Relationship between soluble MICA and the MICA A5.1 homozygous genotype in patients with oral squamous cell carcinoma

NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Polymorphisms in MICA may influence its binding to the NKG2D. The soluble form of MICA is released from the surface of tumor cells of epithelial origin. Whereas MICA expressed on the cell surface stimulates the immunoreceptor natural killer group 2, member D (NKG2D), the secreted form down-regulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between MICA gene microsatellite polymorphisms and serum levels of soluble MICA in patients with oral squamous cell carcinoma (OSCC). We found that patients with OSCC were more likely to have the A5.1 allele when compared to healthy subjects and also more likely to be homozygous for this allele (p = 0.041). Patients with the homozygous A5.1 genotype had higher levels of soluble MICA (p = 0.031) and a lower survival rate (p = 0.026).     

A case of imatinib-resistant GIST treated by sunitinib

We report a case of imatinib-resistant GIST, successfully treated by sunitinib. A 62-year-old man with high-grade fever and a huge abdominal tumor was diagnosed with malignant GIST and multiple liver metastases. We performed total gastrectomy combined with distal pancreatectomy, and splenectomy for palliation. Imatinib at a dose of 300mg/day was administered postoperatively, and the liver metastases was well controlled. After nine months, abdominal dissemination increased, and we raised the dose of imatinib to 400mg/day for the progressive state. Subsequently, we had to discontinue imatinib due to its adverse effects. Because the tumors progressed greatly while imatinib was discontinued, we changed to sunitinib. After wards, tumors reduced and his general condition improved remarkably. Although tumors progressed after five months, he was able to obtain good QOL during the administration of sunitinib. Sunitinib is useful for imatinib-resistant GIST, and may be a promising treatment even for patients with poor PS.     

Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism

Although an immunoregulatory role of aryl hydrocarbon receptor (Ahr) has been demonstrated in T cells and macrophages, little is known about its function in dendritic cells (DC). Here, we show that lipopolysaccharide (LPS) and CpG stimulate Ahr expression in bone marrow-derived dendritic cells (BMDC). Furthermore, we found that Ahr is required to induce indoleamine 2,3-dioxygenase (IDO) expression, an immunosuppressive enzyme that catabolizes tryptophan into kynurenine (Kyn) and other metabolites in DC. In the presence of LPS or CpG, Ahr-deficient (Ahr(-/-)) mature BMDC induced immune responses characterized by reduced Kyn and IL-10 production compared with results observed with tolerogenic mature WT BMDC. In a coculture system with LPS- or CpG-stimulated BMDC and naive T cells, Ahr(-/-) BMDC inhibited naive T-cell differentiation into regulatory T (Treg) cells, which likely facilitated Th17 cell development and promoted naive T-cell proliferation. Addition of synthetic L-Kyn to the coculture system skewed the differentiation of naive T cells to Treg cells rather than Th17 cells. Taken together, our results demonstrate a previously unknown negatively regulatory role for Ahr in DC-mediated immunogenesis in the presence of LPS or CpG, which, in turn, alters the Kyn-dependent generation of Treg cells and Th17 cells from naive T cells.     

Recurrent esophageal cancer with complete response to TS-1 chemotherapy

An 80-year-old man was admitted to our hospital for treatment of recurrent esophageal cancer in December, 2004. He was diagnosed as having esophageal cancer of stage IVa (T2N4M0) in October, 2002, and he received chemoradiotherapy (nedaplatin (CDGP)/5-fluorouracil (5-FU) total 6 course+60 Gy). Afterwards, lymph nodes recurred, and two courses of CDGP/vindesine were given. Then, the primary lesion showed a complete response (CR), and lymph nodes a partial response (PR). In December, 2004, paraesophageal lymph nodes were enlarged to the size of 7 cm. On admission, because of renal disturbance and dementia with advanced age, we chose chemotherapy with TS-1 (100 mg/body/day, three weeks of administration, then two weeks of withdrawal). He had adverse effects of hematotoxicity of grade 3, and non-hematotoxicity of grade 1. He received 6 courses of this regimen and eventually showed CR. Serum SCC was decreased from 4.7 ng/mL to 0.9 ng/mL. At present,the lesions have not recurred during the follow-up for 18 months.     

