Kidney allocation relies on rapid sequential offers to maximize organ utilization, yet patient-level refusal remains poorly characterized. We conducted a retrospective study of kidney refusal encounters across 3 transplant centers over 2 years. Among 841 deceased donor offers where patients were contacted, 108 resulted in patient-level refusals (13%). Donation after circulatory death kidneys represented 51% of offers and 54% of refusals, whereas donation after brain death kidneys comprised 49% of offers and 46% of refusals. Median kidney donor profile index of refused offers was 50.5, and refusals occurred early in allocation (median match sequence, 5; interquartile range, 3-14). Refusal reasons clustered into donor-related concerns: longevity/quality (33.3%), infectious/behavioral risk (23%), patient preference/readiness (15%), logistical constraints (14%), and psychosocial/caregiver limitations (7%). Following refusal, candidates received subsequent offers quickly (median, 7.5 days), and 59% underwent transplantation (median, 46.5 days). Within 24 months, 23% experienced waitlist inactivation or removal. Most refused kidneys (83%) were transplanted elsewhere with acceptable outcomes. Patient-level refusal is common and multifactorial, reflecting dynamic interactions between candidate readiness, preferences, and donor characteristics. Strategies focused on longitudinal education, preference reassessment, and mitigation of psychosocial and logistical barriers may help reduce refusals while preserving patient-centered decision-making and efficient allocation.

Background: Hepatitis C viral infection (HCV) has historically been a leading indication for liver transplantation (LTx), primarily due to its progression to cirrhosis and hepatocellular carcinoma (HCC). However, the advent of direct-acting antiviral agents (DAAs) over a decade ago has revolutionized HCV treatment, achieving sustained virologic response (SVR) in over 90% of patients and potentially altering LTx indications. Aim: To investigate the impact of DAAs on HCV-related indications, with or without HCC, and model future trends in LTx indications. Methods: We retrospectively reviewed 1504 liver transplants performed between 2000 and 2024 at a single center. Patients were categorized into three cohorts: HCV-only, HCC-only, and HCC with HCV co-infection (HCC/HCV). Relative transplant volumes by-year, post-operative outcomes, and HCC recurrence rates were analyzed across pre- and post-DAA eras. ARIMA modeling was employed to project trends in transplant indications through the year 2030. Results: The proportion of transplants for HCV alone declined by 82.3% from 2015 to 2020, while HCC/HCV transplants decreased by 68.8%. Conversely, the total number of transplants for HCC alone increased during this period, with a modest proportional decrease of 8.3% from 2015 to 2020. ARIMA modeling suggests that by 2030, LTxs for HCV alone may be nearly eliminated. The projected proportion of transplants conducted for HCC alone remains the highest of all three study indications at 4.3%. Conclusions: DAAs have reduced LTx due to HCV. By 2030, LTx for HCV-related cirrhosis, particularly without HCC, may be obviated. This underscores the need to reevaluate allocation for emerging oncologic indications.

Biliary complications after orthotopic liver transplantation (OLTx) have a high incidence with inherent risks. Given the rise of obesity and subsequent bariatric surgery, there are new challenges for management, particularly in the setting of bypass anatomy, which is not well described. Trans-gastric remnant endoscopic retrograde cholangiopancreatography (TG-ERCP) is a novel technique that could evolve into a primary tool for the diagnosis and treatment of biliary complications after OLTx. A 35-year-old female with a history of Roux-en-Y gastric bypass (RYGB), decompensated alcoholic cirrhosis, and a MELD of 40 underwent standard OLTx. The postoperative course was complicated by rising liver function tests and common bile duct (CBD) dilatation without graft biliary tree dilation. Due to her bypass anatomy, TG-ERCP was used to diagnose a biliary stricture which was treated with CBD stenting. A gastric remnant gastrostomy tube (G-tube) was placed as easy access for all interval ERCP interventions until stricture resolution. As metabolic dysfunction-associated steatotic liver disease becomes a larger transplant indication, centers will undoubtedly encounter more recipients with RYGB anatomy. When compared to alternative options, TG-ERCP should be the primary tool for the diagnosis and treatment of postoperative biliary complications, given its high success rate with fewer complications and graft vascular injuries. Future cohort-based studies are necessary to validate this approach and the proposed treatment algorithm.

