Endoscopic resection of gastric gastrointestinal stromal tumors originating from the muscularis propria layer in North America: methods and feasibility data.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. In recent years, endoscopic procedures such as endoscopic enucleation (EN) and endoscopic full-thickness resection (EFTR) have been used to resect GISTs. This study aimed to investigate the clinical efficacy, safety, and feasibility of endoscopic resection of GISTs in a North American population. METHODS: A total of 25 patients with gastric submucosal lesions (SML) underwent endoscopic resection from December 2014 to April 2016. Data from cases with histologically proven GISTs originating from the muscularis propria layer (MP-GIST) were collected. The main outcome measures were complete resection rate, operative time, postoperative complications, length of hospital stay, narcotic analgesic requirement, and follow-up outcomes. Surveillance was performed with CT abdomen, and/or EGD along with oncology follow-up at 6- to 24-month intervals. RESULTS: Out of 25 gastric SML, there were 12 histologically proven MP-GIST. Five endophytic MP-GIST were removed by EN, and seven exophytic MP-GIST were removed by EFTR. All lesions were removed en bloc except for one hard to localize exophytic lesion which was completely removed piecemeal. The mean removal time was 79.7 min (range 17-180 min). Nine out of twelve patients required inpatient admission for observation with a mean length of stay of 2.08 days (range 1-4 days). No complications were noted and no narcotic analgesics were required. Pathology reports showed that one GIST was intermediate risk but all others were low-risk lesions. No recurrence has been noted thus far. CONCLUSION: Endoscopic removal of MP-GIST by a trained endoscopist appears to be safe and feasible in North American population. Further studies with greater sample size are necessary to compare endoscopic versus surgical resection of MP-GIST. Comparison of outcomes may support wider use of endoscopic techniques for GIST removal.

Predictors of overlapping autoimmune disease in Neuromyelitis Optica Spectrum disorder (NMOSD): A retrospective analysis in two inner-city hospitals.

BACKGROUND: The coexistence of Neuromyelitis Optica spectrum disorder (NMOSD) with other autoimmune diseases (AD-NMOSD) presents worse clinical outcomes and healthcare costs than NMOSD alone (NMOSD-only). NMOSD and other autoimmune diseases also have a higher prevalence and morbidity in Black. We aim to compare clinical features and treatment responses in NMOSD patients with and without overlapping autoimmunity in a predominantly Black cohort. We further identify predictors associated with each clinical subtype. METHODS: AD-NMOSD (n = 14) and NMOSD-only (n = 27) patients were identified retrospectively. Demographic, clinical, laboratory, imaging, and response to treatment data were examined. RESULTS: Our cohort was predominately Black (82.9%). The prevalence of grouped-comorbidities, history of infections, sensory symptoms, Expanded Disability Status Scale (EDSS) before treatment, double-stranded DNA, antinuclear, ribonucleoprotein, and antiphospholipid antibodies, spinal-cord edema, white matter occipital lesions, and the levels of C-reactive protein, urine protein/creatinine, white blood cell count in cerebrospinal fluid (CSF), were higher in AD-NMOSD patients (p < 0.05 and/or Cramer's V > 30, Cohen's d > 50), whereas the age of males, visual symptoms, serum albumin, platelet count, and optic nerve enhancement were lower. EDSS after treatment improved in both groups being more evident in NMOSD-only patients (p = 0.003, SE = 0.58 vs p = 0.075, SE = 0.51). Other variables had a close to moderate SE, and others did not differ between NMOSD subtypes. A higher frequency of grouped-comorbidities, lower serum albumin, and platelet count were independently associated with a higher risk for AD-NMOSD. CONCLUSIONS: Some clinical features between AD-NMOSD and NMOSD-only patients were similar, while others differed. Comorbidities, serum albumin, and platelet count may be independent predictors of AD-NMOSD.

PTEN is a negative regulator of mitotic checkpoint complex during the cell cycle.

Nuclear PTEN plays an important role during mitosis. To understand the molecular basis by which PTEN mediates mitotic progression, we examined whether PTEN regulated the formation of mitotic checkpoint complex (MCC). We observed that arsenic trioxide, a mitotic inducer, stimulated nuclear translocation of PTEN in a time-dependent manner. PTEN physically interacted with Cdc20 and Mad2, two important components of MCC. Arsenic treatment diminished the physical association of PTEN with BubR1 and Bub3 but not with Cdc20 and Mad2. Our further studies revealed that downregulation of PTEN via RNAi enhanced formation of MCC during the cell cycle. Moreover, PTEN silencing induced chromosomal instability. Given the crucial role of PTEN in suppressing tumor development, our study strongly suggests that PTEN also functions to maintain chromosomal stability, partly through suppressing unscheduled formation of MCC.

Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence.

BACKGROUND: Spindle assembly checkpoint components BubR1 and Sgo1 play a key role in the maintenance of chromosomal instability during cell division. These proteins function to block the anaphase entry until all condensed chromosomes have been attached by the microtubules emanating from both spindle poles. Haplo-insufficiency of either BubR1 or SGO1 results in enhanced chromosomal instability and tumor development in the intestine. Recent studies show that spindle checkpoint proteins also have a role in slowing down the ageing process. Therefore, we want to study whether haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence in mice. METHODS: We took advantage of the availability of BubR1 and SGO1 knockout mice and generated primary murine embryonic fibroblasts (MEFs) with mutations in either BubR1, SGO1, or both and analyzed cellular senescence of the MEFs of various genetic backgrounds. RESULTS: We observed that BubR1(+/-) SGO(+/-) MEFs had an accelerated cellular senescence characterized by morphological changes and expressed senescence-associated ß-galactosidase. In addition, compared with wild-type MEFs or MEFs with a single gene deficiency, BubR1(+/-) SGO1(+/-) MEFs expressed enhanced levels of p21 but not p16. CONCLUSIONS: Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence.

Difference in Cryptococcus neoformans cellular and capsule size in sequential pulmonary and meningeal infection: a postmortem study.

Cryptococcus neoformans is an encapsulated yeast that primarily causes a life-threatening meningoencephalitis in immunosuppressed individuals especially those with HIV/AIDS. Its main virulence factor is its polysaccharide capsule which interferes with complement-mediated phagocytosis. C. neoformans infections ensue following inhalation of small desiccated less encapsulated propagules leading to pulmonary pneumonia or colonization of the host's respiratory tract. Numerous murine experimental studies have shown major discrepancies in cryptococcal cell and capsule enlargement between the lung and brain. In this report, we describe a nonmurine experimental model of the striking variability between cryptococcal cell and capsule size diameters in histology sections of postmortem lung and brain in a fatal cryptococcal infection in a heart transplant recipient.