Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Nat Rev Urol ; 21(6): 329-338, 2024 06.
Article in English | MEDLINE | ID: mdl-38168921

ABSTRACT

Decisions around prostate-specific antigen screening require a patient-centred approach, considering the benefits and risks of potential harm. Using shared decision-making (SDM) can improve men's knowledge and reduce decisional conflict. SDM is supported by evidence, but can be difficult to implement in clinical settings. An inclusive definition of SDM was used in order to determine the prevalence of SDM in prostate cancer screening decisions. Despite consensus among guidelines endorsing SDM practice, the prevalence of SDM occurring before the decision to undergo or forgo prostate-specific antigen testing varied between 11% and 98%, and was higher in studies in which SDM was self-reported by physicians than in patient-reported recollections and observed practices. The influence of trust and continuity in physician-patient relationships were identified as facilitators of SDM, whereas common barriers included limited appointment times and poor health literacy. Decision aids, which can help physicians to convey health information within a limited time frame and give patients increased autonomy over decisions, are underused and were not shown to clearly influence whether SDM occurs. Future studies should focus on methods to facilitate the use of SDM in clinical settings.


Subject(s)
Decision Making, Shared , Early Detection of Cancer , Physician-Patient Relations , Prostatic Neoplasms , Humans , Prostatic Neoplasms/diagnosis , Male , Prostate-Specific Antigen/blood , Patient Participation
2.
Urology ; 184: 157-161, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37774852

ABSTRACT

OBJECTIVE: To identify antibiotic prescribing patterns at the time of foley catheter removal after radical prostatectomy and implement a multi-pronged behavioral intervention to standardize antibiotic use. METHODS: This was a single-institution study examining the prescribing of antibiotics at the time of foley catheter removal after radical prostatectomy. Pre-intervention data were collected retrospectively to establish baselines for antibiotic prescribing, patient characteristics, and urinary tract infection rates. A single dose of an oral antibiotic taken at the time of foley catheter removal was recommended as the standard antibiotic protocol. A multi-pronged behavioral intervention was used to encourage compliance with our protocol. Adherence to the protocol, quantity of antibiotics prescribed, and rate of urinary tract infection were recorded prospectively. Durability of the intervention was evaluated during a post-intervention phase. RESULTS: A total of 416 patients and 6 surgeons were included in the study. Accordance with the standardized antibiotic protocol was 59% in the pre-intervention phase and 91% in the intervention phase (P = .03). No patients in the intervention or post-intervention phase were prescribed more than one dose of an antibiotic. The rate of urinary tract infection did not differ across the study phases. CONCLUSION: Implementation of a multi-pronged behavioral intervention resulted in a high rate of surgeon compliance with a standardized antibiotic protocol. This led to a significant reduction in antibiotic use with no change in the rate of urinary tract infection after foley catheter removal after radical prostatectomy.


Subject(s)
Antibiotic Prophylaxis , Urinary Tract Infections , Male , Humans , Retrospective Studies , Prostatectomy , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/epidemiology , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Catheters
3.
Cancer Cell ; 41(11): 1963-1971.e3, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37890492

ABSTRACT

Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.


Subject(s)
Lung Neoplasms , Protein-Tyrosine Kinases , Male , Humans , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation
4.
BMC Urol ; 23(1): 152, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37777716

ABSTRACT

BACKGROUND: Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group. MAIN BODY: AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy. CONCLUSION: AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.


Subject(s)
Prostatic Neoplasms , Watchful Waiting , Male , Humans , Watchful Waiting/methods , Neoplasm Grading , Quality of Life , Prospective Studies , Retrospective Studies , Prostatic Neoplasms/pathology , Prostate-Specific Antigen
5.
Eur Urol ; 84(2): 191-206, 2023 08.
Article in English | MEDLINE | ID: mdl-37202314

ABSTRACT

CONTEXT: Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies. OBJECTIVE: To systematically review and summarize the current evidence on the descriptive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa. EVIDENCE ACQUISITION: PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728). EVIDENCE SYNTHESIS: Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies. CONCLUSIONS: PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of overdiagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening. PATIENT SUMMARY: Prostate cancer (PCa) remains the second most common cancer among men, and screening for PCa is likely to increase in the future. Improved diagnostic techniques can help reduce the number of men who need to be diagnosed and treated to save one life. Avoidable risk factors for PCa may include factors such as smoking, diet, physical activity, specific medications, and certain occupations.


