Morgan McCourt

Taurolidine Inhibits Tumor Cell Growth In Vitro and In Vivo

AbstractBackground: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD/K12/TRb) in vitro and in vivo. Methods: In the in vitro experiments, DHD/K12/TRb cells were incubated with 5, 10, 15, 25 μg/ml of Taurolidine. Cells incubated in culture medium alone were used as controls. Cell proliferation, cell viability, cell death, and cell apoptosis were measured using commercially available techniques. In the in vivo experiment, BD IX rats were randomized into two groups (n = 10/group). Group A (control) underwent laparotomy and instillation of DHD/K12/TRb tumor cells intraperitoneally followed by phosphate buffered saline (PBS). Group B received Taurolidine (100 mg/kg) instead of PBS. Animals were killed after 24 days and tumor burden assessed by counting the number of tumor nodules in the peritoneal cavity. Results: Incubation of the tumor cells with Taurolidine resulted in a 4-fold decrease in proliferation rates (25 ± 4% vs. 100 ± 28% for controls) and a 4-fold increase in cell necrosis as demonstrated by the increase in LDH release (403 ± 28% vs. 100 ± 26% for controls), at a Taurolidine concentration of 25 μg/ml. A dose-dependent decrease in cell viability was also observed. In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3 ± 1 nodules in Group B animals vs. 649 ± 101 nodules in Group A animals). Conclusions: Taurolidine inhibits the growth of a rat metastatic colorectal tumor cell line in vitro and in vivo and thus may have potential in the prevention of peritoneal metastases.

A Novel Therapeutic Strategy for Attenuating Neutrophil-mediated Lung Injury In Vivo

ObjectiveTo evaluate the effect of inhalation of aerosolized opsonized dead Escherichia coli on inflammatory pulmonary neutrophil (PMN) apoptosis, lung injury, and survival in a PMN-mediated lung injury model in vivo. Summary Background DataNeutrophils that have transmigrated into an inflammatory focus display increased functional capacity and delayed apoptosis, resulting in an increased capacity to injure normal host tissue. The authors have previously shown that E. coli induces PMN apoptosis in vitro. MethodsLung injury mediated by PMNs was established by aortic occlusion and reperfusion. Adult male Sprague-Dawley rats were randomized into four groups: sham ischemia–reperfusion (I/R) treated with intratracheal inhalation of aerosolized normal saline, I/R treated with aerosolized normal saline intratracheally, I/R treated with aerosolized opsonized dead E. coli intratracheally, and I/R treated with aerosolized opsonized dead E. coli and the caspase inhibitor zVAD-FMK intratracheally 5 minutes before reperfusion. Both systemic and bronchoalveolar lavage PMNs were isolated and apoptosis was quantified at 0, 6, 12, 18, and 24 hours. Lung injury parameters including wet/dry lung weight ratio, histology, myeloperoxidase activity, and protein content were also assessed. In addition, a survival study was performed, both in a prophylactic and in a therapeutic setting. ResultsAdministration of aerosolized dead E. coli before the reperfusion injury induced pulmonary PMN apoptosis and reversed the delayed apoptosis evident in the I/R plus normal saline group. There was also a significant improvement in lung injury parameters as well as in survival, both prophylactically as well as therapeutically. ConclusionsDirectly modulating PMN cell death represents a novel mechanism for attenuating PMN-mediated lung injury and may ultimately benefit the outcome in patients with adult respiratory distress syndrome.

