Outcomes of Primary Tumor Excision do not Differ from Non-Resection Methods in Pediatric Mesenchymal Hamartoma of the Liver: A Rapid Systematic Review.

BACKGROUND: To conduct a rapid systematic review comparing the outcomes of primary tumor resection versus non-resection on patients with hepatic mesenchymal hamartoma. METHODS: We searched the Ovid MEDLINE, EMBASE, Scopus, PubMed, Web of Science, and Google Scholar databases from January 1, 2000 to March 31, 2022. Studies that described cases of hepatic mesenchymal hamartoma, including management and outcomes, were included. RESULTS: 62 articles met inclusion criteria with 95 cases in total. Patients were assigned to the primary tumor resection (n = 85) or non-resection (n = 10) cohort based on the described management. Similar rates of morbidity (17% vs 20%) and mortality (6 vs 10%) were identified between cohorts. There were no differences in sex, liver lobe involvement, or tumor size among study groups. CONCLUSIONS: Complete tumor resection should remain the gold standard for hepatic mesenchymal hamartomas when an adequate liver remnant exists. Reports of non-resected tumors demonstrating spontaneous regression or stability with watchful waiting have poor long term follow-up and have inadequate evidence of a true mesenchymal hamartoma diagnosis. LEVEL OF EVIDENCE: Level I.

Comparison of infectious complications with synthetic mesh in ventral hernia repair.

BACKGROUND: Infection can be a devastating complication associated with prosthetic incisional hernia repair. It is unclear whether the type of mesh used affects the risk of infection. METHODS: A retrospective review was performed of all patients who underwent elective incisional hernia repair with permanent prosthetic mesh between January 1, 2000, and August 1, 2007. RESULTS: A total of 176 patients underwent elective incisional hernia repair with mesh. The overall infection rate with the use of goretex (Flagstaff, AZ, USA) was 12 of 86 (14%) and 2 of 90 (2.2%) in cases in which nongoretex material was used (P = .016). In the goretex group, infection rates were significantly higher in open versus laparoscopic cases (26.5% vs 5.8%, P = .030). Methicillin-resistant Staphylococcus aureus was the most common organism recovered. CONCLUSIONS: The risk of mesh infection with the use of goretex was found to be higher than with the use of nongoretex mesh. Laparoscopic placement of goretex reduces this risk of infection. No significant differences in recurrence rates were found.

Spleno-adrenal shunt: a novel alternative for portosystemic decompression in children with portal vein cavernous transformation.

PURPOSE: Children with portal vein cavernous transformation (PVCT) can develop life-threatening variceal hemorrhage from progressive portal hypertension. While spleno-renal shunt ± splenectomy is the most common portosystemic decompression surgery performed in children, we have adopted a modified spleno-adrenal (SA) shunt for complicated PVCT. We describe our 10 year experience focusing on technique evolution and treatment efficacy. METHODS: Between 2001 and 2011, 15 children (9 girls and 6 boys, ages 3-11 years, median: 6 years) with PVCT, portal hypertension, and hypersplenism were treated with SA shunt with splenectomy in Shanghai Children's Medical Center. All children in the study had endoscopy proven active esophageal variceal bleeding requiring multiple transfusions (mean: 4.2 units) with failed sclerotherapy (mean: 2.6 times). Greater omental vein pressure (GVP) approximating portal venous pressure was measured pre- and post-SA shunt. Pre- and post-operative ammonia levels were obtained. Follow-up ranged from 6 months to 10 years (mean: 4.2 ± 2 years). RESULTS: Intra-operative adrenal vein diameter and length ranged from 0.7 to 1.8 cm and 2 to 3 cm, respectively. Intra-operative GVPs pre-and post-SA shunt were (30 ± 11) and (22 ± 7) mmHg, respectively (p<0.01). On follow-up, there have been no recurrences of GI bleeding. Liver function tests remained normal in all children with the exception of elevated post-operative mean blood ammonia levels [Pre (18 ± 7) mmol/L, post (60 ± 17) mmol/L (p<0.05)] in all children. Ammonia levels normalized in all cases on outpatient follow-up. There have been no cases of hepatic encephalopathy, and all have normal age appropriate neurodevelopment (Bayley's assessment). Barium swallow and/or upper endoscopy showed interval resolution of esophageal varices in all children, and vascular ultrasound showed patent shunt anastomosis without stricture in 14 (93%). CONCLUSIONS: The left adrenal vein is a viable conduit for effective selective portosystemic decompression. Similar to the more traditional spleno-renal shunt, SA appears also to have the advantage of preventing hepatic encephalopathy preserving neurodevelopment, although the rise in post-operative ammonia levels was unexpected. Longer follow-up is needed to look for late signs of encephalopathy assessing neurodevelopment long term.

