Proteoglycan core protein in human urine and its possible role on calcium oxalate urolithiasis

BACKGROUND: There are only a few papers reporting on the role of proteoglycan core protein in calcium oxalate stone formation. The present study was carried out to investigate the role of core protein of proteoglycan in human urine on calcium oxalate (CaOx) crystallization. METHODS: Proteoglycans were collected from whole human urine. The covalently bound glycosaminoglycans (GAG) of proteoglycans were then digested by GAG lyase. The inhibitory activity on CaOx crystal growth in vitro was measured before and after enzyme digestion of proteoglycans. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the core protein of proteoglycans and the analysis of amino acid sequence were performed. RESULTS: The core protein showed significant inhibitory activity on CaOx crystal growth, which scarcely changed when compared with that of proteoglycans before enzyme digestion. The SDS-PAGE revealed that the core protein was a single unit with a molecular weight of 26 kDa and amino acid sequencing demonstrated high homology to interalpha-trypsin inhibitor (ITI) light chain (bikunin) with Kunitz inhibitor domain as a core protein. CONCLUSIONS: The results suggested that human urine contains proteoglycans and a major part of them is ITI light chain (bikunin). The Kunitz inhibitor domain, a core protein of bikunin, has significant inhibitory activity on CaOx crystallization without GAG bound covalently to the core protein.     

Significance of random bladder biopsies in superficial bladder cancer

OBJECTIVES: We investigated to what extent biopsies of normal-appearing urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis) showed malignant disease and whether those findings had impact on therapeutical decisions. PATIENTS AND METHODS: 1033 consecutive patients presenting with Ta, T1 or Tis (carcinoma in situ) superficial bladder tumors at increased risk for recurrence underwent multiple random biopsies from normal-appearing urothelium during transurethral resection (TUR). Patients with small, primary, singular tumors (smaller or equal to 1cm) were excluded from random biopsies. RESULTS: No tumor was found in the random biopsies of 905 patients (87.6%). 128 patients (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta: 41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary tumor revealed no signs of malignancy, urothelial bladder cancer was detected in the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21 patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis. Upstaging of the primary, resected tumor by histological examination of the random biopsy material occurred in 75 patients (7%). Altogether, due to the random biopsy results therapy was altered in 70 patients (6.8%) of our series: It changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and cystectomy in 15 patients. CONCLUSIONS: While the clinical significance of random biopsies is still controversial, random biopsy results had strong impact on therapeutical decisions in our series. Regarding random bladder biopsies a simple tool for the urologist to identify high risk groups of patients, we recommend them as part of the routine management of superficial bladder cancer.     

The significance of random bladder biopsies in superficial bladder cancer

Introduction: Today, there is no consensus about taking random bladder biopsies during transurethral resection of superficial bladder tumors for staging and to determine the urothelial abnormalities like dysplasia and carcinoma in situ. The aim of our study was to evaluate the results and indications of random bladder biopsies for primary superficial bladder cancer.Patients and methods: Random bladder biopsies were taken from 84 patients with primary superficial bladder cancer after transurethral resection. 40 patients had Ta and 44 had T1 tumor. The random biopsies were taken from right and left bladder walls, anterior and posterior walls, dome, trigone and prostatic urethra. The incidence of urothelial abnormalities were evaluated according to the stage and grade of the tumor.Results: None of the patients had carcinoma in situ or dysplasia with Ta tumor. In T1 group, 4 patients (9.1%) had carcinoma in situ and 3 patients (6.8%) had dysplasia. There was a statistically significant difference with regard to urothelial abnormalities between groups Ta and T1. The same difference was also seen between low and high grade tumors.Conclusion: In our study, only 7/84 (8.3%) of patients with primary superficial bladder cancer had urothelial abnormalities like carcinoma in situ or dysplasia. All of these pathologies were seen in T1 tumors. According to our results, we believe that random biopsies are not useful in superficial bladder cancers to detect urothelial abnormalities and also do not help for the planning of further treatment.     

Challenges in the interpretation of breast core biopsies

The aim of core needle biopsy (CNB) is to diagnose a breast abnormality prior to open surgical excision. The radiology-pathology correlation helps in interpretation of pathologic findings and is greatly assisted by specimen radiology of all cores performed for calcifications, separation of cores containing calcification from those without, and the availability of the specimen radiograph to the pathologist at the time of reporting. The nature of the imaging abnormality should also be clearly conveyed. CNB is processed in a routine manner for paraffin embedding with preservation of sufficient material in the block for further studies as needed. Possible pitfalls include the loss of calcifications at the time of section cutting, calcium remained in the formalin of the specimen container, and failure to recognize calcium oxalate deposition in the CNB. The challenges of CNB interpretation are complicated by the availability of only limited material, but are generally similar to those encountered in open surgical excision specimens. This discussion focuses on high-risk lesions and lesions that raise management issues. The most prudent approach for the pathologist is to provide sufficient information to prompt a surgical excision without overdiagnosing the lesion, thus placing the patient into the appropriate therapeutic algorithm.     

Urinary bladder biopsies in spinal cord injured patients

STUDY DESIGN: A series of 94 urinary bladder biopsies in spinal cord injured (SCI) patients were histopathologically and statistically analysed. OBJECTIVES: The following hypotheses were examined: (1) The number of clinical bladder infections per year in each patient does not influence the histopathological type of inflammation of the urinary bladder; (2) The duration of the spinal cord lesion does not have a strong effect on the type of inflammation; (3) The different neurological levels (upper and lower motor neuron lesions) do not relate to a specific histopathology. SETTINGS: All patients received their treatment at the Swiss Paraplegic Centre in Nottwil, near Lucerne (Switzerland). METHODS: The samples were taken from the bladder fundus during endoscopic urologic operations. Histopathological standard procedures were carried out. Statistical analysis including Kruskal-Wallis and Chi-square tests were performed. RESULTS: Histopathological analysis showed abnormal alterations of the urinary bladder mucosa in 86 SCI-patients: (91.5%). 63 cases (67.0%) showed a chronic type and 23 cases (24.5%) showed a subacute type of inflammation. A normal urinary bladder was found in eight cases (8.5%). The three hypotheses were statistically not rejected. CONCLUSION: Results demonstrated no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.     

The significance of bladder quadrant biopsies in patients with primary superficial bladder carcinoma

The prognostic significance of dysplasia (D I-III, Tis) based on bladder quadrant biopsies was established in 216 patients with primary urothelial carcinoma of the bladder (stage pTaGI-pTGIII). Collectively within the study, 51 of the 216 patients biopsied (24%) were found with abnormal urothelium. Twelve (6%) have coexistent Tis, and 30 (18%) were found with dysplastic changes D I-III. Further concerns included the incidence of dysplastic changes associated with tumor invasion, tumor dedifferentiation, and the presence of primary multifocal disease. The collective recurrence rate was 43%. However, with inclusion of quadrant biopsies, the predictability of positive biopsy results increased to 63% and the negative rate decreased to 37%.     

Bone core biopsies. Plastic or paraffin?

Plastic embedding of bone core biopsy specimens has been promoted as providing superior morphology, primarily because semi-thin sections can thereby be cut at 1-2 mu. The major disadvantages of plastic embedding are that it increases the technical load, is more expensive, and potentially has its own intrinsic problems, including difficulties in performing special stains and immunoperoxidase studies. In order to investigate the possibility that semi-thin paraffin sections may provide similar morphological results without the intrinsic disadvantages of plastic sections, we examined 45 bone core biopsy specimens that were sufficiently large to process one half in plastic and the other half in paraffin following decalcification. Both were cut at 1-2 mu. Although many plastic sections appear esthetically more pleasing, semi-thin paraffin sections of very high quality can also be obtained routinely. Additional advantages of paraffin sections were the ability to perform peroxidase studies, lower cost, less technologist time, and avoidance of problems occasionally arising with plastic, such as difficulties with impregnation or problems with polymerization. Peroxidase studies were particularly useful in patients with possible myeloma that was not overt on hematoxylin-and-eosin section and in confirming the presence or source of metastatic carcinoma. We therefore recommend the use of semi-thin (1-2 mu) paraffin sections for routine examination of bone core biopsy specimens.     

Calcium-binding protein in human duodenal biopsies

Summary Intestinal calcium-binding protein (CaBP) (molecular weight 10,000) was measured by a specific enzyme-linked immunoadsorbent assay in duodenal biopsies of 94 patients (aged 20–89 years). The patients were examined for complaints of upper abdominal dyspepsia, but no significant pathology was found by gastroduodenoscopy. The median amount of CaBP in duodenal biopsies was 6.0 μg/mg of cytosolic protein with a coefficient of variation of 0.6. No change in the amount of CaBP per mg of cytosolic protein was observed with age. A significant correlation (P<0.001) was found between the concentration of CaBP and s-1,25-dihydroxyvitamin D (1,25(OH)₂D). The amount of CaBP per mg of cytosolic protein did not correlate with immunoreactive parathyroid hormone in serum, and no relation between CaBP and the specific activity of alkaline phosphatase of the mucosal biopsies was found. The results of the present study show a wide variation in the amount of the 10 kDa CaBP in duodenal biopsies of humans and no change with age. Further, a correlation between s-1,25(OH)₂D and CaBP was found.     

