Extended pelvic lymph node dissection at the time of robot-assisted radical prostatectomy: Impact of surgical volume on efficacy and complications in a single-surgeon series

INTRODUCTION: We assessed the impact of surgical volume on perioperative outcomes and complications of robotic extended pelvic lymph node dissection (ePLND). METHODS: From November 2008 to October 2012, a total of 233 consecutive patients with intermediate- or high-risk clinically localized prostate cancer underwent robot-assisted radical prostatectomy (RARP) and ePLND by a single, experienced open and laparoscopic surgeon. Data were prospectively collected. Complications were classified according to the Modified Clavien System. Complications potentially related to ePLND were documented. The minimum follow-up was 3 months. To evaluate the impact of surgical volume on the results, 4 patient subgroups (subgroup 1: cases 1-59; 2: 60-117; 3: 118-175; 4: 176-233) were compared using the Chi-squared and Kruskal-Wallis tests. RESULTS: The mean (range) operative time for ePLND was 79 minutes (range: 48-144), with a steady performance over time (p = 0.784). The count of resected lymph nodes plateaued after 60 procedures (mean [range]: 13 [range: 6-32], 15 [range: 7-34], 17 [range: 8-41], 16 [range: 8-42] in Groups 1 to 4, respectively, p = 0.001). Tumour lymph node involvement was 12% in Groups 1 and 2, 7% in Group 3 and 9% in Group 4 (p = 0.075). Overall, 115 complications were reported in 98/233 patients (42%), with a significant decrease after 175 cases (p = 0.028). In Group 4, 3 patients reported an ePLND-related bleeding requiring open revision. Lymphoceles were detected in 10/233 patients (4.2%) and 1 patient (1.7%) in each of the Groups 2 to 4 required a percutaneous drainage. CONCLUSIONS: A surgeon with extensive experience is expected to achieve a safe learning curve for ePLND during RARP. A learning curve of 60 cases is suggested for optimal lymph node yield

Stem cell therapy in necrotizing enterocolitis: Current state and future directions

Stem cell therapy is a promising treatment modality for necrotizing enterocolitis. Among the many promising stem cells identified to date, it is likely that mesenchymal stem cells will be the most useful and practical cell-based therapies for this condition. Using acellular components such as exosomes or other paracrine mediators are promising as well. Multiple mechanisms are likely at play in the positive effects provided by these cells, and further research is underway to further elucidate these effects

Family care reduces the incidence of neonatal sepsis: A systematic review and meta-analysis

PurposeFamily-involved care in the neonatal intensive care unit (NICU) helps to alleviate neonatal anxiety and promotes breastmilk intake, body growth and neurological development, but its effect on reducing the incidence of neonatal sepsis is not known. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate whether neonates receiving family care have a lower incidence of neonatal sepsis compared to neonates receiving standard NICU care.MethodsMEDLINE, Embase, Web of Science, and CENTRAL were searched for RCTs that compared preterm neonates receiving family care vs. standard NICU care. From 126 articles that were identified and screened, 34 full-text articles were assessed for eligibility, and 5 RCTs were included. The primary outcome was the development of sepsis. The RevMan 5.4 software was used to conduct the Meta-analysis.ResultsThe metanalysis, based on 5 RCTs demonstrated that neonates receiving family-involved care had significantly lower incidence of sepsis (12.0% vs. 16.3%), increased body weight, and reduced length of hospital stay compared to those receiving standard NICU care.ConclusionThis study suggests that family-involved care in NICU can (i) reduce the incidence of neonatal sepsis, (ii) improve growth, and (iii) reduce the length of hospital stay. This study highlights the need for evaluating whether family-involved care improves other neonatal outcomes

An investigation of minimisation criteria

Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way

Remote ischaemic conditioning in necrotising enterocolitis: a phase I feasibility and safety study

OBJECTIVE: Remote ischaemic conditioning (RIC) improves the outcome of experimental necrotising enterocolitis (NEC) by preserving intestinal microcirculation. The feasibility and safety of RIC in preterm infants with NEC are unknown. The study aimed to assess the feasibility and safety of RIC in preterm infants with suspected or confirmed NEC. DESIGN: Phase I non-randomised pilot study conducted in three steps: step A to determine the safe duration of limb ischaemia (up to 4 min); step B to assess the safety of 4 repeated cycles of ischaemia-reperfusion at the maximum tolerated duration of ischaemia determined in step A; step C to assess the safety of applying 4 cycles of ischaemia-reperfusion on two consecutive days. SETTING: Level III neonatal intensive care unit, The Hospital for Sick Children (Toronto, Canada). PATIENTS: Fifteen preterm infants born between 22 and 33 weeks gestational age. INTERVENTION: Four cycles of ischaemia (varying duration) applied to the limb via a manual sphygmomanometer, followed by reperfusion (4 min) and rest (5 min), repeated on two consecutive days. OUTCOMES: The primary outcomes were (1) feasibility defined as RIC being performed as planned in the protocol, and (2) safety defined as perfusion returning to baseline within 4 min after cuff deflation. RESULTS: Four cycles/day of limb ischaemia (4 min) followed by reperfusion (4 min) and a 5 min gap, repeated on two consecutive days was feasible and safe in all neonates with suspected or confirmed NEC. CONCLUSIONS: This study is pivotal for designing a future randomised controlled trial to assess the efficacy of RIC in preterm infants with NEC

Extracellular vesicles isolated from milk can improve gut barrier dysfunction induced by malnutrition

Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in children below the age of five. Severe acute malnutrition (SAM) is associated with intestinal barrier breakdown and epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30–150 nm) can travel to distant target cells through biofluids including milk. Since milk-derived EVs are known to induce intestinal stem cell proliferation, this study aimed to examine their potential efficacy in improving malnutrition-induced atrophy of intestinal mucosa and barrier dysfunction. Mice were fed either a control (18%) or a low protein (1%) diet for 14 days to induce malnutrition. From day 10 to 14, they received either bovine milk EVs or control gavage and were sacrificed on day 15, 4 h after a Fluorescein Isothiocyanate (FITC) dose. Tissue and blood were collected for histological and epithelial barrier function analyses. Mice fed low protein diet developed intestinal villus atrophy and barrier dysfunction. Despite continued low protein diet feeding, milk EV treatment improved intestinal permeability, intestinal architecture and cellular proliferation. Our results suggest that EVs enriched from milk should be further explored as a valuable adjuvant therapy to standard clinical management of malnourished children with high risk of morbidity and mortality

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis

Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis. Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected. Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage. Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis

Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis

Background/aimEstablished indications for surgery in necrotizing enterocolitis (NEC) are pneumoperitoneum and failure to improve or clinical deterioration with medical treatment alone. It has been proposed that infants with intestinal necrosis may benefit from surgery in the absence of one of these indications yet the diagnosis of definitive intestinal necrosis is challenging. Recent data suggest that abdominal ultrasound (US) examination focused on the gastrointestinal tract and the peritoneal cavity may be of utility in this regard. The aim of this study was to evaluate the ability of abdominal US to detect intestinal necrosis in infants with radiographically confirmed NEC.MethodsTwenty-six consecutive infants with Bell stage II or III NEC were prospectively included in the study between September 2013 and July 2014. Infants with a pre-existing indication for surgery were excluded. At least one abdominal US examination was performed in each patient using a standardized previously described method. Surgery was performed at the discretion of the attending surgeon based on clinical and imaging findings. Clinical, radiographic, US, and intra-operative data were recorded to allow comparison between US findings, surgical findings and outcome.ResultsUS demonstrated signs of intestinal necrosis in 5 of the 26 patients. All of these five had laparotomy. Intestinal necrosis requiring resection was confirmed in four and the other was found to have NEC but no necrosis was identified. In 21 patients US did not suggest intestinal necrosis. Of these, only one had surgery in whom NEC but no necrosis was identified. The remaining 20 responded to medical treatment for NEC and were assumed not to have had intestinal necrosis based on improvement without surgical intervention. The sensitivity, specificity, positive predictive value and negative predictive values of US for the detection of bowel necrosis were calculated as 100, 95.4, 80.0, and 100 %, respectively.ConclusionOur prospective findings suggest that abdominal US can identify those infants with NEC who may need surgery by detecting bowel necrosis (prior to the development of perforation or medical deterioration) with high sensitivity and specificity. Early surgical intervention in the clinical pathway of NEC may lead to improved outcomes

International survey on the management of esophageal atresia

IntroductionBecause many aspects of the management of esophageal atresia (EA) are still controversial, we evaluated the practice patterns of this condition across Europe. MethodsA survey was completed by 178 delegates (from 45 [27 European] countries; 88% senior respondents) at the EUPSA-BAPS 2012. ResultsApproximately 66% of respondents work in centers where more than five EA repairs are performed per year. Preoperatively, 81% of respondents request an echocardiogram, and only 43% of respondents routinely perform preoperative bronchoscopy. Approximately 94% of respondents prefer an open approach, which is extrapleural in 71% of respondents. There were no differences in use of thoracoscopy between Europeans (10%) and non-Europeans (11%, p=nonsignificant). Approximately 60% of respondents measure the gap intraoperatively. A transanastomotic tube (90%) and chest drain (69%) are left in situ. Elective paralysis is adopted by 56% of respondents mainly for anastomosis tension (65%). About 72% of respondents routinely request a contrast study on postoperative day 7 (2-14). Approximately 54% of respondents use parenteral nutrition, 40% of respondents start transanastomotic feeds on postoperative day 1, and 89% of respondents start oral feeds after postoperative day 5. Pure EA: 46% of respondents work in centers that repair two or more than two pure EA a year. About 60% of respondents opt for delayed primary anastomosis at 3 months (1-12 months) with gastrostomy formation without esophagostomy. Anastomosis is achieved with open approach by 85% of respondents. About 47% of respondents attempt elongation of esophageal ends via Foker technique (43%) or with serial dilations with bougies (41%). Approximately 67% of respondents always attempt an anastomosis. Gastric interposition is the commonest esophageal substitution. ConclusionMany aspects of EA management are lacking consensus. Minimally invasive repair is still sporadic. We recommend establishment of an EA registry

The outcome of critically ill neonates undergoing laparotomy for necrotising enterocolitis in the neonatal intensive care unit: a 10-year review

Results: 221 infants with NEC were referred for surgical evaluation; 182 (82%) underwent surgery; 15 (8%) required a laparotomy on NICU. Five had NEC totalis, 4 multifocal disease and 6 focal disease. Five had an open and close laparotomy, 8 stoma with/without bowel resection and 2 bowel resection and primary anastomosis. Ten (67%) died at a median of 6.5-hours (2-72) postoperatively; 2 died at 72 and 264-days. The 30-day mortality rate was higher (p = 0.01) among infants undergoing a laparotomy on NICU (10/15; 67%) than in theatre (54/167; 32%). There was no significant difference in mean Paediatric Index of Mortality 2 Scores between survivors and nonsurvivors (p = 0.55). Three (20%) infants remain alive with no or minimal disability at 1.4 (0.5-7.5) years. Conclusion: Laparotomy for NEC on NICU is a treatment option for neonates who are too unstable to transfer to theatre. However, with 67% dying within 6.5-hours and a further 13% after months in hospital, we must consider whether surgery is always in their best interests. Development of a prediction model to help distinguish those at highest risk of long-term morbidity and mortality could help with decision making in this difficult situation