Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model.

CONTEXT: Medical ozone therapy is used for treatment of inflammation in alternative and complementary medicine. It has been reported that the beneficial effects of radiotherapy increased with the addition of medical ozone therapy. OBJECTIVES: This study intended to investigate the antitumor and antiedema effects of ozone therapy when applied in different concentrations in mice with peritoneal carcinomatosis (PC) and to evaluate the contribution of medical ozone therapy to the outcomes for radiotherapy in vivo. DESIGN: Ehrlich ascites carcinoma (EAC) cells were inoculated intraperitoneally (IP) to develop peritoneal carcinomatosis in 60 adult male Swiss albino mice. The animals were divided into 5 groups. Groups 1 and 2 were treated IP for a period of 10 d with daily medical ozone therapy. Group 3 received radiotherapy into the abdomen for 5 d. Groups 4 and 5 were treated with medical ozone therapy for 10 d and radiotherapy for 5 d. Groups 1 and 4 received a 20 mg/L concentration of ozone and groups 2 and 5 received a 40 mg/L concentration. A sixth group acted as controls, and serum physiologic was given to them IP. OUTCOME MEASURES: Changes in body weight and abdominal circumference were measured daily for each mouse. Survival rates of the groups of mice were also determined. The results were compared between groups and were statistically analyzed. RESULTS: Changes in body weights and abdominal circumferences in the different groups were statistically different. The longest survival rates were found for groups 3 and 5, and survival rates for the 5 experimental groups were significantly higher than for the control group. CONCLUSIONS: Medical ozone therapy or radiotherapy was found to be effective when administered alone or concurrently to mice with PC, suggesting that medical ozone therapy might serve as a method of obtaining antiedema and antitumor effects, providing a longer survival time.

ACR-ASTRO practice guideline for the performance of therapy with unsealed radiopharmaceutical sources.

This guideline is intended to guide appropriately trained and licensed physicians performing therapy with unsealed radiopharmaceutical sources. Adherence to this guideline should help to maximize the efficacious use of these procedures, maintain safe conditions, and ensure compliance with applicable regulations. The topics dealt with in this guideline include indications for the use of iodine-131, both for the treatment of hyperthyroidism and thyroid carcinoma. In addition, indications for other less common procedures include those for the use of phosphorous-32 in its liquid and colloidal forms, strontium-89, samarium-153, and the use of Y-90 antibodies.

Comparative dosimetric evaluation of nanotargeted (188)Re-(DXR)-liposome for internal radiotherapy.

UNLABELLED: A dosimetric analysis was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) and radiochemotherapeutic drugs [(188)Re-doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as evaluated in mice. METHODS: Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), (188)Re-liposome, and (188)Re-DXR-liposome were obtained for the estimation of absorbed doses in tumors and normal organs. Two colon carcinoma mouse models were employed: subcutaneous growing solid tumor and malignant ascites pervading tumor models. Radiation-dose estimates for normal tissues and tumors were calculated by using the OLINDA/EXM program. An evaluation of a recommended maximum administered activity (MAA) for the nanotargeted drugs was also made. RESULTS: Mean absorbed doses derived from (188)Re-liposome and (188)Re-DXR-liposome in normal tissues were generally similar to those from (188)Re-BMEDA in intraperitoneal and intravenous administration. Tissue-absorbed dose in the liver was 0.24-0.40 and 0.17-0.26 (mGy/MBq) and in red marrow was 0.033-0.050 and 0.038-0.046 (mGy/MBq), respectively, for (188)Re-liposome and (188)Re-DXR-liposome. Tumor-absorbed doses for the nanotargeted (188)Re-liposome and (188)Re-DXR-liposome were higher than those of (188)Re-BMEDA for both routes of administration (4-26-fold). Dose to red marrow defined the recommended MAA. CONCLUSIONS: Our results suggest that radionuclide and chemoradiotherapeutic passive targeting delivery, using nanoliposomes as the carrier, is feasible and promising in systemic-targeted radionuclide therapy.

Repetitive phosphorus-32 peritoneal instillations in a patient with malignant ascites.