BACKGROUND:The normothermic machine perfusion pump (NMPP) could shape the future of transplantation. Providing ex-vivo optimization, NMPP attenuates ischemic insult while replenishing energy. An understanding of machine perfusion time (MPT) impact and potential clinical benefits is paramount and necessitates exploration. AIM:To investigate the relationship between MPT and post-transplant graft function. METHODS:Retrospective review of the first 50 donation after circulatory death (DCD) grafts preserved using NMPP in a tertiary institution was performed. Essential preservation time points, graft parameters, recipient information, and postoperative outcomes were prospectively recorded. Early allograft dysfunction (EAD), L-Graft7 score and 90-day outcomes were collected for all grafts. The first 20 recipients were allocated into the early group, considered the learning curve population for the center. The subsequent 30 were allocated into the late group. Recipients were also stratified into cohorts depending on MPT, i.e., short (< 8 hours), medium (8-16 hours) and long (> 16 hours). RESULTS:NMPP operational parameters were not predictive of EAD, L-GrAFT7 or 90-day outcomes. The early group had significantly less MPT and cold ischemia time than the late group (553 minutes vs 850 minutes, P < 0.001) and (127.5 minutes vs 154 minutes, P = 0.025), respectively. MPT had no impact in either group. CONCLUSION:Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population, indicating its upper limits, likely beyond 24 hours, are not demonstrated within this study. Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and, if the latter, what is the maximum safe duration. Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.

BACKGROUND Liver transplantation (LT) is the only curative, life-saving option for children and adults with end-stage liver disease. Due to the well-known shortage and heterogeneity of grafts, split LT (SLT) is an attractive strategy to expand the donor pool and reduce waitlist times. Given increased risk of cold ischemia time with SLT, machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes. The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion (NMP) closed circuit device. CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor. The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients. After a mixed in-situ and ex-situ split, in order to improve logistics, the right trisectional graft was placed on a closed circuit NMP device, following an appropriate vascular reconstruction. Both grafts were implanted with excellent short-term outcomes. CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics. We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.

A 72-year-old female renal transplant patient presents for surgical management of a T4aN0 recurrent squamous cell carcinoma of the scalp. She is otherwise healthy. She undergoes resection of her scalp malignancy with bifrontal craniectomy and latissimus dorsi myocutaneous free flap. The deep margin is positive for carcinoma over the sagittal sinus. She receives adjuvant radiation. Her posttreament PET scan is suspicious for recurrence along the superior calvarium. Clinical exam reveals dermal scalp nodules within the recently radiated field. Lesion biopsy diagnoses persistent squamous cell carcinoma. The patient asks her surgeon about treatment options. This is an actual clinical scenario. Immunotherapy is the most effective treatment for recurrent advanced or unresectable cutaneous carcinomas. However, the data are limited for the use of these agents in solid organ transplant (SOT) recipients due to the potential for harm to the patient and/or a transplanted organ. Consideration of immunotherapy poses distinctive decision-making challenges for SOT patients and their physicians. These decisions mandate ethical considerations because they are laden with qualitative judgments. Differences in bioethical perspectives as they relate to this treatment scenario can lead to clinical conflict between patients and/or providers. Cancer societies, including the American Head and Neck Society, have published guidelines that cautiously address the potential benefit but paucity of data for this high-risk therapeutic intervention.1 However, the ethical perspectives surrounding this topic have yet to be outlined. Point: Renal transplant patients with unresectable advanced cutaneous malignancies should be considered for innovative use of immunotherapy, including clinical trials. Physicians may offer immunotherapy to a renal transplant patient with an advanced cutaneous malignancy once maximum weaning of immune suppression and all reasonable alternatives have been exhausted. This intervention can be considered compassionate and medically appropriate. A physician may feel empathy for this patient with limited effective systemic treatment options and may be comfortable proceeding with treatment, as long as the patient has been informed of the risk to the renal allograft and the possible need for dialysis in the event of allograft rejection. Pellegrino describes a virtuous, compassionate physician as one whose scientific