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  • 1
    Language: English
    In: The Journal of Urology, April 2017, Vol.197(4), pp.e570-e571
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2017.02.1349 Byline: Sarah Ottenhof, Rosa Djajadiningrat, Helene Thygesen, Jeroen de Jong, Simon Horenblas, Ekaterina Jordanova Author Affiliation: Amsterdam, Netherlands Article Note: (footnote) Source of Funding: none.
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 2
    Language: English
    In: The Journal of Urology, April 2018, Vol.199(4), pp.e179-e179
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 3
    Language: English
    In: The Journal of Urology, March 2017, Vol.197(3), pp.690-697
    Description: PD-L1 (programmed death ligand 1) inhibits T-cell function and prevents tumor eradication. This is facilitated by PD-L1 positive tumor cells and PD-L1 positive immune cells, and can be prevented by anti-PD-1 (programmed death 1)/PD-L1 immunotherapy. In advanced penile cancer there is a need for new therapeutic strategies. We investigated PD-L1 expression in penile cancers and compared PD-L1 expression with disease specific survival, lymph node metastases at diagnosis and high risk HPV status in a large patient cohort. A total of 213 primary tumors were immunohistochemically stained for PD-L1 and scored for tumor (percentage), stroma (binary) and PD-L1 positive tumor infiltrating macrophages. Additionally, PD-L1 positive tumors were scored for expression pattern, that is diffuse or predominantly present at the tumor-stroma margin. Staining was successful in 200 tumors, of which 75% were high risk HPV negative. Median followup was 62 months. Of 200 tumors 96 (48%) were PD-L1 positive (scored 1% or greater), of which 59 (62%) had a marginal expression pattern and 79 (82%) were high risk HPV negative (p = 0.03). Compared to PD-L1 negative tumors, the PD-L1 expression patterns had different prognostic values in the whole cohort as well as in the high risk HPV negative subgroup. On multivariable analyses a marginal expression pattern was associated with absent lymph node metastases (OR 0.4) while diffuse expression was associated with poor survival (HR 2.58). These results were more prominent in the high risk HPV negative subgroup (OR 0.25, HR 3.92). PD-L1 was expressed in 48% of penile carcinomas and mainly in high risk HPV negative tumors. The pattern of expression was a prognostic factor as marginal expression was associated with absent lymph node metastases and diffuse expression was associated with poor survival.
    Keywords: Penile Neoplasms ; Alphapapillomavirus ; Antigens ; Cd274 ; Tumor escape ; Survival Analysis ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 4
    Language: English
    In: Obesity (Silver Spring, Md.), April 2012, Vol.20(4), pp.748-55
    Description: Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in a number of complications associated with diabetes mellitus including micro- and macrovascular dysfunction. In this study we examine ER stress levels in blood cells isolated from human subjects with metabolic syndrome and in healthy controls. Total RNA and protein were isolated from leukocytes and the levels of specific ER stress markers were quantified by real-time-PCR and immunoblot analysis. Our results indicate that, compared to healthy controls, individuals with metabolic syndrome have elevated mRNA levels of genes indicative of ER stress; including spliced XBP-1 (sXBP-1), Grp78, and CHOP. Induced ER stress levels correlate with blood glucose but not plasma lipid concentration. Furthermore, in healthy individuals, a standard 75 g oral glucose challenge produced a significant elevation in spliced XBP-1 (1.3 fold), Grp78 (2.0 fold), and calreticulin (3.5 fold) mRNA 60 min post challenge and a significant increase in Grp78 (2.0 fold), calreticulin (2.7 fold) protein levels 2 h postchallenge, relative to fasting levels. The UPR was also activated ex vivo, in human leukocytes cultured in the presence of 15 mmol/l glucose, supporting a specific role for glucose. The oral glucose challenge was associated with a significant increase in the expression of inflammatory cytokines, including interleukin (IL)-1α/β, IL-6, and IL-8, that may result from ER stress. These findings suggest that there is an association between both acute and chronic dysglycemia and ER stress in humans.
    Keywords: Endoplasmic Reticulum Stress ; Unfolded Protein Response ; DNA-Binding Proteins -- Metabolism ; Heat-Shock Proteins -- Metabolism ; Hyperglycemia -- Metabolism ; Metabolic Syndrome -- Metabolism ; Monocytes -- Metabolism ; Transcription Factor Chop -- Metabolism ; Transcription Factors -- Metabolism
    ISSN: 19307381
    E-ISSN: 1930-739X
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  • 5
    Language: English
    In: The Journal of Urology, April 2017, Vol.197(4), pp.e1084-e1085
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2017.02.2516 Byline: Adam Baumgarten Author Affiliation: Tampa, FL Article Note: (footnote) Source of Funding: None
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 6
    Language: English
    In: The Journal of Urology, April 2017, Vol.197(4), pp.e975-e975
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.juro.2017.02.2228 Byline: Juan Chipollini, Adam Baumgarten, Dominic Tang Author Affiliation: Tampa, FL Article Note: (footnote) Source of Funding: none
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 7
    Language: English
    In: Translational andrology and urology, October 2017, Vol.6(5), pp.833-838
    Description: Positron emission tomography (PET) imaging with F-fluorodeoxyglucose (FDG) combined with computed tomography (CT) provides functional imaging combined with anatomic information, improving diagnostic accuracy and confidence. Although virtually all primary penile tumors are FDG-avid, PET/CT is not recommended for primary tumor staging as it has limited spatial resolution and is hampered by urinary FDG excretion. The accuracy of PET/CT for lymph node staging seems to improve with the pretest likelihood of metastatic nodes. In groins with normal physical examination, sensitivity is only 57%. In groins with palpably enlarged lymph nodes, sensitivity of PET/CT reaches 96%. For pelvic lymph nodes and distant metastases, PET/CT is more accurate if inguinal metastases are present. However, these results are based on a very limited number of studies. Overall, the role of PET/CT imaging in penile cancer remains ambiguous, especially in inguinal lymph nodes. During staging and follow-up, it may be particularly useful in detecting pelvic lymph node metastases and occult distant metastases prior to systemic chemotherapy and/or extensive surgery, improving selection of patients that are most likely to benefit from such therapies.
