Mediastinal pancreatic pseudocyst with hemorrhage and left gastric artery pseudoaneurysm, managed with left gastric artery embolization and placement of percutaneous trans-hepatic pseudocyst drainage.

Mediastinal pancreatic pseudocyst (MPP) is a rare, but known, complication of both acute and chronic pancreatitis. Most pseudocysts are associated with alcoholic pancreatitis. Recent advances in endoscopic techniques have shown promising results, with reduced chances of infection and recurrence than with percutaneous drainage, but limited availability restricts widespread use. Left gastric artery pseudoaneurysm with mediastinal pseudocyst has not been described in the literature to date. We report a successful resolution of hemorrhagic MPP with embolization of pseudoaneurysm and percutaneous trans-hepatic pseudocyst drainage.

Obstructive jaundice as an initial manifestation of non-hodgkin lymphoma: treatment dilemma and high mortality.

Introduction. Non Hodgkin lymphoma (NHL) presenting with obstructive jaundice is a rare occurrence. Because of rarity of combination, it is seldom considered in differential diagnosis of patients presenting with obstructive jaundice. It is considered treatable due to the chemosensitive nature of the disease and the recent advances in chemotherapy. Case Series. We present a case series of 2 patients with NHL presenting with obstructive jaundice as an initial manifestation. Both patients presented with obstructive jaundice and were diagnosed by CT guided liver biopsy. One patient died of sepsis and multiorgan failure before initiating chemotherapy and the second patient did not choose to undergo chemotherapy. Conclusion. Biliary obstruction is a sign of poor prognosis. The diagnosis of NHL needs to be considered in patients presenting with biliary obstruction. It can be associated with high mortality and poses treatment dilemma.

Impaired hepatitis B vaccine responses during chronic hepatitis C infection: involvement of the PD-1 pathway in regulating CD4(+) T cell responses.

Vaccination for hepatitis B virus (HBV) in the setting of hepatitis C virus (HCV) infection is recommended, but responses to vaccination are blunted when compared to uninfected populations. The mechanism for this failure of immune response in HCV-infected subjects remains unknown but is thought to be a result of lymphocyte dysfunction during chronic viral infection. We have recently demonstrated that PD-1, a novel negative immunomodulator for T cell receptor (TCR) signaling, is involved in T and B lymphocyte dysregulation during chronic HCV infection. In this report, we further investigated the role of the PD-1 pathway in regulation of CD4(+) T cell responses to HBV vaccination in HCV-infected individuals. In a prospective HCV infected cohort, a poor response rate to HBV vaccination as assayed by seroconversion was observed in HCV-infected subjects (53%), while a high response rate was observed in healthy or spontaneously HCV-resolved individuals (94%). CD4(+) T cell responses to ex vivo stimulations of anti-CD3/CD28 antibodies or hepatitis B surface antigen (HBsAg) were found to be lower in HBV vaccine non-responders compared to those responders in HCV-infected individuals who had received a series of HBV immunizations. PD-1 expression on CD4(+) T cells was detected at relatively higher levels in these HBV vaccine non-responders than those who responded, and this was inversely associated with the cell activation status. Importantly, blocking the PD-1 pathway improved T cell activation and proliferation in response to ex vivo HBsAg or anti-CD3/CD28 stimulation in HBV vaccine non-responders. These results suggest that PD-1 signaling may be involved in impairing CD4(+) T cell responses to HBV vaccination in subjects with HCV infection, and raise the possibility that blocking this negative signaling pathway might improve success rates of immunization in the setting of chronic viral infection.

Differential regulation of T and B lymphocytes by PD-1 and SOCS-1 signaling in hepatitis C virus-associated non-Hodgkin's lymphoma.

HCV infection is associated with immune dysregulation and B cell Non-Hodgkins lymphoma (HCV-NHL). We have previously shown in vitro that HCV core protein differentially regulates T and B cell functions through two negative signaling pathways, programmed death-1 (PD-1) and suppressor of cytokine signaling-1 (SOCS-1). In this report, we performed a detailed immunologic analysis of T and B cell functions in the setting of HCV-NHL. We observed that T cells isolated from patients with HCV-NHL exhibited an exhausted phenotype including decreased expression of viral-specific and non-specific activation markers; whereas B cells exhibited an activated phenotype including over-expression of cell activation markers and immunoglobulins compared to healthy subjects. Individuals with HCV alone or NHL alone exhibited abnormal T and B cell phenotypes, but to a lesser extent compared to HCV-NHL. This differential activation of T and B lymphocytes was inversely associated with the expression of PD-1 and SOCS-1. Interestingly, blocking PD-1 during TCR activation inhibited SOCS-1 gene expression, suggesting that these regulatory pathways are linked in T cells. Importantly, blocking PD-1 also restored the impaired T cell functions observed in the setting of HCV-NHL. These results support a coordinated mechanism by which HCV might cause immune dysregulation that is associated to HCV-NHL.

