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Focuses on the effects of the drug colchicine which is used to treat patients diagnosed with Familial Mediterranean fever (FMF). Reference to the disease amyloidosis, a main complication associated with FMF; What is FMF; Symptoms of FMF; Information on the use of colchicine in the treatment of FMF; Details on the long term preventive colchicine therapy for patients with FMF.

Background: Most of the ischemia-reperfusion injury (IR-I) occurs during reperfusion and is mediated by the immune system. In this study we determined whether immunomodulation with hyper-Interleukin-6 (a recombinant designer cytokine composed of interleukin-6 linked to its soluble receptor) is protective against IR-I in mice kidneys. Methods: Hyper-Interleukin-6 (HIL-6) was administered by in vivo plasmid DNA transfection to 10 male mice. Twenty-four hours later, unilateral nephrectomy was done. IR-I immediately followed by closure of the remaining kidney vascular pedicle for 40 min. Seven mice transfected with non-coding control plasmid served as the control group. The functional and morphological effects of IR-I and its effect on mice longevity were explored. This was done by serial blood tests and by histopathology done upon sacrifice of the animals at post-operative day 7. Findings: Mice pretreated with HIL-6 had a mean creatinine level at post-operative day 1 of 35.45 ± 4.03 μmol/l and mean Urea level was 14.18 ± 2.69 mmol/l, whereas mean creatinine was 89.33 ± 69.27 μmol/l ( P = 0.025 ), and mean urea was 38.17 ± 20.77 mmol/l (P = 0.0024 ) in the control group. Histological changes in the control group included inflammatory infiltration, tubular damage, and architectural distortion. These were not seen in the treatment group. Seven days post-operatively the survival rate of treated mice was 100% compared to 50% in the control group ( P = 0.015 ). Interpretation: In this single kidney mouse model, pretreatment with HIL-6 administration effectively protected against IR-I both morphologically and functionally. Further studies are needed to better understand the mechanism and feasibility of using this immunomodulator., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zuaiter, Axelrod, Pizov and Gofrit.)

Objective: To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols., Patients and Methods: Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8] years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12 months after surgery, then annually for a total of 5 years, and then annual ultrasonography indefinitely., Results: After a median follow-up of 10 years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1 cm; these patients were significantly younger than patients with 1.1-3 cm tumours (64.6 vs 68.3 years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7 years in patients with smaller tumours and 3.6 years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5 years, compared to 75.5% in patients with larger tumours., Conclusions: Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1 cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Background: High-grade urothelial carcinomas (UCs) often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with bacillus Calmette-Guerin (BCG). We compared the response, to treatment with BCG, of UC containing glandular, squamous, nested, and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade UC., Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. Forty-one patients with Ta or T1, confirmed by second look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation, 13 patients with squamous differentiation, 9 patients with glandular differentiation, and 7 patients with nested variants. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly., Findings: Patients with variant tumors had similar clinical features to patients with conventional disease, including age, male to female ratio, stage, the presence of Tis, and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC, including 5-year recurrence-free survival (63.5 Vs. 71.5%, p = 0.05), 5-year progression (≥T2)-free survival (60 Vs. 82.5%, p = 0.002), 5-year disease-specific survival (73 Vs. 92.5%, p = 0.0004), and overall survival (66 Vs. 89.5%, 0.05)., Interpretation: A patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5 years compared to 7.5% chance for a patient with conventional high-grade UC.