During the last decade, intraperitoneal injection of phosphorus-32 chromic phosphate (P-32 CP) has been used principally for its initial intended purpose, the palliative management of malignant ascites. The authors describe a patient with a stage IIIB well-differentiated extraovarian peritoneal serous papillary adenocarcinoma. As a palliative treatment for malignant ascites, P-32 CP was instilled intraabdominally eight times. Adverse effects were limited to the third instillation, when abdominal pain occurred as a result of leakage of the P-32 CP in the subcutaneous tissue. The P-32 CP instillations reduced the frequency of paracentesis for almost 1 year, until disease progression prevented palliation. Considering the few palliative options, there could be more widespread use of P-32 CP as a palliative treatment for patients with malignant ascites caused by ovarian cancer or extraovarian peritoneal adenocarcinoma. However, intraperitoneal P-32 CP is not without potential intestinal complications, which must be considered before it is recommended.

Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia.

OBJECTIVE: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). METHODS: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50-1000) administered at a median of six fractions. Four patients received two to six courses. RESULTS: Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1-23) and 4 were alive at 3, 20, 33, and 57 months after RT. CONCLUSIONS: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief.

Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing 211At-labelled monoclonal antibody MOv18.

The aim of this study was to investigate the therapeutic efficacy of 211At-labelled monoclonal antibody given intraperitoneally to nude mice with intraperitoneal growth of a human ovarian cancer cell line. Female nude mice were inoculated intraperitoneally with 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR 3. After about two weeks they were injected with the 211At-labelled specific monoclonal antibody MOv18 intraperitoneally. For comparison, other groups of mice were given the same labelled antibody intravenously, 211At-labelled unspecific antibody C242 intraperitoneally or unalbelled MOv18 intraperitoneally. Six weeks later the animals were sacrificed and the occurrence of tumour and ascites was determined. When the mice were treated with 211At-labelled MOv18 intraperitoneally 9 out of 10 were apparently free of both ascites and tumour compared to none of the mice given unlabelled antibody. 211At-labelled MOv18 given intravenously or 211At-labelled unspecific antibody given intraperitoneally were less effective. Regional radioimmunotherapy with the alpa-emitter 211Astatine seems to be an effective treatment of nude mice with intraperitoneally growing human ovarian cancer. Hopefully this treatment can be given in an adjuvant setting to women with minimal residual ovarian cancer in the future.

Phase I study of 90Y-labeled B72.3 intraperitoneal administration in patients with ovarian cancer: effect of dose and EDTA coadministration on pharmacokinetics and toxicity.

The tumor-associated glycoprotein 72 (TAG-72) antigen is present on a high percentage of tumor types including ovarian carcinomas. Antibody B72.3 is a murine monoclonal recognizing the surface domain of the TAG-72 antigen and has been widely used in human clinical trials. After our initial encouraging studies (M. G. Rosenblum et al., J. Natl. Cancer Inst., 83: 1629-1636, 1991) of tissue disposition, metabolism, and pharmacokinetics in 9 patients with ovarian cancer, we designed an escalating dose, multi-arm Phase I study of 90Y-labeled B72.3 i.p. administration. In the first arm of the study, patients (3 pts/dose level) received an i.p. infusion of either 2 or 10 mg of B72.3 labeled with either 1, 10, 15, or 25 mCi of 90Y. Pharmacokinetic studies demonstrated that concentrations of 90Y-labeled B72.3 persist in peritoneal fluid with half-lives >24 h after i.p. administration. In addition, 90Y-labeled B72.3 was absorbed rapidly into the plasma with peak levels achieved within 48 h, and levels declined slowly thereafter. Cumulative urinary excretion of the 90Y label was 10-20% of the administered dose which suggests significant whole-body retention of the radiolabel. Biopsy specimens of bone and marrow obtained at 72 h after administration demonstrated significant content of the label in bone (0.015% of the dose/g) with relatively little in marrow (0.005% of the dose/g). The maximal tolerated dose was determined to be 10 mCi because of hematological toxicity and platelet suppression. This typically occurred on the 29th day after administration and was thought to be a consequence of the irradiation of the marrow from the bony deposition of the radiolabel. In an effort to suppress the bone uptake of 90Y, patients were treated with a continuous i.v. infusion of EDTA (25 mg/kg/12 h x 6) infused immediately before i.p. administration of the radiolabeled antibody. Patients (3 pts/dose level) were treated with doses of 10, 15, 20, 25, 30, 35, 40, or 45 mCi of 90Y-labeled B72.3 for a total of 38 patients. EDTA administration resulted in significant myeloprotection, which allowed escalation to the maximal tolerated dose of 40 mCi. Dose-limiting toxicity was thrombocytopenia and neutropenia. Studies of plasma and peritoneal fluid pharmacokinetics demonstrate no changes compared with patients without EDTA pretreatment. Cumulative urinary excretion of the radiolabel was not increased in patients pretreated with EDTA compared with the untreated group. However, analysis of biopsy specimens of bone and marrow demonstrated that bone and marrow content of the 90Y label was 15-fold lower (<0.001% injected dose/g) than a companion group without EDTA. Four responses were noted in patients who received 15-30 mCi of 90Y-labeled B72.3 with response durations of 1-12 months. These results demonstrate the myeloprotective ability of EDTA, which allows safe i.p. administration of higher doses of 90Y-labeled B72.3 and, therefore, clearly warrant an expanded Phase II trial in patients with minimal residual disease after standard chemotherapy or for the palliation of refractory ascites.

