Dual role of mesenchymal stem/stromal cells and their cell-free extracellular vesicles in colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

A diagnosis of Birt-Hogg-Dubé syndrome in individuals with Smith-Magenis syndrome: Recommendation for cancer screening.

We report a series of four unrelated adults with Smith-Magenis syndrome (SMS) and concomitant features of Birt-Hogg-Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD-associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second-hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome.

The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

Convalescent plasma therapy in patients with severe COVID-19, A single-arm, retrospective study.

Convalescent plasma (CP) therapy has been suggested as a treatment for emerging viral diseases. Moreover, many studies have been conducted to evaluate the efficacy of COVID-19 CP therapy, with some of them indicating that CP may be a promising treatment for the disease. However, the evidence for CP therapy's effectiveness in severe COVID-19 cases is limited. So, this study aimed to assess the probable effects of CP therapy in patients diagnosed with severe COVID-19. The study was designed as a single-arm, retrospective cohort of patients with severe COVID. Demographic data, laboratory test reports, and convalescent plasma transfusion doses were collected from medical records for patients before and after convalescent plasma transfusion. The clinical outcomes were hospital discharge and death. Also, laboratory parameters considered secondary outcomes. After CP therapy, some symptoms improved, especially in patients under 55 years old, as follows. Respiratory function was significantly enhanced after convalescent plasma transfusion, and the inflammatory biomarkers' values decreased significantly (p < 0.05). Moreover, the estimated median of partial thromboplastin time (PTT) and Prothrombin time (PT) in patients did not change after CP therapy (p > 0.05). Regarding COVID-19 mortality, a strong association was found between older ages and death (p < 0.001). Also, CP transfusion in the early days of admission was effective in treatment outcomes (p = 0.023). Other characteristics, including sex, blood group, number of CP transfusions, and preexisting conditions, did not significantly correlate with mortality. In conclusion, this study demonstrates the effectiveness of CP therapy in patients under the age of 55. Despite some improvement, we could not say that they were entirely due to the CP treatment. More extensive randomized clinical trials that cover different stages of the disease are needed.

Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management.

Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both the MMP-2 and MMP-9 proteins to find the most promising inhibitors as a proposed computational mechanism to treat keratoconus. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, and MMP inhibitors (MMPIs) are usually designed to interact with zinc ion in the catalytic (CAT) domain, thus interfering with enzymatic activity. In our research work, the FDA-approved ophthalmic medications will be investigated as MMPIs, to explore if they can be repurposed for KC treatment. The obtained findings of the docking study suggest that atenolol and ampicillin are able to accommodate into the active sites of MMP-2 and MMP-9. Additionally, both exhibited binding modes similar to inhibitors used as references, with an ability to bind to the zinc of the CAT. Molecular dynamic simulations and the MM-GBSA binding free-energy calculations revealed their stable binding over the course of 50 ns. An additional pharmacophoric study was carried out on MMP-9 (PDB ID: 1GKC) using the co-crystallized ligand as a reference for the future design and screening of the MMP-9 inhibitors. These promising results open the door to further biological research to confirm such theoretical results.

Discovery of Some Heterocyclic Molecules as Bone Morphogenetic Protein 2 (BMP-2)-Inducible Kinase Inhibitors: Virtual Screening, ADME Properties, and Molecular Docking Simulations.

Bone morphogenetic proteins (BMPs) are growth factors that have a vital role in the production of bone, cartilage, ligaments, and tendons. Tumors' upregulation of bone morphogenetic proteins (BMPs) and their receptors are key features of cancer progression. Regulation of the BMP kinase system is a new promising strategy for the development of anti-cancer drugs. In this work, based on a careful literature study, a library of benzothiophene and benzofuran derivatives was subjected to different computational techniques to study the effect of chemical structure changes on the ability of these two scaffolds to target BMP-2 inducible kinase, and to reach promising candidates with proposed activity against BMP-2 inducible kinase. The results of screening against Lipinski's and Veber's Rules produced twenty-one outside eighty-four compounds having drug-like molecular nature. Computational ADMET studies favored ten compounds (11, 26, 27, 29, 30, 31, 34, 35, 65, and 72) with good pharmacokinetic profile. Computational toxicity studies excluded compound 34 to elect nine compounds for molecular docking studies which displayed eight compounds (26, 27, 29, 30, 31, 35, 65, and 72) as promising BMP-2 inducible kinase inhibitors. The nine fascinating compounds will be subjected to extensive screening against serine/threonine kinases to explore their potential against these critical proteins. These promising candidates based on benzothiophene and benzofuran scaffolds deserve further clinical investigation as BMP-2 kinase inhibitors for the treatment of cancer.

Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer.

PURPOSE: The accuracy of biomarker assessment in breast cancer (BC) is paramount for therapy decisions and informs prognosis. We investigated neoadjuvant chemotherapy (NAC) response in HER2-positive BC with respect to immunohistochemistry (IHC) and in situ hybridization (ISH) results. We aimed to determine the role of HER2 protein expression in predicting NAC response and long-term outcome in two HER2-positive groups: IHC 3 + versus IHC 2 + ISH amplified groups. METHODS: This retrospective study included 192 consecutive HER2 + primary BCs diagnosed from 2007 to 2019 treated with NAC and HER2-targeted agent (NACH). There were 158 HER2 3 + and 34 HER2 2 + ISH + cases. Clinicopathological parameters and long-term outcomes were analyzed. RESULTS: The Pathological Complete Response (pCR) rate was 85.7% (72/84) in ER-/HER2 + BCs and was lower in ER + /HER2 + BCs (42.6%, 46/108). The pCR was 55.1% (86/156) in the HER2 3 + group and was only 17.6% in HER2 2 + ISH + group (p < 0.001). Patients who achieved pCR in HER2 2 + ISH + group did not show a significantly higher HER2/CEP17 ratio or HER2 copy number. The overall survival (OS) and progression-free survival (PFS) were significantly higher in pCR compared to non-pCR cases (p = 0.011 and p = 0.015, respectively). CONCLUSIONS: There is significant heterogeneity in response to the NACH regimens in HER2 + cases. Our findings indicate that HER2 IHC score and ER expression determine NACH response in HER2 + BC. We recommend considering HER2 protein expression and ISH value to better select patients and assess the response for HER2-targeted therapy.

Outcomes of upper tract urothelial carcinoma with isolated lymph node involvement following surgical resection: implications for multi-modal management.

BACKGROUND: There are limited data on the oncologic outcomes of upper tract urothelial carcinoma with isolated lymph node (LN) involvement (pN+ M0) following surgical resection. We examined pN+ M0 UTUC in a large, nationwide oncology dataset to characterize its natural history, describe trends in utilization of perioperative chemotherapy, and identify clinicopathologic features associated with survival. METHODS: We identified 794 patients aged 18-89 years who underwent radical nephroureterectomy with lymph node dissection for pN+ M0 UTUC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was created. RESULTS: Median follow-up among survivors was 39.5 months, during which time 555 (70%) patients died. Over the study period, neoadjuvant chemotherapy utilization increased from 6.7 to 14.2% (p = 0.002), while adjuvant chemotherapy utilization remained stable (42.7 to 44.3%; p = 0.86). One-, 5-, and 8-year OS rates were 63.7%, 24.2%, and 18.7%, respectively. On multivariable analysis, older age, larger tumor size, higher pT stage, positive surgical margins, number of positive LNs, and non-receipt of adjuvant chemotherapy were independently associated with worse OS. A simplified risk score consisting of age, tumor size, pT stage, number of positive LNs, and margin status was created with predicted 5-year OS ranging from 12 to 44%. CONCLUSIONS: In this large, contemporary cohort, pN+ M0 UTUC was associated with a 5-year OS of only 24%. Clinicopathologic predictors of survival after surgical resection may improve risk-stratification, counseling, and selection of patients for multimodal management.

Possible role of hypothyroidism in the prognosis of COVID-19.

