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.

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.

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.

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.

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.

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.

The attitude and practice of general surgeons toward cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A cross-sectional study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) mandate well-established HIPEC and oncology centers, which are not available in many medical institutions. This study assessed the knowledge, attitude, and practice toward CRS and HIPEC of general surgeons in Riyadh, Saudi Arabia. PATIENTS AND METHODS: General surgeons (n = 266) from nine hospitals who treat patients with gastrointestinal cancer were surveyed. The responses of surgeons who work in HIPEC and academic centers (Group A) and surgeons working in tertiary and secondary hospitals (Group B) were compared. The survey response rate was 48.1% (128/266). RESULTS: Surgeons in group B treated significantly more patients with peritoneal carcinomatosis per year than surgeons in group A (P = .001). Group B reported having a HIPEC specialist at their hospital, and 71.4% reported that the nearest HIPEC center was within 30 miles, compared to 4.5% of respondents in group A (P = .001). Lack of access to a HIPEC specialist was reported by 15.5% of surgeons in group B and 0% of surgeons in group A (P = .006). HIPEC as a possible therapeutic option for appendiceal cancer was cited by 60.7% of surgeons in group B compared to 84.1% of surgeons in group A (P = .007) and as a therapeutic option for ovarian cancer by 52.4% of surgeons in group B and 81.8% of surgeons in group A (P = .001). CONCLUSION: New strategies are needed to improve the knowledge and implementation of the referral system for HIPEC among general surgeons. Our study was limited by a low response rate.

Large Asymptomatic Retroperitoneal Ganglioneuroma Displacing Major Abdominal Organs and Vessels in an Adult.

BACKGROUND Ganglioneuromas (GNs) are benign neuroblastic tumors. These extra-cranial solid tumors are common in childhood but unusual in adults. Patients with GNs typically do not have any symptoms and the tumors usually are incidental findings. However, if a GN is large enough to compress adjacent organs, complications can occur. Furthermore, even in patients who have incomplete resection of a GN, long-term survival rates are high. After a GN is seen on imaging, the diagnosis usually is made with a biopsy and treatment is with surgery alone. CASE REPORT A 29-year-old woman was referred to General Surgery from the Gynecology Clinic for an incidental finding of an abdominal mass on routine ultrasound for secondary infertility and admitted for an investigation. Abdominal and pelvic computed tomography (CT) and magnetic resonance imaging showed a retroperitoneal mass that measured 6.318×22 cm arising from the paravertebral region with intraspinal extension. The mass was displacing the patient's thoracic aorta, abdominal inferior vena cava, and ureters. A CT-guided biopsy revealed a GN. Debulking surgery was performed and a small amount of residual tumor was left in the paravertebral nerve roots. The patient recovered well with no complications. The diagnosis of GN was confirmed with pathology, which was reviewed by the Tumor Board; the Board agreed that only follow-up in the Surgery Clinic was needed. During the patient's last visit, 10 months after surgery, a follow-up CT scan showed that the residual tumor was stable. CONCLUSIONS GNs are benign abdominal and retroperitoneal tumors that are typically asymptomatic and detected incidentally. Surgical resection is the treatment of choice and even when it is incomplete, the prognosis for patients is excellent.

Cystic Ovarian Leiomyoma in a Patient with Progressive Abdominal Pain.

