Evaluation of apremilast,an oral phosphodiesterase 4 inhibitor,for refractory cutaneous dermatomyositis: A phase 1b clinical trial

Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by cutaneous itchy manifestations, which are frequently refractory and recurrent even after intensive immunosuppressive treatments. To evaluate the effectiveness and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in treating skin-dominant dermatomyositis in which myositis and interstitial lung disease are absent or in remission, we performed this prospective, single-arm, interventional study. A total of five Japanese patients (one male and four females, median [range] age, 64 [37–71] years) with refractory dermatomyositis-associated cutaneous manifestations were recruited and treated with a 12-week course of oral apremilast. Among five enrolled patients, three experienced diarrhea with full-dose apremilast (30 mg twice daily), two of whom withdrew from the study and recovered quickly afterwards. A total of three evaluable female patients (median [range] age, 65 [64–71] years) received apremilast treatment for 12 weeks. A 39.4% reduction from baseline Cutaneous Dermatomyositis Disease Area and Severity Index total activity score, but not the damage score, at week 12 was observed in all three patients. Visual analog scale of itching, and quality of life by Dermatology Life Quality Index were slightly improved in one and two apremilast-treated patients, respectively. As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis-associated cutaneous manifestations in this first phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high-dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required.     

Case of localized scleroderma associated with osteomyelitis

We report a 4-year-old girl presenting with progressive linear scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of localized scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T₂-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with localized scleroderma to evaluate the extension of the inflammation.     

Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration

BACKGROUND AND AIM: The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. METHODS: The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. RESULTS: Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. CONCLUSION: Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients.     

Insulin alters cardiac muscle creatine kinase activity

The expression of mRNAs of creatine kinase (CK)-B and CK-M has been show to be affected by insulin, and myocardial CK-MB activity is suppressed in insulin-deficient rats. We investigated the dose-related effect of insulin on CK-MB activity in cardiac and skeletal muscles. Male Wistar rats were divided into three groups: (1) control group, (2) diabetic group, injected with 65 mg/kg streptozotocin for 4 weeks, and (3) atenolol group, administered 30 mg/kg per day atenolol. Each group was further divided into three subgroups and administered either saline, or 20 (Ins 20) or 30 (Ins 30) U/kg per day insulin. After 3 weeks, the isoenzyme activity of CK and lactate dehydrogenase (LDH) in the left ventricle of the heart (LV) and the major pectoral muscle (PM) was measured. Serum insulin increased and plasma glucose decreased in Ins 20 and Ins 30, dose-dependently, in all three groups. Both CK-MB and -BB activity in LV increased dose-dependently with insulin treatment in the control, diabetes, and atenolol groups, although these changes did not occur in skeletal muscles. CK-MB in LV correlated with the serum insulin levels in all rats, while no correlation was found in the skeletal muscles. These findings suggest that insulin possibly regulates the distribution of CK isoenzymes in rat heart muscle, and that the effect of insulin is not due to the sympathetic drive induced by hypoglycemia. Received: November 8, 1999 / Accepted: February 12, 2000     

Characterization of anti-myocardial autoantibodies in Japanese patients with dilated cardiomyopathy

Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.     

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.     

Implications of arterial anatomy in patients with cancer of the periampullary region

BACKGROUND/AIMS: Preoperative information on arterial anatomy in the peripancreatic and hepatic areas is valuable to any surgeon performing pancreatoduodenectomy. METHODOLOGY: Between 1994 and 1998, 49 patients with periampullary cancer (31 distal bile duct and 18 ampullary tumors) underwent visceral angiography and radical pancreatoduodenectomy with lymphadenectomy. Surgically "significant" arterial variations and their effects on operative management and results were examined retrospectively. RESULTS: Arterial variations were found in 18 patients (37%); 15 (31%) were "significant" and 3 (6%) were "nonsignificant." All 15 patients with "significant" variants required specific type of various preservations of the hepatic arterial system. Intraoperative blood loss, transfused blood units, and operation time were greater in patients with "significant" variations than in patients without (P<0.05). Histopathologic diagnosis, tumor staging, morbidity, and mortality did not differ between the 2 groups. The 5-year survival was 33% for patients with "significant" variations and 63% for patients without (P<0.05). CONCLUSIONS: Information on arterial anatomy in the peripancreatic and hepatic areas is necessary for preoperative evaluation in patients requiring radical pancreatoduodenectomy. Presence of "significant" arterial variations may be considered as one of the negative prognostic factors in patients with periampullary cancer.     

An extramural gastrointestinal stromal tumor of the duodenum mimicking a pancreatic head tumor

We report the case of a 53‐year‐old woman with a gastrointestinal stromal tumor (GIST) of the duodenum that showed only extramural growth, mimicking a pancreatic tumor. Preoperatively, computed tomography (CT) and angiography revealed a hypervascular mass, 3.0 cm in diameter, in the pancreatic head. Hypotonic duodenography showed compression of the second and third portions of the duodenum by the pancreatic lesion. Endoscopic examination showed no specific mucosal abnormalities in the duodenal lumen. The pancreatic head tumor was diagnosed preoperatively as a nonfunctioning islet cell tumor of the pancreas, and the patient underwent pylorus‐preserving pancreaticoduodenectomy. A hard mass was palpated intraoperatively in the pancreatic head region, and neither peritoneal dissemination nor metastasis was detected. Histologically, the tumor was composed of spindle‐shaped cells with a fascicular growth pattern, and only a few mitotic features were seen. Immunohistochemically, most of the tumor cells were positive for c‐kit oncoprotein and CD34, but negative for alpha‐smooth muscle actin and S‐100 protein. Therefore, this neoplasm was finally diagnosed as a duodenal GIST of the uncommitted type. This is a rare case of a duodenal GIST with exclusively extramural growth mimicking a pancreatic head tumor.