Risk factors for local recurrence in patients with pTa/pT1 urinary bladder cancer.

OBJECTIVE: This study evaluated risk factors for local tumour recurrence, defined as recurrence at the same location in the bladder within 18 months after primary resection in patients with newly diagnosed pTa or pT1 bladder cancer. PATIENTS AND METHODS: The study included 472 patients with newly diagnosed pTa/T1 bladder cancer between 1992 and 2001. The patients were followed prospectively in accordance with a control programme and possible risk factors for tumour recurrence were registered. RESULTS: Local tumour recurrence was observed in 164 (35%) patients, another 117 (25%) patients had recurrence at other locations in the bladder (non-local recurrence) and 191 (40%) had no recurrence at all. Tumour size and multiple tumours were significantly associated with a higher risk for developing local recurrence as opposed to non-local recurrence. Tumour category was of borderline statistical significance. Gender and tumour grade were not found to be risk factors for developing local recurrence. CONCLUSION: Tumour size and multiplicity are risk factors for development of recurrence at the same location in the bladder as the primary tumour. Local tumour recurrence may be a result of non-radical primary transurethral resection. One may consider recommending standard re-resection within 6-8 weeks in patients with tumours > 3 cm or those with multiple primary tumours.

Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma.

BACKGROUND: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma. METHODS: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression. RESULTS: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome. CONCLUSIONS: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.

Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer?

OBJECTIVE: To determine whether epidermal growth factor receptor (EGFR) immunostaining of tumour cells is associated with cancer-specific death after cystectomy for locally advanced bladder cancer. PATIENTS AND METHODS: The hospital records of all patients treated with cystectomy for urothelial cancer of the urinary bladder between 1967 and 1992 were reviewed retrospectively. The paraffin-embedded specimens obtained before treatment from 173 patients were processed for immunohistochemical staining, using the monoclonal antibody NCL-EGFR (Novocastra, UK). EGFR immunostaining was considered positive if membrane staining was found in at > or = 20% of tumour cells in one or more fields at > or = 200 (area 0.59 mm2). RESULTS: Most patients (149) received preoperative irradiation and one had neoadjuvant chemotherapy. The mean observation time was 81.3 months; 63 patients (36%) had tumour recurrence within 1-80 months (mean 18.3). Positive EGFR immunostaining was found in 100 patients (58%). The proportion of T2-4 tumours was higher in those EGFR-positive than in those EGFR-negative. Proportional-hazards analysis revealed that clinical stage was significantly associated with cancer-specific death, but EGFR expression was not. CONCLUSION: Although positive immunostaining for EGFR was more frequent in higher stages of locally advanced bladder cancer, this variable was not an independent predictor of outcome after cystectomy.

Reduced mucosal perianastomotic capillary density in rat small intestine with chronic radiation damage.

Anastomoses in an intestine with chronic radiation damage are prone to leakage, possibly due to a reduced blood supply induced by a reduced capillary bed. In an animal model, the numerical capillary density in the perianastomotic area was investigated in intestine with or without chronic radiation damage. A 2-cm segment of rat ileum received a single dose of 21 Gy. Twenty weeks later, when the chronic radiation-induced changes were established, an anastomosis was constructed in this segment and in a corresponding segment in control rats. In situ perfusion fixation of the intestine was done 4 or 7 days after construction of the anastomosis, sections of the intestine were removed surgically, the specimens were embedded in methacrylate plastic and sectioned at 2.5 microm, and capillaries were counted under a light microscope. The circumferential mucosal capillary density was lower in irradiated than in nonirradiated animals at both 4 and 7 days (P < 0.001 and P = 0.04, respectively). This reduction was greater in the mesenteric quadrant than in the other quadrants around the circumference. These results are indicative of a reduced capillary bed in the vicinity of anastomoses in intestine with chronic radiation damage, which might lead to an impeded blood supply and subsequent leakage.

