Michael P. Harlander-Locke

The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center.

Objective:To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure. Background:The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity. Methods:Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified. Results:Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival. Conclusions:We present the worlds largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the “sickest first” allocation approach.

A Novel Prognostic Nomogram Accurately Predicts Hepatocellular Carcinoma Recurrence after Liver Transplantation: Analysis of 865 Consecutive Liver Transplant Recipients

BACKGROUND Although radiologic size criteria (Milan/University of California, San Francisco [UCSF]) have led to improved outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC), recurrence remains a significant challenge. We analyzed our 30-year experience with LT for HCC to identify predictors of recurrence. STUDY DESIGN A novel clinicopathologic risk score and prognostic nomogram predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 865 LT recipients with HCC between 1984 and 2013. RESULTS Overall patient and recurrence-free survivals were 83%, 68%, 60% and 79%, 63%, and 56% at 1-, 3-, and 5-years, respectively. Hepatocellular carcinoma recurred in 117 recipients, with a median time to recurrence of 15 months, involving the lungs (59%), abdomen/pelvis (38%), liver (35%), bone (28%), pleura/mediastinum (12%), and brain (5%). Multivariate predictors of recurrence included tumor grade/differentiation (G4/poor diff hazard ratio [HR] 8.86; G2-3/mod-poor diff HR 2.56), macrovascular (HR 7.82) and microvascular (HR 2.42) invasion, nondownstaged tumors outside Milan criteria (HR 3.02), nonincidental tumors with radiographic maximum diameter ≥ 5 cm (HR 2.71) and <5 cm (HR 1.55), and pretransplant neutrophil-to-lymphocyte ratio (HR 1.77 per log unit), maximum alpha fetoprotein (HR 1.21 per log unit), and total cholesterol (HR 1.14 per SD). A pretransplantation model incorporating only known radiographic and laboratory parameters had improved accuracy in predicting HCC recurrence (C statistic 0.79) compared with both Milan (C statistic 0.64) and UCSF (C statistic 0.64) criteria alone. A novel clinicopathologic prognostic nomogram included explant pathology and had an excellent ability to predict post-transplant recurrence (C statistic 0.85). CONCLUSIONS In the largest single-institution experience with LT for HCC, excellent long-term survival was achieved. Incorporation of routine pretransplantation biomarkers to existing radiographic size criteria significantly improves the ability to predict post-transplant recurrence, and should be considered in recipient selection. A novel clinicopathologic prognostic nomogram accurately predicts HCC recurrence after LT and may guide frequency of post-transplantation surveillance and adjuvant therapy.

Open and laparoscopic treatment of median arcuate ligament syndrome

BACKGROUND Median arcuate ligament syndrome (MALS) is a syndrome associated with chronic abdominal pain and radiographic evidence of celiac artery compression. We compared the evidence for both open and laparoscopic treatment of patients with MALS. METHODS We reviewed the English-language literature between 1963 and 2012. Presenting symptoms, clinical improvement, operative details, and intraoperative and postoperative complications were noted. RESULTS A total of 400 patients underwent surgical (open and laparoscopic) treatment for MALS. Three hundred thirty-nine patients reported immediate postoperative symptom relief (85%). Late recurrence of symptoms was reported in 19 patients in the open group (6.8%) and seven patients in the laparoscopic group (5.7%). Eleven out of 121 patients (9.1%) in the laparoscopic group required open conversion secondary to bleeding. CONCLUSIONS The available evidence demonstrates that both laparoscopic and open ligament release, celiac ganglionectomy, and celiac artery revascularization may provide sustained symptom relief in the majority of patients diagnosed with MALS. The role of arterial revascularization following ligament release remains unclear. The rate of open conversion with the laparoscopic approach is high, but no perioperative deaths have been reported.

