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The objective of this article is to describe surgical techniques for the management of localized penile cancer concurrent with adult acquired buried penis. Penile cancer, while rare, invariably impacts quality of life as the primary surgical management ranges from local excision to total penectomy. Penile cancer has recently been linked to adult acquired buried penis (AABP) with the hypothesis that chronic inflammation of the penis contributes to risk of penile malignancy. Buried penis reconstruction is now a well-described procedure involving escutcheonectomy and split thickness skin grafting which has been shown to improve quality of life in individuals with adult acquired buried penis.This report describes a patient with AABP requiring partial penectomy and inguinal node dissection who also underwent adult acquired buried penis repair during his procedure. A review of cases of buried penis cases was carried out and four other cases of penile cancer were identified who were managed with penile preserving procedures.This combination of surgical techniques strives to improve quality of life and facilitate cancer surveillance without compromising oncologic outcomes.

PDF file - 81K, Verification of IKKe knock down

PDF file - 233K, Viability and invasion of additional ovarian cancer cell lines

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PDF file - 23K, IKK isoform IHC scoring

PDF file - 172K, Validation of IKKe gene signature

INTRODUCTION We describe the effect of a state mandated opioid consent on opioid utilization and multimodal pain use for major pediatric genitourinary surgeries. METHODS All patients who underwent an inpatient pediatric genitourinary surgery at the Children's Hospital of Pittsburgh between August 2015 and February 2020 were identified. Inpatient and outpatient multimodal pain control utilization were assessed. Delayed prescriptions or emergency department visits within 30 days were identified and when applicable referenced against National Surgical Quality Improvement Program data. RESULTS After accounting for a 6-month transition period following policy implementation, 462 major pediatric genitourinary procedures were identified. The frequency of discharge opiate prescriptions decreased from 68.4% prior to the transition period to 10.7% afterward(p

Postoperative opioids are overprescribed in the United States. In November 2016 the State of Pennsylvania required an opioid consent for minors. Our hypothesis is that this mandate decreased postoperative opioid prescriptions in our division.All patients who received a urological outpatient or minor emergency procedure from August 2015 to August 2019 were identified. Surgeries performed within 6 months after mandate implementation were excluded to account for the transition period. Perioperative data including case type were extracted by a clinical data warehouse from preexisting fields within the health record. The frequencies of postoperative prescriptions, delayed prescriptions and emergency department encounters were assessed. A multivariable logistic regression to identify predictors of opioid prescription at discharge was performed.A total of 4,349 patients were analyzed. The frequency of postsurgical opioid prescriptions decreased from 45.3% to 2.6% (p0.001). The median morphine milligram equivalent decreased by 22.5 among children prescribed an opioid (p0.001). Rates of an emergency department visits (3% vs 2.7%) or delayed nonopioid prescriptions (0.8% vs 1.2%) within 30 days of discharge were unchanged (p0.05). Fewer patients received a delayed opioid prescription after mandate implementation (0.03% vs 0.5%, p0.001). Female patients were less likely (OR 0.309, 95% CI 0.195-0.491; p0.001) to receive opioids prior to but not after the mandate (OR 0.309, 95% CI 0.544-2.035; p=0.122). Increasing age was predictive of receiving an opioid before (OR 1.187, 95% CI 1.157-1.218; p0.001) and after (OR 1.241, 95% CI 1.186-1.299; p0.001) the mandate.A state mandated opioid consent for minors greatly reduced post-urological surgery opioid prescription rates without increasing rates of readmission or delayed prescriptions.

