Providers' and survivors' perspectives on the availability and accessibility of surgery in gastrointestinal cancer care.

BACKGROUND: Surgery is essential for gastrointestinal (GI) cancer treatment. Many patients lack access to surgical care that optimizes outcomes. Scarce availability and/or low accessibility of appropriate resources may be the reason for this, especially in economically disadvantaged areas. This study aimed to investigate providers' and survivors' perspectives on barriers and facilitators to the availability and accessibility of surgical care. METHODS: Semistructured interviews informed by surgical disparities and access-to-care conceptual frameworks with purposively selected GI cancer providers and survivors in Alabama and Mississippi were conducted. Survivors were within 3 years of diagnosis of stage I to III esophageal, pancreatic, or colorectal cancer. Transcripts were analyzed using inductive thematic and content analysis techniques. Intercoder agreement was reached at 90 %. RESULTS: The 27 providers included surgeons (n = 11), medical oncologists (n = 2), radiation oncologists (n = 2), a primary care physician (n = 1), nurses (n = 8), and patient navigators (n = 3). This study included 36 survivors with ages ranging from 44 to 87 years. Of the 36 survivors, 21 (58.3 %) were male, and 11 (30.6 %) identified as Black. Responses were grouped into 3 broad categories: (i) transportation/geographic location, (ii) specialized care/testing, and (iii) patient-/provider-related factors. The barriers included lack and cost of transportation, reluctance to travel because of uneasiness with urban centers, low availability of specialized care, overburdened referral centers, provider-related referral biases, and low health literacy. Facilitators included availability of charitable aid, centralizing multidisciplinary care, and efficient appointment scheduling. CONCLUSION: In the Deep South, barriers and facilitators to the availability and accessibility of GI surgical cancer care were identified at the health system, provider, and patient levels, especially for rural residents. Our data suggest targets for improving the use of surgery in GI cancer care.

Preoperative Education is Associated with Adherence to Downstream Components and Outcomes in a Colorectal Surgery Enhanced Recovery Program.

Objective: This study evaluated the association between preoperative education and adherence to downstream components of enhanced recovery programs (ERPs) and surgical outcomes among patients undergoing elective colorectal surgery. Background: ERPs improve outcomes for surgical patients. While preoperative education is an essential component of ERPs, its relationship with other components is unclear. Methods: This was a retrospective cohort study of all ERP patients undergoing elective colorectal surgery from 2019 to 2022. Our institutional ERP database was linked with American College of Surgeons National Surgical Quality Improvement Program data and stratified by adherence to preoperative education. Primary outcomes included adherence to individual ERP components and secondary outcomes included high-level ERP adherence (>70% of components), length of stay (LOS), readmissions, and 30-day complications. Results: A total of 997 patients were included. The mean (SD) age was 56.5 (15.8) years, 686 (57.3%) were female, and 717 (71.9%) were white. On adjusted analysis, patients who received preoperative education (n = 877, 88%) had higher adherence rates for the following ERP components: no prolonged fasting (estimate = +19.6%; P < 0.001), preoperative blocks (+8.0%; P = 0.02), preoperative multimodal analgesia (+18.0%; P < 0.001), early regular diet (+15.9%; P < 0.001), and postoperative multimodal analgesia (+6.4%; P < 0.001). High-level ERP adherence was 13.4% higher (P < 0.01) and LOS was 2.0 days shorter (P < 0.001) for those who received preoperative education. Classification and regression tree analysis identified preoperative education as the first-level predictor for adherence to early regular diet, the second-level predictor for LOS, and the third-level predictor for ERP high-level adherence. Conclusion: Preoperative education is associated with adherence to ERP components and improved surgical outcomes.

Reducing no-show visits and disparities in access: The impact of telemedicine.

BACKGROUND: No-show visits have serious consequences for patients, providers, and healthcare systems as they lead to delays in care, increased costs, and reduced access to services. Telemedicine has emerged as a promising alternative to in-person visits by reducing travel barriers, but risks exacerbating the digital divide. The aim of this study was to assess the impact of telemedicine (video and phone) at a tertiary care academic center on no-show visits compared to in-person visits. METHODS: A retrospective cohort analysis of all weekday clinic visits among in-state adult patients at a single tertiary care center in the southeast from January 2020 to April 2023 was performed. Rates of no-show visits for patients who were seen via phone and video were compared with those who were seen in-person. Demographic and clinical characteristics of these groups were also compared, including age, sex, race/ethnicity, socioeconomic status, and visit type. The primary outcome was the rate of no-show visits for each visit type. RESULTS: Our analysis included 3,105,382 scheduled appointments, of which 81.2% were in-person, 13.4% via video, and 5.4% via phone calls. Compared to in-person visits, phone calls and video visits reduced the odds of no-show visits by 50% (aOR 0.5, CI 0.49-0.51) and 15% (aOR 0.85, CI 0.84-0.86), respectively. Older patients, Black patients, patients furthest from clinic, and patients from counties with the greatest degree of vulnerability and disparities in digital access were more likely to use phone visits. No-shows were more common among non-white, male, and younger patients from counties with lower socioeconomic status. CONCLUSION: Telemedicine effectively reduced no-show visits. However, limiting telemedicine to video-based visits only exacerbated disparities in access. Phone calls allow historically underserved patients from lower socioeconomic backgrounds to access healthcare and should be included within the definition of telemedicine.

Understanding the Impact of Enhanced Recovery Programs on Social Vulnerability, Race, and Colorectal Surgery Outcomes.

BACKGROUND: Increasing social vulnerability, measured by the Social Vulnerability Index, has been associated with worse surgical outcomes. However, less is known about the impact of social vulnerability on patients who underwent colorectal surgery under enhanced recovery programs. OBJECTIVE: We hypothesized that increasing social vulnerability is associated with worse outcomes before enhanced recovery implementation, but that after implementation, disparities in outcomes would be reduced. DESIGN: Retrospective cohort study using multivariable logistic regression to identify associations of social vulnerability and enhanced recovery with outcomes. SETTINGS: Institutional American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Patients undergoing elective colorectal surgery (2010-2020). Enhanced recovery programs were implemented in 2015. Those adhering to 70% or more of enhanced recovery program components were defined as enhanced recovery and all others as nonenhanced recovery. OUTCOMES: Length of stay, complications, and readmissions. RESULTS: Of 1523 patients, 589 (38.7%) were in the enhanced recovery group, with 625 patients (41%) in the lowest third of the Social Vulnerability Index, 411 (27%) in the highest third. There were no differences in Social Vulnerability Index distribution by the enhanced recovery group. On multivariable modeling, social vulnerability was not associated with increased length of stay, complications, or readmissions in the enhanced recovery group. Black race was associated with increased length of stay in both the nonenhanced recovery (OR 1.2; 95% CI, 1.1-1.3) and enhanced recovery groups (OR 1.2; 95% CI, 1.1-1.4). Enhanced recovery adherence was associated with reductions in racial disparities in complications as the Black race was associated with increased odds of complications in the nonenhanced recovery group (OR 1.9; 95% CI, 1.2-3.0) but not in the enhanced recovery group (OR 0.8; 95% CI, 0.4-1.6). LIMITATIONS: Details of potential factors affecting enhanced recovery program adherence were not assessed and are the subject of current work by this team. CONCLUSION: High social vulnerability was not associated with worse outcomes among both enhanced recovery and nonenhanced recovery colorectal patients. Enhanced recovery program adherence was associated with reductions in racial disparities in complication rates. However, disparities in length of stay remain, and work is needed to understand the underlying mechanisms driving these disparities. See Video Abstract . COMPRENDIENDO EL IMPACTO DE LOS PROGRAMAS DE RECUPERACIN MEJORADA EN LA VULNERABILIDAD SOCIAL, LA RAZA Y LOS RESULTADOS DE LA CIRUGA COLORRECTAL: ANTECEDENTES:El aumento de la vulnerabilidad social medida por el índice de vulnerabilidad social se ha asociado con peores resultados quirúrgicos. Sin embargo, se sabe menos sobre el impacto de la vulnerabilidad social en los pacientes de cirugía colorrectal bajo programas de recuperación mejorados.OBJETIVO:Planteamos la hipótesis de que el aumento de la vulnerabilidad social se asocia con peores resultados antes de la implementación de la recuperación mejorada, pero después de la implementación, las disparidades en los resultados se reducirían.DISEÑO:Estudio de cohorte retrospectivo que utilizó regresión logística multivariable para identificar asociaciones de vulnerabilidad social y recuperación mejorada con los resultados.ESCENARIO:Base de datos institucional del Programa de Mejora Nacional de la Calidad de la Cirugía del American College of Surgeons.PACIENTES:Pacientes sometidos a cirugía colorrectal electiva (2010-2020). Programas de recuperación mejorada implementados en 2015. Aquellos que se adhieren a ≥70% de los componentes del programa de recuperación mejorada definidos como recuperación mejorada y todos los demás como recuperación no mejorada.MEDIDAS DE RESULTADO:Duración de la estancia hospitalaria, complicaciones y reingresos.RESULTADOS:De 1.523 pacientes, 589 (38,7%) estaban en el grupo de recuperación mejorada, con 732 (40,3%) pacientes en el tercio más bajo del índice de vulnerabilidad social, 498 (27,4%) en el tercio más alto, y no hubo diferencias en la distribución del índice vulnerabilidad social por grupo de recuperación mejorada. En el modelo multivariable, la vulnerabilidad social no se asoció con una mayor duración de la estancia hospitalaria, complicaciones o reingresos en ninguno de los grupos de recuperación mejorada. La raza negra se asoció con una mayor duración de la estadía tanto en el grupo de recuperación no mejorada (OR1,2, IC95% 1,1-1,3) como en el grupo de recuperación mejorada (OR1,2, IC95% 1,1-1,4). La adherencia a la recuperación mejorada se asoció con reducciones en las disparidades raciales en las complicaciones, ya que la raza negra se asoció con mayores probabilidades de complicaciones en el grupo de recuperación no mejorada (OR1,9, IC95% 1,2-3,0), pero no en el grupo de recuperación mejorada (OR0,8, IC95% 0,4-1,6).LIMITACIONES:No se evaluaron los detalles de los factores potenciales que afectan la adherencia al programa de recuperación mejorada y son el tema del trabajo actual de este equipo.CONCLUSIÓN:La alta vulnerabilidad social no se asoció con peores resultados entre los pacientes colorrectales con recuperación mejorada y sin recuperación mejorada. Una mayor adherencia al programa de recuperación se asoció con reducciones en las disparidades raciales en las tasas de complicaciones. Sin embargo, persisten disparidades en la duración de la estadía y es necesario trabajar para comprender los mecanismos subyacentes que impulsan estas disparidades. (Traducción-Dr. Felipe Bellolio ).

Development of a comprehensive survey to assess key socioecological determinants of health.

BACKGROUND: Although disparities in surgical outcomes are well-documented, our understanding of how socioecological factors drive these disparities remains limited. Comprehensive and efficient assessment tools are needed. This study's objective was to develop and assess the acceptability and feasibility of a comprehensive tool evaluating socioecological determinants of health in patients requiring colorectal surgery. METHODS: In the first phase, a comprehensive socioecological determinant of health assessment tool was developed. A review of validated socioecological health evaluation instruments was conducted, and a 2-step modified Delphi method addressed the length, clarity, appropriateness, and redundancy of each instrument. A comprehensive tool was then finalized. In the second phase, the tool was tested for acceptability and feasibility in adult patients requiring colorectal surgery using a theory-guided framework at 3 Alabama hospitals. Relationships between survey responses and measures of acceptability and feasibility were evaluated using results from initial pilot tests of the survey. RESULTS: In Phase 1, a modified Delphi process led to the development of a comprehensive tool that included 31 socioecological determinants of health (88 questions). Results of acceptability and feasibility were globally positive (>65%) for all domains. Overall, 83% of participants agreed that others would have no trouble completing the survey, 90.4% of respondents reported the survey was not burdensome, 97.6% of patients reported having enough time to complete the survey, and 80.9% agreed the survey was well-integrated into their appointment. CONCLUSION: An 88-item assessment tool measuring 31 socioecological determinants of health was developed with high acceptability and feasibility for patients who required colorectal surgery. This work aids in the development of research needed to understand and address surgical disparities.

Racial disparities in postoperative outcomes persist for patients with inflammatory bowel disease under a colorectal enhanced recovery program.