Objective: To explore the effect of intravesical instillation of green tea extract (GTE) on a rat model of bacterial cystitis., Materials and Methods: In vitro bactericidal properties of GTE were analysed by adding GTE to a suspension of uropathogenic E. coli (UPEC), streaking on MacConkey agar, and incubating overnight. In vivo effects of intravesical instillation of GTE on bacterial cystitis was analysed using a rat model of bacterial cystitis. In all, 42 female Sabra rats weighing 200-260 g were divided into five groups. Parameters measured were bladder weight (percentage of the total rat weight), dipstick urine analysis and histopathological changes in the bladder. Histological changes evaluated were degree of oedema, mixed inflammatory infiltration, urothelial epithelial invasion by neutrophils and reactive atypia., Results: No in vitro bactericidal activity was detected for GTE. Intravesical instillation of GTE did not cause damage to the rat bladders. Intravesical instillation of GTE attenuated the inflammatory response to UPEC-SR71-induced bacterial cystitis in this rat model., Conclusions: Intravesical instillation of GTE attenuated the inflammatory response to UPEC-SR71-induced bacterial cystitis and is a novel approach to the treatment of bacterial cystitis. High concentrations of intravesical GTE did not cause histologically evident damage to the rat bladder. The results of this study are preliminary and further studies will be needed to explore the feasibility of using this approach in humans., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: The pathological grade of bladder cancer has an immense impact on patient treatment and prognosis. While most bladder tumors show pure high or low grade patterns, some show a mixed pattern. We explored the incidence and clinical significance of this phenomenon., Materials and Methods: A total of 642 patients with a mean age of 67.5 years underwent transurethral resection of nonmuscle invasive bladder tumors between June 1998 and December 2008, including 156 and 454 with low and high grade lesions, respectively. In 32 patients (5%) mixed grade tumors were found, defined as low grade tumors with 10% or less of a high grade component. All patients were followed a median of 60 months postoperatively., Results: Mean age, the proportion of men and the proportion of stages Ta/T1 in patients with mixed grade tumors were between those of the high and low grade groups. Five-year recurrence-free survival was similar for high, low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252). Five-year progression-free survival was significantly lower in patients with high grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific survival was significantly worse in patients with high grade tumors (p<0.0001) but similar in those with high and mixed grade lesions (p=0.679)., Conclusions: Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a patient group with unique clinical features. The clinical course of patients with mixed grade tumors parallels that of patients with low grade tumors., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background. Recent data suggest a role for H19 gene in promoting cancer transformation and progression. Cervical cancer, progresses from high-grade lesions (CIN3). At present, it is unclear if CIN lesions express H19. Objectives. To determine H19 expression in patient samples of CIN3 as well as the ability of a construct in which the promoter from the H19 gene drives expression of the diphtheria toxin A chain (DTA) to inhibit cervical cancer cell growth in vitro. Methods. H19 transcript levels were evaluated on 10 biopsies of CIN3 using in situ hybridization. PCR was used to examine H19 expression in cervical cancer cell lines and in two samples from a patient with cervical carcinoma. Cell lines were transfected with H19-DTA to determine its impact on cell number. Results. H19 gene was expressed in the area of CIN3 in 9 out of 10 samples. RT-PCR indicated expression of H19 in cervical cancer samples and in one of the three cell lines examined. Transfection of all cell lines with H19-DTA vector resulted in inhibited cell growth. Conclusions. H19 is expressed in the majority of CIN3 samples. These results suggest that most CIN3 lesions could be targeted by H19-DTA. Further in vivo preclinical studies are thus warranted.

We describe an unusual presentation of metastatic lung adenocarcinoma as malignant retroperitoneal fibrosis (MRPF). The diagnostic challenge, due to the small solitary lung mass and absence of a discrete retroperitoneal mass, was overcome by diagnostic laparoscopy. Molecular analysis of tissue acquired was positive for ALK gene rearrangement. Treatment of the patient with crizotinib reversed MRPF. He was weaned off the nephrostomy tubes and is with stable renal function 11 months after diagnosis.

Background: The management of patients with high-grade non muscle invasive bladder cancer (NMIBC) brings diagnostic and therapeutic challenges. In the current study, we sought to study the natural history of progression to "secondary" muscle-invasive bladder cancer (MIBC)-cancer that developed during follow up of patients presenting with non-muscle invasive bladder cancer (NMIBC)., Methods: Between 1998 and 2008, 760 patients were treated for bladder cancer. Primary MIBC (>=T2) tumors (present upon presentation) were diagnosed in 114 patients. All patients with high-grade NMIBC were treated with intravesical BCG. Mean follow-up was 44 months., Results: Forty patients (6.1%) developed secondary MIBC after a mean period of 21 months from initial diagnosis of bladder cancer. The 2- and 5-year disease-specific survival rates were better for patients with secondary MIBC (90% and 56% compared to 69% and 42% for patients with primary disease, p=0.03). The Kaplan-Meier curves of the two groups were parallel but displaced by approximately 2 years., Conclusion: In the current series, MIBC progression occurred among initially presenting patients with NMIBC in 6.1%. In most patients, the initial diagnosis of NMIBC is correct and muscle invasion occurs after a mean period of about 2 years. This supports a non-radical approach in patients with high-grade T1, Ta or Tis. Meticulous follow-up with liberal biopsy of any suspicious lesion may provide early diagnosis of invasive disease.

The objective of the study is to assess the etiology and prognosis of gross hematuria (GH) in patients with carcinoma of the prostate (CAP). From 1991 to 2011, 81 men (mean age 74.3 years, SD 6.5) with CAP were hospitalized with GH. Primary treatment of CAP was radical surgery in 13 patients (group 1) and nonsurgical therapy in 68 (group 2), mostly radiotherapy (35 cases) and hormonal treatment (25 cases). The common etiologies of GH in group 1 were bladder cancer (38.5%) and urinary infection (23%). In contrast, CAP itself caused GH in 60% of the patients in group 2. Thirty-nine patients (48%) required transurethral surgery to manage GH which was effective in all cases; nevertheless, the prognosis of group 2 patients was dismal with median overall survival of 13 months after sustaining hematuria, compared to 50 months in group 1 (P = 0.0015). We conclude that the etiology of GH in patients with CAP varies according to primary treatment. After radical prostatectomy, it is habitually caused by bladder cancer or infection. When the primary treatment is not surgical, GH is most commonly due to CAP itself. Although surgical intervention is effective in alleviating hematuria of these patients, their prognosis is dismal.

