The Role of External Irradiation in the Treatment of Transitional Cell Carcinoma of the Bladder—A Review of Fifty Cases

Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic Radiology, University of California, San Francisco, between 1957 and 1962, 59 were accepted for radiation treatment. Fifty had transitional cell carcinoma and were treated with supervolt therapy (1 mev or cobalt-60).Two types of tumors were again found suitable for external irradiation: Papillary carcinomas Grades II and III, as long as they have not, or at least have not massively, invaded muscle; and undifferentiated carcinomas, Grade IV, regardless of degree of extension through the pelvis. The former type, if single, is treated by irradiation for the first recurrence after one attempt with radical transurethral resection. In the presence of multiple lesions at the first examination, radiation therapy is given immediately. The latter type is treated by radiation therapy without any attempt at surgical removal.Of 37 patients, Stages A to C, treated more than three years ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no cystoscopic or clinical signs of active disease and had normal bladder function. Of 23 patients treated more than five years ago, eight were alive after five years (35 per cent) and four (17 per cent) remained controlled by radiation therapy alone, with normal bladder function.No major complications were observed. In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in five and a half weeks to 6,000 r in seven weeks.A close cooperation between urologic surgeons and radiotherapists during recent years permits long-range treatment planning from the time of diagnosis, which is essential in the effective therapy of carcinoma of the bladder.     

Carcinoma of the cervix

Studies by eminent surgeons to reevaluate the place of radical operations in the treatment of carcinoma of the cervix-now that extensive procedures have become less hazardous-apparently have led to confusion in some minds as to choice between surgical and radiation therapy. Pending outcome of the studies, general employment of surgical treatment is unwarranted. Radiation is the treatment of choice in most cases, particularly if the lesion is in an early stage, although radical operation is indicated in certain rare early cases in which delivery of an effective dose of radiation to involved areas is technically difficult. Elsewise it appears at present that operation should be used only in cases of stages III or IV carcinoma-in which results by either means of treatment are poor.One hundred and seven patients were treated with a combination of x-ray and radium irradiation. X-ray was used first to reduce the hazard of implanting the radium. The "five-year arrest" rates were as follows: For 22 patients with stage I lesion, 70 per cent; for 31 with stage II, 55.7 per cent; 33 with stage III, 39.7 per cent; 21 with stage IV, 0. Eighteen patients with diagnosis of carcinoma of the cervix who had had subtotal hysterectomy were treated. The stage of the disease could not be determined. In this group the five-year arrest rate was 52 per cent.     

Treatment of Basal Cell Carcinoma of the Eyelids by Radiotherapy

One hundred and nineteen cases of basal cell carcinoma of the eyelid were reviewed to determine the efficacy of radiotherapy for treatment of this lesion. In 61 of 111 patients, the tumour was at the medial canthus or inner third of the lower lid. The greatest incidence was in the 60 to 69 age group. Most of the patients were treated with 85-120 kV radiation and given a dosage of 3000-5000 roentgens. Fifty per cent were followed up for at least four years. There were few complications. There were eight recurrences. Four of these were from a subgroup of 21 patients that had had previous surgery. It is concluded that radiotherapy is a good method of treating basal cell carcinoma of the lid, although previous surgery would appear to increase the likelihood of subsequent recurrence.     

Virus-modified homologus tumor-cell extract in the treatment of vulvar carcinoma

Summary Eight patients with squamous carcinoma of the vulva and two or more positive nodes have received adjunctive immunotherapy with a virus modified homologous cell extract. Seven of eight patients received radiation therapy in addition. Cells derived from the SW962 vulvar carcinoma cell line were infected with PR8/A/34 strain of influenza and a membrane extract was used for immunization. The extract was administered by the intradermal route weekly for three doses and then biweekly for up to 2 years. Each dose is equivalent to 1.5 mg protein. None of the patients have recurred and durations of remission are 24, 24, 22, 22, 21, 16, 7, and 2 months respectively. This compares favourably with similar groups of patients who were treated with surgery alone (22/33 recurred, median recurrence time 14.8 months) or surgery plus radiation therapy (8/9 recurrences, median recurrence time 11.0 months). No serious side effects have occurred with more than 200 doses of extract.Post immunization monitoring has indicated good in vitro and in vivo immunological responses and antibody titers to PR8 increased significantly in five of eight patients.Dr. Rutledge is Head of the Department of Gynecology     

