Lessons learned from lower urinary tract complications of anorectoplasty for imperforate anus with rectourethral/rectovesical fistula: Laparoscopy-assisted versus posterior sagittal approaches

PurposeTo report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP).Methods153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively.ResultsAfter mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1).ConclusionsStrategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero.Level of Evidence: Level III     

Two cases of polymorphic ventricular tachycardia induced by the administration of verapamil against paroxysmal supraventricular tachycardia

Verapamil is widely used for the termination of paroxysmal supraventricular tachycardia (PSVT) with little proarrhythmic effect. We describe two cases of PSVT that changed to non-sustained polymorphic ventricular tachycardia after administration of verapamil. Electrophysiological study revealed atrioventricular nodal reentrant tachycardia in the first case, and atrioventricular reentrant tachycardia due to a concealed left lateral accessory pathway in the second case. Catecholamine-induced automaticity was one of the possible mechanisms of VT in the first case, but the mechanism is unknown in the second case.     

A patient with recurrent rectal cancer in whom pulmonary metastasis disappeared by FOLFOX 4 therapy

We performed FOLFOX 4 therapy in a patient with lung metastasis (a 62-year-old woman) after surgery for rectal cancer and observed both normalization of tumor markers and disappearance of the metastasis. Low anterior resection was performed for progressive rectal cancer, and treatment with UFT and folinate was started one month after surgery. However, tumor markers increased after 2 months of treatment and CT scans showed metastases to both lungs. FOLFOX 4 therapy was started, and tumor markers became normal after four courses, while the lung metastases disappeared after 10 courses. The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea. This treatment appeared to be effective for the inhibition of lung metastasis associated with colorectal cancer.     

Challenges in genetic counseling because of intra‐familial phenotypic variation of oral‐facial‐digital syndrome type 1

Oral‐facial‐digital syndrome type 1 (OFD1; MIM 311200) is characterized by multiple anomalies of the oral cavity, face and digits. We report a family with OFD1, where two female siblings and their mother shared the same mutation of the responsible gene (OFD1) c.1193_1196delAATC. Phenotypic variability was observed among them; the mother showed minimal features of OFD1, whereas her two daughters showed partial features and the full spectrum of OFD1, respectively. Thus, OFD1 was suspected only after a health check‐up during pregnancy of the second patient showing fetal brain anomaly and maternal polycystic kidney. For these reasons, there was a delay in the recognition of OFD1 in this family. Patients with OFD1 show phenotypic variability, which poses challenges for genetic counseling.     

Role of nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia

Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which is mediated through mobilization of EPCs from BM and their recruitment to the ischemic sites. Reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, their role in BM and EPC function is unknown. Here we show that hindlimb ischemia of mice significantly increases Nox2 expression and ROS production in BM-mononuclear cells (BMCs), which is associated with an increase in circulating EPC-like cells. Mice lacking Nox2 show reduction of ischemia-induced flow recovery, ROS levels in BMCs, as well as EPC mobilization from BM. Transplantation of wild-type (WT)-BM into Nox2-deficient mice rescues the defective neovascularization, whereas WT mice transplanted with Nox2-deficient BM show reduced flow recovery and capillary density compared to WT-BM transplanted control. Intravenous infusion of WT- and Nox2-deficient BMCs into WT mice reveals that neovascularization and homing capacity are impaired in Nox2-deficient BMCs in vivo. In vitro, Nox2-deficient c-kit+Lin- BM stem/progenitor cells show impaired chemotaxis and invasion as well as polarization of actins in response to stromal derived factor (SDF), which is associated with blunted SDF-1-mediated phosphorylation of Akt. In conclusion, Nox2-derived ROS in BM play a critical role in mobilization, homing, and angiogenic capacity of EPCs and BM stem/progenitor cells, thereby promoting revascularization of ischemic tissue. Thus, NADPH oxidase in BM and EPCs is potential therapeutic targets for promoting neovascularization in ischemic cardiovascular diseases.     

Appendiceal stump closure in children with complicated appendicitis: a prospective analysis of endoloops versus endostaples

Introduction: Laparoscopic appendectomy (LA) can be performed safely and effectively using endoloops (EL) or endostaples (ES). We compared EL and ES for stump closure during LA for complicated appendicitis in children. Methods: All LA for complicated appendicitis performed between July 2005 and August 2009 were assessed prospectively. EL were used in 37 procedures and ES in 31. Apart from choice of technique which was the personal preference of the attending surgeon, all patients were managed according to the same intraoperative and postoperative protocols. Results: There was no significant difference between mean age at operation; gender ratio; mean preoperative and postoperative white blood cell; mean preoperative and postoperative white blood cell C‐reactive protein; histopathology; mean operating time (EL: 71 minutes; ES: 64 minutes); mean hospitalization (EL: 5.3 days; ES: 5.1 days); febrile period (EL: 2.1 days; ES: 1.9 days); white blood cell normalization (EL: 2.6 days; ES: 2.4 days); and intravenous antibiotic usage (EL: 3.8 days; ES: 3.7 days). There were no intraoperative complications or ICU admissions in either group, but two EL cases required conversion to open surgery (P=NS). Incidences of intra‐abdominal abscess (EL: n=1 or 2.7%; ES: n=1 or 3.2%), transient ileus (EL: n=2 or 5.4%; ES: n=2 or 6.4%), small bowel obstruction (EL: n=0; ES: n=0), and wound infection (EL: n=1 or 2.7%; ES: n=1 or 3.2 %) were not significantly different. Rate of rehospitalization for EL was 2.7% (n=1; colitis), and for ES, it was 3.2% (n=1; intra‐abdominal abscess) (P=NS). Mean cost for EL was US$890, and for ES, it was US$1300. Conclusion: This is the first prospective study comparing EL and ES during LA for complicated appendicitis in children. ES is more expensive, but there was no significant difference in morbidity for this technique, particularly with regard to incidence of postoperative intra‐abdominal abscess.     

