Comparison Between Open and Laparoscopic Repair of Perforated Peptic Ulcer Disease

Background  The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet has been established, although it is not routinely practiced. This prospective study compared laparoscopic and open repair of perforated peptic ulcer disease. We evaluated whether the early results from laparoscopic repair resulted in improved patient outcome compared with conventional open repair. Methods  All patients who underwent repair of perforated peptic ulcer disease during a 12-month period in our unit were included in the study. The primary end points that were evaluated were total operative time, nasogastric tube utilisation, intravenous fluid requirement, total time of urinary catheter and abdominal drainage usage, time taken to return to normal diet, intravenous/intramuscular opiate use, time to full mobilization, and total in-patient hospital stay. Results  Thirty-three patients underwent surgical repair of perforated peptic ulcer disease (19 laparoscopic repairs and 14 open repairs; mean age, 54.2 (range, 32–82) years). There was no increase in total operative time in patients who had undergone laparoscopic repair (mean: 61 minutes laparoscopic versus 57 minutes open). There was significantly less requirement for intravenous/intramuscular opiate analgesia in patients who had undergone laparoscopic repair (mean time to oral analgesia: 1.2 days laparoscopic versus 3.8 days open). In addition there was a significant decrease in the time that the nasogastric tube (mean: 2.1 days laparoscopic versus 3.1 days open), urinary catheter (mean: 2.3 days laparoscopic versus 3.7 days open) and abdominal drain (mean: 2.2 days laparoscopic versus 3.8 days open) were required during the postoperative period. Patients who had undergone laparoscopic repair required less intravenous fluids (mean: 1.4 days laparoscopic versus 3.1 days open) and returned to normal diet (mean: 2.3 days laparoscopic versus 4.8 days open) and full mobilization significantly earlier than those who had undergone open repair (mean: 2.3 days laparoscopic versus 3.3 days open). In addition, patients who had undergone laparoscopic repair required a shorter in-patient hospital stay (mean: 3.1 days laparoscopic versus 4.3 days open). Conclusions  Laparoscopic repair is a viable and safe surgical option for patients with perforated peptic ulcer disease and should be considered for all patients, providing that the necessary expertise is available.     

Alzheimer's disease and smoking: bias in cohort studies

The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender-specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results.     

Psychological distress among adult cancer survivors: importance of survivorship care plan

Purpose

The goal of our study was to better understand the importance of adult cancer survivors (ACS) receiving Survivorship Care Plans (SCP) especially for their psychological well-being. We hypothesize that the receipt of SCP would decrease the likelihood of symptoms of current depression (SCD) in this population.

Methods

We tested our hypothesis by using a representative sample of ACS, more than 1 year from cancer diagnosis, who responded to the 2010 BRFSS survey. We used follow-up care instructions (FCI) and treatment summaries (TS) as a marker of SCP. Weighted multivariable logistic regression models were used to investigate the association between FCI and TS (individually and in combination) and SCD, among short-term (≤5 years from cancer diagnosis) and long-term (>5 years from cancer diagnosis) ACS.

Results

Out of 3191 final study participants, 32.8 % were short-term, and 67.2 % were long-term ACS. Among short-term ACS, the adjusted odds of SCD were 3 times higher (adjusted odds ratio (AOR) 3.14 [95%CI 1.29–7.65]) for those who did not receive TS + FCI than for those who received them both. Among long-term ACS, the adjusted odds of SCD were more than twice higher (AOR 2.18 [95%CI 1.14–4.19]) for those who received FCI and no TS compared to those who received them both.

Conclusion

The present study results emphasize the importance of ACS receiving SCP. Adult cancer survivors may highly benefit from the receipt of SCP not only short-term but also long-term for their overall psychological well-being.

     

Concomitant angiotensin AT1 receptor antagonism and neprilysin inhibition produces omapatrilat-like antihypertensive effects without promoting tracheal plasma extravasation in the rat

Dual inhibition of angiotensin-converting enzyme (ACE) and neprilysin (NEP) by drugs such as omapatrilat produces superior antihypertensive efficacy but cause high incidence of angioedema. We examined whether dual inhibition of angiotensin AT1 receptor (ARB) and NEP (ARB-NEPI, valsartan-candoxatril) provides similar efficacy to omapatrilat without the risk of angioedema. Activity of test compounds at the targets was assayed using fluorescence-based enzyme assays (ACE, NEP, aminopeptidase P) or competition binding assays (AT1). Target engagement in vivo (ACE, AT1, and NEP) was quantified by measuring inhibition of angiotensin-pressor responses and potentiation of atrial natriuretic peptide-induced urinary cyclic guanosine monophosphate (cGMP) output in rats. Tracheal plasma extravasation (TPE) was used as a surrogate to assess propensity of compounds to promote upper airway angioedema. Antihypertensive efficacy in renin-dependent and -independent states was measured in spontaneously hypertensive rats and deoxycorticosterone acetate salt hypertensive rats, respectively. Administration of omapatrilat and coadministration of valsartan and candoxatril blocked angiotensin induced vasopressor responses and potentiated atrial natriuretic peptide-induced increase in urinary cGMP output. In spontaneously hypertensive rats, valsartan, omapatrilat, and valsartan-candoxatril combination all produced reduction in blood pressure to a similar extent, whereas candoxatril was ineffective. In deoxycorticosterone acetate rats, omapatrilat, candoxatril, and valsartan-candoxatril combination but not valsartan produced reduction in blood pressure. Antihypertensive doses of omapatrilat produced robust increases in TPE; by contrast, valsartan, candoxatril, or their combination did not increase TPE. Pretreatment with icatibant, a bradykinin B2 antagonist, abolished omapatrilat-induced TPE but not its antihypertensive effects. On the background of NEP inhibition, suppression of the renin-angiotensin system through ARB and ACE inhibition shows a similar antihypertensive efficacy but exerts differential effects on bradykinin metabolism and TPE indicative of reduced risk of angioedema. Thus, dual AT1 receptor blockade and NEP inhibition is potentially an attractive approach to retain the excellent antihypertensive effects of omapatrilat but with a superior safety profile.     

Long-term outcome after biologic versus mechanical aortic valve replacement in 841 patients

OBJECTIVE: The purpose of this study was to optimize selection criteria of biologic versus mechanical valve prostheses for aortic valve replacement. METHODS: Retrospective analysis was performed for 841 patients undergoing isolated, first-time aortic valve replacement with Carpentier-Edwards (n = 429) or St Jude Medical (n = 412) prostheses. RESULTS: Patients with Carpentier-Edwards and St Jude Medical valves had similar characteristics. Ten-year survival was similar in each group (Carpentier-Edwards 54% 3% versus St Jude Medical 50% 6%; P =.4). Independent predictors of worse survival were older age, renal or lung disease, ejection fraction less than 40%, diabetes, and coronary disease. Carpentier-Edwards versus St Jude Medical prostheses did not affect survival (P =.4). Independent predictors of aortic valve reoperation were younger age and Carpentier-Edwards prosthesis. The linearized rates of thromboembolism were similar, but the linearized rate of hemorrhage was lower with Carpentier-Edwards prostheses (P <.01). Perivalvular leak within 6 months of operation was more likely with St Jude Medical than with Carpentier-Edwards prostheses (P =.02). Estimated 10-year survival free from valve-related morbidity was better for the St Jude Medical valve in patients aged less than 65 years and was better for the Carpentier-Edwards valve in patients aged more than 65 years. Patients with renal disease, lung disease (in patients more than age 60 years), ejection fraction less than 40%, or coronary disease had a life expectancy of less than 10 years. CONCLUSIONS: For first-time, isolated aortic valve replacement, mechanical prostheses should be considered in patients under age 65 years with a life expectancy of at least 10 years. Bioprostheses should be considered in patients over age 65 years or with lung disease (in patients over age 60 years), renal disease, coronary disease, ejection fraction less than 40%, or a life expectancy less than 10 years.     

