Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Dataset of phase I and II immunotherapy clinical trials used for a meta-analysis to assess the role of biomarkers in treatment outcomes in diverse cancers.

We performed a literature search in PubMed to identify phase I/II clinical trials with immunotherapy drugs approved by the Food and Drug Administration (labeled, off-label, and/or combined with investigational immune checkpoint inhibitors or other treatment modalities) from 2018 to 2020. We used the following key words: clinical trials, phase 1, Phase 2; and the following filters: cancer, humans; and selected the checkpoint inhibitors that had been approved by the FDA by March 2021, i.e., "pembrolizumab", "nivolumab", "atezolizumab", "durvalumab", "cemiplimab", "avelumab", and "ipilimumab. Clinical trials with their checkpoint inhibitors as in their labeled indications, off-label use or their combinations with investigational immune checkpoint inhibitors or other treatment modalities were included. Studies describing supportive care or locoregional treatments; cellular, viral, or vaccine therapy; studies in the adjuvant or neoadjuvant setting; and pediatric studies were excluded. Overall, 173 articles reporting on relevant studies were identified. Using these articles, we compiled a data file of study-specific covariates for each study. We recorded the immunotherapeutic agent, tumor type and biomarker, and clinical outcomes (objective response rate and median values [point estimate] and confidence intervals for progression-free survival and overall survival. Using these data, we carried out meta-analyses for the three outcomes and meta-regression on study-specific covariates. The same data could be used for any alternative implementation of meta-analysis and meta-regression, using more structured inference models reflecting different levels of dependence based on the available study-specific covariates.

Percutaneous treatment of renal tumours.

Image-guided ablation is an accepted treatment option in the management of renal cell carcinoma. Percutaneous renal ablation offers the possibility of minimally invasive treatment while attempting to preserve renal function. Over the past several years there have been advances in tools and techniques that have improved procedure safety and patient outcomes. This article provides an updated comprehensive review of percutaneous ablation in the management of renal cell carcinoma.

Correlation between biomarkers and treatment outcomes in diverse cancers: a systematic review and meta-analysis of phase I and II immunotherapy clinical trials.

BACKGROUND: Many immuno-oncology (IO) trials are conducted without biomarker selection. We performed a meta-analysis of phase I/II clinical trials evaluating immune checkpoint inhibitors (ICIs) to determine the association between biomarkers and clinical outcomes, if any. METHODS: A PubMed search for phase I/II clinical trials with drugs approved by the Food and Drug Administration (labelled, off-label, combined with investigational ICIs or other treatment modalities) from 2018 to 2020 was performed. The objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between biomarker-positive and biomarker-negative groups, using studies that explored the correlation of biomarkers with outcomes. RESULTS: Overall, 174 clinical studies that included 19,178 patients were identified, and 132 studies investigated>30 correlative biomarkers that included PD-L1 expression (≥1%, 111 studies), tumour mutational burden (20 studies) and microsatellite instability/mismatch repair deficiency (10 studies). Overall, 123, 46 and 30 cohorts (drugs, tumour types or biomarkers) with 11,692, 3065, and 2256 patient outcomes for ORR, PFS and OS, respectively, were analysed in correlation with biomarkers. Meta-analyses demonstrated that ICIs in patients with biomarker-positive tumours were associated with higher ORR (odds ratio 2.15 [95% CI, 1.79-2.58], p < 0.0001); and longer PFS (hazard ratio [HR] 0.55 [95% CI, 0.45-0.67], p < 0.0001), and OS (HR 0.65 [95% CI, 0.53-0.80], p < 0.0001) compared with those with biomarker-negative tumours. Significance for ORR and PFS was retained in multivariate analysis (p < 0.001) (OS, not included owing to the small number of trials reporting OS). CONCLUSION: Our data suggest that IO biomarkers should be used in patient selection for ICIs. Prospective studies are warranted.

Evaluation of 14-day Concentration-time Curves of Vitamin D3 and 25-Hydroxyvitamin D3 in Healthy Adults With Varying Body Mass Index.

BACKGROUND/AIM: To analyze the concentration-time curves of single-dose oral 25(OH)D3 in comparison with vitamin D3 in healthy adults. PATIENTS AND METHODS: The pharmacokinetics observed over two weeks after orally administering single 900 µg doses of vitamin D3 and 25(OH)D3 to six otherwise healthy vitamin D insufficient/deficient adults participating in a broader randomized, double-blind, crossover, single center trial was analyzed. The study protocol was approved by the institutional review board (H-37167). RESULTS: Individual concentration-time curves revealed that vitamin D3 took longer than 25(OH)D3 to reach its maximal concentration after ingestion in five participants. After 25(OH)D3 ingestion, 25(OH)D3 reached its maximal concentration, dropped rapidly, and plateaued before starting to decrease slowly. There were observable inter-individual variations in the bioavailability of vitamin D3 and 25(OH)D3 and the pattern of changes in 25(OH)D3 concentration after their ingestion. CONCLUSION: Pharmacokinetics of 25(OH)D3 in comparison with vitamin D3 was illustrated and described in this study.

Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model.