Changes in Outcome and Management of Perforated Diverticulitis over a 10 Year Period

Abstract Introduction : Aggressive non-operative intervention and evolving surgical strategies have altered the treatment of perforated diverticulitis in the acute setting. These strategies have predominantly been implemented over the last decade. The aim of this study was to assess the impact of this on patient outcome during their index admission and subsequently. Methods : Consecutive patients admitted with acute diverticulitis between 1999 and 2010 were identified. Patient demographics, treatment strategies and outcomes were collected and analysed. Patients who had an episode of perforated diverticulitis during their index admission were followed. Results : 739 patients were admitted with acute diverticulitis. Of these, 115 (15.7%) had perforated diverticulitis. 53 (47.8%) underwent an intervention. There was a reduction in the mean age of patients admitted with acute diverticulitis of 8.9% over the study period (p = 0.002). There was a significant increase in the use of CT scanning pre-operatively (p < 0.001). ‘Non-resectional’ interventions have emerged in the form of laparoscopic lavage (n = 5) and percutaneous abscess drainage (n = 14). There was associated improved length of stay (p < 0.001). Conclusion : Outcomes for patients with perforated diverticulitis have improved, contributed to in part by an increased use of non-resectional management strategies.

Necrotising fasciitis secondary to intra-abdominal sepsis

Dear Editor: Necrotising fasciitis (NF) is a soft tissue infection where a microorganism or microorganisms spread along superficial and deep fascial planes. NF as a disease entity was first described by Hippocrates circa 500 BC, but it was not until 1952 that the term necrotising fasciitis was coined. The spread is facilitated by bacterial exotoxins such as streptococcal pyrogenic exotoxins (SPEs) A, B, C which are directly toxic. SPEs cause thrombosis of perforator vessels, resulting in tissue necrosis. SPEs also lead to the production of cytokines causing clinical signs, such as sepsis. Surface protein expression increases streptococcal adherence to tissues and also protects bacteria against phagocytosis by neutrophils. Herein, we report a case of NF caused by a perforated rectal carcinoma, and we review the literature to reveal other intra-abdominal causes of necrotising fasciitis. A 53-year-old gentleman was admitted in septic shock with a 7-day history of abdominal pain and limping. The patient had a background history of recent onset diarrhoea and weight loss. On examination, his abdomen was distended, with localised peritonitis in the left iliac fossa. There was a large area of erythema and palpable crepitus on the posterior aspect of his left thigh extending from the gluteal fold to the mid thigh. Proctoscopy revealed frank pus in the rectum with no signs of a perineal source of sepsis. Blood tests showed a white blood cell count of 12.2, and C-reactive protein was 269. He was initially fluid-resuscitated and treated with cefuroxime and metronidazole. Computed tomography (CT) scan of the abdomen and pelvis revealed extensive free air in the left upper thigh. Air fluid levels were also visualised. Within the pelvis, there was circumferential thickening of the sigmoid and rectal wall and extensive pre-rectal inflammatory change and enlarged retrocrural and para-aortic lymph nodes. A provisional diagnosis of necrotising fasciitis secondary to perforated diverticulitis or a perforated neoplasm was made, and the patient proceeded on an emergent basis to a laparoscopy, lavage, and defunctioning transverse colostomy. Ensuing exploration of the left thigh and pelvic floor revealed the offensive purulent material and findings were consistent with necrotising fasciitis. Extensive debridement of all involved tissues, including skin, fascia, and muscles including semi-membranosus, semi-tendinosus, and gracilis was carried out. A washout of wounds and redressing was carried out every 48 h. A split-thickness skin graft was used to close the wounds once the patient had improved clinically 3 weeks later. Microbiology confirmed the presence of Escherichia coli and mixed anaerobes from wound swabs. Histology later confirmed that the debrided tissue was consistent with necrotising fasciitis. Flexible sigmoidoscopy was performed, and a tumour was visualised at 5 cm. Biopsies taken showed evidence of rectal adenocarcinoma. The tumour was staged radiologically as T4N2Mx. Neoadjuvant chemoradiotherapy was used following complete wound healing. The chemotherapy regime included five cycles of 5-fluorouracil (5-FU). Twenty-five fractions of radiotherapy were used. The patient subsequently underwent an abdominoperineal resection. Histology confirmed D. P. O’Leary (*) : E. Myers :M. McCourt Department of Surgery, Cork University Hospital, Wilton, Cork, Ireland e-mail: Olearypeter83@hotmail.com