New Insights in the Setting of Transplant Oncology

: Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required

Serum Concentrations of Aerosolized Tobramycin in Medical, Surgical, and Trauma Patients

Combination antibiotic therapy is often indicated for health care-associated pneumonia due to resistant pathogens and is recommended in the Infectious Diseases Society of America/American Thoracic Society guidelines on the management of community-acquired pneumonia and health care-associated pneumonia (1, 4). Antibiotic aerosolization enhances delivery to the lower respiratory tract while theoretically limiting toxicity. Aerosolized tobramycin (TOBI) is currently approved for use only in patients with cystic fibrosis (CF). According to the manufacturer (2007 tobramycin inhalation solution USP prescribing information, Novartis Pharmaceuticals, East Hanover, NJ), patients with normal renal function do not require routine tobramycin concentration monitoring. However, there is limited evidence of the safety of the use of TOBI in the non-CF population. Brown et al. found TOBI to be safe and to result in a microbiologic cure, but clinical outcomes did not differ from those achieved with systemic therapy (2). Systemic absorption of 40 mg TOBI every 8 h resulted in detectable levels but did not affect renal function. In our safety study, we postulated that non-CF patients would have similar serum tobramycin concentrations and that patients with normal renal function would not have tobramycin-associated renal insufficiency

Serum Concentrations of Aerosolized Tobramycin in Medical, Surgical, and Trauma Patients

Combination antibiotic therapy is often indicated for health care-associated pneumonia due to resistant pathogens and is recommended in the Infectious Diseases Society of America/American Thoracic Society guidelines on the management of community-acquired pneumonia and health care-associated pneumonia (1, 4). Antibiotic aerosolization enhances delivery to the lower respiratory tract while theoretically limiting toxicity. Aerosolized tobramycin (TOBI) is currently approved for use only in patients with cystic fibrosis (CF). According to the manufacturer (2007 tobramycin inhalation solution USP prescribing information, Novartis Pharmaceuticals, East Hanover, NJ), patients with normal renal function do not require routine tobramycin concentration monitoring. However, there is limited evidence of the safety of the use of TOBI in the non-CF population. Brown et al. found TOBI to be safe and to result in a microbiologic cure, but clinical outcomes did not differ from those achieved with systemic therapy (2). Systemic absorption of 40 mg TOBI every 8 h resulted in detectable levels but did not affect renal function. In our safety study, we postulated that non-CF patients would have similar serum tobramycin concentrations and that patients with normal renal function would not have tobramycin-associated renal insufficiency

Long-term outcomes of retransplantation after live donor liver transplantation: A Western experience

Background: Despite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated. Method: We aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant. Results: A total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23–1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44–1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54–4.19; P = .40) were equivalent in those who initially received a living donor liver transplant. Conclusion: Patients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes

Liver transplantation as a new standard of care in patients with perihilar cholangiocarcinoma?:Results from an international benchmark study

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥ 50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤ 5.2%; comprehensive complication index at 1 year of ≤ 33.7; grade ≥ 3 complication rates ≤ 66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n = 106) (62% vs 32%, P < 0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC