Successful treatment of extramedullary tumors with low-dose thalidomide in patients with multiple myeloma

Extramedullary tumor (EMT) is a poor prognostic factor of multiple myeloma (MM). The majority of patients report poor efficacy of thalidomide in MM with EMT, and bortezomib is the preferred choice of treatment. We report two cases of MM with EMTs in which thalidomide was highly beneficial. Case 1 has been in remission for ten months with 100 mg every other day of thalidomide monotherapy, which is the lowest dose to be reported in a successfully treated case of MM with EMT. Case 2 eventually became refractory, but low dose thalidomide gave excellent disease control over a period of eleven weeks, despite the EMT being in a highly aggravated state. Some reports have speculated that EMT cases with preceding bone marrow transplantation (BMT) are an exception and have a good response to thalidomide, but the present two cases have no history of BMT. In conclusion, low dose thalidomide can be effective in MM with EMT and should be considered as a treatment option, especially in the elderly.     

Development of a simple model for predicting need for surgery in patients who initially undergo conservative management for adhesive small bowel obstruction

Background

Among patients with adhesive small bowel obstruction (ASBO) initially managed with a conservative strategy, predicting risk of operation is difficult.

Methods

We investigated ASBO patients at 2 different periods to derive and validate a clinical prediction model for risk of operation.

Results

One hundred fifty-four patients were enrolled into the derivation cohort and 96 into the validation cohort. Based on the derived scoring, including age ≥65 years, presence of ascites, and gastrointestinal drainage volume >500 mL on day 3, each patient was classified into 1 of 4 risk classes from low risk to high risk. When applied to the validation cohort, the positive predictive value (PPV) for operation in the high-risk class was 72%, while the negative predictive value (NPV) in the low-risk class was 100% with high sensitivity (100%) and specificity (96%).

Conclusions

The prediction model performs well for risk stratification of need for surgical intervention following conservative strategy among ASBO patients.     

Enhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells

Background

Hyperglycemia/high glucose may induce apoptosis in diabetic kidney, but the mechanism is not fully understood. Naofen was found as a Shiga toxin (Stx)-2-related protein. Based on renal dysfunction in infection with Stx-producing Escherichia coli and on participation of naofen in apoptosis of human embryonic kidney cells, the present study was undertaken to investigate the mechanism of renal dysfunction in diabetes mellitus with particular reference to naofen.

Methods

In in vivo studies utilizing streptozotocin (STZ)-induced diabetic rats, and also in in vitro cultured rat kidney epithelial (NRK52E) cells, naofen messenger RNA (mRNA) and protein expressions were analyzed. Naofen mRNA location in diabetic kidney was studied by in situ hybridization. Apoptosis was assessed by caspase-3 activity assay.

Results

Rat diabetic kidney showed significant increases in caspase-3 activities and naofen mRNA. Naofen was mainly observed at both proximal and distal urinary tubules. Incubation of NRK52E cells in high glucose medium resulted in elevated naofen mRNA expression, whereas neither interleukin-1, interleukin-6, nor tumor necrosis factor-α elicited such action. Moreover, treatment of NRK52E cells with naofen small interfering RNA (siRNA) inhibited naofen mRNA expression induced by high glucose and blocked the increase in caspase-3 activity.

Conclusions

These data suggest that naofen expression may be upregulated by hyperglycemia, with possible correlation to apoptosis of tubular epithelial cells and thereby to diabetic nephropathy.     

Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease—Serial angioscopic and intravascular ultrasound analysis

BackgroundDiabetes mellitus (DM) is a major risk factor for cardiovascular events. The study purpose was to compare DM and non-DM (nDM) patients in terms of statin-induced change of plaque characteristics using intravascular ultrasound (IVUS) and coronary angioscopy.MethodsPatients with coronary artery disease and hypercholesterolemia who were enrolled to the TWINS were selected and classified into two groups: DM group and nDM group. Eleven DM patients and 28 nDM patients were studied.ResultsLow-density lipoprotein cholesterol levels decreased significantly to a similar extent at weeks 28 and 80 from baseline in DM and nDM (p < 0.001). The mean angioscopic color grades of yellow plaques in DM and nDM were similar at baseline and significantly decreased at week 80 from baseline in both groups, however, the mean change of angioscopic color grade from baseline in DM were not significantly decreased and the mean angioscopic color was significantly higher than that in nDM (1.34 vs. 1.00, p < 0.05) at week 28. IVUS showed plaque volume reduction in both groups (p < 0.01) except at week 80 in DM group, which was not statistically significant different compared to the baseline.ConclusionIn DM patients, plaque volume regression by atorvastatin was shown to be attenuated, and its color improvement was significantly delayed. However, the yellowness became comparable between DM and nDM groups at week 80. These results indicate that patients with DM should be treated by intensive lipid-lowering therapy with atorvastatin for at least 80 weeks to stabilize vulnerable plaque.     

Angioimmunoblastic T-cell lymphoma with intramedullary production of platelet-derived growth factor and possibly complicating myelofibrosis: report of a case with review of the literature

A 65-year-old man was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with bone marrow (BM) infiltration and myelofibrosis (MF). The BM infiltration and the condition of the MF improved following CHOP therapy (cyclophosphamide hydrate, doxorubicin hydrochloride, vincristine sulfate, and prednisolone). After complete remission was achieved, early central nervous system recurrence was noted, with no evidence of BM infiltration or MF. The lymph nodes and BM were examined for cytokines by immunohistochemical staining with monoclonal murine antibodies. The lymphoma cells were positive only for platelet-derived growth factor (PDGF) and negative for basic fibroblast growth factor, fibronectin, vascular endothelial growth factor, transforming growth factor-β (TGF-β), tumor necrosis factor α, interleukin-1β, and interleukin-6. It was thus inferred that the lymphoma cells producing PDGF caused the MF, and that the absence of MF at relapse may have been attributable to the absence of BM infiltration. There have been seven reported cases of AITL with intercurrent MF, although cytokine data (elevations of blood PDGF and TGFβ levels) are available for only one case. The present report is to our knowledge the only report of a case of AITL complicated by MF for which the results of immunohistostaining with anticytokine antibodies are available.