A multi-institutional experience in adventitial cystic disease

AbstractBackgroundAdventitial cystic disease (ACD) is an unusual arteriopathy; case reports and small series constitute the available literature regarding treatment. We sought to examine the presentation, contemporary management, and long-term outcomes using a multi-institutional database.MethodsUsing a standardized database, 14 institutions retrospectively collected demographics, comorbidities, presentation/symptoms, imaging, treatment, and follow-up data on consecutive patients treated for ACD during a 10-year period, using Society for Vascular Surgery reporting standards for limb ischemia. Univariate and multivariate analyses were performed comparing treatment methods and factors associated with recurrent intervention. Life-table analysis was performed to estimate the freedom from reintervention in comparing the various treatment modalities.ResultsForty-seven patients (32 men, 15 women; mean age, 43 years) were identified with ACD involving the popliteal artery (n = 41), radial artery (n = 3), superficial/common femoral artery (n = 2), and common femoral vein (n = 1). Lower extremity claudication was seen in 93% of ACD of the leg arteries, whereas patients with upper extremity ACD had hand or arm pain. Preoperative diagnosis was made in 88% of patients, primarily using cross-sectional imaging of the lower extremity; mean lower extremity ankle-brachial index was 0.71 in the affected limb. Forty-one patients with lower extremity ACD underwent operative repair (resection with interposition graft, 21 patients; cyst resection, 13 patients; cyst resection with bypass graft, 5 patients; cyst resection with patch, 2 patients). Two patients with upper extremity ACD underwent cyst drainage without resection or arterial reconstruction. Complications, including graft infection, thrombosis, hematoma, and wound dehiscence, occurred in 12% of patients. Mean lower extremity ankle-brachial index at 3 months postoperatively improved to 1.07 (P < .001), with an overall mean follow-up of 20 months (range, 0.33-9 years). Eight patients (18%) with lower extremity arterial ACD required reintervention (redo cyst resection, one; thrombectomy, three; redo bypass, one; balloon angioplasty, three) after a mean of 70 days with symptom relief in 88%. Lower extremity patients who underwent cyst resection and interposition or bypass graft were less likely to require reintervention (P = .04). One patient with lower extremity ACD required an above-knee amputation for extensive tissue loss.ConclusionsThis multi-institutional, contemporary experience of ACD examines the treatment and outcomes of ACD. The majority of patients can be identified preoperatively; surgical repair, consisting of cyst excision with arterial reconstruction or bypass alone, provides the best long-term symptomatic relief and reduced need for intervention to maintain patency

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein.

