Referral Process Enhancement: Innovative Approaches and Best Practices.

OBJECTIVE: This study aimed to enhance the efficiency of the referral system at the Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) in Muscat, Oman by reducing the average time for new patients' acceptance and the delay between patient acceptance and their first appointment. METHODS: A one-group pretest-posttest quasi-experimental project was conducted from Quarter 2 of 2022 to Quarter 2 of 2023. Data collected during the pretest and posttest phases were compared to evaluate the impact of interventions on the average days for patient acceptance and the time to first appointment after acceptance. The intervention involved developing a comprehensive referral system incorporating technology development, improved accessibility, orientation materials, internal training, policy formulation, criteria definition, and tailoring acceptance criteria to specialty programs. Awareness campaigns were also conducted to educate patients about the referral process and available transportation options. The project followed the FOCUS PDCA (Find, Organize, Clarify, Understand, Select, Plan, Do, Check, Act) approach for implementation. RESULT: Significant improvements were observed in the oncology referral process, with the average days for patient acceptance decreasing from 4.3 days to 1.3 days post-implementation. Statistical analysis confirmed the significance of this change (F-value = 46.25, p < .0001). Similarly, the average days to first visit appointment after acceptance decreased from 8.6 days to 4.0 days, with statistical support (F-value = 6.29, p < .0). CONCLUSION: This study represents a significant advancement in optimizing the oncology referral process. When considered in conjunction with previous research findings, it underscores the importance of ongoing efforts to enhance efficiency in patient referrals.

Analyzing Cancer Incidence Trends in Oman From 1996 to 2019: A Comprehensive Study of the National Cancer Annual Reports.

PURPOSE: Previous studies have reported that cancer incidence trends in Oman varied by tumor site and sex. No comprehensive analysis of all cancer sites had been reported. The objective of this study is to analyze cancer incidence trends in Oman and calculate the annual percent change (APC) in age-standardized rates (ASRs) for all-cancer and 61 individual cancer sites in Omani men and women from 1996 to 2019. METHODS: We gathered incidence data from The Omani National Cancer Registry for all cancers combined and individual tumor sites. We estimated the APC using Poisson regression. RESULTS: The cancer ASR in the Omani population increased by 23% (from 95/100,000 in 1996 to 117.2/100,000 in 2019), with the increase being more pronounced in females (48% v 7% in males). Among the male population, there was significant increase in the ASRs of colon, rectum, thyroid, and prostate cancers, with APCs of 6.92%, 4.24%, 4.19%, and 2.03%, respectively. Among females, all-cancer incidence showed significant increase (APC = 1.39%), and increasing trends were observed in uterine, colon, rectum, thyroid, and breast cancers (APCs = 7.57%, 7.08%, 5.19%, 5.16%, and 4.19%, respectively). CONCLUSION: The ASR of all-cancer increased significantly in Omani women but not in men. Uterine cancer had the highest APC. Colorectal cancer and thyroid ASR increased in both males and females. Breast and prostate cancers showed increasing trends. Further research is needed to explore factors contributing to increasing cancer incidences.

Predictors of Hypersensitivity Reactions to Platinum-Based Chemotherapy in a Tertiary Care Hospital in Oman: A case control study.

Objectives: This study aimed to estimate the prevalence and evaluate risk factors of hypersensitivity reactions (HSRs) to platinum-based compounds (PBCs) in cancer patients. PBCs play an important role in cancer therapy. However, one of the drawbacks of PBCs is the occasional occurrence of HSRs, which can lead to serious consequences. Methods: This retrospective case control study was conducted from January 2013 to December 2020 at Sultan Qaboos University Hospital, Muscat, Oman and included patients who received any PBC for the management of non-haematological cancers. Data regarding demographic characteristics and diseases and treatment details were collected from the hospital's electronic database. The data were quantitatively described and Student's t-test and Wilcoxon Mann-Whitney tests were used to detect significant differences. Results: A total of 38 cases and 148 matched controls were studied. The prevalence of HSRs to PBCs in the cohort of this study was 4.7% (95% confidence interval: 3.33-6.37%), higher with carboplatin compared with cisplatin and oxaliplatin. The female gender (P = 0.032), concomitant taxanes (P = 0.002) and concurrent radiation (P <0.001) were significant predictors of HSRs to PBCs. The majority of the reactions were of mild to moderate severity, and the rechallenge rate after HSR development was 13%. Conclusion: HSRs to PBCs impact therapy decisions and understanding the risk factors is important to improve treatment outcomes in cancer patients.

Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis.

BACKGROUND: Chromatin immunoprecipitation (ChIP) analysis revealed that the FBXW7 gene and the long non-coding RNA (LINC01588) are potential candidates in epithelial ovarian cancer (EOC) pathogenesis. However, their exact role in EOC is not yet known. Thus, the present study sheds light on the impact of the mutations/ methylation status of the FBXW7 gene. MATERIALS AND METHODS: We used public databases to assess the correlation between mutations/ methylation status and the FBXW7 expression. Furthermore, we performed Pearson's correlation analysis between the FBXW7 gene and LINC01588. We performed gene panel exome sequencing and Methylation-specific PCR (MSP) in HOSE 6-3, MCAS, OVSAHO, and eight EOC patients' samples to validate the bioinformatics results. RESULTS: The FBXW7 gene was less expressed in EOC, particularly in stages III and IV, compared to healthy tissues. Furthermore, bioinformatics analysis, gene panel exome sequencing, and MSP revealed that the FBXW7 gene is neither mutated nor methylated in EOC cell lines and tissues, suggesting alternative mechanisms for FBXW7 gene regulation. Interestingly, Pearson's correlation analysis showed an inverse, significant correlation between the FBXW7 gene and LINC01588  expression, suggesting a potential regulatory role of LINC01588. CONCLUSION: Neither mutations nor methylation is the causative mechanism for the FBXW7 downregulation in EOC, suggesting alternative means involving the lncRNA LINC01588.

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient.

Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.

Patients' knowledge and awareness of safe handling of oral anticancer agents at Sultan Qaboos University Hospital in Oman.

BACKGROUND: Safe handling of oral anticancer agents is of great concern. There is a lack of clear, national guidelines on how patients can safely handle and dispose of unwanted medications. We aimed to evaluate the safe handling, storage, and disposal of oral anticancer drugs among cancer patients and caregivers at home. METHOD: This cross-sectional survey of adult cancer patients (or their adult caregivers) used a closed-ended questionnaire from May 2019 to March 2020. RESULTS: A total of 257 patients (50 ± 15 years; range: 18-93 years) were enrolled; however, only 91% (233/257) reported self-administering oral anticancer medications. Caregivers were more likely to administer oral anticancer agents for patients ≥60 years than those <40 years old (63% vs. 8%; P = 0.001). Most patients (52%; 133/257) did not wash their hands after administering the drug; 74% (164/222) of the respondents reported that their medications were kept in a bedroom cabinet, while 18% (40/222) stored their medications in a refrigerator, and 5% (12/222) in a kitchen cabinet. A total of 55% (68/124) of patients returned their excess oral chemotherapy medications to the hospitals; however, 36% (45/124) disposed of their unused oral chemotherapy drugs in a household garbage container. CONCLUSION: While two-thirds of patients stored their oral anticancer medications properly, more than half used inappropriate handling procedures. Disposal practices were inconsistent and did not adhere to the reported international guidelines.

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient

ABSTRACT Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.

Health-Related Quality of Life, Functioning, and Physical Symptoms of Adult Omani Colorectal Cancer Survivors.

BACKGROUND: Colorectal (CRC) survivors often experience physical and psychological symptoms affecting their health-related quality of life (HRQoL). This study aimed to identify factors impacting HRQoL-related functioning and physical symptoms among adult Omani CRC survivors. METHODS: A cross-sectional study of 124 adult CRC survivors was conducted at the two main oncology referral hospitals in Oman. A validated Arabic version of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire 30 was used to collect data. RESULTS: A total of 118 CRC survivors participated in the study (response rate: 95.2%). The mean age was 52 years and there were an equal number of male and female participants (n = 59 each; 50.0%). A total of 62 survivors (52.5%) had been diagnosed with CRC at stages III or IV. The overall score for global health was high (81.7). With regards to functioning, high mean scores were observed for domains of role (91.0) and social (90.7) functioning. In terms of symptoms, high mean scores were reported for constipation (25.4), insomnia (25.1), pain (20.1), and fatigue (18.9). Survivors under 60 years old (ß=15.5, p=.004) and those with no comorbidities (ß=16.0, p=.001) demonstrated better functional HRQoL. Being male was predictive of better functional HRQoL in the emotional (ß=13.9, p<0.008), cognitive functioning (ß=12.5, p=.013), role functioning (ß=14.0, p=0.006) and physical functioning (ß=17.8, p<0.001) domains. CONCLUSIONS: Healthcare professionals in Oman should implement measures to enhance the HRQoL of CRC survivors, particularly women and those with coexisting morbidities.

