Biomedical subjects
Publications and source records attributed to W F Whitmore.
1. Seminoma may occasionally be rapidly growing, aggressive, radioresistant, and chemotherapy-resistant tumor. 2. Alkylating agents have had the greatest number of trials and have produced the best response rates in the management of seminoma, but a wide range of other agents warrants trials. 3. Adjunct chemotherapy is a logical consideration in patients with stage II and stage III seminoma.
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In 100 consecutive cases of prostatic adenocarcinoma treated by pelvic lymphadenectomy and interstitial implantation of 125I the relationship of tumor stage, size and grade was analyzed relative to the incidence and site of metastases, and the response of the primary tumor to irradiation. High stage, large size and poor histological differentiation were associated with a significantly higher probability of pelvic node metastases. The response of the primary tumor to irradiation was significantly higher among patients with small stage B tumors and/or those with negative pelvic lymph nodes. Important determinants of metastases subsequent to 125I implantation were the large size of the primary tumor, poor histological differentiation, seminal vesicle invasion, large (more than 3 cc) volume of lymph node metastases and absence of local prostatic response to irradiation.
Prostatic involvement by transitional cell carcinoma of the bladder includes a spectrum of histologic patterns. Ductal only or ductal and acinar involvement occurs with or without stromal invasion. Stromal invasion may exist without glandular involvement. Invasive prostatic patterns are most frequent in the setting of high stage invasive bladder tumors and 5-year survival rates for these patients are low. Non-invasive in situ prostatic patterns are usually associated with low stage bladder tumors and 5-year survival approaches that predicted from radical cystectomy for low stage bladder tumor alone. When an invasive pattern is associated with a low stage bladder tumor the 5-year survival rate is determined by the prostatic lesion and is low. Although the survival rate is severely jeopardized by stromal prostatic invasion the prognosis is not hopeless. Preoperative radiotherapy followed by cystoprostatourethrectomy can be expected to produce a 20 per cent 5-year survival rate.
Rectal invasion by benign prostatic hyperplasia occurred subsequent to an open transrectal biopsy of the prostate gland. Frequent transrectal resections of the prostate controlled this unusual lesion initially. However, massive intrarectal regrowth of this clinically malignant but histologically proved benign prostatic enlargement required eventual pelvic exenteration.
The clinicopathologic findings in 37 cases of malignant lymphoma with primary clinical manifestation in the testis were analyzed. Of these cases 34 were classified as histiocytic lymphoma and 3 as lymphocytic lymphoma. Patients usually presented with a painless small testicular mass of short duration. The peak incidence occurred in the fifth through eighth decades. Metachronous testicular involvement was noted in 35 per cent of the cases and simultaneous bilateral involvement in 3 per cent. In 25 per cent of the cases the first manifestation of lymphoma after orchiectomy was in the opposite testis. Regional and distant nodes were equally common sites of lymphoma after orchiectomy. The long-term survival of a few patients after orchiectomy may suggest that some malignant lymphomas are truly primary in the testis. However, the short interval free of disease and the rapid death of most patients imply that most testicular lymphomas are a manifestation of multicentric origin of systemic malignant lymphoma. The over-all 2 and 5-year survival rates were 30 and 20 per cent, respectively. Prospective studies are needed to define the optimal modality of treatment.
We reviewed 23 cases of primary carcinoma of the male urethra and compared the clinical findings, treatment and results to the experiences previously reported. Patients with lesions of the pendulous urethra managed by appropriate amputation of the penis with ilio-inguinal node dissection for groin metastases had a good prognosis, whereas patients with lesions of the bulbo-membranous or prostatic urethra had a poor prognosis. Despite occasional successful results with conservative surgical excision and over-all poor results with radical excision the generally extensive nature of such tumors necessarily makes radical excision the treatment of choice.
Carcinoembryonic antigen was measured in the urine and plasma of 108 patients with several types and various stages of genitourinary cancer. The value of the carcinoembryonic antigen assay as an early indicator of neoplastic disease was evaluated and a correlation was made between the extent of disease and the concentration of urinary and plasma carcinoembryonic antigen. Patients were classified according to stage of tumor involvement as follows: no evidence of disease, non-malignant disease, non-invasive disease, no known metastasis, regional metastasis and disseminated metastasis. The urinary carcinoembryonic antigen levels more closely paralleled the extent of disease than did the plasma carcinoembryonic antigen levels in patients with bladder cancer. Neither urinary nor plasma carcinoembryonic antigen levels were useful in assessing the extent of disease in patients with prostatic or testicular cancer. Studies related to microbiological interference in the carcinoembryonic antigen assay indicated that bacterial counts up to 10(5) organisms per ml. did not interfere. Cytological studies indicated that the presence of white blood cells, atypical cells and malignant cells could result in elevated urinary carcinoembryonic antigen levels.
