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Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients., (© 2024. The Author(s).)

Background: Data on colorectal cancer (CRC) diagnosis to treatment interval (DTI), an index of quality assurance in high-income countries (HICs) is lacking in South Africa. This study aimed to determine DTIs and their impact on CRC survival in a South African cohort., Methods: Participants ( n = 289) from the Colorectal Cancer in South Africa (CRCSA) cohort were identified for inclusion. The DTI was defined as the duration between the diagnosis and initial definitive treatment and categorised into approximate quartiles (Q1-4). The DTI quartiles were 0-14 days, 15-28 days, 29-70 days, and ≥ 71 days. Overall survival (OS) was illustrated using the Kaplan-Meier method and compared between DTI groups using Cox proportional hazards (PH) regression., Results: There was no significant impact of the DTI (as quartiles) on overall CRC survival. The median length of time between DTI in this cohort was 29 days. Significant associations were identified between the DTI and self-reported ethnicity ( p -value = 0.025), the site of the malignancy (colon vs rectum) ( p -value < 0.0001), multidisciplinary team (MDT) review ( p -value = 0.015) and the initial treatment modality ( p -value < 0.0001)., Conclusion: Prolonged DTIs did not significantly impact survival for those with CRC in the CRCSA cohort. Symptom to diagnosis time should be investigated as a determinant of survival., (Copyright© Authors.)

Background: Lifestyle-related factors have been linked with risk for colorectal cancer. Data describing the relationship between lifestyle factors of South African patients who present with colorectal cancer and their survival is sparse., Objectives: The objectives were to describe the profile of patients with colorectal cancer; to determine the association between lifestyle-related factors and survival, and to compare results of patients in the private and public sectors., Methods: A retrospective review and secondary analysis of information of patients with colorectal cancer were conducted. The independent samples t-test and Mann Whitney U test were administered to determine differences in the clinical presentation. Pearson's Chi-Squared and Eta (η) tests were used to determine the association between survival and lifestyle-related factors., Results: Data of 441 patients were included. When compared to the public sector cohort, patients in the private sector cohort were older (p=0.0110), had earlier stages of cancer at the time of diagnosis (p<0.001), had a higher percentage of current alcohol consumption (p<0.001) and had higher survival rates (p<0.001). Waist circumference was shown to have a large-strength effect on survival (η2=0.266)., Conclusion: Emphasis should be placed on anthropometric screening and education to effect long-term behaviour change. Physiotherapists are well placed to provide screening and non-pharmacological interventions for patients with colorectal cancer., (© 2022 Whelan M et al.)

Introduction: There are significant differences in the phenotype of CRC by race in the U.S. A similar CRC phenotype-race relationship also appears to exist in South Africa (SA). However, there is a paucity of comparative data on the presentation and survival of CRC in sub-Saharan African by country of origin or race. This study compares clinicopathologic variables between CRC patients in Nigeria and SA., Methods: From a prospective CRC database, consecutive patients diagnosed between September, 2013 and October, 2018 from the African Research Group for Oncology in South West Nigeria were compared to consecutive patients diagnosed from January, 2016 to October, 2018 from the Colorectal Cancer in South Africa database. Patients with histologically confirmed adenocarcinoma were included. Patients were excluded if they had in-situ disease or no histological diagnosis. Clinical outcomes were calculated from the date of presentation. National census categories were used to define self-reported race in SA., Results: The mean age at presentation in Nigeria (n = 347) was 54.1 years (SD 15.5) compared to 56.8 (SD 13.7) in SA (n = 534). The median age among Black SA (BSA) patients was significantly lower than the median age among White SA (WSA) patients (55 vs. 63, p < 0.001). Right-sided colon cancer was more common in Nigerian (27.4%) and BSA (21.2%) patients compared to WSA patients (15.2%, p < 0.001). Nigerian (39.1%) and BSA (16.7%) patients were also more likely to present with mucinous histology than WSA patients (4.9%, p < 0.001). There was a significant difference in the stage-at-presentation between the cohorts, with a large burden of stage IV disease in the Nigerian cohort (52.6%). Adjusting for stage-at-presentation, there was a significant difference in the median overall survival between country and racial cohorts., Conclusion: There are significant differences in the phenotype of CRC between Nigeria and SA. Nigerian and BSA patients, appear to share characteristics that are different than those of WSA patients. Larger series with tissue banking and next-generation sequencing are needed to better delineate these observed differences., (© 2021. Société Internationale de Chirurgie.)

The aim of this pilot study was to develop logistic regression (LR) and support vector machine (SVM) models that differentiate low from high risk for prolonged hospital length of stay (LOS) in a South African cohort of 383 colorectal cancer patients who underwent surgical resection with curative intent. Additionally, the impact of 10-fold cross-validation (CV), Monte Carlo CV, and bootstrap internal validation methods on the performance of the two models was evaluated. The median LOS was 9 days, and prolonged LOS was defined as greater than 9 days post-operation. Preoperative factors associated with prolonged LOS were a prior history of hypertension and an Eastern Cooperative Oncology Group score between 2 and 4. Postoperative factors related to prolonged LOS were the need for a stoma as part of the surgical procedure and the development of post-surgical complications. The risk of prolonged LOS was higher in male patients and in any patient with lower preoperative hemoglobin. The highest area under the receiving operating characteristics (AU-ROC) was achieved using LR of 0.823 (CI = 0.798-0.849) and SVM of 0.821 (CI = 0.776-0.825), with each model using the Monte Carlo CV method for internal validation. However, bootstrapping resulted in models with slightly lower variability. We found no significant difference between the models across the three internal validation methods. The LR and SVM algorithms used in this study required incorporating important features for optimal hospital LOS predictions. The factors identified in this study, especially postoperative complications, can be employed as a simple and quick test clinicians may flag a patient at risk of prolonged LOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Achilonu, Fabian, Bebington, Singh, Nimako, Eijkemans and Musenge.)

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer., Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts., Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Background: For patients with colorectal cancer, surgical resection of the primary tumour remains the best treatment option. Surgery for colorectal cancer is being performed on patients who would previously not have been considered as suitable candidates. It remains to be seen which factors influence hospital length of stay (LOS) and the development of acute postoperative complications in South African patients., Objectives: The objectives of our study were to determine the modifiable factors that influence patients' development of postoperative complications and hospital LOS and, to identify the types of postoperative complications that develop., Method: A retrospective review and secondary analysis of information in an existing database of patients with colorectal cancer were conducted. Regression analysis statistics were used to determine the predictors of postoperative outcomes. The level of significance at which testing was performed was set at 5% ( p ≤ 0.05)., Results: Data of 125 patients were included. Surgical site infections and postoperative paralytic ileus were the most frequently reported postoperative complications. Preoperative vigorous-intensity physical activity ( p = 0.048, β = -0.000) and functional performance status ( p = 0.05, β = 0.926) significantly predicted hospital LOS and the incidence of postoperative complications, respectively., Conclusion: Preoperative physical activity and functional performance levels are predictors of acute postoperative outcomes in a private South African cohort of patients with colorectal cancer. Future research which includes other modifiable factors is required to make informed suggestions for changes in clinical practice., Clinical Implications: Patients requiring surgery for colorectal cancer should be screened for signs of physical deconditioning and referred for physiotherapy intervention before elective surgery to optimise their recovery., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this research article., (© 2021. The Authors.)

Background: South Africa (SA) has the highest incidence of colorectal cancer (CRC) in Sub-Saharan Africa (SSA). However, there is limited research on CRC recurrence and survival in SA. CRC recurrence and overall survival are highly variable across studies. Accurate prediction of patients at risk can enhance clinical expectations and decisions within the South African CRC patients population. We explored the feasibility of integrating statistical and machine learning (ML) algorithms to achieve higher predictive performance and interpretability in findings. Methods: We selected and compared six algorithms:- logistic regression (LR), naïve Bayes (NB), C5.0, random forest (RF), support vector machine (SVM) and artificial neural network (ANN). Commonly selected features based on OneR and information gain, within 10-fold cross-validation, were used for model development. The validity and stability of the predictive models were further assessed using simulated datasets. Results: The six algorithms achieved high discriminative accuracies (AUC-ROC). ANN achieved the highest AUC-ROC for recurrence (87.0%) and survival (82.0%), and other models showed comparable performance with ANN. We observed no statistical difference in the performance of the models. Features including radiological stage and patient's age, histology, and race are risk factors of CRC recurrence and patient survival, respectively. Conclusions: Based on other studies and what is known in the field, we have affirmed important predictive factors for recurrence and survival using rigorous procedures. Outcomes of this study can be generalised to CRC patient population elsewhere in SA and other SSA countries with similar patient profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Achilonu, Fabian, Bebington, Singh, Eijkemans and Musenge.)

