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We report a gastric cancer patient with positive peritoneal lavage cytology (CY1) who achieved 20-month progression free survival by S-1 monotherapy. An 82-year-old male patient who underwent distal gastrectomy with residual disease for type 4 scirrhous gastric cancer manifesting pyloric stenosis, direct invasion to the pancreas, and CY1. He received S-1 monotherapy postoperatively. His ECOG performance status (PS) was 0. The initial treatment schedule was 100mg/day, twice daily for 4 weeks with a 2-week rest, repeated every 6 weeks. Grade 2 thrombocytopenia at the end of the 5th course of treatment required discontinuation of one course of treatment, and subsequent treatment was continued with a dose reduction to 80mg/day. Afterwards, although treatment was temporarily postponed for 2 weeks, the dose modification enabled him to receive S-1 for 20 months, leading to a relative dose intensity of 81%. There was no evidence of disease progression. The most severe adverse events were transient grade 3 neutropenia as well as leukocytopenia, anemia, and thrombocytopenia, grade 2 each, without gastrointestinal toxicities. His PS was not deteriorated. Although survivalrates of CY1 gastric cancer patients are still poor, our case suggests that S-1 monotherapy is effective against CY1, even for patients aged over 80, if the relative dose intensity is maintained by comprehensive patient management and appropriate dose modification.

The radical treatment of gastric cancer is complete resection of the tumor by surgery. For advanced gastric cancer, a multidisciplinary approach has been attempted to improve patient prognosis. Potentially resectable and curable advanced gastric cancer is treated with routine surgery, followed by postoperative adjuvant chemotherapy. For highly advanced gastric cancer, extended radical surgery or preoperative adjuvant chemotherapy have been attempted. Laparoscopic gastrectomy for advanced gastric cancer has not been widely used because of the difficult surgical technique involved, but enhanced magnification in the surgical field is expected to improve the accuracy of the lymph node dissection procedure. In future, the significance of currently available treatments should be investigated. The key treatment for advanced gastric cancer at present is surgery.

We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient with Waldenström's macroglobulinemia, and case 2 is a patient with marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjögren's syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with rituximab monotherapy, developed serum sickness between 9 and 17 days after the first rituximab infusion, developed fever and arthralgia, and improved soon after corticosteroid treatment. Serum sickness after rituximab treatment for hematological malignancies is very rare as far as we know. We identified three risk factors of serum sickness after rituximab infusion from previous reports and our cases; administration of rituximab alone, the existence of Sjögren's syndrome, and polyclonal hypergammaglobulinemia.

Prostate specific antigen (PSA) failure occurs in 20% to 50% of patients who undergo radical prostatectomy. There is no consensus on how PSA failure should be managed. Recently, salvage radiotherapy is reported to be an effective treatment for PSA failure, and 20%-70% of cases are recurrence-free. The aim of salvage radiotherapy is a cure and this is quite different from other options, for example, endocrine therapy. Salvage radiotherapy is likely to become more important as a treatment for PSA failure after radical prostatectomy.

Platelet activation causes a change in surface expression of several endogenous proteins, such as CD62P, CD63 and CD40L. Therefore, it is possible to analyze the functional in vivo status of the circulating platelet population directly by flow cytometry. In this study we developed the method to be suitable for use in clinical studies. We used EDTA-2K as anticoagulant since the sample anticoagulated with EDTA-2K, sodium citrate or ACD-A showed no difference in the data of activated platelets. We determined whether fixation of sample is necessary. The samples stained before or without fixation showed abnormally high level of activated platelets, indicating that fixation is necessary before staining. It is controversial whether activated platelets circulate in patients with idiopathic thrombocytopenic purpura(ITP). We measured activated platelets in patients with ITP using our optimised method. The percentages of CD62P, CD63 and CD40L positive platelets were significantly high in patients with ITP and 24%, 55% and 36% (respectively) of ITP patients showed elevated level of activated platelets. These data indicate that activated platelets circulate in ITP patients.

We report here a case of sclerosing Sertoli cell tumor of the testis. A 21-year-old male, who complained of right testicular pain, visited a Jikei University affiliated hospital on May 30th, 1999. A small nodule with a diameter of 6 to 7 mm was palpable on the central surface of the right testis. No tumor markers for testicular cancer, such as hCG-beta and alfa-fetoprotein, were elevated. However, ultrasound revealed a hypoechoic mass with increased blood flow. Therefore, we performed right high orchiectomy under the diagnosis of right testicular cancer. Pathological diagnosis of this tumor was sclerosing Sertoli cell tumor. Neither recurrence nor metastasis has been found for 12 months postoperatively.

