Middle meningeal artery embolization for chronic subdural hematoma with cerebrospinal fluid hypovolemia: A report of 2 cases.

BACKGROUND: Chronic subdural hematoma (CSDH) with cerebrospinal fluid hypovolemia syndrome (CHS) remains refractory to standard treatment with hematoma drainage by burr hole and irrigation and/or epidural blood patch. Previously, we reported the utility of middle meningeal artery (MMA) embolization for intractable CSDH. In this study, we present the usefulness of MMA embolization as a treatment for CSDHs with CHSs. CASES: We present two cases of CSDHs with CHSs occurring in patients, 1 treated with burr hole craniotomy and irrigation, and the other treated with the epidural blood patch. Both patients exhibited similar-appearing bilateral relatively-thin hematomas, hyperplasia, and enhanced contrast effects in the dura mater, and extradural hygroma in the cervical portion on enhanced magnetic resonance imaging scans. Also, to reviewing prior literature and imaging findings, they had already undergone conventional treatment. We added MMA embolization treatment and they followed a good course. RESULTS: Despite the known intractable outcomes of patients with CSDHs with CHSs, MMA embolization worked well in the current case series. CONCLUSION: MMA embolization might be considered as a preferred therapeutic option for CSDHs with CHSs in order to buy time before the epidural blood patch starts working.

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients.

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.

The analysis of lymphocyte surface receptors recognized by wheat germ agglutinin for negative regulation of immune responses in cancer patients.

The population of peripheral blood lymphocytes expressing surface receptors for a lectin, wheat germ agglutinin (WGA), which has been shown to recognize the same receptors as the soluble immune suppressor factor (SISF) elaborated from suppressor cells on the lymphocyte surface, was analyzed by using fluorescein isothiocyanate-conjugated WGA on flow cytometry in cancer patients. It was found that the populations of WGA+ lymphocytes in cancer patients were significantly higher than those in either normal volunteers or patients with benign disease and increased with progress of the tumor. The populations decreased after treatment in patients who underwent curative resection of the tumor and in responders of immunochemotherapy but not in those who received non-curative surgery or in non-responders. It was suggested that the increase of receptors for SISF on the lymphocyte surface might play an important role in the negative regulation of immune responses in cancer patients and that WGA might be a useful parameter for immunosuppression.

Interference of the induction of suppressor cells by a streptococcal preparation, OK-432 through the blocking of suppressor inducer T-cells.

The effect of OK-432 on suppressor inducer T cells in the generation of suppressor cells was investigated to determine its mechanism of action as an immunopotentiating agent. Suppressor cell activities induced by sera from patients with advanced cancer (stage III, IV or recurrence) were found to be as high as those induced by Con-A. Suppressor activity induced by Con-A or serum from cancer patients resided in CD8+ T cells, although CD4+ T-cells were required for the induction of suppressor cells. Significant increases in the CD4+2H4+ T cell population after stimulation with either Con-A or sera from the advanced cancer patients were observed when compared with stimulation by normal serum. Stimulation with Con-A induced suppressor cells as well as a significant increase of CD4+2H4+ T-cells. The presence of OK-432 during the generation of suppressor cells, however, significantly reduced the suppressor activity and apparently blocked the increase of CD4+2H4+ T-cells. Thus, it is suggested that OK-432 may interfere with the induction of suppressor cells through the blocking of CD4+2H4+ suppressor inducer T-cells.

[Clinical efficacy of LAK cell adoptive immunotherapy in advanced cancer patients].

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange was investigated as protocol 1 in 24 patients with advanced cancer. For the development of protocol 1, AIT in combination with plasma exchange, OK-432, interleukin-2 (IL-2) and cyclophosphamide was performed as protocol 2, in which LAK cells, OK-432 and IL-2 were administered through the catheter located in the hepatic or bronchial artery. The clinical efficacy of protocol 1 was found in patients with pleural effusion and metastasis to the lung or liver and resulted in 4 partial responses (20%) and 1 minor response of 20 evaluable cases. On the other hand, that of protocol 2 did 1 partial response (20%) in 5 cases. In vitro cytotoxic activity against either Daudi or K 562 tumor cells of peripheral blood lymphocytes from patient given intraaorta administration of OK-432 and IL-2 was tended to increase to be higher than that from nontreated patients. Postoperative immunodepression in esophageal cancer was blocked by AIT, suggesting the usefulness of AIT as a postoperative adjuvant immunotherapy. Thus, target organ of AIT should be limited for better therapeutic effect and the superiority of local AIT in combination with biological response modifiers may be indicated.

[Clinical efficacy of intratumoral administration of BRM in advanced cancer and their mechanism of actions].

The clinical efficacy of intratumoral (IT) administration of BRM in 157 patients with unresectable or recurrent tumors was investigated, and the infiltration of lymphocyte subsets into tumor tissues after IT administration of BRM was immunohistologically examined, to analyse its action mechanism. BRMs used in this study were OK-432, tumor necrosing factor (TNF), whole peptide glucagon (WPG), interferon (IFN)-alpha, IFN-beta, IFN-gamma and interleukin-2 (IL-2). Among them, one hundred thirty-one patients were evaluable for clinical effects, and the therapeutic response rate (CR + PR) was determined in 11/131 (8.4%). Higher therapeutic responses were found in the patients with esophageal cancer, pancreatic cancer and breast cancer, respectively. As for the relationship between the clinical efficacy of IT administration of BRM and the injected sites, the injection into metastatic lesions was more effective than that into the primary or local recurrence. A increase of lymphocyte infiltration after IT BRM immunotherapy and a variety of lymphocyte subsets in tumor tissue injected with any BRMs were found immunohistologically. These results suggest that IT BRM immunotherapy may be effective for the control of tumor growth locally through host-mediated action.