In patients with COVID-19, certain medical conditions could result in poorer clinical outcomes. However, the prognostic role of hypothyroidism in COVID-19 is still unknown. In the present retrospective study, we estimated the prevalence of hypothyroidism in COVID-19 admitted patients in Tehran, Iran. Among 390 COVID-19 admitted patients, 21 hypothyroid cases (5.4%) were found, in which nearly 90% were aged 50 years and older. Regarding the effect of hypothyroidism on COVID-19 mortality, 60 (15.3%) of total patients and 4 (19%) of hypothyroid patients died, and no significant difference was found between the two groups.

Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice.

The current work estimated the antitumour efficacy of melatonin (MLT) on the growth of Ehrlich ascites carcinoma cells inoculated intramuscularly into the hind limbs of female BALB/c mice and to compare its effects with those of adriamycin (ADR). After solid tumours developed, the animals were divided into the three following groups: the tumour-bearing control, MLT-treated (20 mg/kg body weight) and ADR-treated (10 mg/kg body weight) groups. The results showed a significant reduction in the tumour masses of the treated animals in comparison with those of the control group. There were a significant decrease in the malondialdehyde level and a significant elevation of the glutathione concentration and the superoxide dismutase and catalase activities in the MLT and ADR groups. The current study indicated the increased expression levels of P53, caspase-3 and caspase-9 and the decreased expression levels of the rRNA and Bcl2. The MLT and ADR treatments resulted in histological changes, such as a marked degenerative area, the necrosis of neoplastic cells, the appearance of different forms of apoptotic cells and giant cells with condensed chromatin, and a deeply eosinophilic cytoplasm. The MLT and ADR treatments also significantly decreased the Ki-67 protein and vascular endothelial growth factor (VEGF) expression levels in the tumour masses. In conclusion, similar to ADR-treated tumour-bearing mice, MLT suppressed the growth and proliferation of tumour by inducing apoptosis and by inhibiting tumour vascularization. The current data recommend MLT as a safe natural chemotherapeutic adjuvant to overcome cancer progression after a clinical trial validates these results.

Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study.

The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

Anticipated treatment defect versus prostatic abscess: radiographic findings following transurethral convective radiofrequency-induced water vapor thermal ablation.

With the increasing use of minimally invasive technologies for the treatment of benign prostatic enlargement/lower urinary tract symptoms, clinicians must become familiar with the various treatment effects and complications. Here we present a case of treatment defect after transurethral convective radiofrequency-induced water vapor thermal ablation (REZUM) radiographically identified as a prostatic abscess without consideration that the finding may have represented an anticipated treatment defect. This likely led to an unnecessary surgical procedure. This entity should be recognized by urologists and radiologists alike to avoid such interventions in the future.

Innovative root-end filling materials based on calcium-silicates and calcium-phosphates.

This in vitro study evaluated the apical sealing ability, bioactivity and biocompatibility of an experimental calcium silicate-based and two light-curing calcium silicate/calcium-phosphate cements as potential root end filling materials. A calcium silicate Portland-based (Control PC), an experimental calcium silicate (Exp. PC) and two light-curing cements (LC-CaP; LC-Si/CaP) were assessed for their alkalinising activity (pH) and biocompatibility. Single-rooted human canines were endodontically treated, filled with gutta-percha and finally submitted to apicoectomy. Root end fillings were performed using all tested cements, and their apical sealing ability was evaluated up to 4 weeks of immersion in simulated body fluid (SBF). The mineral precipitation at the apical region and the cement adaptation to root dentine were also evaluated through non-destructive optical microscopy both at 24 h and after prolonged water storage (four week). LC-CaP and LC-Si/CaP had neutral pH, the greatest sealing ability (24 h) and excellent cytocompatibility. The Exp. PC cement presented sealing ability after two and four weeks, as well as biocompatibility after four and seven days, similar to LC-CaP and LC-Si/CaP. The control PC cement showed the lowest sealing ability and the greatest cytotoxicity. Mineral precipitation was observed in all groups, while some differences were seen in terms of cement adaptation along the root canal dentine walls. The experimental light-curable cements as well as the experimental PC might be suitable root end filling materials with appropriate (in vitro) sealing ability, biocompatibility and aptitude to induce mineral precipitation.

