Citations

The following paper on gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) includes commentaries on defining esophageal landmarks; new techniques for evaluating upper esophageal sphincter (UES) tone; differential diagnosis of GERD, BE, and hiatal hernia (HH); the use of high‐resolution manometry for evaluation of reflux; the role of fundic relaxation in reflux; the use of 24‐h esophageal pH–impedance testing in differentiating acid from nonacid reflux and its potential inclusion in future Rome criteria; classification of endoscopic findings in GERD; the search for the cell origin that generates BE; and the relationship between BE, Barrett's carcinoma, and obesity.

Various endovascular intraarterial approaches are available for treating patients with acute ischemic stroke who present with severe neurological deficits. Three recent randomized trials—Interventional Management of Stroke (IMS) III, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke (SYNTHESIS Expansion)—evaluated the efficacy of endovascular treatment of acute ischemic stroke and, after failing to demonstrate any significant clinical benefit of endovascular therapies, raised concerns and questions in the medical community regarding the future of endovascular treatment for acute ischemic stroke. In this paper, the authors review the evolution of endovascular treatment strategies for the treatment of acute stroke and provide their interpretation of findings and potential limitations of the three recently published randomized trials. The authors discuss the advantage of stent-retriever technology over earlier endovascular approaches and review the current status and future directions of endovascular acute stroke studies based on lessons learned from previous trials.

BACKGROUND Recombinant interleukin‐2 (rIL‐2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL‐2–activated effector cells. METHODS In the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90‐day course of subcutaneously administered rIL‐2 or no further therapy. The primary objective was to compare disease‐free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low‐dose daily rIL‐2 were given for the expansion of cytotoxic effector cells, each followed by 3‐day high‐dose boluses given to trigger cytotoxicity against minimal residual disease. RESULTS On the protocol‐specified intention‐to‐treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52‐1.09; P = .13); the 5‐year DFS rate was 42% in the observation arm and 53% in the rIL‐2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54‐1.23; P = .34); the 5‐year OS rate was 58% for the observation arm and 63% for the rIL‐2 treatment arm. Twenty‐five of the 107 patients randomized to treatment with rIL‐2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance. CONCLUSIONS The efficacy of immunotherapy with rIL‐2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol‐directed therapy. Neither DFS nor OS was found to be significantly improved. Cancer 2014;120:1010–1017 . © 2013 American Cancer Society .

BACKGROUND The majority of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have low‐risk disease with a < 10% chance of ccRCC‐specific death. DNA sequencing revealed that mutations in BAP1 (BRCA1 associated protein‐1) occur in 5% to 15% of ccRCC cases and are associated with poor outcomes. The vast majority of BAP1 mutations abolish protein expression. In this study, we used a highly sensitive and specific immunohistochemistry (IHC) assay to test whether BAP1 expression is an independent marker of ccRCC‐specific survival, particularly in patients with low‐risk disease. METHODS BAP1 expression was assessed, using IHC, in 1479 patients who underwent nephrectomy to treat clinically localized ccRCC. A centralized pathologist dichotomized patients as either BAP1‐positive or BAP1‐negative. The authors employed Kaplan‐Meier and Cox regression models to associate BAP1 expression with cancer‐specific survival. RESULTS A total of 10.5% of tumors were BAP1‐negative, 84.8% of tumors were BAP1‐positive, and 4.6% of tumors had ambiguous staining for BAP1. Patients with BAP1‐negative tumors have an increased risk of ccRCC‐related death (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 2.28‐4.10; P = 6.77 × 10 −14 ). BAP1 expression remained an independent marker of prognosis after adjusting for the UCLA integrated staging system (UISS) (HR = 1.67; 95% CI = 1.24‐2.25; P < .001). Finally, BAP1 was an independent prognostic marker in low‐risk patients with a Mayo Clinic stage, size, grade, and necrosis (SSIGN) score of ≤ 3 (HR = 3.24; 95% CI = 1.26‐8.33; P = .015). CONCLUSIONS This study used a large patient cohort to demonstrate that BAP1 expression is an independent marker of prognosis in patients with low‐risk (SSIGN≤ 3) ccRCC. Cancer 2014;1059–1067 . © 2014 American Cancer Society .

PurposeTo examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course.Patients and MethodsIn all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients.ResultsAuto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT.ConclusionFor patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation. © 2013 Wiley Periodicals, Inc.

SummaryBackgroundThe population ≥65 years is rapidly increasing, but remarkably little is known about the natural history of abdominal pain with ageing.AimTo prospectively evaluate the natural history of abdominal pain (severity and frequency) in a US population, and evaluate potential risk factors (including somatisation) for the onset and disappearance of abdominal pain with increasing age.MethodsBetween 1988 and 2004, valid self‐report questionnaires that recorded gastrointestinal symptoms including severity and frequency of abdominal pain were mailed to randomly selected cohorts of community residents followed over time. This study identified all respondents who answered abdominal pain questions at an initial and follow‐up survey.ResultsOne thousand nine hundred and thirteen subjects were included (mean age in years at first survey: 48 ± 12 (SD), mean age at second survey: 59 ± 13 (SD); 53% female). The onset and disappearance rate of abdominal pain over the follow‐up were 18% (95% CI, 16, 20) and 47% (43, 50) respectively. The rates of increasing vs. decreasing abdominal pain score were 18% (16, 20) vs. 21% (20, 23) respectively. While younger age at initial survey was associated with the onset of abdominal pain {vs. subjects without abdominal pain, [OR 0.9 (0.7, 1.0)]}, older age at initial survey and times between surveys were associated with the disappearance of abdominal pain {vs. subjects with abdominal pain, [OR 1.2 (1.0, 1.5)]}. Female gender (OR 1.4 [1.0, 2.1]), higher somatisation scores (OR 5.3 [3.2, 8.7]) and larger changes in somatisation score (OR 2.1 [1.4, 3.2]) were positively associated with the onset of abdominal pain.ConclusionIncreasing age is associated with the disappearance of abdominal pain in the community.