The American College of Radiology and the American Brachytherapy Society practice parameter for transperineal permanent brachytherapy of prostate cancer.

Transperineal permanent brachytherapy is a safe and effective treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and the American Brachytherapy Society (ABS) has produced practice parameters for LDR prostate brachytherapy.

ACR Appropriateness Criteria® Locally Advanced, High-Risk Prostate Cancer.

Purpose: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer METHODS:: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR appropriateness criteria: Permanent source brachytherapy for prostate cancer.

Purpose: To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy.

Methods And Materials: The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel.

Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping.

Purpose: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT).

Objective: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity.

Surgical Delay of the Nipple-Areolar Complex in High-risk Nipple-sparing Mastectomy Reconstruction.

As nipple-sparing mastectomy gains increasing popularity, minimizing the risk of nipple necrosis continues to be of critical importance to patients and surgeons. Patients with large or ptotic breasts, scars from previous cosmetic and/or oncologic breast surgery, or previous irradiation have often been denied nipple-sparing mastectomy (NSM) because of increased risk of nipple necrosis. A variety of interventions have been suggested to minimize the ischemic insult to the nipple-areolar complex (NAC).

Pancreatic Cancer from Molecular Pathways to Treatment Opinion.

Pancreatic cancer is considered one of the most lethal malignances. It has been observed that the five year survival rate is less than 5%. Early diagnosis, understanding the risk factors and investigation of the molecular pathways with targeted therapy are the keys for efficient treatment.

Pancreatic cancer from bench to bedside: molecular pathways and treatment options.

In the last forty years the pancreatic cancer treatment has made advances, however; still novel drugs are needed. It is known that the five year survival rate remains around 5%. The best treatment option still remains surgery, if patients are diagnosed early.

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity.

Background: Polymorphic CYP2D6 is primarily responsible for metabolic activation of tamoxifen to endoxifen. We previously reported that by increasing the daily tamoxifen dose to 40 mg/day in CYP2D6 intermediate metabolizer (IM), but not poor metabolizer (PM), patients achieve endoxifen concentrations similar to those of extensive metabolizer patients on 20 mg/day. We expanded enrollment to assess the safety of CYP2D6 genotype-guided dose escalation and investigate concentration differences between races.

Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy.

Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures.

Tyrosine Kinase Inhibitors for the Elderly.

Until few years ago non-specific cytotoxic agents were considered the tip of the arrow as first line treatment for lung cancer. However; age > 75 was considered a major drawback for this kind of therapy. Few exceptions were made by doctors based on the performance status of the patient.

Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications.

miRNAs as potential biomarkers in early breast cancer detection following mammography.

Breast cancer is the most common cancer among American women, except for skin cancers. About 12 % women in the United States will develop invasive breast cancer during their lifetime. Currently one of the most accepted model/theories is that ductal breast cancer (most common type of breast cancer) follows a linear progression: from normal breast epithelial cells to ductal hyperplasia to atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), and finally to invasive ductal carcinoma (IDC).

Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues.

Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer.

Impact of Tumor Size on Probability of Pathologic Complete Response After Neoadjuvant Chemotherapy.

Background: The prospective Neoadjuvant Breast Symphony Trial (NBRST) study found that MammaPrint/BluePrint functional molecular subtype is superior to conventional immunohistochemistry/fluorescence in situ hybridization subtyping for predicting pathologic complete response (pCR) to neoadjuvant chemotherapy. The purpose of this substudy was to determine if the rate of pCR is affected by tumor size.

Methods: The NBRST study includes breast cancer patients who received neoadjuvant chemotherapy.

miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.

MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis.

Differential Targeting of Stem Cells and Differentiated Glioblastomas by NK Cells.

We have recently shown that Natural Killer (NK) cells control survival and differentiation of Cancer Stem-like Cells (CSCs) through two distinct phenotypes of cytotoxic and anergic NK cells, respectively. In this report, brain CSCs and their serum and NK cell differentiated counterparts were studied. Serum-differentiated brain CSCs were significantly less susceptible to NK cells and CTL direct cytotoxicity as well as NK cell mediated Antibody Dependent Cellular Cytotoxicity (ADCC), whereas their CSCs were highly susceptible.

Role of multi-modality therapy in peritoneal carcinomatosis and visceral metastasis: a case report and review of the literature.

