Development of a 3D-Printed High Temperature Resin Cecal Fistula Implant for Long-Term and Minimally Invasive Access to the Gut Microbiome

Microbiota dysbiosis has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological changes affecting the gut-brain neural axis, mental health, and general well-being. However, current animal studies using oral gavage and gnotobiotic animals do not allow for non-invasive long-term access to gut microbiome. The purpose of the present study was to evaluate the feasibility of 3D-printed fistula implants through the body wall and into the cecum of rats to obtain long-term access to gut microbiome. Cecal fistulas were designed and 3D-printed using a high temperature resin (Formlabs; acrylic and methacrylic mixture). Nine male Sprague-Dawley rats underwent the fistula implantation. Food intake, body weight, and body fat were measured to determine the impact of fistula manipulation. Gut microbiome, vagal afferents in the hindbrain, and microglia activation were analyzed to determine if fistula implantation disrupted the gut-brain neural axis. We found that the procedure induced a transient decrease in microbial diversity in the gut that resolved within a few weeks. Fistula implantation had no impact on food intake, body weight, fat mass, or microglia activation. Our study shows that 3D-printed cecal fistula implantation is an effective procedure that allows long-term and minimally invasive access to gut microbiome.

Video-Endoscopic Mobilization of the Gracilis Muscle for Rectourinary Fistula Repair

<b><i>Introduction:</i></b> Transposition of the gracilis has been used in a large number of reconstructive procedures. Its advantage is its proximity to these defects and a good blood supply. Traditionally, the gracilis mobilization is performed by open surgery with one or more incisions. We describe our initial experience with the video-endoscopic mobilization of gracilis. <b><i>Method:</i></b> We described a retrospective review of all patients who underwent gracilis muscle mobilization for treatment of rectourethral fistula, performed by video-endoscopy, between March 2013 and September 2017, for treatment of rectourethral fistula. Also, our surgical technique is described in detail. <b><i>Results:</i></b> Three patients, with a mean age of 66.6 years, underwent the procedures. The mean time for mobilization of the gracilis was 107 min (range 60–145). There was no case of donor area infection, no change in the sensitivity of the medial aspect of the thigh or chronic pain. Conversion to open surgery was not necessary in any case. The hospital discharge occurred in average after 4 days. The bladder catheter was removed after 4 weeks after cystography was performed without evidence of leakage. One patient had a recurrence of the fistula. <b><i>Discussion:</i></b> The gracilis is an excellent choice of tissue to be interposed in reconstructive procedures of the perineal region, especially in the treatment of rectourinary fistulas. However, endoscopic harvest of the gracilis muscle has not yet found its way into everyday practice. The results in the treatment of rectourinary fistulas are excellent, with a success rate of 87.7%. Our rate of 67% is below, probably due to the small number of cases. In open surgery, complications are uncommon; however, approximately half of the patients expressed concern about the painful scar, which can be reduced by minimally invasive access. <b><i>Conclusion:</i></b> Video-endoscopic mobilization of gracilis muscle for the treatment of rectourethral fistula is feasible and safe. Studies comparing this technique with the conventional mobilization are required.

Importance of Laparoscopy to Solve the Diagnostic Dilemma of Abdominal Tuberculosis

Background: Diagnosis of abdominal tuberculosis as well as histopathological confirmation is difficult because of suboptimal access to the intraperitoneal pathology. Laparoscopy provides minimally invasive access to the peritoneal cavity and materials can be collected for confirmation of diagnosis. Objectives: To study the importance of laparoscopy as a tool for the diagnosis of abdominal tuberculosis and initiation of appropriate treatment without delay. Materials & Methods: In this study 25 patients with suspected abdominal tuberculosis were selected within the period of May, 2014 to October, 2014. Diagnostic laparoscopy performed on all patients with biopsy of tissue from accessible sites. Results: Diagnostic laparoscopy with biopsy confirmed the diagnosis in 24 (96%) patients, 23 of these patients (96%) had nodules at different site of abdominal cavity and 19 of these patients (76%) had ascites. In two cases there were nodules over liver surface; biopsy was taken also from both liver nodules. One nodule revealed fibrosis and another nodule revealed tuberculosis. Conclusion: Imaging and culture of ascitic fluid may fail to confirm or exclude abdominal tuberculosis in clinically suspected cases. Laparoscopy with peritoneal tissue biopsy provided rapid and correct diagnosis of abdominal tuberculosis and should be performed early in suspected cases. KYAMC Journal.2021;12(01): 14-17

The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

Showing a steadily increasing cancer-related mortality, the epidemiological evolution of hepatocellular carcinoma (HCC) is concerning. Numerous strategies have attempted to prognosticate HCC but their performance is modest; this is partially due to the heterogeneous biology of this cancer. Current clinical guidelines endorse classifications and scores that use clinical variables, such as the Barcelona Clinic Liver Cancer (BCLC) classification. These algorithms are unlikely to fully recapitulate the genomic complexity of HCC. Integrating molecular readouts on a patient-basis, following a precision-medicine perspective, might be an option to refine prognostic systems. The limited access to HCC tissue samples is an important limitation to these approaches but it could be partially circumvented by using liquid biopsy. This concept consists of the molecular analysis of products derived from a solid tumor and released into biological fluids, mostly into the bloodstream. It offers an easy and minimally-invasive access to DNA, RNA, extracellular vesicles and cells that can be analyzed with next-generation sequencing (NGS) technologies. This review aims to investigate the potential contributions of liquid biopsy in HCC prognostication. The results identified prognostic values for each of the components of liquid biopsy, suggesting that this technology may help refine HCC prognostication.

Manipulation of stimulus waveform and frequency permits targeted fiber activation during vagus nerve stimulation in 2 rodent species

Cervical vagus nerve stimulation (VNS) provides relatively minimally-invasive access to vagal fiber populations innervating most visceral organs, making it an attractive therapy candidate for various diseases. To maximize desired and minimize off-target effects, VNS should be delivered in a fiber-selective manner. We sought to select and optimize parameters that preferentially activate large, intermediate or small-size vagal fibers in 2 animal species, rats and mice. We manipulated stimulus waveform and frequency of short-duration (10-s) stimulus trains (SSTs) at different intensities and measured fiber-specific stimulus-elicited compound action potentials, corresponding cardiorespiratory vagally-mediated responses and neuronal expression of c-FOS in sensory and motor brainstem nuclei. We compiled selectivity indices from those measurements to determine optimal parameters for each fiber type. Large- and intermediate-size fibers are activated by SSTs of 30 Hz frequency, using short-square and long-square or quasi-trapezoidal pulses, respectively, at different optimal intensities for different animals. Small-size fibers are activated by SSTs of frequencies >8KH at high stimulus intensities; using a computational model of vagal fibers we find that sodium channels may underlie this effect. All findings were consistent between rats and mice. Our study provides a robust design and optimization framework for targeting vagal fiber populations for improved safety and efficacy of VNS therapies.