Predictive value of p53 and pRb immunostaining in locally advanced bladder cancer treated with cystectomy.

PURPOSE: We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer. MATERIALS AND METHODS: The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression. RESULTS: An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined. CONCLUSIONS: An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.

Anastomotic blood-flow reduction in rat small intestine with chronic radiation damage.

BACKGROUND/AIMS: Anastomoses in previously irradiated intestine are prone to leakage, possibly due to an impeded blood supply. Whether or not chronic radiation damage actually predisposes to a disturbed blood flow in the vicinity of anastomoses was investigated in the rat small bowel. METHOD: A 2-cm segment of rat ileum was irradiated with a single dose (21 Gy). After 20 weeks an anastomosis was created in the irradiated segment and in the corresponding segment of controls. Another 4 days later local blood flow was studied with the 14C-iodoantipyrine autoradiography technique in 16 sectors around the circumference both in the anastomotic segment and in a segment 4 mm apart. RESULTS: In the anastomotic segment, the average blood flow was reduced in irradiated compared with non-irradiated animals in the mucosal layer (p = 0.034), but not in the muscular layer (p = 0.08). In the mesenteric quadrant blood flow was reduced in irradiated compared with non-irradiated animals, both in the mucosal layer (p = 0.012) and in the muscular layer (p = 0.05). More irradiated than non-irradiated animals showed a blood-flow reduction to 15% or more in 13-16 sectors both in the mucosal (p = 0.015) and the muscular layer (p = 0.04). CONCLUSIONS: The results favor the hypothesis that anastomoses in previously irradiated intestine are vascularly compromized and thereby have an increased risk of leakage.

Transurethral incision versus resection of the prostate for small to medium benign prostatic hyperplasia.

OBJECTIVE: To compare the effects of transurethral incision and resection of the prostate in patients with small to medium benign prostatic hyperplasia. PATIENTS AND METHODS: Patients were assessed preoperatively using the Madsen-Iversen symptom score, post- void residual urine volume, urinary flow and cystoscopy. Those eligible for the study were randomized to undergo either transurethral incision or resection of the prostate. Follow-up visits were scheduled at 2-3.6, 12, 24 and 60 months post-operatively with an assessment by symptom score and urinary flow rate; most patients also underwent cystoscopy at 24 and 60 months. RESULTS: The maximum urinary flow rate was significantly higher in those undergoing resection than incision at all but the last follow-up visits. Cystoscopy 24 months after surgery showed adhesions between the lateral lobes, closed incisions or obstructing prostatic lobes in most of the patients undergoing incision, but not in those resected (P < 0.001, chi-square test). During follow-up, a second transurethral procedure was carried out for persistent or recurrent symptoms, combined with a maximum urinary flow rate of < 10.0 mL/s, in 10 patients who underwent incision and in three who were resected (P = 0.039, chi-square test). CONCLUSION: Transurethral resection is preferable to transurethral incision of the prostate in the treatment of small to medium benign prostatic hyperplasia.

A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma.

PURPOSE: We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma. MATERIALS AND METHODS: Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2. RESULTS: After a median followup of 39 months 49% of the patients given BCG and 34% given mitomycin C were disease-free (p < 0.03), compared to 48 and 35%, respectively, of those with stage Ta or T1 disease, and 54 and 33%, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13% of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10% of the patients. CONCLUSIONS: The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.

Anastomotic healing of small bowel with or without chronic radiation damage in protein-deficient malnourished rats.

