Three-dimensional laparoscopy-assisted bowel resection for cavernous hemangioma of the rectum: Report of two cases.

The safety and feasibility of 3-D laparoscopy-assisted bowel resection were demonstrated in the management of rectal cancer. However, this procedure's role in the management of patients with diffuse cavernous hemangioma of the rectum has not been evaluated. Here, two patients were diagnosed with diffuse cavernous hemangioma of the rectum by colonoscopy and abdominal imaging. One case underwent pull-through transection and coloanal anastomosis in 3-D laparoscopy-assisted surgery. In another patient, 3-D laparoscopy-assisted abdominoperineal resection was performed. The operations were safely performed in both cases. The two patients recovered uneventfully, and satisfactory postoperative outcomes were demonstrated. This report shows that 3-D laparoscopy-assisted bowel resection may be safe and feasible for patients with diffuse cavernous hemangioma of the rectum.

A Nomogram to Predict Adequate Lymph Node Recovery before Resection of Colorectal Cancer.

Increased lymph node count (LNC) has been associated with prolonged survival in colorectal cancer (CRC), but the underlying mechanisms are still poorly understood. The study aims to identify new predictors and develop a preoperative nomogram for predicting the probability of adequate LNC (≥ 12). 501 eligible patients were retrospectively selected to identify clinical-pathological factors associated with LNC ≥ 12 through univariate and multivariate logistic regression analyses. The nomogram was built according to multivariate analyses of preoperative factors. Model performance was assessed with concordance index (c-index) and area under the receiver operating characteristic curve (AUC), followed by internal validation and calibration using 1000-resample bootstrapping. Clinical validity of the nomogram and LNC impact on stage migration were also evaluated. Multivariate analyses showed patient age, CA19-9, circulating lymphocytes, neutrophils, platelets, tumor diameter, histology and deposit significantly correlated with LNC (P < 0.05). The effects were marginal for CEA, anemia and CRC location (0.05 < P < 0.1). The multivariate analyses of preoperative factors suggested decreased age, CEA, CA19-9, neutrophils, proximal location, and increased platelets and diameter were significantly associated with increased probability of LNC ≥ 12 (P < 0.05). The nomogram achieved c-indexes of 0.75 and 0.73 before and after correction for overfitting. The AUC was 0.75 (95% CI, 0.70-0.79) and the clinically valid threshold probabilities were between 10% and 60% for the nomogram to predict LNC < 12. Additionally, increased probability of adequate LNC before surgery was associated with increased LNC and negative lymph nodes rather than increased positive lymph nodes, lymph node ratio, pN stages or AJCC stages. Collectively, the results indicate the LNC is multifactorial and irrelevant to stage migration. The significant correlations with preoperative circulating markers may provide new explanations for LNC-related survival advantage which is reflected by the implication of regional and systemic antitumor immune responses.

A nomogram improves AJCC stages for colorectal cancers by introducing CEA, modified lymph node ratio and negative lymph node count.

Lymph node stages (pN stages) are primary contributors to survival heterogeneity of the 7th AJCC staging system for colorectal cancer (CRC), indicating spaces for modifications. To implement the modifications, we selected eligible CRC patients from the Surveillance Epidemiology and End Results (SEER) database as participants in a training (n = 6675) and a test cohort (n = 6760), and verified tumor deposits to be metastatic lymph nodes to derive modified lymph node count (mLNC), lymph node ratio (mLNR), and positive lymph node count (mPLNC). After multivariate Cox regression analyses with forward stepwise elimination of the mLNC and mPLNC for the training cohort, a nomogram was constructed to predict overall survival (OS) via incorporating preoperative carcinoembryonic antigen, pT stages, negative lymph node count, mLNR and metastasis. Internal validations of the nomogram showed concordance indexes (c-index) of 0.750 (95% CI, 0.736-0.764) and 0.749 before and after corrections for overfitting. Serial performance evaluations indicated that the nomogram outperformed the AJCC stages (c-index = 0.725) with increased accuracy, net benefits, risk assessment ability, but comparable complexity and clinical validity. All the results were reproducible in the test cohort. In summary, the proposed nomogram may serve as an alternative to the AJCC stages. However, validations with longer follow-up periods are required.

Nomograms to predict survival after colorectal cancer resection without preoperative therapy.