[Meigs syndrome with bilateral hydrothorax]. / Sindrome di Meigs con idrotorace bilaterale.

The co-existence of pelvic tumor, hydrothorax and ascites has been known since the last century. The features of this disease were described by Meigs and Cass in 1937; in the same year Roads named it Meigs syndrome. According to the original description this syndrome only included, as pelvic involvement, an ovarian neoplasm; at present it is accepted that hydrothorax and the ascites can also be associated with a uterine tumor, like a fibroma. The existence of either an ovarian or a uterine neoplasm distinguishes the typical Meigs syndrome from a pseudo-Meigs syndrome. The most likely pathogenesis of Meigs syndrome ascribes the formation of the peritoneal and pleural effusion to the filtration of interstitial fluid in the peritoneum through the tumor capsule, and the diffusion to the pleural space, generally at the right side, through the diaphragm lymphatic vessels and the foramen of Bochdalek. Dockerty reported that at least 40% of ovarian tumors had a diameter of more than 6 cm when associated with hydrothorax and ascites. The entity of pleural and peritoneal effusion can be moderate or massive. The effusions generally derive from a transudative process, but they can occasionally contain blood cells. The connection between the pelvic tumor and the effusion is demonstrated by the regression of the latter when the neoplasm is excised. When the pelvic tumor has an ovarian location it derives from the connective tissue of the hilus, it appears during fertile age and has a slow growth, the clinical signs becoming evident in elder age.

Time-gated fluorescence spectroscopy of porphyrin derivatives and aluminium phthalocyanine incorporated in vivo in a murine ascitic tumour model.

The effect of systemic administration on drug uptake at cellular level was evaluated using time-gated fluorescence spectroscopy performed on a murine ascitic tumour model. Mice bearing L1210 leukaemia were injected intraperitoneally or intravenously with 25 mg per kg body weight hematoporphyrin derivative (HpD), 12.5 mg per kg body weight photofrin II (PII), 25 or 5 mg per kg body weight disulphonated aluminium phthalocyanine (AlS2Pc). Every 2 h and for up to 22 or 30 h, mice were sacrificed, leukaemic cells extracted from the peritoneum, washed, and resuspended in buffer for fluorescence measurements. HpD and PII emission spectra were almost identical 12 h after intraperitoneal injection with main peaks at 630 nm and no appreciable changes afterwards. In the first 12 h, the PII fluorescence spectrum was constant, while in the case of HpD a shoulder at 615 nm was detectable. Similar fluorescence behaviour was observed after intravenous administration of porphyrin derivatives. These results seem to confirm that the tumour localizing fraction is the part actually retained by the cells. The AlS2Pc spectrum peaked at 685 nm and did not change in any of our experiments. AlS2Pc is incorporated more rapidly with respect to porphyrins, as was clearly observed in the case of intravenous administration, where the AlS2Pc fluorescence was readily detectable after 2 h, whereas the PII emission became apparent only after 4-6 h.

