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Biomedical subjects

C Dittrich

Publications and source records attributed to C Dittrich.

At least 91 records · Page 5Linked to original sources

[Reversible opening of the blood-brain barrier in the chemotherapy of malignant gliomas].

The concept of a blood brain or blood tumour barrier blocking the passage of lipid insoluble cytoreductive drugs from blood into brain-tumor, leads to a protocol of intraarterial injection of high dose methotrexate (MTX) during reversible, osmotic blood brain barrier disruption (BBBD). Malignant Gliomas of grades III and IV in 9 patients and one primary CNS-lymphoma in one patient have been treated in 2 to 5 sessions per patient with BBBD plus polychemotherapy (MTX, cyclophosphamide, procarbazine). Median progression free intervals (PFI) which are still in continuation are 12.2 months. Median PFI which had been terminated by tumour recurrence are 7.75 months.

Antineoplastic Agents↗

[Interferon alpha 2C in the treatment of 2 patients with AIDS-associated Kaposi sarcoma].

Two patients with AIDS and histologically confirmed Kaposi's sarcoma were treated with 3 X 10(6) U/m2 interferon alpha 2C (rIFN alpha 2C) subcutaneously three times a week. In both cases remissions (7 weeks and more than 9 months) of the tumour lesions were achieved and in one case pretherapeutic moderate thrombocytopenia improved. The positive serum antibody titres to HTLV III-virus showed no conversion. Except for fever (below 39 degrees C) during the first two weeks of IFN treatment in both patients, therapy-requiring hypotonia, mild depression, leucopenia (WHO grade 1) and thrombocytopenia (WHO grade 2) in one patient, no side effects were observed. All the above-mentioned features were reversible after termination of treatment. Further studies to optimize the dosage of rIFN alpha 2C and its time schedule in the treatment of Kaposi's sarcoma in patients with AIDS are recommended.

Acquired Immunodeficiency Syndrome↗

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer.

This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n = 22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n = 28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2-54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p less than 0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a "shifting" of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Therapeutic and prognostic results of a prospective multicenter ovarian cancer study of FIGO stages I and II].

Between April 1980 and December 1985 a prospective controlled and randomized multicenter study of 124 assessable patients with stage I and II epithelial ovarian carcinomas was carried out. The aims of this study were first to verify the value of adjuvant irradiation therapy or combined chemo-irradiation therapy, and second to evaluate the importance of different prognostic factors such as age, histology, tumor grading, and tumor stage. Patients with well-differentiated stage IA tumors did not receive any therapy; patients with undifferentiated stage IA tumors were randomized to "no therapy" or irradiation therapy; patients with stage IB, IIA, and IIB tumors were treated by either irradiation or a combined chemo-irradiation therapy consisting of Adriamycin/Cyclophosphamide. In patients with stage IC and IIC ovarian carcinomas a combined irradiation-polychemotherapy was instituted, consisting either of Adriamycin/Cyclophosphamide or of Adriamycin/Cisplatin. Because of the low number of patients and the relatively good prognosis no definite evaluation of the individual therapeutic modalities could be done. An analysis of all patients showed that differentiation between stage I and stage II ovarian carcinomas is the single most important prognostic factor. After a mean observation time of 42 months (8-71 months) for stage I tumors a 91% probability of three-year survival was attained, in comparison with 57% for stage II tumors. It has not been definitely established that there is a need for adjuvant therapy for stage I tumors and this should be confirmed by further studies. Because of the unfavorable prognosis for patients with stage II ovarian cancer, these patients should be given the same polychemotherapy, including Cisplatin, as patients with advanced ovarian carcinomas.

Antigens, Neoplasm↗

Coupling of mitoxantrone to poly(I).poly(C) reduces absorption after intraperitoneal administration.

Coupling of mitoxantrone (M), an intercalating cytostatic, to macromolecular polynucleotides may reduce side effects after direct intraperitoneal chemotherapy by interfering with systemic absorption of M. We have administered free M (30 mg/m2) or M mixed with poly(I).poly(C) (90 mg/m2) intraperitoneally to 5 patients with peritoneal carcinosis (cross-over study): peak plasma levels (HPLC assay) were 62 +/- 12 versus 28 +/- 4 ng/ml (p less than 0.0025), AUC0-24h were 583 +/- 126 versus 481 +/- 57 ng X h/ml (p less than 0.025). Coupling of M to poly(I).poly(C) seems to reduce M absorption after intraperitoneal administration.