Bovine and porcine transscleral solute transport: influence of lipophilicity and the Choroid-Bruch's layer

PURPOSE: To determine the influence of the choroid-Bruch's layer and solute lipophilicity on in vitro transscleral drug permeability in bovine and porcine eyes. METHODS: The in vitro permeability of two VEGF inhibitory drugs, budesonide and celecoxib, which are lipophilic and neutral at physiologic pH, and of three marker solutes, 3H-mannitol (hydrophilic, neutral), sodium fluorescein (hydrophilic, anionic), and rhodamine 6G (lipophilic, cationic), were determined across freshly excised scleras, with or without the underlying choroid-Bruch's layer. Select studies were performed using porcine sclera with and without choroid-Bruch's layer. Neural retina was removed by exposure of the eyecup to isotonic buffer and wherever required, the retinal pigment epithelial (RPE) layer of the preparation was disrupted and removed by exposure to hypertonic buffer. Because of the poor solubility of celecoxib and budesonide, permeability studies were conducted with 5% wt/vol of hydroxypropyl-beta-cyclodextrin (HPbetaCD). For other solutes, permeability studies were conducted, with and without HPbetaCD. Partitioning of the solutes into bovine sclera and choroid-Bruch's layer was also determined. RESULTS: The calculated log (distribution coefficient) values were -2.89, -0.68, 2.18, 3.12, and 4.02 for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G, respectively. Removal of RPE was confirmed by transmission electron microscopy and differences in the transport of mannitol. The order of the permeability coefficients (Papp) across sclera and sclera-choroid-Bruch's layers in bovine and porcine models was 3H-mannitol > fluorescein > budesonide > celecoxib > rhodamine 6G, with HPbetaCD, and 3H-mannitol > fluorescein > rhodamine 6G, without HPbetaCD. The presence of choroid-Bruch's layer reduced the bovine scleral permeability by 2-, 8-, 16-, 36-, and 50-fold and porcine tissue permeability by 2-, 7-, 15-, 33-, and 40-fold, respectively, for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G. The partition coefficients measured in bovine tissues correlated positively with the log (distribution coefficient) and exhibited a trend opposite that of transport. The partition coefficient ratio of bovine choroid-Bruch's layer to sclera was approximately 1, 1.5, 1.7, 2, and 3.5, respectively, for the solutes, as listed earlier. CONCLUSIONS: The choroid-Bruch's layer is a more significant barrier to drug transport than is sclera. It hinders the transport of lipophilic solutes, especially a cationic solute, more than hydrophilic solutes and in a more dramatic way than does sclera. The reduction in transport across this layer directly correlates with solute binding to the tissue. Understanding the permeability properties of sclera and underlying layers would be beneficial in designing better drugs for transscleral delivery.     

Early Laparoscopic Cholecystectomy Service Provision is Feasible and Safe in the Current UK National Health Service

INTRODUCTION

Despite increasing evidence of the benefits and safety of early laparoscopic cholecystectomy (LC) in acute gallstone disease, it is not widely practised in England. The Royal College of Surgeons of England support the separation of emergency and elective surgical care. The aim of this prospective study was to examine the impact of the implementation of ‘Surgeon of the Week (SoW)’ model on the number of early LCs performed and the efficiency of the emergency theatre activity in our hospital. This study also looked into its implications on specialist registrar training for early LC, and the financial impact to the hospital.

PATIENTS AND METHODS

Between January 2007 and May 2008, demographic data, admission and discharge dates, complications, conversions to an open operation and deaths were collected for all patients who underwent early laparoscopic cholecystectomies. For ease of comparison, patients were divided into Group A representing before introduction of SoW (1 January 2007 to 30 August 2007) and Group B representing after introduction of SoW (1 October 2007 to 31 May 2008). The total numbers of operations performed in the emergency theatre list in the two groups were also calculated.

RESULTS

A total of 1361 emergency operations were performed on the emergency theatre list in Group A, of which 951 were general surgical procedures. In Group B, the numbers of emergency procedures were 1537, of which 1138 were general surgical operations. There was a significant increase in the number of general surgical operations after introduction of SoW (P = 0.013). Before introduction of the SoW rota, 45 early LCs were performed. This increased to 118 after SoW which was significant (P < 0.001). In Group A, the number of early LCs performed by surgical trainees was 10 (22%). In Group B, the number of LCs performed by surgical trainees was 35 (30%; not significant).

CONCLUSIONS

This study has demonstrated an increase in the efficiency of the emergency theatre with an increase in the number of early LCs on their index admission without extra morbidity following implementation of the SOW model in our hospital. We recommend the introduction of a suitable emergency surgical consultant on-call model separating emergency and elective surgical care depending on local circumstances. This can lead to significant cost savings and reduce re-admissions with gallstone-related complications.