Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia

The outcome for adult patients with BCR-ABL–positive acute lymphoblastic leukemia (ALL) remains dismal and long-term survival can hardly be achieved except by allogeneic hematopoietic stem cell transplantation (HSCT). The Japan Adult Leukemia Study Group (JALSG) has recently started a phase 2 trial with intensive chemotherapy and imatinib for newly diagnosed BCR-AB–positive ALL patients, and we present here the interim results for the first 24 patients. All patients except one case of early death (96%) attained complete remission (CR) after a single course of remission induction therapy. Polymerase chain reaction (PCR) negativity was achieved in 28% of the patients on day 28, in 50% on day 63, and in up to 78% during the follow-up period. The toxicity profile was almost similar to that with chemotherapy alone. As a result, 15 patients (63%) could receive an allogeneic HSC transplant during their first CR. Although the number of patients is small and the observation period is too short, the combination therapy is very promising and produces high-quality CR for most newly diagnosed patients with BCR-ABL–positive ALL. This is especially useful because it provides the patients with a better chance to receive an allogeneic HSC transplant.      

Late results of mitral valve repair for mitral regurgitation

Objective: This study was undertaken to evaluate the long-term results of mitral valve repair for mitral regurgitation.Methods: Between 1991 and 2000, 301 patients with mitral regurgitation underwent mitral valve repair. There were 167 men and 134 women whose mean age was 56±14 years. The patients were comprised of 7 patients in Carpentier's type I, 277 patients in type II, and 17 patients in type III. Chordal replacement with expanded polytetrafluoroethylene sutures had been prospectively applied to repair the anterior mitral leaflet prolapse. Ring annuloplasty was performed in 230 patients (76%). The follow-up was complete and mean follow-up was 67±33 months, for a cumulative follow-up of 1,624 patient-years.Results: There were 5 hospital deaths and 11 late deaths (2 cardiac and 9 noncardiac). All survivors except those with stroke were in the New York Heart Association (NYHA) functional class I or II. At 10 years, the actuarial survival was 90±3%, the freedom from embolism was 86±4%, the freedom from reoperation was 96±2%, and the freedom from valve-related events was 77±4%. At 10 years, the freedom from reoperation in the patients with anterior leaflet prolapse was 90±5%.Conclusions: Mitral valve repair is feasible in most patients with mitral regurgitation and is associated with low mortality and low rates of valve related events. Chordal replacement with expanded polytetrafluoroethylene sutures is effective, safe, and durable at long-term follow-up for patients with anterior leaflet prolapse. Read at the Fifty-fifth Annual Meeting of The Japanese Association for Thoracic Surgery, Symposium, Fukuoka, October 9–11, 2002.     

The metabolism of benzyclane [1-benzyl-1-(3-N,N-dimethylaminopropoxy)cycloheptane] in rat and man.

1. Two metabolites, isolated from the urine of rats dosed with bencyclane fumarate, were characterized as cis-1-benzyl-1-(3-N,N-dimethylaminopropoxy)-4-hydroxycycloheptane (metabolite I) and 1-benzyl-1-(3-N,N-dimethylaminopropoxy)-4-oxocycloheptane (metabolite II). 2. Bencyclane and the two metabolites were determined in the urine of rats and volunteers by g.l.c. Metabolite I was a major metabolite in men, being excreted in urine to the extent of 23.5% dose in the first 24 h.     

Influence of prolonged corticosteroid therapy on the outcome of steroid-responsive nephrotic syndrome.

Eighty-six patients (59 males and 27 females) diagnosed with steroid-responsive nephrotic syndrome during childhood were identified. The patients were 20-40 years of age (mean 27.0 +/- 5.0) with a mean follow-up period of 19.5 +/- 5.9 years. All patients had been treated with a long-term tapering corticosteroid therapy. Thirty patients had also received a course of cyclophosphamide (2 mg/kg/day for 12 weeks). Sixty-six had achieved sustained remission off corticosteroids, while 20 were still receiving corticosteroids to maintain remission. None of the 86 patients had proteinuria or renal insufficiency at the time of the study. Mean final heights in males and females were similar (-0.51 +/- 1.21 and -0.23 +/- 1.16 standard deviation score). Mean final height of 20 steroid-dependent patients was significantly less than that of 66 in remission off corticosteroids (p < 0.005). Ten cyclophosphamide-treated patients got married and 9 had at least 1 healthy child. In children with steroid-responsive nephrotic syndrome, the need for corticosteroid therapy to maintain remission may be associated with decreased adult height. Patients who received a 12-week course of cyclophosphamide are likely to be normally fertile as adults.     

POLYPOID COLONIC HAMARTOMATOUS INVERTED POLYP

We herein present a unique polyp diagnosed as polypoid colonic hamartomatous inverted polyp. Colonoscopic examination revealed a clover‐like submucosal tumor about 30 mm in size with a long stalk at the mid‐transverse colon. The polyp consisted of elongated crypts with cystic dilatation located in the submucosal layer. To the best of our knowledge, there have been no previous reports of the same type of pedunculated colonic polyp, similar in appearance to inflammatory myoglandular polyps but covered with a layer of normal mucosa possessing the muscularis mucosae at the uppermost surface of the polyp.     

