The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Defining and Characterizing Frequent Attenders: Systematic Literature Review and Recommendations.

PURPOSE: To decrease cost and improve efficiency, health care organizations have focused on frequent attenders - patients with high health care utilization. Prior studies have investigated singular health care settings, used varying definitions of frequent attendance, and inconsistently identified factors correlated with frequent attendance. The purpose of this article is to suggest a uniform definition of frequent attenders for different health care settings and to determine factors correlated with frequent attendance. METHODS: This systematic review of three databases identified 2761 unique articles; 174 met inclusion criteria. Studies were analyzed for their definition of frequent attenders and factors associated with frequent attendance. RESULTS: Most studies defined frequent attenders by number of health care visits within a set time period (n=115) and top percentile cutoff (n=42). Based on averages across studies, we propose the following frequent attender definitions: for primary care, either the top 10th percentile or at least 10 visits in 12 months; for emergency room, at least 5 visits in 12 months; and for inpatient hospitalization, at least 4 admissions in 12 months. Common factors correlated with frequent attendance were mental health and chronic disease. CONCLUSIONS: We propose definitions of frequent attenders for three common health care settings: primary care, emergency room, and inpatient. Future studies should include mental health and chronic disease, among other factors, when studying this population. Adoption of these recommendations will allow comparisons across studies such that meta-analyses may better determine interventions for more appropriate health care utilization.

Minimally invasive microwave ablation provides excellent long-term outcomes for otherwise inaccessible hepatocellular cancer.

BACKGROUND AND OBJECTIVES: Thermal ablation can be used as a bridge to transplant or with curative intent for hepatocellular carcinoma (HCC). We report our experience with laparoscopic ablation of HCC in patients deemed inaccessible by the percutaneous approach. METHODS: We performed a retrospective review of surgical ablations from 2009 to 2017. Patient demographics, disease and treatment characteristics, and outcomes were abstracted from the medical record. Kaplan-Meier modeling was performed for survival and recurrence. RESULTS: Thirty-three patients were included with a median age of 62 (interquartile range [IQR], 57-67). Most patients were male (76%) and Caucasian (70%). Ninety-seven percent had underlying cirrhosis. Median model for end stage liver disease-sodium was 9.5 (IQR, 8-12). The median maximal diameter of ablated lesions was 2.6 cm (IQR, 1.8-3.0). Thirty-nine lesions were ablated; 97% were completed laparoscopically. The median maximal diameter of the ablation zone was 4.8 cm (IQR, 3.8-5.7) with a median difference of ablation zone to the tumor of 2.0 cm (IQR, 1.5-2.75). Twelve patients received additional treatment. Median disease-free survival was 66.7 months and median follow-up 42.9 months. Disease recurrence occurred in 13 patients (39%)-systemic recurrence in 6%, intrahepatic recurrence in 27% and local recurrence in 6%. CONCLUSION: Laparoscopic thermal ablation of HCC is safe and provides good oncologic outcomes for otherwise inaccessible tumors.

Prostate Biopsy Processing.

OBJECTIVES: Current protocols for processing multiple prostate biopsy cores per case are uneconomical and cumbersome. Tissue fragmentation and loss compromise cancer diagnosis. We sought to study an alternate method to improve processing and diagnosis of prostate cancer. METHODS: Two sets of sextant biopsy specimens from near-identical locations were obtained ex vivo from 48 prostate specimens. One set was processed in the standard fashion while the other was processed using the BxChip, a proprietary biomimetic matrix that accommodates six cores on a single chip. Parameters including grossing, embedding, sectioning and reading time, length of tissue, and degree of fragmentation were compared. RESULTS: A significant reduction (more than threefold) in preanalytical and analytical time was observed using the multiplex method. Nonlinear fragmentation was absent, in contrast to standard processing. CONCLUSIONS: The BxChip reduced tissue fragmentation and increased efficiency of prostate biopsy diagnosis. It also resulted in overall cost savings and significantly increased tissue length.

The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate.

The cell adhesion molecule Nectin-4 is overexpressed in epithelial cancers, including ovarian cancer. The objective of this study was to determine the biological significance of Nectin-4 in the adhesion, aggregation, migration, and proliferation of ovarian cancer cells. Nectin-4 and its binding partner Nectin-1 were detected in patients' primary tumors, omental metastases, and ascites cells. The human cell lines NIH:OVCAR5 and CAOV3 were genetically modified to alter Nectin-4 expression. Cells that overexpressed Nectin-4 adhered to Nectin-1 in a concentration and time-dependent manner, and adhesion was inhibited by antibodies to Nectin-4 and Nectin-1, as well as synthetic Nectin peptides. In functional assays, CAOV3 cells with Nectin-4 knock-down were unable to form spheroids and migrated more slowly than CAOV3 parental cells expressing Nectin-4. NIH:OVCAR5 parental cells proliferated more rapidly, migrated faster, and formed larger spheroids than either the Nectin-4 knock-down or over-expressing cells. Parental cell lines expressed higher levels of epithelial markers and lower levels of mesenchymal markers compared to Nectin-4 knock-down cells, suggesting a role for Nectin-4 in epithelial-mesenchymal transition. Our results demonstrate that Nectin-4 promotes cell-cell adhesion, migration, and proliferation. Understanding the biology of Nectin-4 in ovarian cancer progression is critical to facilitate its development as a novel therapeutic target.

HomeRun Vector Assembly System: a flexible and standardized cloning system for assembly of multi-modular DNA constructs.

Advances in molecular and synthetic biology call for efficient assembly of multi-modular DNA constructs. We hereby present a novel modular cloning method that obviates the need for restriction endonucleases and significantly improves the efficiency in the design and construction of complex DNA molecules by standardizing all DNA elements and cloning reactions. Our system, named HomeRun Vector Assembly System (HVAS), employs a three-tiered vector series that utilizes both multisite gateway cloning and homing endonucleases, with the former building individual functional modules and the latter linking modules into the final construct. As a proof-of-principle, we first built a two-module construct that supported doxycycline-induced expression of green fluorescent protein (GFP). Further, with a three-module construct we showed quantitatively that there was minimal promoter leakage between neighbouring modules. Finally, we developed a method, in vitro Cre recombinase-mediated cassette exchange (RMCE) cloning, to regenerate a gateway destination vector from a previous multisite gateway cloning reaction, allowing access to existing DNA element libraries in conventional gateway entry clones, and simple creation of constructs ready for in vivo RMCE. We believe these methods constitute a useful addition to the standard molecular cloning techniques that could potentially support industrial scale synthesis of DNA constructs.