RESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a poor prognosis cancer with an .aggressive growth profile that is often diagnosed at late stage and that has few curative or therapeutic options. PDAC growth has been linked to alterations in the pancreas microbiome, which could include the presence of the fungus Malassezia. We used RNA-sequencing to compare 14 paired tumor and normal (tumor adjacent) pancreatic cancer samples and found Malassezia RNA in both the PDAC and normal tissues. Although the presence of Malassezia was not correlated with tumor growth, a set of immune- and inflammatory-related genes were up-regulated in the PDAC compared to the normal samples, suggesting that they are involved in tumor progression. Gene set enrichment analysis suggests that activation of the complement cascade pathway and inflammation could be involved in pro PDAC growth.
RESUMO
INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL); is an unusual entity first described in 1990 that predominantly affects middle-aged men and is classified by WHO under peripheral T-cell lymphomas. We present a 26-year-old man with HSCTL treated with a non-CHOP regimen. CASE: A 26 year old immigrant from Cameroon without significant past medical history presented with abdominal discomfort that was first noted 1 month prior at which time he was elbowed in abdomen during a basketball game. His abdominal discomfort continued to gradually worsen and was associated with nausea, vomiting, early satiety and decreased appetite. He developed subjective fever, chills, night sweats, fatigue and epistaxis 3 days prior to presentation. CBC with differential revealed WBC 8 x 103/ul, RBC 4.50 x 103/ul, Hemoglobin 12.9 mg/dl, Hematocrit 38.2 percent , Platelets 30 x 103/ul, elevated monocytes and nRBC's. EBV serology was positive for VCA IgG and Nuclear-antigen Antibody IgG, indicating past infection. Abdominal CT revealed marked hepatosplenomegaly with displacement of abdominal viscera. PET revealed heterogeneously increased FDG uptake in liver and spleen. Bone marrow showed increased cellularity, increased atypical lymphocytes with clustering, and sinusoidal infiltration. Lymphoid cells mainly expressed CD2, CD3 and CD8. Cells were negative for TdT, CD1a, and increase in Ki-67 expression. Bone marrow flow cytometry revealed predominance of atypical gamma/delta T cells. Cytogenetics revealed normal male karyotype. Based on imaging, bone marrow, and flow cytometry, diagnosis of HSCTL was made. The patient was treated with 4 cycles of Ifosfamide, Carboplatin and Etoposide (ICE);. PET showed complete resolution of uptake in liver and spleen. Repeat bone marrow showed no residual disease. He underwent splenectomy and pathology revealed no evidence of residual T-cell lymphoma. The patient then underwent autologous SCT with BEAM (Carmustine-Etoposide-Cytarabine-Melphalan); conditioning. He remains in remission after transplantation. DISCUSSION: Although HSTCL is rare, recognition is important as it is aggressive, refractory to conventional therapies, and carries a uniformly poor prognosis. Conventional therapy consists of CHOP (cyclophosphamide-doxorubicin-vincristine-prednisone); with or without autologous stem cell transplantation (SCT);. A novel approach reported by Hoss et.al with a non-CHOP induction therapy with or without splenectomy followed by autologous SCT may have better outcomes as demonstrated with our case.