Rheolytic Pharmacomechanical Thrombectomy for the Management of Acute Limb Ischemia: Results From the PEARL Registry.

PURPOSE: To present the results of rheolytic pharmacomechanical thrombectomy (PMT) for the management of acute limb ischemia (ALI) as reported in the PEARL Registry (PEripheral Use of AngioJet Rheolytic Thrombectomy with a variety of catheter Lengths). METHODS: A total of 283 patients (mean age 65±13 years; 170 men) presenting with ALI undergoing treatment with the AngioJet System at participating institutions were enrolled in the registry. Rutherford ALI categories included 26% with viable limbs, 38% with marginally threatened limbs, 35% with immediately threatened limbs, and <1% with irreversible damage. Procedure and follow-up data were collected for the calculation of outcomes. To control for patient selection bias, propensity score matching was used to compare outcomes for patients undergoing PMT with or without catheter-directed thrombolysis (CDT). RESULTS: Procedure success was achieved in 235 (83%) of 283 patients. Half of the procedures (147, 52%) were completed without the need for adjunctive CDT. At 12-month follow-up, amputation-free survival and freedom from mortality were 81% and 91%, respectively; 12-month freedom from bleeding requiring transfusion was 91%, and freedom from renal failure was 95%. Subgroup analysis revealed significantly better outcomes in patients without infrapopliteal involvement and those who underwent PMT without CDT. In the matched cohorts, higher rates of procedure success, 12-month amputation-free survival, and 12-month freedom from amputation were observed in the PMT without CDT group (88% vs 74%, p=0.021; 87% vs 72%, p=0.028; 96% vs 81%, p=0.01, respectively). CONCLUSIONS: The results support the use of PMT as a first-line treatment for ALI, providing a rapid reperfusion to the extremity, reduced procedure time, and an acceptable risk profile without compromising limb salvage.

Endovascular Management of Deep Vein Thrombosis with Rheolytic Thrombectomy: Final Report of the Prospective Multicenter PEARL (Peripheral Use of AngioJet Rheolytic Thrombectomy with a Variety of Catheter Lengths) Registry.

PURPOSE: To report procedural and patient outcomes of endovascular treatment for lower-extremity deep vein thrombosis (DVT) with rheolytic thrombectomy (RT). MATERIALS AND METHODS: A total of 32 sites in the United States and Europe enrolled patients with DVT in the Peripheral Use of AngioJet Rheolytic Thrombectomy with a Variety of Catheter Lengths (PEARL) registry. Patient characteristics and outcomes data were collected from consenting patients who underwent rheolytic AngioJet thrombectomy at investigative sites from January 2007 through June 2013. Three hundred twenty-nine patients were enrolled, with 67% of patients undergoing an AngioJet procedure within 14 days of the onset of symptoms. RESULTS: Four treatment approaches using AngioJet thrombectomy were identified: RT without lytic agent in 4% of patients (13 of 329), pharmacomechanical catheter-directed thrombolysis (PCDT) in 35% (115 of 329), PCDT and catheter-directed thrombolysis (CDT) in 52% (172 of 329), and RT in combination with CDT in 9% (29 of 329). Median procedure times for RT alone, PCDT, PCDT/CDT, and RT/CDT were 1.4, 2, 22, and 41 hours, respectively (P < .05, Kruskal-Wallis test). Procedures were completed in less than 24 hours for 73% of patients, with 36% of procedures completed within 6 hours; 86% of procedures required no more than 2 catheter laboratory sessions. The 3-, 6-, and 12-month freedom from rethrombosis rates were 94%, 87%, and 83%, respectively. Major bleeding events occurred in 12 patients (3.6%), but none were related to the AngioJet procedure. CONCLUSIONS: PEARL registry data demonstrate that rheolytic PCDT treatment of DVT is safe and effective, and can potentially reduce the need for concomitant CDT and intensive care.

A human fetal prostate xenograft model of developmental estrogenization.

Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7-, 30-, 90-, 200-, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (ie, CDKN1A, CASP9, ESR2, PTEN, and TP53) was performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200- and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early and later-life estrogenic exposures.