PD-1 modulates regulatory T cells and suppresses T-cell responses in HCV-associated lymphoma.

T regulatory (T(R)) cells suppress T-cell responses that are critical in the development of chronic viral infection and associated malignancies. Programmed death-1 (PD-1) also has a pivotal role in regulation of T-cell functions during chronic viral infection. To examine the role of PD-1 pathway in regulating T(R)-cell functions that inhibit T-cell responses during virus-associated malignancy, T(R) cells were investigated in the setting of hepatitis C virus-associated lymphoma (HCV-L), non-HCV-associated lymphoma (non-HCV-L), HCV infection alone and healthy subjects (HS). Relatively high numbers of CD4(+)CD25(+) and CD8(+)CD25(+) T(R) cells, as well as high levels of PD-1 expressions on these T(R) cells were found in the peripheral blood of subjects with HCV-L compared with those from non-HCV-L or HCV alone or HS. T(R) cells from the HCV-L subjects were capable of suppressing the autogeneic lymphocyte response, and depletion of T(R) cells in peripheral blood mononuclear cells from HCV-L improved T-cell proliferation. Additionally, the suppressed T-cell activation and proliferation in HCV-L was partially restored by blocking the PD-1 pathway ex vivo, resulting in both a reduction in T(R)-cell number and the ability of T(R) to suppress the activity of effector T cells. This study suggests that the PD-1 pathway is involved in regulating T(R) cells that suppress T-cell functions in the setting of HCV-associated B-cell lymphoma.

Candida glabrata liver abscess and fungemia complicating severe calculus cholecystitis in an immunocompetent nondiabetic host.

We report a rare case of Candida glabrata liver abscess and fungemia complicating severe calculus cholecystitis in a 64-year-old female patient who had no history of immunosuppression or diabetes mellitus. The patient underwent cholecystectomy, resection of liver abscess, and systemic antifungal therapy using micafungin.

Abnormal B-cell activation associated with TALL-1 over-expression and SOCS-1 suppression during chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is associated with cirrhosis, autoimmunity and lymphoproliferative disorders. We have previously reported a differential regulation of T and B lymphocytes by HCV core protein in vitro. In this report, we employed a translational approach to characterize the activation status of peripheral B cells from individuals with chronic HCV infection and to explore potential mechanisms for B-cell dysregulation in the setting of HCV infection. In contrast to the T-cell suppression observed in HCV-infected individuals, B cells exhibit a non-specific polyclonal activation phenotype, characterized by significantly higher levels of (1) the early activation marker, CD69, (2) the costimulatory molecule, CD86, and (3) the CCR5 chemokine receptor, CD195, when compared with B cells from healthy donors in response to phytohaemagglutinin (PHA) stimulation. Importantly, tumour necrosis factor- and Apo-L-related leucocyte-expressed ligand-1 (TALL-1), also known as B-lymphocyte stimulator (BLYS), was found to be up-regulated on the surface of B cells from HCV patients in response to PHA as well as HCV core antigen stimulation. This up-regulation of TALL-1 was associated with vigorous memory B-cell responses to viral antigenic stimulation. Additionally, suppressor of cytokine signalling-1 (SOCS-1), a negative feedback immunoregulator that is inhibited in B lymphocytes by HCV core in vitro, was also inhibited in B cells from HCV patients when compared with healthy donors. These findings suggest that TALL-1 over-expression and SOCS-1 suppression are associated with aberrant B-cell activation, providing a plausible basis for the B-cell clonal expansion underlying the lymphoproliferative disorders and autoimmune phenomena observed during chronic HCV infection.

A wayward cyst.

CONTEXT: Pseudocysts are a common complication of acute and chronic pancreatitis. These are usually located within the pancreas but they can occur at other sites as well, including the mediastinum, neck, pelvis and rarely in the liver as in our case. The diagnosis of intrahepatic pancreatic pseudocyst relies on the demonstration of a high amylase level in the sampled cystic fluid in the absence of infection or neoplasm. CASE REPORT: A 60-year-old man with a history of chronic pancreatitis presents with a clinical and laboratory picture suggestive of acute exacerbation of his pancreatitis. A computed tomogram (CT) scan of the abdomen revealed a pancreatic pseudocyst and a cystic lesion involving both lobes of the liver. CT diagnostic aspiration of the intrahepatic cyst revealed high amylase level (greater than 20,000 U/L). The cyst was treated with percutaneous drainage with complete resolution of the cyst. CONCLUSION: In the setting of pancreatitis, intrahepatic pancreatic pseudocyst should be considered in the differential diagnosis of cystic lesion of the liver.