Patricia Houser

OBJECTIVE To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N = 184), 7 mg (N = 182), or 14 mg (N = 181) or to placebo (N = 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment difference [ETD] –0.5% [95% CI –0.7, –0.3], –0.9% [–1.1, –0.7], and –1.2% [–1.4, –1.0] for 3, 7, and 14 mg, respectively; P < 0.001) and body weight (ETD −0.9 kg [95% CI −1.8, −0.0], −2.0 kg [−3.0, −1.0], and −3.3 kg [−4.2, −2.3]; P = 0.0392 for 3 mg, P ≤ 0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater dose-dependent HbA1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4–23.2% of patients vs. 7.1% with placebo; mostly mild to moderate). CONCLUSIONS Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with or without metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide 1 receptor agonists.

BACKGROUND Urine cytology has been used for screening of bladder cancer but has been limited by its low sensitivity. UroVysion is a multiprobe fluorescence in situ hybridization (FISH) assay that detects common chromosome abnormalities in bladder cancers. For this study, the authors evaluated the effectiveness of multiprobe FISH and urine cytology in detecting urothelial cell carcinoma (UCC) in the same urine sample. METHODS In total, 1835 cases with the following criteria were selected: valid results from both the multiprobe FISH assay and urine cytology in the same urine sample, histologic and/or cystoscopic follow‐up within 4 months of the original tests, or at least 3 years of clinical follow‐up information. The results of FISH and cytology were correlated with clinical outcomes derived from a combination of histologic, cystoscopic, and clinical follow‐up information. RESULTS Of 1835 cases, 1045 cases were from patients undergoing surveillance of recurrent UCC, and 790 were for hematuria. The overall sensitivity, specificity, positive predictive value, and negative predictive value in detecting UCC were 61.9%, 89.7%, 53.9%, and 92.4%, respectively, for FISH and 29.1%, 96.9%, 64.4%, and 87.5%, respectively, for cytology. The performance of both FISH and cytology generally was better in the surveillance population and in samples with high‐grade UCC. In 95 of 296 cases with atypical cytology that were proven to have UCC, 61 cases, mostly high‐grade UCC, were positive using the multiprobe FISH assay. CONCLUSIONS The UroVysion multiprobe FISH assay was more sensitive than urine cytology in detecting UCC, but it produced more false‐positive results. The current data suggest that the use of FISH as a reflex test after an equivocal cytologic diagnosis may play an effective role in detecting UCC. Cancer (Cancer Cytopathol) 2013;121:591–597. © 2013 American Cancer Society.

BACKGROUND: On-site evaluation of fine-needle aspiration (FNA) specimens by a pathologist is essential to obtain adequate samples and provide a preliminary diagnosis. Distance from the laboratory can make this difficult. The authors present their experience with on-site evaluation using telecytopathology. METHODS: Dynamic images of cytology smears were captured and processed with a Nikon digital camera system for microscopy and transmitted via Ethernet. A pathologist accessed the real-time images on a computer and interpreted them while communicating with on-site operators over the telephone. Sample adequacy and accuracy of preliminary diagnosis were compared with those obtained by regular on-site evaluation. RESULTS: A total of 429 telecytopathology cases and 363 conventional on-site cases were compared. Specimens were mainly from the pancreas, gastrointestinal tract, liver, and lymph nodes. Adequacy rate was 94.0% for telecytopathology and 97.7% for conventional cases. Preliminary diagnoses of unsatisfactory, adequate (defer), negative/benign, atypical, neoplasm, suspicious, and positive for malignancy were 6.3%, 13.5%, 14.9%, 17.9%, 7.2%, 8.6%, and 31.5% for telecytopathology and 3.9%, 30.6%, 21.5%, 9.6%, 5.0%, 5.2%, and 24.2% for conventional cases. Preliminary and final diagnoses were discrepant in 7 (1.8%) of 371 telecytopathology cases, and in 8 (3.1%) of 252 conventional cases. Difficulty was encountered in some cases in distinguishing pancreatic endocrine neoplasm from lymphoid proliferations, and low grade pancreatic tumors from chronic pancreatitis via telecytopathology. CONCLUSIONS: On-site evaluation of FNA specimens via telecytopathology assures sample adequacy and accurate preliminary diagnosis compared with the conventional method. It allows pathologists to use their time more efficiently and makes on-site evaluations at remote locations possible.

In humans pericentric inversions are rare structural chromosome abnormalities. Reproductive consequences of inversion heterozygosity depend upon many variables such as the chromosomes involved, the location of breakpoints, frequency of crossovers in the inverted segment, functional impairment of the gametes produced, and the viability of unbalanced zygotes that form. Therefore, each pericentric inversion may be studied as a unique mutation. This paper analyzes the segregation of inversion 13 chromosomes resulting from breaks at bands 13p12 and 13q21/22 in 11 apparently unrelated families. Ten of these families were ascertained through malformed fetuses or infants with a recombinant 13 duplication q, deletion p chromosome.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as the diagnostic modality of choice for mass lesions in the pancreas. The objective of the current study was to determine the accuracy and pitfalls of EUS-FNA in the diagnosis of pancreatic lesions in cases that involved follow-up surgical resection. METHODS: Cases of EUS-FNA of pancreatic lesions performed from 2007 to mid-2012 for which subsequent surgical resection was performed were retrieved from the department's database. The accuracy of the cytologic diagnosis was assessed using the histological diagnosis as the gold standard. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. "Neoplastic," "suspicious," and "malignant" were classified as a positive cytologic diagnosis. In one calculation method, "atypical" was also included as a positive cytologic diagnosis whereas in another it was not considered to be a positive cytological result. The cases with a cytologic-histological discrepancy were reviewed to identify sources of errors. RESULTS: A total of 1212 cases from 1104 patients (518 women and 586 men; age range, 18-94 years [average age, 63.5 years]) were identified. Cytologic diagnoses included 52 unsatisfactory, 224 benign, 129 atypical, 140 neoplasm, 35 suspicious, and 632 malignant diagnoses. Of these cases, 397 patients had histological follow-up information available. The sensitivity, specificity, positive predictive value, and negative predictive value were 83.2%, 85.9%, 95.9%, and 56.1%, respectively, with atypical cases excluded from the analysis. When atypical cases were included as a positive cytologic diagnosis, the sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 67.9%, 90.7%, and 58.5%, respectively, and were 73.7%, 87.7%, 95.6%, and 48.0%, respectively, when atypical cases were included as a negative cytologic diagnosis. The major difficulty in EUS-FNA cytology was to differentiate pancreatic mucinous neoplasms from contaminants of gastric mucosa. Other pitfalls included differentiating mucinous neoplasm from extensive pancreatic intraepithelial neoplasia, and endocrine tumor from nesidioblastosis versus acinar cell carcinoma or intrapancreatic spleen. CONCLUSIONS: EUS-FNA is a valuable tool for the diagnosis of pancreatic lesions, especially solid malignant tumors. Cytologic-radiological correlation is essential in differentiating pancreatic mucinous neoplasms from gastric mucosa, because the former usually are found to have characteristic features on imaging. Pathologists should be aware of the pitfalls in the cytologic diagnosis of pancreatic lesions that may significantly change the clinical management of the patients.