Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy.

In a previous publication (Feldmeier et al., Radiother Oncol 1995; 35:138-144) we reported our success in preventing delayed radiation enteropathy in a murine model by the application of hyperbaric oxygen (HBO2). In this study we introduce a histologic morphometric technique for assessing fibrosis in the submucosa of these same animal specimens and relate this assay to the previous results. The histologic morphometry, like the previous gross morphometry and compliance assays, demonstrates a significant protective effect for HBO2. The present assay is related to the previous assays in a statistically significant fashion. The predictive value for the histologic morphometric assay demonstrates a sensitivity of 75% and a specificity of 62.5%. The applicability of this assay to other organ systems and its potential superiority to the compliance assay are discussed.

Radiation therapy for endometrial cancer in patients treated for postoperative recurrence.

PURPOSE: To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence. MATERIALS AND METHODS: Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months). RESULTS: The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control. CONCLUSION: Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to be developed for this high-risk group of patients.

Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the abdomen and pelvis.

Radiation therapy is often utilized as adjunctive or primary treatment for malignancies of the abdomen and pelvis. Radiation complications are infrequent, but can be life threatening or significantly diminish the quality of life. Radiation necrosis is an approved indication for hyperbaric oxygen (HBO2). Previous publications have reported results in treating delayed radiation injuries involving many sites. This paper reports the experience of a single physician group in treating delayed injuries of the abdomen and/or pelvis. Forty-four such patients have been treated since 1979. Of the 41 patients available for follow up, 26 have healed; 6 failed to heal; and 9 patients had an inadequate course of therapy (fewer than 20 treatments). Especially encouraging was the resolution of fistulae in six of eight patients with only three requiring surgery for closure. Overall, the success rate in patients receiving at least 20 HBO2 treatments was 81%. Hyperbaric oxygen is a useful adjunct in treatment of delayed radiation injuries of the pelvis and abdomen.

Hyperbaric oxygen as an adjunctive treatment for delayed radiation injury of the chest wall: a retrospective review of twenty-three cases.

Since 1979, 23 cases of radiation-induced chest wall necrosis have been treated in the Hyperbaric Medicine Departments of Southwest Texas Methodist Hospital and the Nix Hospital, San Antonio, Texas. Eight cases involved soft tissue only. Six of eight (75%) patients with soft tissue involvement healed without requiring surgical debridement, although four patients (50%) did have flaps or grafts. Fifteen patients had bony and soft tissue necrosis. Eight of these patients (53%) resolved with adjunctive hyperbaric oxygen (HBO), but all required aggressive surgical debridement including skeletal resection. Four (27%) had reconstructive flaps as well. Six patients (40%) with bony necrosis who had either no or incomplete debridement failed to heal. Three patients (13%)(two soft tissue and one bony) were found to have residual tumor during HBO and were discontinued from treatment. HBO is an effective adjunctive therapy for soft tissue chest-wall, radiation-induced necrosis, but must be coupled with appropriate debridement to include surgical removal of all necrotic bone to ensure a successful outcome of bony plus soft tissue necrosis.

Whole abdominal radiotherapy and concomitant 5-fluorouracil as adjuvant therapy in advanced colon cancer.