Disease-related lymphocyte cytotoxicity in vitro in patients with transitional cell carcinoma of the urinary bladder. Comparisons with other malignancies,acute cystitis,and healthy donors

Summary Blood lymphocytes from 100 patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) were studied for their cytotoxicity in vitro against a panel of allogeneic tissue culture cell lines. Of the TCC-bladder patients, 45 were untreated for their disease, while 55 had been treated with local radiotherapy up to 12 years before testing. Control lymphocytes were obtained from (1) 45 untreated, age- and sex-matched patients with other neoplastic diseases, mainly urogenital cancers; (2) 19 patients with acute cystitis; and (3) 45 healthy donors. Lymphocytes from individual donors within all five groups were frequently cytotoxic to any one of the target cells. However, the lymphocytes from each of the two TCC-bladder groups were markedly more cytotoxic to two different bladder tumor targets than to control targets derived from normal bladder epithelium, from colon carcinoma, or from malignant melanoma. Similar comparisons made within each of the three control donor groups did not show this. The results indicate that the two bladder tumor targets were not more susceptible to lymphocyte-mediated lysis than the control targets. The mean cytotoxicity displayed by the lymphocytes from both TCC-bladder groups to the bladder tumor targets was significantly higher than that of the cancer control group and that of the healthy donors. No such elevation was seen when the cancer control group or the cystitis patients were compared with healthy donors. Although untreated TCC-patients with a larger tumor burden (stages T3–T4) appeared to be slightly less cytotoxic to all target cells than those with a smaller tumor burden (T1–T2), these differences were not statistically significant. On the other hand, among the treated TCC-patients, in the main those tested more than 1 year and up to 5 years after therapy exhibited a significantly elevated mean cytotoxicity to the bladder tumor targets. Within all five donor groups, the overall cytotoxicity to the bladder tumor targets and the normal bladder targets showed a statistically highly significant correlation. However, while there was no correlation for the untreated TCC-bladder patients and the clinical controls between cytotoxicity to the bladder tumor targets on one hand and non-bladder targets on the other, the cytotoxicity to the bladder tumor targets of the treated TCC-bladder patients was also correlated with that to the colon carcinoma and the melanoma targets. The results indicate that cytotoxicity in both TCC patients and controls reflects recognition by the lymphocytes of a variety of antigens, shared to different degrees by different groups of target cells. Furthermore, in TCC-bladder patients there is a superimposed cytotoxicity, which is related to their disease and which probably reflects reactions against one or several tumor-associated antigens.     

Myasthenia Gravis: Comparative Evaluation of Medical and Surgical Treatment

Sixty-eight patients with myasthenia gravis were evaluated and compared to determine the results of medical and surgical treatment; eight patients with thymoma were evaluated separately. In the group of 30 non-thymoma patients treated medically 50% of patients derived moderate to good improvement over a mean follow-up period of 11 years. Ten per cent of patients in this group died from myasthenia.In the group of 30 non-thymoma patients treated by thymectomy, 83% achieved good to excellent improvement. There was no surgical or myasthenic mortality over a mean follow-up period of nine years.The results of treatment in the eight thymoma patients were decidedly inferior and there was no significant difference between the medically and surgically treated patients. Fifty per cent showed only moderate improvement during a mean follow-up of five years and 50%, after initial improvement, deteriorated later and died from myasthenia between three and four years after thymectomy.Two additional patients had thymoma without myasthenia. Neither of them had developed myasthenia, two years following thymectomy in one case and after 25 years in the other, despite recurrence of the tumour with extensive invasiveness in the very long-standing case.     

Trophoblastic tumors of the uterus-problems of methotrexate therapy

Nineteen patients with trophoblastic tumors of the uterus were evaluated at the University of California San Francisco Medical Center. Eight patients, admitted before 1956, did not receive chemotherapy; the mortality rate was 87.5 per cent. Ten of the remaining 11 patients were given intermittent, intensive Methotrexate therapy; actinomycin D and vincristine were used in treating two patients in whom resistance to Methotrexate developed. The mortality was 10 per cent. Toxicity was a prominent factor but was completely reversible when chemotherapy was stopped.None of the patients showed recurrent disease during follow-up evaluation eight months to five years and eight months after therapy was completed.It is postulated that continuing chemotherapy four to six months after the chorionic gonadotropin titer becomes negative decreases recurrent disease.     

Trophoblastic Tumors of the Uterus—Problems of Methotrexate Therapy

Nineteen patients with trophoblastic tumors of the uterus were evaluated at the University of California San Francisco Medical Center. Eight patients, admitted before 1956, did not receive chemotherapy; the mortality rate was 87.5 per cent. Ten of the remaining 11 patients were given intermittent, intensive Methotrexate therapy; actinomycin D and vincristine were used in treating two patients in whom resistance to Methotrexate developed. The mortality was 10 per cent. Toxicity was a prominent factor but was completely reversible when chemotherapy was stopped.None of the patients showed recurrent disease during follow-up evaluation eight months to five years and eight months after therapy was completed.It is postulated that continuing chemotherapy four to six months after the chorionic gonadotropin titer becomes negative decreases recurrent disease.     

Juvenile malignant lymphomas. 2 Non-Hodgkin lymphomas

Between 1970 and 1978 33 children with Non-Hodgkin-lymphomas at the age of 2-15 years were treated at the university children's hospital of Jena. 27 patients showed the first appearance of the disease, 6 patients had already been treated in other hospitals and were admitted with relapses. The biopsy material was classified or re-classified after the Kiel-classification. Beside the histological classification the surface markers of the malignant cells of NHL-patients were determined. 20 of 33 children were already in stage IV (Ann-Arbor-classification). Among our patients were 6 lymphoblastic NHL of Brukitt type, 10 of the convoluted cell type and 16 unclassified and one lymphoblastic lymphoma. The main localization of the NHL were mediastinum [15] and the gastrointestinal tract [10]. The therapy consisted of irradiation and chemotherapy (2 protocols) and, in case of an abdominal localization, in the attempt at a radical operation. Patients of stage I and stage II showed a complete remission rate of 50 per cent for 3 years; patients of stages III and IV of 20 per cent only. NHL of the convoluted cell type and of the Burkitt-type proved to have worse three-year-remission rates (16 per cent and 27 per cent) than unclassified lymphoblastic NHL (42 per cent).     

CARCINOMA OF THE CERVIX

Studies by eminent surgeons to reevaluate the place of radical operations in the treatment of carcinoma of the cervix—now that extensive procedures have become less hazardous—apparently have led to confusion in some minds as to choice between surgical and radiation therapy. Pending outcome of the studies, general employment of surgical treatment is unwarranted. Radiation is the treatment of choice in most cases, particularly if the lesion is in an early stage, although radical operation is indicated in certain rare early cases in which delivery of an effective dose of radiation to involved areas is technically difficult. Elsewise it appears at present that operation should be used only in cases of stages III or IV carcinoma—in which results by either means of treatment are poor.One hundred and seven patients were treated with a combination of x-ray and radium irradiation. X-ray was used first to reduce the hazard of implanting the radium. The “five-year arrest” rates were as follows: For 22 patients with stage I lesion, 70 per cent; for 31 with stage II, 55.7 per cent; 33 with stage III, 39.7 per cent; 21 with stage IV, 0. Eighteen patients with diagnosis of carcinoma of the cervix who had had subtotal hysterectomy were treated. The stage of the disease could not be determined. In this group the five-year arrest rate was 52 per cent.     

Radiation Therapy in the Treatment of Carcinoma of the Lung

In Ontario in the past 25 years, the death rate from cancer of the lung has shown a substantial increase, ninefold for males and twofold for females. The male:female ratio varied from an average of 8.5:1 to as high as 11.7:1 at the ages 65 to 69. From 1938 to 1958, one-quarter of the total cases (2457) were treated in Ontario Cancer Clinics. Survival rates were: for one year, 20%; three years, 6.5%, and for five years, 3.8%. Fifty-four per cent of surgically treated patients and 63% treated by resection and radiotherapy were alive one year after treatment. Of 821 cases treated with orthovoltage the one-year survival rate was 14%, and of 862 cases treated with cobalt therapy, 23%. It was concluded that this improvement in results may be attributed to the difference in treatment.     

Cytologic detection of urothelial cancer and other abnormalities in a cohort of workers exposed to aromatic amines

A total of 541 members of a cohort at increased risk for occupational bladder cancer underwent a 33-month program of screening with urine cytology. Selected workers received further urologic study with cystoscopy and bladder biopsies. Eight workers had positive or suspicious cytologic findings. Only one of the eight had a prior history of bladder cancer. Biopsies showed invasive carcinoma and/or nonpapillary carcinoma in situ in five workers in this group, severe atypia in one, and no significant abnormality in two. Of 56 workers who had atypical cytologic findings, 16 had bladder biopsies, which showed atypia of flat urothelium in 11, nonpapillary carcinoma in situ in one, noninfiltrating papillary carcinoma in one, and no significant abnormality in three. The cytologic detection of urothelial abnormalities often required more than a single specimen. Since the cohort in this study may develop more bladder cancers with the passage of time, continued follow-up is indicated.     

A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester).

A retrospective study of 932 second trimester terminations between 12-27 weeks gestation was carried out to determine the efficacy of gemeprost for second trimester termination. A single course of 5 x 1 mg gemeprost pessaries was administered every three hours. If abortion had not occurred after the first course of pessaries, a further course of 5 x 1 mg pessaries was administered. Intravenous oxytocin was administered after 36 hours if abortion had not occurred. Eighty per cent and ninety five per cent of patients aborted within 24 and 48 hours respectively. Of the remaining 5 per cent of women, 3 per cent aborted with escalating doses of oxytocin. In the remaining 18 (2 per cent) women, the pregnancies were electively terminated with an alternative method. The median induction-abortion interval was 18.0 hours and 15.0 hours in nulliparous and parous women respectively (P less than 0.0001). The number of pessaries required to induce abortion was not influenced by parity. Significantly more parous women bled more than 500 ml. The incidence of pelvic sepsis (0.1 per cent) and cervical tear (0.1 per cent) was low. Twenty six per cent of women had diarrhoea and 23 per cent vomited following administration of prostaglandin. This study confirmed the efficacy of gemeprost for second trimester termination of pregnancy. This method of termination is safe, non-invasive, simple and has a low complication rate.     

Subacute bacterial endocarditis; a report on 57 patients treated with massive doses of penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment. Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent). Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections. There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

SUBACUTE BACTERIAL ENDOCARDITIS—A Report on 57 Patients Treated with Massive Doses of Penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment.Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent).Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections.There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

Differential sensitivities to gamma radiation of human bladder and testicular tumour cell lines