ImportanceSerum α-fetoprotein (AFP) is a biomarker for hepatocellular carcinomas (HCCs) associated with a more aggressive tumor phenotype and inferior outcomes after a liver transplant (LT). Data on the outcomes for patients with HCCs that do not produce AFP are limited.ObjectiveTo compare characteristics and outcomes among LT recipients with radiographically apparent HCC lesions with AFP-producing tumors or with tumors that do not produce AFP (hereafter referred to as non-AFP-producing tumors), and to identify factors influencing recurrence in LT recipients with non-AFP-producing tumors.Design, setting, and participantsRetrospective analysis at a university transplant center of 665 adults with HCC who underwent an LT during the period from 1989 to 2013. Of the 665 LT recipients, 457 (68.7%) had AFP-producing tumors, and 208 (31.3%) had non-AFP-producing tumors (the maximum AFP level before an LT was ≤10 ng/mL). Dates of study analysis were from August 2015 to June 2016.InterventionLiver transplant.Main outcomes and measuresRecurrence-free survival and recurrence rates.ResultsPatients with non-AFP-producing tumors had radiographic tumor characteristics similar to those of patients with AFP-producing tumors, but, pathologically, they had fewer lesions (25% vs 35% with &gt;2 lesions; P = .03), smaller cumulative tumor diameters (4.2 vs 5.0 cm; P = .02), fewer microvascular (17% vs 22%) and macrovascular (2% vs 9%) invasions (P &lt; .001), and fewer poorly differentiated tumors (15% vs 28%; P &lt; .001). Patients with non-AFP-producing tumors also had significantly superior recurrence-free survival at 1, 3, and 5 years (88%, 74%, and 67% vs 76%, 59%, and 51%, respectively; P = .002) and lower 5-year recurrence rates (8.8% vs 22%; P &lt; .001) than patients with AFP-producing tumors. When stratified by radiologic Milan criteria, 5-year survival was better, and recurrence lowest, among patients with non-AFP-producing tumors within the Milan criteria (71% survival and 6% recurrence), and survival was worse, and recurrence highest, for patients with AFP-producing tumors outside the Milan criteria (40% survival and 42% recurrence; P &lt; .001). Significant predictors of recurrence among patients with non-AFP-producing tumors include radiologic (&gt;2 tumors [HR, 4.98; 95% CI, 1.72-14.4; P = .003]; cumulative diameter [1.70 per log SD; 1.12-2.59; P &lt; .001]; outside the Milan criteria [10.0; 3.7-33.3; P &lt; .001) and pathologic factors (&gt;2 tumors [4.39; 1.32-14.6; P = .02]; cumulative diameter [2.32 per log SD; 1.43-3.77; P = .001]; microvascular [3.07; 1.02-9.24; P = .05] and macrovascular invasion [8.75; 2.15-35.6; P = .002]).Conclusions and relevanceNearly one-third of patients with radiographically apparent HCC have non-AFP-producing tumors that have more favorable pathologic characteristics, lower posttransplant recurrence, and superior survival compared with patients with AFP-producing tumors. Posttransplant HCC recurrence for patients with non-AFP-producing tumors is predicted by important radiologic and pathologic factors, and is negligible for patients within the Milan criteria. Stratifying patients by AFP status in addition to radiological criteria may improve the selection process for and the prioritization of transplant candidates

Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce α-Fetoprotein.

ImportanceSerum α-fetoprotein (AFP) is a biomarker for hepatocellular carcinomas (HCCs) associated with a more aggressive tumor phenotype and inferior outcomes after a liver transplant (LT). Data on the outcomes for patients with HCCs that do not produce AFP are limited.ObjectiveTo compare characteristics and outcomes among LT recipients with radiographically apparent HCC lesions with AFP-producing tumors or with tumors that do not produce AFP (hereafter referred to as non-AFP-producing tumors), and to identify factors influencing recurrence in LT recipients with non-AFP-producing tumors.Design, setting, and participantsRetrospective analysis at a university transplant center of 665 adults with HCC who underwent an LT during the period from 1989 to 2013. Of the 665 LT recipients, 457 (68.7%) had AFP-producing tumors, and 208 (31.3%) had non-AFP-producing tumors (the maximum AFP level before an LT was ≤10 ng/mL). Dates of study analysis were from August 2015 to June 2016.InterventionLiver transplant.Main outcomes and measuresRecurrence-free survival and recurrence rates.ResultsPatients with non-AFP-producing tumors had radiographic tumor characteristics similar to those of patients with AFP-producing tumors, but, pathologically, they had fewer lesions (25% vs 35% with &gt;2 lesions; P = .03), smaller cumulative tumor diameters (4.2 vs 5.0 cm; P = .02), fewer microvascular (17% vs 22%) and macrovascular (2% vs 9%) invasions (P &lt; .001), and fewer poorly differentiated tumors (15% vs 28%; P &lt; .001). Patients with non-AFP-producing tumors also had significantly superior recurrence-free survival at 1, 3, and 5 years (88%, 74%, and 67% vs 76%, 59%, and 51%, respectively; P = .002) and lower 5-year recurrence rates (8.8% vs 22%; P &lt; .001) than patients with AFP-producing tumors. When stratified by radiologic Milan criteria, 5-year survival was better, and recurrence lowest, among patients with non-AFP-producing tumors within the Milan criteria (71% survival and 6% recurrence), and survival was worse, and recurrence highest, for patients with AFP-producing tumors outside the Milan criteria (40% survival and 42% recurrence; P &lt; .001). Significant predictors of recurrence among patients with non-AFP-producing tumors include radiologic (&gt;2 tumors [HR, 4.98; 95% CI, 1.72-14.4; P = .003]; cumulative diameter [1.70 per log SD; 1.12-2.59; P &lt; .001]; outside the Milan criteria [10.0; 3.7-33.3; P &lt; .001) and pathologic factors (&gt;2 tumors [4.39; 1.32-14.6; P = .02]; cumulative diameter [2.32 per log SD; 1.43-3.77; P = .001]; microvascular [3.07; 1.02-9.24; P = .05] and macrovascular invasion [8.75; 2.15-35.6; P = .002]).Conclusions and relevanceNearly one-third of patients with radiographically apparent HCC have non-AFP-producing tumors that have more favorable pathologic characteristics, lower posttransplant recurrence, and superior survival compared with patients with AFP-producing tumors. Posttransplant HCC recurrence for patients with non-AFP-producing tumors is predicted by important radiologic and pathologic factors, and is negligible for patients within the Milan criteria. Stratifying patients by AFP status in addition to radiological criteria may improve the selection process for and the prioritization of transplant candidates

Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model

Importance:Early allograft dysfunction (EAD) following a liver transplant (LT) unequivocally portends adverse graft and patient outcomes, but a widely accepted classification or grading system is lacking. Objective:To develop a model for individualized risk estimation of graft failure after LT and then compare the model's prognostic performance with the existing binary EAD definition (bilirubin level of ≥10 mg/dL on postoperative day 7, international normalized ratio of ≥1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level of &gt;2000 U/L within the first 7 days) and the Model for Early Allograft Function (MEAF) score. Design, Setting, and Participants:This retrospective single-center analysis used a transplant database to identify all adult patients who underwent a primary LT and had data on 10 days of post-LT laboratory variables at the Dumont-UCLA Transplant Center of the David Geffen School of Medicine at UCLA between February 1, 2002, and June 30, 2015. Data collection took place from January 4, 2016, to June 30, 2016. Data analysis was conducted from July 1, 2016, to August 30, 2017. Main Outcomes and Measures:Three-month graft failure-free survival. Results:Of 2021 patients who underwent primary LT over the study period, 2008 (99.4%) had available perioperative data and were included in the analysis. The median (interquartile range [IQR]) age of recipients was 56 (49-62) years, and 1294 recipients (64.4%) were men. Overall survival and graft-failure-free survival rates were 83% and 81% at year 1, 74% and 71% at year 3, and 69% and 65% at year 5, with an 11.1% (222 recipients) incidence of 3-month graft failure or death. Multivariate factors associated with 3-month graft failure-free survival included post-LT aspartate aminotransferase level, international normalized ratio, bilirubin level, and platelet count, measures of which were used to calculate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score. The L-GrAFT model had an excellent C statistic of 0.85, with a significantly superior discrimination of 3-month graft failure-free survival compared with the existing EAD definition (C statistic, 0.68; P &lt; .001) and the MEAF score (C statistic, 0.70; P &lt; .001). Compared with patients with lower L-GrAFT risk, LT recipients in the highest 10th percentile of L-GrAFT scores had higher Model for End-Stage Liver Disease scores (median [IQR], 34 [26-40] vs 31 [25-38]; P = .005); greater need for pretransplant hospitalization (56.8% vs 44.8%; P = .003), renal replacement therapy (42.9% vs 30.5%; P &lt; .001), mechanical ventilation (35.8% vs 18.1%; P &lt; .001), and vasopressors (22.9% vs 11.0%; P &lt; .001); longer cold ischemia times (median [IQR], 436 [311-539] vs 401 [302-506] minutes; P = .04); greater intraoperative blood transfusions (median [IQR], 17 [10-26] vs 10 [6-17] units of packed red blood cells; P &lt; .001); and older donors (median [IQR] age, 47 [28-56] vs 41 [25-52] years; P &lt; .001). Conclusions and Relevance:The L-GrAFT risk score allows a highly accurate, individualized risk estimation of 3-month graft failure following LT that is more accurate than existing EAD and MEAF scores. Multicenter validation may allow for the adoption of the L-GrAFT as a tool for evaluating the need for a retransplant, for establishing standardized grading of early allograft function across transplant centers, and as a highly accurate clinical end point in translational studies aiming to mitigate ischemia or reperfusion injury by modulating donor quality and recipient factors

Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model

Importance:Early allograft dysfunction (EAD) following a liver transplant (LT) unequivocally portends adverse graft and patient outcomes, but a widely accepted classification or grading system is lacking. Objective:To develop a model for individualized risk estimation of graft failure after LT and then compare the model's prognostic performance with the existing binary EAD definition (bilirubin level of ≥10 mg/dL on postoperative day 7, international normalized ratio of ≥1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level of &gt;2000 U/L within the first 7 days) and the Model for Early Allograft Function (MEAF) score. Design, Setting, and Participants:This retrospective single-center analysis used a transplant database to identify all adult patients who underwent a primary LT and had data on 10 days of post-LT laboratory variables at the Dumont-UCLA Transplant Center of the David Geffen School of Medicine at UCLA between February 1, 2002, and June 30, 2015. Data collection took place from January 4, 2016, to June 30, 2016. Data analysis was conducted from July 1, 2016, to August 30, 2017. Main Outcomes and Measures:Three-month graft failure-free survival. Results:Of 2021 patients who underwent primary LT over the study period, 2008 (99.4%) had available perioperative data and were included in the analysis. The median (interquartile range [IQR]) age of recipients was 56 (49-62) years, and 1294 recipients (64.4%) were men. Overall survival and graft-failure-free survival rates were 83% and 81% at year 1, 74% and 71% at year 3, and 69% and 65% at year 5, with an 11.1% (222 recipients) incidence of 3-month graft failure or death. Multivariate factors associated with 3-month graft failure-free survival included post-LT aspartate aminotransferase level, international normalized ratio, bilirubin level, and platelet count, measures of which were used to calculate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score. The L-GrAFT model had an excellent C statistic of 0.85, with a significantly superior discrimination of 3-month graft failure-free survival compared with the existing EAD definition (C statistic, 0.68; P &lt; .001) and the MEAF score (C statistic, 0.70; P &lt; .001). Compared with patients with lower L-GrAFT risk, LT recipients in the highest 10th percentile of L-GrAFT scores had higher Model for End-Stage Liver Disease scores (median [IQR], 34 [26-40] vs 31 [25-38]; P = .005); greater need for pretransplant hospitalization (56.8% vs 44.8%; P = .003), renal replacement therapy (42.9% vs 30.5%; P &lt; .001), mechanical ventilation (35.8% vs 18.1%; P &lt; .001), and vasopressors (22.9% vs 11.0%; P &lt; .001); longer cold ischemia times (median [IQR], 436 [311-539] vs 401 [302-506] minutes; P = .04); greater intraoperative blood transfusions (median [IQR], 17 [10-26] vs 10 [6-17] units of packed red blood cells; P &lt; .001); and older donors (median [IQR] age, 47 [28-56] vs 41 [25-52] years; P &lt; .001). Conclusions and Relevance:The L-GrAFT risk score allows a highly accurate, individualized risk estimation of 3-month graft failure following LT that is more accurate than existing EAD and MEAF scores. Multicenter validation may allow for the adoption of the L-GrAFT as a tool for evaluating the need for a retransplant, for establishing standardized grading of early allograft function across transplant centers, and as a highly accurate clinical end point in translational studies aiming to mitigate ischemia or reperfusion injury by modulating donor quality and recipient factors

Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability and Coagulopathy in Liver Transplant.