Clinical significance of multiple biopsies of nontumorous bladder mucosa in patients with bladder cancer

Multiple biopsy specimens obtained from nontumorous bladder mucosa were investigated histologically. An average of 3.6 specimens was taken in 142 transurethral resection operations for 112 patients with bladder cancer. The histological categories used were normal epithelium, metaplasia, hyperplasia and G1-G3 dysplasia. Thirty-seven patients (27.7%) had G2 less than dysplasia within normal looking bladder mucosa. In patients with high grade bladder cancer, the incidence of the association with dysplasia was 51.7%, which was significantly higher than the rates in patients with low or moderate grade bladder cancer (p less than 0.05). The tumor recurrence was observed in 45 patients of 102 patients who were followed with bladder preservation. The recurrence was seen in 13 of 19 patients (68.4%) with mucosal dysplasia in the previous operation. The rate was significantly higher than 38.6% in patients without dysplasia (p less than 0.05). Thus, the epithelial dysplasia seen in nontumorous bladder mucosa were associated with higher grade bladder tumors more often, and the histology of multiple biopsy specimens might be one of predictors for tumor recurrence in near future.     

Lidocaine as a topical anesthetic for bladder biopsies

The use of lidocaine as a topical anesthetic in bladder biopsies is described. Lidocaine was used in 7 patients undergoing random bladder biopsies and serum lidocaine levels were measured 7 to 10 minutes after instillation. Adequate pain control was noted in each patient with negligible serum lidocaine levels even in the face of denuded bladder mucosa.     

X-ray microanalysis--a method for determination of elements in bladder biopsies

Chemical elements in biopsies of normal human urothelium and transitional cell carcinoma (TCC) are determined by X-ray microanalysis in combination with scanning electron microscopy. The methodology presented is intended to be used in subsequent studies to compare data of normal urothelium and TCC of different stage and grade.     

Diabetic cystopathy: neuropathological examination of urinary bladder biopsies

Neuropathological examination of bladder biopsies was done on 14 patients with severe insulin-dependent adult-onset diabetes and compared with the acetylcholinesterase and S100 staining of 38 control specimens. A decrease in acetylcholinesterase activity, due to axonal degeneration was found in all cases. An increase in S100 positivity was found in the majority and is due to Schwann cell proliferation as a regeneration attempt after demyelination or axonal degeneration. When acetylcholinesterase activity decreases and an S100 density increase is found in a patient with diabetes, this combination is highly suggestive of thorough diabetic cystopathy amenable to early symptomatic treatment.     

Ultrasound guided transrectal core biopsies of the palpably abnormal prostate

Ultrasound imaging and ultrasound guided transrectal core biopsies were performed in 251 consecutive men with abnormal prostates on digital rectal examination. A hypoechoic defect on ultrasound was identified in 227 of 251 patients (90 per cent) corresponding to the area of palpable nodularity or abnormal firmness. A mean of 6.25 biopsies were obtained per patient using a commercially available spring-loaded gun. Biopsies were positive for cancer in 165 of the 251 prostates (66 per cent). Palpable nodules more often were hypoechoic and more often contained cancer than less distinct areas of abnormal firmness on digital examination. Among the clinical stages B1, B2 and B3 nodules 70, 76 and 88 per cent, respectively, were positive for cancer, as were 100 per cent of the clinical stage C prostates. Of 77 abnormally firm, nonnodular prostates 36 per cent were positive for cancer. Random biopsy of the contralateral normal lobe in 56 men with clinical stage B1 or B2 nodules showed cancer present contralaterally in 42 and 60 per cent, respectively; 20 per cent had positive biopsies despite a contralateral isoechoic ultrasound. In 78 patients with prior digitally guided biopsies, ultrasound guided biopsies confirmed previously diagnosed cancers in 94 per cent. However, in 23 of 43 patients (53 per cent) with previous negative digitally guided biopsies, ultrasound guided biopsies made the new diagnosis of cancer. Complications, including post-biopsy fever and bleeding, occurred in 6 of 251 patients (2.4 per cent). The combination of the new spring-loaded biopsy guns and transrectal ultrasound guidance of biopsies provides the urologist with a tool that allows multiple prostate cores to be obtained safely and painlessly, reducing the sampling error and increasing the accuracy in diagnosing prostate cancer in the man with a palpable abnormality of the prostate.     

Intravesical lidocaine: topical anesthesia for bladder mucosal biopsies.

The intravesical instillation of lidocaine solution has been used as a topical form of anesthesia for bladder biopsies. We performed 63 ambulatory procedures in which multiple cold-cup biopsies were obtained during cystoscopy. There was no need for electrocautery. All patients tolerated the procedure well and were discharged from the office immediately thereafter. There were no changes in heart rate or blood pressure during the procedures. Serum concentrations of lidocaine were measured in 10 patients at 5, 10 and 30 minutes, and they were clinically insignificant. This simple office procedure can be used for the diagnosis and followup of patients with carcinoma in situ of the bladder.