Pediatric Surgeons' Adoption of an Innovative Laparoscopic Technique for Inguinal Hernia Repair: A Mixed Methods Study.

Purpose: We studied adoption of an innovative laparoscopic technique for pediatric inguinal hernia repair by pediatric surgeons and pediatric urologists following dissemination of evidence for its benefits. Methods: This mixed methods study included children who received inguinal hernia repairs during 2017-2019 and their surgeons. We examined surgeons' adoption and use of the innovative technique and rates of ipsilateral recurrence and metachronous contralateral repair. In-depth interviews with surgeons were used to identify themes regarding attitudes and practices regarding the adoption of surgical innovations. Results: No ipsilateral recurrences were noted among open repairs after 1.5 years of average follow-up, while 1.54% (7/453) of unilateral and 0.50% (3/606 sides) of bilateral innovative surgeries required ipsilateral repair after 1.3 years of average follow-up. Among unilateral cases, metachronous contralateral repairs were performed in 1.63% (8/490) of open and 0.44% (2/453) of innovative surgeries. Surgeon interviews identified approaches to continued learning and change; the role of departmental culture, norms, and resources; and technical issues specific to pediatric surgery and pediatric inguinal hernia repair. Conclusions: Outcomes may have improved over time as a consequence of learning. Differences among surgeons and departments influenced the speed of adoption. Surgeons linked the collegial model used when adopting the new technique to the apprenticeship model used during their training. We propose research into the collegial model to improve translation of evidence-based surgical innovations into practice. Level of Evidence: Level III.

Long-term follow-up of pediatric open and laparoscopic inguinal hernia repair.

BACKGROUND: Pediatric laparoscopic inguinal hernia repair is not widely accepted. STUDY DESIGN: Children 0-14 years who underwent inguinal hernia repair during 2010-2016 at Kaiser Permanente Northern California were classified into five groups: (1) open unilateral repair without contralateral exploration; (2) open unilateral repair with contralateral laparoscopic exploration ("open+explore"); (3) open bilateral repair; (4) laparoscopic unilateral repair; and (5) laparoscopic bilateral repair. Outcomes included ipsilateral reoperation, metachronous contralateral repair, incision time, and complications. RESULTS: The study included 1697 children. Follow-up averaged 3.6 years after open (N = 1156) and 2.6 years after laparoscopic (N = 541) surgery. Metachronous contralateral repair was performed in 3.8% (26/683) of patients with open unilateral surgery without contralateral exploration, 0.7% (2/275) of open+explore patients, and 0.9% (3/336) of laparoscopic unilateral patients (p < 0.01). Ipsilateral repair was performed in 0.8% (10/1156) of open repairs and 0.3% (2/541) of laparoscopic repairs. Chart review confirmed 5 postoperative infections in 1156 patients with open surgery (0.43%) and 6 infections in 541 patients with laparoscopic surgery (1.11%) (p = 0.11). CONCLUSION: Our study's laparoscopic and open approaches have similar low ipsilateral reoperation rates, incision times, and complications. The use of laparoscopy to visualize the contralateral side resulted in a significantly lower rate of metachronous contralateral repair. LEVEL OF EVIDENCE: Level III.

Minimal access laparoscopic surgery for treatment of ulcerative colitis and familial adenomatous polyposis coli in children and adolescents.

BACKGROUND: Laparoscopic restorative proctocolectomy is standard surgical treatment for patients with ulcerative colitis (UC) and familial adenomatous polyposis coli (FAP). Scar burden can be minimized by reducing the number of laparoscopic ports. The aim of this study is to review the authors' experience with reduced-port laparoscopy in this setting and to compare it with conventional laparoscopy using multiple ports. MATERIALS AND METHODS: Charts of pediatric patients undergoing colectomy for UC or FAP between 2009 and 2012 were retrospectively reviewed. Patients who had the operation performed through one or two multichannel ports were assigned to the minimal access (MA) study group. Patients who had four or five single-channel ports with or without an additional small laparotomy were assigned to the LAP group. RESULTS: Twenty-two patients were identified. Ages at first operation were 2-18 years (median, 13.5 years). There were no conversions to laparotomy and no mortality. Mean operative times for the MA and LAP groups, respectively, were 250 and 284 minutes for abdominal colectomy with end ileostomy (P=.15), 198 and 301 minutes for completion proctectomy with diverting loop ileostomy (DLI) (P=.26), and 455 and 414 minutes for proctocolectomy with ileal pouch-anal anastomosis and DLI (P=.72). A major complication requiring laparotomy occurred in 1 patient (9%) in the MA group and in 2 patients (18%) in the LAP group. CONCLUSIONS: Minimal access laparoscopic surgery for UC and FAP is safe and feasible. A slightly larger incision at the ostomy site facilitates extraction of the specimen and extracorporeal construction of a J-pouch. Operative times and hospital stay are comparable to those with multiport laparoscopy.

