L. Baert

Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

We investigated the phenotype and functional capacities of tumour‐infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n = 20). Three‐colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3+ T cells, with a clear predominance of CD4−CD8+ over CD4+ CD8− T cells, and a marked population of CD4+ CD8+ T cells. Natural killer (NK) cells were also strongly represented (> 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (< 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA‐DR was also elevated on CD3+ TIL, and HLA‐DR expression was further vigorously up‐regulated following ex vivo stimulation with anti‐CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3+ CD4+ TIL displayed a normal capacity to up‐regulate CD25 expression and to secrete both Th1‐type (IL‐2, tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ)) and Th2‐type (IL‐4, IL‐5 and IL‐10) cytokines upon triggering with anti‐CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3+ CD8+ TIL, on the other hand, consistently demonstrated a poor up‐regulation of CD25 upon triggering with anti‐CD3, and displayed poor ex vivo cytolytic activity in an anti‐CD3‐redirected 4‐h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3+ CD4+ TIL in RCC have normal functional capacities, whereas the proportionally major CD3+ CD8+ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.

Transurethral Microwave Hyperthermia for Benign Prostatic Hyperplasia: Preliminary Clinical and Pathological Results

Transurethral microwave hyperthermia is a new conservative treatment modality for benign prostatic hyperplasia. We treated 15 patients with 915 MHz. microwaves delivered transurethrally by a helical applicator. Of the patients 12 showed substantial objective and subjective improvement of obstructive outflow parameters. Significant improvement in objective study parameters included increased mean flow rate (p less than 0.00021), decreased mean residual volume (p less than 0.00001) and decreased mean prostatic volume (p less than 0.0077). Analysis of patterns of failure showed chronic bladder atony, prostate asymmetry and middle lobe configuration as important factors that could explain the failure of hyperthermia in 3 patients. Toxicity was mild, consisting of bladder spasms, perineal pain, dysuria and hematuria. Hyperthermia-induced pathological changes in prostatic tissues, causing periurethral shrinking and secondary dilatation of the prostatic urethra, are described. The reported clinical results of this phase I study are preliminary due to the short followup. A phase II study to optimize transurethral hyperthermia currently is underway. A phase III study is to be phased in comparing hyperthermia with transurethral resection of the prostate.

Interstitial Temperature Measurements During Transurethral Microwave Hyperthermia

Microwave hyperthermia is presently being investigated as a treatment for alleviating the symptoms of urinary outlet obstruction associated with benign prostatic hyperplasia. Two clinical techniques using intracavitary microwave applicators are being evaluated for safety and efficacy at various institutions. The transrectal technique uses a directional microwave radiator that is inserted into the rectum adjacent to the prostate. The transurethral approach uses a symmetrically radiating applicator located within the prostatic urethra. Transrectal prostatic heating techniques require surface cooling to prevent hazardous temperatures in the intervening rectal mucosa. Since transurethral applicators radiate from within the prostatic urethra, heating is confined to the obstructive tissue immediately surrounding the applicator. Concern has been expressed regarding the possibility of thermal injury to the prostate and adjacent rectum during transurethral hyperthermia treatment. In this report we present interstitial temperature measurements of prostatic and rectal temperatures in 5 patients. Temperature was observed to decrease at a rate of about 6C/cm. outward from the applicator. No clinically significant temperature increase was observed beyond 1 cm, outside the prostatic capsule or in the rectal mucosa.

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.

Transurethral hyperthermia for benign prostatic hyperplasia patients with retention

