Granulocyte-colony stimulating factor-producing myeloma with clinical manifestations mimicking chronic neutrophilic leukemia

A 68-year-old man was diagnosed as having bronchial asthma in November 1996. He presented with leukocytosis in June 2002. The WBC count was 29,900/microliter with 82% mature neutrophils showing toxic granules. The neutrophil alkaline phosphatase score and serum level of vitamin B12 were elevated. Bone marrow demonstrated myeloid hyperplasia and plasmacytosis. Cytogenetic and molecular analyses were negative for Philadelphia chromosome and BCR/ABL fusion gene. Lambda-type Bence-Jones protein was detected on the serum and urinary immunoelectrophoresis. The coexistence of chronic neutrophilic leukemia and myeloma was suspected based on the clinical features. The serum level of granulocyte-colony stimulating factor (G-CSF) was elevated. Immunohistochemically, atypical plasma cells were positive for anti G-CSF antibody. Finally, we diagnosed this patient as having a G-CSF-producing myeloma. Treatment with melphalan and prednisolone was initiated without beneficial response. He was then admitted to our hospital for ROAD therapy (ranimustine, vincristine, melphalan, and dexamethasone). The neutrophil count decreased in parallel with the serum G-CSF level. These observations indicated that the neutrophilia in this case was probably caused by a reactive response to G-CSF secreted from the myeloma cells.     

Reconstruction of bilateral branch pulmonary artery stenosis caused by Takayasu's aortitis.

A 63 year-old female presented with dyspnea on exertion. Her chest X-ray showed cardiomegaly, and right ventricular overload and tricuspid regurgitation were detected. Her pulmonary ventilation and blood flow scintigraphy findings were suspicious of pulmonary vascular disease; the diagnosis was pulmonary hypertension and bilateral branch pulmonary artery stenosis. After the inflammation settled, the stenotic bilateral branch pulmonary artery was reconstructed with a prosthetic vessel and the pulmonary pressure normalized immediately. A resected specimen revealed that the stenotic changes were from Takayasu's disease. The patient's postoperative course was uneventful, and pulmonary ventilation and blood scintigraphy returned to an almost normal range. At follow-up 5 years and 6 months after the operation, there was no evidence of pulmonary artery disease (eg, stenosis and/or ischemia) or of any change in the central vessels of the retina, the so-called Takayasu's retinopathy.     

Strictureplasty for short duodenal stenosis in Crohn's disease

Involvement of the gastroduodenum is extremely rare in Crohn's disease. For obstructing duodenal Crohn's disease, bypass procedures have traditionally been selected. However, more recently, strictureplasty has become an acceptable surgical option. We treated two Crohn's disease patients with short proximal duodenal stenosis, using Finney-type strictureplasty. Their postoperative courses were uneventful and they have remained asymptomatic during follow-up periods of more than 5 years, and 4 months, respectively. Owing to the good clinical results of our two patients, we consider strictureplasty to be indicated for short proximal duodenal stenosis in Crohn's disease. Received: October 14, 1999 / Accepted: February 25, 2000     

Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases

Liver tissue engineering using hepatocyte transplantation has been proposed as an alternative to whole-organ transplantation or liver-directed gene therapy to correct various types of hepatic insufficiency. Hepatocytes are not sustained when transplanted under the kidney capsule of syngeneic mice. However, when we transplanted hepatocytes with the extracellular matrix components extracted from Engelbreth-Holm-Swarm cells, hepatocytes survived for at least 140 days and formed small liver tissues. Liver engineering in hemophilia A mice reconstituted 5% to 10% of normal clotting activity, enough to reduce the bleeding time and have a therapeutic benefit. Conversely, the subcutaneous space did not support the persistent survival of hepatocytes with Engelbreth-Holm-Swarm gel matrix. We hypothesized that establishing a local vascular network at the transplantation site would reduce graft loss. To test this idea, we provided a potent angiogenic agent before hepatocyte transplantation into the subcutaneous space. With this procedure, persistent survival was achieved for the length of the experiment (120 days). To establish that these engineered liver tissues also retained their native regeneration potential in vivo, we induced two different modes of proliferative stimulus to the naive liver and confirmed that hepatocytes within the extrahepatic tissues regenerated with activity similar to that of naive liver. In conclusion, our studies indicate that liver tissues can be engineered and maintained at extrahepatic sites, retain their capacity for regeneration in vivo, and used to successfully treat genetic disorders.