INTRODUCTION: Enhanced recovery programs (ERPs) reduce racial disparities in surgical outcomes for general colorectal surgery populations. It is unclear, however, if disparities in IBD populations are impacted by ERPs. METHODS: Retrospective study comparing IBD patients undergoing major elective colorectal operations before (2006-2014) and after (2015-2021) ERP implementation using ACS-NSQIP data. The primary outcome of length of stay (LOS) was analyzed by negative binomial regression, and secondary outcomes (complications and readmissions) by logistic regression. RESULTS: Of 466 IBD patients, 47% were pre-ERP and 53% were ERP patients. In multivariable analysis stratified by ERP period, Black race was associated with increased odds of complications in the pre-ERP (OR 3.6, 95%CI 1.4-9.3) and ERP groups (OR 3.1 95%CI 1.3-7.6). Race was not a predictor of LOS or readmission in either group. High social vulnerability was associated with increased odds of readmission pre-ERP (OR 15.1, 95%CI 2.1-136.3), but this disparity was mitigated under ERPs (OR 1.4, 95%CI 0.4-5.6). CONCLUSION: While ERPs mitigated some disparities by social vulnerability, racial disparities persist in IBD populations even under ERPs. Further work is needed to achieve surgical equity for IBD patients.

Survival after multiple episodes of cardiac arrest.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is widely used in response to cardiac arrest. However, little is known regarding outcomes for those who undergo multiple episodes of cardiac arrest while in the hospital. OBJECTIVES: The purpose of this study was to evaluate the association of multiple cardiac events with in-hospital mortality for patients admitted to our tertiary care hospital who underwent multiple code events. METHODS: We performed a retrospective cohort study on all patients who underwent cardiac arrest from 2012 to 2016. Primary outcome was survival to discharge. Secondary outcomes included post-cardiac-arrest neurologic events (PCANE), non-home discharge, and one-year mortality. RESULTS: There were 622 patients with an overall mortality rate of 78.0%. Patients undergoing CPR for cardiac arrest once during their admission had lower in-hospital mortality rates compared to those that had multiple (68.9% versus 91.3%, p<.01). Subset analysis of those who had multiple episodes of CPR revealed that more than one event within a 24-hour period led to significantly higher in-hospital mortality rates (94.7% versus 74.4%, p<.01). Other variables associated with in-hospital mortality included body mass index, female sex, malignancy, and increased down time per code. Patients that had a non-home discharge were more likely to have sustained a PCANE than those that were discharged home (31.4% versus 3.9%, p<.01). A non-home discharge was associated with higher one-year mortality rates compared to a home discharge (78.4% versus 54.3%, p=.01). CONCLUSION: Multiple codes within a 24-hour period and the average time per code were associated with in-hospital mortality in cardiac arrest patients.

Dysregulation of Lipid and Glucose Homeostasis in Hepatocyte-Specific SLC25A34 Knockout Mice.

Nonalcoholic fatty liver disease (NAFLD) is an epidemic affecting 30% of the US population. It is characterized by insulin resistance, and by defective lipid metabolism and mitochondrial dysfunction in the liver. SLC25A34 is a major repressive target of miR-122, a miR that has a central role in NAFLD and liver cancer. However, little is known about the function of SLC25A34. To investigate SLC25A34 in vitro, mitochondrial respiration and bioenergetics were examined using hepatocytes depleted of Slc25a34 or overexpressing Slc25a34. To test the function of SLC25A34 in vivo, a hepatocyte-specific knockout mouse was generated, and loss of SLC25A34 was assessed in mice maintained on a chow diet and a fast-food diet (FFD), a model for NAFLD. Hepatocytes depleted of Slc25a34 displayed increased mitochondrial biogenesis, lipid synthesis, and ADP/ATP ratio; Slc25a34 overexpression had the opposite effect. In the knockout model on chow diet, SLC25A34 loss modestly affected liver function (altered glucose metabolism was the most pronounced defect). RNA-sequencing revealed changes in metabolic processes, especially fatty acid metabolism. After 2 months on FFD, knockouts had a more severe phenotype, with increased lipid content and impaired glucose tolerance, which was attenuated after longer FFD feeding (6 months). This work thus presents a novel model for studying SLC25A34 in vivo in which SLC25A34 plays a role in mitochondrial respiration and bioenergetics during NAFLD.

Effects of the COVID-19 lockdown on mental health in a UK student sample.