Single-incision pediatric endosurgery (SIPES) splenectomy: a case-control series.

BACKGROUND/PURPOSE: Single-incision pediatric endosurgery (SIPES) is gaining popularity. The aim of this study was to review the authors' experience with SIPES splenectomy and compare it with conventional laparoscopic splenectomy. SUBJECTS AND METHODS: After institutional review board approval, data on SIPES splenectomy in children were collected prospectively. The study group was compared with a control group of patients who were retrospectively identified as having undergone conventional laparoscopic splenectomy during the same time period. RESULTS: Sixteen children underwent SIPES splenectomy. Ages ranged from 1 to 15 years, with a median of 7 years, and weights were between 10 and 70 kg, with a median of 24 kg. The control group was similar in age and weight characteristics. The most common diagnoses were hereditary spherocytosis, sickle cell disease, and immune thrombocytopenic purpura. There were two conversions to open splenectomy in the SIPES group and one in the laparoscopic group. Operative times were 40-190 minutes (median, 84 minutes) in the SIPES group and 51-154 minutes (median, 99 minutes) in the conventional laparoscopic group. CONCLUSIONS: The SIPES technique is well suited for splenectomy. Despite instruments and camera being in-line, working angles are not compromised, and visualization is adequate. Operating time and hospital stay are comparable to those with standard laparoscopic splenectomy, but the cosmetic result may be superior.

Laparoscopic surgery in children with congenital heart disease.

PURPOSE: The study aim was to determine outcomes of children with congenital heart disease who underwent laparoscopic procedures. METHODS: A single-institution, institutional review board-approved, retrospective review was conducted including children younger than 5 years with congenital heart disease who underwent laparoscopic or open abdominal procedures. Patient demographics, operative details, complications, and 30-day mortality were examined. RESULTS: Over 10 years, 111 children with congenital heart disease underwent 121 laparoscopic procedures. Median age was 2.5 months, with 87% being infants. Laparoscopic gastrostomy was the most common procedure (101). There was no intraoperative hemodynamic instability, median operative time was 70 minutes, postoperative complications were low (5%), and all children were alive at 30 days. Only 8 patients required conversion from laparoscopic to open, all secondary to technical issues, not hemodynamic instability. There were 42 children with cardiac disease who underwent 45 open procedures during the study period. There were no significant differences between patient demographics, type of procedure, operative time, complications, or 30-day mortality comparing the open and laparoscopic groups. CONCLUSION: In this review, there were no major contraindications to performing laparoscopic procedures in children with congenital heart disease, and we conclude that it is reasonably safe to perform laparoscopic surgery on these children.

The Cross-technique for single-incision pediatric endosurgical pyloromyotomy.

BACKGROUND: Single-incision pediatric endosurgical (SIPES) pyloromyotomy is frequently used for the treatment of hypertrophic pyloric stenosis at our center. Our initial SIPES approach mirrored the conventional, triangulated laparoscopic pyloromyotomy. Because an increased number of perforations were noted on our initial analysis, a more straightforward Cross-technique SIPES pyloromyotomy was developed. This study compares the current Cross-technique SIPES pyloromyotomy to the previous standard SIPES operation. METHODS: The Cross-technique entails grasping the antrum with the surgeon's left hand instrument, retracting toward the left lower quadrant, and thereby orienting the pylorus obliquely toward the right upper quadrant. The serosal incision and muscular spreading is accomplished using a right-hand instrument that crosses over the left hand grasper. Demographic variables, operative times, estimated blood loss (EBL), complications, conversion rate, and postoperative length of stay were compared. RESULTS: Twenty-nine Cross-technique patients were compared with 23 in the standard group. The Cross-technique was faster than the standard procedure (21 ± 5 vs. 27 ± 12 min, p = 0.03) and EBL was lower (1.3 ± 0.5 vs. 1.7 ± 0.6 ml, p = 0.02). There were two mucosal perforations requiring conversions to triangulated 3-access-site laparoscopy in the standard, and one conversion to open surgery in the Cross-technique group. Patients who underwent cross-technique pyloromyotomy weighed less (3.6 ± 0.6 vs. 4.0 ± 0.5 kg, p = 0.012), but there were no differences in age, gender ratio, conversion rate, or length of stay. There was one postoperative wound infection in the cross-technique, but none in the standard group. No patients required reoperation. All participating surgeons felt that the cross-technique was more ergonomic and easier to perform than the standard SIPES technique. CONCLUSIONS: The Cross-technique appears superior to standard SIPES pyloromyotomy and should be preferentially used for single-incision endosurgical pyloromyotomy for hypertrophic pyloric stenosis.