Subject(s)
Prostatic Neoplasms , Male , Humans , Retrospective Studies , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/pathology , Prostate/pathology , Risk Factors , Prostate-Specific Antigen
6.
Urology ; 177: 81-88, 2023 07.
Article in English | MEDLINE | ID: mdl-37028521

ABSTRACT

OBJECTIVE: To examine the association of area-level socioeconomic status, rural-urban residence, and type of insurance with overall and cancer-specific mortality among patients with muscle-invasive bladder cancer. METHODS: Using the Pennsylvania Cancer Registry, which collects demographic, insurance, and clinical information on every patient with cancer within the state, we identified all patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2016 based on clinical and pathologic staging. We used the Area Deprivation Index (ADI) as a surrogate for socioeconomic status and Rural-Urban Commuting Area codes to classify urban, large town, and rural communities. ADI was reported in quartiles, with 4 representing the lowest socioeconomic status. We fit multivariable logistic regression and Cox models to assess the relationship of these social determinants with overall and cancer-specific survival adjusting for age, sex, race, stage, treatment, rural-urban classification, insurance and ADI. RESULTS: We identified 2597 patients with non-metastatic muscle-invasive bladder cancer. On multivariable analysis, Medicare (hazards ratio [HR] 1.15), Medicaid (HR 1.38), ADI 3 (HR 1.16) and ADI 4 (HR 1.21) were independent predictors of greater overall mortality (all P < 0.05). Female sex and receipt of non-standard treatment were associated with increased overall mortality and bladder cancer-specific mortality. There was no significant difference in both overall and cancer-specific survival between patients who were non-Hispanic White compared to non-White or between those from urban areas, large towns, or rural locations. CONCLUSION: Lower socioeconomic status and Medicare and Medicaid insurance were associated with a greater risk of overall mortality while rural residence was not a significant factor. Implementation of public health programs may help reduce the gap in mortality for low SES at-risk populations.


Subject(s)
Medicare , Urinary Bladder Neoplasms , Humans , Female , Aged , United States/epidemiology , Social Class , Medicaid , Muscles
7.
Urology ; 175: 18-24, 2023 05.
Article in English | MEDLINE | ID: mdl-36868411

ABSTRACT

OBJECTIVE: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. METHODS: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. RESULTS: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60). CONCLUSION: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.


Subject(s)
Anti-Bacterial Agents , Prostate , Male , Humans , Anti-Bacterial Agents/therapeutic use , Prostate/pathology , Antibiotic Prophylaxis/methods , Rectum , Biopsy/adverse effects , Biopsy/methods , Image-Guided Biopsy/methods
8.
Urology ; 170: 221-225, 2022 12.
Article in English | MEDLINE | ID: mdl-36206827

ABSTRACT

INTRODUCTION: 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. TECHNICAL CONSIDERATIONS: 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. CONCLUSIONS: This combination of surgical techniques strives to improve quality of life and facilitate cancer surveillance without compromising oncologic outcomes.


Subject(s)
Penile Neoplasms , Adult , Male , Humans , Penile Neoplasms/surgery , Quality of Life , Penis/surgery , Pelvis , Medical Oncology
9.
Urology ; 167: 56-60, 2022 09.
Article in English | MEDLINE | ID: mdl-35780945

