Citations

Abstract Purpose: Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence. Methods: The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n = 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified. Results: Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) = 2.46, 95% confidence interval (CI), 1.07–5.69, P = 0.035], whereas binary GCC LNR risk class (HR = 1.87, 95% CI, 0.99–3.54, P = 0.054) and mismatch repair (MMR) status (HR = 0.77, 95% CI, 0.36–1.62, P = 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR ≤ 0.20), and low (LNR ≤ 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR = 2.53, 95% CI, 1.24–5.17, P = 0.011). Conclusions: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique. Clin Cancer Res; 20(16); 4361–9. ©2014 AACR.

AbstractBackgroundThere is symptom overlap between gastro‐esophageal reflux disease (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD cases are now more likely mislabeled as GERD.MethodsIn subjects from Olmsted County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates between 1985 and 2009. (ii) Assessment of survey‐based upper gastrointestinal symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD during a medical encounter. (iv) Assess the association between PPI use and GERD and/or FD symptoms and between actual diagnoses received.Key Results(i) Yearly GERD diagnosis rates rose between 1985 and 2009 (325–1866 per 100 000). FD diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100 000 in 2009. (ii) Reported GERD symptoms did not significantly change between three survey waves in the years 1988–2009 (p = 0.052), whereas FD symptoms slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms received a FD diagnosis. (iv) PPI use was associated with documented GERD diagnosis (p < 0.001), however there was no significant association between GERD symptoms and PPI use (p = 0.078).Conclusions & InferencesWe have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic‐ and gender‐based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high‐resolution manometry in noncardiac chest pain; whether pH–impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain.

This paper presents commentaries on how endoluminal antireflux procedures compare to laparoscopic fundoplication; new endoscopic procedures being studied to treat refractory gastroesophageal reflux disease (GERD); the new Stretta; the relationship between obesity and proton pump inhibitor (PPI) resistance; data concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing refractory GERD; whether microscopic esophagitis is relevant in determining symptoms of non‐erosive reflux disease (NERD); how concomitant functional gastrointestinal disorders affect the PPI response in NERD; the evidence that a functional esophagus is associated with inflammatory bowel syndrome (IBS); the role of GABA agonists in the treatment of refractory GERD; the role of biofeedback and antidepressants in refractory GERD; and endoluminal fundoplication using the EsophyX device.

Curricular changes continue at United States medical schools and directors of gross anatomy, microscopic anatomy, neuroscience/neuroanatomy, and embryology courses continue to adjust and modify their offerings. Developing and supplying data related to current trends in anatomical sciences education is important if informed decisions are going to be made in a time of curricular and course revision. Thus, a survey was sent to course directors during the 2012–2013 academic years to gather information on total course hours, lecture and laboratory hours, the type of laboratory experiences, testing and competency evaluation, and the type of curricular approach used at their institution. The data gathered were compared to information obtained from previous surveys and conclusions reached were that only small or no change was observed in total course, lecture and laboratory hours in all four courses; more gross anatomy courses were part of an integrated curriculum since the previous survey; virtual microscopy with and without microscopes was the primary laboratory activity in microscopic anatomy courses; and neuroscience/neuroanatomy and embryology courses were unchanged. Anat Sci Educ 7: 321–325. © 2014 American Association of Anatomists.

Understanding the mechanisms that sustain pluripotency in human embryonic stem cells (hESCs) is an active area of research that may prove useful in regenerative medicine and will provide fundamental information relevant to development and cancer. hESCs and cancer cells share the unique ability to proliferate indefinitely and rapidly. Because the protein survivin is uniquely overexpressed in virtually all human cancers and in hESCs, we sought to investigate its role in supporting the distinctive capabilities of these cell types. Results presented here suggest that survivin contributes to the maintenance of pluripotency and that post‐transcriptional control of survivin isoform expression is selectively regulated by microRNAs. miR‐203 has been extensively studied in human tumors, but has not been characterized in hESCs. We show that miR‐203 expression and activity is consistent with the expression and subcellular localization of survivin isoforms that in turn modulate expression of the Oct4 and Nanog transcription factors to sustain pluripotency. This study contributes to understanding of the complex regulatory mechanisms that govern whether hESCs proliferate or commit to lineages. J. Cell. Physiol. 230: 63–70, 2015. © 2014 Wiley Periodicals, Inc.

Key Points Methylation analysis at ZAP-70 CpG+223 in CLL provides superior prognostic information vs IGHV status or CD38 or ZAP-70 expression. A pyrosequencing method for the feasible assessment of CpG+223 methylation in CLL samples is provided.