O tecido empresarial português é, predominantemente, constituído por micro e pequenas empresas. Considerando a importância destas empresas para a riqueza nacional, assim como as suas especificidades e limitações de gestão, torna-se imperativo contribuir para o conhecimento científico a partir da investigação empírica que permita identificar estratégias que possam ser aplicadas de forma eficaz em tal contexto. Esta investigação focou-se num dos principais setores de atividade económica do país: o setor do vinho, para o qual se constatou existir escassos estudos. Em Portugal, 98% das empresas do setor do vinho são de micro ou pequena dimensão, sendo reconhecida a existência de um investimento limitado em áreas como o marketing e gestão da marca. O propósito desta dissertação foi descrever o processo de gestão da marca nessas empresas, identificando as principais estratégias adotadas e a forma como lidam com as novas tendências do Marketing nas suas práticas. Para tal, efetuou-se um estudo de natureza descritiva e exploratória, com recurso ao método de pesquisa qualitativo, envolvendo a análise de seis estudos de caso. Para a recolha de dados, foram efetuadas entrevistas semiestruturadas a empresários do setor. Com base nos resultados obtidos, foram identificadas especificidades e limitações relevantes na gestão da marca das micro e pequenas empresas estudadas, tanto a nível estratégico como a nível operacional, que deverão ser devidamente consideradas, de modo a se garantir a competitividade destas empresas num setor altamente competitivo. As conclusões obtidas poderão contribuir para investigações futuras na área do marketing e gestão da marca no setor focal.

INTRODUCTION AND OBJECTIVE:Rising antibiotic resistance has driven antibiotic stewardship to minimize antibiotic use while maintaining low peri-procedural infectious complications. Our objective wa...

INTRODUCTION AND OBJECTIVE:Opiate overdose has reached epidemic levels in the United States, and as such several states have implemented various strategies to curb usage. In November 2016 Pennsylva...

INTRODUCTION AND OBJECTIVE:Radical cystectomy is associated with one of the highest readmission rates of any surgery, hovering around 25%. Readmissions occur both at the hospital at which patients ...

To identify patient-level factors that can lead to treatment disparities for muscle invasive bladder cancer, we examine factors associated with receipt of definitive therapy, type of definitive therapy, and neoadjuvant chemotherapy administration in a statewide cohort of muscle-invasive bladder cancer patients.We identified 2,434 patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2015 using the Pennsylvania Cancer Registry. We divided the cohort into three subsamples to examine receipt of treatment: definitive therapy among all muscle-invasive bladder cancer patients (n = 1548), cystectomy (n = 1254) vs. trimodal therapy (n = 294), and neoadjuvant chemotherapy among radical cystectomy patients (n = 1156). Multivariable logistic regression models controlling for patient-level covariates, including insurance status, and socioeconomic disadvantage (based on Area Deprivation Index from census tract data) were estimated to examine factors associated with each treatment outcome.Only 64% of muscle-invasive bladder cancer patients underwent definitive therapy. Those receiving trimodal therapy were more likely to be covered by Medicare than those undergoing cystectomy. Uninsured patients were less likely to undergo definitive treatment and Medicare-insured patients were less likely to undergo cystectomy as their definitive therapy. Patients with greater socioeconomic disadvantage were less likely to receive definitive treatment, undergo cystectomy, or receive neoadjuvant chemotherapy. Over the course of the study period, there was increased neoadjuvant chemotherapy use, but a persistent gap by neighborhood socioeconomic status.Socioeconomic disadvantage and insurance status are patient-level factors associated with suboptimal treatment for muscle-invasive bladder cancer.

