Balloon-occluded retrograde transvenous obliteration for gastric varices: the relationship between the clinical outcome and gastrorenal shunt occlusion

<p>Abstract</p> <p>Background</p> <p>The rupture of gastric varices is associated with high mortality rate. Balloon-occluded retrograde transvenous obliteration (B-RTO), a minimally invasive procedure that was introduced in the mid-1990s, has been widely accepted in Japan. Several reports have indicated that B-RTO yields satisfactory results; however, few reports have discussed the recurrence of gastric varices after this therapy. The purpose of this study is to retrospectively evaluate the technical aspects of B-RTO and the recurrence of gastric varices after treatment with this procedure.</p> <p>Methods</p> <p>B-RTO was performed in 47 patients with gastric varices, who were at a risk of variceal ruptures and who may or may not have had a history of variceal bleeding. We injected a sclerosing agent into the gastric varices for 30-60 minutes. To evaluate the therapeutic efficacy of the technique, we obtained contrast-enhanced computed tomography (CT) scans 5 days after B-RTO. As a general rule, if the gastric varices did not appear thrombosed, we repeated the procedure 7 days after the first procedure.</p> <p>Results</p> <p>B-RTO was a technical success in 37 patients. It was performed once in 26 patients, twice in 6 patients, thrice in 2 patients, and 4 times in 3 patients. Contrast-enhanced CT scans obtained after B-RTO showed thrombosed gastrorenal shunts in 29 patients and patent gastrorenal shunts in 8 patients. The gastric varices recurred in 2 patients who had patent gastrorenal shunts. The overall cumulative relapse-free rate of gastric varices was 90% at 5 years after B-RTO.</p> <p>Conclusions</p> <p>B-RTO is an effective treatment modality for gastric varices. Moreover, obliteration of the gastrorenal shunt as well as the gastric varices appears to be important for the treatment of gastric varices.</p

Outcomes in Two Japanese Adenosine Deaminase-Deficiency Patients Treated by Stem Cell Gene Therapy with No Cytoreductive Conditioning

Objective We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT for ADA deficiency. Patients and Methods Pt 1 was treated at age 4.7 years, whereas pt 2, who had previously received T-cell gene therapy, was treated at age 13 years. Bone marrow CD34(+) cells were harvested after enzyme replacement therapy (ERT) was withdrawn; following transduction of ADA cDNA by the gamma-retroviral vector GCsapM-ADA, they were administered intravenously. No cytoreductive conditioning, at present considered critical for therapeutic benefit, was given before cell infusion. Hematological/immunological reconstitution kinetics, levels of systemic detoxification, gene-marking levels, and proviral insertion sites in hematopoietic cells were assessed. Results Treatment was well tolerated, and no serious adverse events were observed. Engraftment of gene-modified repopulating cells was evidenced by the appearance and maintenance of peripheral lymphocytes expressing functional ADA. Systemic detoxification was moderately achieved, allowing temporary discontinuation of ERT for 6 and 10 years in pt 1 and pt 2, respectively. Recovery of immunity remained partial, with lymphocyte counts in pts 1 and 2, peaked at 408/mm(3) and 1248/mm(3), approximately 2 and 5 years after SCGT. Vector integration site analyses confirmed that hematopoiesis was reconstituted with a limited number of clones, some of which were shown to have myelo-lymphoid potential. Conclusions Outcomes in SCGT for ADA-SCID are described in the context of a unique protocol, which used neither ERT nor cytoreductive conditioning. Although proven safe, immune reconstitution was partial and temporary. Our results reiterate the importance of cytoreductive conditioning to ensure greater benefits from SCGT