The Morphologic Assessment of Rectal Neuroendocrine Tumors

AbstractBackground and aimsThe histopathologic features of rectal neuroendocrine tumors (NETs), including size, lymphovascular invasion, invasion of proper muscle, and mitotic rate, have a limited role to play in determining a treatment plan preoperatively. We aimed to investigate the morphologic parameters associated with metastasis, and to evaluate their predictive value.MethodsBetween January 2000 and May 2011, the medical records and endoscopic findings of 468 patients presenting with rectal NETs at the Samsung Medical Center were analyzed retrospectively. All tumors were classified according to size and endoscopic features such as color, shape, contour, and surface change.ResultsTwenty-one of the 468 patients (4.5%) with rectal NETs had lymph node (LN) metastasis and 11 patients (2.4%) had distant metastasis. Risk factors for metastasis included tumor size (≥10mm in diameter), hyperemic change, polypoid lesions, irregular contours, and surface ulceration (p=0.000). Independent risk factors that were predictive of metastasis on multivariate analysis included tumor size (≥10mm in diameter), hyperemic change, and surface ulceration. As the number of independent risk factors for metastasis increased, the risk of metastasis rose.ConclusionsEndoscopic features such as hyperemic change, polypoid lesions, irregular contours, and surface ulcers with tumor size ≥10mm in diameter are associated with metastasis in rectal NETs. In particular, atypical endoscopic features including hyperemic change, and surface ulcer with tumor size ≥10mm in diameter may help to predict the risk of metastasis of rectal NETs

Screening for Mycobacterium tuberculosis Infection Using Beijing/K Strain-Specific Peptides in a School Outbreak Cohort.

Background: The Beijing strain of Mycobacterium tuberculosis (M. tb) has been most frequently isolated from TB patients in South Korea, and the hyper-virulent Beijing/K genotype is associated with TB outbreaks. To examine the diagnostic potential of Beijing/K-specific peptides, we performed IFN-γ release assays (IGRA) using a MTBK antigen tube containing Beijing/K MTBK_24800, ESAT-6, and CFP-10 peptides in a cohort studied during a school TB outbreak. Methods: A total of 758 contacts were investigated for M. tb infection, and 43 contacts with latent TB infection (LTBI) and 25 active TB patients were enrolled based on serial screening with QuantiFERON-TB Gold In-Tube tests followed by clinical examinations. Blood collected in MTBK antigen tubes was utilized for IGRA and multiplex cytokine bead arrays. Immune responses were retested in 24 patients after TB treatment, and disease progression was investigated in subjects with LTBI. Results: Total proportions of active disease and LTBI during the outbreak were 3.7% (28/758) and 9.2% (70/758), respectively. All clinical isolates had a Beijing/K M. tb genotype. IFN-γ responses to the MTBK antigen identified M. tb infection and distinguished between active disease and LTBI. After anti-TB treatment, IFN-γ responses to the MTBK antigen were significantly reduced, and strong TNF-α responses at diagnosis were dramatically decreased. Conclusions: MTBK antigen-specific IFN-γ has diagnostic potential for differentiating M. tb infection from healthy controls, and between active TB and LTBI as well. In addition, TNF-α is a promising marker for monitoring therapeutic responses. These data provide informative readouts for TB diagnostics and vaccine studies in regions where the Beijing/K strain is endemic

Diagnostic Potential of a PPE Protein Derived from Mycobacterium tuberculosis Beijing/K Strain.

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-?] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-? also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic

A Feasibility Study for Diagnosis of Latent Tuberculosis Infection Using an IGRA Point-of-Care Platform in South Korea.

