Managing varicoceles in children: results with microsurgical varicocelectomy

Authors from New York present their experience of elective varicocelectomy, using microsurgical techniques, in a large series of children. They found the procedure to be safe and effective, and gave a much lower complication rate than the published rate in open varicocelectomy. The results of urethroplasty in post-traumatic paediatric urethral strictures are presented by authors from Mansoura. They found the overall success of one-stage perineal anastomotic repair of such strictures to be excellent, with very little morbidity. OBJECTIVE: To report our experience of microsurgical subinguinal varicocelectomy in boys aged < or = 18 years. PATIENTS AND METHODS: Boys aged < or = 18 years treated with microsurgical varicocelectomy between 1996 and 2000 at one institution were retrospectively reviewed. Indications for surgery included ipsilateral testicular atrophy, large varicocele or pain. Microsurgery was assisted by an operating microscope (x10-25) allowing preservation of the lymphatics, and the testicular and cremasteric arteries. Patient age, varicocele grade, complications and follow-up interval were recorded. RESULTS: In all there were 97 microsurgical subinguinal varicocelectomies (23 bilateral) in 74 boys (mean age 14.7 years). Left-sided varicoceles were significantly larger (mean grade 2.9) than right-sided (mean grade 1.4) varicoceles. The mean follow-up was 9.6 months. There were four complications: two hydroceles, of which one resolved spontaneously after 4 months; one patient had persistent orchialgia that resolved after 8 months; and one developed hypertrophic scarring at the inguinal incision site. There were no infections, haematomas or intraoperative injuries to the vas deferens or testicular arteries. All boys were discharged home on the day of surgery. CONCLUSIONS: Microsurgical subinguinal varicocelectomy in boys is a safe, minimally invasive and effective means of treating varicoceles. Compared with published results of the retroperitoneal mass ligation technique, which has a 15% overall complication rate and a 7-9% hydrocele occurrence rate, the microsurgical subinguinal approach appears to offer less morbidity, with a 1% hydrocele rate. We consider that microsurgical subinguinal varicocelectomy offers the best results with lower morbidity than other techniques.     

Bearbeitung und Transplantation hämatopoetischer Stammzellen

Background

New graft manipulation procedures make it possible to obtain highly purified hematopoietic stem cells from healthy donors.

Patients and Methods

A total of 116 children with leukemias, lymphomas, and nonmalignant diseases received purified (97%) peripheral stem cells from matched unrelated donors or mismatched related (haploidentical) donors.

Results

Acute and chronic GVHD were vastly minimized and a high overall rate of engraftment was achieved. Event-free survival at 5 years was 46% after haploidentical transplantation for children with ALL in remission who otherwise lacked a matched donor. Moreover, excellent results were observed in patients with nonmalignant diseases.

Conclusions

Graft manipulation results in well-characterized transplants with minimal risk of GVHD and makes a donor available for each patient by recruiting the parents. Thus, alternative donors should be strongly considered in all patients who need a stem cell transplantation but lack an identical donor.     

Linac-based radiosurgery or hypofractionated stereotactic radiotherapy in the treatment of large cerebral arteriovenous malformations

PURPOSE: We investigate retrospectively clinical outcome after radiosurgery (RS) or hypofractionated stereotactic radiotherapy (HSRT) in patients with large cerebral arteriovenous malformations (AVMs). METHODS AND MATERIALS: This analysis is based on 48 patients with cerebral AVM greater than 4 cm treated with HSRT or RS at our institution. Fifteen patients received HSRT, with 26 Gy median total dose in 4 to 5 fractions, and 33 patients received RS with 17 Gy median total dose in 4 to 5 fractions. Median target volume was 27 cc in HSRT and 7 cc in RS; median maximum diameter was 6 cm and 5 cm, respectively. Seventeen patients experienced intracranial hemorrhage before treatment. Median follow-up was 2.6 years. RESULTS: The 3-year and 4-year actuarial complete obliteration (CO) after HSRT was 17% and 33% and after RS was 47% and 60%, respectively. Actuarial CO was higher in AVMs less than 5 cm (66% vs. 37% after 4 years). Intracranial hemorrhage after HSRT occurred in 3 of 15 patients after 18 months median, and after RS in 7 of 33 patients after 17 months median. Bleeding risk was significantly higher in patients with prior hemorrhage (p < 0.04). Preexisting neurologic dysfunction improved/dissolved in 50% and remained stable in 45%. CONCLUSIONS: Large AVMs need a long time period to obliterate and show a high bleeding risk. Multimodal treatment strategies are required to reduce treatment volume before radiotherapy.     

