Malignant tumors in tuberous sclerosis complex: a case report and review of the literature.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations. CASE PRESENTATION: A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5'UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient's history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified. CONCLUSIONS: To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion.

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

Metastasis of Rectal Adenocarcinoma to the Penis and Scrotum in an Adult.

We present a unique case of a 74-year-old male with rectal adenocarcinoma and subsequent cutaneous metastases to the penis and scrotum. Although penile and scrotal metastases have been described separately in the literature, no report has documented simultaneous metastases to both sites. Here, we describe our patient's clinical course, treatment, and intervention throughout the timeline of his disease. We also discuss the presentation, evaluation, management, and prognosis of cutaneous metastasis to the penis and scrotum.

The association between body composition, leptin levels and glucose dysregulation in youth with cystic fibrosis.

BACKGROUND: Optimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls. METHODS: In a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, ß-cell insulin secretion and fasting leptin levels were obtained. RESULTS: Of the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group. CONCLUSIONS: This study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD.

Stretched penile length and its associations with testosterone and infertility.

BACKGROUND: Male infertility can be associated with secondary sexual characteristics, hypogonadism, and several findings in the examination of external genitalia. We sought to identify if stretched penile length (SPL) is associated with infertility or baseline testosterone. METHODS: We performed a retrospective review of all males age 18-59 presenting to a Men's health clinic from 2014 to 2017. SPL of patients with infertility were compared to patients with any other complaint. Patients with Peyronie's disease, prior penile surgery, prostatectomy, on testosterone replacement, clomiphene or ß-hCG were excluded from our study. Baseline characteristics were compared between the two groups (infertile vs. other). Linear regression was used to assess the association between infertility and testosterone with SPL after adjusting for patient age, BMI, and race. Scatterplot was used for correlation between testosterone and SPL. RESULTS: Six hundred and sixty-four men were included in our study (161 infertile, 503 other). The unadjusted mean SPL in the infertile group was 12.3 cm compared to 13.4 cm in the other group (P<0.001). The significance remained when adjusted for age, BMI, testosterone and race (12.4 vs. 13.3, P<0.001). Mean total testosterone in the infertile group was not significantly different than the other group (414 vs. 422, P=0.68). Infertile men were younger than the other group (33.2 vs. 42.1 years, P<0.001). BMI did not significantly differ (28.9 vs. 28.9 kg/m2, P=0.57). There was a weak positive correlation between testosterone and penile size in both the infertile group (r=0.20, P=0.01) and the other group (r=0.24, P<0.001). CONCLUSIONS: Though SPL differed amongst our groups, adult testosterone levels did not. If developmental levels of testosterone exposure accounted for some of the differences in SPL between our two groups, these variations did not persist into adulthood. It remains unknown if reduced length is a result of genetic or congenital factors associated with infertility. Further investigation is needed to better understand the association of shorter SPL with male infertility.

Funding Peyronie's disease: funding sources for primary research literature.

The objective was to describe funding sources and publication trends for the primary literature on Peyronie's disease (PD), including direct industry research support. A search of EMBASE, PubMed, Scopus, and Web of Science was performed to identify articles published from 2006 to 2018. Articles not published in English, reviews, case reports, editorials, guidelines, and meta-analysis were excluded from analysis. Data collected included year and journal of publication, major focus, and funding sources. The US Federal Open Payments database was searched for direct industry research payments to authors. Four hundred thirty-seven articles met criteria. The median number of yearly publications was 31. The most frequent publications were Journal of Sexual Medicine (25.6%), Urology (8.9%), BJU International (7.3%), and Journal of Urology (5.7%). Plaque excision/grafting was the most common topic (16.5%) followed by pathophysiology (15.3%), and intralesional therapy (14.9%). Only 15.1% (n = 66) of articles had a funding source with only 2.3% (n = 10) articles receiving any National Institutes of Health (NIH) funding. In total, 4.1% (n = 18) of the articles were industry funded, 61.1% (n = 11) of these from Xiaflex manufacturer Endo/Auxilium. Remaining articles appeared self-funded. There were 1524 unique authors and just 13 received any direct industry funds, totaling US$718,426. Most PD research is self-funded with only a small percentage from NIH or industry.

Selective androgen receptor modulators: the future of androgen therapy?