Introduction: A scarcity of local published data on colorectal cancer (CRC) postoperative complications, including postoperative ileus (POI), exists. POI is a temporary gastrointestinal (GI) state of absent or reduced gastric motility shown to increase patient morbidity, prolong length-of-stay (LOS), and intensify the healthcare resource burden. The pathogenesis of POI involves a neurogenic and inflammatory phase plus a pharmacological component. Aim and Objectives: This study aimed to determine centre-specific preoperative risk factors associated with the development of ileus post elective therapeutic CRC resection. The objectives were to determine whether patient demographics; functional status; comorbidities; GI history; pharmacotherapy (including neoadjuvant chemotherapy); and lastly neoadjuvant radiation and chemoradiation were associated with the development of POI. Method: Patients who underwent CRC resection between January 2016 and May 2019 were retrospectively identified from an existing database. Urgent-or non-therapeutic surgeries; surgeries with the complication anastomotic leak or GI obstruction; patients under 18 at the time of surgery or surgeries preceded by preoperative parenteral nutrition were excluded. A comparison was done of the incidence of exposure in the study cohort to investigated variables as potential risk factors for the complication POI. Results: A total of 155 patient cases were included, and 56 (36%) of them developed POI. Univariate comparison of patients who developed POI with demographic characteristics of patients who did not suggested that women were at lower risk to develop POI compared to men ( p = 0,013; RR 0,56; 95% CI 0,36-0,89). Functional status suggested that all previous smokers were at a higher risk to develop POI compared to lifetime non-smokers ( p = 0,0069; RR 1,78; 95% CI 1,17-2,70). Multivariable comparison of ≤ 5 qualifying parameters showed no significance. Conclusion: The high local incidence of POI in this patient population shows that intervention is required to reduce the POI rate and improve postoperative outcomes. This study suggests that for men and all patients with a history of smoking both, CRC resection preoperative recommendations with the intention to prevent POI should include instructions initiating the activation of preventive strategies like the Enhanced Recovery After Surgery (ERAS) programme. More studies are needed to adequately determine local perioperative risk factors for POI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Watkins, Schellack, Abraham and Bebington.)

Background: Definitive closure of fistula-in-ano poses an ongoing surgical challenge. The OVESCO OTSC ® Proctology Clip (proctology clip) purports to offer improved preservation of the anal sphincter whilst at the same time curing the fistula by closure., Methods: A retrospective record review was conducted for patients who received the proctology clip as part of the management of fistula-in-ano in the Colorectal Unit at Wits Donald Gordon Medical Centre (WDGMC)., Results: There were 19 cases of fistula-in-ano treated with the proctology clip. All were cryptoglandular in origin. The median age was 50 years (IQR 44-56 years) and post-procedure, the median follow-up duration was 145 days (IQR 63-298 days). Overall, 9 procedures were successful (47%). Success rates were higher for simple (66.7%) as opposed to complex (38.5%) fistula-in-ano. For patients who underwent placement of the proctology clip as a primary procedure, the success rate (50%) was slightly better than those who received the clip as a secondary procedure (44.4%)., Conclusion: This preliminary data presents our initial experience using the proctology clip. While these data may serve as a "proof of concept", a multi-centre controlled trial comparing this method to the rectal mucosal advancement flap (RMAF) is needed to determine the role of the proctology clip in the management of fistula-in-ano., (Copyright© Authors.)

Background: The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival., Objectives: To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients., Methods: Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables., Results: There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1 comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis., Conclusions: In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.

Background: Colorectal surgery has developed into an established surgical subspecialty in South Africa, however there is a paucity of data regarding the epidemiology and surgical outcomes of patients with colorectal disease in this country. The objective is to present the findings of a one-year audit of the Wits Donald Gordon Medical Centre (WDGMC) Colorectal Unit with specific reference to indications, surgical procedures and patient outcomes., Method: Patient files from December 2016 to November 2017 were included in a retrospective analysis. The Mann-Whitney U test was used to analyse continuous variables and the Chi-squared test was used to compare categorical variables., Results: During the audit period, 1264 patients were admitted to the Colorectal Unit and a further 564 outpatient endoscopic procedures were performed. There were 306 emergency admissions. 139 elective colorectal resections took place, with a 16% major complication rate, a 12% anastomotic leak rate and no deaths. Rectal resections constituted 66% of the operations and 34% were colonic resections. The median length of stay for all patients undergoing resection was 9 days and there was no statistically significant difference in length of stay between open and laparoscopic cases., Conclusion: The WDGMC Colorectal Unit manages a high volume of patients presenting with the full spectrum of colorectal disease., (Copyright© Authors.)

