Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40.

OBJECTIVE: To determine the association of sex with access to liver transplantation among candidates with the highest possible model for end-stage liver disease score (MELD 40). BACKGROUND: Women with end-stage liver disease are less likely than men to receive liver transplantation due in part to MELD's underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear. METHODS: Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs death/delisting) by sex for 7654 waitlisted liver transplant candidates from 2009 to 2019 who reached MELD 40. Multivariable logistic and competing-risks regression was used to estimate the association of sex with the outcome and adjust for the candidate and donor factors. RESULTS: Women (N = 3019, 39.4%) spent equal time active at MELD 40 (median: 5 vs 5 days, P = 0.28) but had lower offer acceptance (9.2% vs 11.0%, P < 0.01) compared with men (N = 4635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (odds ratio = 0.87, P < 0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely to be transplanted (subdistribution hazard ratio = 0.90, P < 0.01) and more likely to die or be delisted (subdistribution hazard ratio = 1.14, P = 0.02). CONCLUSIONS: Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplantation and worse outcomes compared with men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

A novel microsurgical reconstruction technique in a living-related liver donor hepatic artery dissection using the native hepatic artery.

In living donor liver transplantation, hepatic artery intimal dissection is a rare but devastating complication often resulting in the inability to utilize the graft. We detail the salvage of a dissected donor right hepatic artery utilizing the recipient hepatic artery. After removal of the right lobe, the donor artery was found to have an intimal dissection extending to multiple branches. The liver transplant surgeons requested their plastic microsurgeon colleague to assist with reconstruction. Ultimately, the native recipient hepatic artery was used as a branch graft as the caliber and branching pattern was appropriate. Back table microvascular reconstruction was performed using the explanted recipient hepatic artery branches as a graft to the four donor artery branches. Every anastomosis was assessed with intraoperative doppler; all were patent with acceptable flow characteristics. The patient did well post-operatively with post-operative ultrasounds demonstrating patency of the graft. Four months post-transplantation the patient developed two polymicrobial abscesses that were drained and resolved with normalization of liver function tests. This case highlights how collaboration with a microvascular surgeon enabled the salvage of a living donor graft when faced with a complex arterial dissection.

Novel Benchmark Values for Redo Liver Transplantation: Does the Outcome Justify the Effort?

OBJECTIVE: To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

Expedited evaluation for liver transplantation: A critical look at processes and outcomes.

BACKGROUND: Most patients are listed for liver transplant (LT) following extensive workup as outpatients ("conventional evaluation"). Some patients undergo urgent evaluation as inpatients after being transferred to a transplant center ("expedited evaluation"). We hypothesized that expedited patients would have inferior survival due to disease severity at the time of transplant and shorter workup time. METHODS: Patients who underwent evaluation for LT at our institution between 2012 and 2016 were retrospectively reviewed. The expedited and conventional cohorts were defined as above. Living donor LT recipients, combined liver-kidney recipients, acute liver failure patients, and re-transplant patients were excluded. We compared patient characteristics and overall survival between patients who received a transplant following expedited evaluation and those who did not, and between LT recipients based on expedited or conventional evaluation. RESULTS: Five-hundred and nine patients were included (110 expedited, 399 conventional). There was no difference in graft or patient survival at 1 year for expedited versus conventional LT recipients. In multivariable analysis of overall survival, only Donor Risk Index (HR 1.97, CI 1.04-3.73, P = .037, per unit increase) was associated with increased risk of death. CONCLUSIONS: Patients who underwent expedited evaluation for LT had significant demographic and clinical differences from patients who underwent conventional evaluation, but comparable post-transplant survival.

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

BACKGROUND: While preoperative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown. OBJECTIVES: We aim to identify predonation physiologic evaluation strategies to improve postoperative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and experts' opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation predonation. The outcomes of interest were length of stay, postoperative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662. RESULTS: Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (< 70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8 vs 21.7 kg/m2 , OR 1.67 (1.14-2.48), P = .01) and absent in another (< 30 vs 30-35 kg/m2 , P = .61). One study demonstrated decreased risk for postdonation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on predonation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations. CONCLUSION: Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific predonation BMI cut-off. Abbreviated predonation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong).