ABSTRACT

OBJECTIVE: To examine overall trends in opioid prescribing after ureteroscopy and compared opioid use between private and academic practice settings. We also analyzed the potential for spillover effect from an unrelated opioid-reduction initiative for major oncologic surgery. METHODS: We conducted a retrospective chart review of all ureteroscopies performed within our system at four distinct time points from 2016-2019. We recorded the type and number of opioid pills prescribed and calculated oral morphine equivalents. Analysis included comparison between community and academic hospitals as well as pre- and post-initiative. RESULTS: 555 patients undergoing ureteroscopy and 29 attending surgeons were included in the analysis. The median prescription size per ureteroscopy decreased throughout the study period in both the private and academic settings. From 2016-2017, median oral morphine equivalents (OMEs) decreased from 60 to 0 in the private setting and remained at 0 for the duration of the study period. Opioid reduction in the academic setting lagged behind private practitioners but median OMEs did steadily decrease to 0 in 2019. No significant spillover effect was observed. CONCLUSION: Since 2016, opioid prescribing following ureteroscopy has decreased in both the private and academic practice settings. Notably, private practice urologists achieved a median of 0 opioids 2 years prior to academic urologists. These data suggest that, in some circumstances, academic institutions may have been slower to respond to the opioid epidemic.


Subject(s)
Analgesics, Opioid , Ureteroscopy , Analgesics, Opioid/therapeutic use , Drug Prescriptions , Humans , Morphine Derivatives/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Practice Patterns, Physicians' , Private Practice , Retrospective Studies , Urologists
11.
Urol Oncol ; 40(4): 164.e17-164.e23, 2022 04.
Article in English | MEDLINE | ID: mdl-35022140

ABSTRACT

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Socioeconomic disadvantage and insurance status are patient-level factors associated with suboptimal treatment for muscle-invasive bladder cancer.


Subject(s)
Urinary Bladder Neoplasms , Aged , Cystectomy , Female , Humans , Male , Medicare , Muscles/pathology , Neoadjuvant Therapy , Neoplasm Invasiveness , Registries , Retrospective Studies , United States , Urinary Bladder Neoplasms/pathology
12.
Urol Oncol ; 39(12): 834.e9-834.e20, 2021 12.
Article in English | MEDLINE | ID: mdl-34162498

ABSTRACT

OBJECTIVES: To evaluate the impact of centralized surgical and nonsurgical care (i.e., radiation and chemotherapy) on travel distances and survival outcomes for patients with advanced bladder cancer. Bladder cancer is a disease with high mortality for which treatment access is paramount and survival is superior in patients receiving surgery at high-volume centers. METHODS: Using SEER-Medicare, we identified patients 66 years or older diagnosed with bladder cancer between 2004-2013. We categorized patients as treated with either surgical (i.e., radical cystectomy) or nonsurgical (i.e., radiation or chemotherapy) care. We fit a linear probability model to generate the predicted proportion of patients treated at the top quintile of volume over time and assessed travel distance, 1-year all-cause mortality, and 1-year bladder cancer-specific mortality over time. RESULTS: A total of 6,756 and 10,383 patients underwent surgical and nonsurgical care, respectively. The percentage of patients treated at high-volume centers increased over the study period for both surgical care (53% to 62%) and nonsurgical care (47% to 55%), (both P< 0.001). Median travel distance increased (11.8 to 20.3 miles) for surgical care and (6.5 to 8.3 miles) for nonsurgical care, (both P < 0.001). The 1-year adjusted all-cause mortality and 1-year adjusted bladder-cancer specific mortality decreased significantly for both surgical and nonsurgical care (both P < 0.05). CONCLUSIONS: Over time, centralization of surgical and nonsurgical care for bladder cancer patients increased, which was associated with increasing patient travel distance and decreased all-cause and bladder-cancer specific mortality.


Subject(s)
Health Services Accessibility/standards , SEER Program/standards , Travel/statistics & numerical data , Urinary Bladder Neoplasms/epidemiology , Aged , Female , Humans , Male , Medicare , Survival Analysis , United States , Urinary Bladder Neoplasms/mortality
13.
Cancer ; 127(2): 257-265, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33002197