judgments are morally defensible when they feel the patient's plight.2 The plight of renal transplant patients from cutaneous squamous cell carcinoma has perhaps been underrecognized. As of December 2018, there were 229,887 patients in the United States with a functioning kidney transplant.3 Skin cancer affects 50% of renal transplant patients, and skin cancer is their most common cancer-related cause of death.4, 5 The mortality of skin cancer in SOT patients exceeds that of colon and breast cancer combined—cancers that often warrant aggressive treatment with surgery plus chemotherapy or other intravenous drug administration.6 It is unjust to exclude SOT patients from access to immunotherapy if they have an advanced cutaneous malignancy and no reasonable therapeutic alternative. In 2018, immune therapy was approved by the Food and Drug Administration for patients with metastatic or locally advanced cutaneous squamous cell carcinoma who decline or are ineligible for surgery (R2810-ONC-1423 and R2810-ONC-1540). This drug was not approved for use in transplant patients because the monoclonal antibody blockade that helps immune cells attack cancer cells can also facilitate allograft rejection. Yet, single-institution case reports and a systematic review of the literature demonstrate cautious clinical success in the SOT population.7, 8 Additional clinical trials are underway (NCT03816332, NCT05896839, and NCT04339062). Immune therapy has clinical risks even for patients with competent immune systems, some of which may be life-threatening. The potential for treatment adverse effects alone should not preclude patients from obtaining fair and equitable access to immune therapy for cancer treatment. Balancing the benevolent intent to cure with a physician's directive to do no harm is a challenge in the practice of advanced clinical medicine, when interventions seek to push therapeutic limits. Innovative medicine always requires carefully thought-out strategies for coping with failure.9 Therefore, patients who are asked to participate in such a quest must receive honest and transparent information and must be thoughtfully engaged in discussions regarding toxicity risk and goals of care.9 To this end, international guidelines were published in January 2022 which state expert consensus that SOT patients with advanced cutaneous squamous cell carcinoma may be offered immunotherapy if there is no valid alternative treatment, after careful multidisciplinary assessment and a thorough discussion with the patient on the risk of graft rejection.10 The sanctity of the physician-patient relationship is reinforced by the opportunity for shared decision-making to take place in such life-threatening scenarios. Cancer patients prioritize treatment-associated values, such as cancer cure, longevity, living pain-free, feeling and acting normal, or maintaining a normal appearance differently from one another and from nonpatients.11 Physicians—head and neck surgeons in particular—may know how to navigate a lethal diagnosis when the patient can understand this only marginally at best, but will nevertheless respect the patient's autonomy of treatment choice.12 Head and neck surgeons and oncologists frequently bear witness to suffering when patients near the end of life with advanced cancer. They may see the greatest value in aggressive, though risky, cancer treatments. However, this perspective may be at odds with that of transplant clinicians, who may vocalize a stronger obligation to preserve the allograft. These opposing perspectives may have the greatest potential for conflict within multidisciplinary teams treating renal transplant patients with immune therapy versus those with essential (heart, lung, and liver) transplants. The relative ambiguity regarding how to prioritize competing skin and transplant organ systems may be greatest when the patient can survive without graft survival, on hemodialysis. The optimal outcome for individual patient well-being is unlikely to be generalizable. Value-based multidisciplinary shared decision-making regarding the use of immunotherapy for SOT patients with advanced cutaneous malignancies will be essential for this type of innovative medical care to progress. Such clinical decisions are never made solely by weighing the odds based on empirical data. Instead, they necessarily reflect and incorporate personal values, convictions, and commitments, which are often unspoken and unexamined. Assessment of risk proportionality is integral, but also variable among individuals. Downsizing or slowing the progression of an unresectable cancer may be invaluable to some patients faced with their end of life. Other patients will view hemodialysis as a harm worse than death. Death mediated by organ rejection may be considered unacceptable by some stakeholders, but undesirable yet acceptable to those who fear suffering from terminal, locoregionally advanced disease. Health preference research on this subject could inform the development of clinical tools to advance shared decision-making and to fully utilize immunotherapeutic advancements.13 Facilitating shared decision-making in the