Shusuke Hisano

Eliminating adult T-cell leukaemia cells with ultrasound

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Autopsy Findings in 47 Cases of Adult T-cell Leukemia/Lymphoma in Miyazaki Prefecture, Japan

To identify factors that might improve the prognosis of adult T-cell leukemia/lymphoma (ATL), we reviewed data on 47 autopsied cases of ATL with reference to the complications and cause of death. The primary cause of death was respiratory insufficiency due to pulmonary infection. Respiratory insufficiency was also attributed to the diffuse alveolar damage and pulmonary fibrosis resulting from chemotherapy given and oxygen. About 90% of the cases had infections with one or more pathogens. Cytomegalovirus (CMV) was the most frequent pathogen involved in 35/47 (74.5%) while fungal infections were also commonly seen in 25 of the 47 cases (53.2%). Of these, 17 (70%) had pulmonary aspergillosis. Other neoplasias were present in 10 of the 47 cases, while hypercalcemia was evident in 21 patients. These findings suggest that the prevention and treatment of nosocomial infections and of drug-induced pulmonary toxicity may improve the prognosis and quality of life of ATL patients.

Bone Marrow Findings in Malignant Histiocytosis and/or Malignant Lymphoma with Concurrent Hemophagocytic Syndrome

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. nu lambda and gamma kappa were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients. Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears to be an important factor of profound cytopenia in patients of MH and/or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkins disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.

Sinonasal Malignant Lymphoma of Natural Killer Cell Phenotype Associated with Diffuse Pancreatic Involvement

We report a case of sinonasal lymphoma with a natural killer (NK) phenotype. This 40-year-old man was admitted to our hospital because of left nasal obstruction. Physical examination and computed tomography of the skull revealed a tumor in the left nasal cavity and maxillary sinus. Histopathological examination revealed a diffuse proliferation of pleomorphic lymphoid cells. Imprint cytology showed that tumor cells contained some azurophilic granules, and expressed CD2, CD8, CD16, CD56 and HLA-DR antigens with little expression of other lymphoid or myeloid markers. Southern blot analysis revealed germline configuration for immunoglobulin heavy chain and T-cell receptor genes. These findings indicated that these cells were in fact NK cells. The patients enlarged pancreas was also involved by lymphoma and the pattern of involvement simulated that seen in primary pancreatic lymphoma. Ulcerative colitis (UC) was also present, a rare finding in this disorder.

Detection of pulmonary teleangiectasia using dynamic pulmonary perfusion imaging in patients with liver cirrhosis

Two cases of liver cirrhosis associated with marked hypoxemia are presented. Chest radiographs and cardiopulmonary function showed no abnormalities, except for the low diffusion capacity of carbon monoxide and slight elevation of the shunt ratio (20 and 6.2%, respectively), as estimated under conditions of 100% oxygen inhalation. Pulmonary perfusion imaging with Tc-99m macroaggregated albumin (MAA) revealed a significant radioisotope uptake in the lungs, brain, spleen, and both kidneys. Shunt ratios, estimated by the quantitative radionuclide method, were 60 and 68%, respectively. Dynamic pulmonary perfusion imaging revealed a gradual reduction in uptake in all areas of both lungs. The discrepancy of the shunt ratio between the two methods results from an abnormal dilatation of alveolar capillaries. The gradual reduction of radioactivity In areas of the lungs is caused by the passage of MAA particles through widened pulmonary capillaries.

A randomized phase II trial of low-dose aclarubicin vs very low-dose cytosine arabinoside for treatment of myelodysplastic syndromes

We performed a randomized phase II trial comparing low-dose aclarubicin (LC-ACR) with very low-dose cytosine arabinoside (VLD-AC) in 39 consecutive untreated patients with myelodysplastic syndromes (MDS), including refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t). Nineteen patients received the VLD-AC therapy; 2 good responses (GR) and 2 partial responses (PR) were obtained in 11 patients with RAEB and RAEB-t, while 2 PR were obtained in 8 RA patients. Eighteen patients received the LD-ACR therapy; 2 GR and 4 PR were obtained in 11 RAEB/RAEB-t patients while 2 PR in 7 RA patients. There was no significant difference in the therapeutic effects and survival between these two groups of patients. These observations suggest that the LD-ACR therapy is effective in some patients with MDS and can be used as an alternative to the low-dose Ara-C therapy.

