Simultaneous occurrence of biphenotypic T cell/myeloid lesions involving t(12;13)(p13;q14) in a pediatric patient

This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected.     

Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes.     

Clinicopathological Differences between Proximal and Distal pT3 Colon Cancer and the Clinical Significance of the Depth of Cancer Invasion beyond the Muscularis Propria

Background/Aims: To investigate differences in clinicopathological features between proximal and distal pT3 colon cancers and to determine whether the depth of the cancer invasion beyond the muscularis propria (DBM) serves as an objective indicator of the depth of tumor invasion in proximal colon cancer and in distal colon cancer. Methodology: A total of 207 patients who underwent surgery for proximal and distal pT3 colon cancer between 1996 and 2001 were included in the analysis. Results: No differences were noted between proximal and distal cancers in lymph node metastasis, distant metastasis, lymphatic/venous invasion, histological type and curability of surgical resection, although proximal cancer patients were significantly older. High-grade malignancy appeared to be more commonly noted in the proximal colon cancer cases but there was no significant difference in prognosis between proximal and distal cancer patients. Conclusions: Regarding the correlation between DBM and prognosis, there was a significant decrease in the 5-year survival rate in patients with proximal lesions of DBM 3000μm or more, and patients with distal lesions of DBM 5000μm or more. DBM is thus an objective indicator of depth of tumor invasion for both proximal and distal lesions, a prognostic factor and a guide to determining whether postoperative adjuvant chemotherapy is indicated for pT3 colon cancer cases.     

Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238?bp deletion, and a compound heterozygous FGA1238?bp deletion and novel FGA c.54+3A>C substitution

We identified two afibrinogenemic girls in two Japanese families and performed molecular analysis to clarify the mechanisms of fibrinogen defects. Genetic analyses were performed by PCR amplification of the fibrinogen gene and DNA sequence analysis. To analyze the mechanisms of mature fibrinogen defects in plasma, we cloned minigenes from the proposita's PCR-amplified DNA, transfected them into CHO cells, and sequenced the cDNA amplified with the RT reaction followed by PCR. Sequence analyses indicated that one was caused by a homozygous 1238?bp deletion of the fibrinogen Aα-chain gene (FGAΔ1238) and the other was a compound heterozygous FGAΔ1238 and novel FGA c.54+3A>C substitution. The minigene corresponding to FGAΔ1238 generates two aberrant mRNAs, both of which may induce a frameshift and terminate prematurely. In contrast, the minigene corresponding to FGA c.54+3A>C generates two aberrant mRNAs, one of which may induce a frameshift and terminate prematurely, and the other uses a cryptic 5' splice site in exon 1, resulting in the deletion of six amino acids in signal peptides. Molecular analyses of both genetic variants suggest that the lack of a mature Aα-chain, impaired assembly, and/or secretion of the fibrinogen molecule may lead to afibrinogenemia.     

Lymphomatoidgastropathy mimicking extranodal NK/T cell lymphoma, nasal type: a case report

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, exhibits aggressive tumor behavior and carries a poor prognosis. Recently, lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment. Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type, it is difficult to distinguish between the two conditions by histopathological evaluation only. Here, we report a rare case of lymphomatoid gastropathy in a 57-year-old female. Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body. Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments, at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body. Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3⁺, CD4^-, CD5^-, CD7⁺, CD8^-, CD20^-, CD30^-, CD56⁺, CD79a^- and T-cell-restricted intracellular antigen-1⁺ into gastric mucosa. After treatment for Helicobacter pylori (H. pylori) eradication, the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo. Here, we report a case of H. pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation, and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type. In any case, these lesions are evaluated with biopsy specimens, the possibility of this benign entity should be considered, and excessive treatment should be carefully avoided. Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.     

Ultrasound-guided infraclavicular axillary vein puncture is effective to avoid pinch-off syndrome: a long-term follow-up study

Purpose

Pinch-off syndrome (POS) is a serious complication encountered during the long-term management of totally implantable access ports (TIAPs). The aim of this study was to examine the effect of ultrasound-guided infraclavicular axillary vein puncture to avoid POS in patients with long-term use of a TIAP.

Methods

This was a retrospective review of 207 consecutive TIAPs: one hundred devices implanted using an anatomical landmark technique were used as historical controls (Landmark group), while 107 devices were implanted using an ultrasound (US)-guided puncture method (US group). The pinch-off grade (POG) was determined using chest X-ray findings following the definition of Hinke, and the progression of POG during the follow-up period of the Landmark and US groups was compared.

Results

Sixteen cases in the Landmark group were POG-1 and 3 were POG-2, while all cases in the US group were POG-0 at the time of venipuncture (p < 0.001). Eleven patients in the Landmark group showed some degree of progression of the POG during the follow-up period. In contrast, there were no cases showing progression of the POG in the US group (p = 0.002).

Conclusions

US-guided infraclavicular axillary vein puncture was found to effectively make it possible to avoid POS for the long-term management of TIAPs, as well as at the time of implantation.     

Effects of Nordic Walking Compared to Conventional Walking and Band-Based Resistance Exercise on Fitness in Older Adults

The purpose of this study was to compare the effects of Nordic walking with conventional walking and band-based resistance exercise on functional fitness, static balance and dynamic balance in older adults. Volunteers (n = 65) were divided into four groups: Nordic walking (NW), conventional walking (CW), resistance (RES), and control. Each group performed activity 50-70 min·day⁻¹ (warm-up 10-15 min, main exercise 30-40, and cool down 10-15 min), 3 days·week⁻¹ (NW and CW) or 2 day·week⁻¹ (RES) for 12 wks. Upper-body strength improved (p < 0. 05) in the RES (22.3%) and the NW (11.6%) groups compared to the CW and control groups. Cardio- respiratory fitness improved more in the NW (10.9%) and CW (10.6%) groups compared to the RES and control groups. Upper- and lower-body flexibility also improved in all exercise groups compared to the control group. There were no improvements in balance measures in any group. While all modes of exercise improved various components of fitness, Nordic walking provided the best well-rounded benefits by improving upper-body strength, cardiovascular endurance, and flexibility. Therefore, Nordic walking is recommended as an effective and efficient mode of concurrent exercise to improve overall functional fitness in older adults.

Key Points

• Nordic walking, conventional walking, and resistance training are beneficial for older adults.
• Nordic walking and conventional walking both improve cardio-respiratory fitness while resistance training does not.
• Nordic walking provides additional benefits in upper-body muscular strength compared to conventional walking.
• Nordic walking is an effective and efficient mode of exercise to improve overall fitness in older adults.

Key words: Walking, resistance exercise, concurrent exercise, aging, functional fitness