context of preference-sensitive decisions may require the development of such aids to help patients understand what is at stake and to articulate their preferences and priorities. Decision aids have been employed to support patients through complex surgical choices in various malignancies including breast, ovarian, and colorectal cancer. The responsibility to engage in shared decision-making in this scenario is of particular relevance to head and neck surgeons. Our “survival…as the captain of the team will hinge on his/her ability to adapt to new treatment strategies, to continue to serve the patient as the pivotal team leader, and to serve as the judge among the other therapists,” as stated by former American Head and Neck Society president, Dr K. Thomas Robbins.14 Counterpoint: Medical society should restrict the use of immunotherapy in transplant patients with advanced cutaneous malignancies. Advanced cutaneous malignancies in immunosuppressed SOT patients carry significant clinical morbidity and mortality. The patient in the clinical scenario above cannot be cured with standard interventions, and palliative therapies may be most appropriate. A 2020 systematic review of SOT patients treated for metastatic cancer demonstrated that 51% of patients died from disease progression or underlying disease, and 37% of patients experienced rejection with immunotherapy.7 One-third of all patient deaths were caused by transplant rejection, including 2 deaths in renal transplant patients that declined dialysis. Stage-specific survival for most common cancers is significantly lower in SOT patients compared to the general population.15 For example, 5-year overall colorectal survival in males with renal transplants is 27% versus 75% in the general population. Similarly, mortality from breast cancer in women with renal transplants is 40% greater than that of the general population. In a discussion of guiding patients with advanced head and neck cancer, Elackattu and Jalisi emphasize the value of allowing a patient to die with peace, dignity and in a controlled environment, without diminution from the impact of futile heroic interventions.16 Dr Pellegrino, in his writings on professionalism and virtue, reminds providers to maintain intellectual honesty—to honor medicine as a powerful instrument for good and harm and to prevent harm by acknowledging one's true limitations in treating the patient.2 Although criteria for futility are not clearly met in this scenario, it could be argued that Pellegrino's “good physician” would operate with intellectual honesty and emphasize the limitations of current modern medicine when faced with the scenario, rather than proffering a “Hail Mary” outcome. Patients with advanced cancer diagnoses are particularly vulnerable to coercion or persuasion with respect to treatments viewed as heroic or innovative. Currently, appropriate medical society guidelines do not exist to guide the ethical use of this innovative medication. Consensus is lacking as to whether it is appropriate to offer immunotherapy to a patient who would decline dialysis in the event of renal allograft failure, or to a cardiac or lung transplant patient who has no life-sustaining alternative to graft failure. There is also equipoise as to whether it is most appropriate to make this medication first available to a limited subset of otherwise healthy patients with only locoregional disease, or whether the medication should be offered to the majority of SOT patients, even if distant metastases or major co-morbid conditions are present. As SOT patients are routinely excluded from immunotherapy trials, there is currently limited safety and efficacy data to guide such treatment decisions. This clinical scenario highlights a currently unmet need for formal multidisciplinary clinical collaboration to devise guidelines and optimize therapeutic plans, in order to protect SOT patients and their allografts while maximizing the therapeutic benefit of immunotherapy. In current clinical practice for immunocompetent patients, immunotherapy is an alternative to cosmetically deforming surgical procedures on the head and neck, or for cutaneous disease that may be relatively less amenable to surgery, such as in-transit metastases. It would most benefit the SOT patient for surgeons to formalize criteria that define ethically appropriate use for immunotherapy in this vulnerable population. These criteria would be most helpful if it specifically addressed in-transit metastases, surgeries that may bear significant cosmetic impact but are likely to be successful, and the likelihood of surgical candidacy in the event of the medication's therapeutic benefit and cancer down-staging. It is also important to acknowledge that limits on patient autonomy are reasonable with respect to accessing immunotherapy in situations for which a surgical alternative is present. Prior to the dissemination of this innovative medical practice, the development of an oversight organization could help to ensure that patients receive an appropriate multidisciplinary evaluation at high-volume cancer centers with a qualified head and neck surgeon. Such