Hemodynamic assessment of the left gastric vein in patients with esophageal varices with color Doppler EUS: factors affecting development of esophageal varices

BACKGROUND: An understanding of the development of esophageal varices is important in the evaluation of risk of variceal hemorrhage. To clarify factors affecting the development of esophageal varices, the morphology and hemodynamics of the left gastric vein were analyzed with color Doppler EUS. METHODS: Sixty-seven patients with esophageal varices underwent color Doppler EUS. Seventeen had small varices (F1), 32 had medium varices (F2), and 18 had large varices (F3). RESULTS: Hepatofugal blood flow velocity in the left gastric vein trunk increased as the size of the varices increased (p < 0.0001), whereas the diameter did not increase. The left gastric vein bifurcates into anterior and posterior branches. As the size of the varices enlarged, the branch pattern was more likely to be anterior branch dominant (p = 0.041). There was no significant difference between the 3 size groups of esophageal varices with respect to the size of the paraesophageal collaterals. The detection rate and diameter of the perforating vein increased as the size of the varices increased (p = 0.032 and 0.012, respectively). CONCLUSION: Blood flow velocity in the left gastric vein trunk, branches, and perforating veins may regulate blood flow supplying the esophageal varices and contribute to their development. These findings are important to understanding the pathogenesis of esophageal varices.     

Risk factors of delay in restoration of hepatic reserve capacity and local recurrence after radiofrequency ablation therapy for hepatocellular carcinoma (HCC).

BACKGROUND:: Effects of radiofrequency ablation (RFA) on hepatic reserve capacity have not been evaluated thoroughly thus far. The aim of our study is to evaluate the factors that influence to hepatic reserve capacity and local recurrence after RFA. PATIENTS AND METHODS:: We studied a total of 243 patients (310 nodules). The study parameters included rates of local recurrence after undergoing RFA as well as factors for delaying recovery of post-RFA albumin levels (age, gender, the presence and absence of anti-HCV antibody, platelet count, GPT level, prothrombin time (PT), Child-Pugh grade, pre-RFA albumin level, alpha-fetoprotein (AFP) level, the number of nodules, tumor size in diameter, hepatic blood control and the coagulation volume after undergoing RFA. RESULTS:: Rates of local recurrence were 6.5%, 10.4% and 12.0% at 1, 2 and 3 years after undergoing RFA, respectively. In the hepatic reserve capacity studies, it took 1.9 and 5.8 months for 50% and 80% of cases, respectively, to restore serum albumin levels to pre-treatment levels after undergoing RFA. There were significant differences in the time of delay in restoration of serum albumin levels with regard to two factors: patients' age >/=60 years (p=0.0351) and tumor size over 3.5cm in diameter (p<0.001). CONCLUSION:: We cosidered that RFA is a safe and efficacious modality, but thorough attention was necessary for such patients with tumor size over 3.5cm in diameter before undergoing RFA, especially in elderly patients.     

Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: Risk factors and patterns

Background. The pathogenesis of frequent intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection or local ablation therapy remains uncertain. Risks and patterns of intrahepatic distant recurrence (IDR) of a single, primary HCC lesion after radiofrequency (RF) ablation were examined. Methods. Ninety patients with a single primary HCC lesion of less than 3 cm who had complete RF ablation were enrolled in the study. Risk factors for IDR and the patterns of IDR after RF ablation were analyzed. Results. The median follow-up was 37.4 months. IDR was observed in 44 (48.9%) patients. The cumulative rate of IDR was 10.4%, 52.5%, and 77.0% at 1, 3, and 5 years, respectively. Univariate analysis revealed that a pretreatment serum α-fetoprotein (AFP) level of ≥50 ng/ml (P = 0.0324), a des-γ-carboxy prothrombin (DCP) level of ≥40 mAu/ml (P = 0.006), an ablative margin of <5 mm of the ablation zone (P = 0.0306), and a prothrombin time of <70% (P = 0.0188) were related to IDR. A multivariate stepwise Cox proportional hazards regression model revealed that pretreatment serum AFP and DCP level and the ablative margin were independent risk factors for IDR pretreatment. Serum DCP level ≥ 40 mAu/ml (P = 0.025), local tumor progression (P = 0.011), and ablative margin < 5 mm (P = 0.024) were related to multiple IDR. Conclusions. HCC patients with high serum AFP or DCP before RF ablation should be carefully followed up to monitor any IDR. A suffi cient ablative margin in RF ablation for HCC is required to prevent IDR.     

Distribution of α2-macroglobulin in normal,inflammatory, and tumor tissues in rats

Distribution of uptake and catabolism of intravenously administered¹²⁵l-labeled rat ₂-macroglobulin(¹²⁵I-₂MG) were examined in normal, inflammatory, and tumor tissues of rats. Clearance of intravenously administered [¹²⁵l]₂MG from the circulation was rapid. Accumulation of this compound into inflammatory tissue was 2–3 times more extensive than in normal tissues. The accumulation into sarcoma tissue was much less. Radioactivity in TCA-PTA precipitates remained fairly constant for the first 12 h in inflammatory tissue and for the first 24 h in sarcoma. These patterns of accumulation were never observed in the normal tissues. As the kidney preferentially accumulated large amounts of [¹²⁵l]₂MG in the nondegraded form and its degradation products, the tissue may play a special role in the metabolism of ₂MG. Rapid clearance from the circulation and relatively small amounts of accumulation in tissues suggest that ₂MG may function as a protease inhibitor, mainly in the circulation rather than in the tissues.     

Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival

Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival.     

Subtle disruption of the middle cerebellar peduncles in patients with schizophrenia

Diffusion tensor imaging (DTI) was used to investigate subtle disruption in the middle cerebellar peduncles in patients with schizophrenia. Fractional anisotropy (FA) was measured in 25 patients with schizophrenia and 21 healthy subjects using DTI. The FA of the right and left middle cerebellar peduncles was significantly lower in the schizophrenic patients compared to healthy subjects. FA in the left middle cerebellar peduncles was significantly correlated with the dosage of neuroleptics in patients with schizophrenia. There were no significant differences of mean diffusivity in the right and left middle cerebellar peduncles between patients with schizophrenia and healthy subjects. The findings of the study suggest that antipsychotics may improve the subtle disruption in the middle cerebellar peduncles in patients with schizophrenia.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.     

Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum

Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero‐salivary re‐circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal‐type homeobox 2, and the shifting of carcinogenic N‐nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender‐related difference in NO‐related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO‐related esophageal damage could explain the well‐recognized male predominance in the GERD spectrum in humans.