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Hypophosphatemia has been described in patients undergoing right hepatectomy for liver cancer and in living donors for liver transplantation who also received total parenteral nutrition. At the study centre, significant hypophosphatemia (0.36 mmol/L or less) requiring intravenous replacement was seen in two of the first nine living donors for adult-to-adult liver transplantation. To determine the frequency of hypophosphatemia in living donors, the authors obtained phosphate levels on stored serum samples from postoperative days 0, 1, 3 and 7 in all nine patients, none of whom were on total parenteral nutrition. Within the first week, hypophosphatemia developed in 55.6% of patients and phosphate levels returned to normal by day 7 in all nine patients. One patient had normal phosphate levels during the first week, but had profound hypophosphatemia (0.32 mmol/L) on day 14 when he presented with a Staphylococcus aureus infection of a bile collection and significant hypoxemia. The extent of hepatectomy and the rate of liver regeneration, estimated by baseline and postoperative day 7 volumetric computed tomography scans, did not correlate with the development of hypophosphatemia. In conclusion, hypophosphatemia is common in living donors undergoing right hepatectomy and may be associated with complications. All living donors should be monitored for the development of hypophosphatemia during the first two postoperative weeks.

AbstractGenetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high‐ (≥7 Gleason score) versus low‐grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916‐T variant in 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.

Background: This study examines the efficacy of hypobaric oxygenation as it relates to the elimination of gaseous microemboli (GME) at designated flow, pressure and temperature combinations. Methods: Hypobaric oxygenation was employed for experimental trials (n=60), but not for control trials (n=60), while circuit design, data measurements and testing conditions were maintained for both settings. Hypobaric oxygenation conditions were created by applying 100% oxygen at sub-atmospheric sweep gas pressures of 0.67 atmospheres to the gas phase of an integrated hollow-fiber microporous membrane oxygenator. GME were quantified using an Emboli Detection and Classification system (EDAC), while a continuous air infusion, at a rate of 100 ml/min, was applied to the circuit. Trials were conducted at 37°C, 28°C, and 18°C and at two flow and line pressure combinations of: 3.5 L/min & 150 mmHg and 5 L/min & 200 mmHg. Results: Sub-atmospheric sweep gas pressures allowed adequate oxygenation independent of carbon dioxide removal while significantly reducing the potential entrance of nitrogen into the blood. GME was reduced significantly across all temperatures and flows when compared to control trials; GME counts were reduced by 99.7% post-oxygenator and 99.99% at the arterial cannula. Conclusion: Correlation between the use of hypobaric oxygenation and GME counts suggests hypobaric oxygenation could play a significant role in the reduction of GME.

Treatment of polycystic liver disease (PLD) focuses on symptom improvement. Generic questionnaires lack sensitivity to capture PLD‐related symptoms, a prerequisite to determine effectiveness of therapy. We developed and validated a disease‐specific questionnaire that assesses symptoms in PLD (PLD‐Q). We identified 16 PLD‐related symptoms (total score 0‐100 points) by literature review and interviews with patients and clinicians. The developed PLD‐Q was validated in Dutch (n = 200) and United States (US; n = 203) PLD patients. We assessed the correlation of PLD‐Q total score with European Organization for Research and Treatment of Cancer (EORTC) symptom scale, global health visual analogue scale (VAS) of EQ‐5D, and liver volume. To test discriminative validity, we compared PLD‐Q total scores of patients with different PLD severity stages (Gigot classification) and PLD‐Q total scores of PLD patients with general controls and polycystic kidney disease patients without PLD. Reproducibility was tested by comparing original test scores with 2‐week retest scores. In total, 167 Dutch and 124 US patients returned the questionnaire. Correlation between PLD‐Q total score and EORTC symptom scale (The Netherlands [NL], r = 0.788; US, r = 0.811) and global health VAS (NL, r = −0.517; US, r = −0.593) was good. There was no correlation of PLD‐Q total score with liver volume (NL, r = 0.138; P = 0.236; US, r = 0.254; P = 0.052). Gigot type III individuals scored numerically higher than type II patients (NL, 46 vs. 40; P = 0.089; US, 48 vs. 36; P = 0.055). PLD patients scored higher on the PLD‐Q total score than general controls (NL, 42 vs. 17; US, 40 vs. 13 points) and polycystic kidney disease patients without PLD (22 points). Reproducibility of PLD‐Q was excellent (NL, r = 0.94; US, 0.96). Conclusion: PLD‐Q is a valid, reproducible, and sensitive disease‐specific questionnaire that can be used to assess PLD‐related symptoms in clinical care and future research. (Hepatology 2016;64:151–160)

AbstractPaclitaxel‐induced peripheral neuropathy (PIPN) cannot be predicted from clinical parameters and might have a pharmacogenomic basis. Previous studies identified single nucleotide variants (SNV) associated with PIPN. However, only a subset of findings has been confirmed to date in more than one study, suggesting a need for further re‐testing and validation in additional clinical cohorts. Candidate PIPN‐associated SNVs were identified from the literature. SNVs were retested in 119 patients selected by extreme phenotyping from 269 in NCCTG N08C1 (Alliance) as previously reported. SNV genotyping was performed by a combination of short‐read sequencing analysis and Taqman PCR. These 22 candidate PIPN SNVs were genotyped. Two of these, rs7349683 in the EPHA5 and rs3213619 in ABCB1 were found to be significantly associated with PIPN with an Odds ratios OR = 2.07 (P = 0.02) and OR = 0.12 (P = 0.03), respectively. In addition, three SNVs showed a trend toward a risk‐ or protective effect that was consistent with previous reports. The rs10509681 and rs11572080 in the gene CYP2C8*3 showed risk effect with an OR = 1.49 and rs1056836 in CYP1B1 showed a protective effect with an OR = 0.66. None of the other results supported the previously reported associations, including some SNVs displaying an opposite direction of effect from previous reports, including rs1058930 in CYP2C8, rs17222723 and rs8187710 in ABCC2, rs10771973 in FGD4, rs16916932 in CACNB2 and rs16948748 in PITPNA. Alliance N08C1 validated or supported a minority of previously reported SNV‐PIPN associations. Associations previously reported by multiple studies appeared to have a higher likelihood to be validated by Alliance N08C1.

Purpose There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. Methods We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. Results Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. Conclusion Clinical benefits were associated with symptom self-reporting during cancer care.

SummaryBackgroundReliable tools for patient selection are critical for clinical drug trials.AimTo evaluate a consensus‐based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials.MethodsThis study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150–220 (n = 4); 220–450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14‐day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES‐CD).Results37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test–retest and inter‐reader reliability scores. The MaRIA scores for the terminal ileum had excellent test–retest and inter‐reader reliability, with correlations >0.9. The proximal ileum showed strong within‐reader agreement (0.90–0.96), and fair between‐reader agreement (0.59–0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES‐CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra‐abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%.ConclusionsMagnetic resonance enterography of high‐quality and reproducibility was feasible in a global multi‐ centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.