To investigate the association of female sex with the selected treatment for patients with nonmetastatic muscle-invasive bladder cancer. Sex is a known independent predictor of death from bladder cancer. A potential explanation for this survival disparity is difference in treatment pattern and stage presentation among males and females.Using the surveillance, epidemiology, and end results-medicare data set, we identified 6809 patients initially diagnosed with nonmetastatic muscle-invasive bladder cancer between 2004 and 2014. We fit multivariable logistic regression and Cox models to assess the relationship of sex with treatment modality and survival adjusting for differences in patient characteristics.Of the 6809 patients with nonmetastatic muscle invasive bladder cancer, 2528 (37%) received a radical cystectomy while 4281 (63%) received an alternative bladder sparing intervention. Women were significantly more likely to receive a cystectomy (odds ratios [OR] 1.39; 95% confidence intervals [CI] 1.20-1.61), present at an older age with less comorbidities compared to men (P.001). Women were also found to have worse bladder cancer-specific survival (CSS) than men (hazard ratio [HR] 1.18; 95% CI 1.05-1.32), no difference in overall survival (OS) (female HR 0.93; 0.86-1.01) and lower mortality from other causes (HR 0.78; 95% CI 0.70-0.86). There were no differences in OS and CSS by sex in patients with stage pT4a.Female sex predicted more aggressive treatment with radical cystectomy yet worse cancer-specific survival than males. This sex disparity in CSS reduced the known OS advantage observed in women.

Renal lymphangectasia is a benign malformation of the lymphatics which can be perirenal or peripelvic in location. Diagnosis is made on imaging including ultrasound, computed tomography , or MRI. We present an unusual case of renal lymphangectasia presenting with gross hematuria and flank pain diagnosed on computed tomography.

Background Metastatic breast cancer carries a poor prognosis despite the success of newly targeted therapies. Treatment options remain especially limited for the subtype of triple negative breast cancer (TNBC). Several signaling pathways, including NF-κB, are altered in TNBC, and the complexity of this disease implies multi-faceted pathway interactions. Given that IKKε behaves as an oncogene in breast cancer, we hypothesized that IKKε regulates NF-κB signaling to control diverse oncogenic functions in TNBC. Methods Vector expression and RNA interference were used to investigate the functional role of IKKε in triple-negative breast cancer cells. Viability, protein expression, NF-κB binding activity, invasion, anoikis, and spheroid formation were examined in cells expressing high or low levels of IKKε, in conjunction with p52 RNA interference or MEK inhibition. Results This study found that non-canonical NF-κB p52 levels are inversely proportional to ΙΚΚε, and growth of TNBC cells in anchorage supportive, high-attachment conditions requires IKKε and activated MEK. Growth of these cells in anchorage resistant conditions requires IKKε and activated MEK or p52. In this model, IKKε and MEK cooperate to support overall viability whereas the p52 transcription factor is only required for viability in low attachment conditions, underscoring the contrasting roles of these proteins. Conclusions This study illustrates the diverse functions of IKKε in TNBC and highlights the adaptability of NF-κB signaling in maintaining cancer cell survival under different growth conditions. A better understanding of the diversity of NF-κB signaling may ultimately improve the development of novel therapeutic regimens for TNBC. Electronic supplementary material The online version of this article (10.1186/s12885-018-4507-2) contains supplementary material, which is available to authorized users.

Nutrition plays a role in every aspect of gynecologic cancer care from diagnosis to death. Unfortunately, the topic is not well researched in gynecology oncology and much that is known about nutrition comes from other disciplines. Nutrition and resultant body mass index (BMI) affects a patient’s risk of diagnosis of a gynecologic malignancy, treatment tolerance, complications, and survival. Sadly, 20 % of patients with cancer die of malnutrition rather than their disease. However, not all malnourished patients are thin, as patients with BMIs in the obese range often do not have adequate nutrition. Recent literature challenges previous thoughts about feeding before and after surgery and clearly links obesity and diet quality with survival. More research is needed on the nutrition of patients with gynecologic malignancy, specifically how diet quality interfaces with the tolerance of radiation and chemotherapy.

Inhibitor of IκB kinases (IKK) are key regulators of NF-κB signaling. Three IKK isoforms—α, β, and ϵ—have been linked to oncogenesis, yet the precise components of NF-κB signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-ϵ expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P = 0.03). Therefore, we hypothesized that IKK-ϵ drives ovarian cancer metastasis. IKK-ϵ was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer–specific IKK-ϵ–regulated gene expression signature using stably expressed short hairpin RNA targeting IKK-ϵ. Pathway analysis of the signature indicated that IKK-ϵ regulates expression of genes involved in cell motility and inflammation. We further showed that IKK-ϵ depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKK-ϵ in mice showed decreased aggressiveness, whereas overexpression of IKK-ϵ in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKK-ϵ is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKK-ϵ signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway. Cancer Res; 72(21); 5494–504. ©2012 AACR.

