgery. The median (interquartile range) hospital stay was significantly higher among the SEMS group (13 [8.5] days versus 7 [3] days in the primary surgery group, P<.001). Five patients (20.8%) in the SEMS group developed complications: 2 (8.3%) perforations, 2 (8.3%) obstructions, and 1 (4.2%) stent migrations. CONCLUSION: SEMS is associated with longer hospital stays and short-term serious complications. Further research should be conducted, preferably with a larger sample size. LIMITATIONS: Retrospective design, small sample size. CONFLICT OF INTEREST: None.

Impact of COVID-19 pandemic on patient satisfaction and surgical outcomes: A retrospective and cross sectional study.

OBJECTIVE: The objective of this study was to evaluate the impact of the COVID-19 pandemic on patient satisfaction and surgical outcomes at King Khalid University Hospital in Saudi Arabia. BACKGROUND: The COVID-19 pandemic has greatly affected health care systems across developing and developed countries. Therefore, it is important to understand its impact on various parameters of patient care as regards revised infrastructure and policies in hospitals during the pandemic. METHOD: It is a retrospective cross-sectional study was conducted from 13-3-2020 to 26-4-2020 at King Khalid University Hospital in Saudi Arabia. Patient satisfaction and surgical outcomes were the main outcome measures. RESULTS: 331 participants were included in the study (median age: 53 years; 70% female), and 223 completed the patient's satisfaction survey. 260 of the surgeries were non-oncolog cases (78.6%) compared to 71 oncology cases (21.4%). With respect to the surgical outcomes, 12% of the patients required admission to the ICU, and 10.9% developed postoperative complications, most of which were infectious complications. Only 1.8% (6 patients) were re-admitted to the hospital. Three patients died within 30 days post-op (0.9%), all had emergency surgery. Regarding patient satisfaction, 77.6% and 93% of the patients reported that nurses and doctors, respectively, treated them with courtesy and respect, listened to them carefully, and provided clear explanations to them. 90.3% were satisfied with the hospital sanitary measures. 64.1% stated that they got written instructions at the time of discharge. CONCLUSION: The satisfaction level of patients was high for all the studied domains, and there were a small number of complications with overall good surgical outcomes. That indicates that all the actions and policies that were implemented during the pandemic were proven beneficial for the patients. It is recommended to continue those measures until the COVID-19 pandemic is over.

Long-term outcomes after complete mesocolic excision for colon cancer at a tertiary care center in Saudi Arabia.

BACKGROUND: Data on long-term survival and recurrence of cancer after complete mesocolic excision (CME) for colon cancer has not been reported from our center and related to international data. OBJECTIVE: Describe overall and disease-free survival, survival by surgery site and stage, and recurrence rates after curative surgery. DESIGN: Retrospective chart review. SETTINGS: Academic tertiary care center. PATIENTS AND METHODS: The study included all patients who underwent either laparoscopic or open surgery for colon cancer with curative intent between 2001 and 2011. The colorectal database was reviewed for the following: demographic data, comorbidities, radiologic investigations, clinical stage, type of operation, complications, pathologic assessment, adjuvant treatment, recurrence and survival. Survival and recurrence rates were calculated, and survival curves were generated. MAIN OUTCOME MEASURES: 5-year overall survival, secondary endpoints were 5-year disease-free survival, survival by surgery site and stage, and recurrence rates. SAMPLE SIZE: 220. RESULTS: The mean (SD) age at diagnosis was 57 (13) years (CI 95%: 55-59 years). There were 112 males. Mean (SD) body mass index was 27.6 (5.7) kg/m2 (CI 95%: 27-28). Pathological assessment revealed R0 (microscopically margin-negative) resection in 207 (94%). The overall 5-year survival and disease-free survival was 77.9% and 70%, respectively. The 5-year disease-free survival was 69% for the sigmoid/left colon and 69% for the right colon (difference statistically nonsignificant). Stages at the time of resection were stage 0 for 2 (0.01%) patients, stage I for 18 (8%), stage II for 92 (42%), stage III for 100 (46%), and stage IV for 6 (3%). The 5-year overall survival by stages I, II, III and IV was 94%, 80%, 75% and 50%, respectively (difference statistically non-significant). The overall 5-year recurrence rate was 23.4%. CONCLUSION: The outcomes of surgical treatment for colon cancer at our institution are equivalent to international sites. No difference was noted between left and right colon in terms of survival after CME. LIMITATIONS: Single center, retrospective, small sample size. CONFLICT OF INTEREST: None.

Survival and outcomes after laparoscopic versus open curative resection for colon cancer.

BACKGROUND: Many studies have shown that open and laparoscopicsurgery for resection of colonic cancers produce similar short- and long-term results, but no data have been reported from Saudi Arabia. OBJECTIVE: Compare 3-year disease-free and overall survival after laparoscopic versus open curative resection for potentially curable colon cancer. DESIGN: Multicenter retrospective cohort study. SETTING: Tertiary academic hospital. PATIENTS AND METHODS: We analyzed data of patients who underwent curative resection for potentially curable colon cancer using the laparoscopic or open approach at three tertiary care centers during the period 2000-2015. MAIN OUTCOME MEASURES: Overall and disease-free 3-year survival were the primary endpoints. Secondary endpoints included conversion rate, duration of surgery, length of hospital stay, rate of wound infection, resumption of bowel function, number of lymph nodes retrieved, adequacy of resection and rate of recurrence. Risk factors for recurrence, including complete mesocolic excision, were assessed. SAMPLE SIZE: 721. RESULTS: Patient and tumor characteristics were similar in the two groups except for ASA class ( P<.01), weight ( P<.05) and tumor stage ( P<.05). Over a median follow-up of 46 months, the 3-year overall survival was 76.7% for open resection and 90.3% for laparoscopic colon resection ( P<.05). The 3-year disease-free survival was 55.3% for open colon resection and 64.9% for laparoscopic colon resection ( P=.0714). CONCLUSION: Overall and disease-free survival after the laparoscopic approach for curative resection of colon cancer is comparable to the open approach. LIMITATIONS: Retrospective design and the possibility of selection bias. CONFLICT OF INTEREST: None.

IL-17 and colorectal cancer risk in the Middle East: gene polymorphisms and expression.

BACKGROUND: 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). OBJECTIVE: We investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population. MATERIALS AND METHODS: 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. RESULTS: We observed significant association between rs2275913 in IL-17A and susceptibility to CRC (p = 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 (p = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors. CONCLUSION: 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.

No Differences in Energy Cost of a Predetermined Exercise among Young Overweight/Obese and Undernourished Individuals.

BACKGROUND: Physical activity is an integral part of one's daily life. Obese (Ob) and undernourished (UN) persons are known to underperform physically as compared to normal weight (N) individuals. In this study, we have measured the energy spent to perform a prefixed exercise on treadmill walking and basal heart rate and blood pressure. Body mass index (BMI) and body fat of participating individuals were assessed. Fasting blood sugar and lipid profile were also evaluated. MATERIALS AND METHODS: Eighty-three young individuals (male: 41; female: 42) of medical faculty, Universiti Sultan Zainal Abidin, who volunteered for the study, were recruited. The mean age of the individuals was 19.8 ± 0 years (P < 1.08). The individuals were grouped as N, UN/underweight, and overweight (Ow)/Ob based on BMI. RESULTS: The results of the study revealed that there were no differences in the energy spent on performing the predetermined treadmill walking of 20 min duration among the three groups (a mean of 78 and 70 calories in all male and female subgroups, respectively). The distance covered by the males was 1.6 km while the females covered 1.4 km on treadmill walking in 20 min time. Basal blood pressure and heart rate and fasting blood sugar did not reveal any significant difference among the groups. However, total cholesterol and triglyceride levels were marginally higher in the Ow/Ob groups of male and female individuals as compared to other groups. CONCLUSION: Since the study individuals were very young and competitive by nature and possibly had no major metabolic disturbances, the differences in physical activity performances were not obvious. Possibly, such differences would become apparent only at later stages of life as age advances or when the intensity and duration of exercise are set at higher levels.

Cathepsin B expression in colorectal cancer in a Middle East population: Potential value as a tumor biomarker for late disease stages.

Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70 patients and 20 healthy control subjects using enzyme-linked immunosorbant assay (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection of CTSB protein expression in tissues was carried out using both immunohistochemistry and western blotting techniques. ELISA analysis showed that in sera obtained from CRC patients, the CTSB concentration was significantly higher in late stage patients with lymph node metastases when compared to early stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The majority of tumors studied had detectable CTSB protein expression with significant increased positive staining in tumors cells when compared with matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC compared to late stage CRC was 0.04±0.01 and 0.07±0.02, respectively. Increased mRNA expression was more frequently observed in the advanced cancer stages with lymph node metastases when compared with the control (P=0.002). Mann-Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in early and late tumor stage. A subset of four paired tissue extracts were analyzed by western blotting. The result confirmed a consistent increase in the CTSB protein expression level in tumor tissues compared with that noted in the adjacent normal mucosal cells. These findings indicate that CTSB may be an important prognostic biomarker for late stage CRC and cases with lymph node metastases in the Middle Eastern population. Monitoring serum CTSB in CRC patients may predict and/or diagnose cases with lymph node metastases.

Acquired hypernatremia in a general surgical Intensive Care Unit: Incidence and prognosis.

PURPOSE: Intensive Care Unit (ICU)-acquired hypernatremia (IAH) is a serious electrolyte disturbance that recently was shown to present an independent risk factor for mortality in critically ill patients. IAH has not been widely investigated in Surgical ICU (SICU) patients. No study has specifically investigated IAH epidemiology in the Kingdome of Saudi Arabia (KSA) in general SICU. The objectives of this study are to assess the epidemiological characteristics and prognostic impact of IAH on SICU mortality and outcome in KSA and compare it with international figures. MATERIALS AND METHODS: A retrospective observational study on a prospectively collected data of patients (14 years of age or older) admitted to SICU over 2 years, with normal serum sodium on admission and who developed IAH (serum sodium above 145 mmol/L) from day two of admission. Traumatic brain injury patients with therapeutic target sodium level above 145 mmol/L were excluded. RESULTS: Over 2 years study period, 864 patients were admitted to SICU. A total of 50 (5.8%) developed IAH and were included in the study. Twenty-eight (56%) patients were male. The median age was 47 (14-84) years. The mean (± standard deviation) Acute Physiology and Chronic Health Evaluation II score was 17 ± 6.5. The incident density (the rate of occurrence of IAH per 100 days care for SICU admission for the first episode) was 0.71. Risk factors include mechanical ventilation, male sex, age ≥50 years, postgastrointestinal surgeries, weekend and night admission. SICU mortality was 40%. The SICU and hospital median (range) length of stay was 8.3 (2-53) and 28.8 (3-95), respectively. CONCLUSIONS: IAH is not uncommon in SICU patients and is associated with increased risk of SICU as well as hospital mortality.

Single-incision laparoscopic colorectal surgery: a report of 33 cases in Saudi Arabia.

BACKGROUND: Single-incision laparoscopic surgery (SILS) has gained worldwide acceptance as a minimally invasive technique in colorectal procedures since its introduction in 2008. However, case series on its feasibility and safety in Saudi Arabia are lacking. OBJECTIVE: Evaluate the operative results and clinical outcome of single-port laparoscopic procedures in colorectal surgeries. DESIGN: Retrospective. SETTING: This study was conducted at King Khalid university Hospital, Riyadh, Saudi Arabia. PATIENTS AND METHODS: Demographic and clinical data, including pathology, and intraoperative and postoperative outcomes, were prospectively collected in patients undergoing SILS. This study was conducted during the period from January 2010 and October 2014. MAIN OUTCOME MEASURES: Demographic and postoperative outcomes in patients undergoing SILS colectomies. RESULTS: Thirty-three (33) patients underwent SILS. The mean (SD) age was 51 years (18.2 years), and the average body mass index was 26.6 (6.9) kg/m2. Patients were primarily diagnosed with cancer (n=20/33, 61%), inflammatory bowel disease (n=12/33, 36%) and diverticulitis (n=1/33, 3%). Procedures included anterior resection (n=9/33, 27%), ileocecal resection (n=8/33 24%), hemicolectomy (n=7/33, 21%), extended right hemicolectomy (n=5/33, 15%) and total colectomy (n=4/33, 12%). The mean SD operative time was 212 minutes (76.4 minutes). The mean SD size of the extraction incision was 4.2 (1.7) cm. Six percent of the cases were converted to open (n=2/33), and 9% required placement of an extra port (n=3/33). Four (12%) patients had intraoperative complications, and 30% experienced postoperative complications. The average length of hospital stay was 6.4 (4.3) days. COCNLUSIONS: SILS is technically feasible and safe for patients undergoing colorectal surgery with no unusual complications. However, comparative studies are necessary to validate the potential benefits of SILS over conventional colorectal laparoscopic surgery. LIMITATIONS: The study lacked a comparison to conventional open procedures. Additionally, some evaluation criteria were not considered, including cosmesis, pain control, patient satisfaction and cost effectiveness.

Differential expression of mucins in Middle Eastern patients with colorectal cancer.

Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC.

Polymorphisms of tumor necrosis factor alpha in Middle Eastern population with colorectal cancer.

Tumor necrosis factor-alpha (TNF-α) contributes in inflammation and has been implicated in the development of colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in TNF-α promoter could affect the risk of CRC by regulating TNF-α production. This is the first study to investigate TNF-α SNPs in a Middle Eastern population. In this study, we examined three SNPs in TNF-α for association with CRC. One hundred CRC patients and 100 controls were genotyped for TNF-α -308, -238, and -857 using TaqMan allelic discrimination assay. The TNF-α -238 (G/A) genotype was significantly associated with high risk of CRC (p = 0.003552). The distribution of three genotypes of -238 G/A was significantly different between the controls and CRC patients even after Bonferroni's correction. The AA genotype of -238 G/A SNP was observed at considerably higher proportion (13 %) in CRCs compared to controls (1 %). Additionally, similar to genotypes, the allelic frequencies of -238 G/A were significantly different between the CRC cases and controls (odds ratios (OR) = 7.647, χ (2) = 18.50, p = 0.00002). The genotype frequencies of -308 and -857 were not notably different between the cases and controls. TNF-α -238A may be useful as a screening marker to identify individuals prior to their acquiring CRC in the Saudi population although, further validations in larger cohorts are needed.