Kynurenine monooxygenase regulates inflammation during critical illness and recovery in experimental acute pancreatitis.

Kynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. Here, we show that the KMO product 3-hydroxykynurenine primes innate immune signaling to exacerbate systemic inflammation during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma 3-hydroxykynurenine levels that prime inflammatory gene transcription. 3-Hydroxykynurenine synergizes with interleukin-1ß to cause cellular apoptosis. Critically, mice with elevated 3-hydroxykynurenine succumb fatally earlier and more readily to experimental AP. Therapeutically, blockade with the highly selective KMO inhibitor GSK898 rescues the phenotype, reducing 3-hydroxykynurenine and protecting against critical illness and death. Together, our findings establish KMO and 3-hydroxykynurenine as regulators of inflammation and the innate immune response to sterile inflammation. During critical illness, excess morbidity and death from multiple organ failure can be rescued by systemic KMO blockade.

Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans.

OBJECTIVE: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. SUMMARY BACKGROUND DATA: Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). METHODS: We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). RESULTS: Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. CONCLUSIONS: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.

Survival and new-onset morbidity after critical care admission for acute pancreatitis in Scotland: a national electronic healthcare record linkage cohort study.

INTRODUCTION: Severe acute pancreatitis (AP) requiring critical care admission (ccAP) impacts negatively on long-term survival. OBJECTIVE: To document organ-specific new morbidity and identify risk factors associated with premature mortality after an episode of ccAP. DESIGN: Cohort study. SETTING: Electronic healthcare registries in Scotland. PARTICIPANTS: The ccAP cohort included 1471 patients admitted to critical care with AP between 1 January 2008 and 31 December 2010 followed up until 31 December 2014. The population cohort included 3450 individuals from the general population of Scotland frequency-matched for age, sex and social deprivation. METHODS: Record linkage of routinely collected electronic health data with population matching. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient demographics, comorbidity (Charlson Comorbidity Index), acute physiology, organ support and other critical care data were linked to records of mortality (death certificate data) and new-onset morbidity. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with mortality. RESULTS: 310 patients with AP died during the index admission. Outcomes were not ascertained for five patients, and the deprivation quintile was not known for six patients. 340 of 1150 patients in the resulting postdischarge ccAP cohort died during the follow-up period. Greater comorbidity measured by the Charlson score, prior to ccAP, negatively influenced survival in the hospital and after discharge. The odds of developing new-onset diabetes mellitus after ccAP compared with the general population were 10.70 (95% CI 5.74 to 19.94). A new diagnosis of myocardial infarction, stroke, heart failure, liver disease, peptic ulcer, renal failure, cancer, peripheral vascular disease and lung disease was more frequent in the ccAP cohort than in the general population. CONCLUSIONS: The persistent deleterious impact of severe AP on long-term outcome and survival is multifactorial in origin, influenced by pre-existing patient characteristics and acute episode features. Further mechanistic and epidemiological investigation is warranted.

Emergency general surgery 'Hot Clinics' reduce admission rates and duration of inpatient stay.

OBJECTIVE: To determine the impact of a 'Hot Clinic' (HC) on emergency general surgery patient flow-through. DESIGN: Prospective service evaluation study. SETTING: HC is a four-bedded area coordinated by a specialist nurse. The HC consultant sees emergency patients referred from the emergency department, general practitioners or those in preceding 24 h considered suitable for interim discharge while awaiting investigations and HC reassessment. PATIENTS: All patients with acute abdominal pain were evaluated in three 4 week groups: before (group 1), 1 month (group 2) and 6 months after the HC was introduced (group 3). Interhospital transfers, intrahospital ward referrals and trauma patients were excluded. INTERVENTION: Introduction of consultant-led surgical HC every weekday afternoon. MAIN OUTCOME MEASURES: Proportion of patients admitted under general surgeons, length of inpatient stay and the proportion of patients referred again within 3 months were investigated. RESULTS: 1409 patients were referred, of which 1061 met the inclusion criteria: 307 in group 1, 326 in group 2 and 428 in group 3. There was no difference in gender distribution (p=0.759). Inpatient admissions were significantly reduced (85.0% vs 78.2% vs 54.4%; p<0.001) and the inpatient duration of stay was significantly shorter after HC introduction (median (IQR) (95% CI) 63.8 (29.0-111.6) (51.8 to 72.8) hours vs 48.8 (21.7-101.2) (42.0 to 55.6) hours vs 47.7 (20.9-92.7) (42.8 to 56.9) hours; p=0.011). CONCLUSIONS: Emergency general surgery HCs are associated with significant reductions in admission rates and inpatient bed occupancy. This service redesign has the potential to dramatically relieve pressure on acute surgical services.

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis: a record linkage analysis of Scottish healthcare databases.

OBJECTIVES: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. SETTING: Health boards in Scotland (n=4). PARTICIPANTS: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. METHODS: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. RESULTS: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. CONCLUSIONS: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.

Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.

Systemic inflammation, which results from the massive release of proinflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are not fully understood. We observed that prostaglandin E2 (PGE2), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treatment with EP4 agonists. Mechanistically, we demonstrate that PGE2-EP4 signaling acts directly on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC-IL-22 axis impairs PGE2-mediated inhibition of systemic inflammation. Hence, the ILC-IL-22 axis is essential in protecting against gut barrier dysfunction, enabling PGE2-EP4 signaling to impede systemic inflammation.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P < 0.001) and when contemporaneous and maximum CRP exceeded 100 mg/L (P = 0.048 and P = 0.003 respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544-0.962, and AUC = 0.996, 95% C.I.: 0.982-1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510-0.883, and AUC = 0.800, 95% C.I.: 0.640-0.929). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography, and the number of comet tails present on scans was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.013), those with severe disease (P = 0.001) and when contemporaneous and maximum in-patient C-reactive protein (CRP) exceeded 150 mg/l (P = 0.018 and P = 0.049, respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.803, 95% CI: 0.583-1.000, and AUC = 0.996, 95% CI: 0.983-1.000, respectively). Examining all lung quadrants resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.764, 95% CI: 0.555-0.972, and AUC = 0.704, 95% CI: 0.510-0.898). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.

Keap1-Nrf2 signalling in pancreatic cancer.

Transcription factor NF-E2 p45-related factor 2 (Nrf2, also called Nfe2l2), a master regulator of redox homeostasis, and its dominant negative regulator, Kelch-like ECH-associated protein 1 (Keap1), together tightly control the expression of numerous detoxifying and antioxidant genes. Nrf2 and the 'antioxidant response element' (ARE)-driven genes it controls are frequently upregulated in pancreatic cancer and correlate with poor survival. Upregulation of Nrf2 is, at least in part, K-Ras oncogene-driven and contributes to pancreatic cancer proliferation and chemoresistance. In this review, we aim to provide an overview of Keap1-Nrf2 signalling as it relates to pancreatic cancer, discussing the effects of inhibiting Nrf2 or Nrf2/ARE effector proteins to increase chemosensitivity.

Early organ dysfunction affects long-term survival in acute pancreatitis patients.

BACKGROUND: The effect of early organ dysfunction on long-term survival in acute pancreatitis (AP) patients is unknown. OBJECTIVE: The aim of this study was to ascertain whether early organ dysfunction impacts on long-term survival after an episode of AP. METHODS: A retrospective analysis was performed using survival data sourced from a prospectively maintained database of patients with AP admitted to the Royal Infirmary of Edinburgh during a 5-year period commencing January 2000. A multiple organ dysfunction syndrome (MODS) score of ≥ 2 during the first week of admission was used to define early organ dysfunction. After accounting for in-hospital deaths, long-term survival probabilities were estimated using the Kaplan-Meier test. The prognostic significance of patient characteristics was assessed by univariate and multivariate analyses using Cox's proportional hazards methods. RESULTS: A total of 694 patients were studied (median follow-up: 8.8 years). Patients with early organ dysfunction (MODS group) were found to have died prematurely [mean survival: 10.0 years, 95% confidence interval (CI) 9.4-10.6 years] in comparison with the non-MODS group (mean survival: 11.6 years, 95% CI 11.2-11.9 years) (log-rank test, P = 0.001) after the exclusion of in-hospital deaths. Multivariate analysis confirmed MODS as an independent predictor of long-term survival [hazard ratio (HR): 1.528, 95% CI 1.72-2.176; P = 0.019] along with age (HR: 1.062; P < 0.001), alcohol-related aetiology (HR: 2.027; P = 0.001) and idiopathic aetiology (HR: 1.548; P = 0.048). CONCLUSIONS: Early organ dysfunction in AP is an independent predictor of long-term survival even when in-hospital deaths are accounted for. Negative predictors also include age, and idiopathic and alcohol-related aetiologies.

The management of perforated gastric ulcers.

INTRODUCTION: Perforated gastric ulcers are potentially complicated surgical emergencies and appropriate early management is essential in order to avoid subsequent problems including unnecessary gastrectomy. The aim of this study was to examine the management and outcome of patients with gastric ulcer perforation undergoing emergency laparotomy for peritonitis. METHODS: Patients undergoing laparotomy at the Royal Infirmary of Edinburgh for perforated gastric ulcers were identified from the prospectively maintained Lothian Surgical Audit (LSA) database over the five-year period 2007-2011. Additional data were obtained by review of electronic records and review of case notes. RESULTS: Forty-four patients (25 male, 19 female) were identified. Procedures performed were: 41 omental patch repairs (91%), 2 simple closures (4.5%) and 2 distal gastrectomies (4.5%; both for large perforations). Four perforated gastric tumours were identified (8.8%), 2 of which were suspected intra-operatively and confirmed histologically, 1 had unexpected positive histology and 1 had negative intra-operative histology, but follow-up endoscopy confirmed the presence of carcinoma (1 positive biopsy in 21 follow-up endoscopies); all 4 were managed without initial resection. Median length of stay was 10 days (range 4-68). Overall 7 patients died in hospital (15.9%) and there were 21 morbidities (54.5%). Registrars performed the majority of the procedures (16 alone, 21 supervised) with no significant difference in post-operative morbidity (P = 0.098) or mortality (P = 0.855), compared to consultants. CONCLUSION: Almost all perforated gastric ulcers can be effectively managed by laparotomy and omental patch repair. Initial biopsy and follow-up endoscopy with repeat biopsy is essential to avoid missing an underlying malignancy.

Is there any role for resuscitative emergency department thoracotomy in blunt trauma?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether there is any role for resuscitative emergency department thoracotomy in severe blunt trauma. Emergency thoracotomy is an accepted intervention for patients with penetrating cardiothoracic trauma. However, its role in blunt trauma has been challenged and has been a subject of considerable debate. Altogether, 186 relevant papers were identified, of which 14 represented the best evidence to answer the question. The author, journal, date, country of publication and relevant outcomes are tabulated. The 14 studies comprised 2 systematic reviews and 12 retrospective studies. The systematic review performed by the Trauma Committee of the American College of Surgeons included 42 studies and a cumulative total of 2193 blunt trauma patients who underwent an emergency department thoracotomy, reporting a survival rate of 1.6%. According to this review, 15% of the survivors suffered from neurological sequelae, but survivors from both penetrating and blunt trauma were included. A systematic review comprising 24 studies reported a survival rate of 1.4% among 1047 blunt trauma patients. Of the retrospective studies, 11 report poor survival rates, ranging from 0 to 6%. Only one study reports a higher survival rate (12.2%). Five of the studies reported on the neurological outcome of survivors. The majority of the studies suffered from limitations due to the small number of included cases. The reported survival after an emergency department thoracotomy for blunt trauma is very low in the vast majority of available studies. Furthermore, the neurological sequelae in the few survivors are frequent and severe. Interestingly, some author groups recommend that emergency department thoracotomy should be contraindicated in cases of blunt trauma with no signs of life at the scene of trauma or on arrival at the emergency department. Larger, well-designed series will be required to reach a consensus on valid prognostic factors and specific subgroups of blunt trauma patients with substantial chances of survival.