[Surgical stress and immunosuppression in cancer patients].

The immunosuppression caused by surgical stress in cancer therapy may affect the prognosis of patients by enhancing the residual tumors. An investigation of changes of lymphocyte subsets and suppressor cell activity during the postoperative course was performed for the analysis of the immunosuppression caused by the surgical stress in patients with gastrointestinal cancer. In patients undergoing the surgical stress of total gastrectomy or esophageal resection, CD4+2H4- (helper T) and CD8+CD11-(cytotoxic T) cells significantly depressed on day 1 after operation and remained until day 7. In these patients, CD4+2H4+ (suppressor inducer T) cells significantly increased from just after the operation, remained to increase until day 1 after operation and recovered to the preoperative level thereafter. Concanavalin A-induced suppressor cell activity peaked on day 4 and decreased thereafter. However, in patients with benign disease, decreases of helper and cytotoxic T cells were found to a slight degree. The population of lymphocytes with surface receptors for a soluble suppressor factor significantly increased on day 1 after operation in patients receiving esophageal resection and continued to increase until day 30. In patients with preoperative treatment of PSK and cyclophosphamide, the decreases in helper and cytotoxic T cells and the increase in suppressor inducer T cells were significantly blocked during the postoperative course. Thus, these results indicate that extensive surgical stress such as total gastrectomy and esophageal resection may be attributable to the immunosuppression produced by the induction of suppressor cells, and the necessity of pre- and post- operative immunotherapies may be indicated for a better prognosis.

Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK.

The ability of protein-bound polysaccharide (PSK) to block the suppressive activity of soluble suppressor factor (SSF) was investigated. The suppressive activity of SSF derived from U-937 cells on phytohemagglutinin (PHA)-induced lymphocyte proliferative (LP) response was significantly reduced in the presence of PSK. The release of SSF was not inhibited by the treatment of U-937 cells with PSK. The suppressive activity of SSF on LP response to PHA was significantly decreased by the pretreatment of responder lymphocytes with PSK. Studies to determine lymphocyte receptor activity were performed. PSK competed with wheat germ agglutinin (WGA) which recognized the same receptor as SSF on the surface of the lymphocyte. Neither PSK nor serum competed with anti-CD4 monoclonal antibody. Thus, PSK may inhibit SSF-mediated suppression by competing for specific binding sites on the surface of responder lymphocytes.

Role of the spleen in immunosuppression of gastric cancer: predominance of suppressor precursor and suppressor inducer T cells in the recirculating spleen cells.

In order to analyse the role of the spleen on immunosuppression of gastric cancer, T cell phenotypes in the spleen cells (SC) were investigated by two colour fluorescence flow cytometry, with reference to their suppressor cell activity. Suppressor T cell phenotypes of CD4+2H4+ cells (suppressor/inducer T cells) and CD8+CD11+ (suppressor T cells) were distributed predominantly in SCs from patients with gastric cancer, while they were distributed scarcely in those with liver cirrhosis. Moreover, CD4+2H4+ cells and CD8+CD11+ cells were found predominantly in SCs and splenic vein lymphocytes (SVL) respectively. Among SCs, a significantly higher proportion of CD4+2H4+ cells was found in the recirculating SCs, but fewer were found in the residual SCs. Higher activity of Concanavalin-A induced suppressor cells was found in the former and that of spontaneously activated suppressor cells was found in the latter. These results suggest the suppressor precursor and suppressor/inducer T cells might distribute predominantly in the cells recirculating from the spleen, and that suppressor cells might be matured during the migration from the spleen.

The clinical efficacy of intratumoral OK-432 administration in advanced cancer patients.

The clinical efficacy of intratumoral (IT) OK-432 immunotherapy in advanced cancer patients was investigated. Furthermore, the infiltration of lymphocyte subsets into the tumor tissues after the IT administration of OK-432 was also immunohistologically examined in order to analyze the mechanism of action of OK-432 immunotherapy. Forty-four patients with advanced cancer were treated with IT OK-432 immunotherapy. Ten KE (1 mg) of OK-432 was given either daily or on every second day and repeated as often as possible, the mean frequency of OK-432 injections being 18.1 +/- 14.5 times, ranging between 5 and 25 administrations. Thirty-one of the 44 patients were evaluable, 3 of whom (9.7 per cent) developed a partial response and 5 (16.1 per cent) a minor response. Intratumoral OK-432 immunotherapy, however, did not necessarily prolong the survival time. Leu 1, 3 and 7 reactive cells infiltrated into the tumor tissues treated by OK-432 injection, more frequently, when compared with cells which had been treated by recombinant TNF injection. Thus, it was suggested that IT OK-432 immunotherapy might be effective for the local control of tumor growth through the host mediated action, and that, in combination with systemic therapy, may enhance the clinical effects and prolong the survival time in advanced cancer patients.

The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients.

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.