Plan quality assessment of modern radiosurgery technologies in the treatment of multiple brain metastases.

Stereotactic radiosurgery (SRS) of multiple brain metastases has evolved over the last 40 years allowing centres to treat an increasing number of brain metastases in a single treatment fraction. HyperArcTMplanning optimisation technique is one such development that streamlines the treatment of multiple metastases with a single isocentre. Several studies have investigated the plan quality of HyperArc compared to CyberKnife or Gamma Knife, however there are limited number of studies that include all three modalities. It is the aim of this study to provide an assessment of plan quality between the three SRS platforms across ten patients with multiple brain metastases ranging from three to eight metastases per patient. Strict planning workflows were established to avoid bias towards any particular treatment platform. Plan quality was assessed through dose to organs at risk, Paddick conformity index (PCI), gradient index (GI), global efficiency index (Gη) and dose to normal brain tissue. Results from this study found mean PCI observed across Gamma Knife plans was significantly lower than HyperArc and CyberKnife. HyperArc plans observed significantly shorter beam-on times which were 10 to 20 times faster than CyberKnife and Gamma Knife plans. Gamma Knife and CyberKnife were found to produce plans with significantly superior GI, global efficiency index and the volume of healthy brain receiving greater than 12 Gy (V12Gy) when compared to HyperArc plans. Lesion volume was seen to influence the relative difference in dose metrics between systems. The study revealed that all three treatment modalities produced high quality plans for the SRS treatment of multiple brain metastases, each with respective benefits and limitations.

The anesthetist as cardiologist: a case of heart block identified in the peripartum period.

We describe a case of undiagnosed heart block which was detected during the postpartum surgical repair of a vaginal tear, and the subsequent investigations that confirmed diagnosis of atrio-ventricular heart block.

Pregnancy after laparoscopic ventral mesh rectopexy: implications and outcomes.

AIM: Surgical management of rectal prolapse varies considerably. Most surgeons are reluctant to use ventral mesh rectopexy in young women until they have completed their family. The aim of the present study was to review outcomes of pregnancy following laparoscopic ventral mesh rectopexy from a tertiary referral centre over a 10-year period (2006-2016) and to review the impact on pelvic floor symptoms. METHOD: We undertook a retrospective review of a prospectively compiled database of patients who had undergone laparoscopic ventral rectopexy in a single centre over a 10-year period. Pelvic floor symptom scores (Vaizey for incontinence and Longo for obstructive defaecation) were collected at initial presentation (pre-intervention), post-intervention and after child birth. RESULTS: In all, 954 rectopexies were performed over this 10-year period. 225 (24%) patients were women and under 45 years of age (taken as an arbitrary cut-off for decreased likelihood of pregnancy). Eight (4%) of these patients became pregnant following rectopexy. The interval between rectopexy and delivery was 42 months (21-50). Six patients delivered live babies by elective lower segment caesarean section and two by spontaneous vaginal delivery. Six were first babies and two were second. No mesh related adverse outcome was reported. No difference in pelvic floor symptoms was demonstrated on comparison of post-rectopexy and post-delivery scores. CONCLUSION: This study provides the first description in the English language literature of safe delivery by elective lower segment caesarean section or spontaneous vaginal delivery following laparoscopic ventral mesh rectopexy. No adverse impact on pelvic floor related quality of life was detected.

Iatrogenic common bile duct injuries: Increasing complexity in the laparoscopic era: A prospective cohort study.

PURPOSE: Iatrogenic bile duct injury (BDI) is the most significant associated complication to laparoscopic cholecystectomy (LC). Little is known about the evolution of the pattern of BDI in the era of laparoscopy. The aim of the study is to assess the pattern of post-LC BDIs managed in a tertiary referral centre. METHODS: Post-LC BDI referred over two decades were studied. Demographic data, type of BDI (classified using the Strasberg System), clinical symptoms, diagnostic investigations, timing of referral, post-referral management and morbidity were analysed. The pattern of injury, associated vascular injuries rate and their management were compared over two time periods (1992-2004,2005-2014). RESULTS: 78 BDIs were referred. During the second time period Strasberg A injuries decreased from 14% to 0 and Strasberg E1increased from 4% to 23%, the rate of associated vascular injury was six time higher (3.6% versus 22.7%), more patients had an attempted repair at the index hospital (16% versus 35%) sand fewer patients could be managed without surgical intervention at the referral hospital (28% versus 4%). CONCLUSION: Complexity of referred BDIs and rate of associated vascular injuries have increased over time. These findings led to more patients managed requiring surgical intervention at the referral hospital.

Beware the ischiorectal abscess.

INTRODUCTION: Ischiorectal abscesses have been shown to form sinuses with various deep structures but continuity with the spinal canal is extremely rare. PRESENTATION OF CASE: A previously healthy sixty-five year old man presented emergently with rectal pain, weight loss and recurrent severe tension headaches. He had systemic sepsis and resultant coagulapathy (INR 3.4) which precluded investigation of neurological symptoms by lumbar puncture. MRI rectum demonstrated a well circumscribed fluid collection with direct connection to the spinal canal and containing meningeal tissue. It extended inferiorly to the right ischiorectal fossa and abutted the natal cleft. A radiological diagnosis of ischiorectal abscess which had become continuous with a previously existing anterior sacral myelomeningocoele (ASM) was made. He was treated with broad spectrum antibiotics and a neurosurgical opinion was sought. He remained clinically unwell (septic and coagulopathic) until the abscess fistulated through the perianal skin, draining pus mixed with clear fluid (likely CSF) at which point he improved systemically. DISCUSSION: Few general surgeons would be faced with acute management of complicated ASM. Paucity of literature made application of evidence based medicine difficult. In fit healthy patients surgery is the mainstay of treatment as myelomengingoceles do not regress spontaneously. Conservative management is associated with up to 30% mortality (largely due to bacterial meningitis). The patient in this case was adamant that he did not consent to definitive surgical intervention. CONCLUSION: This case highlights challenges encountered in the management of complicated ASM in a general hospital.

The detrimental impact of the implementation of the European working time directive (EWTD) on surgical senior house officer (SHO) operative experience.

BACKGROUND: Concerns have been voiced regarding the impact of the European Working Time Directive (EWTD) on surgical training. Following its introduction (August 2009) in Wexford General Hospital, Ireland Surgical Senior House Officers (SSHOs) are required to leave the hospital at 10 a.m. the morning after on-call duty. This study investigates the consequences of this practice on operative experience gained by six SSHOs in comparison to their predecessors. METHODS: A prospectively maintained database of surgical procedures was interrogated. Operative experience of SSHOs over a 5-month period (August-December 2009) was compared with that of colleagues 1 year earlier. The primary endpoint was overall operative volume of SSHOs. Subgroup analysis was performed of cases by primary operator versus assistant, intermediate versus minor procedures and by team. Comparison was made of operative volume between Group 1 (pre-EWTD) and Group 2 (post-EWTD). RESULTS: Operative volume for Group 1 (pre-EWTD) was 461 cases. Group 2 (post-EWTD) was involved in a total of 349 operations, showing a decrease of 24% (P=0.006). SSHOs in Group 1 (pre-EWTD) had been the primary operator in 109 cases compared to 87 in Group 2 (post-EWTD), demonstrating a reduction of 20% (P=0.06). Most worryingly, there was a reduction of 63% (P=0.04) in the intermediate cases performed as operating surgeon in Group 2 (post-EWTD). CONCLUSIONS: The present data set demonstrates a significant reduction in operative experience gained by SSHOs after local implementation of the EWTD. A major challenge facing Irish surgical training over the next decade is reduced operative exposure in the clinical setting.

Day of surgery admission for the elective surgical in-patient: successful implementation of the Elective Surgery Programme.