OBJECTIVE: To assess the influence of protein malnutrition on anastomotic healing in rat small bowel with or without chronic radiation damage. DESIGN: Controlled laboratory study. SETTING: University hospital, Sweden. MATERIAL: 60 male Sprague-Dawley rats. INTERVENTION: A short segment of the distal ileum was exteriorised and irradiated (n = 30) or only exposed (n = 30), and 20 weeks later an anastomosis was made within this segment. Two weeks before anastomosis half of the animals in each group received rat chow in which the protein content had been reduced to 25%; standard rat chow was given to the remaining animals. MAIN OUTCOME MEASUREMENTS: Weight changes, anastomotic bursting strength, amount of perianastomotic hydroxyproline, and number of anastomotic complications. RESULTS: 13 animals in the irradiated group and 11 animals in the non-irradiated group died of intestinal obstruction or respiratory distress leaving 17 and 19 animals that could be evaluated. Body weight was significantly reduced in animals with protein restriction (p < 0.001). A two way ANOVA showed an association between bursting strength and irradiation (p = 0.02) but not bursting strength and protein restriction. Anastomotic complications were more common in irradiated than in non-irradiated animals irrespective of the nutrition given (8/8 and 8/9 compared with 2/9 and 2/10, p = 0.0006). CONCLUSION: Protein malnutrition had no influence on anastomotic healing in rat intestine with or without chronic radiation damage.

Anastomotic breaking strength and healing of anastomoses in rat intestine with and without chronic radiation damage.

OBJECTIVE: To assess the influence of chronic radiation damage on anastomotic healing in the small bowel in rats. DESIGN: Controlled laboratory study. SETTING: University hospital, Sweden. MATERIAL: 90 male Sprague-Dawley rats. INTERVENTIONS: A short segment of the distal ileum was exteriorised and irradiated with a single dose (experimental group, n = 45) or exposed only (control group, n = 45). Twenty weeks later resection and anastomosis were done within this segment using 7/0 polypropylene. MAIN OUTCOME MEASURES: The anastomotic breaking strength, the amount of perianastomotic hydroxyproline, and the number of anastomotic complications. RESULTS: The breaking strength and the amount of perianastomotic hydroxyproline were higher in the irradiated than in the non-irradiated group. In contrast, anastomotic complications were significantly more common in irradiated animals. CONCLUSION: Anastomotic complications in irradiated intestine are not related to the amount of perianastomotic collagen or to breaking strength.

p53 and Rb immunostaining in locally advanced bladder cancer: relation to prognostic variables and predictive value for the local response to radical radiotherapy.

The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.

Extent of blood transfusion and cancer-related mortality after cystectomy and urinary diversion for bladder cancer.

OBJECTIVE: To assess the possible adverse effect of peri-operative blood transfusion on cancer-related survival after radical cystectomy for bladder cancer. PATIENTS AND METHODS: The hospital records of 130 patients treated with cystectomy and urinary diversion for bladder cancer between 1967 and 1986 were retrospectively reviewed. RESULTS: Standard proportional hazards estimation revealed tumour stage and radiation response after pre-operative irradiation to be significantly associated with cancer-related mortality, whereas age, tumour grade or the extent of peri-operative blood transfusion were not. In models which allowed time varying effects a significantly changed effect of blood transfusion (> or = 7 versus < or = 6 units) was observed, from an initially insignificantly increased relative hazard (RH) (RH = 1.44 at 6 months) to an insignificantly decreased effect after longer follow-up (RH = 0.53 after 2 years). CONCLUSION: Although no overall association between blood transfusion and cancer-related mortality was found, a tendency towards an increased risk early in the follow-up period was observed if more than 6 units were transfused. However, these results need confirmation in further studies before a restrictive attitude towards peri-operative blood transfusion is recommended.

Polidocanol sclerotherapy for hydroceles and epididymal cysts.

A total of 87 patients with 63 hydroceles and 29 epididymal cysts underwent injection sclerotherapy with polidocanol on an outpatient basis. In the hydrocele group the cure rate after 1 treatment was 67% and the overall cure rate was 87% after a median followup of 14 months. In the group treated for epididymal cyst the corresponding cure rates were 46% and 64%, respectively, with a median followup of 12 months. A low rate of complications was observed. Of 86 evaluable patients 81 (94%) were satisfied with the procedure and the treatment results. Therefore, we recommend injection sclerotherapy with polidocanol as primary treatment for hydroceles and epididymal cysts in patients older than 40 years.