Absorption↗

[Adjuvant chemotherapy in patients with radical resection of stomach cancer: 5-year results of a prospective randomized study].

102 patients with operable gastric carcinoma were randomly allocated to untreated control, polychemotherapy, chemoimmunotherapy. At a median follow-up of 5 years, chemotherapy did not improve the overall survival rate. However, in certain subgroups, patients with lymphnode metastases and intestinal tumor type showed a significant survival benefit when treated with adjuvant chemotherapy. Furthermore, we found the site of first recurrence very closely related to the type of tumor histology. Regardless of the positive effect of chemotherapy in retrospective subset-analysis, we do not generally recommend the use of polychemotherapy in operable gastric carcinoma.

Aged↗

[Current status of interferon therapy].

Interferons (IFN) are potent antiviral, cytostatic-cytotoxic and immunomodulatory agents. Although gene technology has made available an unlimited supply of all different kinds and types of IFN, their basic modes of action have not been clarified up to now. The therapeutic effects proven differ gradually between the individual disease entities. They comprise prophylaxis, prevention of recurrences and direct therapeutic effect, either of reducing the actual disease symptoms, or of inducing a complete recovery. For the following viral diseases a positive therapeutic effect has been shown: infections by herpes-viruses (herpes simplex keratitis , herpes zoster, herpes simplex), cytomegalovirus infections, chronic-hepatitis B virus infection, acute respiratory virus infections by rhino-, corona- and influenza viruses. Especially for the group of virus-associated tumors and papillomas, IFN is considered to be therapeutically effective. IFN has been accepted to be the first line treatment for laryngeal papillomatosis. In condylomata acuminata too, IFN is a potent therapeutic agent. Moreover, IFN represents the most effective therapeutic modality for Kaposi's sarcoma in patient with AIDS. Hairy cell leukemia, malignant lymphoma, multiple myeloma, melanoma and hypernephroma are the malignancies, for which a therapeutic effect of IFN could be proven. Furthermore, IFN is considered to be the therapy of first choice for hairy cell leukemias. Although there are some signs, that IFN could be a potent agent for adjuvant therapy, this question can not be answered - not even on principle - because of lacking sufficient data so far. Up to date, the therapeutic efficacy of IFN seems to be established only for hairy cell leukemia, laryngeal papillomatosis, Kaposi's sarcoma in patients with AIDS and partly for condylomata acuminata. For all other indications, first of all, sufficient phase-II-study data will have to be evaluated, before prospectively controlled studies, comparing the IFN treatment results with placebo and standard therapy results, can be initiated for the individual disease entities. Then, it will be possible to assess the therapeutic efficacy of IFN. Already now, IFN represent a valuable enrichment of the therapeutic modalities for malignancies and viral diseases.

Acquired Immunodeficiency Syndrome↗

Assessment of the human tumor cloning assay for urologic malignancies with special emphasis on bladder cancer.

Specimens of different urologic malignancies such as cancer of the bladder, renal pelvis, prostate, testis and renal cell carcinomas were sent to our laboratory for cultivation with the clonogenic assay. Of the 62 samples--biopsies, bladder barbotages and effusions--48% were considered to be evaluable; the others had to be excluded from evaluation because of negative histologic/cytologic findings, insufficient cell viability, inadequate tumor material, or contamination. All test procedures were done using a slightly modified human tumor cloning assay originally described by Hamburger and Salmon [Science 197: 461-463, 1977]. Overall growth was seen in about one third of all tumors cultivated; the mean colony count being 13 +/- 8, the mean cloning efficiency 0.0026%. About one third of bladder cancer specimens and half of the renal cell carcinomas showed colony growth. No correlation between tumor stage or grade and the overall colony growth rate in vitro was seen. Furthermore, it was impossible to correlate the growth rate in vitro and the overall survival of the patients included in the study.

Biopsy↗

Blood brain barrier modification and chemotherapy. Interventional neuroradiology in the treatment of malignant gliomas.