PURPOSE: This analysis was undertaken to assess whole abdomen radiation therapy and concurrent 5-fluorouracil for toxicity and patterns of failure in high-risk colon cancer patients after curative surgical resection. METHODS: Eighteen patients were treated adjuvantly after curative resection. Four patients (22 percent) had Stage B and 14 (78 percent) had Stage C disease. Histology was poorly differentiated in 4 (22 percent) and moderately differentiated in 14 (78 percent) patients. Four patients received whole abdominal radiation only, 30 Gy at 1 Gy/day. Fourteen patients had an additional locoregional boost of 9.6 to 16 Gy at 1.6 Gy/day. The liver received 19.8 Gy at 0.67 Gy/day. 5-Fluorouracil was given as a continuous infusion during therapy. RESULTS: With a median follow-up of three years, 6 of 18 (33 percent) patients have relapsed. Failure occurred locally in 3 of 18 (17 percent) and distantly in 4 of 18 patients (22 percent). Four of six (67 percent) failures occurred in the liver. The five-year actuarial survival and disease-free survival were 78 percent and 66 percent, respectively. Median elapsed time on radiotherapy was 73 days, with 5 of 18 patients (28 percent) requiring two or more weeks of unplanned treatment breaks. Acute Grade 3 to 4 toxicity (diarrhea, leukopenia) occurred in 3 of 18 patients (17 percent), with late complications (bowel obstruction) occurring in 2 of 18 patients (11 percent). CONCLUSIONS: Whole abdominal radiotherapy with concomitant 5-fluorouracil appears to improve local control but not to prevent liver metastases. Significant toxicity resulted in frequent interruption of therapy and protracted its course. Whether this adjuvant regimen impacts on survival or offers an advantage over locoregional irradiation remains to be studied.

Platelet surface-bound IgG in patients with immune and nonimmune thrombocytopenia.

We quantitated the amount of platelet surface-bound IgG using an 125I monoclonal anti-IgG assay in 149 patients with thrombocytopenia and 260 normal donors. The normal subjects had 122 +/- 5 molecules of IgG/platelet (mean +/- SE). Fifty-five patients with nonimmune thrombocytopenia had 338 +/- 37 molecules of IgG/platelet, whereas 67 patients with immune thrombocytopenia studied at the time of their initial evaluation had 4,120 +/- 494 molecules of IgG/platelet. An analysis of the distribution of values in these two groups indicated that 90% of the patients with immune thrombocytopenia had greater than 800 molecules of IgG/platelet, whereas only 7% of patients with nonimmune thrombocytopenia exceeded this amount. The immune thrombocytopenia patients included 39 idiopathic, 14 secondary, and 14 drug-induced disorders, and they did not significantly differ in their distribution of values for platelet IgG. The nonimmune thrombocytopenic patients included 12 cases with a platelet destructive mechanism; their platelet-bound IgG was similar to that of the other nonimmune patients. Twenty-seven patients with treatment resistant immune thrombocytopenia were also studied they had 2,100 +/- 670 molecules of IgG/platelet. Their values were significantly greater than those of the nonimmune thrombocytopenic patients and not significantly different from those of immune thrombocytopenic group. Their distribution of values was much broader, however, with 33% of patients having less than 800 molecules of IgG/platelet, suggesting possible alternate mechanisms in their thrombocytopenia. Thus, patients with immune thrombocytopenia have a high frequency of elevated IgG on the platelet surface which reflects the pathophysiology of this disorder. Quantitation of platelet-bound IgG provides a useful laboratory tool in the differential between immune and nonimmune thrombocytopenia.

In vitro effects of gammaglobulin (IgG) on human monocyte Fc receptor function. I. Effect on monocyte membrane-associated IgG and Fc receptor-dependent binding of antibody-coated platelets.

Intravenous immunoglobulin (IV IgG) has been reported to be clinically beneficial for the treatment of immune thrombocytopenic purpura (ITP). The mechanism of effect still remains unknown. We examined the in vitro effects of two commercially available IV IgG preparations. Exposure of normal monocytes to IgG in vitro produced a significant increase in monocyte-bound IgG. Prior treatment of the commercial IgG preparations by filtration through a 0.2-micron Millipore filter or ultracentrifugation caused a dramatic decrease in IgG bound to the monocyte surface, indicating that IgG aggregates were responsible for this effect. Exposure of monocytes to IgG levels as high as 150 mg (Sandoglobulin) and 400 mg (Gamimune) did not result in a statistically significant inhibition of monocyte-platelet interaction as examined by a morphologic rosetting assay. Thus, despite the ability of IV IgG preparations to cause substantial increments in monocyte surface IgG, impairment of Fc receptor-mediated monocyte binding of antibody-coated platelets was not observed.

Measurement of platelet surface-bound IgG by a monoclonal 125I-anti-IgG assay.

