Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors.

Calcineurin inhibitors (CNIs) such as cyclosporin A (CSA) and tacrolimus (FK506) are efficacious in patients with steroid-refractory or steroid-dependent ulcerative colitis (UC). We retrospectively investigated patients with refractory UC treated with CNIs to elucidate the prognostic factors for a colectomy. Data from 59 patients (35 men and 24 women) were analyzed. CSA and FK506 were administered by intravenous infusion and peroral administration, respectively. The efficacy of the CNIs was assessed using Seo's complex integrated disease activity index. Categorical data analyses were also conducted. The results revealed that the response rates for CSA and FK506 were similar (CSA, 66.6%; FK506, 63.6%). However, oral FK506 had a slower onset of action than intravenous CSA. The risk factors for CNI non-responsiveness were: i) more than 10,000 mg of prednisolone used prior to CNI treatment; and ii) positivity for cytomegalovirus antigenemia (C7-HRP). The factors affecting the rate of colectomy were: i) CNI non-responsiveness; ii) more than 10,000 mg of prednisolone used prior to the initiation of CNI treatment; and iii) positivity for C7-HRP. The addition of azathioprine (AZA) following CNI treatment significantly reduced the incidence of colectomy. Our results revealed the prognostic factors affecting the efficacy of CNI therapy and the need for colectomy in patients with refractory UC. Importantly, some of these factors may be obtained prior to or shortly following the start of CNI treatment. Furthermore, AZA is an important agent for averting colectomy once a patient responds to CNIs.

The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range.

BACKGROUND: We hypothesized that the severity of dextran sodium sulfate (DSS)-induced colitis could differ between DSS preparations of the same molecular weight, and that this difference may be affected by the sulfur content. To test this, we used three DSS preparations of similar molecular weights but with different sulfur contents. METHODS: Three DSS preparations with molecular weights of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab Depot (The Lab). Epithelial cell lines were used to assess the levels of poly (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week-old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed to investigate the effects of the DSS preparations in vivo. RESULTS: In vitro experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2 cells treated with DSS from USB as compared to The Lab Mice treated with The Lab DSS had significantly decreased body weight losses on day 7 as compared to mice receiving DSS from MP Bio and USB. This result was supported by their DAI score, colon weight/length ratio, and histological scores. CONCLUSION: The severity of colitis can differ between similar DSS preparations of the same molecular weight range. This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation.

Factors affecting the efficacy of cyclosporin A therapy for refractory ulcerative colitis.

BACKGROUND AND AIMS: Cyclosporin A (CSA), an immunosuppressive agent, is highly efficacious in patients with refractory ulcerative colitis (UC). We retrospectively investigated patients with refractory UC treated with CSA therapy to elucidate the efficacy and the prognostic factors. METHODS: Forty-one patients (26 men and 15 women) were enrolled. The efficacy of CSA was assessed at three time points: short- and mid-term assessments took place 2 weeks and 1 year after CSA administration, respectively, and long-term assessments at the end of the observation period. RESULTS: The short-term response rate was 71%. Background analysis revealed risk factors for CSA unresponsiveness: (i) more than 10,000 mg of prednisolone used before CSA treatment; (ii) the presence of circulating (C7-HRP); and (iii) disease duration more than 4 years. The mid-term relapse-free survival rate was 51.0%. The addition of azathioprine (AZA) after CSA treatment significantly suppressed the incidence of relapse at 1 year (72.5% vs 26.7%, P = 0.0237). The overall colectomy-free survival rate was 46.4%, and the induction of AZA after CSA treatment significantly reduced the colectomy rate (66.7% vs 30.5%, P = 0.0419). Among CSA responders, AZA naïve patients had significant lower-probabilities for colectomies compared to patients with prior AZA treatment (22.5% vs 56.7%, P = 0.0309). The administration of CSA was discontinued in five cases. CONCLUSION: Our results revealed factors affecting the efficacy of CSA therapy for patients with refractory UC. AZA is an important agent that maintains disease quiescence once one responds to CSA. However, refractory patients despite AZA treatment are more likely to have consequent colectomies.

[A case of primary Sjögren' s syndrome with pathological findings resembling multicentric Castleman' s disease showed multiple nodular opacities on chest CT scans].

A 49-year-old woman with primary Sjögren's syndrome a few years previously was admitted to our hospital complaining of tongue and skin eruptions, swelling of the face and neck and for examination of liver injury and hypereosinophilia. A blood test revealed leukocytosis with eosinophilia, mild liver injury, polyclonal hypergammaglobulinemia, and positive results for anti-nuclear antibody, anti-SS-A antibody and anti-SS-B antibody. Chest CT scan showed multiple nodular opacities with cavities in peripheral regions of both lungs. Biopsy specimens from the right lower lobe obtained by video-assisted thoracoscopy revealed marked infiltration of plasma cells and lymphocytes in alveolar lumina, lymph follicles with germinal centers in other areas of the pulmonary parenchyma, and lymphocytes infiltrate in alveolar wall adjacent bronchi and bronchioles. The histological diagnosis was pulmonary involvement of multicentric Castleman's disease. This was a rare case of Sjögren's syndrome accompanied by pathological findings of multicentric Castleman' s disease showed multiple nodular opacities in chest CT scans.

Pulmonary artery involvement in Takayasu's arteritis with lung infarction and pulmonary aspergillosis.

We describe a patient with a chronic case of pulmonary involvement of Takayasu's arteritis in the resected lung. A 49-year-old woman was first diagnosed with Takayasu's arteritis at age 30 years. On her first admission, she presented with Takayasu's arteritis and pneumonia with cavitation in the left lung. After recovering from pneumonia, she was treated initially with prednisolone, 30 mg/day, and remained well until she developed hemoptysis at age 34 years. Findings suggesting aspergilloma were found in the same lobe on chest x-ray film when she was 46 years of age. By age 49 years, the hemoptysis became massive, and she was admitted for surgery. Left upper lobectomy and partial resection of S6 and S8 pulmonary segments were performed. Histologic analysis of the resected lung revealed typical pathologic findings of pulmonary artery involvement in Takayasu's arteritis, such as stenosis recanalization and a vessel-in-vessel feature, but not active vasculitis. Infection probably occurred in the cavity of the infarcted tissue. Pulmonary artery involvement is common in Takayasu's arteritis, but the aspergilloma in this corticosteroid-treated patient is an uncommon complication.