Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre

Objectives

Mortality in pancreatic cancer has remained unchanged over the last 20–30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution.

Methods

Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990–1999 and 2000–2009). Predictors of survival were analysed using univariate and multivariate analyses.

Results

Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990–1999 and 2000–2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990–1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome.

Conclusions

Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.     

Early identification of patients at increased risk for hepatic insufficiency,complications and mortality after major hepatectomy

Objective

Total bilirubin (TB) of >7 mg/dl is an accepted definition of postoperative hepatic insufficiency (PHI) given its association with the occurrence of complications and mortality after hepatectomy. The aim of this study was to identify a surrogate marker for PHI early in the postoperative course.

Methods

A single-institution database of patients undergoing major hepatectomy (three or more segments) during 2000–2012 was retrospectively reviewed. Demographic, clinicopathologic and perioperative factors were assessed for their association with PHI, defined as postoperative TB of >7 mg/dl or new ascites. Secondary outcomes included complications, major complications (Clavien–Dindo Grades III–V) and 90-day mortality.

Results

A total of 607 patients undergoing major hepatectomy without bile duct reconstruction were identified. Postoperative hepatic insufficiency occurred in 60 (9.9%) patients. A postoperative day 3 (PoD 3) TB level of ≥3 mg/dl was the only early perioperative factor associated with the development of PHI on multivariate analysis [hazard ratio (HR) = 7.81, 95% confidence interval (CI) 3.74–16.31; P < 0.001]. A PoD 3 TB of ≥3 mg/dl was associated with increased risk for postoperative complications (75.7% versus 53.9%), major complications (45.6% versus 17.6%), and 90-day mortality (15.5% versus 2.3%). This association persisted on multivariate analysis for any complications (HR = 1.98, 95% CI 1.10–3.54; P = 0.022), major complications (HR = 3.18, 95% CI 1.90–5.32; P < 0.001), and 90-day mortality (HR = 8.11, 95% CI 3.00–21.92; P < 0.001).

Conclusions

Total bilirubin of ≥3 mg/dl on PoD 3 after major hepatectomy is associated with PHI, increased complications, major complications and 90-day mortality. This marker may serve as an early postoperative predictor of hepatic insufficiency.     

Early organ dysfunction affects long-term survival in acute pancreatitis patients

Background

The effect of early organ dysfunction on long-term survival in acute pancreatitis (AP) patients is unknown.

Objective

The aim of this study was to ascertain whether early organ dysfunction impacts on long-term survival after an episode of AP.

Methods

A retrospective analysis was performed using survival data sourced from a prospectively maintained database of patients with AP admitted to the Royal Infirmary of Edinburgh during a 5-year period commencing January 2000. A multiple organ dysfunction syndrome (MODS) score of ≥ 2 during the first week of admission was used to define early organ dysfunction. After accounting for in-hospital deaths, long-term survival probabilities were estimated using the Kaplan–Meier test. The prognostic significance of patient characteristics was assessed by univariate and multivariate analyses using Cox''s proportional hazards methods.

Results

A total of 694 patients were studied (median follow-up: 8.8 years). Patients with early organ dysfunction (MODS group) were found to have died prematurely [mean survival: 10.0 years, 95% confidence interval (CI) 9.4–10.6 years] in comparison with the non-MODS group (mean survival: 11.6 years, 95% CI 11.2–11.9 years) (log-rank test, P = 0.001) after the exclusion of in-hospital deaths. Multivariate analysis confirmed MODS as an independent predictor of long-term survival [hazard ratio (HR): 1.528, 95% CI 1.72–2.176; P = 0.019] along with age (HR: 1.062; P < 0.001), alcohol-related aetiology (HR: 2.027; P = 0.001) and idiopathic aetiology (HR: 1.548; P = 0.048).

Conclusions

Early organ dysfunction in AP is an independent predictor of long-term survival even when in-hospital deaths are accounted for. Negative predictors also include age, and idiopathic and alcohol-related aetiologies.     

Is local resection adequate for T1 stage ampullary cancer?