A 24-year-old woman was followed for about ten months with oral administration of prednisolone (22.5-35 mg/d) for autoimmune hepatitis. In June 1995, she noticed fatigue and appetite loss and blood chemistry revealed markedly deteriorated liver function. She was admitted to our hospital. The daily dose of prednisolone was increased to 60 mg. Her elevated levels of transaminases decreased gradually. Administration of azathioprine (100 mg/d) was started with tapering of prednisolone on August 18th. Ten days later, tender cervical lymphadenopathy and high fever occurred. Azathioprine administration was stopped immediately and intravenous antibiotics were given. On September 5th, 50 mg of azathioprine was administered again. Two hours later, the patient complained of intolerable pain from the lumbar region to the knee joints, which subsided following two injections of analgesics within a few hours. However, chills, high fever and hypotension (86/30 mmHg) subsequently developed. No bacterial growth was detected in blood culture. She was discharged on September 12th. On October 4th, she visited our out-patient clinic. The next day, she took one tablet (50 mg) of azathioprine at 10 o'clock. She noted intense pain from the thighs to the knees and calves around noon again. Her home doctor found that she exhibited shock (BP 67/?). She was immediately taken to our department. The same symptoms and signs as the above-mentioned occurred. Azathioprine was considered responsible for these two adverse reactions (shock) as an allergen. Later, systemic lupus eythematosus was diagnosed in 1996. And she died to pulmonary hypertension in May 1999. Physicians should be aware of the potential adverse effect of azathioprine administered in order to manage the patients with autoimmune disorders.

We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count > 500/microliter and a platelet count > 20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

We report on two adult T-cell leukemia (ATL) patients whose levels of serum hyaluronic acid (HA) moved in parallel with the clinical activity of their disease. A 66-year-old man was admitted to our hospital because of unconsciousness and hypotension. Acute type ATL complicated by hypercalcemia and myelofibrosis was diagnosed. Before therapy, the level of patient's serum HA was 2,045 to 4,010 ng/ml (normal range: 50 >). After he achieved complete remission (CR) through chemotherapy, his serum HA was 36 ng/ml. Several months later, however, his ATL relapsed, and his serum HA increased to 393 ng/ml. The other patient was an 80-year-old man who had been admitted on the suspected diagnosis of ATL. Before chemotherapy, his serum HA was high (3,420 ng/ml). After CHOP therapy, he entered CR and his HA decreased to 122 ng/ml. He remains in CR with slightly elevated levels of HA (127 to 212 ng/ml), and is being followed up on an out-patient basis.

Thirty patients (median age of 32 years; range, 6-61) with hematologic disorders received unmanipulated peripheral blood stem cell transplants from HLA-matched or one-antigen-mismatched related donors following myeloablative therapy for acute lymphoblastic leukemia (7), acute myelogenous leukemia (6), chronic myelogenous leukemia (8), myelodysplastic syndrome (3), or other disorders (6). Granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells were collected from donors in 1 to 3 aphereses. The apheresis products contained mean counts of 11.3 x 10(8) (range, 3.8-17.2) nucleated cells/kg and 6.7 x 10(6) (range, 1.3-16.7) CD34+ cells/kg. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporin A plus methotrexate, or FK506 plus methotrexate. All patients received G-CSF following their transplant. Although 1 patient died of pneumonia 6 days after transplantation, the others demonstrated rapid engraftment. Median days to recovery to 500/microliter neutrophils and 20,000/microliter platelets were 13 (range, 8-21) and 14 (range, 1-23) days, respectively. The incidence of acute GVHD grade II-IV was 33%; chronic GVHD developed in 57% of the assessable patients. There were no episodes of graft failure or rejection. Nineteen patients (63%) were alive and in complete remission from 147 to 839 days following their transplant (median follow-up of 560 days). Further follow-up study will be required to assess the incidence of chronic GVHD and graft-versus-leukemia (GVL) effects.

We report a 82-year-old woman with adult onset Still's disease (AOSD), who presented with high fever, skin rash, swollen axillary lymph nodes, accelerated erythrocyte sedimentation rate, leukocytosis, abnormal liver function tests, hypoalbuminemia, negative antinuclear antibody and rheumatoid factor, and lack of renal involvement. Disseminated intravascular coagulation (DIC) was also diagnosed on admission. An antipyretic relieved high fever and DIC soon improved. Three years later, AOSD relapsed accompanied by hypercoagulation and hyperfibrinolysis. The patient developed subdural hematoma and DIC due to a brain contusion. High titers of serum soluble adhesion molecules and soluble thrombomodulin were noted on the first episode of DIC. These findings indicated that endothelial cells were damaged in AOSD complicated by DIC.