ImportanceDamage control (DC) with intra-abdominal packing and delayed reconstruction is an accepted strategy in trauma and acute care surgery but has not been evaluated in liver transplant.ObjectiveTo evaluate the incidence, effect on survival, and predictors of the need for DC using intra-abdominal packing and delayed biliary reconstruction in patients with coagulopathy or hemodynamic instability after liver allograft reperfusion.Design, setting, and participantsWe performed a retrospective analysis of adults undergoing liver transplant at a large transplant center from February 1, 2002, through July 31, 2012.Main outcomes and measuresPredictors of DC, effects on graft, and patient survival.ResultsOf 1813 patients, 150 (8.3%) underwent DC during liver transplant, with 84 (56.0%) requiring a single additional operation for biliary reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional operations. Compared with recipients without DC, patients requiring DC had greater Model for End-stage Liver Disease scores (33 vs 27; P &lt; .001); more frequent pretransplant hospitalization (72.0% vs 47.9%; P &lt; .001), intubation (33.3% vs 19.9%; P &lt; .001), vasopressors (23.2% vs 10.9%; P &lt; .001), renal replacement therapy (49.6% vs 30.3%; P &lt; .001), and prior major abdominal operations (48.3% vs 21.9%; P &lt; .001), including prior liver transplant (29.3% vs 8.9%; P &lt; .001); greater operative transfusion requirements (37 vs 13 units of packed red blood cells; P &lt; .001); worse intraoperative base deficit (10.3 vs 8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P &lt; .001); and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P &lt; .001) ischemia times. Patients who underwent DC followed by a single additional operation for biliary reconstruction and abdominal closure had similar 1-, 3-, and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with recipients not requiring DC. Multivariate predictors of DC included prior liver transplant or major abdominal operation, longer pretransplant recipient and donor length of stay, greater Model for End-stage Liver Disease score, and longer warm and cold ischemia times (C statistic, 0.75).Conclusions and relevanceTo our knowledge, this study represents the first large report of DC as a viable strategy for liver transplant recipients with coagulopathy or hemodynamic instability after allograft reperfusion. In DC recipients not requiring additional operations, outcomes are excellent and comparable to 1-stage liver transplant

Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability and Coagulopathy in Liver Transplant.

ImportanceDamage control (DC) with intra-abdominal packing and delayed reconstruction is an accepted strategy in trauma and acute care surgery but has not been evaluated in liver transplant.ObjectiveTo evaluate the incidence, effect on survival, and predictors of the need for DC using intra-abdominal packing and delayed biliary reconstruction in patients with coagulopathy or hemodynamic instability after liver allograft reperfusion.Design, setting, and participantsWe performed a retrospective analysis of adults undergoing liver transplant at a large transplant center from February 1, 2002, through July 31, 2012.Main outcomes and measuresPredictors of DC, effects on graft, and patient survival.ResultsOf 1813 patients, 150 (8.3%) underwent DC during liver transplant, with 84 (56.0%) requiring a single additional operation for biliary reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional operations. Compared with recipients without DC, patients requiring DC had greater Model for End-stage Liver Disease scores (33 vs 27; P &lt; .001); more frequent pretransplant hospitalization (72.0% vs 47.9%; P &lt; .001), intubation (33.3% vs 19.9%; P &lt; .001), vasopressors (23.2% vs 10.9%; P &lt; .001), renal replacement therapy (49.6% vs 30.3%; P &lt; .001), and prior major abdominal operations (48.3% vs 21.9%; P &lt; .001), including prior liver transplant (29.3% vs 8.9%; P &lt; .001); greater operative transfusion requirements (37 vs 13 units of packed red blood cells; P &lt; .001); worse intraoperative base deficit (10.3 vs 8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P &lt; .001); and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P &lt; .001) ischemia times. Patients who underwent DC followed by a single additional operation for biliary reconstruction and abdominal closure had similar 1-, 3-, and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with recipients not requiring DC. Multivariate predictors of DC included prior liver transplant or major abdominal operation, longer pretransplant recipient and donor length of stay, greater Model for End-stage Liver Disease score, and longer warm and cold ischemia times (C statistic, 0.75).Conclusions and relevanceTo our knowledge, this study represents the first large report of DC as a viable strategy for liver transplant recipients with coagulopathy or hemodynamic instability after allograft reperfusion. In DC recipients not requiring additional operations, outcomes are excellent and comparable to 1-stage liver transplant