Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.

Tightly regulated at the level of transcription, expression of MHC class II molecules varies significantly among gastrointestinal cancers. High levels of MHC class II expression are often associated with a better prognosis, which is indicative of the involvement of CD4 þ lymphocytes in tumor suppression, but the molecular mechanism by which MHC class II expression is regulated remains unclear. In the present study, we investigated the expression of one inducible MHC class II molecule, HLA-DR, and its coactivators in a panel of colorectal and gastric cancer cell lines. Interferon-c induced expression of HLA-DR in 14 of 20 cell lines tested; the remaining six cell lines did not express HLA-DR. Analysis of the expression of transcription factors and coactivators associated with HLA-DR revealed that the loss of CIITA expression was closely associated with the absence of HLA-DR induction. Moreover, DNA methylation of the 5 0 CpG island of CIITA-PIV was detected in all cancer cells that lacked CIITA. The methylation and resultant silencing of CIITA-PIV depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3B, and their genetic inactivation restored CIITA-PIV expression. It thus appears that CIITA methylation is a key mechanism that enables some gastrointestinal cancer cells to escape immune surveillance.

Common variable immunodeficiency (CVID) is a primary immunodeficiency of unknown etiology characterized by low levels of immunoglobulin (Ig)G, failure to make specific antibodies in response to infection or immunization, and variable T-cell abnormalities. Multisystemic granulomatous disease is a well-documented complication of CVID, and its presence is associated with significant morbidity and early mortality. Although the lung is the most common organ system affected, granulomas are also found frequently in other organs, including skin, liver, spleen, and the gastrointestinal tract. Autoimmune disorders are common in these patients, and there appears to be an increased propensity to develop lymphoproliferative disorders. Common physical, radiographic, and laboratory abnormalities in patients with CVID and granulomatous disease include splenomegaly, hilar and mediastinal lymphadenopathy with ground glass or nodular opacities in the lung parenchyma, and reduced T-cell numbers and function. The etiology of granulomatous disease in patients with CVID is unknown, and optimal treatment of granulomatous disease in CVID remains to be established. Further studies are needed to elucidate the underlying etiology of granulomatous lymphoproliferative interstitial lung disease and to delineate appropriate treatments for this disease.

Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality and B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders in people who have secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested- and real time-quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gamma globulin (n = 13) or normal blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver, and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the malignant lymph node. HHV8 infection may be an important factor in the pathogenesis of the interstitial lung disease and lymphoproliferative disorders in patients with CVID.

By presenting immunogenic peptides at the cell surface, major histocompatibility complex (MHC) class II molecules play a key role in the control of adaptive immune responses. Whether expressed constitutively or induced by interferon-g, expression of MHC class II molecules is regulated via coactivator class II transactivator (CIITA); moreover, suppression of their expression is one mechanism by which cancer cells escape host immunity. In this study, we surveyed the relationship between the expression of one MHC class II antigen, HLA -DR, and its coactivators in a group of haematopoietic cell lines, and explored the role of the aberrant DNA methylation in silencing HLA-DR expression. Among 26 cell lines studied, HLA-DR expression was lost from eight T-cell and two myeloid leukaemia cell lines, and this loss was closely associated with suppression of CIITA-PIV expression. Notably, nine of the 10 cell lines that lost CIITA-PIV expression showed methylation of the gene's 5 0 CpG island. Thus, DNA methylation is believed to inhibit the expression of MHC class II molecules in haematopoietic tumour cells by silencing its coactivator, CIITA-PIV. Furthermore, methylation of CIITA-PIV was detected in seven of 32 primary acute myeloid leukaemia specimens, indicating that epigenetic alteration is not a cell line-specific phenomenon. Collectively, these data suggest that, by suppressing expression of MHC class II molecules, epigenetic inactivation of CIITA provides a survival advantage to a subset of haematopoietic tumours.

Primary immunodeficiencies are challenging in primary care settings, where clinicians often encounter patients with a history of recurrent infection. With advances in diagnostics and therapeutics, these disorders have been better understood and more successfully treated, yet their prognosis depends on early recognition of the disorder and initiation of the appropriate management. Because the primary care physician is most often the first physician encountered by a patient with immunodeficiency, primary care practitioners should be familiar with these rare but important disorders. This article provides an overview of the diagnosis and treatment of primary immunodeficiencies and two of the most common primary immunodeficiencies: common variable immunodeficiency and selective IgA deficiency.

Thirteen factors closely related to hospital stay duration and LOS prediction score could predict the prolongation of a patient's hospital stay.

No abstract