From 1989 to 1990, 32 poor surgical risk patients with urinary retention were treated with transurethral microwave hyperthermia at the department of urology, University of Leuven in Belgium. Mean patient age was 73 years (range 58 to 90 years) and mean duration of retention was 4 weeks (range 3 to 12 weeks). Followup ranged from 13 to 82 weeks, with a mean of 31 weeks. Bilobar or trilobar hyperplasia was diagnosed in 25 patients (78%), while 7 (22%) had median lobe or median bar hypertrophy. The mean prostatic volume was 52 cc (range 25 to 150 cc). Transurethral microwave hyperthermia was given with a helical antenna at 915 MHz. once or twice per week. The mean number of transurethral microwave hyperthermia sessions was 8.9 (range 5 to 10). Each session consisted of a 60-minute treatment at a mean maximum temperature of 45.4C (range 43.7 to 47.2C), average temperature 43.9C (range 42.7 to 45.5C) and minimum temperature 42.0C (range 40.2 to 43.0C). The temperature was continuously monitored, including thermal mapping in all patients. Of the 25 patients who presented with bilobar or trilobar hyperplasia 18 (72%) were catheter-free for the duration of followup. Of the 7 median lobe or median bar patients 1 (14%) showed sufficient improvement to warrant catheter removal. This patient, however, had recurrent retention 4 months after transurethral microwave hyperthermia. In patients with bilobar and trilobar hyperplasia a strong correlation was observed among maximum temperature (p = 0.0006), average temperature (p = 0.0033) and treatment response. As expected, no such correlation existed between minimum temperature and response to treatment (p = 0.56). Our study has again demonstrated therapeutic activity in patients with benign prostatic hyperplasia treated with transurethral microwave hyperthermia. A new finding was a strong correlation between temperature and response.

Surgery with adjuvant irradiation in patients with pathologic stage C adenocarcinoma of the prostate

Background. In recent years, the routine use of prostate‐specific antigen (PSA) to detect cancer of the prostate (CaP) early has renewed the controversy regarding radio‐therapy versus radical prostatectomy as the superior definitive treatment. Radiotherapy alone has been reported to result in a high incidence of local recurrence, whereas on the other hand surgical treatment has resulted in a high incidence of microscopic residual tumor. The purpose of this study was to review our treatment results with radical prostatectomy followed by planned courses of postoperative irradiation in patients with pathologic Stage (PS) C disease.

Juxtaglomerular Cell Tumor: Importance of Clinical Suspicion

This case report of a reninoma or juxtaglomerular cell tumor illustrates that careful preoperative radiological investigation and preoperative frozen-section examination does not always lead to a correct diagnosis. The preoperative diagnosis of juxtaglomerular tumors should therefore primarily depend upon clinical suspicion, eventually followed by directed renal vein renin ratio blood sampling. The importance of early preoperative diagnosis and treatment is stressed.

The Role of Prostate-Specific Antigen in the Management of Prostate Cancer

The prostate is the largest male excretory sex gland, secreting four major proteins primarily to the seminal ejaculate. These four proteins are: prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), prostate-specific protein (PSP-94), and human kallikrein 2 (hK2) (Table 14.1). At the present time the biochemical and pathologic mechanisms for the entry of these proteins into the systemic circulation are not well understood.

Relationship of response to transurethral hyperthermia and prostate volume in BPH patients.

A response to transurethral microwave hyperthermia (TUHT) at 915 MHz and its relationship to prostate volume was examined in 63 poor surgical risk benign prostatic hyperplasia (BPH) patients. All patients had moderate-to-severe obstructive signs and symptoms, and received > or = 5 TUHT one-hour sessions. Treatment temperature was controlled on the urethral surface at 45 degrees C +/- 1 degree C. Follow-up ranged from twelve to forty-four months (mean 18 months). The mean prostate volume was 57 cc (range 10-301 cc). There were 40 patients (63%) with prostate volume < or = 50 cc and 23 (37%) with a volume > 50 cc. Treatment failure was seen in 6 patients (10%). It was 10 percent in 40 patients with smaller glands and 9 percent for those 23 with larger prostates, N.S. at p = 0.49. Subjective treatment response was seen in 58 patients (92%). It was 90 percent for the 40 patients with < or = 50 cc prostates vs. 96 percent for the 23 with > 50 cc prostates, N.S. at p = 0.75. This study suggests that the initial prostate volume is not an important parameter predicting response to TUHT.

Vasoactive intestinal polypeptidergic innervation of human urinary bladder in normal and pathological conditions.

Urinary bladder biopsies from 31 multiple sclerosis patients, 9 diabetics, 5 patients after transtrigonal phenolization and 20 control patients were stained for acetylcholinesterase, S100 and vasoactive intestinal polypeptide (VIP). The VIP immunoreactivity was not decreased in all neuropathic bladders and its depletion was not related to cholinergic depletion. There was no correlation between bladder over- or underactivity and VIP content. VIP can act as a modulator of detrusor function in normal conditions. The significance of its depletion in neurogenic bladders needs further elaboration.