Christer Busch

The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder

In October 1997, Dr. F.K. Mostofi assembled a group of individuals interested in bladder neoplasia at a meeting in Washington DC. The participants included urologic pathologists, urologists, urologic oncologists, and basic scientists with an interest in bladder neoplasia. The purpose of this meeting was to discuss bladder terminology and make recommendations to the World Health Organization (WHO) Committee on urothelial tumors. Following this meeting, a group of the urologic pathologists who attended the Washington meeting decided to broaden the representation of the group and arranged a meeting primarily of the members of the International Society of Urologic Pathologists (ISUP) at the 1998 United States and Canadian Academy of Pathology Meeting held in Boston. Massachusetts. At this meeting. issues regarding terminology of bladder lesions, primarily neoplastic and putative preneoplastic lesions, were discussed, resulting in a consensus statement. The WHO/ ISUP consensus classification arises from this consensus conference committees recommendations to the WHO planning committee and their agreement with virtually all of the proposals presented herein. 29 The effort involved in reaching such a consensus was often considerable. Many of those involved in this process have compromised to arrive at a consensus. The aim was to develop a universally acceptable classification system for bladder neoplasia that could be used effectively by pathologists, urologists, and oncologists.

Radical Prostatectomy Versus Watchful Waiting in Localized Prostate Cancer: the Scandinavian Prostate Cancer Group-4 Randomized Trial

BACKGROUND The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. METHODS From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. RESULTS During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001). CONCLUSION Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.

5-YEAR, FOLLOWUP OF A RANDOMIZED PROSPECTIVE STUDY COMPARING MITOMYCIN C AND BACILLUS CALMETTE-GUERIN IN PATIENTS WITH SUPERFICIAL BLADDER CARCINOMA

PURPOSE We report the 5-year followup of a randomized comparison of mitomycin C and bacillus Calmette-Guerin (BCG) in patients with superficial bladder carcinoma. Recurrence, progression and survival rates, crossover results, prognostic factors and long-term side effects were analyzed. MATERIALS AND METHODS A total of 261 patients were enrolled in the study, and the inclusion criteria were primary Tis, dysplasia G2, T1 G3 and multiple recurrent Ta/T1 G1-2 disease. Intravesical instillations of 40 mg. mitomycin C and 120 mg. Pasteur BCG, Danish strain 1331, were given for 2 years. RESULTS After a median followup of 64 months 101 of the 250 evaluable patients (42%) were disease-free. A significant difference was noted in disease-free survival with BCG (p = 0.04), which was most pronounced for stage Tis disease. No difference in tumor progression, or crude or corrected survival was found between the 2 arms. Crossover treatment was successful in 39% of patients with second line BCG and 19% with second line mitomycin C. Independent risk factors for progression were initial p53 status and stage. Only the completion of treatment was predictive of outcome for patients treated with BCG. Bladder shrinkage occurred in 2.4% of patients. CONCLUSIONS Therapy with BCG was superior to mitomycin C for recurrence prophylaxis but no difference was found for progression and survival.

Binding of heparin on the surface of cultured human endothelial cells

Abstract 3H-labelled heparin was shown to bind to the surface of cultured human endothelial cells. The binding was time dependent, saturable, reversible and trypsin sensitive. The binding capacity corresponds to about 106 molecules of heparin per cell. Labelled material released from the cells retained its ability to bind to antithrombin III. Binding of heparin to endothelial cells as well as its release is suggested to be of importance in the pharmacokinetics of heparin and to influence the non-thrombogenic properties of the endothelial lining during heparin therapy.

Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up.

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.

Arterial Hypotension and Hypoxaemia During Total Hip Replacement: The Importance of Thromboplastic Products, Fat Embolism and Acrylic Monomers

Thirteen patients submitted to total hip replacement surgery by the Charnley technique were studied. Operations were performed under epidural analgesia with the patients awake and breathing air. During the surgical procedure, the magnitude of tissue‐thromboplastic activity, the amount of fat globules, the presence of bone marrow cells and the concentrations of acrylic monomers were determined in the pulmonary arterial blood. Simultaneously, arterial blood gases and blood pressure were monitored.

Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population-based study

To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population‐based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen.

Binding of platelet factor 4 to cultured human umbilical vein endothelial cells

Abstract Cultures of human endothelial cells (EC) from umbilical veins were incubated with 125 I-labelled, human platelet factor 4(PF4) at room temperature. A time-dependent, saturable and specific binding of PF4 to EC could be demonstrated with an estimated maximum capacity of about 90 ng/10 5 cells. Heparin(H), heparan sulfate(HS), dermatan sulfate(DS), chondroitin 6-sulfate(C6-S) and chondroitin 4-sulfate (C4-S) competed with the binding site of EC for PF4. The order of potency in this respect was H > HS > DS > C6-S > C4-S. No difference between unfractionated H and H having high or low affinity for anti-thrombin III was noted. High concentrations of protamine sulfate (about 10 −4 M) also inhibited the binding. Specific detachment of cell surface associated HS by platelet heparitinase decreased the binding of PF4 to the EC indicating that HS may be involved as a binding site. The possibility that PF4 may interfere with a heparin-like non-thrombogenic property of the endothelial cell surface is discussed.

Paraffin section storage and immunohistochemistry - Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen

It has been observed that immunoreactivity in paraffin sections decreased during storage. In this study, stored paraffin sections from both biopsy material and cultured cells were assessed for changes in immunoreactivity, using color-based image analysis to quantitate extent and intensity of the stainings. For seven of the 11 antibodies studied, storage at 20 degrees C for 16 weeks reduced the extent of immunostaining compared with that of freshly cut sections. Furthermore, increased storage temperatures resulted in a progressive loss of immunoreactivity. After 2 weeks of storage, at both 4 degrees C and 20 degrees C, p53 protein- and MIB1-antigen expression was significantly reduced regarding extent and intensity. The extent of the immunoreactivity reduced more for p53 protein than for MIB1 antigen, but the intensity did not. Boric acid was used for antigen retrieval on sections stored for 12 weeks at 20 degrees C. For both p53 protein and MIB1 antigen, this resulted in an extent and intensity of immunostaining equal to or higher than (MIB1) that obtained in freshly cut sections, using citrate buffer. Staining of cultured cells confirmed the results from biopsy material on the influence of storage temperature. Fixation time only marginally influenced the storage-related decrease in immunoreactivity. In conclusion, storage of paraffin sections leads to a varying degree of decreased immunoreactivity for several antibodies. The degree is at least partly dependent on storage time and temperature but not fixation time. However, this may be compensated for by optimizing the antigen retrieval protocol.

Benign epithelioid schwannoma

Benign schwannoma (neurilemoma) has various morphologic patterns that may cause problems in differential diagnosis. Although an epithelioid variant of malignant schwannoma simulating carcinoma and melanoma is well recognized, a benign counterpart has not yet been defined. In the current study, we describe five cases of benign epithelioid schwannoma that were in the subcutis (four cases) and the neck of the urinary bladder (one case). The tumors occurred in adults 28-73 years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular, and were composed of epithelioid cells arranged in cords and nests. The benign nature of the lesions was evident by a constellation of features, including small size, sharp circumscription, bland morphology, low proliferative activity (four of five had < or =1% Ki67 immunostaining), and a benign clinical course after either marginal or intralesional excision. All cases had some features of classic schwannoma light microscopically and a high degree of Schwann cell differentiation both ultrastructurally and immunohistochemically. The recognition of benign epithelioid schwannoma is important because it may be misinterpreted as a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.