Treatment and outcomes of aortic endograft infection

OBJECTIVE This study examined the medical and surgical management and outcomes of patients with aortic endograft infection after abdominal endovascular aortic repair (EVAR) or thoracic endovascular aortic repair (TEVAR). METHODS Patients diagnosed with infected aortic endografts after EVAR/TEVAR between January 1, 2004, and January 1, 2014, were reviewed using a standardized, multi-institutional database. Demographic, comorbidity, medical management, surgical, and outcomes data were included. RESULTS An aortic endograft infection was diagnosed in 206 patients (EVAR, n = 180; TEVAR, n = 26) at a mean 22 months after implant. Clinical findings at presentation included pain (66%), fever/chills (66%), and aortic fistula (27%). Ultimately, 197 patients underwent surgical management after a mean of 153 days. In situ aortic replacement was performed in 186 patients (90%) using cryopreserved allograft in 54, neoaortoiliac system in 21, prosthetic in 111 (83% soaked in antibiotic), and 11 patients underwent axillary-(bi)femoral bypass. Graft cultures were primarily polymicrobial (35%) and gram-positive (22%). Mean hospital length of stay was 23 days, with perioperative 30-day morbidity of 35% and mortality of 11%. Of the nine patients managed only medically, four of five TEVAR patients died after mean of 56 days and two of four EVAR patients died; both deaths were graft-related (mean follow-up, 4 months). Nineteen replacement grafts were explanted after a mean of 540 days and were most commonly associated with prosthetic graft material not soaked in antibiotic and extra-anatomic bypass. Mean follow-up was 21 months, with life-table survival of 70%, 65%, 61%, 56%, and 51% at 1, 2, 3, 4, and 5 years, respectively. CONCLUSIONS Aortic endograft infection can be eradicated by excision and in situ or extra-anatomic replacement but is often associated with early postoperative morbidity and mortality and occasionally with a need for late removal for reinfection. Prosthetic graft replacement after explanation is associated with higher reinfection and graft-related complications and decreased survival compared with autogenous reconstruction.

The use of cryopreserved aortoiliac allograft for aortic reconstruction in the United States

BACKGROUND Aortic infections, even with treatment, have a high mortality and risk of recurrent infection and limb loss. Cryopreserved aortoiliac allograft (CAA) has been proposed for aortic reconstruction to improve outcomes in this high-risk population. METHODS A multicenter study using a standardized database was performed at 14 of the 20 highest volume institutions that used CAA for aortic reconstruction in the setting of infection or those at high risk for prosthetic graft infection. RESULTS Two hundred twenty patients (mean age, 65; male:female, 1.6/1) were treated since 2002 for culture positive aortic graft infection (60%), culture negative aortic graft infection (16%), enteric fistula/erosion (15%), infected pseudoaneurysm adjacent to the aortic graft (4%), and other (4%). Intraop cultures indicated infection in 66%. Distal anastomosis was to the femoral artery and iliac. Mean hospital length of stay was 24 days, and 30-day mortality was 9%. Complications occurred in 24% and included persistent sepsis (n = 17), CAA thrombosis (n = 9), CAA rupture (n = 8), recurrent CAA/aortic infection (n = 8), CAA pseudoaneurysm (n = 6), recurrence of aortoenteric fistula (n = 4), and compartment syndrome (n = 1). Patients with full graft excision had significantly better outcomes. Ten (5%) patients required allograft explant. Mean follow-up was 30 ± 3 months. Freedom from graft-related complications, graft explant, and limb loss was 80%, 88%, and 97%, respectively, at 5 years. Primary graft patency was 97% at 5 years, and patient survival was 75% at 1 year and 51% at 5 years. CONCLUSIONS This largest study of CAA indicates that CAA allows aortic reconstruction in the setting of infection or those at high risk for infection with lower early and long-term morbidity and mortality than other previously reported treatment options. Repair with CAA is associated with low rates of aneurysm formation, recurrent infection, aortic blowout, and limb loss. We believe that CAA should be considered a first line treatment of aortic infections.

