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Challenges and Opportunities in Colorectal Cancer

Challenges and Opportunities in Colorectal Cancer

Harrison, T. R., Muhamad, J., & Malova, E. (2022)


Objective: This paper provides a review of current knowledge and trends in research on firefighters cancer risks and risk reduction efforts and calls for future research focused on European and international firefighters to understand and reduce occupational cancer risk.

Cancer incidence: Firefighters face increased occupational cancer risk.  Firefighting has been linked with multiple types of cancer, including bladder, colorectal, brain and central nervous system, non-Hodgkin’s lymphoma, skin melanoma, and prostate and testicular cancer, with several others types of cancer being found at increased rates.

Cancer risks: Increased occupational cancer risk is, in part, related to carcinogenic exposures at fire events and improper use and cleaning of personal protective equipment (PPE), with role and years in service increasing risk.

Risk Perception: Research on efforts to reduce cancer risk are growing, and include examination of firefighter knowledge, attitudes, norms, and behaviors toward decontamination, screening, and healthy eating. Many firefighters report high perceived susceptibility and severity of cancer risk, and identify fire scene exposures, contaminated gear, diet, sleep disruption, chemical exposure from cleaning products, and barriers to medical care as contributing to increased risk.

Risk Reduction: Firefighters have strong desire to reduce cancer risk and report generally favorable attitudes toward decontamination practices and proper gear use, but face barriers to reducing those risks, including lack of knowledge, occupational needs, organizational culture, policy, and lack of resources. Behavioral interventions to reduce cancer risk through decontamination efforts and dietary change have demonstrated positive results, however there is a dearth of research on these efforts, especially with European and international firefighters.

Future Directions: Future research should focus on understanding European and international firefighters’ knowledge, attitudes, and behaviors toward cancer risk reduction, the impact of the built environment on cancer risk (station layout, clean cabs), improved efforts at tracking exposures, use of new technology and virtual reality in training to reduce cancer risk, and improved understanding of firefighter cancer risk by medical professionals.

Cawich, S. O., Wharfe, G., Nimrod, M., Muddeen, A., Mike, K., Ramesh, S., Barrow, M., & Barrow, S. (2022)


Objectives: Opportunistic (ad-hoc) screening for colorectal cancer is practiced in Trinidad & Tobago, but there is no data on the outcomes of opportunistic screening.  We carried out this study to determine the proportion of persons with colorectal ancer who were screen-detected. 

 Methods: We retrospectively audited the records of all patients who underwent colectomies for colorectal cancer at a public hospital over a 10-year period from January 1, 2012 to January 30, 2022. We compared American Joint Committee on Cancer stage based on method of diagnosis (screening vs symptomatic). Descriptive statistical analyses were generated using SPSS version 21.0.

Results: We analyzed 340 patients with colorectal cancer at a mean age of 63.3 years (SD +/- 13.4). There were 52 (15.3%) patients who had diagnoses made at screening and 283 (84.7%) had investigations after developing symptoms. Significantly more screen-detected lesions were early-stage colorectal cancer (73.1% vs 25%; P <0.001). Table 1 compares the cancer stage in both patient groups.

Conclusions: Although significantly more patients with colorectal cancer are diagnosed at early stages by screening, the incidence screen-detected disease in Trinidad & Tobago is low. Most patients present with locally advanced (52%) or metastatic (15%) disease, when the opportunity for curative treatment is reduced. The time has come for policy makers to develop and institute a national screening programme for colorectal cancer in Trinidad & Tobago.

Verduin, W. M., Van Den Helder, R., Janssen, T. W. J., & Houdijk, A. P. J. (2023b)


Background: Muscle and fat influence outcome after colorectal cancer surgery. Little data exist on mortality. Muscle mass (MM) relating to lower mortality is mostly studied in dichotomous approaches as sarcopenia or skeletal muscle index (SMI) but rarely as a continuous variable. For fat, compartments as visceral, subcutaneous, or intramuscular have different metabolic impact but on mortality little is known. Sex dictates muscle and fat mass that also may differ between colon and rectal cancer patients.

Objective:  To study associations of muscle and fat parameters as continuous variables with mortality in men and women after colon or rectal cancer resection.

Design: Retrospective multicenter cohort study

Setting: This study used data of the Dutch Surgical Colorectal Audit from 2011 through 2014 from 8 Dutch teaching hospitals. Body composition was assessed on pre-operative CT scans.

Patients: 2597 colon and 931 rectal cancer patients

Main outcome measures:  Associations of muscle and fat measures with 5- year MR in male and female colon and rectal cancer patients.

Results: Negative associations of MM and SMI and positive associations of muscle fat (MF) and sarcopenia with mortality were found only in male patients.  The effect of MM and sarcopenia was found in both colon and rectal patients whereas SMI had no effect in rectal patients.  Muscle fat associated with higher mortality only in male colon patients.  The only effect of visceral fat was seen in male rectal cancer patients associating with lower mortality.  

Limitations: The retrospective nature of the study

Conclusion:  The male predominance and differences between colon and rectal cancer patients for associations of muscle and fat parameters with colorectal cancer mortality stress the importance of separating males from females and colon from rectal cancer patients in the analysis of body composition effects on mortality.

Garalla, H. M., & El-Sayed, A. M. A. (2023)


Background: Colorectal carcinoma (CRC) is the most common and one of the main causes of mortality and morbidity globally among gastrointestinal tract tumors. A benign polyp is the first step in the multistage pathogenesis of colorectal cancer, which eventually progresses to an adenoma and a carcinoma. Wnt/ βeta-catenin signaling pathway plays an initiating and rate-limiting role in colorectal tumorigenesis.

Aim of the work: To evaluate the association between the immunohistochemistry (expression of E-cadherin, and β-catenin with the histopathological grade, and stage of colorectal cancer.

Materials and Methods: The study was retrospectively collected from the archives of the Department of Pathology in Tobruk Medical Center. Eighty-two histopathologically confirmed cases of adenomas (n = 48) (tubular, villous, and tubulovillous), and colorectal adenocarcinoma (Mucinous, and Non-mucinous) (n = 34) were included in this study over two years (2021-2023). The histopathological diagnosis, grade, and staging of the tumors were obtained. While clinical information was obtained from medical records and pathology reports. immunohistochemical staining was performed for all the cases using E-cadherin and β-catenin antibodies, and the results were analyzed.

Results: A total of 82 patients were studied out of these, 51(62.2%) patients were male, whereas 31 (37.8%) were females with a male: female ratio of 1.6:1. Age ranged from 30 years to 80 years. The mean age was the mean age of 52.9 (SD±15.8). A high prevalence of adenoma cases was observed in the age group 30– 40 years. The peak incidence for both types of colorectal carcinoma was in 61-70 years. By scoring the intensity of β-catenin there are significant correlation of β-catenin expression with tumor grade, stage, lymph node metastasis, and types of adenomas. The intensity of staining of E-cadherin in 48 cases of adenomas was showing high expression in 39 cases (81.3%), and low expression in only 9 cases (18.7%). While, the majority of the patients with CRC (58.8%) had low expression of E-cadherin levels, and (41.2%) had high expression.

Conclusion: Our findings imply that E-cadherin and β-catenin may contribute to the invasion and progression of colorectal cancer, which may serve as prognostic indicators for colorectal carcinoma

Griffith, S., Cawich, S. O., Doyle, A., Chase, C., Hefeji, F., Whitehead, R., Ramkissoon, S., & Padmore, G. (2022)


Background: Fast track protocols (FTPs) have triggered considerable improvements in patients’ perioperative care and are accepted as the standardised approach to patient management in developed countries globally. Although the benefits of FTPs have been illustrated for some time, they are not universally used in developing countries. In the Eastern Caribbean, FTPs are implemented in an ad-hoc manner based on the attending surgeons.

Methods: We designed a comprehensive FTP modified for use in Barbados, an island nation in the Eastern Caribbean. After consensus, the FTPs were introduced into clinical practice at a tertiary referral public hospital. We prospectively evaluated clinical outcomes after introduction of FTP protocols for all patients undergoing colorectal operations from January 1, 2018 to February 1, 2019. The study population was divided into three groups: Group I: full adherence (>16 FTP steps completed), Group II: partial adherence (10-15 FTP steps completed), Group III: non-adherence to FTP protocols (<9 FTP steps observed). In each group, we compared morbidity, mortality, return of bowel function, length of post-operative hospital stay and hospital readmission using SPSS version 20 for statistical analyses. 

Results: Over the study period, there were 27 colorectal operations performed. When the outcomes in group 1 and group 3 were compared, there was a statistically significant reduction in post-operative LOS (3 Vs 8.9 days; P<0.05) and overall morbidity (10% vs 50%; P 0.05) in the full FTP adherence groups.

Conclusions: In this Caribbean healthcare system, FTP implementation resulted in significant improvements in post-operative duration of hospitalization and overall morbidity. The main challenge is to achieve universal buy-in from health care providers in the Caribbean. We believe that the way to achieve this is continued medical education and targeted research to acquire local practice data from the Caribbean. We advocate the incorporation of FTP into colorectal surgical practice for Caribbean hospitals.   

Alanee, S. (2023)


Purpose: To compare C-C chemokine receptor type 5 (CCR5) expression in urothelial carcinoma tissue to other common malignancies using a specific CCR5 inhibitor-based assay.

Methods: We used an immunohistochemistry (IHC) assay to compare the expression of  CCR5 in urothelial carcinoma to different types of common cancer. The IHC assay was based on labeled PRO140 (PRO140 CCR5 Hu IgG4a), a CCR5 inhibitor with potential therapeutic uses. The expression levels were compared using Percent Scores and H-Score methods. 

Results: Quantification of CCR5 expression utilized a panel of 63 evaluable samples from 9 cancer indications as follows: 6 UC, 7 non-small cell lung (NSCL) adenocarcinoma, 9 NSCL squamous cell carcinoma, 5 triple negative breast cancer, 5 breast cancer, 7 pancreatic cancer, 9 colorectal cancer, 7 head, and neck cancer, and 8 sarcoma. Overall, most of the 63 cases evaluated tended to have either H-Scores >175 (highly reactive) (24/63) or <100 (low or non-reactive) (32/63). Urothelial cancer had the highest expression (H score=183.3), while sarcoma exhibited the most moderate expression of CCR5 (H score =23.6).

Conclusions: We show, for the first time, a high expression of CCR5 in the tissue of urothelial carcinoma using an assay based on a safe and effective receptor inhibitor. Our findings may have therapeutic implications if validated in more extensive studies.

The New Frontier of Low-Cost Neoadjuvant Therapy

Guirgis, H. M. (2023)


Background: We previously reported that the 2-year costs of the immune check inhibitors (ICI) were equitable with outcomes. Extended use multiplied costs. Nivolumab neoadjuvant plus chemotherapy improved event-free survival in early resectable lung cancer at low cost. Neoadjuvant is a novel advance in earlier cancer treatment. The targeted therapy Osimertinib is currently utilized as neoadjuvant, adjuvant and in advanced/metastatic lung cancer with cost increasing yearly with further use. We aimed to quantify the cost and savings of ICI and targeted therapy in earlier vs advanced cancer stages in multiple solid tumors.

Methods: Annual 2019-2020 costs of Osimertinib were calculated ad monthly optimal dose x 12. Costs of ICI were calculated as dose x mg/m2 or per 80 kg x price x number of cycles per year.

Results: The 2-year Osimertinib cost in metastatic disease was $496,744, adjuvant 1-year $248,372 and neoadjuvant $31,046. Estimated neoadjuvant cost savings over 1-year were $217,326.

