LiverMap pipeline for 3D imaging of human liver reveals volumetric spatial dysregulation of cirrhotic vasculobiliary architecture.

The liver contains an intricate microstructure that is critical for liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, 2D histopathology - the gold standard for pathological understanding of many liver diseases - can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we utilized immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both non-fibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonation dysregulation, reduction in glutamine synthetase-expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire novel treatments for liver disease.

Comparative assessment of the safety and effectiveness of radiofrequency ablation among elderly medicare beneficiaries with hepatocellular carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) use among patients with hepatocellular carcinoma (HCC) has increased dramatically over the last decade, but assessments outside specialized centers are lacking. This population-based study was intended to evaluate the safety and effectiveness of RFA when used to treat HCC. METHODS: A cohort study of HCC patients (diagnosed 2002-2005) was performed using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Early (≤90-day) mortality and readmission as well as survival among patients undergoing RFA, resection, or no treatment were compared using multivariate and propensity score adjusted Poisson and Cox regression models. RESULTS: Of 2631 patients (mean age 76.1±6.1 years, 65.9% male), 16% underwent RFA (49.6%) or resection (50.4%). Early mortality (13.6 vs. 18.7%, P=.16) and readmission (34.5 vs. 32.1%, P=.60) rates were similar among RFA and resection patients. The 1-year survival after RFA and resection was similar (72.2 vs. 79.7%, P=.18), but beyond 3 years there was a survival benefit among patients undergoing resection (39.2 vs. 58.0%, P<.001). Patients treated with RFA as a sole therapeutic intervention in the 1st year had a similar hazard of death compared with untreated patients (hazard ratio [HR] 0.84, 95% confidence interval [95% CI] 0.54-1.33). CONCLUSIONS: In the general community, patients treated with RFA have a similar risk of early adverse events compared with those treated with resection with no clear survival benefit when used as a sole intervention. Although RFA has been described as a safe and effective treatment for HCC at specialized centers, this experience may not extrapolate to the general community and requires further evaluation.

Enhanced Recovery via Peripheral Nerve Block for Open Hepatectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are now commonplace in many fields of surgery, but only limited data exists for their use in hepatobiliary surgery. We implemented standardized ERAS protocols for all open hepatectomies and replaced thoracic epidurals with a transversus abdominis plane (TAP) block. METHODS: We performed a retrospective cohort study of all patients undergoing open hepatectomy during the 14 months before and 19 months after implementation of an ERAS protocol at our institution (January 2014-September 2016). Trained abstractors reviewed charts for patient demographics, perioperative details, and healthcare utilization. All nursing-reported visual analog scale pain scores were sampled to identify patients with uncontrolled pain (daily mean score > 5). Outcomes included length of stay (LOS), costs, and 30-day readmission. RESULTS: A total of 127 patients (mean age 54.6 ± 13.0 years, 44% female) underwent open liver resection (69 [54%] after ERAS implementation). ERAS protocols were associated with significantly lower rates of ICU admission (47 vs. 13%, p < 0.001), shorter LOS (median 5.3 vs. 4.3 days, p = 0.007), and lower median costs ($3566 less, p = 0.03). Readmission remained low throughout the study period (5% pre-ERAS, 4% during ERAS, p = 0.83). Rates of uncontrolled pain were either the same or better after ERAS implementation through post-operative day #3 (41% pre-ERAS, 23% during ERAS, p = 0.03). DISCUSSION: The use of TAP block for hepatectomy as part of an ERAS protocol is associated with improved quality and cost of care. Surgeons performing liver resections should consider standardization of evidence-based best practices in all patients.

Diagnostic imaging and biopsy use among elderly medicare beneficiaries with hepatocellular carcinoma.

PURPOSE: Diagnostic imaging is effective for evaluating patients suspected of having hepatocellular carcinoma (HCC). Although the diagnosis can be established with imaging alone, diagnostic biopsy may be useful for patients with tumors measuring 1 to 2 cm. To date, biopsy and imaging use among patients with HCC has not been evaluated in the general community. PATIENTS AND METHODS: This cohort study used Surveillance, Epidemiology, and End Results (SEER) -Medicare data (2002-2005) evaluating biopsy, imaging modalities (ultrasound, computed tomography [CT] scan, and/or magnetic resonance imaging [MRI]), and HCC risk factors. RESULTS: Of 3,696 patients, 1,197 (32.4%) underwent one or more biopsies, with no change in yearly biopsy rate (trend test, P = .64). Patients with tumors > 5 cm were most likely to receive biopsies (35.3%), with increasing rates of biopsy for larger tumors (P = .001). Patients who received biopsies underwent more imaging than those who did not (P < .001) and were more likely to have an HCC risk factor. Tumor size > 5 cm in the setting of a concurrent HCC risk factor increased the odds of biopsy. In 47.8% of patients, the diagnostic sequence was not consistent with contemporary evidence-based guidelines. CONCLUSIONS: Despite widespread availability and use of CT scan and MRI, one third of HCC patients undergo biopsy, suggesting a problem with the performance and/or quality of diagnostic imaging or that providers do not believe imaging alone is sufficient to establish the diagnosis. Understanding factors that drive biopsy use may help improve the care of patients with HCC.

Trends in the utilization and impact of radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is rising and radiofrequency ablation (RFA) appears to be increasingly used. The nationwide use and impact of RFA have not been well characterized. STUDY DESIGN: We performed an historical cohort study of US patients 18 years old and older, with a diagnosis of HCC (n = 22,103) using the national Surveillance, Epidemiology, and End Results (SEER) limited-use database (1998 to 2005). Main outcomes measures were receipt of different therapeutic interventions (ablation, RFA, resection, or transplantation) and adjusted 1- and 2-year survivals. RESULTS: A total of 4,924 (22%) patients underwent any intervention, with a 93% increase over the 8-year study period (trend test, p < 0.001). RFA accounted for 43% of this increase. Despite increased use of therapeutic interventions, 1- and 2-year survival rates did not improve over time for patients in the study cohort (48% and 34%, 52% and 37%, 50% and 36%; in 1998, 2002, and 2004, respectively; p = 0.31). Among patients with solitary lesions, adjusted 1- and 2-year survivals remained stable over time after transplantation (97% and 94%, 95% and 89%, 94% and 86% in 1998, 2002, and 2004, respectively; p = 0.99) and RFA (86% and 64%, 76% and 54%, in 2002 and 2004, respectively; p = 0.97), but improved after resection (83% and 71%, 91% and 84%, 97% and 94% in 1998, 2002, and 2004, respectively; p = 0.03). CONCLUSIONS: Use of interventions for the treatment of HCC, and specifically RFA, have markedly increased over time. Because increased use of RFA among patients with potentially resectable disease is likely to occur, and because of a lack of high-level evidence supporting expanded indications, continued evaluation of the indications for RFA and subsequent outcomes among US patients is warranted.