An evidence-based clinical protocol for diagnosis of acute appendicitis decreased the use of computed tomography in children.

PURPOSE: The increased use of computed tomography (CT) to diagnose appendicitis in children has led to a concern for the possibility of increased CT-related cancer morbidity. We designed a clinical protocol for the diagnosis and treatment of appendicitis in children in an attempt to decrease the use of CT scans at our institution. METHODS: Patients who had surgical consultation for suspected appendicitis were placed on the clinical protocol. Data concerning diagnosis and treatment were collected prospectively. Retrospective data from patients admitted to our institution with acute appendicitis before the clinical protocol were collected as historical controls. RESULTS: One hundred twelve patients were diagnosed and treated by our protocol between June and November 2009. Of these, 100 patients underwent an appendectomy for acute appendicitis. They were compared with 146 patients from 2007. In-house CT use decreased from 71.2% to 51.7% (P = .01). Preoperative ultrasound use increased from 2.7% to 21% (P < .001). The negative appendectomy rate increased (6.8% vs 11%, P = .25). CONCLUSIONS: Our findings suggest that the implementation of an evidence-based clinical protocol for the diagnosis and treatment of acute appendicitis in children may safely decrease the use of CT scans and increase the use of ultrasound.

Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury.

BACKGROUND: We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury. METHODS AND RESULTS: C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. Infarct size was measured using triphenyltetrazoliumchloride staining. A c-Jun NH(2)-terminal kinase (JNK) activation was determined by Western blotting, nuclear factor (NF)-kappaB activity was detected by gel-shift assay, and cytokine expression was measured by ribonuclease protection assay. Mice treated with eritoran developed significantly smaller infarcts when compared with mice treated with vehicle alone (21.0+/-6.4% versus 30.9+/-13.9%; P=0.041). Eritoran pretreatment resulted in a reduction in JNK phosphorylation (eritoran versus vehicle: 3.98+/-0.81 versus 7.01+/-2.21-fold increase; P=0.020), less nuclear NF-kappaB translocation (2.70+/-0.35 versus 7.75+/-0.60-fold increase; P=0.00007), and a decrease in cytokine expression (P<0.05). CONCLUSIONS: We conclude that inhibition of TLR4 with eritoran in an in situ murine model significantly reduces MI/R injury and markers of an inflammatory response.

Current treatment of intraabdominal infections.

Although peritonitis has been recognized as a common and complex disease entity since ancient times, the true understanding and pathophysiology, as well as treatment of peritonitis, continue to plague surgeons and physicians. The clinical course and outcome of peritonitis is dependent upon the struggle between the quantity and virulence of the pathogen and host's physiologic reserve, including the ensuing inflammatory response. The current multimodality treatment of intraabdominal infections is based upon the fundamental principles established by Polk in 1979: surgical source control, fluid resuscitation, adequate nutrition, support of failing organ systems, and antibiotics. Although dramatic advances have been made in the pharmacological treatment of intraabdominal infections, mortality for complicated cases remains high. Consequently, future directions in management of peritonitis may require agents that target specific endotoxin receptors, inflammatory signaling molecules, or immunomodulatory moieties.

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.

OBJECTIVES: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats. METHODS: Rats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg . kg(-1) . d(-1)), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg . kg(-1) . d(-1), the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured. RESULTS: Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 +/- 1.9 vs 36.5 +/- 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 +/- 0.52 vs 2.1 +/- 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor alpha and interleukin 1beta were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor alpha: 1.18 +/- 0.36 vs 3.05 +/- 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1beta: 2.2 +/- 0.34 vs 4.4 +/- 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 +/- 0.62 vs 3.1 +/- 0.42 fold-increase, at 1 week). CONCLUSION: FR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension.

FR167653 diminishes infarct size in a murine model of myocardial ischemia-reperfusion injury.

