A case of pulmonary artery intimal sarcoma successfully treated using concurrent chemoradiotherapy and subsequent chemotherapy.

Pulmonary artery intimal sarcoma (PAIS) is a rare malignancy with an extremely poor prognosis. A 43-year-old man visited our hospital with shortness of breath and suddenly experienced cardiopulmonary arrest before he could be examined. After prompt resuscitation, we diagnosed PAIS, but the patient refused to undergo surgery because of the high perioperative mortality risk. Thus, the patient was treated using concurrent chemoradiotherapy with weekly paclitaxel therapy, as well as subsequent chemotherapy. The patient continued chemotherapy for 36 months until he elected to discontinue treatment. To the best of our knowledge, this is the first case of PAIS, which is difficult to resect, that was successfully treated using concurrent chemoradiotherapy and subsequent chemotherapy.

Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. METHODS: We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolar-arterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study. RESULTS: Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. CONCLUSION: Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

Clinical outcomes of ESD for early gastric neoplasms in elderly patients.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard treatment in Japan for early gastric neoplasms. With an increase in elderly population, the number of elderly patients in whom ESD performed has also steadily increased. AIMS AND METHODS: The aim of study was to evaluate the effectiveness of and problems associated with ESD for early gastric neoplasms in elderly patients. Subjects were 514 patients (586 lesions) with early gastric neoplasms performed ESD at two institutions. The patients were classified into an elderly group (age ≥ 75 years) and a nonelderly group (age < 75 years). We compared the characteristics of patients and lesions, treatment results, ESD-related complications and prognosis between the two groups. RESULTS: The elderly group included 200 patients (229 lesions), and the nonelderly group included 314 patients (357 lesions). The incidences of underlying disease, such as hypertension and heart disease, and the rate of antiplatelet agents use were significantly higher in the elderly group. En bloc and curative resection rates were high in both groups. The bleeding rate was significantly higher in the elderly group. Residual disease or recurrence rates were very low in both groups. The death rate due to other diseases was significantly higher in the elderly group. CONCLUSIONS: This study demonstrates the efficacy of ESD in both elderly and nonelderly patients. However, we must be attentive to ESD-related bleeding, death caused by other diseases, and underlying diseases when we perform ESD in elderly patients.

Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels.

BACKGROUND: We evaluated the annual rate of fibrosis progression in chronic hepatitis B and C patients with elevated alanine aminotransferase (ALT) levels. METHODS: Forty-nine chronic hepatitis B patients and 21 chronic hepatitis C patients, each of whom had undergone two or more liver biopsies at an interval of more than 1 year, were enrolled in this retrospective clinical research protocol. The annual rate of fibrosis progression was calculated by dividing the change in fibrosis stage between the first and second liver biopsies by the interval in years between them. RESULTS: The median interval in chronic hepatitis B and C was 3.4 (first and third quartiles, 1.8-4.7) and 3.2 (2.1-6.5) years, respectively. Overall, the mean fibrosis progression rate was 0.21 +/- 0.31 (mean +/- SD) fibrosis units (FU) per year in 49 patients with chronic hepatitis B, and 0.13 +/- 0.18 FU/year in 21 patients with chronic hepatitis C. The ALT level was an independent variable correlating with fibrosis progression. In patients whose median ALT level was 70 IU/l or more, the mean fibrosis progression rate was 0.28 +/- 0.32 FU/year in 36 patients with chronic hepatitis B, and 0.22 +/- 0.23 FU/year in eight patients with chronic hepatitis C. CONCLUSION: This paired-biopsy study of untreated chronic hepatitis B or C demonstrated that fibrosis progression occurred largely in patients with continuously elevated ALT levels even over a relatively short period, and that liver fibrosis might progress by one stage within an average of 4-5 years of follow-up in patients with elevated ALT of 70 IU/l or more.

Serum level of transforming growth factor-beta1 (TGF-beta1) and the expression of TGF-beta receptor type II in peripheral blood mononuclear cells in patients with autoimmune hepatitis.

BACKGROUND/AIMS: To evaluate the association of the immunosuppressive effects of transforming growth factor-beta1 (TGF-beta1) with abnormalities in immune regulation in autoimmune hepatitis (AIH), we investigated the serum level of TGF-beta1 and expression of TGF-beta receptor type II (TbetaRII) in peripheral blood mononuclear cells (PBMC) in patients with AIH. METHODOLOGY: Twenty-two patients with AIH were included in this study. Serum levels of total TGF-beta1 were determined using a specific enzyme-linked immunosorbent assay (ELISA). The expression levels of TbetaRII mRNA were semi-quantitatively determined by ribonuclease (RNase) protection assay specific for TbetaRII. RESULTS: The mean serum level of TGF-beta1 in patients with AIH (230+/-95 ng/mL) was higher than that of healthy controls (137+/-81 ng/mL, p=0.012). The expression level of TbetaRII mRNA in PBMC obtained from AIH patients (0.131+/-0.046) was lower than that in PBMC of patients with chronic hepatitis C (0.186+/-0.074, p=0.019) and that of healthy subjects (0.188+/-0.060, p=0.013). CONCLUSIONS: The present study of TbetaRII mRNA expression in PBMC from patients with AIH suggested that the decreased expression of TbetaRII might contribute partially to abnormalities in immune regulation observed in patients with AIH, despite concomitant up-regulation of TGF-beta1 production.

Suppressive effects of transforming growth factor-beta1 produced by hepatocellular carcinoma cell lines on interferon-gamma production by peripheral blood mononuclear cells.

Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.