Synchronous gastric adenocarcinoma and carcinoid

We report the rare case of a 68-year-old man who had two separate and histologically dissimilar gastric tumors: a poorly differentiated adenocarcinoma and a carcinoid. The latter tumor showed argyrophilic granules (Grimelius technique) and positivity for chromogranin A and neuron-specific enolase stains, confirming the neuroendocrine nature of the neoplasia. The literature concerning this subject is reviewed.     

Increased program cell death-1 expression on T lymphocytes of patients with progressive multifocal leukoencephalopathy

The cellullar immune response is important in the containment of progressive multifocal leukoencephalopathy (PML). We examined program cell death-1 (PD-1) expression, a marker of cellular immune exhaustion, on T lymphocytes in PML. PD-1 expression was elevated on total CD4(+) and CD8(+) T cells (medians 36% and 24%) in PML patients compared with healthy control subjects (medians 14% and 18%; P = 0.0015 and P = 0.033). In PML patients, JC virus (JCV)-specific CD8(+) cytotoxic T lymphocytes expressed PD-1 more frequently than total CD8 T lymphocytes (means 39% and 78%, P = 0.0004). Blocking the PD-1 receptor increased JCV-specific T-cell immune response in a subgroup of PML patients.     

Should we always plan a Fontan completion after a Kawashima procedure?

Objective: To determine the late incidence of pulmonary arteriovenous malformations after bidirectional Glenn in patients with azygos continuation of the inferior vena cava (Kawashima operation). Methods: From 1990 to 2006, 21 patients underwent a Kawashima procedure at a median age of 2.3 years (0.5–8 years). Underlying anatomy included atrioventricular septal defect [14], double-outlet right ventricle [13], pulmonary atresia [3], pulmonary stenosis [11], total anomalous pulmonary venous drainage [4] and bilateral superior vena cavae [14]. Results: There was one hospital death after Kawashima due to low output syndrome. Follow-up was complete in all but one patient. Two patients died 23 days and 4 years after Kawashima following cardiac reinterventions (one atrioventricular valve replacement and one Fontan completion). Thirteen patients developed pulmonary arteriovenous malformations after a median of 4 years (2–9 years) after Kawashima. Freedom from development of arteriovenous malformations was 47% at 5 years (95% CI: 23–69%). A total of 16 patients underwent Fontan completion, 12 for cyanosis related to pulmonary arteriovenous malformations and four for decreased exercise capacity. Only three patients were left without Fontan completion at 4, 9 and 13 years after Kawashima. The two patients who had more than 9 years of follow-up after Kawashima had antegrade flow preserved between the ventricle and the pulmonary arteries. Conclusion: Unless some hepatic blood flow is directed to both lungs, most, if not all patients with a Kawashima procedure will ultimately develop pulmonary arteriovenous malformations. Elective non-fenestrated Fontan completion in the years following Kawashima procedure should be recommended.     

Incarcerated retroperitoneal hernia following total extraperitoneal laparoscopic radical nephrectomy

Small bowel obstruction (SBO) is a common entity encountered in surgical patients. The most common causes of the SBO range from postoperative adhesions to cancer. We present the case of a 55-year-old male who underwent a laparoscopic left radical nephrectomy and presented with an early SBO. An imaging study revealed an obstructive pattern with proximal dilated jejunum with decompressed distal small bowel. The patient underwent an exploratory laparotomy with extensive lysis of adhesions and release/resection of a long segment of incarcerated jejunum from an 8-cm retroperitoneal hernia in the left renal fossa. The patient was discharged home, and at 3-month follow-up no bowel complaints were reported.     

CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.     

Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells

Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. However, the well-known limitations of current reprogramming technologies include low efficiency, slow kinetics, and transgene integration and residual expression. In the present study, we have demonstrated that iPSCs free of transgene and vector sequences could be generated from human BM and CB mononuclear cells using non-integrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1-3 weeks faster compared with the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. Blood-derived iPSC lines lacked rearrangements of IGH and TCR, indicating that their origin is non-B- or non-T-lymphoid cells. When cocultured on OP9, blood-derived iPSCs could be differentiated back to the blood cells, albeit with lower efficiency compared to fibroblast-derived iPSCs. We also generated transgene-free iPSCs from the BM of a patient with chronic myeloid leukemia (CML). CML iPSCs showed a unique complex chromosomal translocation identified in marrow sample while displaying typical embryonic stem cell phenotype and pluripotent differentiation potential. This approach provides an opportunity to explore banked normal and diseased CB and BM samples without the limitations associated with virus-based methods.