Ιmpact of sunitinib-induced hypothyroidism on survival of patients with metastatic renal cancer.

BACKGROUND: Sunitinib plays an important role in managing the metastatic renal cell cancer (mRCC). Sunitinib-induced hypothyroidism is a common side-effect of the drug. There have been attempts to link hypothyroidism with a better clinical outcome in sunitinib-treated (mRCC) patients. Our aim was to relate the impact of hypothyroidism to the survival of these patients. METHODS: We have evaluated 70 patients with mRCC that received sunitinib as a first line treatment. Thyroid-stimulating hormone (TSH) was measured at baseline, after 15 days of treatment (day-15) and at the end of the second cycle (day-75). Biomarker data and correlations with response were analysed with Microsoft Excel. Comparison results from Student's t-test with a p less than 0.05 were considered statistically significant. Kaplan-Meyer and log-rank tests were performed using GraphPad Prism 5 for Windows. RESULTS: Regarding the response to treatment, a progression-free survival (PFS) of 9.47 months and an overall survival (OS) of 22.03 months were demonstrated. Our data are consistent with published data by other authors. On day-15 from the beginning of the treatment an important number of patients exhibited a TSH elevation. On day-15 42.86% had a TSH over the upper normal limit and 50.0% at the end of the second cycle (day-75). TSH increased earlier in patients that exhibited an objective response (× 3.33 times the baseline values on day-15) than patients that exhibited disease stabilisation (× 2.18) or disease progression (× 1.59). Early increases in TSH were associated with a longer PFS (11.92 vs. 8.82 months, p = 0.0476) and a longer OS (3.10 vs. 1.08 years, p = 0.0011). CONCLUSIONS: Early TSH-increase is associated with a clinical benefit. The patients that showed at least a twofold increase of their baseline TSH, responded to therapy by stabilisation or by regression of disease. This is the only study to our knowledge which shows that early increases - 2 weeks from starting the treatment - in TSH levels have a prognostic value. Both PFS and OS of the patients who demonstrated a higher than a twofold rise were significantly longer than the PFS and the OS of the patients that presented a lower or no TSH-increase.

'Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis).

Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear.

Percutaneous Microwave Ablation Versus Robot-Assisted Partial Nephrectomy for Stage I Renal Cell Carcinoma: A Propensity-Matched Cohort Study Focusing Upon Long-Term Follow-Up of Oncologic Outcomes.

PURPOSE: To retrospectively compare long-term oncologic outcomes of percutaneous computed tomography-guided microwave ablation (MWA) and robot-assisted partial nephrectomy (RAPN) for the treatment of stage 1 (T1a and T1b) renal cell carcinoma (RCC) patients. MATERIALS AND METHODS: Institutional database research identified all T1 RCC patients who underwent either MWA or RAPN. Models were adjusted with propensity score matching. Kaplan-Meier log-rank test analyses and Cox proportional hazard regression models were used to compare the oncologic outcomes. Patient and tumor characteristics, technical success as well as oncologic outcomes were evaluated and compared between the 2 groups. RESULTS: After propensity score matching, a total of 71 patients underwent percutaneous MWA (mean age 70 ± 10 years) and 71 underwent RAPN (mean age 60 ± 9 years). At 8-year follow-up, the estimated survival rates for MWA cohort were 98% (95% confidence interval [CI] 95-100%) for overall survival, 97% (95% CI 93-100%) for recurrence-free survival, and 97% (95% CI 93-100%) for metastasis-free survival. The matched cohort that underwent RAPN exhibited survival rates of 100% (95% CI 100-100%) for overall survival, 98% (95% CI 94-100%) for recurrence-free survival, and 98% (95% CI 94-100%) for metastasis-free survival. After performing log-rank testing, these rates were not significantly different (p values of 0.44, 0.67, and 0.67, respectively). CONCLUSION: The results of the present study suggest that both MWA and RAPN are equally effective in terms of oncologic outcome for the treatment of T1 RCC.

Paraganglioma of the Urinary Bladder: A Case Report on a Rare and Unexpected Tumor Location.

Paraganglioma of the urinary bladder is an exceptionally rare tumor. It originates from chromaffin cells, which are responsible for producing catecholamines. We report a unique case of a 74-year-old woman diagnosed with nonfunctional bladder paraganglioma, who presented with macroscopic hematuria and right-sided renal colic but lacked the usual symptoms associated with catecholamine excess. This case highlights the diagnostic challenges of nonfunctional variants of paraganglioma due to their histological similarity to urothelial carcinomas. It underscores the importance of a thorough histological examination and the need for a multidisciplinary approach to establish a diagnosis and determine the optimal treatment strategy. Our case contributes to the sparse literature on this rare condition, and it aims to enhance clinicians' awareness and understanding of urinary bladder paragangliomas.

Experimental isolation and preservation of solid organs before transplantation: effects of pretreatment using four different molecules.

OBJECTIVES: In transplantation surgery, the ischaemic organ and reperfusion impairment after cold storage remains a considerable risk factor for impaired function and potential failure of the grafted organ. Substantial logistical efforts have been undertaken to reduce the cold ischaemic time because the demand for available transplant organs and the periods of cold ischaemia are increasing. METHODS: Four molecules were investigated (erythropoietin, sildenafil, lazaroid [U74389G], octreotide) in individual intravenous infusions 1 hour before the organ was harvested. This study was performed in 30 healthy landrace/large-white pigs (male; >10 weeks old; average weight, 22 ± 2 kg) in groups of six. The organs were studied at harvest, and at 8 and 24 hours post-harvest. RESULTS: The lazaroid molecule increased malondialdehyde (MDA) levels in the liver and pancreas at 8 hours. Hepatic lazaroid molecules improved liver histology at 8 and 24 hours. For kidneys, erythropoietin had a positive effect at 24 hours post-harvest. For the pancreas, octreotide showed better performance. In the lungs, there was less interstitial oedema with erythropoietin and lazaroid compared with the control group at 8 hours post-harvest. CONCLUSION: All molecules had a positive effect and decreased ischaemia/reperfusion graft injury. Thus, pretreatment before organ harvest has a beneficial role.