The Psammomys obesus lives in natural desert habitat on low energy (LE) diet, however when maintained in laboratory conditions with high energy (HE) diet it exhibits pathological metabolic changes resembling those of type 2 diabetes. We have evaluated and correlated the histopathology, metabolic and functional renal alterations occurring in the diabetic Psammomys. Renal function determined by measuring glomerular filtration rate (GFR), protein excretion, protein/creatinine ratio and morpho-immunocytochemical evaluations were performed on HE diet diabetic animals and compared to LE diet control animals. The diabetic animals present a 54% increase in GFR after one month of hyperglycemic condition and a decrease of 47% from baseline values after 4 months. Protein excretion in diabetic animals was 5 folds increased after 4 months. Light microscopy showed an increase in glomeruli size in the diabetic Psammomys, and electron microscopy and immunocytochemical quantitative evaluations revealed accumulation of basement membrane material as well as frequent splitting of the glomerular basement membrane. In addition, glycogen-filled Armanni-Ebstein clear cells were found in the distal tubules including the thick ascending limbs of the diabetic animals. These renal complications in the Psammomys, including changes in GFR with massive proteinuria sustained by physiological and histopathological changes, are very similar to the diabetic nephropathy in human. The Psamommys obesus represents therefore a reliable animal model of diabetic nephropathy.

A 52-yr-old man presented with severe obstructive urinary symptoms. Ten years earlier, a digital rectal examination disclosed a small mass above the prostate, and a computed tomography (CT) scan showed a 3.5-cm cystic tumor of the right seminal vesicle. He had been followed conservatively elsewhere. Reevaluation of the mass with a CT scan and magnetic resonance imaging showed that the mass had grown to a maximal diameter of 14 cm. A transabdominal needle biopsy revealed benign fibromuscular tissue. The tumor was then resected by an open transvesical approach. Pathology was consistent with a benign seminal vesicle cystadenoma. The natural history, pathology, and surgical approach are described., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Transjugular kidney biopsy (TJKB) was first described in 1990. Indications for TJKB include uncorrectable bleeding disorders and conditions precluding the prone position., Objectives: To describe our initial experience with TJKB., Methods: Between February 2008 and December 2009 all patients in whom percutaneous biopsy was contraindicated or unsuccessful underwent image-guided TJKB using a standard set with a 19 gauge core biopsy needle. Prospectively collected data included indication, number of needle passes, contrast dose, tissue yield, and complications., Results: Twelve patients, age range 15-76 years (mean 55), underwent 14 TJKB procedures. Indications for the transjugular route included bleeding diathesis, dyspnea, ventral hernia, ascites, marked obesity, need for concomitant liver biopsy or concomitant insertion of tunneled dialysis catheter, discrepant kidney size, and failed percutaneous attempt. Thirteen biopsies were performed in 11 patients; in one patient TJKB was abandoned due to unfavorable renal vein anatomy. Four patients were premedicated with desmopressin and one with platelet transfusion due to prolonged bleeding time. Three to six passes (mean 3.8) were made per biopsy, with an overall yield of 9.6 +/- 8.2 glomeruli, providing a definite diagnosis in nine patients and a probable diagnosis in two. In two patients the first biopsy attempt yielded insufficient tissue, necessitating a repeat procedure. There were two minor bleeding episodes not requiring intervention. Serum creatinine was unchanged after the procedure and hemoglobin levels asymptomatically dropped by 0.3 +/- 1.0 g/dl within 48 hours, requiring no treatment., Conclusions: TJKB appears to safely allow adequate tissue diagnosis in patients at increased risk for complications from or contraindications to percutaneous renal biopsy.

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068).Patients with non-muscle invasive variants of bladder cancers can be managed with intravesical immunotherapy if tumor is not bulky (>4 cm). Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients, life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.

