Urothelial Carcinoma: Epidemiology and Imaging-Based Review.

Bladder cancer is the 6th most common malignancy in the United States, with urothelial carcinomas comprising over 95% of cases of bladder cancer, and commands a significant disease burden in Rhode Island. Imaging studies can provide valuable diagnostic information for urothelial carcinomas at initial presentation and are routinely used for noninvasive staging, treatment response monitoring, and post-treatment surveillance. This review aims to discuss and highlight three imaging modalities: ultrasonography, computed tomography, and magnetic resonance imaging, with particular focus on the notable features and appearance of urothelial carcinoma on each modality and their relative utility throughout the disease course. A general overview of disease epidemiology and treatment practices is also provided.

Surgical resection, radiotherapy and percutaneous thermal ablation for treatment of stage 1 non-small cell lung cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently, surgical resection is the gold standard of treatment. However, as patients are becoming medically more complex presenting with advanced disease, minimally invasive image-guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with stage 1 NSCLC, with neither hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type. METHODS AND ANALYSIS: We will search electronic databases (MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Cochrane) from their inception to January 2021 to identify randomised controlled trials (RCTs), cluster RCTs and cohort studies comparing survival and clinical outcomes between any two interventions (lobectomy, wedge resection, video-assisted thoracoscopic surgery/robot-assisted thoracoscopic surgery, radiofrequency ablation, microwave ablation, cryoablation and consolidated radiation therapies (external beam radiation therapy, stereotactic body radiation therapy, and 3D conformal radiation therapy). The primary outcomes will include cancer-specific survival, lung disease-free survival, locoregional recurrence, death, toxicity and non-target organ injury. We will also search published and unpublished studies in trial registries and will review references of included studies for possible inclusion. Risk of bias will be assessed using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk of bias assessments. For each outcome, given enough studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network Meta-Analysis tool to assess quality of the evidence for each of the primary outcomes. ETHICS AND DISSEMINATION: We aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for providers in multidisciplinary teams caring for these patients to receive continuing medical education related to these interventions. Data will be made available to readers. PROSPERO REGISTRATION NUMBER: CRD42021276629.

Increased Cytoplasmic Yes-associated Protein (YAP) Expression in Mismatch Repair Protein-Proficient Colorectal Cancer With High-grade Tumor Budding and Reduced Autophagy Activity.

Yes-associated protein (YAP) is a transcriptional coactivator regulated by autophagy that stimulates colorectal cancer (CRC) progression through activation of epithelial-mesenchymal transition (EMT), represented by tumor budding. The associations between these components in CRC are unknown. Archived surgically resected CRCs with known mismatch repair protein (MMR) status were retrieved (n=81; 2010 to 2016). Electronic medical records were reviewed for clinicopathologic variables including pathologic TNM stage and clinical stage. Tumor budding was graded according to consensus guidelines. Cytoplasmic and nuclear YAP and p62 (autophagy substrate) immunoreactivity were semiquantitatively scored within tumor samples. The Student t test, Fisher exact test, χ2 test, and Spearman correlation coefficient were performed with P<0.05 as a significance level. MMR proficiency (MMR-P) status correlated with high-grade tumor budding. The extent of cytoplasmic YAP staining and pathologic N stage was associated with tumor budding in multivariate analysis. Cytoplasmic YAP expression correlated with higher cytoplasmic p62 expression, suggesting an inverse correlation between autophagy activation and cytoplasmic YAP expression. Nuclear YAP expression correlated with pathologic N stage and clinical stage. A correlation between MMR-P status and tumor budding, combined with correlations between cytoplasmic YAP, tumor budding and p62 raise the possibility of 2 distinct neoplastic pathways concerning autophagy and YAP; one displaying relative activation of YAP and EMT, being commonly observed in MMR-P, and another with less active YAP and EMT, but active autophagy, being commonly seen in MMR-deficient CRC. Nuclear YAP staining could be useful in prognostication.

Incidence of composite intestinal adenoma-microcarcinoid in 158 surgically resected polyps and its association with squamous morule.

Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion consisting of adenoma and small well-differentiated neuroendocrine cell clusters at its base. Its incidence is unknown. Benign squamous morule may demonstrate a neuroendocrine phenotype by immunohistochemistry. We investigated the incidence and clinicopathologic features of CIAM in endoscopically unresectable, surgically removed colorectal adenomas and evaluated its association with squamous morule. Archived pathology materials from 158 surgically resected colorectal adenomas were reviewed. 139 (88%) polyps were entirely submitted for microscopic examination. All lymph nodes were negative for adenocarcinoma and neuroendocrine tumor. CIAM was identified in 6 (3.8%) cases. The microcarcinoid (MC) was distributed over a mean of 5.8 mm (range < 1 to 12 mm), and was multifocal in 5 cases. The MC component was positive for synaptophysin in 6, CK5/6 in 4, and ß-catenin in 3 cases. Two of 6 (33.3%) CIAM showed concurrent squamous morule, compared to 4.0% (6 of 152) of adenomas without MC (p < 0.05). At the end of the mean follow-up of 53 months, 4 were free of disease and one patient with previous history of pulmonary large cell neuroendocrine carcinoma (NEC) had a recurrence of NEC. One patient died of an unrelated disease. The incidence of CIAM in surgically removed colorectal adenomas is 3.8%, with an indolent clinical course. Frequent co-expression of CK5/6 and ß-catenin in MC combined with common co-existence of squamous morule in the same polyp suggests shared pathogenesis of MC in CIAM and squamous morule, likely representing altered Wnt/ß-catenin signaling pathway.

The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas.

BACKGROUND: The expression profile of immunohistochemical markers of origin in poorly differentiated neuroendocrine carcinoma (PDNEC) is not well studied. MATERIALS AND METHODS: Seventy-four PDNECs from gastroenteropancreatic (GEP) organs and the lung, including 48 large cell NEC (LCNEC) and 26 small cell carcinomas (SmCC), were subject to immunohistochemical staining for CDX2, TTF1 and ISL1. The staining intensity (1 to 3) and percentage of positive tumor cells [0 (negative), 1 (<50%) and 2 (≥50%)] were assessed. The multiplicative index (maximum 6) was calculated and the average total score (aTS) was determined for each primary site and histologic subtype. RESULTS: In the 38 GEP and 36 lung PDNECs, CDX2, TTF1 and ISL1 staining was observed in 71% (aTS 2.8), 16% (aTS 0.4), 63% (aTS 1.9), and 22% (aTS 0.6), 72% (aTS 2.9) and 92% (aTS 3.8), respectively. GEP PDNECs showed a higher aTS for CDX2 and lower aTS for TTF1 and ISL1, compared to that of lung PDNECs (Student's t-test, p < 0.001). SmCC had a higher aTS for TTF1 and ISL1 (p < 0.001) and lower aTS for CDX2 (p < 0.002) than that of LCNEC. CONCLUSIONS: CDX2 and TTF1 demonstrate potential utility in suggesting the primary site of PDNEC. In addition, CDX2 may be useful in supporting the diagnosis of LCNEC in cases with overlapping or borderline morphology. Utility of ISL1 as an adjunctive diagnostic marker of SmCC remains to be studied.