Neuroblastoma-derived secretory protein is a novel secreted factor overexpressed in neuroblastoma.

Secreted proteins such as growth factors, cytokines, and chemokines play important roles in tumor development. Through expression microarray and bioinformatic analysis, we discovered a novel secreted protein, neuroblastoma-derived secretory protein (NDSP). The NDSP gene is found on chromosome 1q25.2 and encodes a 167 amino acid protein with a putative signal peptide. Using real-time PCR and immunoblotting, we find that NDSP is specifically overexpressed in neuroblastoma at much higher levels than other adult and pediatric malignancies and normal tissues. NDSP is an 18-kDa protein that can be secreted by NDSP-transfected HEK-293T cells, as well as, neuroblastoma cell lines endogenously expressing NDSP. Inhibiting NDSP expression in neuroblastoma cell lines with retrovirally transduced NDSP small hairpin interfering RNA, sh-NDSP, results in decreased cellular proliferation and colony formation. We also find inhibited extracellular signal-regulated kinase (ERK)1/2 phosphorylation in the sh-NDSP cell line. Treating the parental cell line with MAP/ERK kinase 1/2 inhibitors, which diminish ERK1/2 phosphorylation, results in decreased cell proliferation. Culturing these transduced cells with recombinant NDSP, reintroducing NDSP overexpression in the knockdown cell line, or inducing Ras oncogene overexpression for constitutive ERK1/2 activation results in a reversal of the growth-inhibited phenotype and proliferation rates similar to the control cells. In addition, reintroduction of NDSP overexpression in the sh-NDSP cell line results in ERK1/2 phosphorylation similar to control. We conclude that NDSP is specifically overexpressed in neuroblastoma and actively secreted from tumor cells. Furthermore, NDSP serves as a growth factor for neuroblastoma tumor cells through activation of the ERK-mediated proliferation pathway.

Patent ductus arteriosus ligation in neonates: preoperative predictors of poor postoperative outcomes.

PURPOSE: The purpose of this study was to identify preoperative predictors of adverse outcomes in infants undergoing surgical ligation of patent ductus arteriosus (PDA). METHODS: Charts of all neonates who underwent PDA ligation at Texas Children's Hospital (Houston, TX) between 2001 and 2006 were retrospectively reviewed with specific attention to preoperative clinical characteristics, echocardiographic details, operative morbidity, and postoperative outcomes. Infants with other cardiac anomalies or right-to-left or bidirectional PDA shunt were excluded. RESULTS: Eighty-two neonates were included (mean gestational age, 27 weeks; mean birth weight, 1000 g). There were no intraoperative complications. Preoperative symptoms related to respiratory insufficiency, hypotension, apnea, and pulmonary edema improved after ligation (P < .001). Birth weight, age at ligation, and indomethacin use did not correlate with postoperative outcome; however, lower gestational age, lower blood pressure, and lower shunt peak velocity predicted longer time to extubation by multiple analysis techniques (P < .0001). Linear regression (controlling for gestation, birth weight, and mean arterial pressure) showed inverse correlation between peak velocity and postoperative days on the ventilator (95% confidence interval, 47.18 to -12.25; P = .001). CONCLUSION: The PDA ligation can be accomplished safely; however, some neonates have prolonged recovery. Lower gestational age and low peak velocity (<2.6 m/s) at the PDA shunt correlate with lengthened ventilator requirement after surgery.