BACKGROUND: The COVID-19 pandemic and the resulting restrictions placed upon society have had a profound impact on both physical and mental health, particularly for young people. AIMS: The current study assesses the impact of COVID-19 on student mental health. METHOD: Four hundred and thirty four first year Undergraduate students completed a battery of self-report questionnaires (PHQ-P, GAD-7 and SAS-SV) to assess for depression, anxiety and mobile phone addiction respectively with data being collected over a 2 year period. The data from each year was compared (216 and 218 students respectively). RESULTS: A MANOVA revealed that COVID-19 had a significant impact on self-reported levels of depression, anxiety and smartphone addiction-which all significantly increased from the 2020 to the 2021 group. The percentage of students who had a score which warranted a classification of clinical depression increased from 30 to 44%, and for anxiety increased from 22 to 27%-those students who showed a comorbidity across the two rose from 12 to 21%. Smartphone addiction levels rose from 39 to 50%. Correlational analysis showed a significant relationship between Smartphone usage and depression and anxiety. CONCLUSIONS: This research suggests that COVID-19 has had a major impact upon student mental health, and smartphone addiction. The importance of identifying predictive factors of depression and anxiety is emphasised, and suggestions for intervention are discussed.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN). METHODS: Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions. RESULTS: Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 [AJCC 7th edition]). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%-93.9%). CONCLUSION: Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.

Are Tc-99m-Sestamibi Scans in Patients With Secondary Hyperparathyroidism and Renal Failure Needed?

BACKGROUND: Parathyroidectomy for patients with secondary hyperparathyroidism (sHPT) generally requires a four-gland exploration. Some groups have strongly recommended routine preoperative Tc-99m-sestamibi scans; others practice scanning for only selected patients. To determine the utility of sestamibi scans in this patient population, we reviewed our experience. METHODS: We performed a retrospective review of patients who underwent parathyroidectomy for sHPT by one surgeon between 2000 and 2018. Data reviewed included patient demographics, laboratory results, pathology and radiology reports, and clinical and operative notes. RESULTS: Of the 72 patients in the cohort, mean age was 47.2 ± 15.6, and 50% were female. The preoperative mean calcium and parathyroid hormone levels were 9.6 ± 1.1 mg/dL and 1192.1 ± 914.1 pg/mL, respectively. Sestamibi scans were performed in 21 patients (29%). Of these, 17 were reoperative cases. Of all sHPT patients, 27.8% had ectopic glands. In the sestamibi cohort, only four patients had ectopic glands identified on the scan. Among the 51 patients without preoperative imaging, 16 had ectopic glands (26.2% of nonimaged patients). All these 16 ectopic glands were found by the surgeon at the time of operation without the need for preoperative imaging. All patients in the series were cured with a minimum follow-up of 6 mo. CONCLUSIONS: Ectopic parathyroid glands are commonly seen in patients undergoing parathyroidectomy for sHPT. The majority of ectopic glands were successfully identified during the operation without preoperative sestamibi scan. Therefore, routine preoperative Tc-99m-sestamibi scans are not needed for successful parathyroidectomy for sHPT.

Patient reported outcomes in evaluation of chemotherapy toxicity in women with gynecologic malignancies: A pilot study.

OBJECTIVE: Patient reported outcomes (PRO) relating to treatment toxicities have been demonstrated to reliably evaluate adverse events in clinical trials. We assessed the user satisfaction of implementing a focused PRO questionnaire for patients with gynecologic cancers undergoing chemotherapy. METHODS: Patients with gynecologic cancers undergoing chemotherapy were prospectively identified after IRB approval from April 2017 to August 2017. We administered a 24-symptom questionnaire, adapted from the validated PRO version of the Common Terminology Criteria for Adverse Event, to enrolled participants at the beginning of two outpatient visits. Patient and provider satisfaction with use of PRO was assessed afterwards. Descriptive statistics were performed. RESULTS: A total of 44 patients were enrolled. Patients were racially diverse: 52% Caucasian, 18% African-American, 9% Asian, and 20% other; 27% were of Hispanic origin. The majority of patients had ovarian cancer (54%), followed by uterine (29%) and cervical cancer (15%). Ninety-five percent of patient and 97% of provider satisfaction survey responses indicated the PRO questionnaire addressed important symptoms. Nearly all patient and provider responses indicated the PRO questionnaire was easy to use. Sixty-nine percent of patient and 97% of provider responses indicated the questionnaire positively impacted clinical care; 85% of patients wished to use a similar questionnaire throughout treatment. CONCLUSIONS: We have shown that incorporating a focused patient-reported symptom questionnaire into routine outpatient care of gynecological oncology patients undergoing chemotherapy was met with a high degree of patient and provider satisfaction regarding questionnaire content, feasibility, and perception of care improvement.

Endometrial cancer: Molecular markers and management of advanced stage disease.

