Radiomics-based prediction of microsatellite instability in colorectal cancer at initial computed tomography evaluation

Purpose

To predict microsatellite instability (MSI) status of colon cancer on preoperative CT imaging using radiomic analysis.

Methods

This retrospective study involved radiomic analysis of preoperative CT imaging of patients who underwent resection of stage II–III colon cancer from 2004 to 2012. A radiologist blinded to MSI status manually segmented the tumor region on CT images. 254 Intensity-based radiomic features were extracted from the tumor region. Three prediction models were developed with (1) only clinical features, (2) only radiomic features, and (3) “combined” clinical and radiomic features. Patients were randomly separated into training (n = 139) and test (n = 59) sets. The model was constructed from training data only; the test set was reserved for validation only. Model performance was evaluated using AUC, sensitivity, specificity, PPV, and NPV.

Results

Of the total 198 patients, 134 (68%) patients had microsatellite stable tumors and 64 (32%) patients had MSI tumors. The combined model performed slightly better than the other models, predicting MSI with an AUC of 0.80 for the training set and 0.79 for the test set (specificity = 96.8% and 92.5%, respectively), whereas the model with only clinical features achieved an AUC of 0.74 and the model with only radiomic features achieved an AUC of 0.76. The model with clinical features alone had the lowest specificity (70%) compared with the model with radiomic features alone (95%) and the combined model (92.5%).

Conclusions

Preoperative prediction of MSI status via radiomic analysis of preoperative CT adds specificity to clinical assessment and could contribute to personalized treatment selection.

     

Short-term reproducibility of radiomic features in liver parenchyma and liver malignancies on contrast-enhanced CT imaging

Abdominal Radiology - To evaluate the short-term reproducibility of radiomic features in liver parenchyma and liver cancers in patients who underwent consecutive contrast-enhanced CT (CECT) with...     

Molecular correlates of syncytialization in muscle and placenta

Syncytialization is one of the most fundamental processes in life. It is observed during development of muscle and osteoclast, and syncytiotrophoblast formation in placental villi. Syncytialization involves recognition, migration, adhesion and finally cell fusion between two interacting cells. It is an energy-dependent process which is essentially restricted to a small portion of interacting cellular membranes. Such regions of membranes may differ from other regions of cell surface in terms of physico-chemistry and expression of specific protein biomolecules resulting in restriction of this process to cells of specific competence. Despite the fact that membrane biologists have given significant quanta of efforts to understand the basic principle underlying this fundamental process of life, further large scale initiatives have to be undertaken to dissect the underlying molecular correlates central to this event.     

Altered expression of TGF-β1 and TGF-βR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma

In the transforming growth factor β (TGF-β) signaling pathway, TGF-β1 and TGF-β receptor 2 (TGF-βR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-β1 and TGF-βR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-β1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-βR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-β1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-βR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-βR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-β1 and TGF-βR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients.*Mean fold change.     

Percutaneous laser disc decompression: clinical experience at SCTIMST and long term follow up

BACKGROUND: Low backache (LBA) is now increasing in younger population due to misdirected spinal kinetics secondary to improper posture, heavy load lifting and motorbike driving. Hence minimally invasive procedures are increasingly sought after. Among these, PLDD is currently popular and in use. We present our long term follow-up in the use of Nd:YAG laser for PLDD. AIM: To evaluate the efficacy of PLDD in treatment of contained herniation of lumbar discs & long term follow up results. MATERIALS AND METHODS: Forty patients with contained lumbar disc herniation on MRI and who did not respond to 6 weeks conservative treatment were subjected to PLDD. L4-5 disc was treated in 31, L5-S1 in 12 and L1-2 and L3-4 in one each. Nd:YAG laser at 1064 nm was used for the procedure. Total laser energy of 1500-2000 Joules was delivered at the disc space depending upon the size. RESULTS: There was immediate pain relief in 32/40 (80%). According to MacNab criteria good to fair response was seen in 37/40 (92%) and 3 patients (7.5%) responded poorly to this treatment. On follow up which ranged from 1 to 7 years, 34/40 (85%) had pain relief with no need for further treatment. COMPLICATIONS: Significant pain at local puncture site was experienced by 8 (20%), pain during lasing was experienced by one. One patient developed muscular spasm. CONCLUSION: Percutaneous laser disc decompression is a safe, relatively noninvasive and effective treatment modality for contained, nonsequestered, herniated lumbar disc disease in carefully selected patients.     

