Finn Lundbeck

Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

PURPOSE We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. RESULTS The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX < or = 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added. CONCLUSION The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

Early and late treatment-related morbidity following radical cystectomy.

Objective: To evaluate treatment‐related morbidity following cystectomy in a cohort of consecutive bladder cancer patients. The impact of age, comorbid condition, previous pelvic radiotherapy and type of urinary diversion was analysed. Material and Methods: Between 1992 and 1998 the treatment‐related early (<30 days after cystectomy) and late morbidity was recorded in 268 consecutive bladder cancer patients (median age 65 years) undergoing cystectomy and the following types of urinary diversion: ileal conduit, n = 195; orthotopic neobladder, n = 36; continent reservoir, n = 33; and ureterocutaneous diversion, n = 4. Twenty‐four patients had received previous pelvic radiotherapy and 79 had pre‐existing morbidity. The median follow‐up period was 5.4 years. Results: The postoperative mortality rate was 2%. Age >70 years and pre‐existing morbidity (especially cardiovascular disease) significantly increased the mortality rate. No relationship was found between early complication (57%) and re‐exploration rates (17%) and either age, previous radiotherapy, pre‐existing morbidity or type of urinary diversion. Patients undergoing orthotopic neobladder or continent reservoir had a significantly increased risk of calculus formation as well as cystectomy‐related surgical procedures compared to patients undergoing ileal conduit. Age had a significant impact on vitamin B 12 deficiency and renal deterioration, whereas previous pelvic irradiation significantly increased the probability of ureteroenteric stricture and lost renal function. Age and urinary diversion had no impact on hernia, ureteroenteric stricture or pyelonephritis. Conclusion: The risk of treatment‐related morbidity was high and careful patient selection before cystectomy seems important. The lack of standard criteria regarding how to report morbidity makes comparison with other studies difficult.

Neoadjuvant Chemotherapy with Cisplatin and Methotrexate in Patients with Muscle-Invasive Bladder Tumours

This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma of the bladder. In the first trial, local treatment consisted of cystectomy (DAVECA 8901) and in the other trial the treatment was radiotherapy (DAVECA 8902); 153 eligible patients were randomized. The majority of the patients (89%) completed the protocol. The overall time to progression for all 153 patients was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p=0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19.2 months in the group receiving chemotherapy and 16.3 in the group not receiving chemotherapy. The 5-year survival rate was 19% in the group receiving chemotherapy and 24% in the groups not receiving chemotherapy (p=0.98). Late toxicity grade 3 or 4 of the bladder was recorded in 25% of the patients (actuarial rate). Neoadjuvant chemotherapy with cisplatin and methotrexate did not significantly improve disease-free or overall survival in 153 randomized patients with invasive bladder cancer.

Surgical Repair of Vesicovaginal Fistulae: A Ten-year Retrospective Study

OBJECTIVE Vesicovaginal fistulae in the western world generally occur as complications to pelvic surgery or radiation therapy of pelvic cancers. We have reviewed our results of vesicovaginal fistula closure procedures over a 10-year period. PATIENTS AND METHODS From 1985 to 1996, 55 patients were referred to our department due to vesicovaginal fistulae. Five patients had fistulae due to malignant recurrence and one patient was considered inoperable. Thus, 49 patients were operated on. Thirty patients had fistulae resulting from pelvic surgery. Nineteen of the 25 patients admitted with fistulae secondary to radiation therapy of pelvic cancers were operated on. RESULTS Of the 30 patients with postoperative fistulae, 23 had an abdominal repair and 7 a vaginal repair. A success rate of 90% was achieved after a first closure procedure, as 3 patients within a month experienced a recurrence. These three recurrences were all successfully closed in a second operation, augmenting the success rate to 100% in this group of patients. In the group of patients with fistulae caused by irradiation, a urinary diversion was performed in 12 patients, and in 7 patients a primary attempt to close the fistula was made, either by an abdominal approach (2 patients) or by a vaginal approach (5 patients). The fistula recurred in 6 of these 7 patients. Despite several additional attempts to close the recurrent fistulae, only one patient was successfully operated on. CONCLUSION It seems that vesicovaginal fistulae resulting from pelvic surgery, in our hands, can be managed successfully either by an abdominal or vaginal approach. For patients with vesicovaginal fistulae resulting from radiation therapy, a urinary diversion appears to be the method of choice.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: Part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0–4, NX, M1, G1–3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0–2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Cystometric evaluation of early and late irradiation damage to the mouse urinary bladder