PURPOSE: This study aimed to evaluate ichroma™ IGRA-TB, a novel point-of-care platform for assaying IFN-γ release, and to compare it with QuantiFERON-TB Gold In-Tube (QFT-GIT) for identifying Mycobacterium tuberculosis (M. tb) infection. MATERIALS AND METHODS: We recruited 60 healthy subjects, and blood samples were obtained in QFT-GIT blood collection tubes. The blood collection tubes were incubated at 37°C, and culture supernatant was harvested after 18-24 hours. IFN-γ responses were assessed by the ichroma™ IGRA-TB cartridge and the QFT-GIT IFN-γ enzyme-linked immunosorbent assay. Three active TB patients were recruited as a positive control for M. tb infection. RESULTS: The area under the receiver operating characteristic curve of the ichroma™ IGRA-TB test for differentiating between infected and non-infected individuals was 0.9706 (p<0.001). Inconsistent positivity between the two tests was found in three participants who showed weak positive IFN-γ responses (<1.0 IU/mL) with QFT-GIT. However, the two tests had excellent agreement (95.2%, κ=0.91, p<0.001), and a very strong positive correlation was observed between the IFN-γ values of both tests (r=0.91, p<0.001). CONCLUSION: The diagnostic accuracy demonstrated in this study indicates that the ichroma™ IGRA-TB test could be used as a rapid diagnostic method for detecting latent TB infection. It may be particularly beneficial in resource-limited places that require cost-effective laboratory diagnostics

Clues to occult cancer in patients with ischemic stroke.

BACKGROUND: We hypothesized that hidden malignancy could be detected in patients with cryptogenic stroke without active cancer when they showed the distinctive characteristics of cancer-related stroke. METHODS AND FINDINGS: Among 2,562 consecutive patients with acute ischemic stroke, patients with cryptogenic stroke were analyzed and categorized into two groups according to the presence of active cancer: cryptogenic stroke with active cancer (cancer-related stroke, CA-stroke) group and without active cancer (CR-stroke) group. Patients with active lung cancer without stroke were also recruited for comparison purposes (CA-control). Clinical factors, lesion patterns on diffusion-weighted MRI (DWI), and laboratory findings were analyzed among groups. A total of 348 patients with cryptogenic stroke were enrolled in this study. Among them, 71 (20.4%) patients had active cancer at the time of stroke. The D-dimer levels were significantly higher in patients with CA-stroke than those with CR-stroke or CA-control (both p<0.001). Regarding lesion patterns, patients with CA-stroke mostly had multiple lesions in multiple vascular territories, while more than 80% of patients with CR-stroke had single/multiple lesions in a single vascular territory (P<0.001). D-dimer levels (OR 1.11 per 1 µg/mL increase; 95% CI 1.06-1.15; P<0.001) and DWI lesion patterns (OR 7.13; 95% CI 3.42-14.87; P<0.001) were independently associated with CA-stroke. Workup for hidden malignancy was performed during hospitalization in 10 patients who showed elevated D-dimer levels and multiple infarcts involving multiple vascular territories but had no known cancer, and it revealed hidden malignancies in all the patients. CONCLUSION: Patients with CA-stroke have distinctive D-dimer levels and lesion patterns. These characteristics can serve as clues to occult cancer in patients with cryptogenic stroke

A typical example of cryptogenic stroke with active cancer (cancer-related stroke).

<p>The patient was a 55-year-old female, who was diagnosed with metastatic adenocarcinoma of lung one year ago. Neurologic examination revealed motor aphasia, right-central facial paralysis, and right hemiparesis. Initial D-dimer levels were 20.56 µg/mL. Diffusion-weighted MRI (A) shows multiple lesions involving multiple vascular territories. MR angiography (B) reveals no significant stenosis or occlusion of the craniocervical arterial vasculature. Comprehensive workup including transesophageal echocardiogram and 24-hour Holter monitoring demonstrated no sources of cardioembolism.</p

Multiple logistic regression analysis: Independent predictors for cancer-related stroke vs. cryptogenic stroke without active cancer.

<p>DWI indicated diffusion-weighted MRI; OR, odds ratio; CI, confidence interval; Ref, reference; N/A, not applicable.</p