First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension

Purpose

To report results of renal denervation (RDN) with the first catheter-based, non–balloon occlusion ultrasonic system in patients with resistant hypertension.

Effective Management of Pelvic Lymphocysts by Laparoscopic Marsupialfeation

Background and Objectives:

To evaluate laparoscopic transperitoneal marsupialization of pelvic lymphocysts at the time of laparoscopically directed assessment of response to first-line therapy in a population of patients treated for International Federation of Gynecologists and Obstetricians (FIGO) stage IC-IIC epithelial ovarian cancer.

Methods:

Between March 1995 and March 1998, eight patients with FIGO stage IC-IIC serous epithelial ovarian tumors who developed pelvic lymphocysts after primary surgical staging underwent transperitoneal laparoscopically directed marsupialization of lymphocysts at the time of second-look laparoscopy.

Results:

The mean age of the patient population was 50 years (range 23-65 years). The mean length of time required for marsupialization was 30 minutes (range 25-35 minutes). No patient required inpatient postoperative care. No intraoperative complications were observed. Computerized axial tomography (CT) scan of the abdomen and pelvis obtained 12 weeks following surgery failed to demonstrate re-accumulation of lymphocysts among any patient in the study population. With a median follow-up of 20 months (range 3-39 months), no patients have demonstrated pelvic lymphocyst recurrence.

Conclusions and Discussion:

Laparoscopically directed marsupialization of pelvic lymphocysts is technically feasible, safe and effective. Further study of this technique appears to be warranted.     

Predicting ideal outcome after pediatric liver transplantation: An exploratory study using machine learning analyses to leverage Studies of Pediatric Liver Transplantation Data

Machine learning analyses allow for the consideration of numerous variables in order to accommodate complex relationships that would not otherwise be apparent in traditional statistical methods to better classify patient risk. The SPLIT registry data were analyzed to determine whether baseline demographic factors and clinical/biochemical factors in the first‐year post–transplant could predict ideal outcome at 3 years (IO‐3) after LT. Participants who received their first, isolated LT between 2002 and 2006 and had follow‐up data 3 years post–LT were included. IO‐3 was defined as alive at 3 years, normal ALT (<50) or GGT (<50), normal GFR, no non‐liver transplants, no cytopenias, and no PTLD. Heat map analysis and RFA were used to characterize the impact of baseline and 1‐year factors on IO‐3. 887/1482 SPLIT participants met inclusion criteria; 334 had IO‐3. Demographic, biochemical, and clinical variables did not elucidate a visual signal on heat map analysis. RFA identified non‐white race (vs white race), increased length of operation, vascular and biliary complications within 30 days, and duct‐to‐duct biliary anastomosis to be negatively associated with IO‐3. UNOS regions 2 and 5 were also identified as important factors. RFA had an accuracy rate of 0.71 (95% CI: 0.68‐0.74), PPV = 0.83, and NPV = 0.70. RFA identified participant variables that predicted IO‐3. These findings may allow for better risk stratification and personalization of care following pediatric liver transplantation.     

RalA is overactivated in medulloblastoma

Medulloblastoma (MDB) represents a major form of malignant brain tumors in the pediatric population. A vast spectrum of research on MDB has advanced our understanding of the underlying mechanism, however, a significant need still exists to develop novel therapeutics on the basis of gaining new knowledge about the characteristics of cell signaling networks involved. The Ras signaling pathway, one of the most important proto-oncogenic pathways involved in human cancers, has been shown to be involved in the development of neurological malignancies. We have studied an important effector down-stream of Ras, namely RalA (Ras-Like), for the first time and revealed overactivation of RalA in MDB. Affinity precipitation analysis of active RalA (RalA-GTP) in eight MDB cell lines (DAOY, RES256, RES262, UW228-1, UW426, UW473, D283 and D425) revealed that the majority contained elevated levels of active RalA (RalA-GTP) as compared with fetal cerebellar tissue as a normal control. Additionally, total RalA levels were shown to be elevated in 20 MDB patient samples as compared to normal brain tissue. The overall expression of RalA, however, was comparable in cancerous and normal samples. Other important effectors of RalA pathway including RalA binding protein-1 (RalBP1) and protein phosphatase A (PP2A) down-stream of Ral and Aurora kinase A (AKA) as an upstream RalA activator were also investigated in MDB. Considering the lack of specific inhibitors for RalA, we used gene specific silencing in order to inhibit RalA expression. Using a lentivirus expressing anti-RalA shRNA we successfully inhibited RalA expression in MDB and observed a significant reduction in proliferation and invasiveness. Similar results were observed using inhibitors of AKA and geranyl–geranyl transferase (non-specific inhibitors of RalA signaling) in terms of loss of in vivo tumorigenicity in heterotopic nude mouse model. Finally, once tested in cells expressing CD133 (a marker for MDB cancer stem cells), higher levels of RalA activation was observed. These data not only bring RalA to light as an important contributor to the malignant phenotype of MDB but introduces this pathway as a novel target in the treatment of this malignancy.     