Background

Concerns for morbidity after a pancreaticoduodenectomy (PD) has led to practitioners adopting endoscopic resection or ampullectomy in the treatment of T1 ampullary cancer (AC). It was hypothesized that survival for patients undergoing local resection of AC was inferior to those undergoing a PD.

Methods

All the data of patients with AC reported in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2010 were collected. Five-year survival rates according to nodal disease and histological type were compared.

Results

There were 1916 cases of AC; 421 (22%) had T1 disease. Among those with T1 disease, 217 (51%) received endoscopic surveillance, 21 (5%) underwent local resection/ampullectomy, 20 (5%) underwent ampullectomy with regional lymphadenectomy and 163 (39%) underwent PD. For patients with complete nodal staging (PD, n = 163), 35 (22%) had metastatic disease in the nodes. Grade was significantly associated with node positivity (P = 0.007). In multivariate models, survival was improved with either an ampullectomy with regional lymphadenectomy [hazard ratio (HR) 0.19; 95% confidence interval (CI) 0.05–0.61, P < 0.005] or a PD (HR 0.23; 95% CI 0.15–0.36, P < 0.001).

Conclusion

Patients with T1 AC have a high risk for nodal metastases especially if they are higher-grade lesions. Nodal clearance with a lymphadenectomy or a PD is essential for long-term survival in these patients.     

Associations of Soluble CD14 and Endotoxin with Mortality,Cardiovascular Disease,and Progression of Kidney Disease among Patients with CKD

Background and objectives

CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.

Design, setting, participants, & measurements

We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m² for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.

Results

Plasma sCD14 was negatively associated with eGFR (ρ=–0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23–58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=–0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.

Conclusions

Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.     

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Background and objectives

Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-to-perform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.

Design, setting, participants, & measurements

This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan–Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival.

Results

There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P<0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m² increase, 0.96; 95% CI, 0.94 to 0.97; P<0.001), T2 Oxford classification (tubular atrophy/interstitial fibrosis, >50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01).

Conclusions

C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.     

Fibroblast Growth Factor 23 and Cardiovascular Mortality after Kidney Transplantation

Background and objectives

Circulating fibroblast growth factor 23 (FGF23) is associated with adverse cardiovascular outcomes in CKD. Whether FGF23 predicts cardiovascular mortality after kidney transplantation, independent of measures of mineral metabolism and cardiovascular risk factors, is unknown.

Design, setting, participants, & measurements

The association between plasma C-terminal FGF23 and cardiovascular mortality was analyzed in a single-center prospective cohort of 593 stable kidney transplant recipients (mean age ± SD, 52±12 years; 54% male; estimated GFR, 47±16 ml/min per 1.73 m²), at a median of 6.1 (interquartile range, 2.7–11.7) years after transplantation. Multivariate Cox regression models were built, adjusting for measures of renal function and mineral metabolism; Framingham risk factors; the left ventricular wall strain markers midregional fragment of pro–A-type natriuretic peptide (MR-proANP) and N-terminal-pro brain natriuretic peptide (NT-proBNP); and copeptin, the stable C-terminal portion of the precursor of vasopressin.

Results

In multivariate linear regression analysis, MR-proANP (β=0.20, P<0.001), NT-proBNP (β=0.18, P<0.001), and copeptin (β=0.26, P<0.001) were independently associated with FGF23. During follow-up for 7.0 (interquartile range, 6.2–7.5) years, 128 patients (22%) died, of whom 66 (11%) died due to cardiovascular disease; 54 (9%) had graft failure. FGF23 was associated with an higher risk of cardiovascular mortality in a fully adjusted multivariate Cox regression model (hazard ratio [HR], 1.88 [95% confidence interval (CI), 1.11 to 3.19]; P=0.02). FGF23 was also independently associated with all-cause mortality (full model HR, 1.86 [95% CI, 1.27 to 2.73]; P=0.001). Net reclassification improved for both cardiovascular mortality (HR, 0.07 [95% CI, 0.01 to 0.14]; P<0.05) and all-cause mortality (HR, 0.11 [95% CI, 0.05 to 0.18]; P<0.001).