Resolution of pancreatic ascites after low-dose radiation.

We have reported a case of pancreatic ascites that responded to low-dose radiation. Our review of the literature and of the limitations of various treatment methods available suggests that low-dose radiation may have a role in the treatment of patients who are at high risk for surgery.

Whole-abdominal irradiation for the management of gastrointestinal and abdominal manifestations of agnogenic myeloid metaplasia.

A patient with a long-standing history of agnogenic myeloid metaplasia developed weight loss and ascites secondary to gastric/small bowel infiltration and peritoneal implants of myeloid tissue. Moderate doses of radiation were very effective in controlling her gastrointestinal symptoms. In contrast to previous reports, clinical improvement after irradiation was a slow, gradual process, requiring 5 months for complete resolution of the patient's ascites. Hematologic suppression may be profound and careful attention to the rate of change in leukocyte and platelet counts is necessary to avoid severe toxicity.

[The analgesic and resorptive laser therapy of wound infiltrates, seromas and hematomas in episiorrhaphy and perineorrhaphy]. / Analgetichna i rezorbtsionna lazer-terapiia na ranevi infiltrati, seromi i khematomi pri epiziorafii i perineorafii.

The therapeutic effects of helium-neon laser irradiation with density of power (DP) of 100, 90, 80, 70 and 50 mW/cm2 were studied on 126 parturients in respect to occurring analgetic and resorptive action on wound infiltrates, seromas and hematomas after episiorrhaphies and perineorrhaphies. The scanning was made by shifting the laser spot on wound edges and the located around them infiltrates, seromas and hematomas with exposition time of the field of 1.5 min. The most manifested analgetic and resorptive effect of the described early wound complications was achieved by DP of laser irradiation within the range of 100-70 mW/cm2. The density of power of helium-neon laser irradiation of 50 mW/cm2 was slightly effective.

Malignant ascites: review of the literature, and an update on monoclonal antibody-targeted therapy.

Malignant ascites presents a difficult clinical problem, causing discomfort and distress to patients in the later stages of disease. Repeated attempts at palliation are often unsuccessful. In this article, conventional forms of therapy for malignant ascites are reviewed and their limitations outlined. Furthermore, we present data on a new form of therapy: antibody guided irradiation. Pilot studies have produced encouraging results in the management of malignant serous effusions, and further randomised studies are currently in progress.

[Laser therapy of wound infiltrates, seromas and hematomas following gynecologic operations. Clinical research]. / Lazerterapiia na ranevi infiltrati, seromi i khematomi sled ginekologichni operatsii. Klinichni prouchvaniia.

The therapeutic possibilities of helium-neon laser light with densities of power (DP)-100, 90, 80, 70 and mW/cm2 as well as exposition time of the field of 1.5 min were studied in 109 women with skin subcutaneously located wound infiltrates, seromas and hematomas after gynecological operations. Clinical observations were carried out on 32 women with more deeply located (epifascial) infiltrates, irradiated by DP of laser light (LL) of 100 mW/cm2. The initial resorption of inflammatory tissue changes and analgetic effect was established even after 1-3 irradiations with DP of 100,90 and 80 mW/cm2. The final resorption of postoperative wound complications and healing of complicated operative wounds was achieved after irradiation with LL of 100, 90, 80 and 70 mW/cm2 for the shortest intervals (1-3 and 4-6 days). The investigated DP of LL of 50 mW/cm2 was not sufficiently effective for resorption and healing of wound skin and subcutaneously located infiltrations, seromas and hematomas. Resorption of epifascial wound infiltrations by DP of 100 mW/cm2 was not achieved.

The treatment of intraperitoneal malignant disease with monoclonal antibody guided 131I radiotherapy.