Surgical Management of Stable Vitiligo: A Review with Personal Experience

BACKGROUND: Various modalities are available for surgical management of stable, localized patches of vitiligo, which are resistant to conventional medical treatment. Cutaneous surgeons often struggle to select among various methods of surgical treatment that include camouflage tattooing, melanocyte transplants, excision, and melanocyte culture. The advantages, disadvantages, and limitations of all the available modalities are reviewed. OBJECTIVE: The purpose of this review is to find out if any guidelines can be drawn regarding the surgical management of stable vitiligo. METHODS: This article is based on a review of the medical literature and the author's personal experience over the last decade. RESULTS: It is difficult to draw any fixed guidelines from this review. Treatment must be individualized depending upon the site and the extent of involvement. CONCLUSION: Although the retrospective nature of this article limits its validity, discussing the various therapeutic options is of value as continuing medical education. Surgical treatment may be individualized to obtain the best possible cosmetic result.     

Trigeminal Neuralgia in Pregnancy: A Management Challenge

Pregnancy is known to aggravate pre‐existing chronic painful conditions. Trigeminal neuralgia (TN), albeit a disease of the elderly, may afflict pregnant females, which can further complicate its management. Teratogenic effects of the commonly used drugs on the developing fetus limit pharmacological treatment. Moreover, safety of commonly performed interventional therapies is marred by their inherent fetomaternal effects and more importantly the risk for radiation effects on the fetus due to the use of fluoroscopy. This rare coexistence of TN in pregnancy has not been reported before. Here we present a case of TN in a young woman, whose pain was aggravated when she became pregnant, and she was treated successfully by conventional radiofrequency ablation of the Gasserian ganglion.     

Glutathione-conjugate transport by RLIP76 is required for clathrin-dependent endocytosis and chemical carcinogenesis

Targeted depletion of the RALBP1-encoded 76-kDa splice variant, RLIP76, causes marked and sustained regression of human xenografts of lung, colon, prostate, and kidney cancers without toxicity in nude mouse models. We proposed that the remarkable efficacy and broad spectrum of RLIP76-targeted therapy is because its glutathione-conjugate (GS-E) transport activity is required for clathrin-dependent endocytosis (CDE), which regulates all ligand-receptor signaling, and that RLIP76 is required not only for survival of cancer cells but also for their very existence. We studied RLIP76 mutant proteins and the functional consequences of their expression into RLIP76(-/-) MEFs, identified key residues for GS-E binding in RLIP76, established the requirement of RLIP76-mediated GS-E transport for CDE, and showed a direct correlation between GS-E transport activities with CDE. Depletion of RLIP76 nearly completely blocked signaling downstream of EGF in a CDE-dependent manner and Wnt5a signaling in a CDE-independent manner. The seminal prediction of this hypothesis-RLIP76(-/-) mice will be deficient in chemical neoplasia-was confirmed. Benzo[a]pyrene, dimethylbenzanthracene, and phorbol esters are ineffective in causing neoplasia in RLIP76(-/-). PMA-induced skin carcinogenesis in RLIP76(+/+) mouse was suppressed completely by depletion of either PKCα or RLIP76 by siRNA or antisense and could be restored by topical application of RLIP76 protein in RLIP76(-/-) mouse skin. Likewise, chemical pulmonary carcinogenesis was absent in female and nearly absent in male RLIP76(-/-) mice. In RLIP76(-/-) mice, p53, p38, and JNK activation did not occur in response to either carcinogen. Our findings show a fundamental role of RLIP76 in chemical carcinogenesis.