OBJECTIVE: During myocardial ischemia-reperfusion injury, p38 mitogen-activated protein kinase is activated. We examined the effect of a highly specific inhibitor of p38 mitogen-activated protein kinase, FR167653, in an experimental model of regional myocardial ischemia-reperfusion. METHODS: CD-1 mice received FR167653 intraperitoneally 24 hours before 30 minutes of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. The p38 mitogen-activated protein kinase activation and kinase activity were determined by Western blotting with monoclonal antibodies for the phosphorylated from of p38 mitogen-activated protein kinase or its substrate, activating transcription factor 2. Nuclear factor kappaB activity was measured by detecting translocation of nuclear factor kappaB to the nucleus. The expression of inflammatory cytokines was measured by ribonuclease protection assay. RESULTS: Pretreatment of mice with FR167653 before myocardial ischemia-reperfusion resulted in a reduction in p38 mitogen-activated protein kinase phosphorylation (P =.018), an inhibition of p38 mitogen-activated protein kinase activity (P =.047), a smaller amount of nuclear factor kappaB (P =.001), and a decrease in the expression of inflammatory cytokines (tumor necrosis factor alpha: P =.023, interleukin 1beta: P =.038, monocyte chemotactic protein 1: P =.0001) in the heart and the development of a significantly smaller infarct (P =.0069) relative to hearts from mice treated with vehicle alone. Activation of c-Jun N-terminal kinase and extracellular signal-regulated kinase were observed after myocardial ischemia-reperfusion without inhibition by FR167653. CONCLUSION: We conclude that FR167653 selectively inhibits p38 mitogen-activated protein kinase activation and activity during regional myocardial ischemia-reperfusion injury and efficaciously reduces infarct size (by 73.6%). Thus p38 mitogen-activated protein kinase inhibition may have a role in the treatment of myocardial ischemia-reperfusion.

Toll-like receptor 4 mediates ischemia/reperfusion injury of the heart.

BACKGROUND: Restoration of blood flow to the ischemic heart may paradoxically exacerbate tissue injury (ischemia/reperfusion injury). Toll-like receptor 4, expressed on several cell types, including cardiomyocytes, is a mediator of the host inflammatory response to infection. Because ischemia/reperfusion injury is characterized by an acute inflammatory reaction, we investigated toll-like receptor 4 activation in a murine model of regional myocardial ischemia/reperfusion injury. We used C3H/HeJ mice, which express a nonfunctional toll-like receptor 4, to assess the pertinence of this receptor to tissue injury after reperfusion of ischemic myocardium. METHODS: Wild-type mice (C3H/HeN) or toll-like receptor 4 mutant mice (C3H/HeJ) were subjected to 60 minutes of regional myocardial ischemia followed by 2 hours of reperfusion. At the end of reperfusion, the area at risk and the myocardial infarct size were measured as the end point of myocardial ischemia/reperfusion injury. Myocardial mitogen-activated protein kinase activation was measured by Western blotting, and nuclear translocation of nuclear factor-kappaB and activator protein-1 was determined by electrophoretic mobility shift assay. Ischemia/reperfusion-injured myocardium was also assessed by ribonuclease protection assay for expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin-1beta, monocyte chemotactic factor-1, and interleukin-6). RESULTS: The area at risk was similar for all groups after myocardial ischemia/reperfusion injury. There was a 40% reduction in infarct size (as a percentage of the area at risk) in C3H/HeJ mice compared with C3H/HeN mice (P =.001). Within the myocardium, significant activation of c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase was observed in both strains after ischemia and during reperfusion as compared with an absence of mitogen-activated protein kinase activation during sham operations; however, c-Jun N-terminal kinase activity, but not p38 or extracellular signal-regulated kinase activity, was significantly reduced in C3H/HeJ mice (P <.05). In both groups, nuclear factor-kappaB and activator protein-1 nuclear translocation occurred in the myocardium during myocardial ischemia/reperfusion injury, but, by densitometric analysis, nuclear translocation of nuclear factor-kappaB and activator protein-1 was significantly decreased in C3H/HeJ mice compared with C3H/HeN mice. Interleukin-1beta, monocyte chemotactic factor-1, and interleukin-6 were detectable in reperfused ischemic myocardium but were not detected in sham-operated myocardium; the expression of each of these mediators was significantly decreased in the myocardial tissue of C3H/HeJ mice when compared with expression in the control C3H/HeN mouse strain. CONCLUSIONS: Our data suggest that toll-like receptor 4 may mediate, at least in part, myocardial ischemia/reperfusion injury. Inhibition of toll-like receptor 4 activation may be a potential therapeutic target to attenuate ischemia/reperfusion-induced tissue damage in the clinical setting.

Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury.

Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known. Tissue factor (TF) and thrombin, two potent procoagulant and proinflammatory mediators, are recognized to play significant roles in myocardial I/R injury. To investigate the role of TF and thrombin in myocardial I/R injury, we used rabbit and murine in situ coronary artery ligation models. Increased TF mRNA, antigen, and activity were found in ischemic cardiomyocytes. Administration of an inhibitory antirabbit TF monoclonal antibody before or during the onset of ischemia resulted in a significant reduction in infarct size. Functional inhibition of thrombin with hirudin also reduced the infarct size. However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury.