Long‐term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt–Jakob disease

An asymptomatic 74‐year‐old woman, on follow‐up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion‐weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629–632     

Downstaging in Pancreatic Cancer: A Matched Analysis of Patients Resected Following Systemic Treatment of Initially Locally Unresectable Disease

Background

Patients with locally unresectable pancreatic cancer (AJCC stage III) have a median survival of 10?C14?months. The objective of this study was to evaluate outcome of initially unresectable patients who respond to multimodality therapy and undergo resection.

Methods

Using a prospectively collected database, patients were identified who were initially unresectable because of vascular invasion and had sufficient response to nonoperative treatment to undergo resection. Overall survival (OS) was compared with a matched group of patients who were initially resectable. Case matching was performed using a previously validated pancreatic cancer nomogram.

Results

A total of 36 patients with initial stage III disease were identified who underwent resection after treatment with either systemic therapy or chemoradiation. Initial unresectability was determined by operative exploration (n?=?15, 42%) or by cross-sectional imaging (n?=?21, 58%). Resection consisted of pancreaticoduodenectomy (n?=?31, 86%), distal pancreatectomy (n?=?4, 11%), and total pancreatectomy (n?=?1, 3%). Pathology revealed T3 lesions in 26 patients (73%), node positivity in 6 patients (16%), and a negative margin in 30 patients (83%). The median OS in this series was 25?months from resection and 30?months since treatment initiation. There was no difference in OS from time of resection between the initial stage III patients and those who presented with resectable disease (P?=?.35).

Conclusions

In this study, patients who were able to undergo resection following treatment of initial stage III pancreatic cancer experienced survival similar to those who were initially resectable. Resection is indicated in this highly select group of patients.     

Number and Tumor Size Are Not Sufficient Criteria to Select Patients for Liver Transplantation for Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI).

Methods

From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded.

Results

HCC was confirmed in 168 patients (85.7%). The median follow-up was 74?months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P?=?NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P?400?ng/ml and tumor grade G3.

Conclusions

Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.     

Safe Criteria for Less Radical Trachelectomy in Patients with Early-Stage Cervical Cancer: A Multicenter Clinicopathologic Study

Background

To determine the safe criteria for less radical trachelectomy to treat patients with early-stage cervical cancer.

Methods

We reviewed medical records and pathologic slides of 65 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA?CIB1 cervical cancer. The safe criteria for less radical trachelectomy were determined by using three factors such as tumor size ??1?cm, stromal invasion ??5?mm, and no lymphovascular space invasion (LVSI) for minimizing parametrial involvement, lymph node metastasis (LNM), and the need of adjuvant radiotherapy. The diagnostic values were investigated by calculating specificity, negative predictive value for no parametrial involvement, no LNM, and no need of adjuvant radiotherapy.

Results

The median age was 32?years (range 22?C44?years), and the median duration of follow-up was 26?months (range 2?C103?months). Among seven single or combined factors for the safe criteria, (1) tumor size ??1?cm, (2) tumor size ??1?cm and stromal invasion ??5?mm, (3) tumor size ??1?cm and no LVSI, (4) tumor size ??1?cm, stromal invasion ??5?mm, and no LVSI did not show parametrial involvement, LNM, and the need of adjuvant radiotherapy. In particular, tumor size ??1?cm showed the highest specificity (28.1?C29.5%) and negative predictive value (100%). In spite of no difference in progression-free survival (PFS) between tumor size ??1?cm and >1?cm (P?=?0.22), tumor size ??1?cm showed better PFS without disease recurrence than tumor size >1?cm (2-year PFS, 100% vs. 90%).

Conclusions

Less radical trachelectomy may be safe in patients with early-stage cervical cancer who have tumor size ??1?cm.     

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.