Clinical and financial impacts of introducing an endoscopic mucosal resection service for treatment of patients with large colonic polyps into a regional tertiary hospital.

Background and study aims Endoscopic mucosal resection (EMR) of large sessile or laterally spreading colonic lesions is a safe alternative to surgery. We assessed reductions in Surgical Resection (SR) rates and associated clinical and financial benefits following the introduction of an EMR service to a large regional center. Patients and methods Ongoing prospective intention-to-treat analysis of EMR was undertaken from time of service inception in 2009 to 2017. Retrospective data for SR of large sessile/laterally spreading colonic lesions were collected for the period 4 years before commencement of the EMR service (2005 - 2008) and 9 years after its introduction (2009 - 2017). Results From 2005 to 2008, 32 surgical procedures were performed for non-malignant colonic neoplasia (50 % male, median age 68 years, median Length of Stay (LoS) 10 days). Following the introduction of the EMR service, there was a 56 % reduction in the number of patients referred for surgery (32 surgical procedures, 47 % male, median age 70 years, median LoS 8.5 days). During this period, EMR was successfully performed in 183 patients with 216 lesions resected (60 % male, median age 68 years, median LoS 1 day). Compared to the SR group, the EMR cohort had a lower peri-procedural complication rate (7.7 % vs 54.7 %, P  < 0.0001), and shorter average LoS (1 vs 9 days, P  < 0.0001). A cost saving of AUD $ 19 543.5 was seen per lesion removed with EMR compared to SR. Conclusions The introduction of a dedicated EMR service into a large regional center as an alternative to SR can lead to a substantial decrease in unnecessary surgery with subsequent clinical and financial benefits.

Prospective population-based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity.

BACKGROUND AND AIM: We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. METHODS: Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. RESULTS: We report on the early outcomes (median 18 months, range 12-60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P < 0.05). Twenty-four percent of UC patients were hospitalized, most within the first 12 months. Intestinal resection rates were 13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates in UC were 2% and 13% at 1 and 5 years. High C-reactive protein (CRP) at diagnosis was associated with colectomy. CONCLUSIONS: A high rate of inflammatory disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD and UC were identified. In CD, ileal involvement and complex disease behavior are associated with a more severe disease course, while in UC a high CRP predicted this outcome.

Hepatitis C virus treatment in the 'real-world': how well do 'real' patients respond?

BACKGROUND: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. OBJECTIVES: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. METHODS: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. RESULTS: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). CONCLUSIONS: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials.

Calcitonin gene-related peptide stimulates mitosis in the tip of the rat gubernaculum in vitro and provides the chemotactic signals to control gubernacular migration during testicular descent.

BACKGROUND/AIMS: We investigated whether calcitonin gene-related peptide (CGRP) released from sensory genitofemoral nerve branches could stimulate rodent gubernacular growth and provide chemotactic signals for directing inguinoscrotal gubernaculum migration in vitro. MATERIALS AND METHODS: Neonatal rat gubernacula containing a developing cremaster sac (n = 60) were removed at days 0, 2, 4, 6, 8, and 10 (n = 10 per age; n = 5 per experimental group) and placed in organ culture for 24 hours with or without added CGRP (720 nmol/L). The gubernacula were stained for bromodeoxyuridine (BrdU) immunohistochemistry. Cells were counted (3 x 100 cells) in the mesenchymal tip of the gubernaculum to find the percentage of BrdU uptake. A further group of neonatal rat gubernacula (n = 21 per group) were placed in organ culture on an agar platform with 5 agarose beads soaked in either PBS or 10(-6) mol/L CGRP placed approximately 0.8 to 1 mm on each side of the tip of the cremaster sac. After 72 hours, the position of the gubernaculum was compared with its starting position and any deviation measured. RESULTS: Exogenous CGRP caused a significant increase in BrdU uptake in the tip of the gubernaculum in 0-day-old rats compared with control cultures. Two-way analysis of variance in the cellular proliferation pattern between gubernacula cultured +/- CGRP between 0 and 10 days showed a significant difference (P < .001). The cultures containing CGRP-impregnated beads caused significant (P < .01) deviation of the tip of the gubernaculum toward the beads, whereas the controls demonstrated no net movement of the tip. CONCLUSIONS: These studies demonstrate that mitosis in the tip of the rat gubernaculum is significantly increased in response to CGRP in vitro. Also, CGRP may provide chemotactic signals to control inguinoscrotal gubernacular migration in the rat.

The role of hepatocyte growth factor in the humoral regulation of inguinal hernia closure.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is proposed to indirectly cause inguinal hernia closure via hepatocyte growth factor (HGF). Studies have shown that CGRP and HGF cause processus vaginalis (PV) fusion in vitro. We localized the HGF receptor in the PV and tested whether CGRP was responsible for HGF release. METHOD: Hernial sacs collected from 20 children (15 males, 4 females, 1 XY female) undergoing inguinal hernia repair were immunohistochemically stained for HGF receptor (c-met). Parietal peritoneum was stained for comparison. Hernial sacs from another 16 children (12 males, 4 females), with each sac divided into 4, were cultured, with and without CGRP, for 24 and 48 hours. Hepatocyte growth factor content was then assayed in the culture medium (4/16 children) and tissue extracts (12/16 children), using enzyme-linked immunosorbent assay. Children were aged 1 month to 10 years. Data were analyzed using paired Student t tests. RESULTS: C-met localized to the PV epithelial surface in 17 of 20 hernial sacs and in the parietal peritoneum. Hepatocyte growth factor levels increased over time in 4 of 4 culture medium assays, with a significant difference in 1 of 4. Seven of 12 tissue extract assays had significant differences; however, 3 of 7 had decreased HGF levels. CONCLUSION: The presence of HGF receptors in the PV is consistent with a role for HGF in triggering epithelial-mesenchymal transformation during inguinal hernia closure. The presence of HGF receptors in the parietal peritoneum suggests that regulation of this process is complex. Enzyme-linked immunosorbent assay results indicate that, in a subset of patients, exogenous CGRP may be responsible for HGF elevation and potentially implicates deficient endogenous CGRP as one cause for inguinal hernia patency.

Testicular descent, cryptorchidism and inguinal hernia: the Melbourne perspective.

Cryptorchidism is the commonest congenital genitourinary anomaly in males and results when the testis does not descend into its normal intrascrotal position during development. In full-term infants, the incidence is approximately 3% at birth. Cryptorchidism results in several abnormalities, including attenuated spermatogenesis, infertility and a greater risk of malignancy. The normal mechanism of testicular descent appears to be multi-staged, with various anatomical factors and hormonal influences, but the exact process is still unclear. In this article we review the current theories of normal testicular descent, with a focus on the hormones and anatomical factors, and current treatments for undescended testis.

The gubernaculum in testicular descent and cryptorchidism.

The gubernaculum plays an essential role in the complex mechanism of testicular descent and inguinal hernia closure. Understanding this complex developmental process is gradually allowing us insight into how to regulate normal descent and also treat maldescended testes.