Introduction: Treatment for advanced stage colorectal cancer with synchronous peritoneal carcinomatosis (PC) and hepatic metastasis (HM) has progressed significantly over the past 10 years.

Case Report: We present the case of a 39-year-old female patient with stage IV colorectal cancer with bilateral HM, pulmonary oligometastatic disease, and diffuse PC who underwent hyperthermic intraperitoneal chemotherapy (HIPEC) and complete cytoreductive surgery (CRS) for her intra-abdominal disease. The patient had an uneventful immediate post-operative recovery, and subsequently tolerated multiple cycles of adjuvant chemotherapy and percutaneous radiofrequency ablation of pulmonary lesions.

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

Background: Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.

Methods: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency.

In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles.

Aims: A prospectively enrolled patient cohort was used to assess whether the prediction of CYP2D6 phenotype activity from genotype data could be improved by reclassification of diplotypes or alleles.

Methods: Three hundred and fifty-five patients receiving tamoxifen 20 mg were genotyped for CYP2D6 and tamoxifen metabolite concentrations were measured. The endoxifen : N-desmethly-tamoxifen metabolic ratio, as a surrogate of CYP2D6 activity, was compared across four diplotypes (EM/IM, EM/PM, IM/IM, IM/PM) that are typically collapsed into an intermediate metabolizer (IM) phenotype.

Significance of Circulating Tumor Cells in Metastatic Triple-Negative Breast Cancer Patients within a Randomized, Phase II Trial: TBCRC 019.

Purpose: Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). We tested whether EpCAM-based capture system (CellSearch) is effective in patients with triple-negative (TN) MBC, and whether CTC apoptosis and clustering enhances the prognostic role of CTC.

Experimental Design: CTC enumeration and apoptosis were determined using the CXC CellSearch kit at baseline and days 15 and 29 in blood drawn from TN MBC patients who participated in a prospective randomized phase II trial of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without tigatuzumab.

Management of Inguinal Involvement of Peritoneal Surface Malignancies by Cytoreduction and HIPEC with Inguinal Perfusion.

Background: Achieving complete cytoreduction of peritoneal surface malignancies (PSM) can be challenging. In most cases, delivery of heated intra-peritoneal chemotherapy (HIPEC) is straightforward. However, using the closed technique in some cases may be technically challenging; for example, in patients requiring abdominal closure using a large synthetic mesh.

Colon Cancer Associated Transcript-1 (CCAT1) Expression in Adenocarcinoma of the Stomach.

Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC).

Pathway and network approaches for identification of cancer signature markers from omics data.

The advancement of high throughput omic technologies during the past few years has made it possible to perform many complex assays in a much shorter time than the traditional approaches. The rapid accumulation and wide availability of omic data generated by these technologies offer great opportunities to unravel disease mechanisms, but also presents significant challenges to extract knowledge from such massive data and to evaluate the findings. To address these challenges, a number of pathway and network based approaches have been introduced.

Differential impact of tumor-infiltrating immune cells on basal and luminal cells: implications for tumor invasion and metastasis.

Background/aim: Regarding the impact of tumor-infiltrating immune cells on tumor cells, many contradictory reports have been published. We have hypothesized that these controversies result from differences in tissue types and tumor stages, in which immune cells are variably distributed and differentially associated with epithelial cells. Our current study compared the pattern and frequency of physical association of tumor-infiltrating immune cells with different parenchymal cells of human breast and prostate tumors harboring normal, hyperplastic, in situ, and invasive components.

Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors.

In this paper, we provide evidence that anergized NK cells through secreted factors and direct cell-cell contact have the ability to induce differentiation of healthy dental pulp stem cells and stem cell of apical papillae as well as transformed oral squamous cancer stem cell (OSCSC) and Mia-Paca-2, poorly differentiated stem-like pancreatic tumors, resulting in their resistance to NK cell-mediated cytotoxicity. Induction of NK cell resistance and differentiation in the stem cells correlated with the increased expression of CD54, B7H1, and MHC class I, and mediated by the combination of membrane-bound or secreted IFN-γ and TNF-α from the NK cells since antibodies to both cytokines and not each one alone were able to inhibit differentiation or resistance to NK cells. Similarly, antibodies to both TNF-α and IFN-γ were required to prevent NK-mediated inhibition of cell growth, and restored the numbers of the stem cells to the levels obtained when stem cells were cultured in the absence of anergized NK cells.