Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

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.

Pre-transplant T-cell Clonality: An Observational Study of a Biomarker for Prediction of Sepsis in Liver Transplant Recipients.

OBJECTIVE: This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT). SUMMARY BACKGROUND DATA: Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation. METHODS: Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48 hours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables. RESULTS: Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12 months post-LT, respectively, when compared to recipients with lower (<0.072) clonality. T-cell repertoire clonality was the only predictor of sepsis 3 months post-LT in multivariate analysis (C-Statistic, 0.75). Adequate treatment resulted in equivalent survival rates between both groups: (93.4% vs 96.2%, respectively, P = 0.41) at 12 months post-LT. CONCLUSIONS: T-cell repertoire clonality is a novel biomarker predictor of sepsis before development of clinical symptoms. Early sepsis monitoring and management may reduce post-LT mortality. These findings have implications for developing sepsis-prevention protocols in transplantation and potentially other populations.

Donation after circulatory death liver transplantation: An in-depth analysis and propensity score-matched comparison.

BACKGROUND: Careful donor-recipient matching and reduced ischemia times have improved outcomes following donation after circulatory death (DCD) liver transplantation (LT). This study examines a single-center experience with DCD LT including high-acuity and hospitalized recipients. METHODS: DCD LT outcomes were compared to a propensity score-matched (PSM) donation after brain death (DBD) LT cohort (1:4); 32 DCD LT patients and 128 PSM DBD LT patients transplanted from 2008 to 2018 were included. Analyses included Kaplan-Meier estimates and Cox proportional hazards models examining patient and graft survival. RESULTS: Median MELD score in the DCD LT cohort was 22, with median MELD of 27 for DCD LT recipients with decompensated cirrhosis. No difference in mortality or graft loss was found (p < .05) between DCD LT and PSM DBD LT at 3 years post-transplant, nor was DCD an independent risk factor for patient or graft survival. Post-LT severe acute kidney injury was similar in both groups. Ischemic-type biliary lesions (ITBL) occurred in 6.3% (n = 2) of DCD LT recipients, resulting in 1 graft loss and 1 death. CONCLUSION: This study supports that DCD LT outcomes can be similar to DBD LT, with a low rate of ITBL, in a cohort including high-acuity recipients. Strict donor selection criteria, ischemia time minimization, and avoiding futile donor/recipient combinations are essential considerations.

Thirty-day mortality underestimates the risk of early death after major resections for thoracic malignancies.

BACKGROUND: Operative mortality rates are of great interest to surgeons, patients, policy makers, and payers as a metric for quality assessment. Thirty-day mortality and discharge mortality have been presumed to capture procedure-related deaths. However, many patients die after the 30-day mark or are transferred to other facilities or to home and die there, leading to the underreporting of surgically related deaths. We hypothesized that a longer period of observation would address these concerns and provide a more accurate measure of operative mortality. METHODS: We retrospectively reviewed institutional databases of patients undergoing resection for lung cancer, esophageal cancer, and mesothelioma. Mortality rates at 30 and 90 days were calculated with 95% confidence intervals (CIs). RESULTS: From 1999 to 2012, 7,646 surgical resections were performed: 6,119 for lung cancer, 1,258 for esophageal cancer, and 269 for mesothelioma. Among the different cancers and across operations, the additional mortality from day 31 to 90 (1.4%; 95% CI, 1.2% to 1.8%; n=111) was similar to that by day 30 (1.2%; 95% CI, 1.0% to 1.5%; n=95), resulting in overall 90-day mortality (2.7%; 95% CI, 2.3% to 3.1%; n=206) that was more than double the 30-day mortality. CONCLUSIONS: Among patients who have undergone operations for thoracic malignancies, mortality attributable to the operation occurs beyond the first 30 postsurgical days as well as after hospital discharge. Because cancer operations constitute a large portion of general thoracic surgery, we recommend national databases consider the inclusion of 90-day mortality in their data collection.

Second primary lung cancers: smokers versus nonsmokers after resection of stage I lung adenocarcinoma.

BACKGROUND: Smokers have a higher risk of developing non-small cell lung cancer (NSCLC) than never-smokers, but the relative risk of developing second primary lung cancer (SPLC) is unclear. Determining the risk of SPLC in smokers versus never-smokers after treatment of an initial cancer may help guide recommendations for long-term surveillance. METHODS: Patients who underwent resection for stage I adenocarcinoma were identified from a prospectively maintained institutional database. Patients with other histologies, synchronous lesions, or who received neoadjuvant or adjuvant therapy were excluded. The SPLCs were identified based on Martini criteria. RESULTS: From 1995 to 2012, a total of 2,151 patients underwent resection for stage I adenocarcinoma (308 never-smokers [14%] and 1,843 ever-smokers [86%]). SPLC developed in 30 never-smokers (9.9%) and 145 ever-smokers (7.8%). The SPLC was detected by surveillance computed tomography scan in the majority of patients (161; 92%). In total, 87% of never-smokers and 83% of ever-smokers had stage I SPLC. There was no significant difference in the cumulative incidence of SPLC between never-smokers and ever-smokers (p = 0.18) in a competing-risks analysis. The cumulative incidence at 10 years was 20.3% for never-smokers and 18.2% for ever-smokers. CONCLUSIONS: Although smokers have a greater risk of NSCLC, the risk of a second primary cancer developing after resection of stage I lung cancer is comparable between smokers and never-smokers. The majority of these second primary cancers are detectable at a curable stage. Ongoing postoperative surveillance should be recommended for all patients regardless of smoking status.

Recurrence patterns after resection of soft tissue sarcomas of the chest wall.

BACKGROUND: Soft tissue sarcoma (STS) of the chest wall is uncommon, and our knowledge is limited to small, single institutional case series. Although some series have examined prognostic factors for survival with this rare set of neoplasms, our knowledge of the patterns of relapse is limited. METHODS: We performed a retrospective review of a prospectively maintained database of consecutive patients treated for STS of the chest wall. Predictors of survival and recurrence were analyzed using Cox and competing-risk regression analyses. RESULTS: From 1989 to 2011, 192 patients underwent resection for STS of the chest wall. The most common histopathologic type was desmoid (33 [17%]), followed by undifferentiated pleomorphic sarcoma (32 [16%]), liposarcoma (22 [11%]), and myxofibrosarcoma (22 [11%]). The median follow-up was 50.9 months. The 5- and 10-year survival rates were 73% and 61%, respectively. Recurrences occurred in 45 patients (23%): 17 developed local recurrences, and 28 developed distant recurrences. Among the patients who developed recurrences, the median time to event was 11.6 months for local recurrences and 13.5 months for distant recurrences. The most common histologic type among recurrences was undifferentiated pleomorphic sarcoma (n = 12), and the most common site of distant recurrences was lung (n = 18). The primary treatment modality for both local and distant recurrences was surgical resection; median survival after recurrence was 19.4 months. CONCLUSIONS: Recurrences of STS are common after surgical resection. Although local or distant recurrences can occur soon after surgery, both can often be treated with resection, producing reasonable outcomes.