Left sleeve Basal segmentectomy for broncholithiasis.

Broncholithiasis is an uncommon pulmonary problem that may present with life-threatening complications. We report one case of broncholithiasis. A 49-year-old female presented with hemoptysis. Chest X-ray and computed tomography (CT) showed left interlobar lymph node calcification near the interlobar pulmonary artery, and calcification continued into the basal bronchus. Bronchoscopy demonstrated pedunculated granulation tissue in the left B8 bronchus obstructing the lumen. We did not recommend endobronchial removal because of the risk of bleeding, so we proposed surgical treatment. We performed left basal segmentectomy associated with bronchoplasty to preserve pulmonary function. It is important to gain proximal control of the pulmonary artery before dissection of its branches and to approach the pulmonary artery from the periphery to avoid massive intraoperative bleeding. The intrabroncholuminal stone was composed of 61% calcium carbonate and 39% calcium phosphate. The postoperative course was not eventful, and the bronchoscopical findings confirmed a good surgical outcome.     

Effect of the Day of Administration on the Developmental Toxicity of Tributyltin Chloride in Rats

The objective of this study was to determine the susceptible day for the teratogenicity of tributyltin chloride (TBTCI) by a single administration on one of the days during organogenesis. Pregnant rats were given a single dose of TBTCI by gastric intubation at 100 mg/kg on either day 7, day 8, or day 9 and at 200 mg/kg on either day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, or day 15 of pregnancy. The maternal body weight gain in the period immediately following administration in all TBTCI-treated groups was significantly decreased. A significant increase in the incidence of postimplantation loss was found after administration of TBTCI on day 7, day 8, and day 9 at 100 and 200 mg/kg and on day 10 and day 11 at 200 mg/kg. A significantly increased incidence of fetuses with external malformations was detected when TBTCI was given on day 8 at 100 and 200 mg/kg and on day 11, day 12, day 13, and day 14 at 200 mg/kg, and the most pronounced effect occurred after administration on day 13 of pregnancy. Cleft palate was observed exclusively after administration during late organogenesis. It could be concluded that the manifestation and susceptibility of the developmental toxicity of TBTCI vary with the developmental stages at the time of administration and that TBTCI has the biphasic sensitivity to teratogenicity on day 8 and days 11–14 of pregnancy. Received: 1 July 1996/Revised: 28 November 1996     

A case of Williams syndrome with p47-phox-deficient chronic granulomatous disease]

A 2-month-old boy with a characteristic elfin face was diagnosed as having Williams syndrome by means of specific fluorescence in situ hybridization (FISH) analysis for a chromosomal microdeletion located in 7q11.23. He was suspected to have immunodeficiency because of a persistent enlargement of axillary lymphnodes after immunization with Bacille Calmette-Guerin (BCG) vaccine since 7 month-old of age. The nitroblue tetrazolium test (NBT) and the chemiluminescence test revealed an absence of superoxide production. Western blotting and DNA sequence analysis confirmed the diagnosis of p47-phox-deficient autosomal recessive chronic granulomatous disease (CGD) (A47 degrees CGD). The predominant genetic defect in A47 degrees CGD was a GT deletion at the beginning of exon 2 in neutrophil cytosol factor 1 gene (NCF1) located in 7q11.23. It suggests that CGD in this patient resulted from the hemizygosity of recessive genetic mutation in NCF1 located at 7q11.23 associated with Williams syndrome. In such a disease with the chromosomal microdeletion like Williams syndrome, we should consider a combination with autosomal recessive diseases, the genes of which are located in the hemizygous region.     

Effect of conditioning regimen on the outcome of bone marrow transplantation from an unrelated donor.

Little information is available regarding the effect of the conditioning regimen on the outcome of bone marrow transplantation (BMT) from an unrelated donor. Therefore, we retrospectively compared the outcome after a cyclophosphamide/total body irradiation (Cy-TBI) regimen, an intensified Cy-TBI regimen (Cy-TBI+), a busulfan and cyclophosphamide (Bu-Cy) regimen, and a Bu-Cy regimen with total lymphoid irradiation (Bu-Cy-TLI). Clinical data of 1875 adult patients who underwent unmanipulated unrelated BMT for leukemia or myelodysplastic syndrome by using 1 of the 4 regimens between 1993 and 2002 were extracted from the database of the Japan Marrow Donor Program. The effect of the conditioning regimen was adjusted for other independent significant factors by multivariate analyses. The Cy-TBI regimen was significantly better than the Bu-Cy regimen with regard to the incidence of engraftment failure (odds ratio, 2.49; P = .046) and overall survival (relative risk [RR], 1.31; P = .050). The Bu-Cy-TLI regimen decreased relapse (RR, 0.13; P = .039) but increased nonrelapse mortality (RR, 1.89; P = .0061). The Cy-TBI+ regimen resulted in increased nonrelapse mortality (RR, 1.48; P = .0003) and inferior survival (RR, 1.45; P < .0001). The results of this retrospective study suggested that the Cy-TBI regimen was superior to other regimens in unrelated BMT.