Emerging presence of Actinomyces in perianal and pilonidal infection.

Actinomyces is a rare aetiology of infections affecting the perianal region and natal cleft. Recognition of this microorganism is essential to deliver targeted antimicrobial therapy following surgical intervention. We present a series of 15 pilonidal and perianal infections associated with this microorganism. Actinomyces turicensis was the only strain of Actinomyces isolated. A total of 14 out of 15 cases had concomitant microorganisms isolated from microbiology specimens. Mixed anaerobes (n = 14) were the most common concomitant pathogens followed by Streptococcus milleri (n = 3), Staphylococcus aureus (n = 1), Citrobacter (n = 1) and Coliform bacteria (n = 1). All patients, except one who was pregnant at time of diagnosis, underwent surgical drainage with or without further oral antibiotic therapy. Coloproctologists need to consider Actinomyces as a clinically significant pathogen in the context of perianal and pilonidal infections.

Long-term outcomes of patients with poor prognostic factors following transanal endoscopic microsurgery for early rectal cancer.

AIM: Management of early rectal cancer following transanal microscopic anal surgery poses a management dilemma when the histopathology reveals poor prognostic features, due to high risk of local recurrence. The aim of this study is to evaluate the oncological outcomes of such patients who undergo surgery with total mesorectal excision (TME), receive adjuvant chemo/radiotherapy (CRDT/RT) or receive close surveillance only (no further treatment). METHODS: We identified patients with poor prognostic factors-pT2 adenocarcinoma, poor differentiation, deep submucosal invasion (Kikuchi SM3), lymphovascular invasion, tumour budding or R1 resection margin-between 1 September 2012 and 31 January 2020 and report their oncological outcomes. RESULTS: Of the 53 patients, 18 had TME, 14 had CRDT and 14 had RT; seven patients did not have any further treatment. The median follow-up was 48 months, 12 developed recurrence and six died. Overall, 5-year survival (OS) was 88.9% and disease-free survival (DFS) was 79.2%. Compared to the surgical group, in which there were eight recurrences and two deaths, there were zero recurrences or deaths in the CRDT group, log-rank test P = 0.206 for OS and P = 0.005 for DFS. The 5-year survival rates in the RT and surveillance only groups were OS 78.6%, DFS 85.7% and OS 71.5%, DFS 71% respectively. TME assessment in the surgical group revealed Grade 3 quality in seven of the 16 available reports. CONCLUSION: These findings support the strategy of adjuvant CRDT as first line treatment for patients undergoing transanal endoscopic microsurgery for early rectal cancer with poor prognostic factors on initial histological assessment.

Real-World Clinical Practice of Intensified Chemotherapies for Metastatic Pancreatic Cancer: Results from a Pan-European Questionnaire Study.

INTRODUCTION: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe. METHODS: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer. RESULTS: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer. CONCLUSION: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.

What operation for recurrent rectal prolapse after previous Delorme's procedure? A practical reality.