The natural history, management and prognosis of scrotal carcinoma are reviewed in 19 cases and a method to stage the tumor is presented. Ten patients were rendered free of evidence of cancer, 9 of whom have survived more than 5 years. Wide local excision of the primary lesion with radical ilioinguinal dissection for proved inguinal lymph node metastases is the present recommendation. For non-resectable regional metastatic disease no treatment of established effectiveness is available. Irradiation has produced benefit on rare occasions and hemipelvectomy may be considered in selected cases.
There is a high probability of urethral carcinoma in patients who have had cystectomy for carcinoma of the urinary bladder, and their survival is poor when the disease is sufficiently advanced to be symptomatic or tumor is visible endoscopically. This study was undertaken to evaluate urethral cytology as a means of detecting and diagnosing in situ and invasive carcinoma of the urethral remnant following cystectomy. A total of 109 cytology specimens were examined from 65 patients who had cystectomy for bladder cancer. "Positive" or "suspicious" cytologic diagnoses of cancer were made on 28 patients; 24 had urethrectomy and 11 proved to have invasive carcinoma, 10 had carcinoma in situ and three had atypia or metaplastic changes in the urethra. One of 37 patients with "negative" cytologic diagnoses was found to have a low-grade carcinoma. It is suggested that all patients who undergo cystectomy without urethrectomy be followed with urethral cytological examination at regular intervals for an indefinite period.
The role of the regional lymph nodes in cancer is controversial. Non-neoplastic changes in lymph node histology can be correlated with prognosis for some tumour types and reactivity has been interpreted as evidence of an immune response to the tumour. Attempts to correlate the patterns of retroperitoneal lymph node activity with prognosis in patients with seminoma and non-seminoma germinal testicular tumours have not been successful. The implications of these findings are discussed.
Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.
This is a summary presentation on certain aspects of an experience with the use of radical cystectomy with or without prior irradiation in the treatment of selected patients with bladder cancer at the Memorial Sloan-Kettering Cancer Center.
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Solitary metastasis is uncommon, occurring in 1.6% to 3.2% of patients with renal cell carcinoma. Because of the potential of survival, amputation of an extremity with a metastasis is frequently advocated, particularly after successful nephrectomy. The cure rate with amputation is approximately 30%. Cryosurgery for treatment of localized and limited bony metastasis in an alternative to more radical surgery. This is a report of follow-up observation of the original series of cases as well as the addition of 4 new cases with multiple metastasis.
Fifty patients with testicular carcinoma, 45 with prostatic neoplasm, 84 with bladder carcinoma, and 13 with benign bladder papilloma were evaluated for skin reactivity to DNCB and other intradermal antigens. Correlation between pathologic staging and skin-test reactivity was sought. Reaction to DNCB among patients with testis tumors was more significantly depressed by chemotherapy than by the extent of retroperitoneal or distant metastatic disease indicating that skin testing as a means of following the course of disease or of predicting survival may be limited by alterations caused by chemotherapy. DNCB reactivity did not correlate with the prognosis for the different stages of disease, but follow-up studies of individual patient survival are needed for substantiation. Depression of DNCB reactivity exists among patients with prostatic carcinoma whether the disease is localized or widely metastatic. Only lengthy follow-up will determine if there is any correlation of reactivity with survival in individual patients. DNCB reactivity among patients with bladder tumors shows progressive reduction with increasing stage disease and lends support to the evidence suggesting immune deficiency in patients with bladder neoplasm.
An analysis of 45 cryptorchids (by history or examination) with a testicular cancer treated at Memorial Hospital, between 1934 and 1973, is presented. Twenty-five patients had the cryptorchid state repaired at ages four to 27 years, either spontaneously or by orchiopexy or hormonal therapy. Ipsilateral (24) or contralateral (one) intrascrotal testis tumors developed four to 47 years later. Twenty cryptorchid patients presented with ipsilateral inguinal (eleven), abdominal (seven), or contralateral intrascrotal (two) tumors. There were 18 pure seminomas, 17 embryonal carcinomas, nine teratocarcinomas, and one reticulum cell sarcoma. Five year survival rates as estimated by the product-limit method were 60% for the unrepaired cases and 41% for the repaired cases. The survival seems to follow histologic type and anatomical stage, whether the testis is within the scrotum or not. Five year survival similarly estimated was 78% in the seminomas and 29% in the other tumors. Twelve of thirteen survivors (including nine with seminoma) received postoperative irradiation to the regional lymphatics and eleven were without recurrent tumor for periods ranging from six to 28 years.
Cis-dichlorodiammineplatinum(II) (DDP) was given at a dose of 1.25 or 1.6 mg/kg to 24 patients with advanced measurable, urinary tract cancer. Eight patients (35%) achieved a partial remission and four additional patients had a minor response. There were 14 patients with epidermoid (transitional cell) bladder cancer who had had no prior chemotherapy and all eight partial responders were in this group. DDP appears to be one of the more active antineoplastic agents in bladder cancer.