Renal regenerative capacity related to stem cell reserve in nephrectomized rats.

PURPOSE: On the new era of stem cell therapy, the present experimental study was conducted to investigate renal regenerative capacity related to kidney stem cell reserve in different nephrectomy (Nx) models. METHODS: Three- and eight-week-old rats (n = 168) were randomly divided into four groups to include control and three Nx subgroups (1/6 Nx, 1/2 Nx, and 5/6 Nx) (Fig. 1). On post-Nx days 15, 30 and 60, kidney specimens were obtained to determine renal regenerative capacity. The specimens were examined with immunofluorescence. CD90/CD105 and Ki-67 expressions were determined as stem cell and cellular proliferation markers, respectively. Fig. 1 Intraoperative photographs showing three different types of nephrectomies (unilateral total Nx has not been shown in 5/6 Nx group) RESULTS: CD90 and CD105 expressions were stronger in glomeruli, but Ki-67 expressions were present only in tubuli. When all Nx types and post-Nx days were considered, both 3- and 8-week-old rats undergone 5/6 Nx had the highest glomerular CD90 and CD105 double expressions. While the expressions gradually increased toward the day 60 in 3-weeks old rats, 8-week-old rats had almost stable double expressions. The strongest tubular Ki-67 expressions were seen in 5/6 Nx groups of both in 3- and 8-week-old rats. The expressions were strongest on day 15 and then gradually decreased. Ipsilateral 1/6 Nx groups had stronger Ki-67 expression than contralateral ones in both age groups. CONCLUSIONS: Kidneys may pose a regenerative response to tissue/volume loss through its own CD90- and CD105-related stem cell reserve which mainly takes place in glomeruli and seems to have some interactions with Ki-67-related tubular proliferative process. This response supports that kidney stem cells may have a potential to overcome tissue/volume loss-related damage.

Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Multidisciplinary Management of Pediatric Hepatoblastoma: A 20-Year Single-Center Experience.

BACKGROUND: Hepatoblastoma is rare cancer that responds well to risk-based chemotherapy, and surgical treatment is needed to achieve complete remission and satisfactory survival rates in hepatoblastoma patients. In this study, we evaluated the clinical features and treatment outcomes of pediatric hepatoblastoma patients treated in our clinic. METHODS: Eighteen patients with hepatoblastoma who were treated and followed up in our center between June 1999 and June 2020 were analyzed retrospectively. All patients were evaluated by a multidisciplinary team and managed using a risk-based protocol (SIOPEL-1 and SIOPEL-3). RESULTS: The patients' mean age at diagnosis was 38.33 ± 52.34 months. Sixteen patients (89%) received neoadjuvant chemotherapy, and 2 patients (11%) who underwent complete mass excision at diagnosis received adjuvant chemotherapy. After neoadjuvant therapy, the tumor was completely resected in 8 patients (45%), while liver transplantation was performed in 6 patients (34%) because complete resection of the tumor was not possible. Two patients died before surgical treatment. One patient relapsed with lung metastasis after salvage chemotherapy. She is alive without disease at 64 months. The mean follow-up time was 59.3 ± 49.8 months; 5-year overall and disease-free survival rates were 88.9% and 80.8%, respectively. The 5-year overall survival rate was 100% for both liver transplant and resected patients, whereas 5-year disease-free survival was lower in transplant patients (75% vs 100%, P < .001). CONCLUSION: Multidisciplinary follow-up is especially important for patients who may need liver transplantation. Some patients may benefit from new treatment options such as radiofrequency ablation and cyberknife treatment.

Patients with disorders of sex development undergoing surgical treatment: A psychosocial evaluation in adolescence.

The surgical outcomes of disorders on sex development (DSD) are comparatively well studied in the literature, whereas studies investigating its impacts on mental health are scarce. In this study, we aimed to evaluate psychiatric diagnoses, sex roles, quality of life, and adolescents who were surgically treated because of DSD as well as parental attitudes in their parents. The study group consisted of 19 patients diagnosed with DSD and the control group consisted of 20 age- and gender-matched healthy peers. The Kiddie-Schedule for Affective Disorders and Schizophrenia was performed by a child and adolescent psychiatrist to assess the psychiatric diagnoses. To evaluate quality of life (QoL) and sex roles, The Pediatric Quality of Life Inventory (PedsQL), and the Bem Sex Role Inventory were used, respectively. Mothers completed the PedsQL-Parent Form and the Parental Attitude Research Instrument (PARI). Of 19 children in the patient group, 14 (73.7%) had a past or current history of at least one psychiatric disorder. The most common psychiatric disorder was major depression. There was no significant difference between the two groups in terms of sex roles. A statistically significant difference was found between the study and control groups in four factor scores of the PARI. While there was no significant difference between the groups in terms of the children's QoL scores, parent-proxy reports of psychosocial health scores and total QoL scores of the study group were significantly lower than the controls. This finding shows that parents perceived the QoL of their children with DSD as worse than their healthy peers, probably due to their concerns for the future. In conclusion, it is important to identify and treat the psychiatric disorders concomitant in patients with DSD.