Gamma radiation sensitivities of continuous cell lines from nine human tumours were measured, comparing four derived from transitional cell carcinomas of the bladder with five from non-seminomatous germ cell tumours of the testis. The testicular cells were significantly more radiosensitive than the bladder cells, corresponding to the response to therapy of these tumour types in patients. These observations indicate that radiosensitivity is retained in vitro and is an inherent property of the testicular tumour cells. These gamma radiation sensitivities were compared with those of SV40-transformed fibroblasts derived from a normal individual and one with the heritable disease, ataxia-telangiectasia (A-T). The bladder cells had gamma radiation sensitivities similar to that of the SV40-transformed normal line. The testicular cells were hypersensitive to gamma radiation, although not as sensitive as the SV40-transformed A-T line. A-T cells, unlike those derived from normal individuals, continue to synthesize DNA at a normal rate following radiation exposure, prompting a comparison of the kinetics of DNA synthesis in three bladder and three testicular tumour cell lines. One of the bladder and two testicular lines showed a reduced inhibition when compared to the other tumour cell lines and the SV40-transformed normal line. Thus there was no clear association between DNA synthesis inhibition and radiosensitivity.     

Ammoidin (xanthotoxin) in the treatment of vitiligo

Eighteen patients with vitiligo were treated with two crystalline substances, xanthotoxin (Ammoidin) and imperatorin (Ammidin) from the plant Ammi majus. Four patients improved more than 50 per cent. One had complete cure, but depigmentation recurred after a few months. Six patients had moderate improvement (less than 50 per cent), three had slight repigmentation, and in five cases there was no improvement. These results are similar to those reported by other investigators.Pronounced local inflammatory reactions are to be expected after exposure to ultraviolet light in nearly all patients treated with xanthotoxin. In one case prolonged sensitivity to sunlight, manifest by vesiculating dermatitis, occurred.     

Cancer of the Nasopharynx

Of 75 consecutive patients with nasopharyngeal cancer treated at UCLA Center for Health Sciences, 42 were eligible for long-term study. Fourteen (33 percent) survived five years, and one survived ten years. Since the management of nasopharyngeal cancer is primarily irradiation, a well-planned aggressive treatment program using supravoltage therapy is recommended. In spite of cranial nerve involvement or skull erosion, radiation therapy occasionally may offer long term control of the disease.     

Needle biopsy in diagnosis of prostatic cancer

Four methods available for the diagnosis of carcinoma of the prostate-digital rectal evaluation, prostatic smear, needle biopsy and open perineal or transurethral biopsy-were studied and correlated.One hundred ten patients with clinical indications of cancer of the prostate were subjected to needle biopsy and open perineal or transurethral biopsy. Seventy of the same patients had prostatic smear examination. Using the open perineal biopsy or the positive transurethral biopsy as the standard, the accuracy of prostatic palpation, prostatic smear and needle biopsy were obtained.A high degree of correlation (74 per cent) was demonstrated between digital rectal evaluation and positive surgical biopsies in both early and late cases. There were 17 false positive clinical diagnoses. The prostatic smear showed an overall correlation of 45 per cent when compared with the results of positive surgical biopsy. The overall accuracy of needle biopsy was 73 per cent. However, in the last 39 cases, including eight in which the carcinomas were of groups A and B (curable), the needle accuracy was 100 per cent. When there is clinical indication of malignant disease of the prostate, needle biopsy of the lesion is warranted and should be done before definitive or palliative treatment is undertaken.     

Brushing cytology in biliary tract obstruction

During a period of eight years (1980 to 1987), cytologic samples were obtained by brushing and reverse screw devices from 54 patients undergoing transhepatic cholangiography for evaluation of obstructive jaundice. Eight patients were excluded from this study, seven for inadequate follow-up and one because of unsatisfactory cytologic material. Of the remaining cases, 32 were cytologically diagnosed as adenocarcinomas; all but one patient proved to have malignant disease by histologic examination and/or through clinical follow-up. These included 21 pancreatic carcinomas, 6 bile duct carcinomas, 1 ampullary carcinoma, 1 gallbladder carcinoma and 2 metastatic carcinomas. In one case, the diagnosis of malignancy was found to be in error upon review of the cytologic smears. Of 14 patients with negative cytologic diagnoses, 7 were found to have malignant neoplasms and 7 had benign diseases. These findings indicate that, while a positive cytologic diagnosis is a reliable indicator of a malignant biliary obstruction, a negative result does not exclude malignancy.