The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

AIM: Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. METHOD: This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. RESULTS: Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. CONCLUSION: Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

Case Report: Thrombotic-Thrombocytopenic Purpura Following Ipilimumab and Nivolumab Combination Immunotherapy for Metastatic Melanoma.

A man in his early 50s presented with small bowel obstruction, requiring emergency laparoscopic small bowel resection for the metastatic melanoma of the jejunum with no identifiable primary lesion. One week after his first treatment with ipilimumab and nivolumab, he presented with diffuse abdominal pain, constipation, and fatigue. A computerized tomography scan did not identify a cause for his symptoms. This was rapidly followed by thrombocytopenia on day 11 and then anemia. He commenced intravenous corticosteroids for a suspected diagnosis of immune-related thrombocytopenia. On day 15, a generalized onset motor seizure occurred, and despite plasmapheresis later that day, the patient died from fatal immune-related thrombotic thrombocytopenic purpura (TTP). This was confirmed with suppressed ADAMTS13 (<5%) testing on day 14. Immune-related TTP is a rare and, in this case, fatal immune- related adverse event. Further studies are required to identify additional immunosuppressive management for immune-related TTP.

Prophylactic negative wound therapy in laparotomy wounds (PROPEL trial): randomized controlled trial.

BACKGROUND: Superficial surgical site infections are a common post-operative complication. They also place a considerable financial burden on healthcare. The use of prophylactic negative pressure wound therapy has been advocated to reduce wound infection rates. However, there is debate around its routine use. The purpose of this trial is to determine if prophylactic negative pressure wound therapy reduces post-operative wound complications in patients undergoing laparotomy. METHODS/DESIGN: This multi-centre randomised controlled trial will compare standard surgical dressings (control) to two competing negative pressure wound therapy dressings (Prevena™ and PICO™). All patients will be over 18 years, who are undergoing an emergency or elective laparotomy. It is intended to enrol a total of 271 patients for the trial. DISCUSSION: The PROPEL trial is a multi-centre randomised controlled trial of patients undergoing laparotomy. The comparison of standard treatment to two commercially available NPWT will help provide consensus on the routine management of laparotomy wounds. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT number NCT03871023).

An evaluation of the quality and content of web-based stoma information.

AIM: Although the internet is commonly the first port of call for medical information, it provides unregulated data of variable quality. We aimed to evaluate commonly accessed web-based information on intestinal stomas using validated and novel scoring systems. METHOD: The keywords 'stoma', 'colostomy', 'ileostomy' and 'bowel bag' were entered into the most commonly used internet search engines (Google, Bing and Yahoo). The first ten websites from each search were analysed using the validated Journal of the American Medical Association (JAMA) benchmark criteria and DISCERN scoring systems. A novel stoma-specific score was devised and applied. RESULTS: Forty-three unique websites were identified. The majority (49%) were from nonprofit or governmental agencies and 9% were from commercial entities. The mean total DISCERN score for all websites was 42.4 ± 10.2 (maximum possible score = 75). The mean JAMA and stoma-specific scores were 2.1 ± 1.0 (maximum possible score = 4) and 12.9 ± 6.1 (maximum possible score = 27). The lowest JAMA scores were in the category of attribution, with 70% of websites lacking references for the information provided. A total of 88% displayed disclosure/paid advertiser information. Surgery was described in 67%. An image or diagram was provided in 58% and in 72% a stoma therapist/nurse was mentioned. Information on when to seek medical help was provided in 51%. CONCLUSION: Web-based information on stomas is of variable content and quality. Authorship and information sources are often unclear. Only half provided information on when to seek medical help for complications including high output and dehydration. These findings should be highlighted to patients who utilize the internet to obtain information on stomas.

Self-expanding metal stent insertion by colorectal surgeons in the management of obstructing colorectal cancers: a 6-year experience.

BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients presenting with colorectal cancer as an acute large bowel obstruction may obviate emergency surgery, potentially effectively palliating incurable cancers and acting as a bridge to surgery in patients with operable tumours. We present our experience with stenting for malignant acute large bowel obstruction over a 6-year period (2006-2011). METHODS: A prospectively compiled colorectal cancer database was reviewed to identify all patients presenting to our unit with malignant acute large bowel obstruction who had stenting carried out to achieve colonic decompression. All 44 procedures were performed by colorectal surgeons using a combined endoscopic and fluoroscopic technique. RESULTS: Overall, successful decompression was achieved in 42 patients by SEMS insertion (95.5%). Technical and clinical success was achieved in all 30 patients undergoing stenting as a palliative measure (100%). There was no clinical perforation in any of the 44 patients. CONCLUSIONS: SEMSs insertion is a safe and effective technique for colonic decompression in the setting of acute malignant large bowel obstruction as either a palliative measure or as a bridge to subsequent resection.

Internal hernia following total gastrectomy with Roux-en-Y reconstruction.

Internal herniation is a well-described complication after a gastric bypass, particularly when performed laparoscopically, although it is rarely described following a total gastrectomy. A 55-year-old lady presented with a 24-hour history of vomiting and rigors 10 months after a radical total gastrectomy with Roux-en-Y reconstruction for a gastric adenocarcinoma. Computed tomography (CT) showed a complete small bowel obstruction and a mesenteric swirl sign, indicating a possible internal hernia. The entire small bowel was found at laparotomy to have migrated through the mesenteric defect adjacent to the site of the previous jejunojejunostomy and was dark purple and aperistaltic. The small bowel was reduced through the defect. At a second laparotomy, the small bowel looked healthy and the defect was repaired. Postoperative recovery was unremarkable. Of numerous signs described, the mesenteric swirl sign is considered the best indicator on CT of an internal hernia following Roux-en-Y reconstruction in gastric bypass surgery. A swirl sign on CT in a patient with abdominal pain should always raise the suspicion of an internal hernia.

Clinical, molecular and epidemiological description of a cluster of community-associated methicillin-resistant Staphylococcus aureus isolates from injecting drug users with bacteraemia.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an increasing problem, predominantly in previously healthy individuals including notable risk groups such as the homeless, those who play close-contact sports, military personnel, men who have sex with men (MSM) and injecting drug users (IDUs). Over a 5-month period, four IDUs were admitted to Addenbrooke's Hospital, Cambridge, UK, with MRSA bacteraemia. All four patients presented with complex clinical features, with more than one focus of infection, and were linked epidemiologically. The atypical antibiogram of the MRSA isolates (ciprofloxacin-susceptible) prompted further characterization, both phenotypically (antibiotic resistance typing; phage typing) and genotypically (detection of toxin genes by PCR; pulsed-field gel electrophoresis (PFGE); Staphylococcal chromosome cassette (SCC) mec typing; multi-locus sequence typing (MLST)). All four isolates had similar antibiograms, were Panton-Valentine Leucocidin (PVL) toxin gene-negative, harboured SCCmec type IV and were closely related as shown by phage typing and PFGE. These isolates were representatives of a community-associated clone, ST1-MRSA-IV, known to be circulating in IDUs in the UK since 2001. This paper presents a detailed description of the clinical, microbiological and epidemiological features of a series of CA-MRSA bacteraemias in IDUs in the UK.

Growth arrest-specific gene 6 expression in human breast cancer.

Growth arrest-specific gene 6 (Gas6), identified in 1995, acts as the ligand to the Axl/Tyro3 family of tyrosine kinase receptors and exerts mitogenic activity when bound to these receptors. Overexpression of the Axl/Tyro3 receptor family has been found in breast, ovarian and lung tumours. Gas6 is upregulated 23-fold by progesterone acting through the progesterone receptor B (PRB). Recently, Gas6 has been shown to be a target for overexpression and amplification in breast cancer. Quantitative real-time PCR analysis was used to determine the levels of Gas6 mRNA expression in 49 primary breast carcinomas. Expression of PRB protein was evaluated immunohistochemically with a commercially available PRB antibody. The results showed a positive association between PRB protein and Gas6 mRNA levels (P=0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity (P=0.0002), younger age at diagnosis (P=0.04), smaller size of tumours (P=0.02), low Nottingham prognostic index scores (P=0.03) and low nuclear morphology (P=0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue.