We have described the use of a monoclonal 125I-labeled anti-IgG (125I-MA) to assay IgG antibody displayed on the surface of platelets from normal and immune thrombocytopenic patients and reported levels of IgG 10-100-fold lower than previous studies. This report describes the immunologic characteristics of the 125I-MA and the assay for surface IgG. The 125I-MA has a high binding affinity for surface-displayed IgG (2.22 X 10(9) M-1), reacts equally well with all four subclasses of IgG and not at all with IgM or IgA. In our assay, the binding of 125I-MA was found to be greater than or equal to 99% specific for IgG (no nonspecific association of 125I-MA with platelets) and the binding ratio of 125I-MA to IgG displayed on the cell surface was 0.91 (close to unity). Finally, platelet lysates were found to contain large amounts of IgG protein (39,597 +/- 27,418 molecules/platelet) as compared to surface-displayed IgG (124 +/- 86 molecules/platelet). This assay has excellent characteristics for quantitation of IgG on platelets and the discrepancy with other techniques may, in part, be due to intentional or inadvertent lysis of platelets during assay conditions.

Immune hemolytic anemia following administration of antithymocyte globulin.

Antithymocyte globulin is commonly used as a therapy for rejection of transplanted organs. Its use can be associated with many side effects. We report a significant hemolytic anemia following therapy with horse-derived antithymocyte globulin. Several commercial Coombs' sera failed to yield a positive Coombs' test with the patient's erythrocytes; however, we were able to detect horse immunoglobulin on the patient's cells as well as on control red cells incubated with this particular preparation of antithymocyte globulin.

Human monocyte interaction with antibody-coated platelets. I. General characteristics.

The interaction of human monocytes with antibody-coated and normal platelets was studied using an assay system that employed rate zonal centrifugation to separate monocyte-associated (bound) platelets from free platelets. At a monocyte:platelet ratio of 1:10, monocytes bound 21.2 +/- 6.6% of antibody-coated platelets and less than 2.2 +/- 1.3% of control platelets. Monocyte binding of antibody-coated platelets was rapid and inhibited by monomeric IgG and staphylococcal protein A. Specific binding was positively related to the number of monocytes present and the amount of IgG displayed on the platelet surface. Transmission and scanning electron micrographs illustrate the membrane binding of antibody-coated platelets to monocytes and suggest that phagocytosis of platelet targets occurs as well. Thus, these observations indicate that monocytes can participate in Fc-receptor binding of anti-PlA1-sensitized platelets. This novel assay may be useful in the analysis of monocyte-macrophage Fc-receptor interaction with platelets sensitized with IgG from both iso- and autoimmune disorders as well as in the characterization of treatment modalities which may alter monocyte Fc-receptor recognition and binding.

Immune thrombocytopenic purpura. Use of a 125I-labeled antihuman IgG monoclonal antibody to quantify platelet-bound IgG.

We used a radiolabeled monoclonal antibody to the Fc portion of human IgG to measure platelet-bound IgG in 54 thrombocytopenic patients and in 48 normal controls. The control group had a mean (+/- 1 S.D.) of 169 +/- 79 IgG molecules bound per platelet--10 to 100 times lower than values generally reported with other assay techniques. Sixteen of 17 patients with untreated thrombocytopenic purpura considered to be of immune origin had values ranging from 790 to 13,095--levels well above those found in normal subjects and in patients with "nonimmune" thrombocytopenia (246 +/- 156). In a second group, consisting of 11 patients with "immune" thrombocytopenic purpura who did not respond to conventional therapy (corticosteroids or splenectomy), the values were quite divergent: two patients had levels in the normal range, three had levels in the range of subjects with nonimmune thrombocytopenia, and six had much higher levels. Measurement of platelet-bound IgG with this monoclonal-antibody technique can help differentiate between immune and nonimmune thrombocytopenias. Low platelet counts in patients who have immune thrombocytopenia according to clinical criteria but are resistant to therapy may be related to factors other than IgG antibody.