Liver-First Resection in Patients With Synchronous Colorectal Liver Metastases Is Associated with Inferior Recurrence-Free Survival: Reconsidering the Importance of the Primary Cancer.

BACKGROUND: Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based upon treatment sequencing are understudied. OBJECTIVE: This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the three treatment strategies, with respect to early or delayed removal of the primary tumor. DESIGN: Retrospective analysis of prospectively maintained database, with 1:1 propensity-matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches. SETTINGS: Single-institution, tertiary cancer center. PATIENTS: Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003-2019. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. Median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by three-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not significantly differ between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28/simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3-year: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3-years (79% versus 80%, p = 0.95) or 5-years (59% versus 59%, p > 0.99). LIMITATIONS: This study has a retrospective design and limited sample size. CONCLUSIONS: A liver-first approach is associated with worse recurrence free-survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. Prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection is recommended. See Video Abstract.

Colonic Microbial Abundances Predict Adenoma Formers.

OBJECTIVE: We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. SUMMARY BACKGROUND DATA: Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. METHODS: Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma 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. RESULTS: 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). CONCLUSION: Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.

Transanal total mesorectal excision outcomes for advanced rectal cancer in a complex surgical population.

BACKGROUND: Total mesorectal excision (TME) is the gold standard for oncologic resection in low and mid rectal cancers. However, abdominal approaches to TME can be hampered by poor visibility, inadequate retraction, and distal margin delineation. Transanal TME (taTME) is a promising hybrid technique that was developed to mitigate the difficulties of operating in the low pelvis and to optimize the circumferential resection and distal margins. METHODS: The objective of this study was to characterize our experience implementing taTME at our institution in a technically challenging patient population. We performed a retrospective review of consecutive patients who underwent taTMEs between November 2013 and May 2019 for rectal cancer at a tertiary community cancer center. Outcome measures included pathologic grading of TME specimen, post-operative complications, and oncologic outcomes. RESULTS: Forty-four patients with mid and low rectal cancer underwent low anterior resection via taTME. The most common staging modality was rectal MRI which demonstrated T3 or T4 tumors in 89% of our patients prior to neoadjuvant. Eighty-six percent of patients underwent neoadjuvant chemoradiation. The initial cases were performed sequentially as a single team, but we later transitioned to a synchronous, two-team approach. Ninety-one percent of TME grades were complete or near complete. Only one patient (2.3%) had a positive circumferential margin. Six patients developed anastomotic leaks with an overall anastomotic complication rate of 18.2%. Two patients (4.5%) with primary rectal cancer developed local recurrence, one of which developed multifocal local recurrence. CONCLUSIONS: Using the taTME approach on selected locally advanced low rectal cancers, especially in technically complex irradiated and obese male patients, has yielded comparably safe and effective outcomes to laparoscopic proctectomy.

Chest binding in context: stigma, fear, and lack of information drive negative outcomes.

Chest binding or 'binding' is a practice used by many trans and nonbinary people assigned a female sex at birth to achieve a flatter chest contour and affirm their gender. Binding allows individuals to affirm their gender in a temporary, reversible way. While many individuals who bind report negative physical symptoms, binding also often carries significant benefits for mental health and safety. In this commentary, we explain what the data do and do not say about the physical risks of binding and describe how decreasing stigma around binding will substantially reduce physical risks associated with binding and increase the benefits of the practice. As with any intervention, individuals should make an informed decision about the risks and benefits of binding. If negative physical symptoms arise, individuals can consider adjusting their binding practice or working with a healthcare provider to address these concerns.

Diagnosis and Treatment of Anal Squamous Cell Carcinoma.

CASE SUMMARY: A 61-year-old woman with ongoing tobacco use was referred to a colorectal surgery clinic after a screening colonoscopy found irregular lesions at the dentate line with biopsies revealing a high-grade squamous intraepithelial lesion. She reported scant bleeding and irregular bowel function, but no incontinence. She has a history of abnormal Papanicolaou tests, but has since undergone a hysterectomy and has no history of immunosuppressive treatment or HIV. She was taken for an examination under anesthesia that revealing a 2.5-cm mass in the anal canal and was biopsied. Pathological examination confirmed anal squamous cell carcinoma (ASCC) with strongly positive p16 staining. A CT of her chest, abdomen, and pelvis did not reveal metastatic disease. She was referred to medical and radiation oncology for radiation therapy with concurrent chemotherapy (5-fluorouracil (5-FU) and mitomycin C). Subsequent office examination with anoscopy 3 months after treatment demonstrated an anterior scar without residual tumor.

Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Early onset colorectal cancer (age ≤45 y) is increasing and associated with advanced disease. Although distinct molecular subtypes of colorectal cancer have been characterized, it is unclear whether age-related molecular differences exist. OBJECTIVE: We sought to identify differences in gene expression between early and late-onset (age ≥65 y) colorectal cancer. DESIGN: We performed a review of our institution's colorectal cancer registry and identified patients with colorectal cancer with tissue specimens available for analysis. We used the Cancer Genome Atlas to initially identify differences in gene expression between early and late-onset colorectal cancer. In vitro experiments were performed on 2 colorectal cancer cell lines. SETTINGS: The study was conducted at a tertiary medical center. PATIENTS: Patients with early onset (n = 28) or late onset (age ≥65 y; n = 38) at time of diagnosis were included. MAIN OUTCOME MEASURES: The primary outcome was differential gene expression in patients with early versus late-onset colorectal cancer. The secondary outcome was patient mortality. RESULTS: Seven genes had increased expression in younger patients using The Cancer Genome Atlas. Only PEG10 was sufficiently expressed with quantitative polymerase chain reaction and had increased expression in our early onset group. Multivariable linear regression analysis identified age as a significant independent predictor of increased PEG10 expression. Outcomes data from The Cancer Genome Atlas suggests that PEG10 is associated with poor overall survival. In vitro studies in HCT-116 and HT-29 cell lines showed that PEG10 contributes to cellular proliferation and invasion in colorectal cancer. LIMITATIONS: Tissue samples were from formalin-fixed, paraffin-embedded sections. Many patients did not have mutational status for review. CONCLUSIONS: PEG10 is differentially expressed in early onset colorectal cancer and may functionally contribute to tumor cell proliferation and invasion. An increase in PEG10 expression correlates with decreased overall survival. See Video Abstract at http://links.lww.com/DCR/B343. LA EXPRESIÓN DIFERENCIAL DE PEG10 CONTRIBUYE A LA ENFERMEDAD AGRESIVA EN EL CÁNCER COLORRECTAL DE INICIO TEMPRANO VERSUS INICIO TARDÍO: El cáncer colorrectal es una de las principales causas de muerte relacionada con el cáncer. El cáncer colorrectal de inicio temprano (edad ≤45 años) está en aumento y asociado con enfermedad avanzada. Aunque se han caracterizado distintos subtipos moleculares del cáncer colorrectal, no está claro si existen diferencias moleculares relacionadas con la edad.Se buscó identificar diferencias en la expresión génica entre el cáncer colorrectal de inicio temprano y tardío (edad ≥ 65 años).Realizamos una revisión del registro de cáncer colorrectal de nuestra institución e identificamos pacientes con cáncer colorrectal con muestras de tejido disponibles para su análisis. Utilizamos el Atlas del Genoma del Cáncer para identificar inicialmente las diferencias en la expresión génica entre el cáncer colorrectal de inicio temprano y de inicio tardío. Se realizaron experimentos in vitro en dos líneas celulares de cáncer colorrectal.El estudio se realizó en un centro médico de tercer nivel.Se incluyeron pacientes con inicio temprano (n = 28) e inicio tardío (edad ≥65 años, n = 38) al momento del diagnóstico.El resultado primario fue la expresión diferencial de genes en pacientes con cáncer colorrectal de inicio temprano versus tardío. El resultado secundario fue la mortalidad de los pacientes.Siete genes aumentaron su expresión en pacientes más jóvenes usando el Atlas del Genoma del Cáncer. Solo PEG10 se expresó suficientemente con la reacción en cadena de la polimerasa cuantitativa y tuvo una mayor expresión en nuestro grupo de inicio temprano. El análisis de regresión lineal multivariable identificó la edad como un predictor independiente significativo del aumento de la expresión de PEG10. Los datos de resultados de el Atlas del Genoma del Cáncer sugieren que PEG10 está asociado con una pobre supervivencia general. Los estudios in vitro en líneas celulares HCT-116 y HT-29 mostraron que PEG10 contribuye a la proliferación e invasión celular en el cáncer colorrectal.Las muestras de tejido fueron de portaobjetos embebidos en parafina fijados con formalina. Muchos pacientes no tenían el estado de mutación para su revisión.El PEG10 se expresa diferencialmente en el cáncer colorrectal de inicio temprano y puede contribuir funcionalmente a la proliferación e invasión de células tumorales. El aumento en la expresión de PEG10 se correlaciona con la disminución de la supervivencia general. Consulte Video Resumen en http://links.lww.com/DCR/B343.