The impact of ablation of incompetent superficial and perforator veins on ulcer healing rates

OBJECTIVE We assessed the impact of endovenous ablation of incompetent superficial (great saphenous [GSV] and small saphenous [SSV]) and perforator (posterior tibial [PTPV]) veins on the healing rate of venous ulcers in patients who had failed conventional compression therapy. METHODS Patients with CEAP 6 ulcers were treated with weekly compression in a dedicated wound care center. Ulcer size and depth were tracked prospectively. Those ulcers that showed no measurable improvement after >5 weeks of compression therapy underwent ablation of at least one incompetent vein. RESULTS We performed 140 consecutive endovenous ablation procedures (74 superficial and 66 perforator) on 110 venous ulcers in 88 limbs. Ulcers had been present for 71 ± 6 months with an initial ulcer area of 23 ± 6 cm(2). Following successful ablation, the healing rate for healed ulcers improved from + 1.0 ± .1 cm(2)/month to -4.4 ± .1 cm(2)/month (P > .05). Ulcer healing rate for healed ulcers, based on the last vein ablated, was GSV = 6.4 cm(2)/month, SSV = 4.8 cm(2)/month, and PTPV = 2.9 cm(2)/month. After a minimum observation period of 6 months (mean follow up, 12 ± 1.25 months), 76.3% of patients healed in 142 ± 14 days. Twelve patients with 26 ulcers did not heal: two patients died from unrelated illnesses, six patients are still actively healing, and four patients have been lost to follow up. Of the healed ulcers, four patients with six ulcers (7.1%) recurred; two have rehealed. CONCLUSION There is measurable and significant reduction in ulcer size and ultimate healing following ablation of incompetent superficial and perforator veins in patients who have failed conventional compression therapy.

Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients.

OBJECTIVES To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT). BACKGROUND Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis. METHODS Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified. RESULTS Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence-free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75). CONCLUSIONS Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT strategies to maximize cPR would enhance posttransplant cancer outcomes.

Management of endovenous heat-induced thrombus using a classification system and treatment algorithm following segmental thermal ablation of the small saphenous vein

OBJECTIVE We evaluated our experience with segmental radiofrequency ablation (RFA) of the small saphenous vein (SSV), a less common procedure than great saphenous vein ablation, and developed a classification system and algorithm for endovenous heat-induced thrombus (EHIT), based on modifications of our prior algorithm of EHIT following great saphenous ablation. METHODS Endovenous ablation was performed on symptomatic patients with incompetent SSVs following a minimum of 3 months of compression therapy. Demographic data, risk factors, CEAP classification, procedure details, and follow-up data were recorded. A four-tier classification system and treatment algorithm was developed, based on EHIT proximity to the popliteal vein. RESULTS Eighty limbs (in 76 patients) were treated with RFA of the SSV between January 2008 and August 2012. Duplex ultrasound was performed between 24 and 72 hours postprocedure in all patients. Ablation was successful in 98.7% (79/80) of procedures. Sixty-eight (85%) patients had level A closures (≥ 1 mm caudal to popliteal vein) and 10 patients (13%) had level B closures (flush with popliteal vein) and were observed. Two limbs (3%) had EHIT extending into the popliteal vein (level C) and were treated with outpatient low-molecular-weight heparin anticoagulation. Thrombus retracted to the level of the saphenopopliteal junction in both patients following a short course of anticoagulation. No patient developed an occlusive deep vein thrombosis (DVT) (level D). Mean follow-up period was 6.2 months; no patient had small saphenous recanalization, occlusive DVT, or pulmonary embolus. The presence or absence of the Giacomini vein was not predictive of level B and C closure. CONCLUSIONS RFA of the SSV in symptomatic patients has a high success rate with a low risk of DVT. A classification system and treatment protocol based on the level of EHIT in relation to the saphenopopliteal junction is useful in managing patients. The approach to patients with thrombus flush with the popliteal vein or bulging has not been previously defined; our outcomes were excellent, using our treatment algorithm.

Current treatment of renal artery aneurysms may be too aggressive

OBJECTIVE Most studies recommend repair of renal artery aneurysms (RAAs) >2 cm in diameter in asymptomatic patients, but other studies have suggested that their natural history may be more benign. We hypothesized that rupture and death in patients with asymptomatic RAAs is low and that current recommendations for RAA treatment at 2 cm may be too aggressive. METHODS Retrospective review of all RAAs treated at a tertiary care medical center from 2002 to 2012. RESULTS Fifty-nine RAA were identified in 40 patients (mean age at diagnosis, 56 years; male:female ratio, 17:23); 31 were saccular, 8 were fusiform, and 5 were bilobed. Twenty-nine patients were asymptomatic; the remainder of patients presented with hematuria (n = 4), abdominal pain (n = 3), difficult-to-control hypertension (n = 3), or flank pain (n = 2). Aneurysm location included the main renal artery bifurcation (n = 35), main trunk (n = 7), primary branch (n = 6), pole artery (n = 6), and secondary branch (n = 1). Operative management of RAAs included vein patch (n = 6), prosthetic patch (n = 4), primary repair (n = 3), plication (n = 1), patch and implantation (n = 1), and ex vivo repair (n = 1). Eight asymptomatic RAAs were treated surgically (mean RAA diameter = 2.4 ± 0.1 cm, range, 2-3 cm), with the remaining 33 asymptomatic RAAs being managed conservatively (mean RAA diameter = 1.4 ± 0.1 cm, range, 0.6-2.6 cm). Mean hospital length of stay was 4 days, with no late postoperative complications and 0% mortality. Non-operated patients were followed for a mean of 36 ± 9 months, with no late acute complications and 0% mortality. Mean RAA growth rate of patients with multiple imaging studies was 0.60 ± 0.16 mm/y. CONCLUSIONS The rate of aneurysm rupture and death in our untreated RAA patients is zero, the growth rate is 0.60 ± 0.16 mm/y, and there were no adverse outcomes in asymptomatic RAAs >2 cm that were observed. We may currently be too aggressive in treating asymptomatic RAAs.

Combined treatment with compression therapy and ablation of incompetent superficial and perforating veins reduces ulcer recurrence in patients with CEAP 5 venous disease

OBJECTIVE Patients with healed venous ulcers often experience recurrence of ulceration, despite the use of long-term compression therapy. This study examines the effect of closing incompetent superficial and/or perforating veins on ulcer recurrence rates in patients with CEAP 5 who have progressive lipodermatosclerosis and impending ulceration. METHODS Endovenous ablation was performed on patients with CEAP 5 disease and incompetent superficial and/or perforator veins and increasing lipodermatosclerosis and/or progressive malleolar pain. A minimum of 3 months of compressive therapy was attempted before endovenous ablation of incompetent veins. Demographic data, risk factors, CEAP classification, procedural details, and postoperative status were all recorded. Patients underwent duplex ultrasound scans before ablation to assess for deep, superficial, and perforator venous incompetence as well as postoperatively to confirm successful ablation. RESULTS Twenty-eight endovenous ablation procedures (superficial = 19; perforator = 9) were performed on 20 patients (limbs = 21). The mean patient age was 73 years old (range, 45-93 years) and the mean body mass index was 29.5 (18.9-58.4). Ninety-five percent of patients previously wore compression stockings (20-30 mm Hg = 9; 30-40 mm Hg = 10; none = 1) for a mean time of 23.3 months (range, 3-52 months) since the prior ulcer healed. Indications for venous ablation were increasing malleolar pain (55%) and/or lipodermatosclerosis (70%). Technical success rates for the ablation procedures were 100% for superficial veins and 89% for perforators (96.4% overall). All patients underwent closure of at least one incompetent vein. Postoperatively, 95% of patients were compliant with wearing compression stockings (20-30 mm Hg = 8; 30-40 mm Hg = 11; none = 1). Ulcer recurrence rates were 0% at 6 months and 4.8% at 12 and 18 months. These data compare with prior studies showing an ulcer recurrence rate up to 67% at 12 months with compression alone. CONCLUSION Patients with CEAP 5 healed venous ulcers that undergo endovenous ablation of incompetent superficial and perforating veins and maintain compression have reduced ulcer recurrence rates compared with historical controls that are treated with compression alone.