Pulmonary toxicities of immune check point inhibitors in the management of cancer: mini review.

Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune response might lead to mild to severe immune-related adverse events (irAEs). Pulmonary toxicity, though often referred to as Immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis), covers a broad and overlapping spectrum of pulmonary manifestations and has been described in < 10% of patients receiving ICI either alone or in combination. However, the actual numbers in real-world populations are high, and are likely to increase as the therapeutic indications for ICIs continue to expand to include other malignancies. Drug withdrawal is the mainstay of treatment for ICI-pneumonitis. However, a good number of patients with higher grades of toxicity may need corticosteroids. Patients with refractory disease need additional immunosuppressive agents. In this brief review, we succinctly discuss the incidence, risk factors, mechanisms, clinical and radiologic manifestations, diagnosis and summarize the current management strategies of ICI-pneumonitis.

SOCS3 gene silencing does not occur through methylation and mutations in gastric cancer.

Gastric cancer (GC) is ranked the third leading cause of cancer-related deaths worldwide. Mutations and epigenetic alterations in several essential genes, including p53, KRAS, PIK3CA, FAT4 and ARID1A, are often reported. Furthermore, loss of SOCS3 expression was reported in GC, suggesting its tumor suppressor role. To assess the mutational and methylation status of SOCS3, we performed gene panel exome sequencing on 47 human GC samples. The SOCS3 gene was rarely mutated, suggesting alternative regulation mechanisms, such as promoter hypermethylation and/or long non-coding RNAs (lncRNAs). We first explored SOCS3 promoter methylation status in 44 human GC samples by methylation-specific PCR (MS-PCR). Thirteen out of forty-four patients (29.5%) displayed a methylation pattern. Then, to see whether SOCS3 expression is silenced by CpG methylation, we examined publicly available databases (cbioportal and The Cancer Genome Atlas (TCGA)). The analysis revealed ß values lower than 0.1, indicating hypo-methylation in healthy and GC samples. Moreover, moderate methylation (ß < 0.4) and high methylation (ß > 0.4) did not affect the free survival, suggesting that methylation is unlikely to be the mechanism ruling SOCS3 silencing in GC. Next, to assess the regulatory effects of lncRNAs on SOCS3, we silenced the AC125807.2-lncRNA and quantified the SOCS3 gene expression in AGS and NCI-N87 gastric cancer cell line. SOCS3 was found to be downregulated following AC125807.2-lncRNA silencing in AGS cells, suggesting the potential implication of lncRNA AC125807.2 in SOCS3 regulation. However, in NCI-N87 cells, there was no significant change in SOCS3 expression. In conclusion, neither mutations nor hypermethylation was associated with the SOCS3 downregulation in GC, and alternative mechanisms, including non-coding RNAs-mediated gene silencing, may be proposed.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT. METHODS: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes. RESULTS: A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively). CONCLUSIONS: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Beliefs and Perceptions About Cancer Diagnosis and Treatment-Seeking and Decision-Making Behaviors Among Omani Patients with Cancer: A Single-Center Study.

A cancer diagnosis is associated with anxiety and psychological distress. Cultural and societal factors greatly affect the complex process of coping mechanisms and decision making. Omani patients receiving cancer treatment at Sultan Qaboos University Hospital in Oman were interviewed about their perceptions regarding cancer, treatment, outcome, and decision making. Out of a total of 360 approached, 216 patients consented. The median age was 42 years. The results showed that 60.6% of patients considered cancer diagnosis as a test from God, 13.9% considered it as a result of an evil eye, 40% believed prayers treat cancer. Fifty-six percent of participants wanted to make treatment decisions themselves, while 2.3% preferred their family to make decisions. Our findings suggest that perceptions about cancer in Oman are specific and are associated with religion and sociocultural background.

Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.

OBJECTIVES: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. METHODS: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. RESULTS: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. CONCLUSION: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.

E2F5 Promotes the Malignancy of Ovarian Cancer Via the Regulation of Hippo and Wnt Pathways.

