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).     

The clinical and economic efficacies of short courses of azithromycin in acute sinusitis]

A randomized study of a 3-day course of azithromycin therapy (500 mg once daily) vs. a 10-day course of co-amoxiclav therapy (625 mg thrice daily) in patients with acute sinusitis was performed with an account of the GCP criteria. One hundred patients in 2 groups each of 50 persons were enrolled. The estimates of the patient body temperature, headache, pain on palpation in the area of the accessory nasal sinuses, nasal cavity stuffing, nasal discharge nature and the nose mucous membrane appearance were recorded prior to the treatment, in 72 hours and on the 10th-12th and 26th-30th days of the treatment. The microbiological analysis of the punctate from the accessory nasal sinuses was undertaken before the antibiotic therapy and 72 hours after its start. The economic analysis included the cost of the antibiotic therapy course, hospitalization term, medical manipulations and laboratory tests as well as the cost/efficacy index. The frequency of the relapses within 6 months after the cure was estimated in the two groups compared. In 72 hours and on the 10th-12th days after the treatment start the efficacy of azithromycin was significantly higher than that of co-amoxiclav. The cure was stated in 41 (82 per cent) and 26 (52 per cent) patients on the 10th-12th days, in 6 (12 per cent) and 21 (42 per cent) patients the improvement was stated and the fail was stated in 3 (6 per cent) and 2 (4 per cent) patients respectively. The efficacy of the drugs on the 26th-30th days after the treatment start did not differ. The isolates of Staphylococcus aureus and Streptococcus pyogenes were the main pathogens. The bacteriologic eradication was recorded in 29 (90.6 per cent) patients treated with azithromycin and only in 18 (69.2 per cent) patients treated with co-amoxiclav. Adverse reactions and relapses of the disease within 6 months after the cure were more frequent in the patients treated with co-amoxiclav. The cost of the azithromycin therapy was significantly lower. It was shown that the shortened course of the azithromycin therapy provided earlier cure of the patients with acute sinusitis, better tolerance of the drug, less frequent adverse reactions, lower cost as compared to the use of co-amoxiclav and no relapses.     

Clinical use of rubomycin in neuroblastoma in children]

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.     

La laparotomie dans la maladie de Hodgkin: signification de l'atteinte de la rate.

We retrospectively reviewed 224 cases of Hodgkin''s disease, in 120 of which staging laparotomy was performed. The surgical findings in cases of clinical stage I or II disease with supradiaphragmatic presentation or clinical stage III disease did not influence the treatment plans. Of the 64 patients with positive results of laparotomy (splenic or lymph node involvement or both) 51 had splenic involvement; their 5-year survival rate, 57%, was similar to that of the patients with clinical or pathological stage III disease - 58% and 54% respectively. At laparotomy 11 patients with pathological stage III disease were found to have isolated splenic involvement; their 5-year survival rate, 64%, was not appreciably different from that of the patients with clinical stage II disease, 70%; both groups were treated with radiotherapy only. From this study we can conclude that splenic involvement in Hodgkin''s disease has no deleterious effect on survival and that splenic irradiation seems to be as effective as splenectomy in controlling the disease.     

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.     

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.     

Experience with using aclarubicin in the treatment of acute leukemia and blast crisis of chronic myeloid leukemia]

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.     

Decreased tuftsin concentrations in patients who have undergone splenectomy.

Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin''s disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin''s disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin''s disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin''s disease should perhaps be reconsidered.     

Changes in immune status in patients undergoing splenectomy for the staging of Hodgkin's disease.

The immune status of 17 patients with Hodgkin''s disease was studied before and after splenectomy (undertaken in staging laparotomy) and during chemotherapy or after radiotherapy. The findings were compared with those in 19 patients not selected for splenectomy. Serum IgA and IgM levels became significantly lower after treatment in the splenectomy group. Cell-mediated immunity was depressed mainly in patients receiving quadruple cytotoxic chemotherapy. Neutrophil function was normal or enhanced and was unchanged after splenectomy and treatment despite changes in neutrophil counts. Three patients who underwent splenectomy suffered fatal septicaemia. These results suggest that humoral immunity is depressed by treatment in patients who have undergon splenectomy, and the benefits of early accurate staging must be weighed against the likelihood of infective complications.     

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin''s disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin''s disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.     

Gonococcal sensitivity to penicillin in women with gonorrhea relapse and reinfection]

Penicillin sensitivity of gonococci isolated from patients with relapses and reinfection of gonorrhea was studied. The results of the study were compared with those of the sensitivity tests in primary patients. The gonococcal strains with decreased sensitivity to penicillin were isolated from 82 per cent of the gonorrhea relapses, 47.8 per cent of the patients with reinfection and 33.2 per cent of the primary patients. The average sensitivity of the gonococcal strains isolated from the patients with relapses was 0.404 U/ml, while that in the primary patients and the patients with reinfection was 0.136 U/ml. Strains sensitive to 0.6--1.2 U/ml predominated among gonococci with decreased sensitivity in the patients with relapses, while in the primary patients and the ones with reinfection the value amounted to 0.1--0.2 U/ml. The penicillin sensitivity of gonococci may be used as a parameter in differential diagnosis of relapses and reinfection of gonorrhea.     

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.     

Purulent complications in the surgical treatment of patients with mouth cancer and their prevention]

Local purulent complications after surgical operations for mouth cancer were recorded in 49 (61.3 per cent) out of 80 cases and were mainly due to associations of 2 or more pathogens. The analysis of the factors influencing the development of the complications showed that there was no reliable increase in the number of the complications in the patients subjected at the first stage to the treatment with various antitumor agents: 17 (53.1 per cent) events in the group of the patients subjected to radiotherapy in a total focal dose of 40 Gy, 8 (72.7 per cent) events in the group of the patients subjected to radiotherapy in a dose of more than 60 Gy, 13 (59.1 per cent) events in the group of the patients treated with antitumor drugs and 8 (66.7 per cent) events in the group of the patients operated at the first stage of the treatment. The incidence of osteomyelitis was significantly higher in the group of the patients subjected to radiotherapy before the operation: 13 (30.2 per cent) events vs. 2 (5.4 per cent) in the group of the patients not subjected to radiotherapy. With increasing of the radiation dose, the incidence of osteomyelitis as well increased: 8 (25.0 per cent) osteomyelitis events in the group of the patients subjected to radiotherapy in a dose of 40 Gy and 5 (45.5 per cent) events in the group of the patients subjected to radiotherapy in a dose of more than 60 Gy. The method of osteosynthesis of the lower maxilla with titanium miniplates was also of great importance. The use of various schemes for antibiotic prophylaxis of wound infection in such patients was equally efficient.     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS-Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or "posterior" poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in "anterior" poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease. Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results. Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis. Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus. Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent. An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

Adriamycin in the combined chemotherapy of small-cell lung cancer

The results of combined chemotherapy and chemoradiotherapy of 158 patients with small cell lung cancer are presented. Adriamycin was used as one of the components of the induction chemotherapy of 98 out of the 158 patients. Chemoradiotherapy (nitrosomethylurea, methotrexate, CCNU, adriamycin, vincristine, DTIC, radiotherapy) was performed according to 4 schemes and combined chemotherapy (cyclophosphamide, adriamycin, methotrexate, or CCNU, cyclophosphamide, methotrexate plus adriamycin, vincristine, natulan) was performed according to 2 schemes. The total efficacy (complete and partial regression) of the 6 schemes averaged to 80 per cent. The number of patients with complete regression amounted to 29 per cent. Long-term survival for more than 2 years was observed in 17 per cent of the patients. No signs of metastases or relapses for 5 years were recorded in 6 per cent of patients. Adriamycin is one of the most active antitumor drugs in combined chemotherapy and chemoradiotherapy of small cell lung cancer.     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS—Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or “posterior” poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in “anterior” poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease.Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results.Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis.Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus.Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent.An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

Various methods of using lincomycin for treating acute and chronic hematogenic osteomyelitis in children]

Comparative data on the treatment of 209 children with acute and chronic hematogenic osteomyelitis are presented; 128 patients hospitalized before 1974 were treated with antibiotics, mainly penicillin and streptomycin without sensitivity testing. From 1974 81 children were treated with lincomycin; 80 per cent of the isolates were sensitive to this antibiotic. In lincomycin therapy the method of electrophoresis on the disease focus, intrabone administration of the drug and administration of the drug into the bone cavity together with the blood clot during surgical interventions in cases with chronic hematogenic osteomyelitis were used. A marked decrease in the rate of the chronic forms of the disease was registered (from 77.2 to 8.8 per cent).     

Severity of notified whooping cough.

An analysis was made of the severity of over 8000 cases of whooping cough notified from October 1974 to March 1975. Ten per cent of these patients were admitted to hospital and there were 10 deaths. Severity was directly related to age, the disease being most severe in children under 1 year, especially those under 6 months. There was some evidence that previous vaccination reduced the severity of the disease, but the vaccination programme does not cover very young children, and for them whooping cough is a dangerous disease.     

Intensive investigation in management of Hodgkin's disease.

Ninety-eight patients with clinically localised Hodgkin''s disease underwent laparotomy and splenectomy to determine the extent of microscopic spread. In 68 patients the procedure was carried out for untreated disease apparently confined above the diaphragm. Abdominal disease cannot be confidently excluded on the basis of non-invasive investigation at presentation. Clinical assessment of splenic disease was unreliable unless gross splenomegaly was present. Pedal lymphography was accurate in assessing para-aortic and iliac disease but of no value in assessing other intra-abdominal lymph node involvement, including that of the mesenteric lymph node. Trephine bone marrow biopsy findings were normal in all patients before surgery, and only one patient was found to have diseased bone marrow by Stryker-saw biopsy at operation. Liver disease was identified at operation in nine patients, some of whom were asymptomatic with clinically undetectable splenic and nodal disease. Detailed clinical staging failed to detect disease in one-third of patients who underwent laparotomy. These studies show that if radiotherapy is to remain the treatment of choice for disease truly localised to lymph nodes a detailed staging procedure, including laparotomy and splenectomy, remains essential. The value of this potentially curative treatment is considerably diminished in the patient who has been inadequately staged.     

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)