Comparative molecular subtypes of index and metachronous gastric adenocarcinomas: a study of 42 Korean patients.

To date, there have been no studies comparing the molecular subtypes of Index gastric cancers (IGCs) and metachronous gastric cancers (MGCs). We evaluated a cohort of 42 patients with 43 IGCs and 45 MGCs. Molecular subtyping was performed by immunohistochemistry of mismatch repair (MMR) proteins, E-cadherin, p53, and Epstein-Barr virus- (EBV-) in situ hybridization (ISH).

Lipophilicity Determines Routes of Uptake and Clearance, and Toxicity of an Alpha-Particle-Emitting Peptide Receptor Radiotherapy.

Lipophilicity is explored in the biodistribution (BD), pharmacokinetics (PK), radiation dosimetry (RD), and toxicity of an internally administered targeted alpha-particle therapy (TAT) under development for the treatment of metastatic melanoma. The TAT conjugate is comprised of the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate), conjugated to melanocortin receptor 1 specific peptidic ligand (MC1RL) using a linker moiety and chelation of the Ac radiometal. A set of conjugates were prepared with a range of lipophilicities (log values) by varying the chemical properties of the linker.

Preclinical evaluation of [Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms.

Purpose: There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide Lu ([Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [Ac]Ac-DOTA-TATE in patients that were refractory to [Lu]Lu-DOTA-TATE.

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

Purpose: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy.

Methods: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014.

Primary tumor size thresholds in stage IA testicular seminoma: Implications for adjuvant therapy after orchiectomy and survival.

Objectives: Primary tumor size (PTS) is the main prognostic factor for relapse in clinical stage (CS) IA testicular seminoma (T1N0M0S0) and the 8th edition of the Tumor-Node-Metastasis staging system now subcategorizes pT1 tumors into pT1a and pT1b based on PTS (<3 cm and ≥3 cm, respectively). We attempted to assess PTS as a prognosticator for overall survival (OS) in CS IA seminoma and to evaluate the comparative effectiveness of active surveillance (AS) versus adjuvant therapy (AT) in patients with large primary tumors (LPT).

Methods And Materials: In the National Cancer Database (2004-2014), 2455 (47.

Melanocortin 1 Receptor-Targeted α-Particle Therapy for Metastatic Uveal Melanoma.

New effective therapies are greatly needed for metastatic uveal melanoma, which has a very poor prognosis with a median survival of less than 1 y. The melanocortin 1 receptor (MC1R) is expressed in 94% of uveal melanoma metastases, and a MC1R-specific ligand (MC1RL) with high affinity and selectivity for MC1R was previously developed. The Ac-DOTA-MC1RL conjugate was synthesized in high radiochemical yield and purity and was tested in vitro for biostability and for MC1R-specific cytotoxicity in uveal melanoma cells, and the lanthanum-DOTA-MC1RL analog was tested for binding affinity.

Trends in use of bilateral prophylactic mastectomy vs high-risk surveillance in unaffected carriers of inherited breast cancer syndromes in the Inherited Cancer Registry (ICARE).

Purpose: Awareness of inherited breast cancer has increased bilateral prophylactic mastectomy (BPM) among unaffected genetic mutation carriers, yet many still choose surveillance. We aimed to identify differences among women electing BPM vs high-risk surveillance.

Methods: Participants from an IRB-approved database recruited from 11/2000 to 01/2017 with a deleterious/pathogenic, variant suspected deleterious, or likely pathogenic mutation in ≥ 1 of 11 genes with increased risk for breast cancer (per 2017 NCCN guidelines) were identified.

Epidural anesthesia and cancer outcomes in bladder cancer patients: is it the technique or the medication? A matched-cohort analysis from a tertiary referral center.

Background: The perioperative period can be a critical period with long-term implications on cancer-related outcomes. In this study, we evaluate the influence of regional anesthesia on cancer-specific outcomes in a radical cystectomy (RC) cohort of patients.

Methods: We performed a retrospective analysis of patients with clinically-nonmetastatic urothelial carcinoma of the bladder who underwent RC at our institution from 2008 to 2012.

The Value of Neutrophil to Lymphocyte Ratio in Patients Undergoing Cytoreductive Nephrectomy with Thrombectomy.

Background: The neutrophil-lymphocyte ratio (NLR) is an established signature of inflammation used for evaluating renal cell carcinoma (RCC).

Objective: To determine the utility of NLR and its relationship with known risk factors associated with poor survival in patients with metastatic RCC and tumor thrombus undergoing cytoreductive nephrectomy (CN).

Design, Setting, And Participants: Prognostic variables were reviewed for patients undergoing CN with thrombectomy between 2000 and 2014 from six different institutions.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Penile Squamous Cell Carcinoma Patients Undergoing Inguinal Lymph Node Dissection.

Background: Further biomarkers are warranted to improve prognostic stratification of penile squamous cell carcinoma (PSCC) patients undergoing inguinal lymph node dissection (ILND).

Objective: To assess the prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in PSCC patients undergoing ILND and to investigate its role in predicting pathologic node-positive (pN+) disease.

Design, Setting, And Participants: In total, 84 consecutive patients undergoing ILND for PSCC at our institution between 1994 and 2014 were identified.

Cell-surface marker discovery for lung cancer.

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step.

Pathologic Predictors of Survival During Lymph Node Dissection for Metastatic Renal-Cell Carcinoma: Results From a Multicenter Collaboration.

Purpose: To determine the therapeutic value of lymph node dissection (LND) during cytoreductive nephrectomy (CN) and assess predictors of cancer-specific survival (CSS) in metastatic renal-cell carcinoma.

Patients And Methods: We identified 293 consecutive patients treated with CN at 4 academic institutions from March 2000 to May 2015. LND was performed in 187 patients (63.

A novel approach to improving efficiency and cost saving in preoperative blood preparation.

Background: Preoperative ordering of blood products has been an area of optimization due to considerable variability among physicians; overpreparation can lead to extra costs and underpreparation of blood can potentially compromise patient safety.

Study Design And Methods: We examined the potential cost savings of extending the storage interval of a presurgical type-and-screen sample from 7 to 14 days, thereby reducing the need for a new specimen on the day of surgery.

Results: Sensitivity analysis showed annual cost savings for our institution to be an estimated $38,770 ($22,420-$73,120).

Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives.

Context: Islet autoantibodies are markers of type 1 diabetes, and an increase in number of autoantibodies detected during the preclinical phase predicts progression to overt disease.

Objective: To refine the effect of age in relation to islet antibody type on progression from single to multiple autoantibodies in relatives of people with type 1 diabetes.

Research Design And Methods: We examined 994 relatives with normal glucose tolerance who were positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention.

The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes.

Aims/hypothesis: Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention.

Methods: The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study.

Background: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials.

Materials And Methods: Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study.

Use of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of the risk classification of type 1 diabetes.

OBJECTIVE We studied the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of type 1 diabetes (T1D) risk classification in TrialNet Natural History Study (TNNHS) participants. RESEARCH DESIGN AND METHODS The cumulative incidence of T1D was compared between normoglycemic individuals with DPTRS values >7.00 and dysglycemic individuals in the TNNHS (n = 991).

The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

Objective: We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).

Research Design And Methods: TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A.

The application of the diabetes prevention trial-type 1 risk score for identifying a preclinical state of type 1 diabetes.

Objective: We assessed the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T1D) within 2 years.

Research Design And Methods: The DPTRS was previously developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BMI.

Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.

Objective: We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A).

Research Design And Methods: For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives.

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies.

Background: Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR.

Methods: One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs.

Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the TrialNet Natural History Study.

Objective: We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS).

Research Design And Methods: Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS intervals was compared between the TNNHS and DPT-1 cohorts.

Increased cyclin D3 expression significantly correlates with p27 nuclear positivity in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors, the most common mesenchymal tumors of the gastrointestinal tract, are characterized by strong expression of c-Kit protein. Recently, it has been shown that gastrointestinal stromal tumors may also contain alterations of genes involved in the regulation of cell cycle. In this study, we evaluate the prevalence and clinical significance of cyclin D1 and D3, Ki-67, p27, and retinoblastoma protein expression in a group of 50 human gastrointestinal stromal tumors selected from the files of the Moffitt Cancer Center.

Altered expression of cell cycle regulatory proteins in benign and malignant bone and soft tissue neoplasms.

Background: The binding of cyclins to cyclin-dependent kinases regulates cell proliferation. Overexpression of cyclins is believed to deregulate the cell cycle in human tumors. Here the expression of G1 cyclins D1 and D3, and of Ki-67 in a variety of bone and soft tissue sarcomas was assessed as compared to adjacent normal tissue and to a subset of leiomyomas.