Purpose: Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States.Patients and Methods: The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007.Results: We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001).Conclusion: In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis.

Signaling through the high affinity IgE receptor FcϵRI on human basophils and rodent mast cells is decreased by co-aggregating these receptors to the low affinity IgG receptor FcγRII. We used a recently described fusion protein, GE2, which is composed of key portions of the human γ1 and the human ϵ heavy chains, to dissect the mechanisms that lead to human mast cell and basophil inhibition through co-aggregation of FcγRII and FcϵRI. Unstimulated human mast cells derived from umbilical cord blood express the immunoreceptor tyrosine-based inhibitory motif-containing receptor FcγRII but not FcγRI or FcγRIII. Interaction of the mast cells with GE2 alone did not cause degranulation. Co-aggregating FcϵRI and FcγRII with GE2 1) significantly inhibited IgE-mediated histamine release, cytokine production, and Ca²⁺ mobilization, 2) reduced the antigen-induced morphological changes associated with mast cell degranulation, 3) reduced the tyrosine phosphorylation of several cellular substrates, and 4) increased the tyrosine phosphorylation of the adapter protein downstream of kinase 1 (p62^dok; Dok), growth factor receptor-bound protein 2 (Grb2), and SH2 domain containing inositol 5-phosphatase (SHIP). Tyrosine phosphorylation of Dok was associated with increased binding to Grb2. Surprisingly, in non-stimulated cells, there were complexes of phosphorylated SHIP-Grb2-Dok that were lost upon IgE receptor activation but retained under conditions of Fcϵ-Fcγ co-aggregation. Finally, studies using mast cells from Dok-1 knock-out mice showed that IgE alone triggers degranulation supporting an inhibitory role for Dok degranulation. Our results demonstrate how human FcϵRI-mediated responses can be inhibited by co-aggregation with FcγRIIB and implicate Dok, SHIP, and Grb2 as key intermediates in regulating antigen-induced mediator release.

Little is known about the epidemiology of rectal carcinoids in the United States since the implementation of screening colonoscopy. The goal of this study was to identify epidemiological differences between rectal and small intestinal carcinoids. This study was retrospective in design. Surveillance, Epidemiology and End Results registry data from 1992 to 2008 were examined. Patients with rectal carcinoids included those with carcinoid tumors of the rectum. Patients with small intestinal carcinoids included those with carcinoids in the duodenum, jejunum, or ileum. Epidemiological characteristics of rectal carcinoids were identified and compared with small intestinal carcinoids using multiple variable logistic regression. Patients with rectal carcinoids were more likely to be women (OR, 1.196 (95% CI, 1.090-1.311); p < 0.001). Rectal carcinoids were more common among all minorities, including Asians (OR, 10.063 (95% CI, 8.330-12.157); p < 0.001), blacks (OR, 1.994 (95% CI, 1.770-2.246); p < 0.001), and Hispanics (OR, 2.682 (95% CI, 2.291-3.141), p < 0.001). Patients in the 50- to 59-year age group (OR, 0.752 (95% CI, 0.599-0.944); p = 0.014) were more likely to be diagnosed with rectal carcinoids than those in the 60- to 69-year (OR, 0.481 (95% CI, 0.383-0.605); p < 0.001) and ≥70-year age groups (OR, 0.220 (95% CI, 0.175-0.277); p < 0.001). Rectal carcinoids were more likely to be diagnosed in the screening colonoscopy era among the 50- to 59-year age group (OR, 1.432 (95% CI, 1.082-1.895); p = 0.012). Since the implementation of screening colonoscopy in 2000, the proportion of patients diagnosed with rectal carcinoids has been greater than the proportion diagnosed with small intestinal carcinoids in every year except 2001, and the proportion of patients diagnosed with rectal carcinoids after 2000 has been greater than the proportion diagnosed with small intestinal carcinoids in 12 of 13 Surveillance, Epidemiology, and End Results registry reporting agencies. Rectal carcinoids and small intestinal carcinoids are epidemiologically distinct tumors with unique presentations. In the era of screening colonoscopy, rectal carcinoids are the more common tumor.

We hypothesized that the addition of mitral valve replacement or repair (MVR) to implantation of continuous-flow left ventricular assist device (cf-LVAD) may further decrease pulmonary vascular resistance (PVR) over Heartmate II (HMII) implantation alone. Patients undergoing MVR with concomitant HMII implantation were compared with those undergoing HMII implantation alone. Of the 57 patients undergoing cf-LVAD implantation, 21 (36.8%) underwent concomitant MVR and 36 (63.2%) underwent cf-LVAD implantation alone. Patients receiving MVR had greater decrement in PVR (59.4% vs. 35.2%, p = 0.01). Decrease in end-diastolic diameter was greater for patients receiving MVR but did not reach statistical significance (18.2 vs. 13.5 mm, p = 0.33). Duration of mechanical ventilation (121.6 vs. 181.4 hours, p = 0.45) and inotropic support (162.4 vs. 153.2 hours, p = 0.86), change in creatinine (0.19 vs. -0.26 mg/dl, p = 0.34), increase in bilirubin (2.54 vs. 1.55 mg/dl, p = 0.63), intensive care unit stay (168.0 vs. 231.5 hours, p = 0.38), and overall length of stay (32.0 vs. 42.5 days, p = 0.75) were similar. There was no difference in survival at 3 months (89.7% vs. 83.3%) and 1 year (83.7 vs. 67.3%, p = 0.34). Addition of MVR may result in greater decrement of PVR than HMII implantation alone. This may permit certain patients thought to be ineligible for transplantation to become candidates.