Phase 2 study of oral thalidomide-cyclophosphamide-dexamethasone for recurrent/refractory adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm with various clinical manifestations and heterogeneous prognoses. No standard therapy is available for recurrent/refractory LCH patients. This single-center, single-arm, phase 2 study enrolled 32 patients diagnosed with recurrent/refractory LCH. The TCD regimen (thalidomide 100 mg daily, cyclophosphamide 300 mg/m2 Day 1, 8, 15, and dexamethasone 40 mg Day 1, 8, 15, 22 every 4 weeks) was administered for 12 cycles and thalidomide alone as maintenance for 12 months. The primary endpoint was event-free survival (EFS). Events were defined as progression during or after TCD therapy or death from any cause. After a median follow-up of 22 months (range 5-24 months), no patient died of all causes. The overall response rate was 87.5%, including 18 patients (56.3%) achieving complete remission and 10 patients (31.3%) as partial remission. The estimated 24-month EFS was 64.0%. Patients with risk organ involvement had similar EFS compared to patients without risk organ involvement (P = 0.38). The common toxicities of TCD regimen include grade 1-2 neutropenia (18.8%), grade 1-2 constipation (12.5%), grade 1-2 tiredness (9.4%) and grade 2 peripheral neuropathy (12.5%). Oral thalidomide, cyclophosphamide and dexamethasone are effective and safe regimen for recurrent/refractory LCH patients, particularly for patients with risk organ involvement.

[Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer].

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ 2=4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.

Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

G-protein-coupled receptor kinase 2 in pancreatic cancer: clinicopathologic and prognostic significance.

G-protein-coupled receptor kinase 2 (GRK2) was found to regulate biological behaviors in some cancers, including pancreatic cancer (PC). However, its clinicopathologic and prognostic implications in cancer remain unclear. This study was designed to address the issues in PC. Expression of GRK2 was measured by Western blotting and tissue microarray-based immunohistochemical staining in 3 and 171 patients with PC, respectively. The H-score was used to evaluate the staining results. In addition, GRK2 expression was correlated with clinicopathologic variables and overall survival. Finally, the prognostic value of GRK2 was validated in a publically available PC dataset, GSE21501. It was suggested that GRK2 expression was highly up-regulated in 2 out of 3 tumor samples, in contrast to corresponding non-tumor ones. Furthermore, H-score of GRK2 staining was significantly higher in tumor than in non-tumor tissues. Tumoral expression of GRK2 was significantly associated with T stage. Univariate analysis showed that high GRK2 expression in tumor tissues was predictive for poor overall survival of PC. However, GRK2 expression was not identified as an independent prognostic marker in multivariate Cox regression test, although close to the statistical significance. In dataset GSE21501, GRK2 was also revealed to be prognostic. Our data establish that GRK2 is overexpressed in PC, and might serve as a potential indicator of unfavorable prognosis.