ABSTRACT

BACKGROUND: Surgeons play a pivotal role in combating the opioid crisis that currently grips the United States. Changing surgeon behavior is difficult, and the degree to which behavioral science can steer surgeons toward decreased opioid prescribing is unclear. METHODS: This was a single-institution, single-arm, pre- and postintervention study examining the prescribing of opioids by urologists for adult patients undergoing prostatectomy or nephrectomy. The primary outcome was the quantity of opioids prescribed in oral morphine equivalents (OMEs) after hospital discharge. The primary exposure was a multipronged behavioral intervention designed to decrease opioid prescribing. The intervention had 3 components: 1) formal education, 2) individual audit feedback, and 3) peer comparison performance feedback. There were 3 phases to the study: a pre-intervention phase, an intervention phase, and a washout phase. RESULTS: Three hundred eighty-two patients underwent prostatectomy, and 306 patients underwent nephrectomy. The median OMEs decreased from 195 to 19 in the prostatectomy patients and from 200 to 0 in the nephrectomy patients (P < .05 for both). The median OMEs prescribed did not increase during the washout phase. Prostatectomy patients discharged with opioids had higher levels of anxiety than patients discharged without opioids (P < .05). Otherwise, prostatectomy and nephrectomy patients discharged with and without opioids did not differ in their perception of postoperative pain management, activity levels, psychiatric symptoms, or somatic symptoms (P > .05 for all). CONCLUSIONS: Implementing a multipronged behavioral intervention significantly reduced opioid prescribing for patients undergoing prostatectomy or nephrectomy without compromising patient-reported outcomes.


Subject(s)
Analgesics, Opioid/administration & dosage , Drug Prescriptions/statistics & numerical data , Morphine/administration & dosage , Nephrectomy , Pain Management/methods , Pain, Postoperative/drug therapy , Prostatectomy , Administration, Oral , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Pain Management/psychology , Patient Reported Outcome Measures , Surgeons/psychology , Treatment Outcome , United States , Urologists/psychology
14.
Can J Urol ; 27(1): 10138-10141, 2020 02.
Article in English | MEDLINE | ID: mdl-32065873

ABSTRACT

Renal artery aneurysms can present with gross hematuria and are potentially life-threatening in cases of rupture. We report a case of a young male with no prior genitourinary history who presents to an emergency department with sudden onset gross hematuria, clot retention, and right-sided flank pain. On evaluation, he was found to have a renal artery aneurysm bleeding into his collecting system and underwent renal artery embolization and rapid resolution of his hematuria. Renal vascular pathology should be considered in the differential diagnosis and timely diagnosis of this condition is imperative as surgical interventions have proven to be life-saving.


Subject(s)
Aneurysm/complications , Hematuria/etiology , Renal Artery , Adult , Humans , Male , Severity of Illness Index
15.
J Urol ; 203(3): 551-552, 2020 03.
Article in English | MEDLINE | ID: mdl-31769721
16.
Eur Urol Focus ; 6(6): 1168-1169, 2020 11 15.
Article in English | MEDLINE | ID: mdl-31563546

ABSTRACT

In urology, whether a surgeon needs to prescribe narcotics after minimally invasive surgery used to be a grey zone. We no longer believe that it is necessary to give opioids to opioid-naïve patients undergoing minimally invasive urologic surgery, with few exceptions.


Subject(s)
Analgesics, Opioid/therapeutic use , Pain, Postoperative/drug therapy , Urologic Surgical Procedures , Drug Utilization/trends , Humans , Minimally Invasive Surgical Procedures , Opioid Epidemic/prevention & control , Postoperative Care , Practice Patterns, Physicians'/trends , Urologic Surgical Procedures/methods , Urology
17.
Urology ; 133: 229-233, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31369750

ABSTRACT

OBJECTIVE: To determine the prevalence of penile cancer in patients with adult acquired buried penis (AABP). Penile cancer is a rare but aggressive cancer. Several case reports have recently been published that indicate that AABP may increase the risk of penile cancer. MATERIALS AND METHODS: A retrospective review was conducted of adults diagnosed with AABP and penile cancer between January, 2008 and December, 2018 seen at a tertiary referral center. Demographics including age, BMI, comorbidities, etiology of AABP, smoking history, circumcision status, and premalignant lesions (condyloma, lichen sclerosus [LS] carcinoma in situ [CIS]) were recorded. For patients with penile cancer, AJCC staging, grade, TNM staging and treatments were recorded. Basic descriptive statistics were performed for the overall cohort. We used Chi-square tests and Fisher exact tests to compare differences between patients with benign pathology and patients with malignant or pre-malignant pathology. RESULTS: We identified 150 patients with the diagnosis of AABP. The prevalence of penile squamous cell carcinoma was 7%. There was a 35% rate of premalignant lesions. This study is limited by its retrospective and single-institution nature. CONCLUSION: AABP is a condition that incorporates multiple risk factors for penile cancer. The prevalence of penile cancer appears to be higher in patients with AABP; however, more data are needed to confirm these initial findings. Patients with AABP should be counseled on these risks and should be considered for buried penis repair if a physical examination cannot be performed.