Postoperative interventional neuroradiology was performed in patients with malignant gliomas to increase target efficacy of chemotherapy. In 8 glioma patients the blood brain or blood tumor barrier was reversibly opened by intraarterial injection of hyperosmolar fluid (Mannitol 25%). One additional patient had primary lymphoma of the central nervous system. During barrier modification chemotherapeutic agents were applied intraarterially and intravenously. A total of 22 blood brain barrier modification procedures have been carried out until now, ranging from one to five per patient. A presently continuing tumor regression or tumor progression free intervals have been noted in 5 patients. Therapeutic effects are being evaluated from repeated computed tomography and single photon emission computed tomography examinations.

Adult↗

Monitoring the cytotoxic potential of a sequential polychemotherapy (adriamycin/cisplatin-vincristine/cyclophosphamide-high dose methotrexate) in patients with advanced ovarian cancer with the tumor marker CA-125.

The cytotoxic efficacy of a new sequential chemotherapy, called changing-scheme (adriamycin/cisplatin-vincristine/cyclophosphamide-HD-methotrexate), was investigated parallel to the course of CA-125 serum levels. Sixty-three percent of the women studied achieved remission under this chemotherapy. A correlation between clinically proven tumor stage and CA-125 serum level was found in 90%. The cytotoxic potential of the three single parts of the changing-scheme was demonstrated based on decreasing CA-125 serum levels. The value of the tumor marker CA-125 for the follow-up of patients with malignant ovarian tumors is discussed in detail.

Antigens, Neoplasm↗

[Abdominal computerized tomography in the after-care of ovarian cancers].

The diagnostic capacity of abdominal CT as a follow-up in ovarian cancer is demonstrated on 67 patients verified by a second-look operation. In the diagnosis of recurrence CT has a sensitivity of 83%, a specificity of 94% and an overall accuracy of 88%. With local recurrence or residual tumours CT has an accuracy of 91%, with liver metastases of 94%. The accuracy in finding peritoneal carcinosis is 84%. Ascites proved to be a sure sign of peritoneal carcinosis. Because of its high sensitivity second-look operation can be avoided in case of a positive report. In a negative report a second-look operation will be necessary to verify the success of therapy. In the follow-up of ovarian cancer CT should be performed every 6 month during the first 2 years and yearly for another 3 years.

Female↗

Effect of adjuvant chemo- or immunotherapy on the prognosis of colorectal cancer operated for cure.

After radical surgery for colorectal cancer, 178 patients with a Dukes' B or C tumour were randomly assigned to one of three groups: A, controls (n = 62); B, chemotherapy (n = 59); C, immunotherapy (n = 57). Randomization criteria (age, sex, Dukes' stage, localization of tumour, operative procedure) were evenly distributed throughout the groups. After a median observation time of 30 months, statistical analyses were performed: survival and probability to be free of recurrence was described by Kaplan-Meier estimates of the survival function; for comparison of these survival functions, Breslow's test was used. Overall analyses show no benefit in the treatment group compared to controls. Separate analyses by Dukes' stages showed that in patients with Dukes' C tumours the probability of survival 40 months after surgery was 72 per cent in group C, 51 per cent in group B, and 33 per cent in group A. The differences between groups C and A, and B and A were statistically significant (P less than 0.02 and P less than 0.03 respectively). For a Dukes' C tumour the probability to be free of distant metastases at 30 months after surgery was 80 per cent in group B, 68 per cent in group C and 52 per cent in group A. Also for a Dukes' C tumour the probability to be free of liver metastases at 21 months after surgery was 83 per cent in group B, 81 per cent in group C, and 54 per cent in group A (significant differences: B-A and C-A P less than 0.04 for both). There was no influence on the estimated incidence of local recurrences for stage Dukes' C. Patients with a Dukes' B tumour did not benefit from either of the adjuvant therapy schemes.

Adjuvants, Immunologic↗

The human tumour cloning assay in the management of breast cancer patients.

A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01).

Breast Neoplasms↗

[Results of the first Austrian multicenter ovarian cancer study: prospective randomized comparison of sequential chemotherapy (adriamycin/cisplatin--vincristine/cyclophosphamide--methotrexate) with 2 standard protocols (adriamycin/cyclophosphamide or adriamycin/cisplatin) in stage III and IV patients].

