Endoscopic stricturotomy with pulsed argon plasma and balloon dilation for refractory benign colorectal strictures: a case series.

Benign strictures of the colon and rectum affect a sizable portion of patients who have an underlying inflammatory disease or who have undergone recent surgery. Etiologies include inflammatory bowel disease (IBD), post-surgical ischemia, anastomotic strictures, non-steroidal anti-inflammatory drugs (NSAIDs), and complicated diverticulitis. Refractory colorectal strictures are very difficult to manage and often require repeated and different treatment options. We report a novel technique using argon plasma coagulation (APC) with endoscopic balloon dilation (EBD) as a safe and effective treatment modality for refractory benign colorectal strictures. Four patients with symptomatic benign colorectal strictures were referred for endoscopic treatment. In all cases (two females and two males; average age 62 years), the endoscopic and radiographic assessment showed significant strictures (diameter, 4-13 mm). The stricture was secondary to Crohn's disease in one patient and anastomotic strictures in the other three patients. Endoscopic stricturotomy through fulguration and tissue destruction using argon plasma at 1.5 liters/minute, effect 2, and 40 watts was performed, followed by EBD. All patients were treated by one advanced endoscopist. The primary outcomes were the efficiency and safety of endoscopic stricturotomy with pulsed argon plasma and balloon dilation. The resolution of stricture was achieved in all patients. No complications were reported. We believe that combined APC with EBD is a safe and effective technique in the treatment of benign colonic stricture.

Impact of the Affordable Care Act Medicaid Expansion on Reimbursement in Emergency General Surgery.

BACKGROUND: Kentucky had one of the nation's largest increases in insurance coverage with the Affordable Care Act's (ACA) Medicaid expansion, quadrupling the proportion of Kentuckians with insurance coverage. This study compares reimbursement rates for surgical procedures performed by emergency general surgery (EGS) services at the University of Kentucky (UK) before and after Medicaid expansion in January 2014. METHODS: This IRB-approved, single-institution study retrospectively evaluated all patients undergoing surgical treatment by our EGS team from 1/1/2011 to 12/31/2016. We queried operative records for the most frequently performed procedures by the EGS service. We reviewed patient electronic medical records and hospital financial records to identify insurance status, diagnosis codes, and expected hospital reimbursements, based on UK Hospital's procedure/payer accounting models. RESULTS: Four thousand six hundred ninety-three patient procedures met inclusion criteria; 46.5% of these came before ACA expansion and 53.5% after expansion. The most frequent procedures performed were incision and drainage, laparoscopic appendectomy, laparoscopic cholecystectomy, and exploratory laparotomy. After ACA expansion, the proportion of patients with Medicaid nearly doubled (19.8% vs. 35.6%, p < 0.001). Concomitantly, there was a more than fivefold decrease in the uninsured patient population after expansion (23.3% vs. 4.6%, p < 0.001), and mean hospital reimbursement increased for laparoscopic appendectomy (13.7%, p < 0.001), laparoscopic cholecystectomy (50.7%, p < 0.001), and incision and drainage (70.2%, p < 0.001). CONCLUSION: After ACA expansion, there was a sustained decrease in proportion of uninsured patients and a concomitant sustained increase in proportion of patients with access to Medicaid services in the EGS operative population, leading to increased mean hospital reimbursements and decreased patient financial burden.

Rural-Urban Differences in Breast Reconstruction Utilization Following Oncologic Resection.

BACKGROUND: Breast reconstruction (BR) is the reconstructive surgical technique that focuses on restoring normal form and function to the breast following oncologic resection. The goal of this study was to determine if BR disparities exist among rural female patients in Kentucky. METHODS: A retrospective (2006-2015), population-based cohort study was conducted on breast cancer patients (stages I-III) treated with mastectomy with or without BR. We used 2013 Beale codes to stratify patients according to geographic status. Chi-square tests were used to examine the association of BR along the rural-urban continuum. A multivariate logistic regression model controlling for patient, disease, and treatment factors was used to predict BR. The likelihood of BR was reported in odds ratios (OR) using a 95% confidence interval (CI). RESULTS: Overall, 10,032 patients met study criteria. Of those, 2,159 (21.5%) underwent BR. The rate of BR among urban, near-metro, and rural patients was 31.1%, 20.4%, and 13.4%, respectively (P < .001). Multivariate analysis revealed that women from near metro (OR 0.54, CI: 0.47-0.61; P < .001) and rural areas (OR 0.36, CI: 0.31-0.41; P < .001) were less likely to undergo BR than women from urban areas. CONCLUSION: Although BR benefits are well documented, women from rural Kentucky undergo BR at lower rates and are less likely to receive BR than their urban counterparts. Efforts should seek to promote equitable access to BR for all patients, including those from rural areas.

Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor-intact or heterozygous skin.

Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss-of-function MC1R allele are also melanoma-prone. Using the K14-Scf C57BL/6J animal model whose skin is characterized by lifelong retention of interfollicular epidermal melanocytes like that of the human, we studied pigmentary, UV responses, and DNA repair capacity in the skin of variant Mc1r background. Topical application of forskolin, a skin-permeable pharmacologic activator of cAMP induction to mimic native Mc1r signaling, increased epidermal eumelanin levels, increased the capacity of Mc1r-heterozygous skin to resist UV-mediated inflammation, and enhanced the skin's ability to clear UV photolesions from DNA. Interestingly, topical cAMP induction also promoted melanin accumulation, UV resistance, and accelerated clearance in Mc1r fully intact skin. Together, our findings suggest that heterozygous Mc1r loss is associated with an intermediately melanized and DNA repair-proficient epidermal phenotype and that topical cAMP induction enhances UV resistance in Mc1r-heterozygous or Mc1r-wild-type individuals by increasing eumelanin deposition and by improving nucleotide excision repair.

cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.

Sirtuin 1-mediated deacetylation of XPA DNA repair protein enhances its interaction with ATR protein and promotes cAMP-induced DNA repair of UV damage.

Blunted melanocortin 1 receptor (MC1R) signaling promotes melanocyte genomic instability in part by attenuating cAMP-mediated DNA repair responses, particularly nucleotide excision repair (NER), which recognizes and clears mutagenic photodamage. cAMP-enhanced NER is mediated by interactions between the ataxia telangiectasia-mutated and Rad3-related (ATR) and xeroderma pigmentosum complementation group A (XPA) proteins. We now report a critical role for sirtuin 1 (SIRT1) in regulating ATR-mediated phosphorylation of XPA. SIRT1 deacetylates XPA at residues Lys-63, Lys-67, and Lys-215 to promote interactions with ATR. Mutant XPA containing acetylation mimetics at residues Lys-63, Lys-67, and Lys-215 exhibit blunted UV-dependent ATR-XPA interactions even in the presence of cAMP signals. ATR-mediated phosphorylation of XPA on Ser-196 enhances cAMP-mediated optimization of NER and is promoted by SIRT1-mediated deacetylation of XPA on Lys-63, Lys-67, and Lys-215. Interference with ATR-mediated XPA phosphorylation at Ser-196 by persistent acetylation of XPA at Lys-63, Lys-67, and Lys-215 delays repair of UV-induced DNA damage and attenuates cAMP-enhanced NER. Our study identifies a regulatory ATR-SIRT1-XPA axis in cAMP-mediated regulation melanocyte genomic stability, involving SIRT1-mediated deacetylation (Lys-63, Lys-67, and Lys-215) and ATR-dependent phosphorylation (Ser-196) post-translational modifications of the core NER factor XPA.