Conclusions

Plasma FGF23 is independently associated with cardiovascular and all-cause mortality after kidney transplantation. The association remained significant after adjustment for measures of mineral metabolism and cardiovascular risk factors.     

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Introduction

As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.

Methods

Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study''s objective was to identify pre-operative predictors of early death (<12 months) after a resection.

Results

The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24–85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136–7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038–10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis.

Conclusion

The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.     

Vascular Calcification in Patients with Nondialysis CKD over 3 Years

Background and objectives

Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed.

Design, setting, participants, & measurements

The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models.

Results

VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17–36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event–free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression.

Conclusions

VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.     

Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma

Background:

To determine factors associated with outcomes and microvascular invasion (MVI) in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC).

Methods:

Between July 1996 and August 2008 at the Universities of Kentucky or Tennessee, LT recipients were retrospectively analysed.

Results:

One hundred and one patients had HCC in the explanted liver; one patient was excluded because of fibrolamellar histology. Seventy-nine (79%) were male and 81 (81%) were older than 50. HCC was incidental in 32 patients (32%). Median follow-up was 31 months. Ten patients (10%) developed recurrence, which was associated with poor survival (P= 0.006). Overall 1-, 3-, and 5-year survival rates were 87%, 69% and 62%, respectively. Excluding patients with lymph node metastasis (LNM) or MVI yielded 91%, 81% and 75% survival at the same time points. MVI was independently associated with recurrence (OR 28.40, 95% CI 1.77–456.48, P= 0.018) and decreased survival (OR 4.70, 95% CI 1.24–17.80, P= 0.023), and LNM with decreased survival (OR 6.05, 95% CI 1.23–29.71, P= 0.027). Tumour size (OR 4.1, 95% CI 1.2–13.5, P= 0.013) and alpha-fetoproptein (AFP) > 100 (OR 5.0, 95% CI 1.4–18.1, P= 0.006) were associated with MVI.

Conclusions:

MVI greatly increases the risk of recurrence and death after LT for HCC, and is strongly associated with tumour size and AFP > 100.     

Body Composition and Survival in Dialysis Patients: Results from an International Cohort Study

Background and objectives

High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival.

Design, setting, participants, & measurements

Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan–Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression.

Results

In 37,345 hemodialysis patients, median (25th–75th percentile) LTI and FTI were 12.2 (10.3–14.5) and 9.8 (6.6–12.4) kg/m², respectively. Median (25th–75th percentile) follow-up time was 266 (132–379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th–90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m² and FTI between 4 and 15 kg/m² (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI–low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI–high FTI).

Conclusions

This large international study indicates best survival in patients with both LTI and FTI in the 10th–90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.     

Hypophosphataemia after major hepatectomy and the risk of post-operative hepatic insufficiency and mortality: an analysis of 719 patients

Background

Hypophosphataemia after a hepatectomy suggests hepatic regeneration. It was hypothesized that the absence of hypophosphataemia is associated with post-operative hepatic insufficiency (PHI) and complications.

Methods

Patients who underwent a major hepatectomy from 2000–2012 at a single institution were identified. Post-operative serum phosphorus levels were assessed. Primary outcomes were PHI (peak bilirubin >7 mg/dl), major complications, and 30- and 90-day mortality.

Results

Seven hundred and nineteen out of 749 patients had post-operative phosphorus levels available. PHI and major complications occurred in 63 (8.8%) and 169 (23.5%) patients, respectively. Thirty- and 90-day mortality were 4.0% and 5.4%, respectively. The median phosphorus level on post-operative-day (POD) 2 was 2.2 mg/dl; 231 patients (32.1%) had phosphorus >2.4 on POD2.Patients with POD2 phosphorus >2.4 had a significantly higher incidence of PHI, major complications and mortality. On multivariate analysis, POD2 phosphorus >2.4 remained a significant risk factor for PHI [(hazard ratio HR):1.78; 95% confidence interval (CI):1.02–3.17; P = 0.048], major complications (HR:1.57; 95%CI:1.02–2.47; P = 0.049), 30-day mortality (HR:2.70; 95%CI:1.08–6.76; P = 0.034) and 90-day mortality (HR:2.51; 95%CI:1.03–6.15; P = 0.044). Similarly, patients whose phosphorus level reached nadir after POD3 had higher PHI, major complications and mortality.

Conclusion

Elevated POD2 phosphorus levels >2.4 mg/dl and a delayed nadir in phosphorus beyond POD3 are associated with increased post-operative hepatic insufficiency, major complications and early mortality. Failure to develop hypophosphataemia within 72 h after a major hepatectomy may reflect insufficient liver remnant regeneration.     

Left Atrial Volume and Adverse Cardiovascular Outcomes in Unselected Patients with and without CKD

Background and objectives

Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters.

Design, setting, participants, & measurements

There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m², n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure.

Results

Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m² had significantly lower event-free survival than patients with normal (<28 ml/m²) or mildly dilated LAVI (28–32 ml/m²) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m². Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint.

Conclusions

Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events.     

Total pancreatectomy: a national study

Background:

Total pancreatectomy (TP) is performed for various indications. Historically, morbidity and mortality have been high. Recent series reporting improved peri-operative mortality have renewed interest in TP. We performed a national review of TP including indication, patient/hospital characteristics, complications and peri-operative mortality.

Methods:

The Nationwide Inpatient Sample (NIS) was queried to identify TPs performed during 1998 to 2006. Univariate analyses were used to compare patient/hospital characteristics. Multivariable logistic regression was performed to identify predictors of in-hospital mortality. Post-operative complications/disposition were assessed.

Results:

From 1998 to 2006, 4013 weighted patient-discharges occurred for TP. Fifty-three per cent were male; mean age 58 years. Indication: neoplastic disease 67.8%. Post-operative complications occurred in 28%. Univariate analyses: TPs increased significantly (1998, n= 384 vs. 2006 n= 494, P < 0.01). 77.1% of TPs occurred in teaching hospitals (P < 0.0001), 86.4% in hospitals performing <five pancreatectomies/year (P < 0.0001). In-patient mortality was 8.5% with a significant decrease (12.4% 1998–2000 vs. 5.9% 2002–2006, P < 0.01). Multivariable analyses: advanced age [referent ≤50 years; ≥70 Adjusted odds ratio (AOR) 3.4, 95% confidence interval (CI) 1.33–8.67], select patient comorbidities and year (referent = 2004–2006; 1998–2000 AOR 2.70; 95% CI 1.41–5.14) independently predicted in-patient mortality whereas hospital surgical volume did not.

Discussion:

TP is increasingly performed nationwide with a concomitant decrease in peri-operative mortality. Patient characteristics, rather than hospital volume, predicted increased mortality.     

Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression

Background and objectives

Common apolipoprotein L1 (APOL1) variants are associated with increased risk of progressive CKD; however, not all individuals with high–risk APOL1 variants experience CKD progression. Identification of factors contributing to heterogeneity has important scientific and clinical implications.

Design, setting, participants, & measurements

Using multivariable Cox models, we analyzed data from 693 participants in the African American Study of Kidney Disease and Hypertension to identify factors that modify the association between APOL1 genotypes and CKD progression (doubling of serum creatinine or incident ESRD).

Results

Participant mean age was 54 years old, median GFR was 49 ml/min per 1.73 m², and 23% had the APOL1 high–risk genotype (two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288 (42%) participants experienced CKD progression. As previously reported, the high-risk genotype was associated with higher risk of CKD progression compared with the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI], 1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI, 1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index ≥30 versus <30 kg/m²; P interaction =0.04) and increased urinary excretion of urea nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30 for urine urea nitrogen ≥8 versus <8 g/d; P interaction =0.04) were associated with lower APOL1–associated risk for CKD progression, these findings were not robust in sensitivity analyses with alternative cut points. No other sociodemographic (e.g., education and income), clinical (e.g., systolic BP and smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or fibroblast growth factor 23) variables modified the association between APOL1 and CKD progression (P interaction >0.05 for each).