RING finger-dependent ubiquitination by PRAJA is dependent on TGF-beta and potentially defines the functional status of the tumor suppressor ELF

In gastrointestinal cells, biological signals for transforming growth factor-beta (TGF-beta) are transduced through transmembrane serine/threonine kinase receptors that signal to Smad proteins. Smad4, a tumor suppressor, is often mutated in human gastrointestinal cancers. The mechanism of Smad4 inactivation, however, remains uncertain and could be through E3-mediated ubiquitination of Smad4/adaptor protein complexes. Disruption of ELF (embryonic liver fodrin), a Smad4 adaptor protein, modulates TGF-beta signaling. We have found that PRAJA, a RING-H2 protein, interacts with ELF in a TGF-beta-dependent manner, with a fivefold increase of PRAJA expression and a subsequent decrease in ELF and Smad4 expression, in gastrointestinal cancer cell lines (P < 0.05). Strikingly, PRAJA manifests substantial E3-dependent ubiquitination of ELF and Smad3, but not Smad4. Delta-PRAJA, which has a deleted RING finger domain at the C terminus, abolishes ubiquitination of ELF. A stable cell line that overexpresses PRAJA exhibits low levels of ELF in comparison to a Delta-PRAJA stable cell line, where ELF expression is high compared to normal controls. The alteration of ELF and/or Smad4 expression and/or function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by a high-level expression of PRAJA in gastrointestinal cancers. In hepatocytes, half-life (t(1/2)) and rate constant for degradation (k(D)) of ELF is 1.91 h and 21.72 min(-1) when coupled with ectopic expression of PRAJA in cells stimulated by TGF-beta, compared to PRAJA-transfected unstimulated cells (t(1/2) = 4.33 h and k(D) = 9.6 min(-1)). These studies reveal a mechanism for tumorigenesis whereby defects in adaptor proteins for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin-mediated pathway.     

Requirement of epidermal growth factor receptor for hyperplasia induced by E5, a high-risk human papillomavirus oncogene

Multicellular organisms rely on complex networks of signaling cascades for development, homeostasis, and responses to the environment. These networks involve diffusible signaling molecules, their receptors, and a variety of downstream effectors. Alterations in the expression or function of any one of these factors can contribute to disease, including cancer. Many viruses have been implicated in cancer, and some of these modulate cellular signal transduction cascades to carry out their life cycles. High-risk human papillomaviruses (HPVs), the causative agents of most cervical and anogenital cancers, encode three oncogenes. One of these, E5, has been postulated to transform cells in tissue culture by modulating growth factor receptors. In this study, we generate and characterize transgenic mice in which the E5 gene of the most common high-risk HPV, HPV16, is targeted to the basal layer of the stratified squamous epithelium. In these mice, E5 alters the growth and differentiation of stratified epithelia and induces epithelial tumors at a high frequency. Through the analysis of these mice, we show a requirement of the epidermal growth factor receptor for the hyperplastic properties of E5.     

Catheter placement for lysis of spontaneous intracerebral hematomas: does a catheter position in the core of the hematoma allow more effective and faster hematoma lysis?

For the fibrinolytic therapy of intracerebral hematomas (ICH) using recombinant tissue plasminogen activator (rtPA), a catheter position in the core of the hematoma along the largest clot diameter was assumed to be optimal for an effective clot lysis. However, it never had been proven that core position indeed enhances clot lysis if compared with less optimal catheter positions. In this study, the impact of the catheter position on the effectiveness and on the time course of clot lysis was evaluated. We analyzed the catheter position using a relative error calculating the distance perpendicular to the catheter’s center in relation to hematoma’s diameter and evaluated the relative hematoma volume reduction (RVR). The correlation of the RVR with the catheter position was evaluated. Additionally, we tried to identify patterns of clot lysis with different catheter positions. The patient’s outcome at discharge was evaluated using the Glasgow outcome score. A total of 105 patients were included in the study. The mean hematoma volume was 56 ml. The overall RVR was 62.7 %. In 69 patients, a catheter position in the core of the clot was achieved. We found no significant correlation between catheter position and hematoma RVR (linear regression, p = 0.14). Core catheter position leads to more symmetrical hematoma RVR. Faster clot lysis happens in the vicinity of the catheter openings. We found no significant difference in the patient’s outcome dependent on the catheter position (linear regression, p = 0.90). The catheter position in the core of the hematoma along its largest diameter does not significantly influence the effectiveness of clot lysis after rtPA application.