Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. I. Thymic-dependent lymphocytic blastogenesis.

Thymic-dependent lymphocytic blastogenesis of peripheral blood lymphocytes of 59 patients with varying stages of prostatic cancer to the non-specific plant mitogen, phytohaemagglutinin (PHA) and the correlation of their responsiveness with the clinical stage of malignancy and level of alpha2-globulin have been evaluated. Patients within each of the four stages of malignancy possessed statistically significant extrinsic (noted in 40 (68%) of 59 patients) and intrinsic (noted in 21 (47%) of 45 patients) aberrations of their lymphocytic responsiveness to PHA compared with the responsiveness of a control population of non-cancer patients. The observed aberrations were, however, not significantly different between each stage nor did they correlate with the stage of disease. Similarly, levels of alpha2-globulin, while significantly elevated within each stage, as compared with the levels in the control population, no significant differences or correlation with the stage of disease was observed. Of interest, perhaps pending further study, were observations of the increased frequency of the number of patients with a significant elevation of alpha2 with a progression of malignancy from localized to invasive and metastatic disease. A similar trend in the incidence of the association of aberrations of lymphocytic reactivity with elevated levels of alpha2 were also noted with a progression of disease. The present confirmatory observations of a recent study in this laboratory of diminished cellular responsiveness in patients with prostatic cancer may be of considerable relevance in directing the therapeutic management of the patient - lest the therapy selected be further debilitating providing reduced surveillance - metastization of tumour cells, and alteration of tumour-host homeostasis.     

Alterations in host responsiveness in patients with prostatic cancer following cryosurgery or transurethral resection.

Anesthesia, stress, trauma or the operation per se have been reported to result in alterations of host resistance in a wide range of diseases. The effect of such changes on the thymolymphatic system of patients with prostatic cancer is not known. While evaluating in vitro parameters of cellular immunologic responsiveness in patients with prostatic cancer, we have observed a depression two to seven days following cryosurgery or transurethral resection (TUR) of the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBL). Contrary to the reduced proliferation of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte proliferation, particularly if involving tumor-cloned T-cells, may provide reduced surveillance to potential metastatic tumor cells leading to an alteration of tumor-host homeostasis. The potential of reduced surveillance, at least in the case of TUR, appears to be supported by observations that patients dying from prostatic cancer at our institution had an antecedent TUR. Identifying those patients with changes in responsiveness before surgery, as well as those prone to develop or undergo further reductions in responsiveness after surgery, would appear to be relevant in the management of patient with prostatic as well as other malignancies. Pre- and/or postoperative immunotherapy in such patients may be indicated.     

Serum proteins in prostatic cancer. II. Effect on in vitro cell-mediated immunologic responsiveness.

The sera from patients with prostatic cancer have been observed to posses an unidentified factor capable of inhibiting the migration of leukocytes and the proliferative response to the nonspecific mitogen, phytohemagglutinin. Observation of inhibition of these two suggested in vitro correlates fo cell-mediated immunologic responsiveness emphasizes (1) the importance to the adjunctive diagnosis and prognosis of patients with malignancy of identifying the presence of abnormal serum proteins, and (2) the role of humoral inhibitory or "immunoregulatory" factors as potential abrogators of mechanisms of host resistance, for example, immunologic surveillance, and thus the degree to whcih the host may respond to his tumor.     

Modulatory effects of oestrogen on immunologic responsiveness. I. Inhibition of DNA synthesis in peripheral blood lymphocytes from patients with Peyronie's disease, prostatic cancer and transsexuals and a commentary.