Metastatic breast cancer carries a poor prognosis despite the success of newly targeted therapies and treatment options remain especially limited for the subtype of triple negative breast cancer (TNBC). Several signaling pathways, including NF-κB, are altered in TNBC. Given that ΙΚΚε behaves as an oncogene in breast cancer we hypothesized that IKKε regulates classical or alternative NF-κB signaling to control diverse oncogenic functions in TNBC. Vector expression and RNA interference were used to investigate the functional role of IKKε in triple-negative breast cancer cells. Viability, protein expression, NF-κB binding activity, invasion, anoikis, and spheroid formation were examined in cells expressing high or low levels of IKKε in conjunction with alternative NF-κB p52 RNA interference or MEK inhibition. Our data show that p52 protein levels and binding activity are inversely proportional to ΙΚΚε. Moreover, knockdown of IKKε leads to increased expression of p52 and the p52-regulated gene CXCL1. This interaction was confirmed by CHiP-PCR experiments showing increased binding of p52 in the CXCL1 promoter of cells with IKKε knockdown relative to control. We further found that IKKε and MEK were required for growth in anchorage supportive conditions whereas p52 was required in anchorage resistant conditions. Western blots confirm diminished IKKε expression and enhanced p52 processing in anchorage resistant conditions relative to anchorage supportive conditions. In this model, IKKε and MEK cooperate to support growth of cancer cells in the attached, anchored environment, whereas p52 is required for growth in unattached 3-D environment. These studies reveal novel information about the role of IKKε in TNBC and highlight the adaptability of NF-κB signaling in maintaining cancer cell survival under different growth conditions. Current studies are underway to clarify the mechanism of IKKε regulation of p52. A better understanding of the diversity of NF-κB signaling may ultimately improve the development of novel therapeutic regimens for TNBC. Citation Format: Carrie D. House, Valentina Grajales, Michelle Ozaki, Elizabeth Jordan, Helmae Wubneh, Danielle Kimble, Marianne Kim, Christina M. Annunziata. IKK-epsilon supports anchorage independent growth via alternative NF-kB signaling in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5470.

Metastatic breast cancer carries a poor prognosis despite the success of newly targeted therapies. Treatment options remain especially limited for the subtype of triple negative breast cancer (TNBC). Several signaling pathways, including NF-κB, are altered in TNBC, and the complexity of this disease implies multifaceted pathway interactions and compensatory signaling. We hypothesized that a subset of TNBCs expresses IKKϵ to promote a specific NF-κB signaling program that can enhance metastatic potential. Our data suggest that IKKϵ supports MEK activation and suppresses non-canonical signaling by the p52 NF-κB transcription factor. We found that NF-κB p52 expression is inversely proportional to activated MEK. We further demonstrate that IKKϵ and MEK cooperate to support viability and invasion potential under adherent conditions, whereas the p52 transcription factor supports viability under non-adherent conditions, underscoring the contrasting roles of these proteins. This study illustrates the diverse roles of NF-κB signaling components in TNBC, and highlights the adaptability of NF-κB in maintaining cancer cell survival under different microenvironments. A better understanding of the diversity of NF-κB signaling may ultimately improve the development of novel therapeutic regimens for TNBC. Citation Format: Carrie House, Valentina Grajales, Helmae Wubneh, Danielle Kimble, Marianne Kim, Christina Annunziata. IKKϵ maintains MEK activation and suppresses non-canonical NF-κB signaling in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1955. doi:10.1158/1538-7445.AM2015-1955