Background: Raman molecular imaging (RMI) is an optical technology that combines the molecular chemical analysis of Raman spectroscopy with high-definition digital microscopic visualization. This approach permits visualization of the physical architecture and molecular environment of cells in the urine. The Raman spectrum of a cell is a complex product of its chemical bonds., Objective: In this work, we studied the possibility of using the Raman spectrum of epithelial cells in voided urine for diagnosing urothelial carcinoma (UC)., Design, Setting, and Participants: Raman signals were obtained from UC tissue, then from UC touch preps obtained from surgical specimens and studied using the FALCON microscope (ChemImage, Pittsburgh, PA, USA), with a×100 collection objective and green laser illumination (532 nm). Then, urine samples were obtained from 340 patients, including 116 patients without UC, 92 patients with low-grade tumors, and 132 patients with high-grade tumors. Spectra were obtained from an average of five cells per slide., Measurements: Raman spectroscopy of cells from bladder cancer (BCa) tissues and patients., Results and Limitations: The Raman spectra from UC tissue demonstrate a distinct peak at a 1584 cm(-1) wave shift not present in benign tissues. The height of this peak correlated with the tumor's grade. The signal obtained from epithelial cells correctly diagnosed BCa with sensitivity of 92% (100% of the high-grade tumors), specificity of 91%, and a positive predictive value of 94% and a negative predictive value of 88%. The signal correctly assigned a tumor's grade in 73.9% of the low-grade tumors and 98.5% of the high-grade tumors. RMI for diagnosis of BCa is limited by the need for specialized equipment and training of laboratory personnel., Conclusions: RMI has the potential to become a powerful diagnostic tool that allows noninvasive, accurate diagnosis of UC., (Copyright © 2010 European Association of Urology. All rights reserved.)

Aim: To examine the hypothesis that the risk of high-grade bladder cancer can be predicted using noninvasively obtained data., Patients and Methods: We retrospectively analyzed the database of 431 patients that had transurethral resection of first-time bladder tumors between June 1998 and December 2009. Pre-operative parameters evaluated were: patients' age; gender; sonographic tumor diameter, number and location of tumor inside the bladder; presence of hydronephrosis, and results of urinary cytology. Parameters that showed significance in multivariate analysis were incorporated into the nomogram., Results: Multivariate analysis of the data showed that patient's age, the presence of hydronephrosis, sonographic tumor diameter (risk of a high-grade tumor: 14, 29, 43.3, 55.7 and 69.4% at diameters: 0.5-1.5, 1.6-2, 2.1-2.5, 2.6-3 and >3 cm, respectively), location of tumor in the bladder (risk of high-grade tumor: 28.8, 47, 67.5 and 90.5% in the lateral walls, posterior/base, anterior and dome, respectively), and urinary cytology were all highly significant and independent predictors of high-grade tumors. A nomogram constructed using these variables scored an area of 0.853 in the ROC curve., Conclusions: The risk of high-grade bladder tumor can be accurately predicted using non-invasively obtained information. This prediction can help to triage patients with newly detected bladder cancer for biopsy., (Copyright © 2011 S. Karger AG, Basel.)

Disturbed kidney function is a common occurrence after bone-marrow transplantation. Sepsis, nephrotoxic medications, thrombotic microangiopathy and injury related to haemodynamic alterations are frequently accountable. Recently, attention has been given to immune-mediated glomerular damage, related to graft-versus-host disease. Herein we describe the fatal course of a nephrotic syndrome complicating allogeneic stem cell transplantation in a young woman with long-standing paroxysmal nocturnal haemoglobinuria. A post-mortem kidney biopsy revealed amyloidosis of the AA type. Physicians should be aware of the possibility that infections and inflammation accompanying the post-transplantation period may rarely promote the development of systemic amyloidosis or exacerbate silent pre-existing disease.

Objective: To evaluate the efficacy of transurethral prostatectomy (TURP) followed by bacillus Calmette-Guérin (BCG) immunotherapy in patients with prostatic urothelial carcinoma (PUC) and compare the results of studies using combined TURP and BCG with studies in which TURP was not performed., Patients and Methods: Patients with bladder cancer and PUC were treated with TURP followed by six weekly intravesical instillations of BCG. Response was determined and monitored by periodic bladder and prostatic urethra biopsies and urinary cytology. Also, the outcome of previous series using similar methodology was compared with the outcome of studies in which TURP was not performed., Results: In all, 20 patients with PUC were treated with TURP followed by intravesical instillations of BCG. The median follow-up was 52.5 months. All patients had an initial complete response (CR). The prostatic urethra 5-year recurrence-free survival rate was 90%. However, bladder and prostatic urethra 5-year recurrence-free survival rate was only 30%. Five patients (25%) died from urothelial carcinoma (UC) after a median period of 58.5 months (two from bladder cancer metastases and three from upper tract metastases). The long-term prostatic urethra CR rate in studies using TURP before immunotherapy was significantly higher than the CR rate in studies using immunotherapy alone (P < 0.001). However, there was no difference when bladder and prostatic urethra CR rates were considered together (P = 0.54)., Conclusion: In patients with PUC, TURP before BCG immunotherapy eliminates PUC in most cases, and is probably the preferred treatment for this disease. The risk of UC-specific mortality in these patients is high.