Seven patients with small volume ovarian carcinoma, remaining after conventional therapy with surgery and a platinum containing chemotherapy regimen, were treated with intraperitoneal monoclonal antibody guided radiotherapy. 100 mCi131I conjugated to 10 mg of monoclonal antibody were injected i.p. in 2,000 ml peritoneal dialysis fluid. Patients were evaluated 3 months later; 3 had clinical progressive disease while third look laparotomy demonstrated progressive disease in 3 of the remaining 4 patients. The seventh patient did not have a third look laparotomy and is currently inevaluable for response. Five patients with recurrent malignant ascites not controlled by diuretics or repeated paracentesis were similarly treated with 75-170 mCi131I conjugated to 10 mg monoclonal antibody. In three patients the ascites was controlled for a mean of 4 months. One patient died too early to assess the control of his ascites but tumour cells disappeared from the ascitic fluid after therapy. In the patient whose ascites were not controlled, a subpopulation of antigen-negative tumour cells was demonstrated. This study was unable to demonstrate a therapeutic benefit for i.p. injected monoclonal antibody guided radiotherapy for solid intraperitoneal tumour but suggests that it may be capable of controlling the accumulation of antigen positive malignant ascites.

Antibody-guided irradiation of malignant ascites in ovarian cancer: a new therapeutic method possessing specificity against cancer cells.

Immunocytology of ascitic fluid of a patient with ovarian cancer demonstrated reactivity with two tumor-associated monoclonal antibodies, AUA1 and HMFG2. AUA1 radiolabeled with 48.6 mCi 131I was given intraperitoneally. There was a reduction in the rate of reaccumulation of ascites. Cytology of recurrent ascites revealed reactivity with antibody HMFG2 but not AUA1. The patient was further treated intraperitoneally with 39.0 mCi 131I-labeled HMFG2. There has been no reaccumulation of ascites. It is concluded that antibody-guided irradiation may be an effective treatment of malignant ascites secondary to ovarian cancer. Furthermore, this case illustrates the specificity of antibody interactions in the mediation of therapeutic effect and the possibility of tumor selection after irradiation with a single monoclonal antibody. If specificity plays a role, all major specificities should be covered by an appropriate panel of radioactively labeled antibodies. It is recommended that for comprehensive therapy of malignant ascites secondary to ovarian cancer, a mixture of antibodies such as HMFG2 and AUA1 should be used.

Complete response of granulosa cell tumor metastatic to liver after hepatic irradiation: a case report.

A case of granulosa cell tumor of the ovary with extensive metastases to the liver was treated by a course of fractionated hepatic irradiation consisting of 30.00 Gray delivered to the whole liver, followed by boost to gross disease for a total dose of 50.00 Gray given in six weeks. This was followed by complete tumor response with normal liver function tests, and computed tomography demonstrated a normal liver two years after radiotherapy. Liver metastases from granulosa cell tumor of the ovary are unusual, and little information has been published regarding management of this problem.

Suppression of hepatic hematopoiesis with radioactive gold (198Au).

A patient with idiopathic myelofibrosis of some 20 yr duration developed esophageal varices and ascites. No explanation for increased portal pressure other than hepatic hematopoiesis was found. Consequently, a trial of cobalt irradiation to the liver was undertaken with definite but transient decrease in ascites. Subsequently, two courses of radioactive colloidal gold were given, again with definite but transient beneficial effects on the degree of ascites. This latter benefit occurred without suppression of marrow function.

Radioactivity in blood and urine following intraperitoneal instillation of chromic phosphate in patients with and without ascites.

Systemic distribution of radioactive colloidal chromic phosphate P 32 after intraperitoneal instillation was studied in 10 patients with ovarian or endometrial malignancies. Seven patients without ascites received chromic phosphate P 32 for positive peritoneal washings, rupture of the capsule of the cyst during operation, or minimal Stage III disease. Three patients received chromic phosphate P 32 for recurrent ascites after multiple abdominal paracenteses. Blood and urine radioactivity measurements were performed at selected intervals. There was a clear statistically significant difference (p less than 0.01) between chromic phosphate P 32 activity levels in whole blood, red blood cells, and plasma in patients with and without ascites.