AIM: To report our experience with perineal repair (Delorme's procedure) of rectal prolapse with particular focus on treatment of the recurrence. METHODS: Clinical records of 40 patients who underwent Delorme's procedure between 2003 and 2014 were reviewed to obtain the following data: Gender; duration of symptoms, length of prolapse, operation time, ASA grade, length of post-operative stay, procedure-related complications, development and treatment of recurrent prolapse. Analysis of post-operative complications, rate and time of recurrence and factors influencing the choice of the procedure for recurrent disease was conducted. Continuous variables were expressed as the median with interquartile range (IQR). Statistical analysis was carried out using the Fisher exact test. RESULTS: Median age at the time of surgery was 76 years (IQR: 71-81.5) and there were 38 females and 2 males. The median duration of symptoms was 6 mo (IQR: 3.5-12) and majority of patients presented electively whereas four patients presented in the emergency department with irreducible rectal prolapse. The median length of prolapse was 5 cm (IQR: 5-7), median operative time was 100 min (IQR: 85-120) and median post-operative stay was 4 d (IQR: 3-6). Approximately 16% of the patients suffered minor complications such as - urinary retention, delayed defaecation and infected haematoma. One patient died constituting post-operative mortality of 2.5%. Median follow-up was 6.5 mo (IQR: 2.15-16). Overall recurrence rate was 28% (n = 12). Recurrence rate for patients undergoing an urgent Delorme's procedure who presented as an emergency was higher (75.0%) compared to those treated electively (20.5%), P value 0.034. Median time interval from surgery to the development of recurrence was 16 mo (IQR: 5-30). There were three patients who developed an early recurrence, within two weeks of the initial procedure. The management of the recurrent prolapse was as follows: No further intervention (n = 1), repeat Delorme's procedure (n = 3), Altemeier's procedure (n = 5) and rectopexy with faecal diversion (n = 3). One patient was lost during follow up. CONCLUSION: Delorme's procedure is a suitable treatment for rectal prolapse due to low morbidity and mortality and acceptable rate of recurrence. The management of the recurrent rectal prolapse is often restricted to the pelvic approach by the same patient-related factors that influenced the choice of the initial operation, i.e., Delorme's procedure. Early recurrence developing within days or weeks often represents a technical failure and may require abdominal rectopexy with faecal diversion.

Stigmergy co-ordinates multicellular collective behaviours during Myxococcus xanthus surface migration.

Surface translocation by the soil bacterium Myxococcus xanthus is a complex multicellular phenomenon that entails two motility systems. However, the mechanisms by which the activities of individual cells are coordinated to manifest this collective behaviour are currently unclear. Here we have developed a novel assay that enables detailed microscopic examination of M. xanthus motility at the interstitial interface between solidified nutrient medium and a glass coverslip. Under these conditions, M. xanthus motility is characterised by extensive micro-morphological patterning that is considerably more elaborate than occurs at an air-surface interface. We have found that during motility on solidified nutrient medium, M. xanthus forges an interconnected furrow network that is lined with an extracellular matrix comprised of exopolysaccharides, extracellular lipids, membrane vesicles and an unidentified slime. Our observations have revealed that M. xanthus motility on solidified nutrient medium is a stigmergic phenomenon in which multi-cellular collective behaviours are co-ordinated through trail-following that is guided by physical furrows and extracellular matrix materials.

Small Molecule Inhibitors of Cyclophilin D To Protect Mitochondrial Function as a Potential Treatment for Acute Pancreatitis.

Opening of the mitochondrial permeability transition pore (MPTP) causes mitochondrial dysfunction and necrosis in acute pancreatitis (AP), a condition without specific drug treatment. Cyclophilin D (CypD) is a mitochondrial matrix peptidyl-prolyl isomerase that regulates the MPTP and is a drug target for AP. We have synthesized urea-based small molecule inhibitors of cyclophilins and tested them against CypD using binding and isomerase activity assays. Thermodynamic profiles of the CypD/inhibitor interactions were determined by isothermal titration calorimetry. Seven new high-resolution crystal structures of CypD-inhibitor complexes were obtained to guide compound optimization. Compounds 4, 13, 14, and 19 were tested in freshly isolated murine pancreatic acinar cells (PACs) to determine inhibition of toxin-induced loss of mitochondrial membrane potential (ΔΨm) and necrotic cell death pathway activation. Compound 19 was found to have a Kd of 410 nM and a favorable thermodynamic profile, and it showed significant protection of ΔΨm and reduced necrosis of murine as well as human PACs. Compound 19 holds significant promise for future lead optimization.

Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP.

OBJECTIVE: Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. DESIGN: We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. RESULTS: MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. CONCLUSIONS: This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease.