From June 1980 to December 1982 164 patients with ovarian cancer stage III and IV were randomized into the three-legged Austrian Ovarian Cancer Study. A new polychemotherapy, known as the "changing-scheme" (adriamycin/cisplatinum--vincristine/cyclophosphamide--high dose methotrexate), developed in Vienna, was compared with adriamycin/cyclophosphamide and adriamycin/cisplatinum. The risk factors were stratified by means of special computer-assisted randomization. The first study evaluation in 1982 showed a significant advantage for the changing-scheme with regard to recurrence-free interval and survival (Mantel test: p less than 0.01, Breslow test: p less than 0.03). No difference was found between the combinations of adriamycin/cyclophosphamide and adriamycin/cisplatinum. At the second study evaluation in June 1984 the differences previously observed were no longe present to the same significant extent. The changing-scheme continued to be superior for the subgroups of patients with highly differentiated tumors, without ascites, with larger postoperative tumor burden and with liver metastases. The use of this therapy is be recommended for women with advanced ovarian cancer, especially in consideration of the much lower toxicity caused by the less frequent cisplatinum administrations as compared to the adriamycin/cisplatinum combination.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical significance of the tumor marker CA-125 for the preoperative diagnosis and postoperative management of patients with malignant ovarian cancers].

The ovarian carcinoma-associated antigen CA-125 was determined in 144 women with various gynecological tumors (ovarian, breast, uterine), by using the heterologous monoclonal antibody OC-125. In 90% of the malignant ovarian tumors positive CA-125 values were correct, whereas their negative values were correct in 88% of the benign ovarian lesions. In 90% of the 58 patients with malignant tumors, where it was possible to observe tumor marker concentrations as well as the simultaneous tumor behaviour, a good correlation was found. Therefore, CA-125 serum determinations seem to be useful in the preoperative assessment of the importance of palpable ovarian tumors, as a parameter for evaluating therapeutic measures, and for early detection of recurrences of ovarian tumors.

Adult↗

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.

Biopsy↗

Carcinoembryonic antigen (CEA) plasma level determination in the management of gastric cancer patients.

Carcinoembryonic antigen (CEA) levels of 161 patients with gastric cancer and of 12 patients with noncarcinomatous diseases of the stomach were retrospectively analyzed. In this study, we examined the correlation between CEA level and histologic type, T and N stage, and the value of the preoperative CEA determination for diagnosis, operability and prognosis for patients with gastric cancer. Summarizing our results: There exist significant higher CEA levels in patients with gastric cancer in comparison with patients with noncarcinomatous disease of the stomach (p less than 0.01), but the absolute CEA titer is not a reliable parameter for the prediction of the existence or absence of gastric cancer for the individual patient. A positive correlation between the CEA level and the histologic type in the subgroup of radically operable patients was found, the intestinal type having lower titers (p less than 0.05). The operability of two different histologic entities (diffuse or intestinal type) was equally high. No conclusion can be drawn from CEA plasma levels concerning the operability of the individual gastric cancer patient; on one hand, 30% of the patients with normal preoperative CEA titers could not be radically operated, whereas 34% of the patients with elevated preoperative CEA titers (greater than 5.0 ng/ml) had radical surgery. Furthermore, the absolute value of the preoperative CEA level does not predict the course of the disease, whereas continuously rising postoperative CEA levels are indicative of tumor progression.

Aged↗

[Plasmapheresis in extra-intestinal manifestations of Crohn's disease].

An assessment was undertaken of the value of plasmapheresis in patients with circulating immune complexes and/or extraintestinal manifestations of Crohn's disease (arthritis, iridocyclitis, erythema nodosum, pyoderma gangrenosum, stomatitis, fever). In 17 patients aged 20 to 50 years (median 34 years) 46 plasmaphereses were performed using a continuous flow-cell separator. Before and after plasmaphereses the concentrations of circulating immune complexes, of complement C4, of the immunoglobulins IgG and IgM and of the proteins alpha-1-antitrypsin, CRP, prealbumin and beta-lipoprotein were determined. 71% of patients given plasmaphereses showed clinical remission of the extraintestinal manifestations and 85% demonstrated a reduction of circulating immune complexes. Clinical follow-up of the patients was documented by the Crohn's Disease Activity Index (CDAI), which was reduced by plasmaphereses to a highly significant degree (p less than 0.005). For patients displaying an acute phase of Crohn's disease with extraintestinal manifestations and/or circulating immune complexes plasmapheresis represents an effective mode of therapy, which, moreover, lacks serious side effects.

Adult↗