Comparison of Biliary Complications Rates After Brain Death, Donation After Circulatory Death, and Living-Donor Liver Transplantation: A Single-Center Cohort Study.

Donation-after-circulatory-death (DCD), donation-after-brain-death (DBD), and living-donation (LD) are the three possible options for liver transplantation (LT), each with unique benefits and complication rates. We aimed to compare DCD-, DBD-, and LD-LT-specific graft survival and biliary complications (BC). We collected data on 138 DCD-, 3,027 DBD- and 318 LD-LTs adult recipients from a single center and analyzed patient/graft survival. BC (leak and anastomotic/non-anastomotic stricture (AS/NAS)) were analyzed in a subset of 414 patients. One-/five-year graft survival were 88.6%/70.0% for DCD-LT, 92.6%/79.9% for DBD-LT, and, 91.7%/82.9% for LD-LT. DCD-LTs had a 1.7-/1.3-fold adjusted risk of losing their graft compared to DBD-LT and LD-LT, respectively (p < 0.010/0.403). Bile leaks were present in 10.1% (DCD-LTs), 7.2% (DBD-LTs), and 36.2% (LD-LTs) (ORs, DBD/LD vs. DCD: 0.7/4.2, p = 0.402/<0.001). AS developed in 28.3% DCD-LTs, 18.1% DBD-LTs, and 43.5% LD-LTs (ORs, DBD/LD vs. DCD: 0.5/1.8, p = 0.018/0.006). NAS was present in 15.2% DCD-LTs, 1.4% DBDs-LT, and 4.3% LD-LTs (ORs, DBD/LD vs. DCD: 0.1/0.3, p = 0.001/0.005). LTs w/o BC had better liver graft survival compared to any other groups with BC. DCD-LT and LD-LT had excellent graft survival despite significantly higher BC rates compared to DBD-LT. DCD-LT represents a valid alternative whose importance should increase further with machine/perfusion systems.

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain.

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines.

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.

Enhanced Stress Resilience Training in Surgeons: Iterative Adaptation and Biopsychosocial Effects in 2 Small Randomized Trials.

OBJECTIVE: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers. SUMMARY OF BACKGROUND AND DATA: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown. METHODS: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity"). RESULTS: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls. CONCLUSIONS: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

Standardizing Discharge Opioid Prescriptions in Kidney Transplant Patients Decreases Opioid Usage.

BACKGROUND: Kidney transplant recipients are frequently prescribed excess opioids at discharge relative to their inpatient requirements. Recipients who fill prescriptions after transplant have an increased risk of death and graft loss. This study examined the impact of standardized prescriptions on discharge amount and number of outpatient refills. MATERIALS AND METHODS: A historical cohort (Group 1) was compared to a cohort without patient-controlled analgesia (Group 2) and a cohort in which providers prescribed no opioids to patients who required none on the day prior to discharge, and 10 pills to those who required opioids on the day prior (Group 3). Demographics, oral morphine equivalents (OMEs) prescribed on the day prior to and at discharge, and outpatient refills were collected. RESULTS: 270 recipients were included. There was a nonsignificant trend towards lower OMEs on the day prior to discharge in Groups 2 and 3. Nonopioid adjunct use increased (P < 0.001). Discharge OMEs significantly decreased (mean 87.2 in Group 1, 62.8 in Group 2, 26.6 in Group 3, P< 0.001). The number of patients discharged without opioids increased (23.8% of Group 1, 37.5% of Group 2, 60.6% of Group 3, P < 0.001). Group 3, Asian descent, and lower OMEs on the day prior were factors significantly associated with decreased discharge OMEs on multivariable linear regression. Twelve percent of Group 2 and 2% of Group 3 patients received an outpatient refill (P = 0.02). CONCLUSIONS: A protocol targeting discharge opioids significantly reduced the amount of opioids prescribed in kidney transplant recipients; most patients subsequently received no opioids at discharge.