A reduction in the phytohaemagglutinin-induced transformation of peripheral blood lymphocytes from patients with Peyronie's disease and prostate cancer and transsexuals cultured in autologous and homologous serum following the receipt of oestrogen therapy has been observed. Reduction of lymphocyte transformation in patients with prostatic cancer and without malignancy receiving oestrogen, i.e., Peyronie's disease and transsexuals, suggests that this reduction is related to the mode of therapy rather than to malignancy or a particular pathologic state. No direct evidence exists that the observed in vitro aberrations of lymphocytic responsiveness are reflective of host compromise, but these observations are of potential relevance in terms of their implications in the therapeutic management of patients with prostatic cancer and other hormonally-dependent tumours, e.g., of the breast, as well as responsive diseases, through their effect on cellular immunocompetence and suitability of hormonally treated patients as prospective candidates for adjuvant immunotherapy. The possible relevance of the present observations to the suggested association between uterine cancer and prolonged administration of diethylstilboesterol, as well as that between development of vaginal tumours in offspring and maternal ingestion during pregnancy, also remains of potential concern, pending further investigation.     

The possible role of transurethral resection in the dissemination of prostatic cancer.

Prostatic carcinoma often reveals two different forms of tumour growth: (1) vigorous, almost therapy-resistant local growth, with absent or very slow metastasis (group 1), and (2) slight local growth responsive to therapy, combined however with swiftly forming distant metastasis (group 2). Two groups of such patients were examined in relation to primary findings and clinical course. Two factors were found in which they markedly differ. (1) The histological findings: in group 1 significantly more mature cancer forms appeared. (2) Treatment: a strikingly higher number of transurethral resections were performed upon in group 2 patient. The difference in the clinical development of prostatic cancer seems to be due to variations in the biology (as yet unknown) but may be partly to operative interference.     

Clinical studies of transurethral resection in patients with benign prostatic hypertrophy

During the last 9 years, 1,892 patients underwent surgery of the prostate. Benign prostatic hypertrophy (BPH) accounted for 1,812 cases, and prostatic cancer 80 cases. In the case of BPH, transurethral resection was done in 1,645 cases, cryosurgery in 136 cases, and suprapubic prostatectomy in 31 cases. Latent cancer was detected in 54 (3.3%) of the BPH cases. The average patient age of the patients with latent cancer (73.6 +/- 6.9 years) was higher than that of those without latent cancer (69.5 +/- 7.7 years). This suggested a significant relationship between the age of the patient and the occurrence of latent cancer.     

Serum proteins in prostatic cancer VI. Reduction of the suppressive ("blocking"?) properties of serum on in vitro parameters of cell-mediated immunologic responsiveness following cryosurgery.

Preliminary studies of sera from prostatic cancer patients have indicated a reduction in the presence of suppressive ('blocking'?) properties of in vitro parameters of cell-mediated immunologic responsiveness induced by a non-specific mitogen (phytohaemagglutinin) in association with a decrease in the level of alpha2-globulin and favourable clinical response following cryosurgery. The origin of the immunosuppression factor(s) migrating on electrophoresis in the alpha2-globulin fraction of serum remains to be identified. Earlier demonstration of suppression of leucocyte migration by factors elaborated from tumour cells and recent observations of the suppression of lymphocytic reactivity by seminal plasma and coaguloprostatic fluid suggest that suppression and reduction or abrogation of the suppressive properties of serum following cryosurgical destruction of tumour may be attributed to a reduction in soluble prostatic tumour-associated antigen shed into the circlation by previously viable tumour. Such antigen while not at a sufficient concentration to engender an immunologic response in the aging and tumour-burdened host, may, however, have been sufficient to pre-empt the effector limb of cell-mediated responsiveness contributing to the observed suppression of lymphocytic reactivity. Cryosurgery, resulting in necrosis and cell death with depletion of the primary source of antigen might thereby have permitted a previously overwhelmed host to respond, viz., the favourable clinical response observed.     

Experiences with cryosurgery in the management of benign prostatic obstruction.

Cryosurgery of the prostate gland has been used on mainly unfit patients for ten years as an alternative to open and endoscopic surgery in over 250 patients. With the use of a simple "rule of thumb" technique, blind cryosurgery can be recommended as causing few complications. Furthermore, the patient's early discharge from hospital can be achieved. Long-term functional results are satisfactory. More complicated techniques have been described and are mentioned, but as a result of experience simplicity of technique is recommended.     

Evaluation of uroflowmetry in different groups of patients after transurethral resection of prostatic adenoma

One hundred patients after transurethral prostatectomy (TURP) were examined. The patients’ age, presence or absence of urinary tract infection, time after TURP, and the size of adenoma were taken into consideration in the assessment of uroflowmetry. It was found that with the passage of time all parameters have improved. Comparison of the results of uroflowmetry performed in patients with large or small adenomas showed that TURP was successful in both groups. Infection was found to affect the volume of the bladder, but it had no significant influence on other uroflowmetry parameters or on residual urine. The age of the operated patients seemed to have no influence on the results of flowmetry after TURP.     

Comparison of long-term results of transurethral incision of the prostate with transurethral resection of the prostate, in patients with benign prostatic hypertrophy

One hundred patients with benign prostatic hypertrophy (BPH) were randomized to transurethral incision (TUIP) or transurethral resection of the prostate (TURP). The average prostate weight before operation was not more than 30.0 g. Indications for the operations were based on the disease history, physical examination, digital rectal examination, laboratory values, and pressure-flow examination. All operations were performed with patients under spinal anesthesia. TUIP was performed with a Collins knife, and TURP was performed with a resectoscope. Follow-up was performed 24 months after the operations. After treatment there were statistically significant daytime and nocturnal reduction in voiding frequencies of 2.9 and 1.7, respectively, after TUIP, and 2.0 and 1.5 after TURP. In both groups, there occurred significantly better maximal flow rate from 7.6 mL/s to 16.9 mL/s in group I and from 6.9 mL/s to 17.6 mL/s in group II. The mean values of linearized passive urethral resistance relation in both groups significantly decreased from 3.6 +/- 0.6 to 1.0 +/- 0.5 after TUIP and from 3.9 +/- 04 to 1.4 +/- 0.5 after TURP. The TUIP procedure is effective and safe for patients with a small number of complications.     

Clinical study on prostatic cancer detected incidentally by transurethral resection of the prostate

Transurethral resection of the prostate (TUR-P) was performed on 463 consecutive patients with clinically diagnosed benign prostatic hyperplasia (BPH) between April 1994 and June 2000. Pathological examinations of resected prostatic tissues revealed prostatic cancer in 15 (3.2%) of them. Eight (53.3%) of them were in stage A1, and 7 (46.7%) in stage A2. Between 15 cases with prostatic cancer and those with BPH, clinical features including age, serum prostate specific antigen (PSA) levels, prostatic volume, PSA density (PSAD), and resected prostatic tissue weight were compared. As a result, age was the only parameter related with prostatic cancer with a statistically significant difference. The higher the age, prostate cancer was found more frequently. Postoperatively, radical prostatectomy and antiandrogen therapy were performed in 1 and 9 cases, respectively. The remaining 5 cases are being followed with no treatment for prostatic cancer, and have shown no findings suggesting recurrence. These 15 cases are all living disease-free at present. It seems of importance to explain preoperatively the possible detection of prostatic cancer in association with TUR-P, particularly for elderly patients aged 80 years or older.     

Subjective and clinical results after transurethral resection and suprapubic prostatectomy in benign prostatic hypertrophy.

This study was performed after a mean postoperative period of approximately 2 years. Results after transurethral resection (TUR) appeared to be inferior to results after suprapubic prostatectomy in patients' subjective symptomatology concerning frequency, nocturia, urinary stream complaints and incontinence. Late postoperative complications were found in a greater extent after TUR. TUR showed more often pathologic uroflow and pathologic residual urine data. Generally speaking, the results after suprapubic prostatectomy were substantially more satisfactory than the results after TUR.     

Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma

Patients with prostatic carcinoma on oral oestrogen therapy have an altered coagulation system and suffer cardiovascular side effects. Oestrogens--especially oral oestrogens--are potent inducers of liver synthesised proteins, including coagulation factors. We have assessed the effect of non-oral oestrogen on the coagulation system in patients with prostatic carcinoma. Twelve patients were given monthly intramuscular injections of 320 mg polyoestradiol phosphate (PEP). No additional oestrogens were given. No change was found in any of the coagulation factors, including factor VII, with the exception of a significant decrease in antithrombin III. No patient, including 38 patients treated with PEP, had any cardiovascular complications after a mean follow-up period of 12.9 +/- 0.7 months; 76% of the patients responded to treatment. Parenteral administration of oestrogen caused a less marked change in the coagulation system than oral administration and should be the treatment of choice for prostatic carcinoma.     

Internal urethrotomy of the prostatic urethra or transurethral resection in benign prostatic hyperplasia.

Transurethral resection of the prostate is the most common technique for the treatment of benign prostatic enlargement. The inconveniences of prostatic resection are retrograde ejaculation and bladder neck stenosis in small prostates. A randomized prospective trial was done to compare the results of conventional transurethral resection of the prostate in 22 patients and urethrotomy of the prostatic urethra in 27 with respect to postoperative retrograde ejaculation, persistent urinary symptomatology and maximal flow rates. After a mean followup of 25 months we concluded that internal urethrotomy of the prostatic urethra is the operation of choice in patients with a prostate of up to 30 gm.     

Radical transurethral resection in the management of muscle-invasive bladder cancer

The morbidity of radical cystectomy and early reports of good results have stimulated interest in radical transurethral resection of bladder tumors (TURBT) for muscle-invasive transitional-cell carcinoma of the bladder. Various investigators have used surgery alone or with adjuvant or neoadjuvant chemotherapy or radiation. Further research is necessary to define the indications, but at present, radical TURBT for muscle-invasive cancer appears to be appropriate for patients too ill to undergo radical cystectomy, those who decline the open operation, and those enrolled in clinical trials of this approach to bladder cancer.     

经尿道前列腺切除术对BPH患者夜尿症及睡眠质量的改善作用

目的:探讨经尿道前列腺切除术(TURP)对伴有夜尿症的良性前列腺增生(BPH)患者夜尿症及睡眠质量的改善作用。方法:回顾性分析2016年12月至2018年12月北京大学人民医院收治的122例BPH患者的病例资料。年龄(69.7±7.9)岁。伴糖尿病20例,高血压病40例。前列腺体积(64.4±41.2)ml,体质指数(24.3±2.7)kg/m 2。术前国际前列腺症状评分(IPSS)(20.5±5.5)分,夜尿次数(IPSS问题7)(4.4±1.9)次,无干扰睡眠时间(hours of undisturbed sleep,HUS)(1.7±1.0)h(其中HUS<3 h者110例),夜尿症生活质量评分(N-QOL)(24.9±6.3)分,生活质量评分(QOL)(4.4±0.9)分。111例完善尿动力学检查,最大尿流率(6.4±3.1)ml/s,最大膀胱容量(318.5±83.6)ml,残余尿量(153.9±158.9)ml,最大逼尿肌压力(78.4±35.5)cmH 2O(1 cmH 2O=0.098 kPa),其中逼尿肌肌力下降27例,膀胱过度活动症18例,膀胱有效容量下降9例,膀胱出口梗阻60例。42例术前有效膀胱容量<200 ml,其中最大膀胱容量>200 ml组33例,夜尿次数(4.5±1.9)次;最大膀胱容量≤200 ml组9例,夜尿次数(4.7±1.7)次。122例均行TURP治疗。记录术后IPSS、夜尿次数(IPSS评分问题7)、HUS、NQOL、QOL变化情况。比较最大膀胱容量≤200 ml组和>200 ml组术后夜尿症状改善情况。结果:122例术后随访3~20个月。术后IPSS(4.9±4.2)分,夜尿次数(1.9±1.2)次,HUS(3.4±1.3)h(其中91例HUS≥3 h,缓解率达82.7%),N-QOL(37.3±6.7)分,QOL(0.8±0.9)分,与术前比较差异均有统计学意义(P<0.05)。96例夜尿次数较术前改善≥50%。术后夜尿≥2次68例,<2次54例,两组术前IPSS总分[(21.8±5.3)分与(19.2±5.5)分]差异有统计学意义(P<0.05)。最大膀胱容量≤200ml组术后夜尿次数(3.4±1.5)次,与术前比较差异无统计学差异(P=0.12),最大膀胱容量>200 ml组术后夜尿次数(1.9±1.1)次,与术前比较差异有统计学差异(P<0.05)。结论:TURP可以显著延长伴有夜尿症的BPH患者的HUS,提高患者生活质量及睡眠质量。TURP可减少部分BPH患者夜尿次数,术前IPSS总分高以及最大膀胱容量≤200 ml是伴有夜尿症BPH患者术后夜尿症状无改善的危险因素。     