BACKGROUND Ovarian leiomyomas are rare, benign, smooth muscle, solid tumors that occur in women aged 20 to 65 years. Because their histology is benign, the prognosis for patients is good. We report the case of a patient with a huge ovarian leiomyoma who presented to the General Surgery Clinic with chronic abdominal pain and progressive abdominal distention. CASE REPORT A 45-year-old woman with a history of multiple myomectomies and a total abdominal hysterectomy with right oophorectomy presented to the General Surgery Clinic with abdominal pain and a 4-year history of progressive distention. After being examined, the patient underwent an exploratory laparotomy, during which a pelvic cyst was found that measured 3930.2 cm, was filled with serous fluid (10.5 L), and occupied most of the abdominal space. The surgery went smoothly and there were no complications during or after the procedure. The patient was discharged home 7 days later in stable condition. Postoperative pathology using hematoxylin and eosin staining and immunohistochemistry with desmin and alpha-smooth muscle actin resulted in a diagnosis of leiomyoma with cystic degeneration. When the patient was seen in the outpatient clinic 2 weeks and 3 and 6 months after surgery, her tumor markers were within normal limits. Abdominal and pelvic computed tomography scans performed at the 6-month visit showed resolution of the loculated intraperitoneal fluid and no gross local recurrence of the tumor. CONCLUSIONS Ovarian leiomyomas are difficult to diagnose preoperatively. Suspicion for one should be high, however, in patients who present with a large cystic mass in adnexal tissues, especially if they have a history of hysterectomy and oophorectomy.

Colorectal Schistosomiasis Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Metastatic Colon Adenocarcinoma: A Case Report.

BACKGROUND Colorectal cancer is one of the most common cancers in men and women worldwide. There are several studies showing an association between chronic schistosomiasis infection and colorectal cancer. CASE REPORT A 53-year-old woman presented with recurrent metastatic colon cancer involving the peritoneum and bilateral adnexa. The patient then underwent exploratory laparotomy that involved abdominal wall deposit resection, omentectomy, redo left hemicolectomy, peritonectomy, diaphragmatic stripping, and total abdominal hysterectomy with bilateral salpingectomy-oophorectomy, as well as hyperthermic intraperitoneal chemotherapy (HIPEC). She also underwent adjuvant chemotherapy, but on her 6th cycle, the patient suffered intolerable anal pain, diarrhea, and rectal bleeding. Her colonoscopy showed extended circumferential inflammation with loses of vascular pattern and a few rectal ulcers going up to the anastomosis site. Biopsy revealed Schistosoma mansoni eggs and marked ischemic changes. She was then managed with a single dose of Praziquantel. CONCLUSIONS Colorectal schistosomiasis infection is a rare cause of such common presentations especially in postoperative settings in a patient with recurrent metastatic colon cancer. The use of multimodality investigations and high clinical suspicion were needed for the diagnosis and to exclude other common etiologies.

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.

A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer. METHODS: Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/- 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA. RESULTS: In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells. CONCLUSION: Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.

Two Histologically Different Primary Malignancies: Synchronous Obstructive Descending Colon Adenocarcinoma and Appendicular Carcinoid Tumor.

BACKGROUND Synchronous primary tumors are defined as 2 or more different histological tumors discovered in one patient at the same time or within a period of 6 months. Colorectal cancer is one of the most common cancers in the United States. Inversely, synchronous colorectal cancer and carcinoid tumors are rare. Carcinoid tumors can be classified into functioning and non-functioning tumors. Carcinoid tumors are steadily increasing in incidence. There is only 1 case reported in the literature as synchronous colorectal cancer and appendicular carcinoid. The difficulty is to manage 2 different types of malignancies at the same time. An optimal medical or chemotherapy strategy is needed. CASE REPORT A 29-year-old woman presented to the emergency room carrying with her computerized tomography (CT) abdomen and pelvic images showing bowel obstruction. Investigations confirmed an obstructing descending colon mass. She underwent colonoscopic stenting as emergency treatment with multiple biopsies. The pathology report came back positive for adenocarcinoma, and we planned to proceed with surgery. Intraoperatively, she was found to have an appendicular mass. The surgical team decided to proceed with laparoscopic-assisted subtotal colectomy. The postoperative course was uneventful, with no complications. The patient was discharged on postoperative day 6 in stable condition. CONCLUSIONS Synchronous colorectal cancer and carcinoid tumors are rare malignancies. The challenge is to find an optimal medical or chemotherapy strategy to manage both malignancies.