Obesity is a risk factor for progression to kidney transplant waitlisting after liver transplantation.

BACKGROUND: Non-alcoholic steatohepatitis has emerged as a leading cause of cirrhosis, and obesity-associated comorbidities, including renal disease, have increased in prevalence. Obesity predisposes the kidney to hyperfiltration injury, potentially impairing acute kidney injury recovery. Identification of patients at risk for renal dysfunction is impeded by poor performance of renal function estimating equations among cirrhotics. To better understand obesity among cirrhotics and renal disease progression, we examined likelihood of kidney transplantation (KT) waitlisting after liver transplant alone (LTA) by obesity class. METHODS: 68 607 LTA recipients were identified in SRTR (2005-2018). Fine and Gray competing risks models were used to analyze likelihood of KT waitlisting. RESULTS: 27.4% of recipients were obese (BMI ≥ 30 kg/m2 ) and were 10% more likely to require KT waitlisting (aHR: 1.10, 95%CI: 1.01-1.20). Risk was highest among recipients with Classes II and III obesity (BMI: ≥35 kg/m2 ) (aHR: 1.37, 95%CI: 1.17-1.56). Moreover, recipients with Classes II and III obesity were 57% more likely to require KT waitlisting within one year post-LTA (aHR: 1.57, 95%CI: 1.18-2.10) compared to non-obese recipients. DISCUSSION: These findings suggest obesity was a risk factor for renal recovery failure and/or renal disease progression post-LTA and may confound identification of renal dysfunction and/or prediction of renal recovery among cirrhotics.

"The use of bilateral continuous erector spinae plane blocks for postoperative analgesia after right-sided living donor hepatectomy: A feasibility study".

BACKGROUND: Postoperative pain after living donor hepatectomy is significant. Postoperative coagulopathy may limit the use of epidural analgesia, the gold standard for pain control in abdominal surgery. The erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we examined the effect of continuous ESPB, administered via catheters, on perioperative opioid requirements after right living donor hepatectomies for liver transplantation. METHODS: We performed a retrospective cohort study in patients undergoing right living donor hepatectomy. Twenty-four patients who received preoperative ESPB were compared to 51 historical controls who did not receive regional anesthesia. The primary endpoint was the total amount of oral morphine equivalents (OMEs) required on the day of surgery and postoperative day (POD) 1. RESULTS: Patients in the ESPB group required a lower total amount of OMEs on the day of surgery and POD 1 [141 (107-188) mg] compared the control group [293 (220-380) mg; P < .001]. CONCLUSIONS: The use of continuous ESPB significantly reduced opioid consumption following right living donor hepatectomy.

Bi-organ paired exchange-Sentinel case of a liver-kidney swap.

Organ transplantation is the optimal treatment for patients with end stage liver disease and end stage renal disease. However, due to the imbalance in the demand and supply of deceased organs, most transplant centers worldwide have consciously pursued a strategy for living donation. Paired exchanges were introduced as a means to bypass various biologic incompatibilities (blood- and tissue-typing), while expanding the living donor pool. This shift in paradigm has introduced new ethical concerns that have hitherto been unaddressed, especially with nondirected, altruistic living donors. So far, transplant communities have focused efforts on separate liver- and kidney-paired exchanges, whereas the concept of a transorgan paired exchange has been theorized and could potentially facilitate a greater number of transplants. We describe the performance of the first successful liver-kidney swap.

Living Donor Liver Transplantation for Alcoholic Liver Disease.