Insight into long-term histological, proliferative and apoptotic modifications in ileal orthotopic neobladder and conduit mucosa.

AIMS AND BACKGROUND: To assess the long-term histological, apoptotic and proliferating alterations of the intestinal mucosa of ileal conduits and orthotopic neobladders. METHODS: Fifty patients (46 males, 4 females), aged 52-78 years, who underwent urinary diversion with either ileal orthotopic neobladder (group ON, 20 patients) or conduit (group IC, 30 patients) from 2001 to 2005, were included in this prospective study. Ileal samples were collected during surgery (controls) and by random mucosal biopsies 6, 12, 24, 36 and 48 months later. Histological (villi height, crypt depth, eosinophil cell count), proliferation (Ki67 immunochemistry), and apoptotic (Bcl-2 immunochemistry, TUNEL) parameters were assessed. RESULTS: During the 4-year follow-up, we recorded progressive villi area, height and crypt depth reduction, mucosa flattening, and inflammatory and eosinophilic infiltration. Villi height: crypt depth ratio showed a statistically significant difference (P < 0.05) between the two groups from the 6th month. Dysplasia, metaplasia, and neoplasia were not observed. Bcl-2 values showed a progressive increase until 24 months in group ON and 12 months in group IC, followed by a decline thereafter. Ki-67 values showed a progressive increase after 6 months in group ON and an increase until 24 months followed by a decline thereafter in group IC. TUNEL showed two peaks, at 24 and 48 months. CONCLUSIONS: Histological adaptation was revealed in both groups, with statistically significant differences in favor of orthotopic substitution. Proliferative and apoptotic pathways are implicated as demonstrated by relevant modifications of Bcl-2, Ki-67 and TUNEL, in accord with the histological adaptation.

Pathological review of internal genitalia after anterior exenteration for bladder cancer in women. Evaluating risk factors for female organ involvement.

To evaluate cancer involvement of internal female genitalia of patients undergoing anterior exenteration for clinically organ confined transitional cell carcinoma of the bladder, and identify potential preoperative risk factors. Charts and anterior exenteration specimens from 54 women with clinically organ confined transitional cell bladder cancer were retrospectively reviewed. Emphasis was given to the presence of internal genitalia involvement and or primary gynecologic pathology. Unsuspected internal genitalia involvement was reported in only three patients (5.7%). The vagina was involved in two cases (3.8%) while the uterus in one (1.9%). In all cases involvement was due to direst extension from bladder tumors of the base and dome respectively. No preoperative variable could predict internal genitalia involvement in a statistical significant manner. Benign pathology of the female reproductive organs was observed in six patients and involved in all cases the uterus (11.5%). Internal genitalia involvement after radical cystectomy for TCC tumors of the bladder is rare (5.8%). Preoperative risk factors could not be identified although all involved genitalia were seen in tumors of the bladder dome and base. Therefore large multi-institutional studies are needed in order to identify preoperative risk factors for internal genitalia involvement in females with bladder cancer.

The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and angiogenesis markers in hyperplastic and malignant prostate tissue.

BACKGROUND: The process of ingrowth of new blood vessels is stimulated by the action of vascular endothelial growth factor (VEGF), while it may be simultaneously related to the degree of tissue hypoxia. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a protein of cellular response to hypoxia. The relationship between hypoxia and angiogenesis in patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa) was examined. MATERIALS AND METHODS: One hundred and seventy (170) prostatic tissue samples were immunohistochemically evaluated. The microvessel density (MVD) was calculated by CD34 immunostaining; the angiogenetic profile was further assessed using a monoclonal antibody against VEGF. HIF-1alpha immunoreaction was recognized through nuclear staining of positive cells. RESULTS: CD34, VEGF and HIF-1alpha staining reactions were significantly higher in the PCa group than in the BPH group. In both groups, an interrelationship between the immunoexpression of CD34 and HIF-1alpha, VEGF and HIF-1alpha, as well as VEGF and CD34 was detected. CONCLUSION: MVD, VEGF cytoplasmic immunoreactivity and HIF-1alpha immunoreaction were more prominent in PCa than in BPH and were also significantly associated with high-grade carcinomas.

Pseudosarcomatous myofibroblastic lesion of the urinary bladder: a rare entity posing a diagnostic challenge and therapeutic dilemma.

BACKGROUND: Pseudosarcomatous myofibroblastic lesions of the urinary bladder are relatively rare entities of an uncertain pathogenesis and benign indolent nature. CASE PRESENTATION: We present an extremely rare case of an ALK-1-positive pseudosarcomatous myofibroblastic lesion of the urinary bladder, which was initially misinterpreted as a low-grade leiomyosarcoma of myxoid subtype on histologic examination owing to prominent atypia, high mitotic activity, abnormal mitotic figures and infiltration of the bladder wall. Although the histologic features were suggestive of a sarcoma, the correct diagnosis was finally established and radical surgical treatment was subsequently avoided. The patient is currently free of disease without any evidence of tumor recurrence or metastasis at 3 years post-operatively. CONCLUSION: The key differentiating point rests in distinguishing the aforementioned mass forming lesion from the myxoid subtype of low-grade leiomyosarcoma in order to avoid unnecessary radical therapy.