Long-term follow-up evaluation of endoscopic sclerotherapy for dilated gastrojejunostomy after gastric bypass

Background

Endoscopic sclerotherapy using sodium morrhuate has been used to treat patients with weight regain after Roux-en-Y gastric bypass whose presumed etiology is loss of restriction due to gastrojejunostomy dilation. Weight loss and stability have been demonstrated in several studies with short-term follow-up evaluation.

Methods

This retrospective review evaluated all the patients who underwent sclerotherapy for a dilated gastrojejunostomy between 2007 and 2012.

Results

The study identified 48 patients with a mean follow-up period of 22 months (range 12–60 months). The mean age of these patients was 47.5 ± 10.5 years, and 92 % were women. The average weight loss from the primary procedure was 132.5 ± 54.82 lb, and the average weight regain from the lowest weight to the maximum weight before sclerotherapy was 46 ± 40.32 lb. The median number of sclerotherapy sessions was two (range 1–4). The pre-procedure mean gastrojejunostomy diameter was 20 ± 3.6 mm, and the mean volume of sodium morrhuate injected per session was 12.8 ± 3.7 ml. The average weight loss from sclerotherapy to the final documented weight was 3.17 ± 19.70 lb, which was not statistically significant. The following variables in the multivariate analysis were not associated with statistically significant weight loss: volume of sodium morrhuate, patient age, gastrojejunostomy diameter, number of sclerotherapy sessions, decrease in gastrojejunostomy diameter between the first and second sessions, and number of follow-up years. Weight stabilization or loss was achieved by 58 % of our cohort, with a mean weight loss of 15.9 ± 14.6 lb in this subgroup.

Conclusion

The long-term follow-up evaluation of patients undergoing sclerotherapy of the gastrojejunostomy for weight regain after gastric bypass showed only a marginal weight loss, which was not statistically significant in our study population, although more than 50 % of the patients achieved weight loss or stabilization.     

Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function

NKX3.1, a gene mapped to 8p21, is a member of the NK class of homeodomain proteins and is expressed primarily in the prostate. NKX3.1 exerts a growth-suppressive and differentiating effect on prostate epithelial cells. Because of its known functions and its location within a chromosomal region where evidence for prostate cancer linkage and somatic loss of heterozygosity is found, we hypothesize that sequence variants in the NKX3.1 gene increase prostate cancer risk. To address this, we first resequenced the NKX3.1 gene in 159 probands of hereditary prostate cancer families recruited at Johns Hopkins Hospital; each family has at least three first-degree relatives affected with prostate cancer. Twenty-one germ-line variants were identified in this analysis, including one previously described common nonsynonymous change (R52C), two novel rare nonsynonymous changes (A17T and T164A), and a novel common 18-bp deletion in the promoter. Overall, the germ-line variants were significantly linked to prostate cancer, with a peak heterogeneity logarithm of odds of 2.04 (P = 0.002) at the NKX3.1 gene. The rare nonsynonymous change, T164A, located in the homeobox domain of the gene, segregated with prostate cancer in a family with three affected brothers and one unaffected brother. Importantly, nuclear magnetic resonance solution structure analysis and circular dichroism studies showed this specific mutation to affect the stability of the homeodomain of the NKX3.1 protein and decreased binding to its cognate DNA recognition sequence. These results suggest that germ-line sequence variants in NKX3.1 may play a role in susceptibility to hereditary prostate cancer and underscore a role for NKX3.1 as a prostate cancer gatekeeper.     

Extent and severity of coronary artery disease by coronary CT angiography is associated with elevated left ventricular diastolic pressures and worsening diastolic function

BackgroundPatients with flow-limiting coronary stenoses exhibit elevated left ventricular end-diastolic pressure (LVEDP) and abnormal left ventricular (LV) relaxation.ObjectiveWe investigated the relationship of extent and severity of coronary artery disease (CAD) by coronary CT angiography (CTA) to LVEDP and measures of LV diastolic dysfunction.MethodsWe identified consecutive patients undergoing coronary CTA and transthoracic echocardiography who were assessed for diastolic function. CAD was evaluated on a per-patient, per-vessel, and per-segment basis for intraluminal diameter stenosis by using an 18-segment model (0 = none, 1 = 1%–49%, 2 = 50%–69%, and 3 = 70%–100%) and summed over segments to obtain overall coronary plaque burden (segment stenosis score [SSS]; maximum = 54). Transthoracic echocardiography evaluated mitral inflow E wave-to-A wave ratio, tissue Doppler early mitral annual tissue velocity axial excursion, stage of diastolic dysfunction, and LV dimensions and estimated LVEDP from the ratio of mitral inflow velocity to early mitral annular (medial) tissue velocity.ResultsFour hundred seventy-eight patients (57% women; mean age, 57.9 ± 14.6 years; 24.9% prior CAD) comprised the study population. Increasing per-patient maximal coronary stenosis, number of vessels with obstructive stenosis, and SSS were associated with increased LVEDP. The prevalence of advanced diastolic dysfunction increased with greater number of obstructive vessels. In multivariable analyses, SSS was associated with increased LVEDP (0.8 mm Hg per tertile increase in SSS, 0.5–1.1; P < .001); reduced E′ axial excursion (?0.3; 95% confidence interval [CI], ?0.5 to ?0.1; P = .001), increased LV mass index (1.6 g/m² per tertile increase in SSS; P = .04), and increased relative wall thickness (0.005; 95% CI, 0.004–0.009; P = .03), with consistent relationships persisting even among persons with per-patient maximal stenosis <50% and LV ejection fraction ≥55%.ConclusionsExtent and severity of obstructive as well as nonobstructive CAD by coronary CTA are associated with increased LVEDP and measures of diastolic dysfunction.