Total cryosurgery of the prostate versus standard cryosurgery versus radical prostatectomy: comparison of early results and the role of transurethral resection in cryosurgery.

PURPOSE: Results of standard cryosurgery of the prostate for prostate cancer in 49 patients were compared to those of destruction of the urethra during or after cryosurgery with subsequent transurethral resection or total freezing of the prostate (total cryosurgery) in 27. These results were compared to those of radical surgery in 83 patients with similar age, stage and grade of disease, and prostate specific antigen (PSA). MATERIALS AND METHODS: The 76 cryosurgery cases included all of those treated by 1 surgeon (R. S. G.) for localized prostate cancer after July 1, 1995. The 83 radical perineal prostatectomy cases consisted of all of those treated by another surgeon during the study period and by R. S. G. before cryosurgery use. Success was defined as a PSA of 0.2 or less 6 months after the procedure and a stricter standard, 0.0 PSA, was also assessed. RESULTS: The success rate was 96% for total cryosurgery, 48.9% for standard cryosurgery and 73.4% for radical surgery. Using 0.0 PSA as a criterion, 66.7% of total cryosurgery, 16.3% of standard cryosurgery and 48.2% of radical surgery cases were successfully treated. CONCLUSIONS: Total cryosurgical destruction of the prostate may offer new opportunities for cancer treatment heretofore unrecognized and should undergo more investigational analysis.     

Post-brachytherapy transurethral resection of the prostate in patients with localized prostate cancer

PURPOSE: We assessed the rate and results of transurethral resection of the prostate (TURP) in patients previously treated with brachytherapy as monotherapy for localized prostate cancer. MATERIALS AND METHODS: From May 1998 to May 2003, 600 patients with localized prostate cancer were treated with brachytherapy at our institution. Brachytherapy was performed as monotherapy with curative intent for clinically localized prostate cancer without adjuvant treatment in patients with clinical stages T1c (68.4%) or T2a (31.6%) disease. -Iodine and palladium implants were used in 583 and 7 patients, respectively. A real-time interactive implantation technique was used in all but the first 17 patients, who were treated using a preplanned technique. RESULTS: Of the 600 patients 19 (3.1%) underwent TURP after brachytherapy. Among the patients with acute urinary retention the median interval between prostate brachytherapy and urinary retention was 2 months (range 0.5 to 32). No TURP was done within 6 months after implant. The median interval between prostate brachytherapy and TURP was 7 months (range 6 to 41) and median prostate specific antigen (PSA) before TURP was 0.5 ng/ml (range 0.04 to 3.4). In the 19 patients the median weight of resected prostatic tissue was 8 gm (range 2 to 19) and 1 to 11 seeds were removed (median 5). The perioperative and postoperative courses were uneventful. There was no TURP related incontinence. With a median followup of 28 months after brachytherapy (range 7 to 48) no patient had clinical or biochemical evidence of disease progression, and for the group of 19 patients who underwent TURP median serum PSA at the end of followup was 0.38 ng/ml (range 0.03 to 3.4). CONCLUSIONS: After brachytherapy as monotherapy, TURP can be done safely if indicated. In our experience the resection of prostatic tissue along with a limited number of seeds at least 6 months after implantation did not impair PSA based biological and clinical results of brachy-therapy.