Nonhemolytic transfusion reactions, especially urticaria and anaphylactoid reaction, are believed to be due to plasma protein antigen in the blood products. We have investigated the frequency of transfusion reactions in 59 administrated patients who were interviewed after transfusion. 79(21.5%) of 367 transfusions were associated with transfusion reactions. Transfusion reactions were urticaria (41%), itching (34%) and fever (17%), and no hemolytic transfusion reaction, transfusion-associated graft-versus-host disease or anaphylactoid reaction was observed. We investigated the relationship between the nonhemolytic transfusion reactions and anti-C2,-C4, -albumin and -fibrinogen antibodies. The significant relationship between anti-C2 and -C4 antibodies, but not anti-albumin and -fibrinogen antibodies, were observed with transfusion reactions, especially with urticaria and itching.

Using a panel of phospholipid(PL) antigens, we have established an enzyme linked immunosorbent assay (ELISA) for measuring both IgG and IgM type anti-phospholipid antibodies (APA) in sera from patients with systemic lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP) and recurrent fetal abortion (RFA). The percentage of anticardiolipin antibody (aCL) positive patients was increased in SLE (73% for IgG, 74% for IgM), ITP (24% for IgG, 8% for IgM) and RFA (20% for IgG, 52% for IgM) as compared with normal controls. The percentage of other APAs in each disease was significantly different from one another, suggesting the existence of disease-specific APA in these autoimmune disorders. We consider that it is important to analyze these APAs for the investigation of pathogenesis of autoimmune disorders.

We examined anti-neutrophil antibodies in 12 patients with various disorders using enzyme-linked immunosorbent assay (ELISA), and the results obtained by ELISA were compared with those obtained by leukocyte agglutination test (LAT) and granulocyte cytotoxicity test (GCT). IgG anti-neutrophil antibody was positive in 7 of 12 patients, and IgM type antibody was positive in 6 patients. There was a significant correlation between IgG and IgM anti-neutrophil antibodies. The results obtained by ELISA were not in accord with those obtained by LAT or GCT. In addition, we examined anti-neutrophil antibodies in serially collected serum samples from two patients with immune neutropenia. The results obtained by ELISA correlated with their neutrophil counts, suggesting that anti-neutrophil antibodies detected by ELISA have pathological relevance.

A 45-year-old woman with Bence-Jones type multiple myeloma was treated with natural type alpha-interferon (Namalwa interferon), 3 million IU every other day subcutaneously. After about 5 months, she developed hemolytic anemia. However, screening tests for autoantibodies, including direct and indirect antiglobulin (Coombs' tests), were negative. This report is the first case in which hemolytic anemia appeared to be caused by natural type alpha-interferon. It is likely that interferons will be used in treating increasing numbers of patients and that more patients will develop this complication.

Dr Kira et al. (Lancet 1991, 338: 64-65) stress the high incidence of the co-infection with HTLV-I and HTLV-II in the HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) detected by a polymerase chain reaction (PCR). They showed that 67% of HAM/TSP patients and 6% of healthy carriers had the co-infection. They suggested the co-infection might be important for the development of the myelopathy. Recently, we have analyzed the seropositivity of antibodies to HTLV-I and II in Adult T-cell Leukemia (ATL), HAM/TSP and carriers in Japan using SELECT-HTLV (IAF Biochem International Inc., Montreal, Canada). This system was a solid phase enzyme immunoassay utilizing synthetic peptides to differentiate between antibodies to type I and II. We examined 101 samples (31 ATL patients, 20 HAM/TSP and 50 carriers) which were all positive with the particle agglutination (PA, Fujirebio, Tokyo) and ELISA (Eisai, Tokyo). All samples were negative with HTLV-II and positive with HTLV-I. The results of our serological survey suggested that HTLV-II did not associate with the etiology of ATL and HAM/TSP in Japan.

ATL (adult T-cell leukemia) is the first human cancer known to be caused by a retrovirus. ATL cells show usually positive for CD2, CD3, CD4, CD25 and HLA-DR, but negative for CD8. They produce a variety of cytokines, including IL-1, IL-2, TNF, ADF and PTHrP. PTHrP is considered to be responsible for hypercalcemia which is frequently observed in ATL. Recently, we reported two unusual cases of HTLV-I associated malignancy; 1) a case of CD4 and 8 double negative tumor affecting mainly gastrointestinal tract and 2) a case mimicking small cell lung cancer. IL-2-toxin, a conjugate of IL-2 and diphtheria toxin, has been prepared as a recombinant product and evaluated for the suppressive effect to ATL cells. Clinical trail of IL-2-toxin is now anticipated.