The present study reports a simple, non-invasive, in vivo method for detecting early and late radiation damage to the mouse urinary bladder using transurethral bladder filling. The study also describes a useful experimental model for irradiation of mouse urinary bladder without any concomitant irradiation of the rectum and bony structures and maximal shielding of the small intestine. Within 30 days after single fraction bladder irradiation at 5-30 Gy, repeated cystometric investigations reveal a change in the reservoir function of the bladder illustrated by a considerable dose-dependent decrease in the compliance of the bladder wall. The changes in the reservoir function is reversible hence the bladder function is restored after another month. At various time intervals after the irradiation, however, the late radiation damage appears, the time of manifestation being dose-dependent. This final change is irreversible and consistent with the clinically known contracted bladder.

Complications and neobladder function of the Hautmann orthotopic ileal neobladder

Authors from Denmark describe the complications of the orthotopic Hautmann ileal neobladder, and the function of the neobladder in their experience. They found a relatively high rate of complications, but felt that most of these were minor, requiring only a minimal amount of intervention. They also found the function to resemble that of the native bladder.

Bladder filling in mice: an experimental in vivo model to evaluate the reservoir function of the urinary bladder in a long term study.

We report a simple, reproducible, and low-invasive in vivo method for repeated examination of bladder well properties in mice. Over a period of 21 days transurethral bladder fillings were performed every second day on the same animal. Analysis of the bladder volume at an intravesical pressure of 10 and 20 mm. Hg and at the leakage point showed no trend during the 21 day study period with regard to changes in bladder volume. The model has been applied to a group of mice treated with a single fraction bladder irradiation dose of 20 Gy. These mice were investigated repeatedly during the following year. The end point selected for data evaluation in the irradiated group of mice was a 50% decrease in bladder volume at an intravesical pressure of 20 mm. Hg relative to the control value (bladder volume before irradiation). The results clearly demonstrate a biphasic change in the bladder reservoir function, in the form of an acute, reversible change, a period of normalization and then a late irreversible damage. The latter stage is consistent with the clinically found contracted bladder. In a control group there was no significant change in bladder volume during the study period of more than 200 days. The model thus appears feasible for future studies of bladder irradiation damage.

Sentinel lymph-node biopsy in patients with squamous cell carcinoma of the penis

To evaluate a single‐centre experience with sentinel lymph‐node biopsy (SLNB) as a staging procedure in patients with squamous cell carcinoma (SCC) of the penis.

Prognostic factors, pattern of recurrence and survival in a danish bladder cancer cohort treated with radical cystectomy

A cohort of 248 consecutive patients with bladder cancer undergoing radical cystectomy between 1992 and 98 was retrospectively followed from diagnosis until death. Prognostic factors, pattern of recurrence and survival were analysed. Pathological T and N, angiolymphatic and perineural invasion had an independent prognostic influence on survival. Patients without muscle-invasive tumour (Ta, T1) had a good prognosis, whereas patients with primarily superficial tumour progressing to muscle-invasive tumour had a significantly poorer outcome. Forty-six percent of these patients developed recurrences in the follow-up period, with a median time from recurrence to death of 5 months. The 5-year disease-specific survival for all 248 patients was 57%. Patients with pT4b or N+ all died within 3 years. Patients with positive lymph nodes or T4b were not curable with cystectomy alone. Patients with advanced T or with perineural/vessel invasion are in need of improved treatment options. Patients with superficial tumours at high risk of progression should be offered early cystectomy.