Altered Hemodynamics Associated with Pathogenesis of the Vertebral Artery Dissecting Aneurysms

The etiology of the vertebral dissecting aneurysms is largely unknown, and they frequently occurs in relatively healthy young men. Objectives and Methods. A series of 57 consecutive cases defined by angiography were evaluated with regard to deviation in the course of the affected and contralateral vertebral arteries. Division was into 3 types: Type I without any deviation, Type II with mild-to-moderate deviation but not over the midline; and Type III with marked deviation over to the contralateral side beyond the midline. Results. The most frequent type of VA running was Type III for the affected and Type I nonaffected side, with this being found in all 17 patients except one. All of the Type III dissections occurred just proximal to a tortuous portion, while in cases with Type-I- and Type-II-affected sides, the majority (33 of 39) occurred near the union of the vertebral artery. In 10 of 57, a non-dominant side was affected, all except one being of Type I or II. With 12 recent patients assessed angiographically in detail for hemodynamics, eleven patients showed contrast material retrograde inflowing into the pseudolumen from the distal portion of the dissection site. Turbulent blood flow was recognized in all of these patients with retrograde inflow. Conclusions. Turbulent blood flow is one etiology of vertebral artery dissection aneurysms, with the sites in the majority of the cases being just proximal to a tortuous portion or union of vessels. In cases with dissection proximal to the tortuous course of the vertebral artery, retrograde inflow will occur more frequently than antegrade, which should be taken into account in designing therapeutic strategies

Minor contribution of cytotoxic T lymphocyte antigen 4 and programmed cell death 1 ligand 1 in immune tolerance against mouse thyrotropin receptor in mice

We have previously shown that wild type (wt) mice exhibit susceptibility to immunization with human (h) thyrotropin receptor (TSHR), but resistance to mouse (m) TSHR, while TSHR knockout (KO) mice are susceptible to mTSHR, indicating the existence of robust immune tolerance against the mTSHR in wt mice. This tolerance may be mediated by either centrally or peripherally. We here explored the contribution of a peripheral arm of immune tolerance against the mTSHR by using antibodies to deplete regulatory T cells (Tregs), to antagonize co-inhibitory molecules and/or to stimulate co-stimulatory molecules. Antagonistic anti-co-inhibitory molecules, cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 ligand 1 (PDL1), induced only low levels of anti-TSHR antibodies without induction of hyperthyroidism in a mouse Graves\u27model. In this experimental setting, antibody levels were significantly higher in THSR+/- mice than wt mice. However, agonistic anti-co-stimulatory molecules, CD40 and CD137, and Treg-depleting anti-CD25 antibodies showed no effect. All these data suggest that peripheral immune tolerance against the mTSHR may play a minor role, and imply the importance of central tolerance, in immune tolerance against mTSHR in mice. Additional studies on central tolerance to the mTSHR will be necessary for completely delineating the mechanisms for immune tolerance against mTSHR in mice

Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

The influence of partial gastrectomy for gastric cancer on the spontaneous disappearance of Helicobacter pylori: A single‐center prospective study

Abstract Background/Aims Helicobacter pylori (HP) eradication is recommended after endoscopic treatment of early gastric cancer (EGC). Cases of spontaneous HP resolution after partial gastrectomy due to environmental changes have been reported; however, there is no evidence for the efficacy of HP eradication in suppressing carcinogenesis and also no reports on the natural history of HP after partial gastrectomy in gastric cancer (GC). To report the natural history of HP in patients with GC and HP infection after partial gastrectomy. Methods and Results We prospectively studied the rate of spontaneous disappearance of HP after partial gastrectomy in patients with GC. From April 2016 to May 2020, 80 patients underwent partial gastrectomy, including 9 cases of proximal gastrectomy (PG), and 71 cases of distal gastrectomy (DG). The presence of HP was confirmed in the stool antigen test 1 year after operation, HP infection persisted in 46 patients (57.5%) and disappeared in 34 patients (42.5%). In univariate analysis, only proton pump inhibitor (PPI) use was a significant contributing factor for the spontaneous resolution of HP infection, especially in the DG group. However, there was no difference in the rates of HP disappearance between Billroth‐I and Roux‐en‐Y reconstructions in the DG group. Conclusion The HP spontaneously disappeared in 42.5% of the GC patients within 1 year after partial gastrectomy. Further investigation in a larger cohort is needed to elucidate the underlying mechanisms