Treatment of Vesicoureteral Reflux Detected After Renal Transplant in Pediatric Patients: A Single-Center Experience.

OBJECTIVE: In children who undergo renal transplant, vesicoureteral reflux on the transplanted kidney is a serious complication that may result in organ loss. In this study, we aimed to evaluate the results of endoscopic and open surgical techniques in the treatment of patients with recurrent urinary tract infections and vesicoureteral reflux after renal transplant. MATERIAL AND METHODS: The files of pediatric patients who underwent renal transplant in our hospital between January 2016 and January 2019 were evaluated retrospectively. In this single-center analysis, we investigated the incidence of vesicoureteral reflux in the kidney transplant recipients and the results of various approaches to treat it. RESULTS: Eighty pediatric patients underwent renal transplant between January 2016 and January 2019. Fourteen of those patients (17.5%, 7 female and 7 male) were diagnosed with vesicoureteral reflux in the postoperative period. Twelve of 14 patients received endoscopic injections as the first treatment. Clinical or radiological success was achieved in 5 patients (5 of 15 injection treatments, 33%); in 4 patients (4/12, 33.3%) success was after the first endoscopic injection treatment, and in 1 patient (1/3, 33.3%) success was after the second injection. Meanwhile, clinical or radiological success was achieved in 6 of 7 patients who underwent redo ureteroneocystostomy (6/7, 85.7%). CONCLUSION: Although symptomatic vesicoureteral reflux after renal transplant is rare in pediatric patients, it is an important cause of morbidity as it requires recurrent surgical procedures. Although endoscopic treatment is safe and minimally invasive, the success rate is lower than expected, and redo of ureteral reimplant may be required in most cases.

Multidirectional and simultaneous evaluation of gastroschisis-related intestinal damage in chick embryos.

PURPOSE: In a chick model of gastroschisis, we aimed to investigate the morphological/cellular, molecular, and ultrastructural changes taking place in gastroschisis-related intestinal damage (GRID). METHODS: 13-Day fertilized eggs were divided into two groups. CONTROL GROUP: chorio-amnio-allontoic membranes opened and abdominal wall exposed. Gastroschisis group: an anterior abdominal wall defect created after opening membranes. Embryos from both groups were surgically removed on post-fertilization day 19. Intestinal samples were obtained for histopathology, immunohistochemistry, molecular biology, and electron microscopy. RESULTS: The histopathological grade of intestinal damage which primarily involved mucosal structures was significantly higher in the gastroschisis group when compared to the control group (p<0.001). Immunohistochemically, E-cadherin and synaptophysin immunoreactivity in the gastroschisis group was significantly lower than control group (p<0.05 and p<0.01, respectively), whereas there was no significant difference in laminin and type-4 collagen immunoreactivity between the groups (p>0.05). Molecular analyses indicated a significant decrease in NFκB and IκB expression in the gastroschisis group (p<0.05 and p=0.001, respectively). Electron microscopy showed that the gastroschisis group had considerable ultrastructural damage, manifested by apoptosis in all layers. CONCLUSIONS: GRID affected all layers but was more prominent in mucosa. The damage may depend on E-cadherin and synaptophysin downregulation. Increased apoptotic activity, associated with decreased NFκB and IκB expression, may be an important component of this multifactorial damaging process.

Epimorphin expression in a rat model of pulmonary hypoplasia associated with congenital diaphragmatic hernia.