Results of window operation for primary hydrocele.

The window operation for hydrocele repair has been reported to be a safe out-patient procedure, with few complications and relapses. In this pilot study the procedure could be safely done on an out-patient basis and the rate of complications (8%) was comparable to that of other procedures. However, 21/23 evaluated hydroceles relapsed and retreatment with a second window operation led to further relapses within a short time. Eight patients with 11 hydroceles required another procedure. We have therefore abandoned the window operation for hydrocele repair.

Cystectomy and urinary diversion during twenty years--complications and metabolic implications.

A retrospective analysis of 130 cases of cystectomy and urinary diversion for bladder carcinoma was performed. A logistic regression analysis found preoperative irradiation to be associated with early complications (p = 0.014), whereas no such association was observed with late complications. Metabolic evaluation in 51 surviving patients revealed hyperchloremia in 17 patients (33%) and hyperchloremic acidosis in 2 cases (4%). Vitamin B12 deficiency was found in 11 patients (22%), all of whom had preoperative irradiation or reservoir procedures performed. Routine evaluation of vitamin B12 serum levels should be carried out at follow-up in these groups of patients.

Prognosis of surgically treated radiation-induced damage to the intestine.

A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were postoperative intestinal leak (P < 0.05) and operation for fistula or perforation (P < 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P < 0.001) by the choice of bypass as operative procedure (P < 0.01) and by operation for fistula or perforation (P < 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible.

Adverse effects of perioperative blood transfusion in patients with colorectal cancer.

OBJECTIVE: To assess the effects of perioperative blood transfusion on cancer related survival and infective complications after radical operations for colorectal cancer. DESIGN: Retrospective study. SETTING: District hospital in Sweden. SUBJECTS: 217 patients who fulfilled the criteria for inclusion, out of 392 consecutive patients operated on for colorectal cancer between 1975 and 1979. MAIN OUTCOME MEASURES: Morbidity and cancer related mortality depending on whether blood was transfused and, if so, how much. RESULTS: Dukes' stage (p < 0.001), rectal tumours (p < 0.05) and the number of units transfused (p < 0.05) were significantly associated with cancer related mortality. Patients with rectal cancer transfused with 1-2 units had significantly better survival than those transfused with more than 4 units (p < 0.05), but this was not the case for colonic tumours. There was no significant association between blood transfusion and the incidence of infective complications. CONCLUSION: Though there seems to be an association between the number of units of blood transfused and cancer related survival in patients with rectal cancer, this does not necessarily imply causation. We recommend that until this is clarified by large, prospective investigations, autologous blood should be used whenever possible, and unnecessary blood transfusion should be avoided.

Bladder carcinoma--a 20-year review of radical irradiation therapy.

Between 1967 and 1986, 319 patients, judged unsuitable for cystectomy, were scheduled to receive curative radiation treatment for transitional cell cancer of the urinary bladder. Crude and corrected 5-year survival for all stages were 18% and 28%, respectively. Corrected 5-year survival by stage was: T1-57%, T2-31%, T3-16% and T4-6%. Fifty-seven patients (18%) never completed the scheduled treatment and all but two of them died in a short time from tumour progression. Local response could be evaluated in 179 of the 262 patients, who completed the radiation treatment. In 130 patients (73%) complete local response was observed and 49 patients (27%) had persistent tumour. Corrected 5-year survival in the responder group was 53% compared to 8% in the non-responder group. Intestinal complications occurred in 51 patients, of whom 24 were operated upon and another four died before operation from radiation-induced intestinal complications. More than 80% of all intestinal and/or urinary tract complications were observed within 3 years after irradiation. During this period, special attention should be paid to detect and treat radiation complications to prevent fistula formation or perforation, with poor prognosis. The dose per radiation fraction and the radiation technique appeared to be the most important factors for the development of intestinal complications.