Histochemical and morphological examination of proliferation and apoptosis in human first trimester villous trophoblast

BACKGROUND: Our present knowledge about trophoblast turnover in human first trimester placental villi based on multiparametric examination of proliferation and apoptosis is limited. METHODS: Human villous placentae collected during 6, 7 and 8 weeks (n = 10/each group) of gestation were examined for trophoblast proliferation and apoptosis based on quantitative analyses of immunopositive Fas, tumor necrosis factor receptor 1 (TNFR1), cytokeratin 18 fragment (18f), number of proliferating cell nuclear antigen (PCNA), Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive nuclei, scores of mitotic and apoptotic indices and ultrastructural characteristics. RESULTS: Mitotic index in cytotrophoblast higher (P < 0.05) at 6 week compared with 7 and 8 weeks of gestation showed significant (P < 0.05) negative correlation between its prevalence and gestational age. Syncytiotrophoblast exhibited higher number of TUNEL positive nuclei (P < 0.01), TUNEL positive apoptotic nuclei (P < 0.05) and apoptotic index (P < 0.05) compared with cytotrophoblast at same gestational age. Positive correlations found between cytokeratin 18f and apoptotic index (P < 0.01), Fas and apoptotic index (P < 0.01), TUNEL positive nuclei and apoptotic index (P < 0.05), cytokeratin 18f and Fas (P < 0.01), whereas cytokeratin 18f (P < 0.05) and Fas (P < 0.05) showed positive correlation only with TUNEL positive apoptotic nuclear data. Phalangeal intrusions of syncytiotrophoblast between transitional cytotrophoblasts showed apposed plasma membranes bearing thickened membrane leaflets, inter-membranous gaps enclosing membranous invaginations, liposome-like particles; patches of membrane seen to be dissolved resulting in cytoplasmic continuity typical of syncytial formation. CONCLUSION: Cellular remodeling of first trimester villous placenta requires a complex homeodynamics involving proliferation in cytotrophoblast, development-associated syncytialization and apoptosis in syncytiotrophoblast.     

Effect of (Ala8,13,18)-magainin II amide on human trophoblast cells in vitro

Magainins are cationic peptides with anti-bacterial and anti-tumor properties. The anti-nidatory function of a synthetic analogue of magainin, (Ala8,13,18)-magainin II amide, has earlier been reported, and it has been indicated that placental trophoblast cells could be a target of magainin resulting in its contragestational action. The aim of the present study was to examine the effect of (Ala8,13,18)-magainin II amide (100 ng/ml and 1000 ng/ml) on attachment efficiency, viability, differentiation in terms of hCG secretion and invasive function of isolated first trimester, human placental trophoblast cells grown on rat-tail collagen type-I matrix in primary cell culture. In the present experimental model, magainin was not found to affect human trophoblast cell functions in vitro.     

Managed care and preventable hospitalization among Medicaid adults

OBJECTIVE: The study examines the association between managed care enrollment and preventable hospitalization patterns of adult Medicaid enrollees hospitalized in four states. DATA SOURCES/STUDY SETTING: Hospital discharge data from the Healthcare Cost and Utilization Project (HCUP) database of the Agency for Healthcare Research and Quality (AHRQ) for New York (NY), Pennsylvania (PA), Wisconsin (WI), and Tennessee (TN) residents in the age group 20-64 hospitalized in those states, linked to the Area Resource File (ARF) and American Hospital Association (AHA) survey files for 1997. STUDY DESIGN: The study uses separate logistic models for each state comparing preventable admissions with marker admissions (urgent, insensitive to primary care). The model controls for socioeconomic and demographic variables, and severity of illness. PRINCIPAL FINDINGS: Consistently in different states, private health maintenance organization (HMO) enrollment was associated with fewer preventable admissions than marker admissions, compared to private fee-for-service (FFS). However, Medicaid managed care enrollment was not associated with a reduction in preventable admissions, compared to Medicaid FFS. CONCLUSIONS: Our analysis suggests that the preventable hospitalization pattern for private HMO enrollees differs significantly from that for commercial FFS enrollees. However, little difference is found between Medicaid HMO enrollees and Medicaid FFS patients. The findings did not vary by the level of Medicaid managed care penetration in the study states.