PURPOSE: The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains unclear. Interactions between the epithelium and surrounding mesenchyme play an important role in normal lung morphogenesis. Epimorphin, a stromal protein, plays a role in epithelial morphogenesis and lung branching, both of which are involved in pulmonary hypoplasia. In this study, we aimed to examine the relationship between epimorphin and pulmonary hypoplasia associated with CDH in an animal model. METHODS: Time-pregnant rats were exposed to nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D16 and D20, and were divided into control, hypoplastic lungs with CDH (CDH+), and hypoplastic lungs without CDH (CDH-). Both lungs of each fetus were removed and subjected to morphometric and molecular biologic analyses. Lung-to-body weight ratios were calculated. Pulmonary RNA was extracted, and relative mRNA level of epimorphin was determined by quantitative real-time PCR (qRT-PCR). Protein expression of epimorphin was investigated by Western blotting. RESULTS: In groups D16 and D20, lung-to-body weight ratios in subgroups CDH+ were significantly lower than those of controls and CDH-. The relative mRNA expression levels of epimorphin were significantly increased in both lungs in subgroup CDH+ compared with controls and CDH- on D16. Pulmonary epimorphin gene expression levels were significantly decreased in CDH+ group on D20 compared to controls. Western blotting confirmed the qRT-PCR results showing decreased pulmonary epimorphin protein expression in CDH+ hypoplastic lungs compared to controls on D20. CONCLUSION: Our study shows that there is an association between the epimorphin expression and pulmonary hypoplasia associated with CDH. Although the cause-effect relationship is far from being established, epimorphin-related mechanisms have a more critical role in early (D16) developmental stage.

Mixed gonadal dysgenesis in a patient with de novo tas(Y;19)(p11.3;q13.4) and 45,X mosaicism.

We report a patient with a de novo telomeric association between chromosomes 19 and Y in conjunction with mixed gonadal dysgenesis. The patient was first admitted to the clinic because of abnormal external genitalia. Laparoscopic evaluation revealed (1) a rudimentary uterus, one fallopian tube, and a small gonad resembling an ovary on the right side, and (2) an immature fallopian tube, a vas deferens, and a gonad resembling a testis on the left side. Conventional cytogenetic analysis performed on cultivated peripheral blood cells, and tissue obtained from the phallus and a gonadal structure which resembled a testis revealed two different cell lines with the 46,X,tas (Y;19)(p11.3;q13.4) and 45,X karyotype. Y chromosome microdeletion analysis showed that the patient did not have any genomic deletions in the AZFa, b, c, or SRY regions on the long arm of the Y chromosome. This is the first report of a patient with mixed gonadal dysgenesis that is accompanied by a telomeric association between chromosomes 19 and Y with 45,X mosaicism.

The effects of three specific conditions related to critical care on adrenal function in children.

PURPOSE: To evaluate the effects of three specific conditions related to critical care on adrenal function with special regard to the levels of serum cortisol, corticotropin (ACTH), dehydroepiandrosterone sulfate, and cytokines. METHODS: The study enrolled a total of 74 children who were divided into three groups. Group 1 comprised 23 patients who had acute critical illness (ACI) associated with severe sepsis/septic shock. Group 2 comprised 27 patients who had ACI without sepsis. Group 3 comprised 24 patients who underwent major surgery. Blood samples were obtained for baseline measurements and a low-dose ACTH stimulation test (LD-ST) was performed. Serial ACTH and cortisol levels were measured with an interval of 3 days and LD-ST was repeated on day 14 for all groups. RESULTS: Baseline cortisol, ACTH, and dehydroepiandrosterone sulfate levels were significantly higher in patients with adrenal insufficiency (AI) than those of without AI. AI was detected in four patients in group 1, seven in group 2, and ten in group 3. Consecutive cortisol and ACTH levels did not differ significantly among the groups. On day 14, the recovery rate in patients with AI was 82 % in the whole group. Patient's age and interleukin-10 level were found to be independent predictors of AI. CONCLUSIONS: A considerable proportion of patients in these three groups had AI with a high spontaneous recovery rate in 2 weeks. The presence of sepsis was not associated with an increased risk of AI. Our serial cortisol and ACTH values in these different groups could be used as reference values for further studies.

Renal cell carcinoma presented with hypocalcemia in an adolescent.

Renal cell carcinoma is very rare in childhood. It is a different entity from its adult counterpart. We report a case of renal cell carcinoma presented with hypocalcemia in a 16-year-old girl that is, to the best of our knowledge, the first such published incident. The patient was treated by radical nephrectomy with regional lymphadenectomy. Hypocalcemia amended after surgery. Neither chemotherapy nor radiotherapy was given. She has remained disease free for 34 months.

Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report.

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

An unusual localization of embryonal rhabdomyosarcoma in a neonate.

Rhabdomyosarcoma (RMS) is a common, highly malignant, uniformly fatal childhood malignancy, which presents extremely rarely in the neonatal period; there are only a few reports about this tumor in this age group. While the primary tumor may arise virtually anywhere in the body, the extremity, orbit and genitourinary region are the most frequent sites; the retromammary region is extremely rare. Herein, we report a neonate with embryonal RMS arising from the anterior chest wall musculature at birth.

Does noncomplicated acute appendicitis cause bacterial translocation?

It is unknown whether noncomplicated acute appendicitis cause bacterial translocation. In this study, we aimed to test development of the bacterial translocation in the patients who were operated for acute appendicitis. In this prospective study, 10 control patients who underwent elective operations because of other reasons, and 18 patients with noncomplicated acute appendicitis were evaluated. No patients took prophylactic antibiotic. After laparotomy, samples were obtained from peritoneal leaf just close to wound edge, and peritoneal swab culture from right paracolic region. Before appendectomy, a mesenteric lymph node (MLN) adjacent to the terminal ileum was taken out. Tissue samples were placed in a sterile container for microbiological analysis, and 10% formalin for histopathological analysis. Control samples had no bacterial translocation. Only 3 of 18 (16.6%) patients with appendicitis included bacterial translocation to MLN. There was no significant difference between both groups. No bacterial colonization was detected in the peritoneal tissue and peritoneal swab culture. Peritoneal tissue injury score was 2 +/- 1.4 in controls and 2.8 +/- 1.7 in the patients with appendicitis (P>0.05). MLN injury score was 2.5 +/- 1.3 in controls and 3.2 +/- 1.5 in the patients with appendicitis (P>0.05). No patient developed wound and systemic infection. No significant bacterial translocation frequency and tissue injury score was identified in the children with noncomplicated acute appendicitis. This result suggests that antibiotic prophylaxis may be unnecessary in such patients.

Midline dorsal plication to repair recurrent chordee at reoperation for hypospadias surgery complication.

PURPOSE: Midline dorsal plication is an efficient and safe surgical technique to correct chordee. We investigated the efficacy of midline dorsal plication for recurrent chordee in complicated hypospadias reoperations. MATERIALS AND METHODS: We retrospectively evaluated the charts of 25 boys who underwent reoperation between 1999 and 2004 due to complications of primary hypospadias repair other than meatal stenosis. A total of 15 cases were initially managed elsewhere for primary repair or complications. The etiology of recurrent chordee was defined at surgical correction. When recurrent chordee was noted a midline dorsal plication was performed. RESULTS: Of 25 patients 10 had previously undergone chordee repair. Nine of these patients were observed to have recurrent chordee and 1 had de novo chordee. A total of 10 patients had recurrent or delayed onset chordee. Mean patient age at primary repair was 6.28 years (range 1 to 33). Mean age at last operation for chordee was 15.9 years (range 4 to 66). Mean interval to recurrent chordee was 6 years (range 1 to 16), excluding a 66-year-old blind patient who did not know when recurrent chordee developed. Five patients had chordee recur before puberty at a mean interval of 2.6 years. Mean reoperation rate was 2.4 for recurrent chordee cases and 2.6 for chordee-free cases. Mean followup after midline dorsal plication for recurrent chordee repair was 22 months (range 8 to 56), while mean followup in pubertal and postpubertal cases was 20 months. No recurrence of chordee or surgery related morbidity was observed after recurrent chordee repair by midline dorsal plication. CONCLUSIONS: Chordee may recur during puberty following successful chordee repair. The midline dorsal plication technique is simple, efficient and safe even in patients who have undergone multiple surgeries for hypospadias and chordee repair.

The comparative effect of single dose mivacurium during sevoflurane or propofol anesthesia in children.