Conclusions

Sociodemographic factors and common risk factors for CKD progression do not seem to alter APOL1–related CKD progression. Additional investigation is needed to identify nontraditional factors that may affect the association between APOL1 and progressive CKD.     

Postoperative mortality and need for transitional care following liver resection for metastatic disease in elderly patients: a population-level analysis of 4026 patients

Objectives

The goal of this study was to characterize the association of age with postoperative mortality and need for transitional care following hepatectomy for liver metastases.

Methods

A retrospective cohort study using the Nationwide Inpatient Sample (2005–2008) was performed. Patients undergoing hepatectomy for liver metastases were categorized by age as: Young (aged <65 years); Old (aged 65–74 years), and Oldest (aged ≥75 years). Multivariate logistic regression analyses were performed to identify predictors of in-hospital mortality and need for transitional care (non-home discharge).

Results

A total of 4026 patients were identified; 36.6% (n = 1475) were elderly (aged ≥65 years). Rates of in-hospital mortality and non-home discharge increased with advancing age group [1.3% vs. 2.2% vs. 3.3% (P = 0.005) and 2.1% vs. 6.1% vs. 18.3% (P < 0.001), respectively]. Independent predictors of in-hospital mortality were age within the Oldest category [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.19–4.12] and a Deyo Comorbidity Index score of ≥3 (OR 6.95, 95% CI 3.55–13.60). Independent predictors for need for transitional care were age within the Old group (OR 2.44, 95% CI 1.66–3.58), age within the Oldest group (OR 8.48, 95% CI 5.87–12.24), a Deyo score of 1 (OR 2.00, 95% CI 1.40–2.85), a Deyo score of 2 (OR 4.70, 95% CI 2.93–7.56), a Deyo score of ≥3 (OR 6.41, 95% CI 3.67–11.20), and female gender (OR 1.56, 95% CI 1.15–2.11).

Conclusions

Although increasing age was associated with higher risk for in-hospital mortality, the absolute risk was low and within accepted ranges, and comorbidity was the primary driver of mortality. Conversely, need for transitional care was significantly more common in elderly patients. Therefore, liver resection for metastases is safe in well-selected elderly patients, although consideration should be made for potential transitional care needs.     

Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors

Background and objectives

The quality and age of donor organs are known to have a major effect on patient and graft outcomes, but it is uncertain whether this association is uniform for all recipients. We aimed to determine whether the use of expanded criteria deceased donor (ECD) kidneys for transplantation compared with standard criteria deceased donor (SCD) kidneys has a different association with survival in younger (age <60 years old) compared with older (age ≥60 years old) recipients.

Design, setting, participants, & measurements

Using data from the Australian and New Zealand Dialysis and Transplant Registry (1997–2009), we compared the risk of all-cause mortality and death with functioning graft among younger and older recipients who had received either an SCD or an ECD kidney using the adjusted Cox proportional hazard models.

Results

In total, 3822 patients were transplanted between 1997 and 2009. Over a follow-up period of 21,249 person-years (a median duration of 5.3 years [interquartile range, 2.22–8.6 years]), 567 recipients (n=385 for those age <60 years old; n=182 for those age ≥60 years old) died. Recipient age was an effect modifier between donor types, all-cause mortality, and death with functioning graft (P values for interaction were 0.05 and 0.04, respectively). In younger recipients, there was an excess risk of all-cause mortality (adjusted hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.23 to 1.97) and death with functioning graft (adjusted HR, 1.72; 95% CI, 1.28 to 2.29) after transplantation with ECD kidneys compared with SCD kidneys, but there was no statistically significant association among older recipients (adjusted HR, 1.11; 95% CI, 0.80 to 1.54 and adjusted HR, 1.30; 95% CI, 0.89 to 1.89, respectively). This excess risk was largely caused by death from cardiovascular disease.

Conclusions

There was an excess risk of all-cause mortality and death with functioning graft when younger recipients were transplanted with ECD kidneys compared with SCD kidneys. These findings suggest that caution is needed in allocating ECD kidneys to younger recipients.     

Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKD

Background and objectives

Risk of hospitalizations is increased in patients with CKD. We sought to examine the association between rate of kidney function decline and risk of hospitalization in a cohort of patients with early CKD.

Design, settings, participants, & measurements

We built a cohort of 247,888 United States veterans who had at least one eGFR measurement between October 1999 and September 2003 and an additional eGFR between October 2003 and September 2004. We selected patients whose initial eGFR was between 45 and 59 ml/min per 1.73 m². Rate of eGFR change (in milliliters per minute per 1.73 m² per year) was categorized as no decline (>0), mild (0 to −1, and served as the referent group), moderate (−1 to −5), or severe (>−5) eGFR decline. We built survival models to examine the association between the rate of kidney function decline and the risk of hospitalization and readmission and linear regression to estimate length of hospital stay.

Results

Over a median observation of 9 years (interquartile range, 5.28–9.00), patients with moderate and severe eGFR decline exhibited a higher risk of hospitalizations (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.19 to 1.26; and HR, 1.33; 95% CI, 1.28 to 1.39, respectively). Among patients with moderate and severe eGFR decline, the association between the rate of decline and the risk of hospitalizations was more pronounced with an increased number of hospitalizations (P<0.01). Patients with moderate and severe eGFR decline had a higher risk of readmission (HR, 1.19; 95% CI, 1.13 to 1.26; and HR, 1.53; 95% CI, 1.43 to 1.63, respectively). Among patients with severe eGFR decline, the association between the rate of kidney function decline and the risk of readmission was stronger with an increased number of readmissions (P<0.01). Patients with moderate and severe eGFR decline experienced an additional length of stay of 1.40 (95% CI, 0.88 to 1.92) and 5.00 days per year (95% CI, 4.34 to 5.66), respectively.

Conclusions

The rate of kidney function decline is associated with a higher risk of hospitalizations, readmissions, and prolonged length of hospital stay.     

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

Background and objectives

Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis.

Design, setting, participants, & measurements

Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up.

Results

In total, 258 patients (145 men) with a mean age of 57.0±14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤32.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5–48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan–Meier analysis revealed the incidence of first heart failure event in the high–indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001).

Conclusions

Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.     

Evaluation of prognostic factors among patients with chronic graft-versus-host disease

Background

Chronic graft-versus-host disease (cGVHD) is a major complication after allogeneic stem cell transplantation with an adverse effect on both mortality and morbidity. In 2005, the National Institute of Health proposed new criteria for diagnosis and classification of chronic graft-versus-host disease for clinical trials. New sub-categories were recognized such as late onset acute graft-versus-host disease and overlap syndrome.

Design and Methods

We evaluated the prognostic impact of the new sub-categories as well as the clinical scoring system proposed by the National Institute of Health in a retrospective, multicenter study of 820 patients undergoing allogeneic stem cell transplantation between 2000 and 2006 at 3 different institutions. Patients were retrospectively categorized according to the National Institute of Health criteria from patients’ medical histories.

Results

As far as the new sub-categories are concerned, in univariate analysis diagnosis of overlap syndrome adversely affected the outcome. Also, the number of organs involved for a cut-off value of 4 significantly influenced both cGVHD related mortality and survival. In multivariate analysis, in addition to NIH score, platelet count and performance score at the time of cGVHD diagnosis, plus gut involvement, significantly influenced outcome. These 3 variables allowed us to develop a simple score system which identifies 4 subgroups of patients with 84%, 64%, 43% and 0% overall survival at five years after cGVHD diagnosis (score 0: HR=15.96 (95% CI: 6.85–37.17), P<0.001; score 1: HR=5.47 (95% CI: 2.6–11.5), P<0.001; score 2: HR=2.8 (95% CI: 1.32–5.93), P=0.007).

Conclusions

In summary, we have identified a powerful and simple tool to discriminate different subgroups of patients in terms of chronic graft-versus-host disease related mortality and survival.