Factors affecting long-term compliance of osteoporotic patients with bisphosphonate treatment and QOL assessment in actual practice: alendronate and risedronate

The aim of our study was to examine compliance with a daily dose of 5 mg alendronate (ALN) and 2.5 mg risedronate (RDN) in actual practice, and to determine the causes of noncompliance through a questionnaire. In addition, we studied the quality of life (QOL) of patients through another disease-related questionnaire. The overall compliance rate remained at approximately 40% one year after the initial dose. The rates did not differ significantly between the ALN group (783 patients) and the RDN group (491 patients). The compliances in the female group and the rheumatism group were better than in the male group and the nonrheumatism group. From the questionnaire, 36% of noncompliant patients showed adverse effects (AEs), and the other noncompliant patients stopped the medication in spite of having no AEs. A logistic regression analysis of factors that might have affected long-term compliance included AEs, an understanding of the disease, the method of ingestion, visiting medical facilities, the shape of the tablet, the cost of the drug, and the explanation of the doctor or pharmacist. This analysis showed that noncompliance occurred mainly due to AEs, the inconvenience of visiting a medical facility, unusual methods of ingestion, and a poor understanding of the disease. According to the results of the questionnaire for QOL assessment, the patients who continued the medication for more than 1 year had improved scores for pain in both the ALN and RDN groups. Osteoporotic treatment needs long-term patient compliance. To improve compliance, it is very important that doctors and pharmacists ensure that patients understand the purpose of this therapy.     

Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response

Application of ultrasound-mediated destruction of microbubbles (US + Bubble) to skeletal muscle creates capillary ruptures leading to leakage of the cell components. We studied whether US + Bubble combined with bone-marrow-derived mononuclear cells (BM-MNCs) infusion enables the targeted delivery of endothelial-lineage cells into the myocardium and improves cardiac function of the cardiomyopathy model due to the paucity of neocapillary formation. Pulsed US was applied to the anterior chest of BIOTO2 cardiomyopathy hamsters for 90 s after the intravenous injection of microbubble (Optison) followed by infusion of BM-MNCs. Cardiac samples from US + microbubble + BM-MNCs (US + Bubble + BM), US + Bubble, US + BM without Bubble, and saline infusion control groups were analyzed 12 weeks after treatment. Labeled BM-MNCs transplanted by US + Bubble were found to be mainly localized in the microvessels, but not by US stimulation without microbubble (121.2 +/- 24.5 vs. 2.80 +/- 1.30 cells/mm2, P < 0.001). Capillary densities in US + Bubble + BM group were increased 1.7-fold (P < 0.05) over the control, and neither US + Bubble nor US + BM enhanced neocapillary formation. 99mTc-Tetrofosmin scintigraphy revealed that blood perfusion area in the US + Bubble + BM group was 48% greater than the control (P < 0.01). US + Bubble stimulation induces the expression of adhesion molecules (VCAM-1 and ICAM-1) in capillaries, and the US + Bubble-mediated supply of BM-MNCs increased the myocardial content of VEGF and bFGF. The left ventricular wt/body wt, area of cardiac fibrosis, and apoptotic cell numbers in the US + Bubble + BM group significantly (P < 0.05) decreased by 82%, 73%, and 64% relative to the control, respectively. The cardiac function in myopathic hamsters (assessed by fractional shortening) was markedly improved 36% (P < 0.05) by US + Bubble + BM treatment. Targeted delivery of BM-MNCs by US + Bubble to the myocardium of the cardiomyopathic hamster increased the capillary densities and regional blood flow and inhibited cardiac remodeling, resulting in the prevention of heart failure. This non-invasive cell delivery system may be useful as a novel efficient approach for angiogenic cell therapy to the myocardium.     

Hirschsprung's disease: diagnosis using monoclonal antibody 171B5.

A new reliable immunohistochemical method for diagnosing Hirschsprung's disease (HD) using our unique monoclonal antibody (MAb) 171B5 against synaptic vesicles is described. Fresh frozen sections of rectal tissues were used from 13 patients with HD aged 2 weeks to 13 months; 9 had rectosigmoid HD and 4 had total colonic aganglionosis (TCA). Comparable normal colonic and rectal specimens were also obtained from 13 age-matched controls. All specimens were labeled with MAb 171B5, to demonstrate neuronal innervation patterns of both mucosa and submucosa. In all control specimens, many synapses arranged in variciform plexuses were seen in the lamina propria, a moderate number in the muscularis mucosae, and dense clusters in the submucosal plexus. In all aganglionic specimens, only scanty numbers of synapses which were not organized in variciform plexuses were seen in the lamina propria, none in the muscularis mucosae, and a few in the submucosa. These findings suggest that MAb 171B5 immunohistochemistry on the lamina propria alone can differentiate between normal and aganglionic bowel and appears to be a reliable and useful method for detecting HD on suction rectal biopsy.