Colorectal cancer (CRC) is more prevalent in south-central Asian countries, particularly the Afghan population. Screening for CRC in the Afghan population has always been challenging, primarily due to the tribal and social cultures, lack of facilities, and lack of education. The United States (US) will soon face a significantly massive influx of Afghan refugees. It becomes imperative to initiate and implement effective measures regarding CRC screening in these refugee populations. The current review article aims to identify the most likely challenges faced for CRC screening in this Afghan refugee population in the US and address the possible measures to overcome these challenges.

/pdf/colorectal-cancer-screening-challenges-in-the-recent-afghan-2zu747e6.pdf

Colorectal Cancer Screening Challenges in the Recent Afghan Refugee Population: A Comprehensive Review Article

Many solid tumors present with perineural invasion (PNI), and innervation correlates with worsened prognosis. The effects that commonly administered therapies such as radiation therapy (RT) have on PNI status remain unknown. We investigated the contribution of RT on the nervous system and elucidated the implications that increased nerve signaling can have on tumor burden using our previously developed orthotopic murine model of rectal cancer (RC) and our targeted and clinically relevant short-course RT (SCRT) regimen.Medical charts for patients with RC treated at the Wilmot Cancer Institute were obtained and PNI status was analyzed. Human data were accompanied by an orthotopic murine model of RC. Briefly, luciferase-expressing murine colon-38 (MC38-luc) tumor cells were injected orthotopically into the rectal wall of C57BL6 mice. Targeted SCRT (5 gray (Gy) per fraction for 5 consecutive fractions) was administered to the tumor. Intratumoral innervation was determined by immunohistochemistry (IHC), local norepinephrine (NE) concentration was quantified by enzyme-linked immunosorbent assay (ELISA), and β2-adrenergic receptor (B2AR) expression was assessed by flow cytometry. Chronic NE signaling was mirrored by daily isoproterenol treatment, and the effect on tumor burden was determined by overall survival, presence of metastatic lesions, and tumor size. Isoproterenol signaling was inhibited by administration of propranolol.Human RC patients with PNI have decreased overall survival compared with patients without PNI. In our mouse model, SCRT induced the expression of genes involved in neurogenesis, increased local NE secretion, and upregulated B2AR expression. Treating mice with isoproterenol resulted in decreased overall survival, increased rate of metastasis, and reduced SCRT efficacy. Interestingly, the isoproterenol-induced decrease in SCRT efficacy could be abrogated by blocking the BAR through the use of propranolol, suggesting a direct role of BAR stimulation on impairing SCRT responses.Our results indicate that while SCRT is a valuable treatment, it is accompanied by adverse effects on the nervous system that may impede the efficacy of therapy and promote tumor burden. Therefore, we could speculate that therapies aimed at targeting this signaling cascade or impairing nerve growth in combination with SCRT may prove beneficial in future cancer treatment. 

Radiotherapy exacerbates tumor-promoting innervation and nerve signaling in rectal cancer.

Simple Summary The bodily response to cancer treatment is difficult to track in real time. This study aimed to demonstrate the possible application of magnetic resonance imaging (MRI) as a non-invasive and non-radiative modality to evaluate cancer response to therapy. We injected a fluorinated contrast agent in mouse models of breast and colon cancer to tag and track macrophages in real time. Longitudinal tracking of macrophages in tumors following radiation therapy via MRI provided a means of analyzing the tumor microenvironment without the need for a biopsy. It was shown that tumor-associated macrophage recruitment can be quantified through magnetic resonance imaging. Moreover, the findings suggest that macrophage response to radiation therapy is dependent on several factors including tumor origin. Since tumor recurrence following therapy is a major barrier following treatment, this imaging technique will be extremely beneficial in the future analysis of inflammation’s role in that process. Abstract Background: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. Methods: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous 19F nanoemulsion injection, followed by a baseline 19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and 9F signal using MRI. Results: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. Conclusion: These results demonstrate the potential of 19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.

Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy

Introduction Rectal cancer remains a leading cause of cancer morbidity and mortality in the United States. Currently, total mesorectal excision (TME) is the standard therapy for patients with T2N0 (stage IB) rectal cancer. Whether adjuvant radiation therapy provides a survival benefit to these patients or exposes them to unnecessary toxicity remains controversial and unproven to date. This study examined a large cohort of Stage 1B rectal cancer patients who underwent surgical resection and received adjuvant radiation in order to determine the demographic, clinical, and pathologic factors impacting prognosis and survival. Methods Demographic and clinical data on 4,054 Stage 1B rectal cancer patients were abstracted from the Surveillance Epidemiology and End Result (SEER) database (1973-2010). Statistical analysis was performed with SPSS v20.0 software (IBM Corp., Armonk, NY) using the chi-square test, paired t-test, multivariate analysis, and Kaplan-Meier functions. Results Among 4,054 patients with stage IB rectal cancer, 2,364 (58.3%) had surgery only, 1,477 (36.4%) received combination surgery and radiation (CSR), 139 (3.4%) received radiation only, and 74 (1.8%) received no therapy. Most stage IB patients in the surgery only and CSR groups were male (65.8 and 64%) and Caucasian (78.2% and 74.2%), p 4 cm (24%), while fewer were 60 (OR 2.4), poorly differentiated (OR 1.7) or undifferentiated grade (OR 2.6), and tumor size >2 cm (OR 1.5) as independently associated with increased mortality in the CSR group (p<0.05) while female gender conferred a survival advantage (OR 0.8), p<0.01. Conclusions In the current cohort, CSR was utilized most often in young male Caucasian patients presenting with less advanced disease as compared to other treatment groups. The overall survival is prolonged and overall mortality is lower in patients receiving CSR; however, increased cancer-related mortality with the use of CSR implies that survival benefits may be attributable to favorable non-tumor-related factors such as age, gender, and race. CSR should not replace surgery alone as the standard of care for all Stage IB rectal cancer patients at this time. However, all T2N0 rectal cancer patients should be enrolled in randomized control trials to allow for more defined multimodality management to optimize clinical outcomes for these patients.

Adjuvant Radiation Survival Benefits in Patients with Stage 1B Rectal Cancer: A Population-based Study from the Surveillance Epidemiology and End Result Database (1973-2010).

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Adjuvant Radiation Survival Benefits in Patients with Stage 1B Rectal Cancer: A Population-based Study from the Surveillance Epidemiology and End Result Database (1973-2010).