Predictors of sperm recovery after cryopreservation in testicular cancer.

Our objective was to identify predictors of improved postthaw semen quality in men with testicular cancer banking sperm for fertility preservation. We reviewed 173 individual semen samples provided by 67 men with testicular germ cell tumor (TGCT) who cryopreserved sperm before gonadotoxic treatment between 1994 and 2010 at our tertiary university medical center. Our main outcomes measures were independent predictors for the greater postthaw total motile count (TMC) in men with TGCT. Men with NSGCT were more likely to be younger (P < 0.01) and had high cancer stage (II or III, P < 0.01) compared with men with seminoma. In our multiple regression model, NSGCT histology, use of density gradient purification, and fresh TMC > median fresh TMC each had increased odds of a postthaw TMC greater than median postthaw TMC. Interestingly, age, advanced cancer stage (II or III), rapid freezing protocol, and motility enhancer did not show increased odds of improved postthaw TMC in our models. In conclusion, men with TGCT or poor fresh TMC should consider preserving additional vials (at least 15 vials) before oncologic treatment. Density gradient purification should be routinely used to optimize postthaw TMC in men with TGCT. Larger, randomized studies evaluating cancer stage and various cryopreservation techniques are needed to assist in counseling men with TGCT regarding fertility preservation and optimizing cryosurvival.

Totally intracorporeal robot-assisted laparoscopic reverse seven ileal ureteric reconstruction.

We describe the first reported case of completely intracorporeal robot-assisted laparoscopic reverse seven ileal ureteric reconstruction. The patient was a woman with bilateral, long segment ureteric strictures secondary to pelvic surgery and radiation. This report demonstrates that robotic reconstruction is a viable option even in a complex patient with a hostile abdomen.

Fibroblast growth factor signaling regulates the expansion of A6-expressing hepatocytes in association with AKT-dependent ß-catenin activation.

BACKGROUND & AIMS: Fibroblast Growth Factors (FGFs) promote the proliferation and survival of hepatic progenitor cells (HPCs) via AKT-dependent ß-catenin activation. Moreover, the emergence of hepatocytes expressing the HPC marker A6 during 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury is mediated partly by FGF and ß-catenin signaling. Herein, we investigate the role of FGF signaling and AKT-mediated ß-catenin activation in acute DDC liver injury. METHODS: Transgenic mice were fed DDC chow for 14days concurrent with either Fgf10 over-expression or inhibition of FGF signaling via expression of soluble dominant-negative FGF Receptor (R)-2IIIb. RESULTS: After 14days of DDC treatment, there was an increase in periportal cells expressing FGFR1, FGFR2, and AKT-activated phospho-Serine 552 (pSer552) ß-Catenin in association with up-regulation of genes encoding the FGFR2IIIb ligands, Fgf7, Fgf10, and Fgf22. In response to Fgf10 over-expression, there was an increase in the number of pSer552-ß-Catenin((positive)+ive) periportal cells as well as cells co-positive for A6 and hepatocyte marker, Hepatocyte Nuclear Factor-4α (HNF4α). A similar expansion of A6(+ive) cells was observed after Fgf10 over-expression with regular chow and after partial hepatectomy during ethanol toxicity. Inhibition of FGF signaling increased the periportal A6(+ive)HNF4α(+ive) cell population while reducing centrolobular A6(+ive) HNF4α(+ive) cells. AKT inhibition with Wortmannin attenuated FGF10-mediated A6(+ive)HNF4α(+ive) cell expansion. In vitro analyses using FGF10 treated HepG2 cells demonstrated AKT-mediated ß-Catenin activation but not enhanced cell migration. CONCLUSIONS: During acute DDC treatment, FGF signaling promotes the expansion of A6-expressing liver cells partly via AKT-dependent activation of ß-Catenin expansion of A6(+ive) periportal cells and possibly by reprogramming of centrolobular hepatocytes.

Prune belly syndrome associated with cloacal anomaly, patent urachal remnant, and omphalocele in a female infant.

Prune belly syndrome (PBS), megacystis-microcolon-intestinal hypoperistalsis (MMIH), and omphalocele-exstrophy of the bladder-imperforate anus-spine abnormalities complex (OEIS) are rare congenital malformations of the newborn that lead to incomplete formation of the gastrointestinal and genitourinary tract systems. To date, incomplete mesodermal development is identified as the cause for all these complex genetic syndromes even if the etiology is still unknown. We present an original case sharing characteristics common to PBS, MMIH, and OEIS complex, without a clear inclination toward any particular one. This case hints toward a common pathway in the creation of the 3 syndromes. We hypothesize that they are a spectrum of malformations based on the time frame when the mesoderm fails to create a normal interaction between infraumbilical mesoderm, urorectal septum, lumbosacral somites in the formation of the abdominal wall and the genitourinary and lower gastrointestinal tracts.

Expansion of hepatic tumor progenitor cells in Pten-null mice requires liver injury and is reversed by loss of AKT2.

BACKGROUND & AIMS: The tumor suppressor PTEN inhibits AKT2 signaling; both are aberrantly expressed in liver tumors. We investigated how PTEN and AKT2 regulate liver carcinogenesis. Loss of PTEN leads to spontaneous development of liver tumors from progenitor cells. We investigated how the loss of PTEN activates liver progenitor cells and induces tumorigenesis. METHODS: We studied mice with liver-specific disruptions in Pten and the combination of Pten and Akt2 to investigate mechanisms of liver carcinogenesis. RESULTS: PTEN loss leads to hepatic injury and establishes selective pressure for tumor-initiating cells (TICs), which proliferate to form mixed-lineage tumors. The Pten-null mice had increasing levels of hepatic injury before proliferation of hepatic progenitors. Attenuation of hepatic injury by deletion of Akt2 reduced progenitor cell proliferation and delayed tumor development. In Pten/Akt2-null mice given 3,5-diethoxycarbonyl-1,4 dihydrocollidine (DDC), we found that the primary effect of AKT2 loss was attenuation of hepatic injury and not inhibition of progenitor-cell proliferation in response to injury. CONCLUSIONS: Liver carcinogenesis in Pten-null mice requires not only the transformation of TICs but selection pressure from hepatic injury and cell death, which activates TICs. Further research is required to elucidate the mechanism for hepatic injury and its relationship with TIC activation.

Open lung biopsy in pediatric patients with respiratory failure after abdominal transplantation.

To understand the utility of open lung biopsy (OLB) in the evaluation of respiratory failure in pediatric abdominal organ transplant we reviewed the records of nine children in this patient population who underwent an OLB. Eight of nine patients had undergone a previous non-diagnostic bronchoalveolar lavage. Biopsies were performed at the bedside in the pediatric intensive care unit and tissue was processed by the Department of Pathology with special stains for infectious agents. There were no significant complications of OLB. A specific treatable etiology was identified in four patients (respiratory syncytial virus, adenovirus, graft-vs.-host disease and post-transplant lymphoproliferative disease), leading to a change in therapy and survival in two. Overall survival was 44%. Given the low morbidity, OLB as performed in this study appears appropriate in this patient population.