Citations

AbstractThe aim of the present review is to summarize the current evidence on the role of pelvic and para‐aortic lymphadenectomy in endometrial cancer. In 1988, the International Federation of Obstetrics and Gynecology recommended surgical staging for endometrial cancer patients. However, 25 years later, the role of lymph node dissection remains controversial. Although the findings of two large independent randomized trials suggested that pelvic lymphadenectomy provides only adjunctive morbidity with no clear influence on survival outcomes, the studies have many pitfalls that limit interpretation of the results. Theoretically, lymphadenectomy may help identify patients with metastatic dissemination, who may benefit from adjuvant therapy, thus reducing radiation‐related morbidity. Also, lymphadenectomy may eradicate metastatic disease. Because lymphatic spread is relatively uncommon, our main effort should be directed at identifying patients who may potentially benefit from lymph node dissection, thus reducing the rate of unnecessary treatment and associated morbidity. This review will discuss the role of lymphadenectomy in endometrial cancer, focusing on patient selection, extension of the surgical procedure, postoperative outcomes, quality of life and costs. The need for new surgical studies and efficacious systemic drugs is recommended.

BackgroundPatients with disorders of gastrointestinal function may undergo unnecessary treatment if misdiagnosed as motility disorders.ObjectiveTo report on clinical features, medical, surgical, and psychiatric comorbidities, and prior treatments of a patient cohort diagnosed concurrently with nonpsychogenic rumination syndrome and pelvic floor dysfunction (also termed rectal evacuation disorder).MethodsFrom a consecutive series (1994–2013) of 438 outpatients with rectal evacuation disorders in the practice of a single gastroenterologist at a tertiary care centre, 57 adolescents or adults were diagnosed with concomitant rumination syndrome. All underwent formal psychological assessment or completed validated questionnaires.ResultsAll 57 patients (95% female) fulfilled Rome III criteria for rumination syndrome; rectal evacuation disorder was confirmed by testing of anal sphincter pressures and rectal balloon evacuation. Prior to diagnosis, most patients underwent multiple medical and surgical treatments (gastrostomy, gastric fundoplication, other gastric surgery, ileostomy, colectomy) for their symptoms. Psychological comorbidity was identified in 93% of patients. Patients were managed predominantly with psychological and behavioural approaches: diaphragmatic breathing for rumination and biofeedback retraining for pelvic floor dysfunction.ConclusionsAwareness of concomitant rectal evacuation disorder and rumination syndrome and prompt identification of psychological comorbidity are keys to instituting behavioural and psychological methods to avoid unnecessary treatment.

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF <60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF <30%, would affect a minuscule number of patients (0.3%). Conversely, EF <45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF >60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF <45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF <45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges >60%, with EF dropping <60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

SummaryBackgroundHighly selective 5‐HT4agonists have been suggested for the treatment of chronic constipation (CC).AimTo assess the effects of highly selective 5‐HT4agonists (prucalopride, velusetrag or naronapride) on patient‐important clinical efficacy outcomes and safety in adults withCC.MethodsWe searched the medical literature in January 2013 usingMEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5‐HT4agonists in adults withCC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention‐to‐treat analyses, pooled using a random‐effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI).ResultsMain outcomes included stool frequency, Patient‐Assessment of Constipation Quality of Life (PAC‐QOL),PACof symptoms (PAC‐SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5‐HT4agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95%CI1.23–2.79); mean ≥1SCBMover baseline (RR = 1.57; 95%CI1.19, 2.06); ≥1 point improvement inPAC‐QOLandPAC‐SYMscores. The only active comparator trial of prucalopride andPEG3350 suggestedPEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5‐HT4agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride.ConclusionDemonstration of efficacy on patient‐important outcomes and a favourable safety profile support the continued use and development of highly selective 5–HT4agonists in the treatment of chronic constipation.

Abstract Background: Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. Methods: We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. Results: From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32–2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Conclusion: Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer. Impact: SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. Cancer Epidemiol Biomarkers Prev; 22(12); 2384–94. ©2013 AACR.

The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D ( n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes ( ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P < 0.05). In the 633-person cohort, FGFR4 rs434434 was associated with symptom phenotype ( P = 0.027) and rs1966265 with 24-h colonic transit ( P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D.

