Diagnosis of prolactinoma in two male‐to‐female transsexual subjects following high‐dose cross‐sex hormone therapy

Male‐to‐female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self‐adminstration of cross‐sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male‐to‐female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male‐to‐female transsexual persons, one in a 41‐year‐old subject who had used nonsupervised high‐dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.     

Characteristics of low‐density and high‐density lipoprotein subclasses in pediatric renal transplant recipients

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) particles and their associations with carotid intima‐media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)‐cholesterol (sdLDL‐C) and sdLDL‐apolipoprotein B (sdLDL‐apoB) using heparin‐magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL‐C (P < 0.01) and sdLDL‐apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL‐C and sdLDL‐apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small‐sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.     

Short‐term physiological response to high‐frequency‐actuated pVAD support

Ventricular assist devices (VADs) are an established treatment option for heart failure (HF). However, the devices are often plagued by material‐related hemocompatibility issues. In contrast to continuous flow VADs with high shear stresses, pulsatile VADs (pVADs) offer the potential for an endothelial cell coating that promises to prevent many adverse events caused by an insufficient hemocompatibility. However, their size and weight often precludes their intracorporeal implantation. A reduction of the pump body size and weight of the pump could be achieved by an increase in the stroke frequency while maintaining a similar cardiac output. We present a new pVAD system consisting of a pump and an actuator specifically designed for actuation frequencies of up to 240 bpm. In vitro and in vivo results of the short‐term reaction of the cardiovascular system show no significant changes in left ventricular and aortic pressure between actuation frequencies from 60 to 240 bpm. The aortic pulsatility increases when the actuation frequency is raised while the heart rate remains unaffected in vivo. These results lead us to the conclusion that the cardiovascular system tolerates short‐term increases of the pVAD stroke frequencies.     

Three‐dimensional high‐density co‐culture with primary tenocytes induces tenogenic differentiation in mesenchymal stem cells

Mesenchymal stem cells (MSCs) have potential applications in regenerative medicine and tissue engineering and may represent an attractive option for tendon repair and regeneration. Thus far the ability of MSCs to differentiate into tenocytes in vitro has not been investigated. Experiments were performed with and without growth factors (IGF‐1, TGF‐β1, IGF‐1/TGF‐β1, PDGF‐BB, and BMP‐12), in co‐cultures of tenocytes and MSCs mixed in different ratios and by culturing MSCs with spent media obtained from primary tenocytes. Tenogenesis was induced in MSCs through a combination of treatment with IGF‐1 and TGF‐β1, in high‐density co‐cultures and through cultivation with the spent media from primary tenocytes. Electron microscopy and immunoblotting were used to demonstrate up‐regulation of collagen I/III, decorin, tenomodulin, β1‐Integrin, MAPKinase pathway (Shc, Erk1/2), and scleraxis in the co‐cultures and provide simultaneous evidence for the inhibition of apoptosis. In monolayer co‐cultures extensive intercellular contacts between MSCs and tenocytes were observed. Cells actively exchanged vesicles, which were labeled by using immunofluorescence and immunogold techniques, suggesting the uptake and interchange of soluble factors produced by the MSCs and/or tenocytes. We conclude that MSCs possess tenogenic differentiation potential when provided with relevant stimuli and a suitable microenvironment. This approach may prove to be of practical benefit in future tissue engineering and tendon regenerative medicine research. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1351–1360, 2011     

Prognostic significance of high‐grade dysplasia in colorectal adenomas

Aim Colonoscopy to detect and remove polyps has contributed to a reduction in colorectal carcinoma. Three‐year follow up is recommended for patients considered to be at high risk (at least three adenomas, adenoma ≥ 1 cm, villous or high‐grade features). Our study focused on patients diagnosed with high‐grade dysplasia with regard to initial management and follow up. Method A search of patients who had had endoscopic removal of a high‐grade adenoma was carried out. Patients with the following were excluded: follow up of < 1 year, polyposis syndromes, prior colon cancer and a diagnosis of adenocarcinoma within 6 months following initial diagnosis. Results Eighty‐three patients treated between 1999 and 2007 for high‐grade dysplasia (HGD) in a colorectal adenoma were identified. Over a median follow‐up period of 4 years, 53 (64%) developed further adenomatous polyps. Among these, 7% had an adenoma with HGD or an adenocarcinoma. In all these patients, the initial high‐grade adenoma was > 1 cm in diameter. Initial follow‐up colonoscopy was performed on average 7 months following the initial diagnosis. Ten per cent of patients underwent prophylactic segmental resection, and 6% received argon laser therapy. Conclusion The study demonstrates that patients who have a colorectal adenoma > 1 cm with HGD may be at high risk of developing further adenomas with HGD or carcinoma. Close follow up is warranted.     

Exendin‐4 shows no effects on the prostatic index in high‐fat‐diet‐fed rat with benign prostatic hyperplasia by improving insulin resistance

Benign prostatic hyperplasia (BPH) is a prevalent disease globally, and accumulating evidence has indicated an association between BPH, insulin resistance (IR) and diabetes. Exendin‐4 is widely used in clinics, which could enhance the proliferation of pancreatic β cells. The ability of exendin‐4 to promote tumorigenesis has been of concern, and whether exendin‐4 would enhance the propagation of BPH is not fully understood. We aimed to determine whether glucagon‐like peptide‐1 receptors (GLP‐1Rs) were expressed in rat prostate and to determine the effect of exendin‐4 on prostate of BPH. Male Wistar rats were used and assigned to six groups: normal diet (ND), high‐fat diet (HFD), HFD + exendin‐4, HFD + BPH, HFD + BPH + exendin‐4 and HFD + BPH + rosiglitazone group. After castration, steroids were injected subcutaneously for 4 weeks to induce BPH. Rats were kept on high‐fat diet to induce IR. Treatment groups were treated with exendin‐4 and rosiglitazone. Prostatic index and HOMA‐IR index were used to evaluate the prostatic hyperplasia status and the degree of IR respectively. The expression of GLP‐1R was indicated not only by immunohistochemistry, but also by Western blot analysis. The expression of GLP‐1R was significantly higher, and HOMA‐IR index and body weight significantly decreased after administration of exendin‐4. However, no significant differences in the prostatic index were observed between exendin‐4 treatment groups and non‐exendin‐4 treatment groups. Prostatic index was not influenced by exendin‐4 maybe by improving IR and weight loss.     

APOL1 high‐risk genotypes and renal transplantation

The discovery of apolipoprotein L1 (APOL1) gene variants and its association with kidney disease in African‐Americans represent a significant breakthrough in understanding the genetic basis of ancestry‐based differences in a public health problem. The role these variants play in renal transplantation is still incompletely understood. This article reviews the epidemiologic data and current reports of APOL1 variant pathogenesis in transplantation. We examine existing data on outcomes in APOL1 high‐risk kidneys, high‐risk APOL1 recipients, live donors with high‐risk mutations and non–renal transplantation of high‐risk APOL1 organs. We discuss the rapidly evolving role and potential pros and cons of APOL1 genotyping of donors and recipients in transplantation. Finally, we highlight the ongoing nationwide National Institutes of Health‐sponsored “APOL1 Long‐term Kidney Transplantation Outcomes (APOLLO)” study, which will quantify outcomes and “second hits” in pertinent to APOL1 high‐risk variants in renal transplantation.     

Early oncological outcomes of robot‐assisted radical prostatectomy for high‐grade prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence‐free survival (BCRFS) after robot‐assisted radical prostatectomy (RARP).

PATIENTS AND METHODS

Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan–Meier method and log‐rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling.

RESULTS

The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow‐up was 23 (10–46) months and 19 (7–37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se ) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS.

CONCLUSIONS

Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high‐grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours.     

Early quality of life outcomes in patients with prostate cancer managed by high‐dose‐rate brachytherapy as monotherapy

Objectives: To evaluate the early quality of life outcomes in prostate cancer patients managed by high‐dose‐rate brachytherapy as monotherapy. Methods: A total of 51 patients with cT1c–T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69 years, and the average initial serum prostate‐specific antigen was 10.98 ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir‐192 and seven fractions of 6.5 Gy within 3.5 days for a total prescribed dose of 45.5 Gy. For high‐risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6 months, and continued after high‐dose‐rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy‐Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate‐specific antigen and diagnostic imaging. Adverse events were also recorded. Results: The Functional Assessment of Cancer Therapy‐Prostate scores decreased for a few months after high‐dose‐rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2 weeks after treatment for each of its items and their sum, and it returned to baseline after 12 weeks. Sexual function decreased at 2 and 4 weeks, and recovered after 12 weeks. Severe complications were rare. Within a median follow up of 17.2 months, two patients showed a prostate‐specific antigen recurrence. Conclusions: High‐dose‐rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life.     

Transrectal high‐intensity focused ultrasound for treatment of localized prostate cancer

Objectives: To assess the long‐term outcomes of transrectal high‐intensity focused ultrasound (HIFU) for patients with localized prostate cancer. Methods: From May 2003 to present, 137 consecutive patients with T1‐2 prostate cancer were treated using the Sonablate 500 and then followed for more than 12 months after their last HIFU treatment. A prostate biopsy was routinely carried out at 6 months and serum prostate‐specific antigen (PSA) was measured every 3 months after HIFU. Oncological outcomes as well as treatment‐related complications were assessed. Disease‐free survival (DFS) was judged using the Phoenix definition (PSA nadir + 2 ng/mL), negative histological findings and no local or distant metastasis. Results: The median follow up after HIFU was 36 months (range 12–84 months). No patients received adjuvant therapy during this period. The PSA nadir occurred at 2 months after HIFU and the median level was 0.07 ng/mL (0.01–2.01 ng/mL). Of the 133 patients who underwent prostate biopsy or transurethral resection of the prostate at 6 months or later after HIFU, six were positive for cancer cells (4.5%). There were no major postoperative complications, but urge incontinence (16 cases) and dysuria (33 cases) occurred after removal of the urethral catheter. The 5‐year DFS rate was 78% based on these criteria, and 91%, 81% and 62% in the low‐, intermediate‐ and high‐risk group, respectively. Conclusions: HIFU represents an effective, repeatable and minimally invasive treatment. It is particularly effective for low‐ and intermediate‐risk patients, and it should be considered as an option for localized prostate cancer.