New Advances in the Treatment of Metastatic Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extremely poor overall survival (OS) compared to other solid tumours. As the incidence of the disease is rising and the treatment options are limited, PDAC is projected to be the 2nd leading cause of cancer-related deaths in the United States by 2030. A majority of patients are not eligible for curative resection at the time of diagnosis, and those that are resected will often relapse within the first few years after surgery. SUMMARY: Until recently, the nucleoside analogue gemcitabine has been the standard of care for patients with non-resectable PDAC with only marginal effects on OS. In 2011, the gemcitabine-free FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) showed a significant survival advantage for patients with metastatic PDAC in a phase III trial. In 2013, the Metastatic Pancreatic Adenocarcinoma Trial phase III trial with nano- formulated albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine also resulted in a significant survival extension compared to gemcitabine monotherapy. However, both intensified therapy regimens show a broad spectrum of side effects and patients need to be carefully selected for the most appropriate protocol. KEY MESSAGE: In this study, recent advances in the chemotherapeutic options available to treat metastatic PDAC and their implications for today's treatment choices are reviewed.

Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models.

BACKGROUND & AIMS: Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release-activated calcium modulator ORAI1 is the most abundant Ca(2+) entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. METHODS: Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. RESULTS: GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. CONCLUSIONS: Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis.

Validation of the moderate severity category of acute pancreatitis defined by determinant-based classification.

BACKGROUND: Recent international multidisciplinary consultation proposed the use of local (sterile or infected pancreatic necrosis) and/or systemic determinants (organ failure) in the stratification of acute pancreatitis. The present study was to validate the moderate severity category by international multidisciplinary consultation definitions. METHODS: Ninety-two consecutive patients with severe acute pancreatitis (according to the 1992 Atlanta classification) were classified into (i) moderate acute pancreatitis group with the presence of sterile (peri-) pancreatic necrosis and/or transient organ failure; and (ii) severe/critical acute pancreatitis group with the presence of sterile or infected pancreatic necrosis and/or persistent organ failure. Demographic and clinical outcomes were compared between the two groups. RESULTS: Compared with the severe/critical group (n=59), the moderate group (n=33) had lower clinical and computerized tomographic scores (both P<0.05). They also had a lower incidence of pancreatic necrosis (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0% vs 27.1%, P=0.001), and shorter hospital stay (15+/-5 vs 27+/-12 days; P<0.001). A subgroup analysis showed that the moderate group also had significantly lower ICU admission rates, shorter hospital stay and lower rate of infection compared with the severe group (n=51). No patients died in the moderate group but 7 patients died in the severe/critical group (4 for severe group). CONCLUSIONS: Our data suggest that the definition of moderate acute pancreatitis, as suggested by the international multidisciplinary consultation as sterile (peri-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.

Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis.

OBJECTIVES: This study aimed to conduct a single-center prospective trial of short-term continuous high-volume hemofiltration (HVHF) in patients with predicted severe acute pancreatitis (SAP). METHODS: Patients with acute pancreatitis with Acute Physiology and Chronic Health Evaluation II scores of greater than 15 on admission between January 2008 and December 2010 were allocated to receive either optimal standard therapy or 72 hours of continuous HVHF on an alternate basis, beginning as soon as possible after admission. Biomarkers and clinical outcomes were compared between the 2 groups. RESULTS: A total of 61 patients received either conventional therapy (n = 29) or HVHF (n = 32). High-volume hemofiltration treatment was associated with a significant reduction in the incidence of renal failure (P = 0.013), infected pancreatic necrosis (P = 0.048), length of hospitalization (P = 0.005), mortality (P = 0.033), as well as duration of renal (P < 0.001), respiratory (P = 0.002), and hepatic failure (P = 0.001). Acute Physiology and Chronic Health Evaluation II score and C-reactive protein and interleukin 6 levels were significantly reduced after the start of HVHF on days 1, 3, and 7 (all, P < 0.05). CONCLUSIONS: This study suggests that short-term HVHF may reduce local and systemic complications and mortality in patients with SAP with Acute Physiology and Chronic Health Evaluation score of greater than 15.

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis.

OBJECTIVE: Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. DESIGN: Intracellular calcium ([Ca(2+)](C)), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. RESULTS: Inhibition of OME with 4-MP converted predominantly transient [Ca(2+)](C) rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. CONCLUSIONS: A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation.

Urinary trypsinogen-2 for diagnosing acute pancreatitis: a meta-analysis.

BACKGROUND: Currently, serum amylase and lipase are the most popular laboratory markers for early diagnosis of acute pancreatitis with reasonable sensitivity and specificity. Urinary trypsinogen-2 (UT-2) has been increasingly used but its clinical value for the diagnosis of acute pancreatitis and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has not yet been systematically assessed. DATA SOURCES: A comprehensive search was carried out using PubMed (MEDLINE), Embase, and Web of Science for clinical trials, which studied the usefulness of UT-2 as a diagnostic marker for acute pancreatitis. Sensitivity, specificity and the diagnostic odds ratios (DORs) with 95% confidence interval (CI) were calculated for each study and were compared with serum amylase and lipase. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: A total of 18 studies were included. The pooled sensitivity and specificity of UT-2 for the diagnosis of acute pancreatitis were 80% and 92%, respectively (AUC=0.96, DOR=65.63, 95% CI: 31.65-139.09). The diagnostic value of UT-2 was comparable to serum amylase but was weaker than serum lipase. The pooled sensitivity and specificity for the diagnosis of post-ERCP pancreatitis were 86% and 94%, respectively (AUC=0.92, DOR=77.68, 95% CI: 24.99-241.48). CONCLUSIONS: UT-2 as a rapid test could be potentially used for the diagnosis of post-ERCP pancreatitis and to an extent, acute pancreatitis. Further studies are warranted to confirm these results.

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: a meta-analysis.

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.

Bacteriophage receptor binding protein based assays for the simultaneous detection of Campylobacter jejuni and Campylobacter coli.

Campylobacter jejuni and Campylobacter coli are the most common bacterial causes of foodborne gastroenteritis which is occasionally followed by a debilitating neuropathy known as Guillain-Barré syndrome. Rapid and specific detection of these pathogens is very important for effective control and quick treatment of infection. Most of the diagnostics available for these organisms are time consuming and require technical expertise with expensive instruments and reagents to perform. Bacteriophages bind to their host specifically through their receptor binding proteins (RBPs), which can be exploited for pathogen detection. We recently sequenced the genome of C. jejuni phage NCTC12673 and identified its putative host receptor binding protein, Gp047. In the current study, we localized the receptor binding domain to the C-terminal quarter of Gp047. CC-Gp047 could be produced recombinantly and was capable of agglutinating both C. jejuni and C. coli cells unlike the host range of the parent phage which is limited to a subset of C. jejuni isolates. The agglutination procedure could be performed within minutes on a glass slide at room temperature and was not hindered by the presence of buffers or nutrient media. This agglutination assay showed 100% specificity and the sensitivity was 95% for C. jejuni (n = 40) and 90% for C. coli (n = 19). CC-Gp047 was also expressed as a fusion with enhanced green fluorescent protein (EGFP). Chimeric EGFP_CC-Gp047 was able to specifically label C. jejuni and C. coli cells in mixed cultures allowing for the detection of these pathogens by fluorescent microscopy. This study describes a simple and rapid method for the detection of C. jejuni and C. coli using engineered phage RBPs and offers a promising new diagnostics platform for healthcare and surveillance laboratories.

Roux-en-Y versus Billroth†I†reconstruction after distal gastrectomy for gastric cancer: a meta-analysis.

AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth I (B-I) anastomosis after distal gastrectomy (DG) for gastric cancer. METHODS: A literature search was performed to identify studies comparing R-Y with B-I after DG for gastric cancer from January 1990 to November 2012 in Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in The Cochrane Library. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed or random effects model. Operative outcomes such as operation time, intraoperative blood loss and postoperative outcomes such as anastomotic leakage and stricture, bile reflux, remnant gastritis, reflux esophagitis, dumping symptoms, delayed gastric emptying and hospital stay were the main outcomes assessed. Meta-analyses were performed using RevMan 5.0 software (Cochrane library). RESULTS: Four randomized controlled trials (RCTs) and 9 non-randomized observational clinical studies (OCS) involving 478 and 1402 patients respectively were included. Meta-analysis of RCTs revealed that R-Y reconstruction was associated with a reduced bile reflux (OR 0.04, 95%CI: 0.01, 0.14; P < 0.00 001) and remnant gastritis (OR 0.43, 95%CI: 0.28, 0.66; P = 0.0001), however needing a longer operation time (WMD 40.02, 95%CI: 13.93, 66.11; P = 0.003). Meta-analysis of OCS also revealed R-Y reconstruction had a lower incidence of bile reflux (OR 0.21, 95%CI: 0.08, 0.54; P = 0.001), remnant gastritis (OR 0.18, 95%CI: 0.11, 0.29; P < 0.00 001) and reflux esophagitis (OR 0.48, 95%CI: 0.26, 0.89; P = 0.02). However, this reconstruction method was found to be associated with a longer operation time (WMD 31.30, 95%CI: 12.99, 49.60; P = 0.0008). CONCLUSION: This systematic review point towards some clinical advantages that are rendered by R-Y compared to B-I reconstruction post DG. However there is a need for further adequately powered, well-designed RCTs comparing the same.

Early oral refeeding wisdom in patients with mild acute pancreatitis.

OBJECTIVES: To evaluate the safety and efficacy of early oral refeeding (EORF) in patients with mild acute pancreatitis (AP) and to investigate the optimal duration to commence EORF. METHODS: A prospective, randomized, controlled trial was conducted in patients with mild AP. Patients with EORF (started oral feeding once they subjectively felt hungry) were compared with patients receiving routine oral refeeding (RORF) for time interval between disease onset and initiation of oral refeeding, total length of hospitalization (LOH), postrefeeding LOH, and adverse gastrointestinal events. RESULTS: There were 75 and 74 patients in the EORF group and the RORF group, respectively, with comparable baseline characteristics. Patients in the EORF group started refeeding significantly earlier than those in the RORF group (4.56 ± 1.53 vs 6.75 ± 2.29 days; P < 0.05). Moreover, patients in the EORF group had significantly shorter total (6.8 ± 2.1 vs 10.4 ± 4.1 days; P < 0.01) and post refeeding LOH (2.24 ± 0.52 vs 3.27 ± 0.61 days; P < 0.01). There was no significant difference in adverse gastrointestinal events between the 2 groups. CONCLUSION: In patients with mild AP, EORF, with the subjective feeling of hunger, is safe, feasible, and reduces LOH.

Stigmergy: A key driver of self-organization in bacterial biofilms.

Bacterial biofilms are complex multicellular communities that are often associated with the emergence of large-scale patterns across the biofilm. How bacteria self-organize to form these structured communities is an area of active research. We have recently determined that the emergence of an intricate network of trails that forms during the twitching motility mediated expansion of Pseudomonas aeruginosa biofilms is attributed to an interconnected furrow system that is forged in the solidified nutrient media by aggregates of cells as they migrate across the media surface. This network acts as a means for self-organization of collective behavior during biofilm expansion as the cells following these vanguard aggregates were preferentially confined within the furrow network resulting in the formation of an intricate network of trails of cells. Here we further explore the process by which the intricate network of trails emerges. We have determined that the formation of the intricate network of furrows is associated with significant remodeling of the sub-stratum underlying the biofilm. The concept of stigmergy has been used to describe a variety of self-organization processes observed in higher organisms and abiotic systems that involve indirect communication via persistent cues in the environment left by individuals that influence the behavior of other individuals of the group at a later point in time. We propose that the concept of stigmergy can also be applied to describe self-organization of bacterial biofilms and can be included in the repertoire of systems used by bacteria to coordinate complex multicellular behaviors.

Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma.