Pembrolizumab $134,796 annual cost was the median of 5- evaluated ICI. It is used as adjuvant at half the 2-year cost. Extended therapy by 6-12 months, beyond the 2-year approval, added an extra $67,398-$134,796.

Durvalumab following chemo-radiation, (Pacific) was approved in unresectable stage III NSCLC x 1-year at $148,007, saving a 2nd year-cost. Adjuvant Atezolizumab 1-year cost in 1st-line was $124,761. Approval was based on improving the disease-free survival using 4 cycles + chemo in resected stage II-IIIA lung (Impower010), Cost was $35,644 cost with $89,117 savings.

In the neoadjuvant space, Nivolumab + chemotherapy improved event-free survival in resectable lung cancer (Forde, 2022) at $31,425, saving $137,423. In early-stage triple negative breast cancer (GeparoNuevo-NCTO2685059), 8-cycle Durvalumab prolonged survival at $45,464. Cemiplimab x 4-cycle in stage II to IV, cutaneous squamous-cell carcinoma resulted in complete pathological response (Gross, 2022) at $35,652 vs 1-year $125,108. In early colorectal cancer (NICHE-2), 2-cycle Nivolumab plus 1- low-dose Ipilimumab followed by surgery resulted in major pathological response at $24,927.

Conclusions: Neoadjuvant Osimertinib and ICI cost a small fraction resulting in significant savings in early-stage lung cancer treatment. Cost advantages in other solid tumors warrant further confirmation.

Kanagaraj C., Mohanapriya B, Aravindh S, Sathyapriya A, and Suresh S N (2023)


Colorectal cancer is the third leading affected in men after lung and prostate cancer tumours and in women after lung and breast cancers. Current food habitation as potential risk factors for the growth of colorectal cancer include lack of physical activity, alcohol consumption, smoking, a low fiber and high fat nutrition, obesity and inadequate fruit and vegetable usage. Eclipta prostrata (L). is commonly found on roadsides and waste lands. It is annual herbaceous plant have a long history of traditional values; medicines use which is various part of the world especially in tropical, subtropical regional widely. This herbs already found the curative properties and has been utilized as analgesic, antibacterial, antihepatotoxic, antihaemorrhagic, antihyperglycemic, antioxidant, immunomodulatory properties and it is considered as a good rejuvenator too. Present study to find the in vitro cytotoxic effect of methanolic extract against the Human Colorectal Adenocarcinoma cells. Cancer cells were treated with different concentration of extract and incubated for 24hours and the cytotoxic effect was observed in microscopy and cell viability was determined by 2,5-diphenyl-2H-tetrazolium bromide assay shows half maximal inhibitory concentration shows 62.44 µg/ml. The nuclear 4’6-diamidino-2-phenylindole staining was performed and confirm the existence of apoptosis morphological changes of the cells were studied. Besides, this study to continue the identification of specific metabolites from methanolic extract of Eclipta prostrata (L.) recommended for the discovery of potential anti-proliferative and anticancer compounds.

Bagus, B. I. (2023)


Starting in 2020 and continuing for 2 years thereafter, the COVID-19 pandemic has greatly affected routine clinical practice, particularly in treating patients with gastrointestinal cancer. Delay, postponement or refusal to continue multimodal treatment have increased the number of emergency cases, and consequently patient morbidity and mortality.

Many recommendations have been announced to guide the adaptation of clinical practice during and after the COVID-19 pandemic. Although early diagnosis and screening should proceed as usual before the pandemic, adjuvant treatment for patients with gastrointestinal cancer should be evaluated in the future. For example, during the pandemic, most recommendations state that adjuvant treatment for patients with colorectal cancer is still required, and many adaptations have been suggested according to local conditions.

In some instances, 6 months of adjuvant chemotherapy has been modified to an optional 3 month duration. A common challenge is that most patients remain unsure about the decreased chemotherapy duration, although many guidelines recommend this modified treatment strategy. Short term follow up has already indicated promising clinical outcomes of this modified adjuvant duration, but the long-term outcomes remain to be evaluated.

Bowen, D. J., Dusic, E., & Makhnoon, S. (2022)


Cascade genetic testing, a highly effective method of identifying high penetrance cancer risk mutations in the family, is a promising method of prevention. Cascade testing is defined as directed genetic testing of at-risk relatives of individuals known to have actionable mutations However, it is tremendously underutilized in clinical practice, and the reasons are complex and diverse. We discuss these reasons and consider areas of research for key findings, strengths and weaknesses. We offer testable solutions for increasing interest and use of cascade testing opportunities in families and in clinical practice using colorectal cancer as an example. This area of clinical research has great potential to save lives by improving cancer prevention and early detection in families at high genetic risk, and should be actively pursued with resources and ideas. 

Michel, A., & Pumpalova, Y. S. (2023)


Background: Colorectal cancer (CRC) is the 3rd most common cancer worldwide, and a major contributor to cancer-related mortality. In contrast to declining CRC incidence and mortality rates across high-income countries, the CRC burden is increasing in low- and middle-income countries. Although CRC screening has been shown to be a cost-effective intervention that decreases CRC incidence and mortality, screening programs remain an unmet need in most low- and middle-income countries. This article reviews evidence on existing CRC screening efforts in middle income countries, where the majority of new CRC cases and deaths are projected to occur over the next decade.

Aims: The aim of this study was to identify and describe opportunistic and organized CRC screening programs in middle income countries and to identify barriers and facilitators of such programs.

Methods: We identified countries defined as middle income countries by the World Bank and conducted a scoping literature review using PubMed, Google Scholar, and ScienceDirect. For each country, we identified whether CRC screening guidelines or programs exist on the national, regional, or local levels, and summarized data on screening methods and uptake, when this information was available. We also summarized published literature describing barriers and facilitators to CRC screening in middle income countries.

Results: Of the 108 countries defined as middle income countries by the World Bank, we identified CRC screening programs in six lower-middle income countries and 23 upper-middle income countries. Most countries have opportunistic CRC screening guidelines/programs. Countries with organized CRC screening programs had higher screening uptake rates, although very few have achieved CRC screening coverage rates of >50% of the eligible population. Most programs were initiated less than 10 years ago, limiting ability to evaluate effect on CRC incidence and mortality. Several barriers to CRC screening were identified, including lack of physician buy in, participant knowledge and resources, and participant fear of screening.

Conclusions: While there has been growth of CRC screening programs in the last decade with the initiation of both opportunistic and organized screening programs in middle income countries, there remain significant barriers to the uptake and implementation of such programs.

Alfred, J., Clifford, R., Dixon, S., & Kalaiselvan, R. (2023)


Introduction: There are over 42,000 new cases of colorectal cancer diagnosed every year in the UK alone, a third of those being rectal in origin. Although there has been significant progress in the treatment of rectal cancer, overall, 5-year survival can still be as low as 17% for those with advanced disease. We aimed to assess the impact on of overall survival and quality of life of primary tumour resection in the palliative setting.

Method: A literature search was performed using Pubmed and Cochrane databases in March 2022. Bias was assessed using the Joanna Briggs institute checklist.

Results: Seven papers were included in the review; all retrospective cohort. A total of 809 patients underwent rectal resection in the presence of metastatic disease +/- adjuvant therapy. The median age was 61years, 59.7% male. 68.6% of patients presented with liver metastasis at the time of diagnosis. The most commonly reported symptoms preoperatively were bleeding and tenesmus. 4-50% of patients in each cohort underwent neoadjuvant therapy. Highest 30-day mortality reported was 7.3%. Both studies comparing resection v none demonstrated a higher overall survival for those undergoing surgery, with one showing 1year overall

survival 65v20%. Quality of life was not addressed across the literature.

Conclusion: Although there is some evidence to show a favourable overall survival for patients undergoing primary tumour resection in the palliative setting, this data is mainly old and across a heterogeneous population. A larger scale prospective study would be required to assess its potential role and impact upon quality of life. 

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