PubMed · 13016087
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V TOSOVSKY. 1952. [Traumatic chylothorax].. https://pubmed.ncbi.nlm.nih.gov/13016087/
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A new class of intact bispecific antibodies shows unmet effector qualities by activation of not only T cells but also simultaneous activation of Fcgamma receptor type I/III+ cells (macrophages, NK-cells and DC). These trifunctional antibodies (trAb) lead to efficient specific killing of targeted tumor cells without any pre- or co-stimulation. This concept was investigated in vivo in patients with malignant ascites in a clinical situation that allowed monitoring of tumor cell elimination and correlation with clinical effects. In a prospective study, 8 patients with malignant ascites due to peritoneal carcinomatosis were treated with intraperitoneal application of trAb, which bound either the EpCAM- or Her2/neu-antigen on tumor cells. Treatment consisted of 4-6 applications within 9-23 days with a total amount of 145-940 microg. Seven of eight patients required no further paracentesis during follow-up or until death with a mean paracentesis-free interval of 38 weeks (median = 21.5, range = 4-136). Tumor cell monitoring showed a complete elimination of tumor cells in ascites already at total doses as low as 40-140 microg. Clinical response with disappearance of ascites accumulation was seen in all patients, which was correlated with elimination of tumor cells (p = 0.0014). Severe adverse events were not observed. Clinically relevant side effects were fever, moderate abdominal pain and skin reactions. Intraperitoneal immunotherapy with trAb showed convincing efficacy in patients with malignant ascites. This treatment offers new therapeutic options for patients with peritoneal carcinomatosis.
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HISTORY AND CLINICAL FINDINGS: A 61-year-old man with dyspnea and diffuse abdominal pain due to increasing ascites caused by liver cirrhosis of unknown etiology was admitted for consideration of transjugular intrahepatic portosystemic stent-shunting (TIPSS). The patient's medical history included paroxysmal nocturnal hemoglobinuria (PNH), presenting as slight hemolysis diagnosed 24 years previously. One year before the patient underwent radical retropubic prostatectomy for a localized prostate cancer. Shortly after this intervention he developed ascites. INVESTIGATIONS: Color Doppler ultrasonography revealed an abnormal flow in the major hepatic veins. Transjugular liver biopsy indicated hepatic a circulatory disorder. Hepatic venography revealed the so-called "spider web" pattern characteristic for the Budd-Chiari syndrome. The hypercoagulable state due to paroxysmal nocturnal hemoglobinuria was accentuated by manipulation on the prostate during prostatectomy and presumably resulted in a thrombotic obstruction of the hepatic veins. TREATMENT AND CLINICAL COURSE: After exclusion of contraindications a transjugular intrahepatic portosystemic stent shunt (TIPSS) was performed, which led to a decrease of portal pressure. Signs of portal hypertension such as esophageal varices and ascites resolved completely. The patient has been free of complaints for one year. CONCLUSION: We assume that a hypercoagulopathy due to asymptomatic paroxysmal nocturnal hemoglobinuria resulted in Budd-Chiari syndrome when boosted by postoperative release of procoagulation factors in the thrombokinase-rich prostate. TIPSS is a therapeutic option in these patients.