Background: E2F5 is a transcription factor that is overexpressed in the early stages of ovarian cancer and has been suggested as a potential biomarker for early detection. In this study, we aimed to examine the role of E2F5 in invasion and proliferation of ovarian cancer cells. Materials and Methods: We performed cell viability, colony formation, and invasion assays using ovarian cancer cells treated with siRNA to knock down the E2F5 gene. The regulatory effects of E2F5 on proteins involved in the apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by western blotting following E2F5 repression. In addition, we analyzed data available on Gene Expression Profiling Interactive Analysis for correlations between E2F5 and YAP, ß-catenin, cyclin D1, cdk4, and caspase-9. Results: E2F5 was highly expressed in ovarian cancer cell lines and samples when compared to the nonmalignant tissues. Downregulation of E2F5 inhibited cell viability and invasion and promoted the phosphorylation of YAP, GSK-3-ß, ß-catenin, and retinoblastoma. However, cyclin D1, cdk4, and caspase-9 were downregulated when compared to control. Conclusion: Overall, E2F5 promotes ovarian carcinogenesis via the regulation of Hippo and Wnt pathways.

Complications and Management of Totally Implantable Central Venous Access Ports in Cancer Patients at a University Hospital in Oman.

OBJECTIVES: Totally implantable central venous access ports (port-a-caths) are increasingly used for the safe administration of chemotherapy; however, their use is associated with complications. This study reviews patterns of complications, reasons for premature removal and the duration of the use of port-a-caths in patients receiving cancer treatment at Sultan Qaboos University Hospital (SQUH) and compares the infection rate with the literature and the researchers' experiences. METHODS: This retrospective follow-up study included patients who had received cancer treatment through a port-a-cath and were admitted to SQUH between January 2007 and April 2019. Demographic features, underlying diagnosis, clinical stage, treatment, duration of use and the cause of premature removal of the port-a-cath were recorded. RESULTS: A total of 516 port-a-caths were inserted in 482 cancer patients. The majority of devices were implanted by interventional radiologists (n = 459; 89.0%) and the right internal jugular vein was most frequently accessed (n = 396; 76.7%). The mean indwelling time of a port-a-cath was 288 days (range: 3-1,872 days) for patients with complications and 550 days (range: 7-3,123 days) for patients without complications. Port-a-cath-related infection was the main complication (n = 63; 12.2%). Patient age, gender, treatment intent, underlying diagnosis, clinical stage, chemotherapy regimen, number of treatment courses, operator implanting the port, the type of micro-organism isolated from the port-a-cath and body mass index were significant factors affecting catheter indwelling time (P <0.05). On multivariate analysis, however, none of the factors was found to be significant. CONCLUSION: Infection was the most common complication necessitating port-a-cath removal. The infection rate was much lower than the researchers' previous experience and compares favorably with several published reports.

Symptom Perceptions and Help-Seeking Behaviours of Omani Patients Diagnosed with Late-Stage Colorectal Cancer: A Qualitative Study.

OBJECTIVE: Colorectal cancer (CRC) is the fourth leading cause of mortality in Oman, with most patients diagnosed at advanced stages. Early diagnosis of CRC improves prognosis and survival rate. The aim of this study was to explore the symptom perceptions and help-seeking behaviours (HSBs) of Omani patients diagnosed with late-stage CRC. METHODS: Semi-structured individual interviews were conducted with 16 patients. RESULTS: Four main themes emerged, including normalisation and ignorance (patients felt healthy, perceived symptoms as not being serious and related to dietary habits, concealed them or prioritised work and family commitments), self-empowerment and self-management (patients were stubborn, employed 'wait and see' approach, used symptomatic or herbal treatments), disclosure and seeking help (patients disclosed symptoms to family members or friends, sought medical help only when symptoms worsened, visited faith healers or travelled abroad for treatment) and healthcare professionals (patients attributed treatment or diagnosis delays to lack of continuity of care, loss of trust in doctors or delays in referral). CONCLUSION: Patients attributed delays in CRC diagnosis to several factors based on their perceptions of symptoms. Most HSBs driven by sociocultural and emotional causes. Increased awareness of CRC symptoms and modifying HSBs can encourage early diagnosis. Prompting patients to disclose CRC-related symptoms may aid referral decisions.

Rarest of the Rare Metastatic Tubulocystic Carcinoma of Kidney.

Tubulocystic carcinoma of the kidney is a rare neoplasm with <100 case reports. Patients are usually asymptomatic and have a relatively indolent disease course occurring predominantly in males. These tumors rarely metastasize. It was previously considered to have some similarities to various other renal cancers, although this tumor has distinct macroscopic, microscopic, and immunohistochemical features. It is now a well-established entity in renal neoplastic pathology. Herein we present a case of metastatic tubulocystic carcinoma presenting with bony metastasis.