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We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation.Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions.Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, non-adenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures.One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53).Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.

Despite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (≤50 years old) and late onset (≥65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. Our data demonstrate that the immune microenvironment in early onset CRC is unique, location dependent, and associated with worse outcomes.

Purpose of review Laryngeal nerve injury, resulting in speech and swallowing dysfunction, is a feared complication of thyroid operations. Routine visualization of the recurrent laryngeal nerve (RLN) has decreased the likelihood of nerve injury, and intraoperative nerve monitoring has been applied in the hope of further enhancing safety. Recent findings There is conflicting evidence about the value of nerve monitoring during thyroid operations, despite ample research. The data favor nerve monitoring in certain situations, such as neck re-explorations, contralateral RLN injury, extensive or challenging dissections, invasive tumors or large goiters, and nonrecurrent or branching recurrent laryngeal nerves. Continuous intraoperative nerve monitoring may reduce the chances of excessive traction, which is the most common mechanism of injury. Nerve monitoring may also identify and protect the external branches of the superior laryngeal nerve. Summary Surgeons should routinely identify recurrent laryngeal nerves during thyroid operations, and intraoperative nerve monitoring might be a useful adjunct to prevent injury. As a result of the relatively low probability of permanent recurrent laryngeal nerve injury, it is difficult to establish the absolute value of nerve monitoring. Further research may focus on continuous nerve monitoring and intraoperative monitoring of the external branches of the superior laryngeal nerves.

Despite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (≤50 years old) and late onset (≥65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. Our data demonstrate that the immune microenvironment in early onset CRC is unique, location dependent, and associated with worse outcomes. We propose that age specific immune signatures in the colorectal immune microenvironment can be used as biomarkers for prognosis as well as the development of targeted immune modulatory agents. Citation Format: Ivy H. Gardner, Ragavan Siddarthan, Katherine Watson, Elizabeth Dewey, Rebecca Ruhl, Xiangnan Guan, Zheng Xia, Liana V. Tsikitis, Sudarshan Anand. Innate immune genes distinguish the immune microenvironment of early onset colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-031.

214 Background: Over the past 35 years, there has been a significant increase in the number of patients below the recommended initial screening age (50 years old) diagnosed with colorectal cancer (CRC). Early onset colorectal cancer is more likely to occur in non-white patients, be located in the rectum, be diagnosed at a more advanced stage, and have concerning pathological features. The immune microenvironment in CRC is a key player in disease progression, therapy response, and overall survival. However, the role of the immune microenvironment in early onset CRC, particularly in rectal cancer has not been investigated. This study aims to characterize the immune microenvironment of early onset ( 50 years old) and late onset ( 65 years old) colon and rectal cancer patients. Methods: We used Nanostring immune profiling to analyze FFPE surgical specimens and identified genes that were differentially expressed between early and late onset colon and rectal cancer groups. We validate our results with qPCR. The differentially expressed genes in the rectal cancer cohort were compared to our analysis of a publically available database (GSE8721) of gene expression profiles for 203 rectal cancer and 160 matched normal mucosa samples. Immunohistochemistry (IHC) was performed on FFPE colorectal specimens for CXCL3. Results: Using Nanostring, we identified two genes that were differentially expressed between early and late onset colon cancer (IFITM1, CXCL3) and two genes in the rectal cancer cohort (FLT3, SAA1). CXCL3 has increased expression in late onset colon cancer utilizing qPCR and IHC. High expression of CXCL3 in both IHC and qPCR is associated with improved disease free survival. Analysis of the GSE8721 database also showed that FLT3 and SAA1 were differentially expressed in early versus late onset rectal cancer. Using qPCR, FLT3 is increased in early onset rectal cancer specimens compare to late onset rectal cancer, early and late onset colon cancer, and normal colon. Conclusions: There are distinct differences in the immune microenvironment between early and late onset colon and rectal cancer that may hold the potential for targeted therapeutics.

In order to improve transgender individuals' access to healthcare, primary care physicians and specialists alike should be knowledgeable about transgender medicine. This review is intended to provide concise transgender hormone treatment guidelines.Transgender individuals report that the lack of knowledgeable providers represents the greatest barrier to transgender medical care. Hormone treatments are generally well tolerated and greatly benefit transgender patients. After physicians recognize that gender identity is stable, hormone treatments for transgender patients are often straightforward. A practical target for hormone therapy for transgender men (female to male) is to increase testosterone levels to the normal male physiological range (300-1000 ng/dl) by administering testosterone. A practical target for hormone therapy for transgender women (male to female) is to decrease testosterone levels to the normal female range (30-100 ng/dl) without supra-physiological levels of estradiol (200 pg/ml) by administering an antiandrogen and estrogen. Patients should be monitored every 3 months for the first year and then every 6-12 months for hormonal effects.Although more studies are required, recently published transgender medical treatment guidelines provide a good start toward making care of transgender patients more generalized and accessible to healthcare providers.

Background An elevated odds ratio for venous thromboembolism (VTE) prompted development of a Caprini risk assessment and risk-based prophylaxis protocol for all general surgery patients. This system includes pre- and postoperative prophylactic heparin as well as extended courses of low molecular weight heparin for high-risk patients. This study evaluated the safety of this chemoprophylaxis program in thyroid and parathyroid surgery. Study Design A retrospective review was conducted of all general surgery patients undergoing thyroid or parathyroid operations after implementation of the Caprini prophylaxis protocol. Descriptive statistics were performed to evaluate bleeding complications, risk score categories, and chemoprophylaxis. Results Of 1,012 consecutive patients, 72% were determined to be at low/moderate risk for VTE, 26% were high risk, and 2% were highest risk. Only 29% of eligible high/highest-risk patients actually received extended prophylaxis after discharge. Fifteen patients (1.5%) developed wound hematomas that required evacuations, 12 of them within 24 hours of the index operation. Among patients who developed bleeding complications, 5 (33%) had Caprini scores indicating low/moderate-risk for VTE, and 10 (67%) were in the high/highest-risk categories. Only 1 patient developed a delayed hematoma that required a return to the hospital for evacuation. One patient developed a VTE complication. Conclusions Although the incidence of VTE is quite low for patients undergoing thyroid and parathyroid operations, the Caprini prophylaxis protocol identifies a subset of high-risk patients who may benefit from extended VTE prophylaxis without the likelihood of added harm. Conversely, Caprini scores might also select low-risk patients who require no chemoprophylaxis, possibly reducing risks of hemorrhage.