MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P?=?0.0257) and poor prognosis (P?=?0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.     

Comparison of Patient Characteristics and Outcomes of Contralateral Prophylactic Mastectomy and Unilateral Total Mastectomy in Breast Cancer Patients

Background

There has been an increasing trend toward contralateral prophylactic mastectomy (CPM) in the management of breast cancer (BCa). This study??s objective was to compare clinicopathologic characteristics of BCa patients who elected CPM to those who elected unilateral total mastectomy (UTM) and to determine whether CPM improved survival.

Methods

Comparison was performed on 355 patients with stage 0?CIII BCa matched by age and stage who underwent mastectomy from 1995 to 2008: 177 patients had CPM; 178 patients had UTM. Clinicopathological characteristics and survival outcomes were analyzed.

Results

Women who underwent preoperative MRI were twice as likely to have CPM (40.9 vs. 19.7%, P?P?=?0.001; 64.3 vs. 41.4%, P?P?=?0.04, respectively). CPM patients elected nipple preservation (26 vs. 5.2%, P?P?P?=?0.01). CPM identified occult BCa in 11 patients (6.6%), and three UTM patients (1.7%) developed contralateral BCa. With median follow-up of 61?months, by univariable/multivariable analyses, CPM did not improve overall, disease-free, or distant metastases-free survival.

Conclusion

Factors that may influence choice of CPM included preoperative MRI, history of prior breast biopsies, immediate reconstruction, nipple preservation, family history, and BRCA status. Those who chose CPM did not have improved survival.     

Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis

Background

Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.

Methods

From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.

Results

Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3?cm, P?=?0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P?=?0.01), synchronous liver metastasis (62 vs. 21%, P?P?P?=?0.01) and size (P?P?=?0.04), but not in the presence of radiographic calcifications.

Conclusions

Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.     

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy: Indications, Aims, and Results: A Systematic Review of the Literature

Purpose

To evaluate laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with neoadjuvant, adjuvant, or palliative purpose in order to discuss potential clinical implications.

Methods

A systematic search of PubMed??s Medline through August 2011 using the keywords laparoscopic, hyperthermic, and chemotherapy.

Results

Eight studies encompassing a total of 183 patients were considered. The indications for laparoscopic HIPEC was neoadjuvant in 5 patients, adjuvant in 102 patients, and palliative in 76 patients. There were 13 minor complications not requiring repeat operation, and no deaths related to procedure were recorded. When performed to treat refractory malignant ascites, the procedure was effective in 95?% of cases.

Conclusions

Laparoscopic HIPEC appears to be a safe and effective procedure when performed to treat malignant ascites refractory to less aggressive treatments. The effectiveness of laparoscopy to perform HIPEC with neoadjuvant or adjuvant purpose needs to be confirmed by further studies.     

Simple Enucleation Versus Radical Nephrectomy in the Treatment of pT1a and pT1b Renal Cell Carcinoma

Background

Simple tumor enucleation (TE) showed excellent oncologic results in large retrospective series. No study has compared oncologic outcomes after TE and radical nephrectomy (RN) for the treatment of pT1 renal cell carcinoma (RCC). The aim of the present study is to compare the oncologic outcomes after TE and RN in pT1 RCCs.

Methods

We retrospectively analyzed 475 patients who underwent TE or RN for pT1 RCC, N0, M0, between 1995 and 2007. TE was performed in 332 patients and RN in 143. Local recurrence, progression-free survival (PFS), and cancer-specific survival (CSS) were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions, and differences were assessed with the log rank statistic. Univariate and multivariate Cox regression models were also used.

Results

The 5- and 10-year PFS estimates were 91.3 and 88.7% after RN and 95.3 and 92.8% after TE (P?=?NS), respectively. The 5- and 10-year CSS estimates were 92.1 and 89.4% after RN and 94.4% (5- and 10-year CSS) after TE (P?=?NS), respectively. No statistically significant differences between RN and TE were found after adjusting CSS probabilities according to age at surgery, grade, stage, or clear cell subtype. Surgical treatment was not a predictor of PFS or CSS by both univariate and multivariate analyses. The potential limitation of this study is that the data originate from a retrospective review.

Conclusions

TE can achieve oncologic results similar to those of RN for the treatment of pT1 RCCs, provided tumors are carefully selected on the basis of their safe and complete removal.     

The New American Joint Committee on Cancer/International Union Against Cancer Staging System for Adenocarcinoma of the Stomach: Increased Complexity without Clear Improvement in Predictive Accuracy

Purpose

To evaluate the changes in the 7th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the 6th edition; to compare the predictive accuracy of the two staging systems.

Methods

In a combined database containing 2,196 patients who underwent an R0 resection for gastric adenocarcinoma, differences between the two staging systems were evaluated and stage-specific survival estimates compared. Concordance probability and Brier scores were estimated for both systems to examine the predictive accuracy.

Results

Nodal status cutoff values were changed, leading to a more even distribution for the redefined N1, N2, and N3 group. AJCC 6th edition stage II reflected a highly heterogeneous population, which is now adequately subdivided in the AJCC 7th edition into stages IIA, IIB, and IIIA. The predictive accuracy of N classification improved significantly as measured by concordance. Despite increased complexity, the predictive accuracy of AJCC 7th stage grouping was significantly worse than that of the AJCC 6th edition.

Discussion

The increased complexity of the 7th edition staging system is accompanied by improvements in the predictive value of nodal staging as compared to the 6th edition, but it was no better in overall stage-specific predictive accuracy. Future refinements of the tumor, node, metastasis staging system should consider whether increased complexity is balanced by improved prognostic accuracy.     

Relationship Between Diffusion-Weighted Magnetic Resonance Imaging and Histological Tumor Grading of Hepatocellular Carcinoma

Background

Intrahepatic and extrahepatic recurrence remains a significant problem for hepatocellular carcinoma (HCC). The aim of this study was to determine the usefulness of diffusion-weighted magnetic resonance imaging (DWI) for histological tumor grading and preoperative prediction of early HCC recurrence within 6 months of operation.

Methods

A total of 44 patients who had undergone hepatic resection for HCC (50 nodules) were reviewed retrospectively. DWI was performed within 30 days before hepatectomy, and apparent diffusion coefficients (ADCs) were measured using 2 methods: mean ADC and minimum-spot ADC. Relationships between ADCs and histological differentiation and between ADCs and early recurrence of HCC were analyzed.

Results

Mean ADC was significantly lower in poorly differentiated HCC (n = 18, 1.07 ± 0.15 × 10^?3 mm²/s) than in moderately differentiated HCC (n = 29, 1.29 ± 0.21 × 10^?3 mm²/s; P < .05). Minimum-spot ADC was significantly lower in poorly differentiated HCC (n = 18, 0.69 ± 0.19 × 10^?3 mm²/s) than in well-differentiated HCC (n = 3, 1.15 ± 0.10 × 10^?3 mm²; P < .01) or in moderately differentiated HCC (n = 29, 0.98 ± 0.18 × 10^?3 mm²/s; P < .0001). Of 34 patients who were able to be observed for >6 months after resection, 9 showed early recurrence. Minimum-spot ADC was significantly lower in patients with early recurrence (n = 9, 0.64 ± 0.24 × 10^?3 mm²/s) than in patients without early recurrence (n = 25, 0.88 ± 0.19 × 10^?3 mm²/s; P < .05). On multivariate analysis, minimum-spot ADC was a significant risk factor for early recurrence (P < .05).

Conclusion

Quantitative measurement of ADC of HCC with magnetic resonance diffusion weighted imaging is a promising functional imaging tool in the prediction of histological grade and early recurrence before treatment.     

Creating an Academy of Medical Educators: How and Where to Start

Background

While most faculty members want to improve as teachers, they neither know where their educational strengths and weaknesses lie nor where or how to begin to effect a change in their teaching abilities. The lack of actionable, directed and specific feedback, and sensible and sensitive metrics to assess performance and improvement complicates the attainment of educational excellence.

Purpose

The purpose of this article was to outline a series of specific steps that medical education programs can take to enhance the quality of teaching, promote teaching excellence, elevate the status and value of medical educators, and stimulate the creation of innovative teaching programs and curricula.

Methods

To achieve these goals at the Hospital for Special Surgery, the Academy of Rheumatology Medical Educators was formed. The academy had the following goals: (1) create within our institution a mission which advances and supports educators, (2) establish a membership composed of distinguished educators, (3) create a formal organizational structure with designated leadership, (4) dedicate resources that fund mission-related initiatives and research, and (5) establish a plan for promoting teachers as well as enhancing and advancing educational scholarship.

Results

The Hospital for Special Surgery Academy of Rheumatology Medical Educators was recently formed to address these goals by promoting teaching and learning of musculoskeletal skills in an environment that is supportive to educators and trainees and provides much needed resources for teachers.

Summary

The development of a pilot academy of medical educators represents one of the high-priority goals of those institutions that wish to elevate and enrich their teaching through a structured, proven approach.     

Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion in Women with Heavily Pretreated Recurrent Ovarian Cancer

Background

Limited data are available on the use of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (HIPEC) in patients with recurrent stage III ovarian cancer.

Methods

Patients with recurrent, heavily pretreated ovarian cancer were enrolled onto a phase II multimodal protocol consisting of extensive cytoreduction followed by HIPEC.

Results

Forty-two women were treated from October 2002 until January 2009. Chemoperfusion was performed with cisplatin in 59% and oxaliplatin in 41% of patients. A macroscopically complete resection was achieved in 50% of patients. No mortality occurred, and the major morbidity rate was 21%. After a mean follow-up of 21?months, median overall survival (OS) was 37?months (95% confidence interval 12.2?C61.8) and median progression-free survival was 13?months (95% confidence interval 6.9?C19.1). In univariate analysis, OS was influenced by completeness of cytoreduction, type of chemoperfusion drug, nodal status, and tumor grade. In a Cox regression model, only completeness of cytoreduction (hazard ratio 0.06?C0.8, P?=?.022) and tumor grade (hazard ratio 1.23?C12.6, P?=?.021) were independent predictors of OS.

Conclusions

In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease.