Laparoscopic or open paediatric inguinal hernia repair - a systematic review.

INTRODUCTION: Inguinal hernia repair is the most common surgical procedure in paediatric patients. Despite limited evidence, an increasing number of surgeons suggest laparoscopic repair as an alternative to the gold standard of open repair. This review critically analysed post-operative clinical outcome on open versus laparoscopic inguinal hernia repair in paediatric patients. Before initiating the study, recurrence was defined as the primary outcome, and secondary outcomes were early post-operative pain, operation time and surgical site infections. METHODS: The PRISMA guidelines were followed. Using strict inclusion and exclusion criteria, the following databases were searched: MEDLINE, Cochrane Library, Web of Science and Embase (May 2019). Retrospective and uncontrolled studies were excluded. RESULTS: Five studies were identified, four randomised controlled trials (n = 272) and one controlled prospective study (n = 85) which included a total of 357 patients. Generally, the studies included few patients, were highly heterogenic and were overall of moderate quality. With a follow-up time ranging from three months to 14 years, there was no difference in recurrence rate after unilateral open (0-2%) versus unilateral laparoscopic (0-4%) or bilateral open versus bilateral laparoscopic repair (n = 281; p > 0.05 in all studies). There were no other significant differences in any of the outcomes, including post-operative pain (p > 0.05). CONCLUSIONS: There is no solid evidence that clinical outcome is improved after laparoscopic paediatric inguinal hernia repair compared with the gold standard.

Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia.

BACKGROUND: Investigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa. METHODS: Biopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/ß-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE2) signaling. Colonic mucosal contents of PGE2 and PGE2 metabolites were determined by use of ELISA. RESULTS: We found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls. CONCLUSION: Present study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p = 0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.

[Treatment for tongue-tie].

Ankyloglossia, or tongue-tie, is a congenital malformation, in which a short, lingual frenulum or a tight genioglossus muscle restricts tongue movement. In newborns, the reported prevalence is 2-11%. However, only 18% of newborns, in whom clinical findings suggest ankyloglossia, develop symptoms. Several randomised clinical trials report a significant reduction in maternal nipple pain after frenotomy. Frenotomy is a low-procedure surgery, but the benefits are sparsely documented. Parents should be presented with risk and benefits, before a frenotomy is offered.

Combined activity of COX-1 and COX-2 is increased in non-neoplastic colonic mucosa from colorectal neoplasia patients.

BACKGROUND: Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. METHODS: Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). RESULTS: Combined COX-1 and COX-2 activity was higher in CRN-pts, p = 0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. CONCLUSIONS: In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

Acetylcholine-related proteins in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia.

The pathogenesis of colorectal neoplasia (CRN) has been associated with altered non-neuronal acetylcholine (ACh) metabolism. The aim of this study was to characterize expression, function, and cellular location of ACh-related proteins in biopsies obtained from endoscopic normal-appearing sigmoid colon in patients with and without CRN. Messenger-RNA (mRNA) levels of 17 ACh-related proteins were quantified by rt-qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique. Finally, cellular localization of choline transporter-like proteins (CTLs) and butyryl-cholinesterase enzyme (BChE) was determined by immunohistochemistry. mRNA expression of CTL1 and CTL4 was increased in patients with CRN (P = 0.002 and P = 0.04, respectively). In functional experiments, baseline SCC was increased in CRN patients. ACh induced rapid biphasic changes in SCC. An initial decreasing phase was observed in the minority of CRN patients versus the majority of controls (25% vs 69%, respectively, P = 0.031). For the second increasing phase of SCC, data indicated ACh-activation of two receptors. For both parts of the biphasic response, the half maximal effective concentration and maximal responses showed no difference between patient groups. Immunohistochemistry demonstrated CTL1, 3 and 4 and BChE to be localized to colonic crypt cells. We conclude that CRN is associated with increased expression of CTL1 and CTL4, augmented basal prostaglandin-dependent secretion, and altered functional channel response to ACh in human endoscopic normal-appearing colonic mucosa. The immunohistochemical findings support CTL1, CTL3, CTL4, and BChE to be involved in non-neuronal mucosal ACh metabolism.

Phosphodiesterases in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia.

BACKGROUND: Intracellular signaling through cyclic nucleotides, both cyclic AMP and cyclic GMP, is altered in colorectal cancer. Accordingly, it is hypothesized that an underlying mechanism for colorectal neoplasia involves altered function of phosphodiesterases (PDEs), which affects cyclic nucleotide degradation. Here we present an approach to evaluate the function of selected cyclic nucleotide-PDEs in colonic endoscopic biopsies from non-neoplastic appearing mucosa. METHODS: Biopsies were obtained from patients with and without colorectal neoplasia. Activities of PDEs were characterized functionally by measurements of transepithelial ion transport and their expression and localization by employing real-time qPCR and immunohistochemistry. RESULTS: In functional studies PDE subtype-4 displayed lower activity in colorectal neoplasia patients (p = 0.006). Furthermore, real-time qPCR analysis showed overexpression of subtype PDE4B (p = 0.002) and subtype PDE5A (p = 0.02) in colorectal neoplasia patients. Finally, immunohistochemistry for 7 PDE isozymes demonstrated the presence of all 7 isozymes, albeit with weak reactions, and with no differences in localization between colorectal neoplasia and control patients. Of note, quantification of PDE subtype immunostaining revealed a lower amount of PDE3A (p = 0.04) and a higher amount of PDE4B (p = 0.02) in samples from colorectal neoplasia patients. CONCLUSION: In conclusion, functional data indicated lower activity of PDE4 subtypes while expressional and abundance data indicated a higher expression of PDE4B in patients with colorectal neoplasia. We suggest that cyclic nucleotide-PDE4B is overexpressed as a malfunctioning protein in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia. If a predisposition of reduced PDE4B activity in colonic mucosa from colorectal neoplasia patients is substantiated further, this subtype could be a potential novel early diagnostic risk marker and may even be a target for future medical preventive treatment of colorectal cancer.

Medical students as facilitators for laparoscopic simulator training.

BACKGROUND: Teaching basic clinical skills to student peers and residents by medical students has previously been shown effective. This study examines if medical students can facilitate laparoscopic procedural tasks to residents using a virtual reality simulator. METHODS: This was a retrospective study comparing 2 groups of gynecology residents. One group was instructed by 2 student facilitators, and a resident facilitator instructed the other group. Facilitators in both the groups were experienced in laparoscopic simulator training. The outcome measures were time and repetitions to complete a laparoscopic simulator training program. RESULTS: A total of 51 residents participated: 15 in the student-facilitated group and 36 in the resident-facilitated group after 18 and 7 residents dropped out, respectively. The student-facilitated group averaged 230 minutes, while the resident-facilitated group averaged 200 minutes (p = 0.724). To complete the final examination module, the student-facilitated group required 19.5 repetitions vs 39.2 in the resident-facilitated group (p = 0.007). CONCLUSION: Our findings suggest that students can be used as facilitators as an alternative to residents when practicing on a laparoscopic virtual reality simulator.