AIMS: Alcoholic liver disease (ALD) is now a well-recognized indication for liver transplantation. This paper reviews existing literature on living donor liver transplantation (LDLT) for ALD and presents data from a single, high volume United States liver transplant center. METHODS: For the literature review, a PubMed search was undertaken using the search terms 'living donor' and 'alcoholic liver disease'. Studies were included that presented outcome data for patients who underwent LDLT for ALD. For the single-center data collection, all patients who underwent LDLT from 2003 to 2016 at our center were reviewed and the data for recipients with ALD was subsequently analyzed and compared with those patients who underwent LDLT for other indications. RESULTS: Of 110 studies that resulted from the PubMed query, only 5 contained data that was relevant to this manuscript. These studies represented data collected from two Asian countries: one single center in Korea and a collection of centers in Japan. The relapse rate following LDLT for ALD ranged from 7.9% to 22%, and pre-transplant abstinence did not impact post-transplant relapse in any of these studies. For the single-center data, of 136 LDLT performed at our institution during the time period, 22 were performed for ALD. There was no difference in 1- or 5-year survival between patients transplanted for ALD and those transplanted for other etiologies (94.7% vs. 93.4%, P = 0.79 and 78.9% vs. 87.5%, P = 0.6). CONCLUSION: There is a very limited amount of data available on LDLT for ALD. Existing data suggests that LDLT for ALD results in excellent outcomes. SHORT SUMMARY: Published data on living donor liver transplantation (LDLT) for alcoholic liver disease (ALD) are limited. One- and five-year survival rates range from 82% to 100% and 78% to 87%, respectively. Rates of alcohol relapse following transplant appear low, ranging from 7% to 23%; 6-month abstinence periods prior to LDLT for ALD do not appear to have a significant impact on relapse.

Patient perceptions of female surgeons: how surgeon demeanor and type of surgery affect patient preference.

BACKGROUND: As more women become surgeons, knowledge of patient perceptions is necessary to educate this new pool of surgeons on how to maximize patient trust and foster the optimal surgeon-patient relationship. MATERIALS AND METHODS: Patients in a general medicine clinic in San Francisco were surveyed. Study respondents read one of the eight short scenarios that differed by surgeon gender, surgery type (lung cancer versus breast cancer), and surgeon demeanor (more masculine--agentic versus more feminine--communal). In all scenarios, the surgeon was described as accomplished and well trained. After reading the short description, respondents rated five items from 0-5, which were averaged to create a measure of preference. RESULTS: Based on the 476 completed surveys, respondents did not have a significant preference for either female or male surgeons (P = 0.76). We found a significant interaction in respondent choice between the surgeon demeanor and the type of surgery (P < 0.05). Respondents preferred an agentic surgeon for lung cancer surgery and a communal surgeon for breast cancer surgery regardless of surgeon or respondent gender. No other interactions or main effects were statistically significant. CONCLUSIONS: Our respondents did not overtly prefer a surgeon based on gender, which suggests that patients may not contribute to the traditional gender biases reported by female surgeons. Further work needs to be done to determine if our results can be replicated in different geographic regions and if there is gender stereotyping within the field of surgery.

Ex vivo split-liver transplantation: the true right/left split.

BACKGROUND: Successful left lateral segment (sectionectomy) and right trisegmentectomy (trisectionectomy) split-liver transplantation (SLT) have been achieved. However, there are few reports of the use of true right/left splitting in SLT. METHODS: A single-centre retrospective review of true right/left ex vivo split-liver transplants performed during the period 1993-2010 was conducted. Nine cadaveric liver grafts underwent splitting and the resultant 18 allografts were used in transplants performed at the study centre. RESULTS: In the nine right lobe recipients, 10-year patient and graft survival rates were both 74%. There were no vascular complications, one biliary complication and one re-exploration. In the nine left lobe recipients, 10-year patient and graft survival rates were 78% and 66%, respectively. Postoperative complications included six biliary complications, four of which required surgical revision and all of which occurred within 5 months of transplantation, and two vascular complications, including one early hepatic artery thrombosis (HAT) and one late HAT, one of which required retransplantation. Five left lobe recipients required re-exploration, and one patient developed small-for-size syndrome following SLT, which resolved with conservative measures. CONCLUSIONS: True right/left ex vivo SLT remains a viable option for facilitating the expansion of the adult cadaver donor pool and allows for excellent patient and graft survival. Postoperative morbidity remains high, especially in recipients of the left lobe graft, and must be balanced with the benefits to be derived from transplant.