Lactic acidosis complicating adult T-cell leukemia: report of two cases

To the editor: Lactic acidosis is a complication of severe tissue hypoxia in patients with shock, the so-called lactic acidosis type A. Lactic acidosis occurs spontaneously in patients with severe liver disease, uncontrolled diabetes mellitus, and malignant neoplasm, the so-called lactic acidosis type B (1-3). Lactic acidosis is a serious complication of hematopoietic malignancies; about 50 % die of this complication (4, 5). We report on 2 patients with lactic acidosis associated with relapses of ATL, one with the smouldering and the other with the chronic type of ATL. Patient 1, was a 46-year-old male with smouldering ATL; the WBC increased to 147.5 x 109/1 (ATL cells 93.5%) 9 months after disease onset. He developed cyanosis and Kussmaul-like respirations, and became somnolent. Arterial blood gas analysis revealed metabolic acidosis with a pH of 7.197, PO, 82.5 mmHg, PCO, 15.4mmHg, HCO, 5.8 mEq/l, and 0, SAT 92.6%. The serum level of lactic acid rose markedly to 34.4 mEq/l (normal, less than 2.0 mEq/l) and the anion gap was 37.2 mEq/l (normal, less than 12mEq/l). A total of 120mEq of sodium bicarbonate was administered intravenously. Treatment with mitoxantrone 10 mg, and etoposide 100 mg/m2, was started within 120 hours of the onset of acidosis. Blood gas analysis revealed a pH of 7.489, PO, 92.8 mmHg, PCO, 41.4 mmHg, HCO, 3 1.2 mEq/l and 0, SAT 92.8%. The lactic acid level was near normal at 1.6 mEq/l. The ATL cells decreased to 70%, and the hepatobiliary enzymes (T.Bi1. 2.4-0.5 mg/dl, GOT 1784 13 Ujl, GPT 191-+21 U/l and LDH 5832-365 Ujl) returned to the normal range (Table 1). The LA in this case is thus considered to be type B. Patient 2, a 55-yr-old male, was diagnosed as suffering from the chronic type of ATL complicated by liver cirrhosis (LC). He developed disseminated intravascular coagulation (DIC) 7 months after the onset, exhibiting mucosal bleeding and tarry stools. Gabexate (FOY) 2000 mg/day was administered without improvement in the DIC. He developed a generalized rash typical of ATL. The WBC again rose to 25.5 x 109/1 (ATL cells 54.5%). One week later, he suddenly became dyspneic. Arterial blood gas analysis then showed pH 7.18, PO, 82 mmHg, PCO, 12.4 mmHg, and HCO, 4.4 mEq/l, indicating metabolic acidosis. The lactic acid level was 37.7 mEq/l and the anion gap was 35.6 mEq/l. A total of 160 mEq of sodium bicarbonate was administered intravenously to treat the LA. The administration of etoposide (100 mg/m2) was also begun. While bicarbonate temporarily improved the acidosis, the lactate level again rose rapidly, and the patient died 33 hours later. Autopsy revealed widespread infiltration of ATL cells into various organs with LC and DIC. Thus, the acidosis in this case is considered to be a combination of types A and B lactic acidosis. The LA associated with hemopoietic malignancy is generally attributed to circulatory impairment; an increased production of lactate by the tumors, and/or by an impaired metabolism of hepatic lactate (6). Since the normal liver is able to increase the utilization of lactate via gluconeogenesis and oxidation by up to 10-fold (6), an enhanced production of lactate by the tumor also does not explain the marked lacticacideniia. Gary et al. (4) reported that the infiltration of tumor cells into the liver was observed in 25 cases of malignant lymphoma with LA, and noted that the gluconeogenesis of normal liver cells was decreased in those cases. Concerning the LA without tissue anoxia in a leukemia patient, Field et al. considered that the LA was due to the packing of bone marrow with leukemia cells leading to an insufficient supply of oxygen to the cells followed by anaerobic glycolysis (5). Both our patients showed an increase in leukemic cells and hepatopathy. In addition, Case 2 developed LC and DIC. In Case 1, effective chemotherapy induced a decrease of ATL cells and a normalization of the lactate level. In Case 2, it is suggested that the patient’s circulatory status was impaired by DIC. The presence of LC decreased his rate of lactate utilization, and he died. Alkali therapy is generally administered as symptomatic treatment for LA. However, its utility is questionable in the critically ill. Cooper et al. reported that bicarbonate does not improve the hemodynamics of patients who are critically ill with LA (7). Sodium bicarbonate administration has been re-

Hemorrhage from abdominal non-Hodgkin's lymphoma treated successfully by emergency transcatheter arterial embolization.

A 49‐year‐old Japanese woman with follicular lymphoma who presented with severe abdominal and back pain is reported. She was known to have malignant lymphoma and had been previously treated with combination chemotherapy. An abdominal tumor occurring at the root of the mesentery and involving the superior mesenteric artery (SMA) had been diagnosed by computed tomography (CT), magnetic resonance imaging, and abdominal angiography. Emergent ultrasonography and CT findings showed intraperitoneal bleeding from the abdominal tumor. Selective SMA angiography revealed extravasation from a small branch originating from the dorsal pancreatic artery, which was embolized through a catheter by using platinum coils. It should be noted that a large tumor of malignant lymphoma, involving large vessels, may bleed, and in such a case selective transcatheter arterial embolization may be one of the effective modalities for hemostasis.