Selective androgen receptor modulators (SARMs) are small molecule drugs that function as either androgen receptor (AR) agonists or antagonists. Variability in AR regulatory proteins in target tissues permits SARMs to selectively elicit anabolic benefits while eschewing the pitfalls of traditional androgen therapy. SARMs have few side effects and excellent oral and transdermal bioavailability and may, therefore, represent viable alternatives to current androgen therapies. SARMs have been studied as possible therapies for many conditions, including osteoporosis, Alzheimer's disease, breast cancer, stress urinary incontinence (SUI), prostate cancer (PCa), benign prostatic hyperplasia (BPH), male contraception, hypogonadism, Duchenne muscular dystrophy (DMD), and sarcopenia/muscle wasting/cancer cachexia. While there are no indications for SARMs currently approved by the Food and Drug Administration (FDA), many potential applications are still being explored, and results are promising. In this review, we examine the literature assessing the use of SARMS for a number of indications.

Safety and Clinical Outcomes of Robot-Assisted Radical Prostatectomy in Kidney Transplant Patients: A Systematic Review.

OBJECTIVE: To evaluate the safety and outcomes of robot-assisted radical prostatectomy (RARP) in renal transplant recipients (RTRs) based on available literature. MATERIALS AND METHODS: A literature search was performed using PubMed, Embase, and Web of Science through "robot" AND "prostatectomy" AND "transplant." Three authors separately reviewed the records to select the relevant articles with any discrepancies solved by open discussion. Patient age, prostate-specific antigen, Gleason score, and tumor stage were recorded as well as intraoperative and postoperative complications, length of stay, surgical margin status, and disease recurrence, if provided. The operative techniques and modification/adjustments to standard port placements were also reviewed. We also include our case report in this review. RESULTS: We retrieved 10 articles reporting clinical data on RARP for kidney transplant patients, including 5 case series (level 4) and 5 case reports (level 4). A total of 35 kidney transplant recipients undergoing RARP were analyzed in this systematic review, one case in our institution included. None of the cases had major technical difficulties precluding the operation. Technical modifications to the standard technique were described in 10 of the 11 articles specifically including modifications to port placement (54% of patients), development of the space of Retzius (60% of patients), and performance of lymphadenectomy. Mean operative time was 220 minutes. Perioperative complication rate was 17.1% (6 of 35 patients), with only one Clavien III or greater complication. The rate of positive surgical margins was found to be 31.4%. Data on biochemical recurrence revealed a combined rate of 18.1%. CONCLUSIONS: RARP is technically feasible for treating localized prostate cancer in RTRs. Graft function did not deteriorate in any patient. Modifications to the standard technique should be considered specifically for port placement, development of the space of Retzius, and performance of lymphadenectomy. Oncologic outcomes remain difficult to interpret given the small number of reported cases.

Intraoperative utilization of advanced imaging modalities in a complex kidney stone case: a pilot case study.

PURPOSE: Despite the increasing use of advanced 3D imaging techniques and 3D printing, these techniques have not yet been comprehensively compared in a surgical setting. The purpose of this study is to explore the effectiveness of five different advanced imaging modalities during a complex renal surgical procedure. METHODS: A patient with a horseshoe kidney and multiple large, symptomatic stones that had failed Extracorporeal Shock Wave Lithotripsy (ESWL) and ureteroscopy treatment was used for this evaluation. CT data were used to generate five different imaging modalities, including a 3D printed model, three different volume rendered models, and a geometric CAD model. A survey was used to evaluate the quality and breadth of the imaging modalities during four different phases of the laparoscopic procedure. RESULTS: In the case of a complex kidney procedure, the CAD model, 3D print, volume render on an autostereoscopic 3D display, interactive and basic volume render models demonstrated added insight and complemented the surgical procedure. CAD manual segmentation allowed tissue layers and/or kidney stones to be made colorful and semi-transparent, allowing easier navigation through abnormal vasculature. The 3D print allowed for simultaneous visualization of renal pelvis and surrounding vasculature. CONCLUSIONS: Our preliminary exploration indicates that various advanced imaging modalities, when properly utilized and supported during surgery, can be useful in complementing the CT data and laparoscopic display. This study suggests that various imaging modalities, such as ones utilized in this case, can be beneficial intraoperatively depending on the surgical step involved and may be more helpful than 3D printed models. We also present factors to consider when evaluating advanced imaging modalities during complex surgery.