Precision Oncology in Gastrointestinal and Colorectal Cancer Surgery.

Precision medicine is used to treat gastrointestinal malignancies including esophageal, gastric, small bowel, colorectal, and pancreatic cancers. Cutting-edge assays to detect and treat these cancers are active areas of research and will soon become standard of care. Colorectal cancer is a prime example of precision oncology as disease site is no longer the final determinate of treatment. Here, the authors describe how leveraging an understanding of tumor biology translates to individualized patient care using evidence-based practices.

Effect of Medicaid expansion on inflammatory bowel disease and healthcare utilization.

BACKGROUND: Kentucky was among the first to adopt Medicaid expansion, resulting in reducing uninsured rates from 14.3% to 6.4%. We hypothesize that Medicaid expansion resulted in increased elective healthcare utilization and reductions in emergency treatments by patients suffering Inflammatory Bowel Disease (IBD). METHODS: The Hospital Inpatient Discharge and Outpatient Services Database (HIDOSD) identified all encounters related to IBD from 2009 to 2020 in Kentucky. Several demographic variables were compared in pre- and post-Medicaid expansion adoption. RESULTS: Our study analyzed 3386 pre-expansion and 24,255 post-expansion encounters for IBD patients. Results showed that hospitalization rates dropped (47.7%-8.4%), outpatient visits increased (52.3%-91.6%) and Emergency visits decreased (36.7%-11.4%). Admission following a clinical referral similarly increased with a corresponding drop in emergency room admissions. Hospital costs and lengths of stay also dropped following Medicaid expansion. CONCLUSION: In the IBD population, Medicaid expansion improved access to preventative care, reduced hospital costs by decreasing emergency care, and increased elective care pathways.

Phase I Safety and Feasibility Pilot of Hepatic Artery Infusion Chemotherapy in a Rural Catchment Area Using The Codman Vascular Catheter with The Medtronic SynchroMed II Pump for Intrahepatic Cancers.

BACKGROUND: Discontinuation of the Codman 3000 pump in 2018 left no Food and Drug Administration (FDA)-approved hepatic artery infusion (HAI) device for unresectable colorectal liver metastases (uCLM) and intrahepatic cholangiocarcinoma (uIHC). Historically, HAI has been performed at academic medical centers in large metropolitan areas, which are often inaccessible to rural patients. Consequently, feasibility of dissemination of HAI to rural populations is unknown. PATIENTS AND METHODS: Under an FDA investigational device exemption, we opened the only HAI program in Kentucky and enrolled patients with uCLM and uIHC in a phase I clinical trial. The trial examined the safety of the hybrid Codman catheter/Medtronic SynchroMed II pump (hCMP) combination, defined as successful completion of one cycle of HAI chemotherapy. Rural feasibility was assessed by number of missed pump fills appointments. RESULTS: A total of 21 patients (n = 17 uCLM, n = 4 uIHC) underwent hCMP implantation before accrual was stopped early owing to FDA approval of the Intera 3000 pump. 20/21 (95%) patients met the primary safety endpoint. Serious adverse events (AEs) included a grade 5 coronavirus disease 2019 (COVID-19) infection (n = 1) and a grade 3 catheter erosion into the bowel (n = 1). Biliary sclerosis developed in two patients (9.5%). Median distance to infusion center was 47.6 miles (2-138 miles), and 62% were from Appalachia, yet there were no missed pump fill appointments. The 2-year overall survival was 82.4% (uCLM) and 50% (uIHC). CONCLUSIONS: The hCMP device had an acceptable safety profile. Despite the complexity of starting a new HAI program, early results showed feasibility for HAI delivery in a rural catchment area and comparable outcomes to larger urban-based HAI centers.

Impact of the Affordable Care Act on Providing Equitable Healthcare Access for IBD in the Kentucky Appalachian Region.

BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown. OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area. DESIGN: This study was a retrospective, descriptive, and ecological study. SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database. PATIENTS: All encounters for IBD care for 2009-2020 for patients from the Eastern Kentucky Appalachian region were included. MAIN OUTCOME MEASURES: The primary outcomes measured were proportions of inpatient and emergency encounters, total hospital charge, and hospital length of stay. RESULTS: Eight hundred twenty-five preexpansion and 5726 postexpansion encounters were identified. Postexpansion demonstrated decreases in the uninsured (9.2%-1.0%; p < 0.001), inpatient encounters (42.7%-8.1%; p < 0.001), emergency admissions (36.7%-12.3%; p < 0.001), admissions from the emergency department (8.0%-0.2%; p < 0.001), median total hospital charge ($7080-$3260; p < 0.001), and median total hospital length of stay (4-3 days; p < 0.001). Similarly, postexpansion demonstrated increases in Medicaid coverage (18.8%-27.7%; p < 0.001), outpatient encounters (57.3%-91.9%; p < 0.001), elective admissions (46.9%-76.2%; p < 0.001), admissions from the clinic (78.4%-90.2%; p < 0.001), and discharges to home (43.8%-88.2%; p < 0.001). LIMITATIONS: This study is subject to the limitations inherent in being retrospective and using a partially de-identified database. CONCLUSION: This study is the first to demonstrate the changes in trends in care after Medicaid expansion for patients with IBD in the Commonwealth of Kentucky, especially Appalachian Kentucky, showing significantly increased outpatient care utilization, reduced emergency department encounters, and decreased length of stays. IMPACTO DE LA LEY DEL CUIDADO DE SALUD A BAJO PRECIO EN LA PROVISIN DE ACCESO EQUITATIVO A LA ATENCIN MDICA PARA LA ENFERMEDAD INFLAMATORIA INTESTINAL EN LA REGIN DE LOS APALACHES DE KENTUCKY: ANTECEDENTES: La expansión de Medicaid mejoró la cobertura de seguro para pacientes con enfermedades crónicas y bajos ingresos. Se desconoce el efecto de la expansión de Medicaid en pacientes con enfermedad inflamatoria intestinal de comunidades de alta pobreza.OBJETIVO: Este estudio tuvo como objetivo evaluar el impacto de la expansión de Medicaid en Kentucky en la atención de pacientes con enfermedad inflamatoria intestinal de la comunidad de los Apalaches del este de Kentucky, un área históricamente empobrecida.DISEÑO: Este estudio fue un estudio retrospectivo, descriptivo, ecológico.ESCENARIO: Este estudio se realizó en Kentucky utilizando la base de datos de servicios ambulatorios y de alta hospitalaria en pacientes hospitalizados.PACIENTES: Se incluyeron todos los encuentros para la atención de la enfermedad inflamatoria intestinal de 2009-2020 para pacientes de la región de los Apalaches del este de Kentucky.MEDIDAS DE RESULTADO PRINCIPALES: Los resultados primarios medidos fueron proporciones de encuentros de pacientes hospitalizados y de emergencia, cargo hospitalario total y duración de la estancia hospitalaria.RESULTADOS: Se identificaron 825 encuentros previos a la expansión y 5726 posteriores a la expansión. La posexpansión demostró disminuciones en los no asegurados (9.2% a 1.0%, p < 0.001), encuentros de pacientes hospitalizados (42.7% a 8.1%, p < 0.001), admisiones de emergencia (36.7% a 12.3%, p < 0,001), admisiones desde el servicio de urgencias (8.0% a 0.2%, p < 0.001), la mediana de los gastos hospitalarios totales ($7080 a $3260, p < 0.001) y la mediana de la estancia hospitalaria total (4 a 3 días, p < 0.001). De manera similar, la cobertura de Medicaid (18.8% a 27.7%, p < 0.001), consultas ambulatorias (57.3% a 91.9%, p < 0.001), admisiones electivas (46.9% a 76.2%, p < 0.001), admisiones desde la clínica (78.4% al 90.2%, p < 0.001), y las altas domiciliarias (43.8% al 88.2%, p < 0.001) aumentaron después de la expansión.LIMITACIONES: Este estudio está sujeto a las limitaciones inherentes de ser retrospectivo y utilizar una base de datos parcialmente desidentificada.CONCLUSIONES: Este estudio es el primero en demostrar los cambios en las tendencias en la atención después de la expansión de Medicaid para pacientes con enfermedad inflamatoria intestinal en el Estado de Kentucky, especialmente en los Apalaches de Kentucky, mostrando un aumento significativo en la utilización de la atención ambulatoria, visitas reducidas al departamento de emergencias y menor duración de la estancia hospitalaria. (Traducción-Dr. Jorge Silva Velazco ).

Creation of EGD-Derived Gastric Cancer Organoids to Predict Treatment Responses.

Gastric adenocarcinoma (GAd) is the third leading cause of cancer-related deaths worldwide. Most patients require perioperative chemotherapy, yet methods to accurately predict responses to therapy are lacking. Thus, patients may be unnecessarily exposed to considerable toxicities. Here, we present a novel methodology using patient-derived organoids (PDOs) that rapidly and accurately predicts the chemotherapy efficacy for GAd patients. Methods:Endoscopic GAd biopsies were obtained from 19 patients, shipped overnight, and PDOs were developed within 24 h. Drug sensitivity testing was performed on PDO single-cells with current standard-of-care systemic GAd regimens and cell viability was measured. Whole exome sequencing was used to confirm the consistency of tumor-related gene mutations and copy number alterations between primary tumors, PDOs, and PDO single-cells. Results:Overall, 15 of 19 biopsies (79%) were appropriate for PDO creation and single-cell expansion within 24 h of specimen collection and overnight shipment. With our PDO single-cell technique, PDOs (53%) were successfully developed. Subsequently, two PDO lines were subjected to drug sensitivity testing within 12 days from initial biopsy procurement. Drug sensitivity assays revealed unique treatment response profiles for combination drug regimens in both of the two unique PDOs, which corresponded with the clinical response. Conclusions:The successful creation of PDOs within 24 h of endoscopic biopsy and rapid drug testing within 2 weeks demonstrate the feasibility of our novel approach for future applications in clinical decision making. This proof of concept sets the foundation for future clinical trials using PDOs to predict clinical responses to GAd therapies.

Starting a successful hepatic artery infusion pump program: A practical guide.

Implementation of a successful hepatic artery infusion pump program requires numerous factors to be in place, and the lack of any of these may lead to program failure. First and foremost, hepatic artery infusion pump programs must have adequate surgical expertise in the complex technical aspects of hepatic artery infusion pump implantation and postoperative management. Most new hepatic artery infusion pump programs are initiated by a surgeon and led in conjunction with a medical oncologist. Medical oncology experience in floxuridine dosing is critical in maximizing the treatment doses and the number of cycles administered while avoiding biliary toxicity. This is facilitated by collaboration with an engaged pharmacy team. To have adequate patient volume for a successful program, internal and external stakeholders must have buy-in, including surgical and medical oncology colleagues unfamiliar with hepatic artery infusion pumps, colorectal surgery, and other referring providers. Programmatic support must be obtained from the hospital, cancer center, and department administration. Day-to-day pump access for chemotherapy and maintenance saline fills must be performed by appropriately trained infusion nurses to avoid complications. Nuclear and diagnostic radiology experience is key to identifying extrahepatic perfusion and hepatic artery infusion pump-specific complications. Additionally, skilled interventional radiologists and gastroenterologists are necessary to identify and treat rare complications rapidly. Finally, given the current rapid expansion of hepatic artery infusion pump programs, new programs must identify engaged mentors to help guide patient selection, navigate the nuanced issues that may arise, and provide advice in the case of complications. Although hepatic artery infusion pump dissemination outside of several major tertiary centers previously had stalled, establishing a successful and active hepatic artery infusion pump is feasible with appropriate training, mentorship, and thoughtful assembly of a dedicated multidisciplinary team.

The Development of Investigator-Initiated Clinical Trials in Surgical Oncology.

Investigator-initiated trials (IITs) are designed by principal investigators who identify important, unaddressed clinical gaps and opportunities to answer these questions through clinical trials. Surgical oncologists are poised to lead IITs due to their multidisciplinary clinical practice and substantial research background. The process of developing, organizing, and implementing IITs is multifaceted and involves important steps including (but not limited to) navigating regulatory requirements, obtaining funding, and meeting enrollment targets. Here, the authors explore the steps, methodology, and barriers of IIT development by surgical oncologists and highlight the importance of IITs in oncology.

Transcription yield of fully 2'-modified RNA can be increased by the addition of thermostabilizing mutations to T7 RNA polymerase mutants.

On average, mutations are deleterious to proteins. Mutations conferring new function to a protein often come at the expense of protein folding or stability, reducing overall activity. Over the years, a panel of T7 RNA polymerases have been designed or evolved to accept nucleotides with modified ribose moieties. These modified RNAs have proven useful, especially in vivo, but the transcriptional yields tend to be quite low. Here we show that mutations previously shown to increase the thermal tolerance of T7 RNA polymerase can increase the activity of mutants with expanded substrate range. The resulting polymerase mutants can be used to generate 2'-O-methyl modified RNA with yields much higher than enzymes currently employed.