Granulocyte colony stimulating factor alters the phenotype of neuroblastoma cells: implications for disease-free survival of high-risk patients.

INTRODUCTION: Granulocyte colony stimulating factor (GCSF) is commonly used for the treatment of chemotherapy-induced neutropenia. Despite high-dose intensive chemotherapy for advanced-stage neuroblastoma, the survival rate remains poor. Granulocyte colony stimulating factor therapy is quite common in these children; thus, we questioned its effect on neuroblastoma cells. We hypothesized that exogenous GCSF stimulates the proliferation and invasive character of neuroblastoma cells. METHODS: Expression of a GCSF receptor in 5 different neuroblastoma cell lines was determined by polymerase chain reaction. In addition, we determined the effect of increasing doses of GCSF (0, 1 ng/mL, 10 ng/mL, 1 microg/mL, and 10 microg/mL) on DNA synthesis (BrdU assay), invasiveness (Matrigel invasion chambers), and cell proliferation. RESULTS: We tested 5 neuroblastoma cell lines; all expressed the GCSF receptor. Granulocyte colony stimulating factor treatment resulted in significantly increased proliferation of SK-N-SH, SK-N-AS, and SHSY-5Y cells. Likewise, increased invasiveness of SK-N-SH cells was observed with GCSF treatment. CONCLUSIONS: Our results indicate that neuroblastoma cell lines express the GCSF receptor and respond to exogenous GCSF by increased proliferation and invasiveness. These findings suggest that GCSF may stimulate the growth of neuroblastoma cells in patients undergoing high-dose chemotherapy with GCSF rescue and could have a significant impact on the ability to eradicate these tumors.

Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia.

It has been shown that the novel synthetic triterpenoid CDDO inhibits proliferation and induces differentiation and apoptosis in myeloid leukemia cells. In the current study the effects of the C-28 methyl ester of CDDO, CDDO-Me, were analyzed on cell growth and apoptosis of leukemic cell lines and primary acute myelogenous leukemia (AML). CDDO-Me decreased the viability of leukemic cell lines, including multidrug resistant (MDR)-1-overexpressing, p53(null) HL-60-Dox and of primary AML cells, and it was 3- to 5-fold more active than CDDO. CDDO-Me induced a loss of mitochondrial membrane potential, induction of caspase-3 cleavage, increase in annexin V binding and DNA fragmentation, suggesting the induction of apoptosis. CDDO-Me induced pro-apoptotic Bax protein that preceded caspase activation. Furthermore, CDDO-Me inhibited the activation of ERK1/2, as determined by the inhibition of mitochondrial ERK1/2 phosphorylation, and it blocked Bcl-2 phosphorylation, rendering Bcl-2 less anti-apoptotic. CDDO-Me induced granulo-monocytic differentiation in HL-60 cells and monocytic differentiation in primary cells. Of significance, colony formation of AML progenitors was significantly inhibited in a dose-dependent fashion, whereas normal CD34(+) progenitor cells were less affected. Combinations with ATRA or the RXR-specific ligand LG100268 enhanced the effects of CDDO-Me on cell viability and terminal differentiation of myeloid leukemic cell lines. In conclusion, CDDO-Me is an MDR-1- and a p53-independent compound that exerts strong antiproliferative, apoptotic, and differentiating effects in myeloid leukemic cell lines and in primary AML samples when given in submicromolar concentrations. Differential effects of CDDO-Me on leukemic and normal progenitor cells suggest that CDDO-Me has potential as a novel compound in the treatment of hematologic malignancies.