Single-Port Laparoscopic Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is one of the treatment options in low-grade appendiceal mucinous neoplasm with peritoneal dissemination. The minimal invasive surgery approach was introduced to the field after years of traditional open technique. Multi-port laparoscopic and robotic techniques were reported with good short-term outcomes in very selected patients with low PCI scores. We describe here the first single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. CASE REPORT We present a case of low-grade appendiceal mucinous neoplasm with peritoneal dissemination, in which single-port laparoscopic approach of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was completed through a 5.5-cm incision. A 35-year-old man with no medical illness underwent laparoscopic appendectomy for acute appendicitis 3 months earlier. Postoperative surgical pathology reported a low-grade appendiceal mucinous neoplasm with positive margin. After complete assessment and Tumor Board discussion, the patient was scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. A single gel port access was inserted through a 5.5-cm peri-umbilical incision. The Peritoneal Cancer Index score was 4, and the decision was made to proceed with partial cecectomy, omentectomy, peritonectomy, and hyperthermic intraperitoneal chemotherapy with the Sugarbaker mitomycin C-based regimen. Postoperative care was carried out following the Enhanced Recovery After Surgery protocol. The patient was discharged on day 3 without any complications. CONCLUSIONS A single-port laparoscopic approach in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is safe and feasible in very selected patients, and has the advantage of direct visualization and palpation through the incision to determine more accurate Peritoneal Cancer Index assessment in comparison to other MIS approaches. Nevertheless, additional prospective studies are needed.

A Perforated Colonic Neuroendocrine Tumor with Liver Metastasis: A Case Report and Literature Review.

BACKGROUND Neuroendocrine neoplasms (NENs) originate from cells of the endocrine and nervous systems, and they are rarely encountered in colorectal cases with no specific symptoms. The incidence and prevalence of NENs of the large bowel are increasing. Malignant colonic types are known to have poor diagnosis. The mean age of colonic NENs is the seventh decade, and the risk of NENs is increased 4-fold with affected first-degree family members. CASE REPORT A 57-year-old male patient presented to our Emergency Department with a 5-day history of severe generalized abdominal pain associated with worsening abdominal distension, history of night sweats, and weight loss. A CT scan of the abdomen and pelvis demonstrated a large heterogeneously enhancing neoplastic mass lesion involving the splenic flexure of the colon surrounded by fat stranding with a small contained leak, in addition to multiple metastatic hypodense focal hepatic lesions. Multiple lymph nodes under 1 cm in size were also noted. The patient underwent exploratory laparotomy, subtotal colectomy, ileostomy creation, and washout. The histopathological exam revealed high-grade invasive colonic neuroendocrine carcinoma, which was pT4N2bM1c, while the peritoneal lesion was metastatic carcinoma. The patient was then referred to the multidisciplinary tumor board. CONCLUSIONS Unusual presentation of neuroendocrine tumors is shown to be expected. Since colorectal NECs are rare, highly aggressive diseases and usually discovered very late, individualization of management, as well as additional research, is required.

Perforated mucocele of the appendix in the left upper quadrant: A challenging anatomy and an improvised surgical technique.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a feared complication of appendicular mucocele perforation. Although a rare disease, its major sequel mandates recognition and early intervention. Intestinal malrotation is mostly asymptomatic in adults. Its significance arises when it complicates another coinciding condition by confusing the presentation, leading to delay in diagnosis and treatment. PMP and incidental finding of gut malrotation in adults are two rare events, and the chance of both occurring in the same patient is very slim. This can complicate the clinical picture and lead to devastating outcomes. PRESENTATION OF THE CASE: We present a case of PMP in a patient with gut malrotation, managed with cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). DISCUSSION: Management with CRS/HIPEC has been found to improve outcomes for patients with PMP. However, the extensive disease and abnormal anatomy of the patient in our report proposed unique intraoperative challenges. Preserving part of the colon was possible with an improvised surgical technique that we used which proved to be safe and effective. CONCLUSION: Early recognition and consideration of uncommon but serious surgical conditions are essential for improved patient outcomes. To our knowledge, this is the first report in the English literature that describes the use of CRS/HIPEC for PMP in a case of intestinal malrotation. This improvised surgical technique was found to be safe and can provide a surgical solution for preserving part of the colon in selected patients.

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.