Characterisation of Exiguobacterium aurantiacum isolates from blood cultures of six patients.

Exiguobacterium spp. are alkaliphilic, halotolerant, non-spore-forming Gram-positive bacilli, hitherto uncharacterized from human infections. Six isolates of Exiguobacterium aurantiacum were obtained from patients with bacteraemia, three of whom had myeloma. All isolates formed orange-yellow pigmented colonies on blood agar, were catalase- and DNase-positive, and grew on nutrient agar at pH 10 and in the presence of NaCl 6% w/v. The six isolates were susceptible to all antimicrobial agents tested and were uniform in their fatty acid and mass spectrum profiles.

Knee arthrodesis with the Wichita Fusion Nail: an outcome comparison.

UNLABELLED: The Wichita Fusion Nail (WFN) is a knee arthrodesis stabilization system that employs compression via an intramedullary rod. It was designed for use in the salvage of the irretrievably failed total knee arthroplasty and other severe knee pathologies. Questionnaires covering the fusion success rate, fusion time, and complication rate were obtained from 33 surgeons who were among the first to use the device. Data from these questionnaires were analyzed to determine if the rate of successful fusion was close to 100%, which was the primary hypothesis of this study. The average time required to achieve fusion and the rate of complications were also calculated and compared to similar results available in the literature. The results for 44 selected patients were included and it was determined that all achieved fusion for a success rate of 100%. This compared favorably with reported success rates in the range of 54% to 96%. The average fusion time was 15.5 weeks. Complications included: six delayed unions, three deep infections, and two periimplant fractures for a major complications rate of 20.4%. Both the fusion times and complication rate compared favorably with other reported results. Surgeons using the device for the first time had outcomes equal to those of more experienced users. Our results demonstrated that a rate of successful arthrodesis close to 100% could be consistently achieved with the WFN. Overall, the WFN facilitated an improved outcome for a previously difficult procedure. LEVEL OF EVIDENCE: Therapeutic study, level IV (case series). See the Guidelines for Authors for a complete description of level of evidence.

Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord.

Proton MR spectroscopy ((1)H-MRS) provides indices of neuronal damage in the central nervous system (CNS); however, it has not been extensively applied in the spinal cord. This work describes an optimized proton spectroscopy protocol for examination of the human cervical spinal cord. B(0) field mapping of the cord revealed periodic inhomogeneities due to susceptibility differences with surrounding tissue. By combining field maps and experimental data, we found that the optimum voxel size was 9 x 7 x 35 mm(3) placed with the inferior end of the voxel above vertebral body C2. Metabolite concentrations were determined in the cervical cord in six healthy controls by short-echo point-resolved spectroscopy (PRESS) volume localization. The results were compared with metabolite concentrations in the brainstem, cerebellum, and cortex in the same individuals. The concentrations in the cervical cord were as follows: N-acetyl-aspartate (NAA) 17.3 +/- 0.5, creatine (Cr) 9.5 +/- 0.9, and choline 2.7 +/- 0.5 mmol/l. The NAA concentration was significantly lower in the cord than in the brainstem (Mann-Whitney, P < 0.025), and higher than in the cortex (P < 0.005) and cerebellum (P < 0.005). Cr was significantly lower in the cord than in the cerebellum (P < 0.05). There were no significant differences between Cr concentrations in the spinal cord compared to the cortex and brainstem.

Disseminated Aspergillus terreus infection arising from cutaneous inoculation treated with caspofungin.

A case of disseminated Aspergillus terreus infection in a patient with prolonged neutropenia after stem cell transplant for myeloma is reported. The isolate was resistant to amphotericin B in vitro, and the patient was successfully managed with surgical debridement and the recently licensed antifungal agent caspofungin. There are many challenges associated with treating invasive aspergillosis, particularly that due to A. terreus, and the early use of caspofungin should be considered.