    Keywords: 18f-Fluorodeoxyglucose (Fdg) ; Pet/CT ; Penile Cancer ; Fluorodeoxyglucose ; Imaging
    ISSN: 2223-4691
    ISSN: 22234683
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  • 8
    Language: English
    In: The Journal of Urology, May 2018, Vol.199(5), pp.1233-1237
    Description: We evaluated recurrence outcomes of penile sparing surgery in what is to our knowledge the largest multicenter cohort of patients to date. We retrospectively identified patients treated with penile sparing surgery from May 1990 to July 2016 at 5 tertiary referral institutions. Treatments consisted of circumcision, wide local excision, laser therapy with or without local excision, partial or total glansectomy and glans resurfacing. The study primary end point was local recurrence-free survival, defined from initial treatment to time of local recurrence and estimated with the Kaplan-Meier method. After applying study exclusion criteria 1,188 patients were included in analysis. During the median followup of 43.0 months there were 252 local recurrences (21.2%), of which 99 (39.3%) developed in year 1. Median time to local recurrence was 16.3 months and the 5-year local recurrence-free survival incidence was 73.6%. When stratified by stage, the 5-year local recurrence-free survival rate was 75.0%, 71.4% and 75.9% in Ta/Tis, T1 and T2 cases, respectively (log rank p = 0.748). Of the recurrences 58.3% were treated with repeat organ sparing procedures and the secondary partial (total) penectomy rate was 19.0%. Only margin status was significantly associated with local recurrence on multivariate analysis (p = 0.001). Study limitations included the retrospective design and the heterogeneous clinical approach. Penile sparing surgery can provide excellent local control for superficial penile tumors as well as for appropriately selected invasive lesions. Strict followup in the early postoperative period is highly recommended.
    Keywords: Penile Neoplasms ; Neoplasm Recurrence ; Local ; Organ Sparing Treatments ; Carcinoma ; Squamous Cell ; Mortality ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 9
    Language: English
    In: The Journal of Urology, September 2016, Vol.196(3), pp.919-925
    Description: Urethral reconstruction is performed for urethral stricture or hypospadias correction. Research on urethral tissue engineering is increasing. Because the corpus spongiosum is important to support the urethra, urethral tissue engineering should ideally be combined with reconstruction of a corpus spongiosum. We describe a method to visualize and measure the architecture of the corpus spongiosum, which is needed for scaffold design. The penis was dissected from 2 unembalmed male cadavers. One penis was flaccid and the other was erect, as induced by saline infusion. Both were frozen in ice. At 6 sites sections were obtained in the transverse and frontal directions. After digitalizing the stained sections the images were edited, area measurements were taken and a 3-dimensional reconstruction was made. In transverse sections the mean area of the vascular lumen was 60% and 77% in the flaccid and the erect corpus spongiosum, and in frontal sections it was 53% and 74%, respectively. This indicated a 129% transverse increase and a 140% longitudinal increase in erection. Section sites did not essentially differ except in the glans penis. Frontal sections showed larger vascular cavities and more incomplete septae than transverse sections. This study provides what is to our knowledge novel information on corpus spongiosum architecture, which is relevant for scaffold design in tissue engineering. The study protocol can be used in future research with a larger number of specimens and more extensive analyses.
    Keywords: Penis ; Urethra ; Blood Vessels ; Models, Anatomic ; Tissue Engineering ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 10
    In: BJU International, March 2018, Vol.121(3), pp.393-398
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.14037/abstract Byline: Juan Chipollini, Sylvia Yan, Sarah R. Ottenhof, Yao Zhu, Desiree Draeger, Adam S. Baumgarten, Dominic H. Tang, Chris Protzel, Ding-wei Ye, Oliver W. Hakenberg, Simon Horenblas, Nicholas A. Watkin, Philippe E. Spiess Keywords: carcinoma in situ; recurrence; #PenileCancer Objectives To evaluate recurrence after penile-sparing surgery (PSS) in the management of carcinoma in situ (CIS) of the penis in a large multicentre cohort of patients. Patients and Methods We identified consecutive patients from five major academic centres, treated between June 1986 and November 2014, who underwent PSS for pathologically proven penile CIS. The primary outcome was local recurrence-free survival (RFS), which was estimated using the Kaplan-Meier method. Results A total of 205 patients were identified. Treatment methods included circumcision, glansectomy, wide local excision, laser therapy and total glans resurfacing. Over a median (interquartile range [IQR]) follow-up of 40 (26-65.6) months, there were 48 local recurrences, with 45.8% occurring in the first year and 81.3% occurring by year 5. The majority of recurrences were observed in the laser group (58.3%). The median (IQR) time to local recurrence was 15.9 (5.66-26.14) months. The 1- 2- and 5-year RFS rates were 88.4, 85.6 and 75%, respectively, and the median (IQR) RFS time was 106.5 (80.2-132.2) months. Conclusions Among patients with penile CIS selected for surgical management, durable responses at intermediate- to long-term follow-up were noted. For those with glandular CIS, glans resurfacing offered the best outcomes. CAPTION(S): Fig. S1 Overall survival based on recurrence status. Table S1 Univariable and multivariable Cox proportional hazard ratio (HR) for factors associated with local recurrence. Table S2 Management of local and regional recurrences.
    Keywords: Carcinoma In Situ ; Recurrence ; #Penilecancer
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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