Age-related changes in osseous anatomy, alignment, and range of motion of the cervical spine. Part I: Radiographic data from over 1,200 asymptomatic subjects

Purpose

This study aimed to establish radiographic standard values for cervical spine morphometry, alignment, and range of motion (ROM) in both male and female in each decade of life between the 3rd and 8th and to elucidate these age-related changes.

Methods

A total of 1,230 asymptomatic volunteers underwent anteroposterior (AP), lateral, flexion, and extension radiography of the cervical spine. There were at least 100 men and 100 women in each decade of life between the 3rd and 8th. AP diameter of the spinal canal, vertebral body, and disc were measured at each level from the 2nd to 7th cervical vertebra (C2–C7). C2–C7 sagittal alignment and ROM during flexion and extension were calculated using a computer digitizer.

Results

The AP diameter of the spinal canal was 15.8 ± 1.5 [mean ± standard deviation (SD)] mm at the mid-C5 level, and 15.5 ± 2.0 mm at the C5/6 disc level. The disc height was 5.8 ± 1.3 mm at the C5/6 level, which was the minimum height, and the maximum height was at the C6/7 level. Both the AP diameter of the spinal canal and disc height decreased gradually with increasing age. The C2–C7 sagittal alignment and total ROM were 13.9 ± 12.3° in lordosis and 55.3 ± 16.0°, respectively. The C2–C7 lordotic angle was 8.0 ± 11.8° in the 3rd decade and increased to 19.7 ± 11.3 in the 8th decade, whereas the C2–C7 ROM was 67.7 ± 17.0° in the 3rd decade and decreased to 45.0 ± 12.5 in the 8th decade. The extension ROM decreased more than the flexion ROM, and lordotic alignment progressed with increasing age. There was a significant difference in C2–C7 alignment and ROM between men and women.

Conclusions

The standard values and age-related changes in cervical anatomy, alignment, and ROM for males and females in each decade between the 3rd and 8th were established. Cervical lordosis in the neutral position develops with aging, while extension ROM decreases gradually. These data will be useful as normal values for the sake of comparison in clinical practice.     

Clinical outcomes of living donor liver transplantation for hepatitis C virus (HCV)-positive patients

BACKGROUND: Whether hepatitis C virus recurrence occurs earlier and with greater severity for living donor liver transplantation (LDLT) than for deceased donor liver transplantation (DDLT) has recently become a subject of debate. METHODS: We retrospectively evaluated clinical outcomes for a cohort of 91 HCV-positive patients who underwent LDLT at Kyoto University with a median follow-up period of 25 months. RESULTS: Overall 5-year patient survival for HCV patients was similar to that for non-HCV patients (n=209) who underwent right-lobe LDLT at our institute (69% vs. 71%). Survival rate of patients without HCC (n=34) tended to be better than that of patients with HCC (n=57) (82% vs. 60%, P=0.069). According to annual liver biopsy, rate of fibrosis progression to stage 2 or more (representing significant fibrosis) was 39% at 2 years after LDLT. Univariate analysis showed that female recipient and male donor represented significant risk factors for significant fibrosis. Progression to severe recurrence (defined as the presence of liver cirrhosis (F4) in a liver biopsy and/or the development of clinical decompensation) was observed in five patients. CONCLUSIONS: Postoperative patient survival was similar for HCV-positive and -negative recipients in our adult LDLT series. Rates of progression to severe disease due to HCV recurrence seemed comparable between our LDLT recipients and DDLT recipients described in the literature. Although longer-term follow-up is required, our results suggest that LDLT can produce acceptable outcomes also for patients suffering from HCV-related cirrhosis.     

Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.

In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with 相似文献   

成人活体肝移植

活体肝移植（LDLT）最初作为一种降低等待做肝移植患者死亡率的方法。日本京都大学LDLT开始于1990年6月,移植例数逐年增加,临床应用范围从小儿扩展到成人。肝脏右叶移植物的应用在LDLT具有重要临床意义,已经成为成人间LDLT标准方法。由于肝脏右叶移植物在LDLT移植后成功应用,近年来成人LDLT例数显著增加,自1990年6月至2005年12月,京都大学附属病院已完成了1140例LDLT手术,其中包括477例成人LDLT手术（年龄大于18岁）。HBV和HCV相关性肝硬化和肝癌是LDLT最常见的适应证,截至2005年12月,随访统计结果表明成人LDLT术后总的5年生存率为69．1％。     

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.