OBSERVED DEFICIENCIES IN MEDICAL STUDENT KNOWLEDGE OF TRANSGENDER AND INTERSEX HEALTH.

OBJECTIVE: Lesbian, gay, bisexual, transgender, and intersex (LGBTI) patients face many well-documented disparities in care which among transgender and intersex people can often be traced to providers' lack of knowledge. METHODS: We administered surveys to examine the self-assessed knowledge and attitudes of all medical students at Boston University regarding different LGBTI subpopulations. Survey questions were based on a Likert scale from 1 to 5; analysis was conducted with Wilcoxon rank sum tests. RESULTS: Overall there was a response rate of 24%, with the number of responses varying by class. Three of the 4 surveyed classes reported lower knowledge about transgender health than LGB health. Every class reported significantly lower knowledge of intersex health in comparison to LGB. Comfort with transgender or with intersex patients was lower than with LGB patients for all surveyed classes. Students across all self-identified groups (LGBTI, ally, not an ally) reported significantly lower average responses for knowledge and comfort regarding transgender or intersex health in comparison to that of LGB. Students in their preclinical years reported lower levels of knowledge in comparison with students in their clinical years. Students who identified as LGBTI reported significantly higher knowledge and comfort with only LGB and transgender health when compared with students who didn't identify as LGBTI. Respondents more frequently requested additional learning opportunities in transgender and intersex health than in LGB health. CONCLUSION: Self-reported knowledge of transgender and intersex health lags behind knowledge of LGB health, though these deficits appear partially responsive to targeted educational intervention. ABBREVIATIONS: BUSM = Boston University School of Medicine LGB = lesbian, gay, and bisexual LGBT = lesbian, gay, bisexual, and transgender LGBTI = lesbian, gay, bisexual, transgender, and intersex M1 = first-year medical student class M2 = second-year medical student class M3 = third-year medical student class M4 = fourth-year medical student class.

Dietary and lifestyle associations with microbiome diversity.

BACKGROUND: Microbial dysbiosis has been closely linked with colorectal cancer development. However, data is limited regarding the relationship of the mucosal microbiome, adenomatous polyps and dietary habits. Understanding these associations may elucidate pathways for risk stratification according to diet. RESULTS: Patients undergoing screening colonoscopy were included in our prospective, single center study and divided into adenoma or no adenoma cohorts. Oral, fecal, and mucosal samples were obtained. Microbial DNA was extracted, and amplicon libraries generated using primers for the 16S rRNA gene V4 region. Patient and dietary information was collected. Of 104 participants, 44% presented with polyps, which were predominantly tubular adenomas (87%). Adenoma formation and multiple patient dietary and lifestyle characteristics were associated with mucosal microbiome diversity. Lifestyle factors included age, body mass index, adenoma number, and dietary consumption of red meats, processed meats, vegetables, fruit, grain, fermented foods and alcohol. CONCLUSION: In this study we showed associations between dietary habits, adenoma formation and the mucosal microbiome. These early findings suggest that ongoing research into diet modification may help reduce adenoma formation and subsequently the development of CRC.

Time to First Onset of Chest Binding-Related Symptoms in Transgender Youth.