Endometrial cancer is the most prevalent gynecologic cancer in the United States. Over the last 10 years, death rates from endometrial cancer have been rising about 1.4% per year. Traditionally endometrial cancer treatment has been driven by stage and histology. Recent studies have, however, shown that cancers of the same stage and histology have very distinct molecular and genomic profiles. Translational research is progressing rapidly and endometrial cancer-specific precision medicine is evolving. The first tissue agnostic therapy based on the molecular profile of the tumor was approved by the FDA this year. The approval of immune checkpoint inhibitor, pembrolizumab (anti-PD-1), for all solid tumors with defective DNA mismatch repair, could benefit 20-30% of patients with advanced endometrial cancer. Other genomic changes and molecular markers in endometrial cancer, such as hormone receptor status, could lead to more tailored therapy in the future. Pre-clinical and clinical investigations of targeted therapies suggest efficacy for some agents. Single agent targeted therapies, however, have modest activity. Identifying biomarkers that effectively determine response to targeted therapy remains a challenge. The next generation of clinical trials will focus on novel combinations and how to best utilize the advances that have been made in sequencing technology and bioinformatics. Although there is currently an immense body of data and many options for obtaining genomic characteristics of endometrial cancer, how to interpret and utilize this data is still being explored. This review will summarize the important trials that have led to the treatment options we have for advanced and/or recurrent endometrial cancer and discuss the important studies that have led to a better understanding of the distinctive molecular and genomic profiles within endometrial cancer. We will review the current status of biomarker-driven targeted therapy in endometrial cancer and the rationale behind ongoing clinical trials that are utilizing novel targeted agents.

Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer.

Ovarian cancer is the fifth leading cause of cancer-related deaths in females in the United States. There were an estimated 22,440 new cases and 14,080 deaths due to ovarian cancer in 2017. Most patients present with advanced-stage disease, revealing the urgent need for new therapeutic strategies targeting pathways of tumorigenesis and chemotherapy resistance. While multiple genomic changes contribute to the progression of this aggressive disease, it has become increasingly evident that epigenetic events play a pivotal role in ovarian cancer development. One of the well-studied epigenetic modifiers, the histone methyltransferase EZH2, is a member of polycomb repressive complex 2 (PRC2) and is commonly involved in transcriptional repression. EZH2 is the enzymatic catalytic subunit of the PRC2 complex that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). In ovarian cancer, EZH2 is commonly overexpressed and therefore potentially serves as an effective therapeutic target. Multiple small-molecule inhibitors are being developed to target EZH2, which are now in clinical trials. Thus, in this review, we highlight the progress made in EZH2-related research in ovarian cancer and discuss the potential utility of targeting EZH2 with available small-molecule inhibitors for ovarian cancer. Mol Cancer Ther; 17(3); 591-602. ©2018 AACR.

An experimental means of transmitting pancreas disease in Atlantic salmon Salmo salar L. fry in freshwater.

A challenge model for pancreas disease in Atlantic salmon, Salmo salar L. fry, was developed comparing two salmonid alphavirus (SAV) subtypes: SAV1 and SAV5. Viral doses of 3 × 10(5) TCID50  mL(-1) for SAV1 and 3 × 10(4) for SAV5 were tested in triplicate tanks, each containing 450 salmon fry. Cumulative mortalities of 1.2% were recorded. Titres of virus recovered from the mortalities ranged from 10(2) to 10(7) TCID50  mL(-1) . Fry were sampled at 3, 5 and 7.5 weeks post-challenge. Sampling after 3 weeks revealed a high prevalence of infection in the absence of clinical signs, and infectious virus was recovered from 80% and 43% of sampled fry infected with SAV1 and SAV5, respectively. After 5 weeks pancreas, heart and red skeletal muscle lesions were generally observed, whilst degeneration in white skeletal muscle was observed only in fish infected with SAV1. In situ hybridisation confirmed the presence of viral genome in infected pancreas, heart and muscle. After 7.5 weeks, infectious virus (both isolates) was recovered from 13.3% of the fish sampled, with a viral titre of 10(2) TCID50  mL(-1) . Clearly, salmon fry are susceptible to SAV infection and pancreas disease.

Phase 1 study of nab-paclitaxel, cisplatin and 5-fluorouracil as induction chemotherapy followed by concurrent chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the oropharynx.