Background and Aim: Cancer is one of the foremost causes of morbidity and mortality worldwide. Globally, colorectal cancer (CRC) is the third most diagnosed and fourth most important cause of cancer death. A total of 70% of all CRC-related deaths occur in low- and middle-income countries. In Sub-Saharan Africa (SSA), estimating the burden of CRC is difficult. Only 27 of 43 SSA countries have formalized cancer registration systems; data quality is variable and national coverage rare., Methods: This is a multidisciplinary, longitudinal cohort study started in January 2016. Patients >18 years with histologically confirmed primary adenocarcinoma of the colon and rectum, diagnosed within the previous 12 months, are eligible. Participants were assessed and were followed up for 3 years. Baseline information, including demographics, socioeconomic status, family history, medical and surgical non-cancer-related history, dietary history, colonoscopic findings, staging at presentation, treatment, and disease recurrence, is collected, as well as blood tests and histology results. Outcomes include disease recurrence (local and metastatic) and survival., Results and Conclusion: This study aims to describe the clinical presentation, management, and outcomes of adults with CRC in a multiethnic, urban South African population. It will be the first prospective study to describe clinical presentation, demographics, risk factors, treatment, and outcomes according to population group, from both private and state health-care facilities in Johannesburg, South Africa. The results of this study will be relevant not only to South Africa but also to other SSA countries undergoing similar rates of rapid urbanization and epidemiological transition.

Background: Passive faecal incontinence (FI) due to a defect of the internal anal sphincter is a distressing condition and can be difficult to manage medically and surgically. The use of a trans-anally injected bulking agent to improve continence has been published internationally with contradictory results., Method: Patients with passive FI due to confirmed internal anal sphincter deficits that had been treated with PermacolTM injections were followed up. They were asked to complete the Wexner faecal incontinence scores and Rockwood QoL scores for both their pre- and post-treatment continence state., Results: Of the 14 patients who completed the questionnaires, most were women with a mean (SD) age of 56.4 (13.4) years. The majority of the patients had a history of a predisposing event. They reported a significant improvement in both the Wexner scores (p < 0.0005) and the Rockwood QoL (p=0.004), including all subsections. The Wexner scores and the Rockwood scores were significantly correlated post-procedure (r= -0.6186; p=0.0183). There were no significant correlations between change in scores and time after procedure., Conclusion: Trans-anal submucosal PermacolTM injections produced a significant improvement in both faecal continence and quality of life scores in patients with passive faecal incontinence for up to two years.

The precise biochemical nature of malignant transformation remains elusive. This article reviews some of the current theories of oncogenesis and aims to synthesize these concepts into a possible schema for the origins of malignant transformation, using a cell-programmed origin for neoplastic progression. It is proposed that cell transformation in malignancy is initiated by injury but finds ultimate promulgation through cellular, self-determined, epigenetic events. Explanations for this arrangement are sought in evolutionary models and our knowledge of cell biology. The proposed mechanisms have not been experimentally validated, but will hopefully stimulate further research., (Copyright© Authors.)

Purpose: The management of colonic injury has changed in recent years. This study sought to evaluate current surgical management of injuries to the colon in a busy urban trauma centre, in the light of our increasing confidence in primary repair and evolving understanding of the concepts and practice of damage control surgery., Methods: A retrospective analysis was made of consecutive patients presenting with colonic injury from January 1 to December 31 1998. Patients without full-thickness lesions of the colon were excluded, as were patients who died within 24 h of admission. Demographic data, wounding patterns and clinical course were studied., Results: One hundred twenty-seven patients were analyzed. Management without colostomy was achieved in 84% of cases. Patients who underwent diversion of the faecal stream had increased morbidity and hospital stay compared to equivalent patients who were repaired primarily. The important subgroup of patients who underwent damage control or abbreviated laparotomy is discussed., Conclusion: This study further strengthens the validity of direct repair or resection and primary anastomosis for colonic injury. Strategies to deal with the subgroup of patients at very high risk of postoperative complications are suggested.