BACKGROUND AND AIMS: The aim of this prospective cross-sectional study was to determine the impact of (1) ring fencing in-patient general surgical beds and (2) introducing a pre-operative assessment clinic (PAC) on the day of surgery admission (DOSA) rate in a single Irish institution. The secondary aim was to analyse the impact of an increased rate of DOSA on cost efficiency and patient satisfaction. METHODS: An 18-month period was examined following ring-fencing of elective and emergency surgical beds. A PAC was established during the study period. Prospectively collected data pertaining to all surgical admissions were retrieved using patient administration system software (Powerterm Pro, Eircom Software) and a database of performance information from Irish Public Health Services (HealthStat). RESULTS: Ring-fencing and PAC establishment was associated with a significant increase in the overall DOSA rate from 56 to 85%, surpassing the national target rate of DOSA (75%). Data relating specifically to general surgery admissions mirrored this increase in DOSA rate from a median of 5 patients per month, before the advent of ring-fencing and PAC, to 42 patients per month (p < 0.0387). 100 patient surveys demonstrated high levels of satisfaction with DOSA, with a preference compared to admission one night pre-operatively. Cost analysis demonstrated overall savings of 340,370 Euro from this change in practice. CONCLUSION: The present study supports the practice of DOSA through the introduction of ring-fenced surgical beds and PAC. This has been shown to improve hospital resource utilisation and streamline surgical service provision in these economically challenging times.

Management of the acute appendix mass: a survey of surgical practice.

Management of the appendix mass is controversial with no consensus in the literature. Traditionally, the approach has been conservative followed by interval appendicectomy. A survey was distributed to 117 surgeons (100 consultants and 17 final year specialist registrars) to determine how the appendix mass is currently treated in Ireland. In total, 70 surgeons responded. 51 (73%) adopt a conservative approach initially. 48 (68%) favoured interval appendicectomy at six weeks after a period of successful conservative management. 34 (49%) gave risk of recurrence as the reason for performing interval appendicectomy and 16 (22%) would perform interval appendicectomy in order to obtain histological analysis to outrule caecal or appendiceal neoplasm. 44 (63%) opted for a laparoscopic rather than an open approach for interval appendicectomy. No consensus exists in Ireland for management of the appendix mass presenting acutely. The present series demonstrates a trend towards conservative approach initially followed by interval appendicectomy.

Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta isoform appears to play a predominant role in exerting non-genomic effects.

Differential protein abundance and function of UT-B urea transporters in human colon.

Facilitative UT-B urea transporters enable the passage of urea across cell membranes. Gastrointestinal urea transporters are thought to play a significant role in the urea nitrogen salvaging process that occurs between mammalian hosts and their gut bacteria. This study investigated the expression of UT-B urea transporters in different segments of human colon. Immunoblot analysis showed that human colon expressed a 35-kDa glycosylated UT-B protein in the colonic mucosa. The 35-kDa UT-B transporter was predominantly located in plasma membrane-enriched samples (P < 0.001; n = 6), and its expression was greater in the ascending colon compared with the descending colon (P < 0.01; n = 3). At the cellular level, UT-B transporters were located throughout colonocytes situated in the upper portion of the colonic crypts. Bidirectional trans-epithelial urea transport was significantly greater in the ascending colon than the descending colon (P < 0.05; n = 6). In addition, the facilitative urea transporter inhibitor 1,3,dimethylurea significantly reduced urea transport in the ascending colon (P < 0.05; n = 6) but had no effect in the descending colon (NS; n = 6). These results illustrate differential protein abundance of functional UT-B protein in different sections of the human colon, strongly correlating to regions that contain the largest populations of intestinal bacteria. This study suggests an important role for UT-B urea transporters in maintaining the symbiotic relationship between humans and their gut bacteria.

Cyclic AMP-mediated chloride secretion is induced by prostaglandin F2alpha in human isolated colon.

BACKGROUND AND PURPOSE: Prostaglandin F(2alpha) (PGF(2alpha)) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF(2alpha) on electrophysiological parameters in isolated human colonic mucosa. EXPERIMENTAL APPROACH: Ion transport was measured as changes in short-circuit current across human colonic epithelia mounted in Ussing chambers. Colonic crypts were isolated by calcium chelation and cyclic adenosine monophosphate (cAMP) was measured by ELISA. KEY RESULTS: PGF(2alpha) stimulated chloride secretion in a concentration-dependent manner with an EC(50) of 130 nM. The PGF(2alpha) induced increase in chloride secretion was inhibited by AL8810 (10 microM), a specific PGF(2alpha) receptor antagonist. In addition, PGF(2alpha) (1 microM) significantly increased levels of cAMP in isolated colonic crypts. CONCLUSIONS AND IMPLICATIONS: PGF(2alpha) stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states.

Estrogen and gastrointestinal malignancy.

The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.