Research Spotlight

Harlander-Locke, M. P., P. F. Lawrence, A. Ali, E. Bae, J. Kohn, C. Abularrage, M. Ricci, G. W. Lemmon, S. Peralta and J. Hsu (2017). “Cryopreserved venous allograft is an acceptable conduit in patients with current or prior angioaccess graft infection.” J Vasc Surg: 2017 Jun [Epub ahead of print].

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OBJECTIVE: The durability of cryopreserved allograft has been previously demonstrated in the setting of infection. The objective of this study was to examine the safety, efficacy, patency, and cost per day of graft patency associated with using cryopreserved allograft (vein and artery) for hemodialysis access in patients with no autogenous tissue for native fistula creation and with arteriovenous graft infection or in patients at high risk for infection. METHODS: Patients implanted with cryopreserved allograft for hemodialysis access between January 2004 and January 2014 were reviewed using a standardized, multi-institutional database that evaluated demographic, comorbidity, procedural, and outcomes data. RESULTS: There were 457 patients who underwent placement of cryopreserved vein (femoral: n = 337, saphenous: n = 11) or artery (femoral: n = 109) for hemodialysis access at 20 hospitals. Primary indications for allograft use included high risk of infection in 191 patients (42%), history of infected prosthetic graft in 169 (37%), and current infection in 97 (21%). Grafts were placed more frequently in the arm (78%) than in the groin, with no difference in allograft conduit used. Mean time from placement to first hemodialysis use was 46 days (median, 34 days). Duration of functional graft use was 40 +/- 7 months for cryopreserved vein and 21 +/- 8 months for cryopreserved artery (P < .05), and mean number of procedures required to maintain patency at follow-up of 58 +/- 21 months was 1.6 for artery and 0.9 for vein (P < .05). Local access complications occurred in 32% of patients and included late thrombosis (14%), graft stenosis (9%), late infection (9%), arteriovenous access malfunction (7%), early thrombosis (3%), and early infection (3%). Early and late infections both occurred more frequently in the groin (P = .030, P = .017, respectively), and late thrombosis occurred more frequently with cryopreserved artery (P < .001). Of the 82 patients (18%) in whom the cryopreserved allograft was placed in the same location as the excised infected prosthetic graft, 13 had infection of the allograft during the study period (early: n = 4; late: n = 9), with no significant difference in infection rate (P = .312) compared with the remainder of the study population. The 1-, 3-, and 5-year primary patency was 58%, 35%, and 17% for cryopreserved femoral vein and 49%, 17%, and 8% for artery, respectively (P < .001). Secondary patency at 1, 3, and 5 years was 90%, 78%, and 58% for cryopreserved femoral vein and 75%, 53%, and 42% for artery, respectively (P < .001). Mean allograft fee per day of graft patency was $4.78 for cryopreserved vein and $6.97 for artery (P < .05), excluding interventional costs to maintain patency. CONCLUSIONS: Cryopreserved allograft provides an excellent conduit for angioaccess when autogenous tissue is not available in patients with current or past conduit infection. Cryopreserved vein was associated with higher patency and a lower cost per day of graft patency. Cryopreserved allograft allows for immediate reconstruction through areas of infection, reduces the need for staged procedures, and allows early use for dialysis.

Hoverman, J. R., C. Taniguchi, K. Eagye, S. Mikan, A. Kalisiak, S. Ash-Lee and R. Henschel (2017). “If we don’t ask, our patients might never tell: The impact of the routine use of a patient values assessment.” J Oncol Pract: 2017 Jun [Epub ahead of print].

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PURPOSE: Good communication can be associated with better end-of-life outcomes. The US Oncology Network developed and tested a Values Assessment (VA) for facilitating advance care planning (ACP). The results of the first 1,268 patients are reported. METHODS: The VA consists of 10 questions of the format “How valuable is it to me to…” (eg, “…know that I am not a burden to my family, friends, or helpers?”). Responses were on a four-point scale from unsure to very valuable. VA data on 1,286 patients with metastatic cancer from April 1, 2013, to July 31, 2015, were extracted from the electronic health record, including demographics, diagnosis, stage, chemotherapy, and outcomes (hospice enrollment, place of death). These demographics were compared by using the chi2 or Fisher’s exact test or the Wilcoxon rank sum test for continuous variables. RESULTS: A total of 1,268 patients completed the VA (56.7% were >/= 65 years of age, 57.8% completed advance directives [ADs]). There were 438 deaths of which 308 had a place of death or a hospice enrollment recorded. Of these, 78% died at home or inpatient hospice; 14.6% died in the hospital. Hospice enrollment with ADs was 76.1% and without, 60.9%. Median length of stay in hospice was 21 days with ADs versus 12.5 days without. Chemotherapy in the last 14 days of life was 8.8% with ADs and 15.5% without. The VA was well accepted by patients. CONCLUSION: A VA as a routine part of practice is feasible and scalable. It facilitates ACP discussions that lead to ADs. The results suggest that VA and ACP lead to less-aggressive care at the end of life.

McAdams, S. B., J. Funk, A. Navetta, M. El Tayeb and M. R. Humphreys (2017). “Holmium laser enucleation of the prostate after prostatic urethral lift surgery: Feasibility and technical considerations from a multi-institutional case series.” J Endourol: 2017 Jun [Epub ahead of print].

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INTRODUCTION AND OBJECTIVE: Prostatic urethral lift (PUL) is gaining popularity for the treatment of symptomatic benign prostatic hyperplasia (BPH). We describe the feasibility and considerations of performing holmium laser enucleation of the prostate (HoLEP) as a salvage therapy after previous PUL. METHODS: Men who have undergone HoLEP after PUL were retrospectively identified from three institutions with surgeons experienced in HoLEP. Subjects were characterized by age, time from PUL procedure (months) to HoLEP surgery, indication for retreatment, and pre-operative prostate volume by ultrasound. Outcomes of interest included enucleation time, morcellation time, morcellator type, weight of tissue resected, and Clavien complications. We also summarize findings related to location of PUL device implants, and the effect of the implants on the enucleation and morcellation portions of the procedure. RESULTS: From 12/15/2015 to 10/31/2016 seven men age 51-78 years underwent HoLEP at a median of 8.6 months (range 3-18) after PUL. In each case PUL had been performed with a variable number of UroLift (NeoTract Inc.) device implants. In several cases implants were found to reside in areas other than where intended by usual PUL technique. In one case performed for refractory pain the device implant was not identified during HoLEP, but was subsequently removed from the outer bladder wall via a robotic trans-abdominal procedure, resulting in improvement of pain at six weeks. The reciprocating morcellator system (Lumenis Versacut) tended to jam with each implant requiring a pause for withdrawal of the morcellator and manual removal from the blade, whereas the oscillating system (Wolf Piranha) tended to morcellate around the device components, and required grasper retrieval of device components. There were no complications. CONCLUSIONS: HoLEP can be performed safely and effectively post PUL, however morcellation of the adenoma tissue is complicated by metallic implants of the PUL dev.

O’Leary, J. G., A. J. Demetris, A. Philippe, R. Freeman, J. Cai, H. Heidecke, C. Smith, B. Hart, L. W. Jennings, R. Catar, M. Everly, G. B. Klintmalm and D. Dragun (2017). “Non-hla antibodies impact on c4d staining, stellate cell activation and fibrosis in liver allografts.” Transplantation: 2017 Jun [Epub ahead of print].

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BACKGROUND: Recent data has shown an increased risk for rejection, fibrosis progression, and death in liver transplant (LT) recipients with preformed or de novo HLA donor-specific alloantibodies (DSA). However, the role of non-HLA autoantibodies and the interaction between HLA DSA and non-HLA autoantibodies remains uncharacterized. METHODS: We analyzed 1269 primary LT recipients from 1/2000-4/2009 with known HLA DSA status for Angiotensin II Type-1 Receptor and Endothelin-1 Type A receptor autoantibodies(anti-AT1R-Abs and anti-ETAR-Abs respectively) pre-LT and year-1 post-LT. RESULTS: Preformed non-HLA autoantibodies alone did not impact outcomes. In multivariable modeling, the combination of preformed non-HLA autoantibodies and HLA-DSA were associated with an increased risk for death [Hazard Ratio (HR)=1.66; p=0.02] especially if the HLA DSA was of the IgG3 subclass (HR=2.28; p=0.01). A single de novo non-HLA autoantibody was associated with an increased risk for TCMR or AMR rejection(68% vs. 41%, p=0.01) and fibrosis progression (HR=1.84; p=0.02). Biopsies with de novo non-HLA autoantibodies revealed a new sinusoidal C4d staining pattern when compared to HLA DSA(71% vs. 3%; p<0.001). Liver sinusoidal endothelial cell(LSEC) activation and stellate cell activation was increased in patients with non-HLA autoantibodies in the location of C4d positivity. CONCLUSIONS: A non-HLA autoantibody combined with a preformed HLA DSA is associated with an increased mortality risk. Isolated de novo anti-AT1R-Abs and/or anti-ETAR-Abs are associated with an increased risk of rejection and fibrosis progression. The novel location of C4d staining in proximity to LSEC capillarization and stellate cell activation demonstrates allograft injury in proximity to non-HLA autoantibody binding.

Wu, N., Q. Nguyen, Y. Wan, T. Zhou, J. Venter, G. A. Frampton, S. DeMorrow, D. Pan, F. Meng, S. Glaser, G. Alpini and H. Bai (2017). “The hippo signaling functions through the notch signaling to regulate intrahepatic bile duct development in mammals.” Lab Invest 97(7): 843-853.

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The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.