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.     

RT-PCR Increases Detection of Submicroscopic Peritoneal Metastases in Gastric Cancer and Has Prognostic Significance

Background  

Positive peritoneal cytology confers the same prognosis as clinical stage IV disease in gastric cancer. Conventional cytology examination, however, has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT-PCR) may have increased sensitivity and provide more accurate staging information.     

Does gonadotropin-releasing hormone agonist cause luteolysis by inducing apoptosis of the human granulosa-luteal cells?

Journal of Assisted Reproduction and Genetics - To evaluates the effect of different modes of final follicular maturation triggering on the degree of apoptosis of granulosa cells (GCs) and the...     

Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma

Overexpression of antiapoptotic members of the Bcl-2 family are observed in approximately 80% of B-cell lymphomas, contributing to intrinsic and acquired drug resistance. Nullifying antiapoptotic function can potentially overcome this in-trinsic and acquired drug resistance. AT-101 is a BH3 mimetic known to be a potent inhibitor of antiapoptotic Bcl-2 family members including Bcl-2, Bcl-X_L, and Mcl-1. In vitro, AT-101 exhibits concentration- and time-dependent cytotoxicity against lymphoma and multiple myeloma cell lines, enhancing the activity of cytotoxic agents. The IC₅₀ for AT-101 is between 1 and 10 µM for a diverse panel of B-cell lymphomas. AT-101 was synergistic with carfilzomib (C), etoposide (E), doxorubicin (D), and 4-hydroxycyclophosphamide (4-HC) in mantle cell lymphoma (MCL) lines. In a transformed large B-cell lymphoma line (RL), AT-101 was synergistic when sequentially combined with 4-HC, but not when both drugs were added simultaneously. AT-101 also induced potent mitochondrial membrane depolarization (m) and apoptosis when combined with carfilzomib, but not with bortezomib in MCL. In severe combined immunodeficient (SCID) beige mouse models of drug-resistant B-cell lymphoma, 35 mg/kg per day of AT-101 was safe and efficacious. The addition of AT-101 to cyclophosphamide (Cy) and rituximab (R) in a schedule-dependent manner enhanced the efficacy of the conventional therapy.      

Assessment of clinical,biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 10⁸ WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1β, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid.Level of evidence: IV.     

Diurnal Alterations of Refraction,Anterior Segment Biometrics,and Intraocular Pressure in Long-Time Dehydration due to Religious Fasting

Purpose: To investigate the effects of dehydration due to fasting on diurnal changes of intraocular pressure, anterior segment biometrics, and refraction. Subjects and methods: The intraocular pressures, anterior segment biometrics (axial length: AL; Central corneal thickness: CCT; Lens thickness: LT; Anterior chamber depth: ACD), and refractive measurements of 30 eyes of 15 fasting healthy male volunteers were recorded at 8:00 in the morning and 17:00 in the evening in the Ramadan of 2013 and two months later. The results were compared and the statistical analyses were performed using the Rstudio software version 0.98.501. The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk test) to determine whether or not they were normally distributed. Results: The refractive values remained stable in the fasting as well as in the control period (p?=?0.384). The axial length measured slightly shorter in the fasting period (p?=?0.001). The corneal thickness presented a diurnal variation, in which the cornea measured thinner in the evening. The difference between the fasting and control period was not statistically significant (p?=?0.359). The major differences were observed in the anterior chamber depth and IOP. The ACD was shallower in the evening during the fasting period, where it was deeper in the control period. The diurnal IOP difference was greater in the fasting period than the control period. Both were statistically significant (p?=?0.001). The LT remained unchanged in both periods. Conclusions: The major difference was shown in the anterior chamber shallowing in the evening hours and IOP. Our study contributes the hypothesis that the posterior segment of the eye is more responsible for the axial length alterations and normovolemia has a more dominant influence on diurnal IOP changes.     

Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer.

Metastatic prostate cancer may respond initially to hormone suppression, with involution of tumor sites, but ultimate tumor progression is inevitable. Our aim was to detect the proportion of bone and soft-tissue lesions that represent metabolically active tumor sites in patients with progressive metastatic prostate cancer. METHODS: In a prospective study, we compared 18F-FDG and L-methyl-11C-methionine (11C-methionine) PET with conventional imaging modalities (CIM), which included the combination of 99mTc-methylene diphosphonate scintigraphy, CT, or MRI. Twelve patients with prostate cancer, increasing levels of prostate-specific antigen (PSA), and at least 1 site (index lesion) with new or increasing disease on CIM were studied. The total numbers of soft-tissue and bone-tissue lesions, in a site-by-site comparison, were calculated for all imaging modalities. RESULTS: The sensitivities of 18F-FDG PET and 11C-methionine PET were 48% (167/348 lesions) and 72.1% (251/348 lesions), respectively, with CIM being used as the 100% reference (348/348). 11C-Methionine PET identified significantly more lesions than 18F-FDG PET (P < 0.01). All 12 patients with progressive metastatic prostate cancer had at least 1 lesion site of active metabolism for 18F-FDG or 11C-methionine, which could be used as an index lesion to monitor the metabolic response to therapy. A significant proportion of lesions (26%) had no detectable metabolism of 18F-FDG or 11C-methionine. Although technical factors cannot be totally excluded, we believe that metabolically inactive sites may be necrotic or dormant. More than 95% (251/258) of metabolically active sites (72% of the total number of lesions detected by CIM) metabolize 11C-methionine. 18F-FDG uptake is more variable, with 65% of metabolically active sites (48% of the total number of lesions detected by CIM). CONCLUSION: These findings reflect the different biologic characteristics of the lesions in a heterogeneous tumor such as prostate cancer and suggest that a time-dependent metabolic cascade may occur in advanced prostate cancer, with initial uptake of 11C-methionine in dormant sites followed by increased uptake of 18F-FDG during progression of disease.     

Reproducibility of 3D proton spectroscopy in the human brain.

The inter- and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy (1H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, +/-1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm(3) voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels) or time (by performing serial follow-ups).