Inguinoscrotal extension of a pancreatic collection: a rare complication of pancreatitis-case report and review of the literature.

Pancreatitis associated with the extension of a pancreatic collection, pseudocyst or abscess into the groin is a rare phenomenon with few reports in the English literature. Nevertheless, it remains a clinically important differential diagnosis as it may be mistaken for more common pathologies in the groin and with a subsequent unnecessary surgical intervention. A case of this rare complication of pancreatitis is reported, together with a review of the literature.

Quality review of an adverse incident reporting system and root cause analysis of serious adverse surgical incidents in a teaching hospital of Scotland.

BACKGROUND: A significant proportion of surgical patients are unintentionally harmed during their hospital stay. Root Cause Analysis (RCA) aims to determine the aetiology of adverse incidents that lead to patient harm and produce a series of recommendations, which would minimise the risk of recurrence of similar events, if appropriately applied to clinical practice. A review of the quality of the adverse incident reporting system and the RCA of serious adverse incidents at the Department of Surgery of Ninewells hospital, in Dundee, United Kingdom was performed. METHODS: The Adverse Incident Management (AIM) database of the Department of Surgery of Ninewells Hospital was retrospectively reviewed. Details of all serious (red, sentinel) incidents recorded between May 2004 and December 2009, including the RCA reports and outcomes, where applicable, were reviewed. Additional related information was gathered by interviewing the involved members of staff. RESULTS: The total number of reported surgical incidents was 3142, of which 81 (2.58%) cases had been reported as red or sentinel. 19 of the 81 incidents (23.4%) had been inappropriately reported as red. In 31 reports (38.2%) vital information with regards to the details of the adverse incidents had not been recorded. In 12 cases (14.8%) the description of incidents was of poor quality. RCA was performed for 47 cases (58%) and only 12 cases (15%) received recommendations aiming to improve clinical practice. CONCLUSION: The results of our study demonstrate the need for improvement in the quality of incident reporting. There are enormous benefits to be gained by this time and resource consuming process, however appropriate staff training on the use of this system is a pre-requisite. Furthermore, sufficient support and resources are required for the implementation of RCA recommendations in clinical practice.

Is early laparoscopic cholecystectomy for acute cholecystitis preferable to delayed surgery?: Best evidence topic (BET).

A best evidence topic was written according to a structured protocol. The question addressed was whether early laparoscopic cholecystectomy (ELC) in patients presenting with a short history of acute cholecystitis provides better post-operative outcomes than a delayed laparoscopic cholecystectomy (DLC). A total of 92 papers were found using the reported searches of which 10 represented the best evidence; 3 meta-analyses, 4 randomized control trials, 1 prospective controlled study and 2 retrospective cohort studies were included. The authors, date, journal, study type, population, main outcome measures and results were tabulated. No significant difference in complication or conversion rates were shown between the ELC and the DLC group, in the meta-analyses of Gurusamy et al, Lau et al and Siddiqui et al. The ELC group had a decreased hospital stay whereas the DLC group presented a considerable risk for subsequent emergency surgery during the interval period, with a high rate of conversion to open cholecystectomy. All three meta-analyses were based on the randomized control trials of Lo et al, Lai et al, Kolla et al and Johansson et al; the results of each study are summarized. We conclude that there is strong evidence that early laparoscopic cholecystectomy for acute cholecystitis offers an advantage in the length of hospital stay without increasing the morbidity or mortality. The operating time in ELC can be longer, however the incidence of serious complications (i.e. common bile duct injury), is comparable to the DLC group. Larger randomized studies are required before solid conclusions are reached.

Idiopathic spontaneous haemoperitoneum due to a ruptured middle colic artery aneurysm.

INTRODUCTION: Idiopathic spontaneous intra-abdominal haemorrhage is a rare, but challenging condition, associated with high mortality if not managed appropriately. The preoperative diagnosis is difficult, despite the recent advances in imaging. We present the clinical manifestations of this condition, as well as the available diagnostic and therapeutic modalities. PRESENTATION OF CASE: We report a case of a spontaneously ruptured dissecting aneurysm of the middle colic artery, which was managed with an emergency laparotomy and aneurysmatectomy. Interestingly, no evidence of vasculitis, infection or collagen disease was discovered during the histopathology examination of the specimen. DISCUSSION: The treatment of idiopathic spontaneous intra-abdominal haemorrhage revolves around patient resuscitation and management of the source of bleeding. In case of a ruptured aneurysm of the middle colic artery, the surgical management includes emergency laparotomy, arterial ligation and resection of the aneurysm. Transarterial embolisation has been suggested as a safe and less invasive alternative approach. CONCLUSION: A ruptured middle colic artery aneurysm should be included in the differential diagnosis of any unexplained intra-abdominal haemorrhage. Aneurysmatectomy is the treatment of choice, with radiologic interventional techniques gaining ground in the management of this entity.

Laparoscopic management for carcinoid metastasis to the spleen.

We report a rare case of a laparoscopic splenectomy performed for a carcinoid metastasis. The patient represented with pleuritic left-sided chest pain from pleural deposits 9 years following resection of a primary lung carcinoid tumour. They were found to have a 4.7 cm splenic lesion on CT with a probable left acetabular metastasis demonstrated on Gallium PET scan. The patient underwent laparoscopic splenectomy for debulking treatment of the splenic lesion that was confirmed to be a splenic metastasis of the resected carcinoid lung tumour. Following an uncomplicated recovery, the patient was discharged on the second postoperative day. On discharge, she received adjuvant therapy with Lutetium 177 DOTATATE. This is the first report of a carcinoid splenic metastasis successfully treated with laparoscopic splenectomy.

Laparoscopic management of spigelian hernias.

PURPOSE: Spigelian hernias are rare, and their treatment has traditionally been by open surgery. Laparoscopic management is however, becoming more popular. The aim of our review is to examine the existing evidence regarding the safety and effectiveness of the laparoscopic approach to the management of spigelian hernias. METHODS: A systematic literature search was carried out including Medline with PubMed as the search engine, and Ovid, Embase, Cochrane Collaboration, and Google Scholar databases to identify articles in English language reporting on laparoscopic management of spigelian hernias. RESULTS: Thirty-three articles were found, with a total number of 84 successfully managed cases, reported from 1992 to 2009. No recurrences (0%) and minimal morbidity (2.3%) are reported. Furthermore, the reported hospital stay of patients was remarkably short. CONCLUSIONS: Current data suggest that the laparoscopic approach to the management of spigelian hernias is safe and effective, both in the elective and emergency setting.

Preventing intraperitoneal adhesions with atorvastatin and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats.

OBJECTIVES: The aim of this study was to compare the effectiveness of atorvastatin with the sodium hyaluronate/carboxymethylcellulose (HA/CMC, Seprafilm; Genzyme; Genzyme Biosurgery Corporation, Cambridge, MA) in preventing postoperative intraperitoneal adhesion formation in rats. METHODS: Sixty Wistar rats underwent a laparotomy, and adhesions A were induced by cecal abrasion. The animals were divided into 4 groups: group 1, control A; group 2, (A + atorvastatin); group 3, (A + HA/CMC), and group 4, (A + atorvastatin + HA/CMC). The atorvastatin (groups 2 and 4) and HA/CMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 14 days, adhesions were classified by 2 independent surgeons. RESULTS: The adhesion scores (mean +/- standard deviation) for groups 1, 2, 3, and 4 were 2.93 +/- .59, 1.85 +/- 1.07, 1.80 +/- .86, and 1.93 +/- .70, respectively. The differences in adhesion scores among all 3 preventive groups (groups 2, 3, and 4) were statistically significant when compared with the control group (P = .005, P = .002, and P = .009, respectively). CONCLUSIONS: These data suggest that atorvastatin, administered intraperitoneally, is as effective as HA/CMC without an expectable additive effect in preventing postoperative adhesions in rats.