BACKGROUND AND OBJECTIVES: Most transgender individuals assigned female at birth use chest binding (ie, wearing a tight garment to flatten chest tissue for the purpose of gender expression), often beginning in adolescence, to explore their gender identity. Although binding is often critical for mental health, negative physical side effects, ranging from chronic pain to rib fractures, are common. Time to first onset of symptoms is unknown. METHODS: A community-engaged, online, cross-sectional survey ("The Binding Health Project") enrolled 1800 assigned female at birth or intersex individuals who had ever used chest binding. Lifetime prevalence of 27 pain, musculoskeletal, neurologic, gastrointestinal, generalized, respiratory, and skin or soft tissue symptoms related to binding was assessed. Nonparametric likelihood estimation methods were used to estimate survival curves. RESULTS: More than one-half (56%) of participants had begun binding by age 21, and 30% had begun by age 18. In 18 of 27 symptoms, the majority of people who go on to experience the event will do so within the first binding-year, but several skin-related and rare but serious outcomes (eg, rib fracture) took longer to occur. Pain presents rapidly but continues to rise in intensity over time, peaking at >5 years of binding. CONCLUSIONS: Although many symptoms emerge quickly, others can take years to develop. Individuals and their clinicians can use this information to make informed decisions on how to structure binding practices and top surgery timing while meeting goals related to gender expression and mental health. Access to puberty blockers may delay initiation of binding, preventing binding-related symptoms in youth.

A Distinct Innate Immune Signature of Early Onset Colorectal Cancer.

Despite a decrease in the prevalence of colorectal cancer (CRC) over the last 40 y, the prevalence of CRC in people under 50 y old is increasing around the globe. Early onset (≤50 y old) and late onset (≥65 y 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 formalin-fixed paraffin-embedded 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 CRC 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. We also performed gain-of-function experiments with CFD and SAA1 in s.c. tumor models and found that CFD is associated with higher tumor volumes, impacted several immune genes, and impacted three genes in mice that were also found to be differentially expressed in early onset CRC (EGR1, PSMB9, and CXCL9). Our data demonstrate that the immune microenvironment, characterized by a distinct innate immune response signature in early onset CRC, is unique, location dependent, and might contribute to worse outcomes.

Benign anorectal disease: hemorrhoids, fissures, and fistulas.

Hemorrhoids, anal fissures, and fistulas are common benign anorectal diseases that have a significant impact on patients' lives. They are primarily encountered by primary care providers, including internists, gastroenterologists, pediatricians, gynecologists, and emergency care providers. Most complex anorectal disease cases are referred to colorectal surgeons. Knowledge of these disease processes is essential for proper treatment and follow up. Hemorrhoids and fissures frequently benefit from non-operative treatment; they may, however, require surgical procedures. The treatment of anorectal abscess and fistulas is mainly surgical. The aim of this review is to examine the etiology, diagnosis, medical, and surgical treatment for these benign anorectal diseases.

Chest Binding and Care Seeking Among Transmasculine Adults: A Cross-Sectional Study.

Purpose: Chest binding, or compressing the chest tissue, is a common practice among transmasculine individuals that can promote mental health, but frequently results in negative physical health symptoms. The purpose of this study was to assess the prevalence and correlates of care seeking for binding-related health concerns among transmasculine adults. Methods: Descriptive statistics were calculated and logistic regression models were run using data from the Binding Health Project, a cross-sectional online survey among transgender adults who had practiced chest binding (n=1800). The analysis was restricted to transmasculine individuals who had consistent access to health care and were female assigned at birth or intersex (n=1273). Results: Of 1273 participants, 88.9% had experienced at least one binding-related symptom and 82.3% believed that it was important to discuss chest binding with their health care provider, while 14.8% had sought care related to binding. Participants reporting pain, musculoskeletal, or neurological symptoms had 3.19, 1.85, and 1.72 times the adjusted odds, respectively, of seeking care compared to those who did not report those symptoms (95% confidence intervals [CIs]: 1.38-7.37; 1.12-3.06; 1.10-2.68). Care seeking was associated with feeling safe and comfortable initiating a conversation about binding with one's provider (adjusted odds ratio [AOR]=2.07, 95% CI 1.32-3.24). Care seeking was not significantly associated with feeling comfortable receiving a chest examination (AOR=1.07, 95% CI 0.71-1.62). Conclusion: Low rates of care seeking for binding-related symptoms may be driven by lack of access to a provider with whom patients feel safe and comfortable, rather than by general discomfort with chest examinations. While transmasculine patients may be most likely to present with musculoskeletal, neurological, or pain-related concerns, providers should also assess for other symptoms. Providers should be familiar with the benefits and potential complications of binding and initiate non-stigmatizing positive discussions about binding with their transmasculine patients.

Intraoperative nerve monitoring during thyroid surgery.

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.

Progress on the road to better medical care for transgender patients.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.