BACKGROUND: The predictive accuracy of the American Joint Committee on Cancer (AJCC) stages of colorectal cancer (CRC) is mediocre. This study aimed to develop postoperative nomograms to predict cancer-specific survival (CSS) and overall survival (OS) after CRC resection without preoperative therapy. METHODS: Eligible patients with stage I to IV CRC (n = 56072) diagnosed from 2004 to 2010 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were allocated into training (n = 27,700), contemporary (n = 3158), and prospective (n = 25,214) validation cohorts. Clinically important variables were incorporated and selected using the Akaike information criterion in multivariate Cox regressions to derive nomograms with the training cohort. The performance of the nomograms was assessed and externally testified using the concordance index (c-index), bootstrap validation, calibration, time-dependent receiver-operating characteristic curves, Kaplan-Meier curves, mosaic plots, and decision curve analysis (DCA). Performance of the conventional AJCC stages was also compared with the nomograms using similar statistics. RESULTS: The nomograms for CSS and OS shared common predictors: sex, age, race, marital status, preoperative carcinoembryonic antigen status, surgical extent, tumor size, location, histology, differentiation, infiltration depth, lymph node count, lymph node ratio, and metastasis. The c-indexes of the nomograms for CSS and OS were 0.816 (95 % CI 0.810-0.822) and 0.777 (95 % CI 0.772-0.782), respectively. Performance evaluations showed that the nomograms achieved considerable predictive accuracy, appreciable reliability, and significant clinical validity with wide practical threshold probabilities, while the results remained reproducible when applied to the validation cohorts. Additionally, model comparisons and DCA proved that the nomograms excelled in stratifying each AJCC stage into three significant prognostic subgroups, allowing for more robust risk classification with an improved net benefit. CONCLUSIONS: We propose two prognostic nomograms that exhibit improved predictive accuracy and net benefit for patients who have undergone CRC resection. The established nomograms are intended for risk assessment and selection of suitable patients who may benefit from adjuvant therapy and intensified follow-up after surgery. Independent external validations may still be required.

MiRNA-107 inhibits proliferation and migration by targeting CDK8 in breast cancer.

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression pattern of microRNA-107 (miR-107) in human breast cancer, and its potential role in disease pathogenesis. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-107 in 30 breast cancer specimens and adjacent normal breast tissues. MTT and colony formation assays, transwell and wound healing test, cell cycle assays were conducted to explore the potential function of miR-107 in human MDA-MB-231 breast cancer cells. Luciferase reporter assays were employed to validate regulation of a putative target of miR-107. The effect of modulating miR-107 on endogenous levels of this target were subsequently confirmed via Western blotting. RESULTS: miR-107 expression was relatively decreased in breast cancer specimens compared with adjacent normal tissues (P<0.01). Overexpression of miR-107 suppressed MDA-MB-231 cell proliferation and migration, meanwhile the cells were arrested at G0/G1 phase. Luciferase assays using a reporter carrying a putative miR-107 target site in the 3', untranslated region (3'-UTR) of CDK8 revealed that miR-107 directly targets CDK8. Overexpression of miR-107 led to downregulation of CDK8 at the mRNA and protein level, as assessed by Western blotting. CONCLUSIONS: miR-107 may play an important role in breast cancer progression, which might negatively regulate the expression of CDK8 and inhibit the proliferation and migration of MDA-MB-231 cell line.

siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells.

UNLABELLED: CDK8 is a cyclin-dependent kinase (CDK) member of the mediator complex that couples transcriptional regulators to the basal transcriptional machinery, and it has been investigated for possible tumor promoting functions. However, it is unclear whether CDK8 is involved in breast tumor cells growth. The aim of this study was to determine whether the suppression of CDK8 by small interfering RNA (siRNA) inhibits the growth of human breast cancer cell. METHODS: CDK8-siRNA transfection was used to silencing the CDK8 gene in established breast cancer cell line, MDA-MB-231 and MCF-7, successful transfection being confirmed by Real-time PCR and could be shown by Western Blotting. CDK8 deletion caused significant decline in cell proliferation was observed in breast cancer cell lines as investigated by MTS assay, the number and size of the colonies formed were also significantly reduced in the absence of CDK8. Furthermore, transwell test were conducted to explore the migration of breast cancer cells. Moreover CDK8 gene knockdown arrested cell cycle. RESULTS: CDK8 mRNA expression was reduced after transfection with CDK8-siRNA, and protein expression had a similar trend. Transfection of CDK8-siRNA suppressed breast cancer cells proliferation and migration; meanwhile the cells were arrested at G0/G1 phase. CONCLUSIONS: CDK8 plays an essential role in breast cancer progression, which might inhibit the proliferation and migration in breast cancer cells.

Clinical significance of NOB1 expression in breast infiltrating ductal carcinoma.

BACKGROUND: NIN/RPN Binding protein 1 homologue (NOBp1), encoded by NOB1 gene, was reported to play an essential role in the oncogenesis and prognosis of carcinomas. We conducted a study to reveal its expression and clinical significance in breast infiltrating ductal carcinoma. METHODS: To explore the relationship between NOB1 expression and the clinical TNM (cTNM), 162 patients who undergone surgery were involved in the study. Compared to healthy tissues, abnormal localization and higher level of NOB1 in tumor cells was observed by Immunohistochemistry staining. Real-time PCR and western-blotting verified the up-regulation of NOB1 in carcinoma individuals. RESULTS: A significant correlation between high level of NOB1 and the T stage, lymph node metastasis and cTNM was shown. Furthermore, patients with higher level of NOB1 predicted a declined overall survival (OS). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of NOB1 was an independent prognostic factor in breast infiltrating ductal carcinoma. CONCLUSIONS: In summary, our present study clarify that the aberrant expression of NOB1 in breast infiltrating ductal carcinoma is possibly involved with tumorigenesis and development, and the NOB1 protein could act as a potential biomarker for prognosis assessment of breast infiltrating ductal carcinoma. Related mechanism is worthy of further investigation.