BACKGROUND: Induction chemotherapy followed by concurrent chemoradiation (CRT) (sequential therapy) has been evaluated in the treatment of locoregionally-advanced squamous cell cancer of the head and neck (LA-SCCHN), with docetaxel, cisplatin (P) and 5-flurouracil (F) shown to be superior to PF doublet. Nab-paclitaxel (A) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel. METHODS: A phase I trial [Clinical trials.gov identifier NCT00731380] to assess the safety and efficacy of nab-paclitaxel+cisplatin+5-fluorouracil (APF) as induction chemotherapy for three cycles, followed by concurrent carboplatin (area-under-curve (AUC) 1.5 weekly) with radiation therapy (RT) (70 Gy/35 fractions), was conducted using a 3+3 design in patients with previously untreated LA-SCCHN. Dose-limiting toxicities (DLTs) included: standard haematologic and non-haematologic toxicities, treatment delays, inability to complete ⩾95% of RT and skin/mucosal toxicity related to RT assessed from day 1 of treatment to 8 weeks after completion of CRT. RESULTS: 17 patients with oropharyngeal cancer were enrolled in three dose levels, with 15 patients evaluable for DLT. The median age was 54 years (range, 44-65 years), 14 patients were male, and 11 patients' tumours were p16 positive and four negative. Grade 3/4 adverse events during APF (%total number of cycles) were hyponatraemia (14%) neutropenia (10%), lymphopaenia (4%) and thrombocytopenia (2%) during 49 evaluable APF cycles. Febrile neutropenia occurred during one cycle of treatment. CONCLUSION: The recommended phase 2 dose of APF is nab-paclitaxel 100mg/m(2) days 1 and 8, cisplatin 75 mg/mg(2) day 1 and 5-fluorouracil 1000 mg/m(2)/day×96 h days 1-4, every 3 weeks, for three cycles prior to CRT.

Studies on the effect of temperature and pH on the inactivation of fish viral and bacterial pathogens.

Disposal of fish by-products in the European Community must comply with Regulation (EC) No 1069/2009 which categorizes animal by-products according to risk, and specifies methods of disposal of by-products according to that risk. There is provision under the regulation for composting or ensiling to be used for by-products from aquatic animals. Biosecurity considerations require knowledge of the parameters of time and temperature, or time and pH, required to inactivate any fish pathogens that may be present. To provide those data, we undertook laboratory studies on the inactivation of a number of fish pathogenic viruses and bacteria at 60 °C, pH 4.0 and pH 12.0 as a preliminary to conducting subsequent trials with the most resistant viruses and bacteria in fish tissues. The most resistant bacterium to 60 °C, pH 4.0 as well as pH 12.0 was Lactococcus garvieae. Its concentration was reduced to the level of sensitivity of the test after 24-48 h exposure to 60 °C, but it survived for at least 7 days at pH 4.0 and 14 days at pH 12.0. The most resistant virus to 60 °C was infectious pancreatic necrosis virus, and to pH 12.0 was infectious salmon anaemia virus. The majority of the viruses tested survived exposure to pH 4.0 for up to 28 days. The results suggest that the process of acid ensiling alone is not an effective method for the inactivation of many viral and bacterial pathogens, and fish by-products would need further treatment by a method approved under the regulation following ensiling, whereas alkaline or heat treatment are likely to provide an increased degree of biosecurity for on-farm processing of mortalities.

Studies on the inactivation of selected viral and bacterial fish pathogens at high pH for waste disposal purposes.

This study investigated the use of alkaline hydrolysis at ambient temperature for inactivation of selected fish pathogens in fish tissues under conditions approximating those that are likely to be found in the aquaculture industry. Infectious salmon anaemia virus (ISAV) and Lactococcus garvieae have been determined in a previous study to be the most resistant virus and bacteria to pH 12 from a wide range of viruses and bacteria tested. They were spiked at high titres into fish extracts that were then treated with 1 m sodium hydroxide (NaOH). Viable L. garvieae was not detected in the treated fish extract after 1 h, and ISAV was not detected after 24-h exposure. Field mortalities of Atlantic salmon, Salmo salar L., caused by infectious pancreatic necrosis virus were treated by alkaline hydrolysis at ambient temperature. The macerated fish mortalities contained a high titre of virus (3.38 × 108 TCID50 g⁻¹) that was reduced to approximately 2.2 × 10³ TCID50 g⁻¹ after 24-h exposure to NaOH, and virus was not detected after exposure for 48 h. The results suggest that alkaline hydrolysis at ambient temperature has potential as a biosecure treatment method for fish by-products containing fish pathogens.