AIM: To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC). METHODS: PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012. Two authors independently assessed the trials for inclusion and extracted the data. Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed effects (Mantel-Haenszel method) or random effects models (DerSimonian and Laird method). Evaluated endpoints were operative outcomes (operation time, intraoperative blood loss, blood transfusion requirement), postoperative outcomes (liver failure, cirrhotic decompensation/ascites, bile leakage, postoperative bleeding, pulmonary complications, intraabdominal abscess, mortality, hospital stay and oncologic outcomes (positive resection margins and tumor recurrence). RESULTS: Fifteen eligible non-randomized studies were identified, out of which, 9 high-quality studies involving 550 patients were included, with 234 patients in the LLR group and 316 patients in the OLR group. LLR was associated with significantly lower intraoperative blood loss, based on six studies with 333 patients [WMD: -129.48 mL; 95%CI: -224.76-(-34.21) mL; P = 0.008]. Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups. The LLR group had lower blood transfusion requirement (OR: 0.49; 95%CI: 0.26-0.91; P = 0.02). While analyzing hospital stay, six studies with 333 patients were included. Patients in the LLR group were found to have shorter hospital stay [WMD: -3.19 d; 95%CI: -4.09-(-2.28) d; P < 0.00001] than their OLR counterpart. Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups. The LLR group appeared to have a lower incidence of postoperative ascites (OR: 0.32; 95%CI: 0.16-0.61; P = 0.0006) as compared with OLR patients. Similarly, fewer patients had liver failure in the LLR group than in the OLR group (OR: 0.15; 95%CI: 0.02-0.95; P = 0.04). However, no significant differences were found between the two approaches with regards to operation time [WMD: 4.69 min; 95%CI: -22.62-32 min; P = 0.74], bile leakage (OR: 0.55; 95%CI: 0.10-3.12; P = 0.50), postoperative bleeding (OR: 0.54; 95%CI: 0.20-1.45; P = 0.22), pulmonary complications (OR: 0.43; 95%CI: 0.18-1.04; P = 0.06), intra-abdominal abscesses (OR: 0.21; 95%CI: 0.01-4.53; P = 0.32), mortality (OR: 0.46; 95%CI: 0.14-1.51; P = 0.20), presence of positive resection margins (OR: 0.59; 95%CI: 0.21-1.62; P = 0.31) and tumor recurrence (OR: 0.95; 95%CI: 0.62-1.46; P = 0.81). CONCLUSION: LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence. However, further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.

A systematic review and meta-analysis of studies comparing laparoscopic and open distal pancreatectomy.

OBJECTIVES: Currently, laparoscopic distal pancreatectomy (LDP) is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review compares outcomes of the laparoscopic technique with those of open distal pancreatectomy (ODP) and assesses the efficacy, safety and feasibility of each type of procedure. METHODS: Comparative studies published between January 1996 and April 2012 were included. Studies were selected based on specific inclusion and exclusion criteria. Evaluated endpoints were operative outcomes, postoperative recovery and postoperative complications. RESULTS: Fifteen non-randomized comparative studies that recruited a total of 1456 patients were analysed. Rates of conversion from LDP to open surgery ranged from 0% to 30%. Patients undergoing LDP had less intraoperative blood loss [weighted mean difference (WMD) -263.36.59 ml, 95% confidence interval (CI) -330.48 to -196.23 ml], fewer blood transfusions [odds ratio (OR) 0.28, 95% CI 0.11-0.76], shorter hospital stay (WMD -4.98 days, 95% CI -7.04 to -2.92 days), a higher rate of splenic preservation (OR 2.98, 95% CI 2.18-3.91), earlier oral intake (WMD -2.63 days, 95% CI -4.23 to 1.03 days) and fewer surgical site infections (OR 0.37, 95% CI 0.18-0.75). However, there were no differences between the two approaches with regard to operation time, time to first flatus and the occurrence of pancreatic fistula and other postoperative complications. CONCLUSIONS: Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analyses. It may be a safe and feasible option for patients with lesions in the body and tail of the pancreas. However, randomized controlled trials should be undertaken to confirm the relevance of these early findings.