an organization could capture adverse events, including graft failure and patient deaths, for complete data transparency. Much ethical consideration and policy work has yet to be done on behalf of physicians and the pharmaceutical industry to protect this vulnerable SOT patient population from unnecessary harm prior to treatment dissemination. Oncologists, too, may benefit from clear society consensus guidelines. From an ethics-legal perspective, this may be protective, as providers may fear blame and retribution from patients or their family members in the event of transplant organ rejection. Additionally, there may be alternative practical strategies to minimize SOT recipients' risk of death from cutaneous squamous cell carcinoma. Health care dollars could be invested in dermatologic prevention strategies, such as frequent routine skin cancer exams, topical therapies, or clinical navigation staff that facilitate rapid access to early surgical intervention. In current practice, immunosuppression weaning is contentious because it disturbs a tenuous equilibrium that has been maintained successfully for decades. Weaning may only be considered at the time of first advanced skin cancer diagnosis, even in situations of frequent multiple and recurrent skin cancers. Prolonged duration and type of immune suppression increase SOT patient susceptibility to cutaneous squamous cell carcinoma. This often clinically manifests as a crescendo-like uptick in the rate of annual skin cancers. Earlier weaning strategies or transition to alternative immunosuppressive medication regimens with a less direct relationship with skin cancer, such as sirolimus, could be prioritized in select patients who have faced several decades of immunosuppression, thereby modifying the probability of advanced or unresectable cancer development. The drama is a dilemma of cure or palliation wrapped about the emotional core of that person with science, drugs, technology, mysticism and hope.17 Catherine H. Frenkel, contributions include actual patient scenario clinical management and authorship of manuscript and clinical scenario content; Ana S. Iltis, contribution includes ethical analysis of manuscript content; Vincent Casingal, contribution includes manuscript content authorship and reviews specific to solid organ transplant data presentation; Jennifer Atlas, contributions include actual patient scenario clinical management, and authorship of manuscript and clinical scenario content. None None.

Background: Recent data have demonstrated a lower incidence of cytomegalovirus (CMV) disease utilizing preemptive CMV treatment compared to universal prophylaxis in CMV seronegative liver transplant recipients who receive allografts from CMV seropositive donors (donor-positive [D+]recipient-negative [R-]). However, there are little data on the feasibility and outcomes after switching transplant center protocols from universal CMV prophylaxis to preemptive treatment. Methods: All D+R- adult liver transplant recipients underwent pharmacist-led weekly monitoring of World Health Organization standardized quantitative plasma CMV deoxyribonucleic acid (DNA) after transplant for 6 months. Valganciclovir was started when plasma CMV viral load (VL) reached 100 IU/mL. All patients who were at least 12 months post-liver transplant were retrospectively reviewed for incidence of CMV DNAemia and CMV disease in this cohort study. Results: Among 30 CMV D+R- liver transplant recipients, 23 (77%) developed target CMV DNAemia (>= 100 IU/mL) at a median of 26 (range: 10-37) days after transplant with a median peak CMV VL of 947 IU/mL. Valganciclovir was started promptly with a median lag time of 1 (range: 0-5) day. There were no differences in surgical or infectious complications and readmission rates between patients with and without CMV DNAemia. Two patients had possible CMV disease in the first 6 months. None developed CMV disease in 6-12 months posttransplant. Only two patients who developed CMV DNAemia had acute cellular rejection, and none had graft loss or death. Weekly CMV polymerase chain reaction (PCR) testing was late on only three occasions for all patients before reaching the target CMV VL (<4%). Among those who remained nonviremic, 85% of scheduled weekly CMV PCR testing was completed in the first 3 months. Conclusion: Preemptive CMV treatment in high-risk liver transplant recipients is feasible and safe. There was a low rate of CMV disease in the first 12 months post-liver transplant with a pharmacist-led protocol.

The number of patients presenting with cirrhosis with kidney injury and the potential need for SLKT is increasing. In 2017, standardized criteria were implemented to identify candidates for SLKT as well as criteria for prioritizing LTA recipients for kidney transplant if they developed kidney failure, which is referred to as the 'safety net rule.' Goal of the safety net rule is to provide a pathway that provides increased priority to LTA recipients with renal failure who may have previously undergone SLKT. This article reviews the pros and cons of the safety net rule for liver transplant recipients who develop ESRD.