Background and Purpose— The prognostic significance of subarachnoid extension of intracerebral hemorrhage was determined in the INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2) study. Methods— INTERACT2 was an open randomized controlled trial of early intensive compared with guideline-recommended blood pressure lowering in patients with elevated systolic blood pressure within 6 hours of intracerebral hemorrhage. Independent predictors of death or major disability (scores 3–6 on the modified Rankin Scale) at 90 days were analyzed in logistic regression models. Results— Of 2582 participants, 192 (7%) had subarachnoid extension, which was associated with larger hematoma volumes ( P <0.0001) and higher National Institute of Health Stroke Scale score ( P <0.0001). Subarachnoid extension predicted death or major disability at 90 days (71% versus 53%; unadjusted odds ratio, 2.25; 95% confidence interval, 1.63–3.10; P <0.0001). The association remained significant after adjusting for age, region, lipid-lowering therapy, systolic blood pressure, glucose, location of hematoma, intraventricular extension, and randomized treatment (odds ratio, 2.17; 95% confidence interval, 1.50–3.14; P <0.0001), but not after further adjustment for baseline hematoma volume ( P =0.62). Conclusions— Subarachnoid extension of intracerebral hemorrhage is associated with poor prognosis, which is determined by a larger volume of the underlying intraparenchymal hematoma. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

People with NIDDM are resistant to insulin. The present studies sought to determine whether the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is impaired. To address this question, basal insulin concentrations were maintained constant with an exogenous insulin infusion, while endogenous hormone secretion was inhibited by somatostatin. The integrated glycemic response above baseline during identical prandial glucose infusions was greater (1,411 ± 94 vs. 938 ± 45 mmol/l per 5 h; P &lt; 0.01) in the diabetic subjects than in the nondiabetic subjects, indicating a decrease in net glucose effectiveness. [6-3H]glucose also was infused to determine whether the decrease in net glucose effectiveness was due to a decrease in the ability of glucose to stimulate its own uptake and/or to suppress its own production. Despite identical rates of tracer infusion, the increment in plasma concentration of [6-3H]glucose was higher (4.50 ± 0.29 vs. 3.16 ± 0.21 × 105 dpm/ml per 5 h; P &lt; 0.05) in the diabetic subjects than in the nondiabetic subjects. This was due to both a decrease (P &lt; 0.05) in the ability of glucose to stimulate its own disappearance via mass action and to a greater (P &lt; 0.01) inhibitory effect of glucose on its own clearance. The increase in glucose concentration resulted in prompt and comparable suppression of endogenous glucose production in both groups. Under these optimized conditions, indexes of glucose effectiveness calculated with both the “cold” and “hot” minimal models also were lower (P &lt; 0.05) in the diabetic subjects than in the nondiabetic subjects and were highly correlated (r = 0.94–0.99; P &lt; 0.001) with the indexes of glucose effectiveness calculated from the increments above baseline of glucose and [6-3H]glucose concentration. We conclude that the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is abnormal in people with NIDDM.

Both glucose and insulin are important regulators of glucose uptake and hepatic glucose release. Because insulin concentrations rarely if ever increase under daily living conditions, unless glucose concentrations also increase, we sought to determine whether hepatic and extrahepatic responses to changes in insulin and glucose concentration are impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). To address this question, glucose metabolism was measured in diabetic and nondiabetic subjects. A computer-driven infusion system was used to produce a nondiabetic postprandial insulin profile in both groups while sufficient exogenous glucose was infused to mimic nondiabetic postprandial glucose concentrations. Although NIDDM was associated with greater (P &lt; 0.05) hepatic glucose release both before and during the prandial insulin infusion, suppression did not differ in the diabetic and nondiabetic subjects (−1.06 ± 0.20 vs. −0.86 ± 0.15 mmol/kg every 4 h). In contrast, stimulation of both glucose disappearance (0.77 ± 0.27 vs. 1.68 ± 0.27 mmol/kg every 4 h) and forearm glucose uptake (187 ± 81 vs. 550 ± 149 μmol/dl every 4 h) was lower (P &lt; 0.05) in diabetic than in nondiabetic subjects. Thus, despite increased basal rates of glucose production, obese individuals with NIDDM had decreased stimulation of glucose disappearance but normal suppression of hepatic glucose release in response to nondiabetic prandial glucose and insulin concentrations. These data indicate that the increase in glucose that occurs with carbohydrate ingestion is likely to compensate for hepatic but not extrahepatic insulin resistance.