Mixed epithelial endocrine neoplasms of the colon and rectum - An evolution over time: A systematic review.

BACKGROUND: Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM: To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS: A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms ["mixed tumors colon" OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS: In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs). CONCLUSION: MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.

Primary pulmonary/pleural melanoma in a 13 year-old presenting as pleural effusion.

Melanoma in children, adolescents, and young adults is uncommon and reported almost exclusively as cutaneous melanoma. Melanoma presenting as a pleural effusion is very rare in adults and not reported in the pediatric population. Additionally, primary pulmonary melanoma is overall very rare and undocumented in pediatric patients. Furthermore, the distinction between a primary pulmonary/pleural melanoma versus a regressed cutaneous melanoma with pulmonary/pleural metastases remains extremely challenging. We discuss a case of a previously healthy 13-year-old girl that presented with a left-sided pleural effusion. Investigations revealed a large mediastinal mass, left-sided pleural and pulmonary nodules, a sacral mass, and bone marrow infiltration. The neoplasm was subsequently diagnosed by morphology and immunocytochemistry with histological correlation as malignant melanoma. As no mucosal, eye, or cutaneous lesions were identified, we deliberate the likelihood of a regressed cutaneous melanoma with metastases versus primary pulmonary/pleural melanoma with pleural effusion and discuss its diagnostic approach.

Catharanthine dilates small mesenteric arteries and decreases heart rate and cardiac contractility by inhibition of voltage-operated calcium channels on vascular smooth muscle cells and cardiomyocytes.

Catharanthine is a constituent of anticancer vinca alkaloids. Its cardiovascular effects have not been investigated. This study compares the in vivo hemodynamic as well as in vitro effects of catharanthine on isolated blood vessels, vascular smooth muscle cells (VSMCs), and cardiomyocytes. Intravenous administration of catharanthine (0.5-20 mg/kg) to anesthetized rats induced rapid, dose-dependent decreases in blood pressure (BP), heart rate (HR), left ventricular blood pressure, cardiac contractility (dP/dt(max)), and the slope of the end-systolic pressure-volume relationship (ESPVR) curve. Catharanthine evoked concentration-dependent decreases (I(max) >98%) in endothelium-independent tonic responses of aortic rings to phenylephrine (PE) and KCl (IC(50) = 28 µM for PE and IC(50) = 34 µM for KCl) and of third-order branches of the small mesenteric artery (MA) (IC(50) = 3 µM for PE and IC(50) = 6 µM for KCl). Catharanthine also increased the inner vessel wall diameter (IC(50) = 10 µM) and reduced intracellular free Ca(2+) levels (IC(50) = 16 µM) in PE-constricted MAs. Patch-clamp studies demonstrated that catharanthine inhibited voltage-operated L-type Ca(2+) channel (VOCC) currents in cardiomyocytes and VSMCs (IC(50) = 220 µM and IC(50) = 8 µM, respectively) of MA. Catharanthine lowers BP, HR, left ventricular systolic blood pressure, and dP/dt(max) and ESPVR likely via inhibition of VOCCs in both VSMCs and cardiomyocytes. Since smaller vessels such as the third-order branches of MAs are more sensitive to VOCC blockade than conduit vessels (aorta), the primary site of action of catharanthine for lowering mean arterial pressure appears to be the resistance vasculature, whereas blockade of cardiac VOCCs may contribute to the reduction in HR and cardiac contractility seen with this agent.

Unusual retrorectal lesion.

Retrorectal lesions are rare entities. We report the complete clinicopathological details of an unusual retrorectal lesion composed of low-grade endometrioid adenocarcinoma and propose that this is a malignant change in pluripotent cells arising within a long-standing retrorectal tailgut lesion. To the best of our knowledge, this is the first case report of this malignancy in a retrorectal tailgut cyst.