Subject(s)
Penile Diseases/complications , Penile Neoplasms/complications , Penile Neoplasms/epidemiology , Adult , Humans , Male , Middle Aged , Obesity/complications , Penile Diseases/etiology , Prevalence , Retrospective Studies
18.
Laryngoscope ; 125(12): 2656-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26153255

ABSTRACT

Chronic invasive fungal sinusitis (CIFS) is a rare but potentially aggressive form of invasive fungal disease that occurs in immunocompetent patients. We report a case of CIFS in an otherwise healthy young adult associated with intranasal illicit drug abuse. The patient presented with nonhealing nasal septal and palatal perforations. Biopsy demonstrated invasive Aspergillus flavus requiring surgical debridement and extended intravenous antifungal therapy. Tissue necrosis and ulceration related to intranasal drug use should be recognized as a potential risk factor for invasive fungal sinusitis.


Subject(s)
Aspergillosis/etiology , Aspergillus flavus , Sinusitis/microbiology , Substance-Related Disorders/complications , Administration, Intranasal , Debridement , Humans , Male , Nasal Surgical Procedures/methods , Sinusitis/surgery , Young Adult
19.
Lab Invest ; 94(5): 517-27, 2014 May.
Article in English | MEDLINE | ID: mdl-24638272

ABSTRACT

Normal pancreatic epithelium progresses through various stages of pancreatic intraepithelial neoplasms (PanINs) in the development of pancreatic ductal adenocarcinoma (PDAC). Transcriptional regulation of this progression is poorly understood. In mouse, the hepatic nuclear factor 6 (Hnf6) transcription factor is expressed in ductal cells and at lower levels in acinar cells of the adult pancreas, but not in mature endocrine cells. Hnf6 is critical for terminal differentiation of the ductal epithelium during embryonic development and for pancreatic endocrine cell specification. We previously showed that, in mice, loss of Hnf6 from the pancreatic epithelium during organogenesis results in increased duct proliferation and altered duct architecture, increased periductal fibrosis and acinar-to-ductal metaplasia. Here we show that decreased expression of HNF6 is strongly correlated with increased severity of PanIN lesions in samples of human pancreata and is absent from >90% of PDAC. Mouse models in which cancer progression can be analyzed from the earliest stages that are seldom accessible in humans support a role for Hnf6 loss in progression from early- to late-stage PanIN and PDAC. In addition, gene expression analyses of human pancreatic cancer reveal decreased expression of HNF6 and its direct and indirect target genes compared with normal tissue and upregulation of genes that act in opposition to HNF6 and its targets. The negative correlation between HNF6 expression and pancreatic cancer progression suggests that HNF6 maintains pancreatic epithelial homeostasis in humans, and that its loss contributes to the progression from PanIN to ductal adenocarcinoma. Insight on the role of HNF6 in pancreatic cancer development could lead to its use as a biomarker for early detection and prognosis.


Subject(s)
Carcinoma, Pancreatic Ductal/metabolism , Hepatocyte Nuclear Factor 6/deficiency , Hepatocyte Nuclear Factor 6/genetics , Liver Neoplasms, Experimental/metabolism , Pancreatic Neoplasms/metabolism , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Disease Progression , Hepatocyte Nuclear Factor 6/metabolism , Homeostasis/genetics , Humans , Liver Neoplasms, Experimental/genetics , Liver Neoplasms, Experimental/pathology , Mice , Mice, Inbred C57BL , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...