BACKGROUND: We aimed to randomly compare intubating conditions, recovery characteristics and neuromuscular effects of single dose of mivacurium (0.2 mg.kg(-1)) during sevoflurane vs. propofol anesthesia in 60 healthy children, undergoing inguinal surgery. METHODS: All children were randomly allocated to receive 2 mg.kg(-1) propofol iv or sevoflurane 8% inspired concentration for induction of anesthesia. Anaesthesia was maintained with 66% nitrous oxide in oxygen and 100-120 microg.kg(-1) propofol or sevoflurane approximately 2-3% inspired concentration with controlled ventilation. The ulnar nerve was stimulated at the wrist by a train-of four (TOF) stimulus every 20 s and neuromuscular function was measured at the adductor pollicis. When the response to TOF was stable, 0.2 mg.kg(-1) mivacurium was given. The trachea was intubated successfully at the first attempt in all patients. RESULTS: Onset time following a single dose of mivacurium was shorter in the sevoflurane group (2.99 min), than in the propofol group (4.42 min). The times to 25, 50, 75, and 90% recovery were significantly longer in the sevoflurane group (13.1, 15.7, 18.6, and 21.2 min, respectively) than in the propofol group (11.4, 13.2, 14.4, and 17.2 min respectively). TOF ratios of 50, 70, and 90% were significantly occurred later in sevoflurane group than propofol group. CONCLUSIONS: Our results indicate that when compared with propofol group, the sevoflurane group had an accelerated onset and a delayed recovery of neuromuscular block induced by mivacurium in children.

Severe ischemia of the glans penis following circumcision: a successful treatment via pentoxifylline.

Severe ischemia or necrosis of glans penis is rare. We report the case of an 11-year-old boy with severe glanular ischemia occurring 24 h after circumcision. This was successfully treated with pentoxifylline injection for 5 days, and while the black color of the glans penis changed to brownish at 48 h, appearances were close to normal at 5 days. The patient did not require any surgical intervention, and was discharged without sequelae. We suggest that pentoxifylline might be considered as a treatment of choice for severe ischemia of glans penis.

Currarino syndrome associated with penoscrotal inversion and perineal fissure.

We present an unusual case of Currarino syndrome with a mucosa-lined deep perineal fissure extending to the sacrum, penoscrotal transposition, perineal hypospadias, and a penile ventral skin defect. The child had a sigmoid diverting colostomy because of high anal atresia. Magnetic resonance imaging illustrated absence of the levator ani and muscle complex in the pelvis. At 15 months, perianal examination pointed out a fistula orifice and a sac related to the fistula at the left side of the perineal fissure. The fistula, a fluid-filled sac extending to the sacrum, and mucosa overlying the perineal fissure were removed en bloc. The neck of the sac was ligated and divided at the level of the distal sacrum. In the same session, a Glenn-Anderson procedure was performed for penoscrotal transposition, and the penile chordee was released. X-ray showed a bony deformity of the sacrococcygeal region in the shape of a scimitar. Histopathological examination demonstrated that the sac contained glial neuronal islands and nerve fibers. The boy has no neurologic deficits and seems to be well. To our knowledge, these associated malformations are extremely rare.

Comparison of hypospadiac and normal preputial vascular anatomy.

PURPOSE: Data about the differences between the vascularization of normal and hypospadiac prepuce are lacking. We investigated the course of the preputial arterial blood vessels in normal controls and children with hypospadias by using transillumination, arterial methylene blue injection and 3-dimensional (3-D) reconstruction of serial histological sections focusing on arterial vessels. MATERIALS AND METHODS: Prepuce of 48 normal controls and 15 children with hypospadias was transilluminated by a front and back lighting technique and then photographed. All of the normal and 12 of hypospadiac prepuces not used for urethroplasty or penile body skin reconstruction were removed. The blood vessels of normal prepuce were also identified after arterial injection of methylene blue. Selected prepuce of normal controls and children with hypospadias was serially sectioned, and arterial and venous vessels were histologically distinguished. A 3-D computer reconstruction of the arterial system of normal and hypospadiac prepuces was performed. RESULTS: We confirmed the reliability of the transillumination technique to describe the arterial vascular anatomy of the prepuce by comparing the transillumination to methylene blue injection and 3-D reconstruction of histological sections. We classified the arterial vascular anatomy of normal prepuce as 1 artery predominant (41.67%), 2 arteries predominant (25%), H-type arching artery (12.5%) and net-like arterial system (20.83%). However, hypospadiac prepuce revealed a net-like arterial system more frequently (50%). We noted that the frequency of net-like arterial system was higher in more severe hypospadiac prepuce. CONCLUSIONS: Understanding the differences between normal and hypospadiac prepuce vascular anatomy is germane to hypospadias surgery. The arterial blood supply of the hypospadiac prepuce is different than normal. A better knowledge of the vascular anatomy of the hypospadiac prepuce may improve the surgical results of hypospadias repair.