With a better understanding of the natural history of hepatocellular carcinoma (HCC) and the improvement in imaging, locoregional therapies, surgical techniques, and postoperative care, patients with ...HCC are now managed by a multidisciplinary team. Partial hepatic resection can be curative in patients developing HCC in the setting of normal liver parenchyma and in patients with early cirrhosis but well-preserved hepatic synthetic function. Liver transplantation offers the best long-term survival and lowest incidence of tumor recurrence in select patients with HCC and underlying cirrhosis. This article discusses the role of surgical resection and liver transplantation in the management of HCC.
BACKGROUNDAlthough surgical technique in living donor liver transplantation (LDLT) has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably ...disparate.
METHODSA questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19 009 LDLTs responded.
RESULTSCenters were categorized into predominantly LDLT (18) or deceased donor liver transplantation (6), and high- (10) or low-volume (14) centers. At most centers, the minimum acceptable graft-to-recipient weight ratio was 0.7 or less (67%), and remnant was 30% (75%). The median upper limit of donor age was 60 years and body mass index of 33 kg/m. At 63% centers, age influenced the upper limit of body mass index inversely. Majority preferred aspartate transaminase and alanine transaminase less than 50 IU/mL. Most accepted donors with nondebilitating mild mental or physical disability and rejected donors with treated coronary artery disease, cerebrovascular accident and nonbrain, nonskin primary malignancies. Opinions were divided about previous psychiatric illness, substance abuse and abdominal surgery. Most performed selective liver biopsy, commonly for steatosis, raised transaminases and 1 or more features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high-volume centers. There was no standard policy for preoperative or peroperative cholangiogram.
CONCLUSIONSThis first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety.
Women with cirrhosis awaiting liver transplantation are less likely to receive a transplant and more likely to die than men. While differences in body size and estimation of kidney function are ...well‐studied contributors to this gender inequity, what has received relatively little mention as a potential contributing factor is the possibility of implicit bias. Implicit bias is defined as “any unconscious or unacknowledged preference that affects a person's outlook or behavior.” The undeniable presence of implicit bias, a factor that is known to negatively influence health outcomes for women, within our health care system means that patients interacting within our transplant system may still experience unequal treatment despite our best efforts to modify the allocation system at the national level. Awareness of this additional source of gender‐based disparities is the first step. In this article, we posit that implicit bias in liver transplantation may exacerbate the gender inequity in transplant access and provide examples in the literature to support this assertion. Lastly, we offer strategies that could be applied at the individual or the healthcare delivery system levels to help reduce the influence of implicit bias on the gender inequity in liver transplantation.
The authors assert that implicit bias in liver transplantation may exacerbate gender inequity in transplant access and offer mitigating strategies that could be applied at the individual or the healthcare delivery system levels.
The epidermal growth factor receptor (EGFR) remains one of the best molecules for developing targeted therapy for multiple human malignancies, including head and neck squamous cell carcinoma (HNSCC). ...Small molecule inhibitors or antibodies targeting EGFR have been extensively developed in recent decades. Immunotoxin (IT)‑based therapy, which combines cell surface binding ligands or antibodies with a peptide toxin, represents another cancer treatment option. A total of 3 diphtheria toxin (DT)‑based fusion toxins that target human EGFR‑monovalent EGFR IT (mono‑EGF‑IT), bivalent EGFR IT (bi‑EGF‑IT), and a bispecific IT targeting both EGFR and interleukin‑2 receptor (bis‑EGF/IL2‑IT) were recently generated by the authors. Improved efficacy and reduced toxicity of bi‑EGF‑IT compared with mono‑EGF‑IT in immunocompromised HNSCC mouse models was reported. In the present study, bis‑EGF/IL2‑IT were generated using a unique DT‑resistant yeast expression system and evaluated the
and
efficacy and toxicity of the 3 EGF‑ITs in immunocompetent mice. The results demonstrated that while the three EGF‑ITs had different efficacies
and
against HNSCC, bi‑EGF‑IT and bis‑EGF/IL2‑IT had significantly improved
efficacy and remarkably less off‑target toxicity compared with mono‑EGF‑IT. In addition, bis‑EGF/IL2‑IT was superior to bi‑EGF‑IT in reducing tumor size and prolonging survival in the metastatic model. These data suggested that targeting either the tumor immune microenvironment or enhancing the binding affinity could improve the efficacy of IT‑based therapy. Bi‑EGF‑IT and bis‑EGF/IL2‑IT represent improved candidates for IT‑based therapy for future clinical development.
IMPORTANCE: Despite the acceptance of living-donor liver transplant (LDLT) as a lifesaving procedure for end-stage liver disease, it remains underused in the United States. Quantification of lifetime ...survival benefit and the Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score range at which benefit outweighs risk in LDLT is necessary to demonstrate its safety and effectiveness. OBJECTIVE: To assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients database of 119 275 US liver transplant candidates and recipients from January 1, 2012, to September 2, 2021. Liver transplant candidates aged 18 years or older who were assigned to the wait list (N = 116 455) or received LDLT (N = 2820) were included. Patients listed for retransplant or multiorgan transplant and those with prior kidney or liver transplants were excluded. EXPOSURES: Living-donor liver transplant vs remaining on the wait list. MAIN OUTCOMES AND MEASURES: The primary outcome of this study was life-years saved from receiving an LDLT. Secondary outcomes included 1-year relative mortality and risk, time to equal risk, time to equal survival, and the MELD-Na score at which that survival benefit was obtained for individuals who received an LDLT compared with that for individuals who remained on the wait list. MELD-Na score ranges from 6 to 40 and is well correlated with short-term survival. Higher MELD-Na scores (>20) are associated with an increased risk of death. RESULTS: The mean (SD) age of the 119 275 study participants was 55.1 (11.2) years, 63% were male, 0.9% were American Indian or Alaska Native, 4.3% were Asian, 8.2% were Black or African American, 15.8% were Hispanic or Latino, 0.2% were Native Hawaiian or Other Pacific Islander, and 70.2% were White. Mortality risk and survival models confirmed a significant survival benefit for patients receiving an LDLT who had a MELD-Na score of 11 or higher (adjusted hazard ratio, 0.64 95% CI, 0.47-0.88; P = .006). Living-donor liver transplant recipients gained an additional 13 to 17 life-years compared with patients who never received an LDLT. CONCLUSIONS AND RELEVANCE: An LDLT is associated with a substantial survival benefit to patients with end-stage liver disease even at MELD-Na scores as low as 11. The findings of this study suggest that the life-years gained are comparable to or greater than those conferred by any other lifesaving procedure or by a deceased-donor liver transplant. This study’s findings challenge current perceptions regarding when LDLT survival benefit occurs.
The authors add additional context to Khan et al.'s report (page 3573‐3582), highlighting challenges associated with utilizing operative time as a measure of skill acquisition and discuss the issue ...in the larger context of fellowship training and the need for continued development and refinement after fellowship.
IMPORTANCE: Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score–based liver allocation system, prompting national ...debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics. OBJECTIVE: To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018. EXPOSURE: Liver transplant waiting list. MAIN OUTCOMES AND MEASURES: Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements. RESULTS: Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean SD age, 54.7 11.3 years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean SD age, 55.7 10.1 years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio aHR, 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women). CONCLUSIONS AND RELEVANCE: Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.
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