BACKGROUND: First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. METHODS: We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. RESULTS: For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days). CONCLUSIONS: Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.

PURPOSE: PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [18F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [18F]-JK-PSMA-7 under ADT. PROCEDURES: We examined the performance of [18F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [68Ga]PSMA-11 or [18F]DCFPyL (second cohort). Finally, we compared detection rates between [18F]-JK-PSMA-7, [68Ga]PSMA-11, and [18F]DCFPyL. RESULTS: In the first cohort, we detected [18F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10-5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10-2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [68Ga]PSMA-11 or [18F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10-2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [18F]-JK-PSMA-7 and [68Ga]PSMA-11 or [18F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295). CONCLUSION: [18F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.

Proteome-wide identification of HSP70/HSC70 chaperone clients in human cells.

The 70 kDa heat shock protein (HSP70) family of chaperones are the front line of protection from stress-induced misfolding and aggregation of polypeptides in most organisms and are responsible for promoting the stability, folding, and degradation of clients to maintain cellular protein homeostasis. Here, we demonstrate quantitative identification of HSP70 and 71 kDa heat shock cognate (HSC70) clients using a ubiquitin-mediated proximity tagging strategy and show that, despite their high degree of similarity, these enzymes have largely nonoverlapping specificities. Both proteins show a preference for association with newly synthesized polypeptides, but each responds differently to changes in the stoichiometry of proteins in obligate multi-subunit complexes. In addition, expression of an amyotrophic lateral sclerosis (ALS)-associated superoxide dismutase 1 (SOD1) mutant protein induces changes in HSP70 and HSC70 client association and aggregation toward polypeptides with predicted disorder, indicating that there are global effects from a single misfolded protein that extend to many clients within chaperone networks. Together these findings show that the ubiquitin-activated interaction trap (UBAIT) fusion system can efficiently isolate the complex interactome of HSP chaperone family proteins under normal and stress conditions.

A Step-Up Approach to Infected Abdominal Fluid Collections: Not Just for Pancreatitis.

Background: More than 145,500 abdominal abscesses occur annually in the U.S. Percutaneous catheter drainage (PCD) is the primary treatment for clinically significant intra-abdominal collections (IACs), but only approximately 90% of all IACs are treatable with PCD. This leaves a significant number of patients facing long courses of management, including multiple interventions. Minimally invasive debridement techniques are now employed regularly for the treatment of infected necrosis caused by acute pancreatitis. We describe the use of minimally invasive videoscopic debridement techniques employed as part of a "step-up" approach to resolve IACs of other etiologies that are unresponsive to PCD. Methods: Data of all patients undergoing this procedure at a tertiary referral academic center from 2015 to 2017 after failure of different PCD techniques were analyzed retrospectively. Results: Four men and two women, mean age 54.6 years (range 26-70 years), with refractory IACs (mean drainage time 91.3 days; mean number of drainage procedures 4.6) following a variety of surgical interventions and inflammatory conditions underwent either video-assisted retroperitoneal debridement or sinus tract endoscopic debridement with a rigid or flexible endoscope. Technical success was achieved in all cases, and clinical success was observed in five cases. No immediate procedural complications were detected. The mean hospital stay and post-procedure drainage times were 5.5 and 25.2 days, respectively. There were no recurrent IACs. Conclusion: Minimally invasive debridement techniques can safely resolve IACs refractory to standard PCD techniques. Employment of these techniques as part of a step-up approach may reduce the morbidity and duration of drainage for the thousands of patients treated annually who have refractory IACs, whatever their etiology.

Evidence for inoculum size and gas interfaces as critical factors in bacterial biofilm formation on magnesium implants in an animal model.

Infections of medical implants caused by bacterial biofilms are a major clinical problem. Bacterial colonization is predicted to be prevented by alkaline magnesium surfaces. However, in experimental animal studies, magnesium implants prolonged infections. The reason for this peculiarity likely lies within the ‒still largely hypothetical‒ mechanism by which infection arises. Investigating subcutaneous magnesium implants infected with bioluminescent Pseudomonas aeruginosa via in vivo imaging, we found that the rate of implant infections was critically dependent on a surprisingly high quantity of injected bacteria. At high inocula, bacteria were antibiotic-refractory immediately after infection. High cell densities are known to limit nutrient availability, restricting proliferation and trigger quorum sensing which could both contribute to the rapid initial resistance. We propose that gas bubbles such as those formed during magnesium corrosion, can then act as interfaces that support biofilm formation and permit long-term survival. This model could provide an explanation for the apparent ineffectiveness of innovative contact-dependent bactericidal implant surfaces in patients. In addition, the model points toward air bubbles in tissue, either by inclusion during surgery or by spontaneous gas bubble formation later on, could constitute a key risk factor for clinical implant infections.

Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model.

OBJECTIVES: To gain insight into the natural history and carcinogenesis pathway of Pancreatic Intraepithelial Neoplasia (PanIN) lesions by building a calibrated simulation model of PanIN progression to pancreatic ductal adenocarcinoma (PDAC) METHODS: We revised a previously validated simulation model of solid PDAC, calibrating the model to fit data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and published literature on PanIN prevalence by age. We estimated the likelihood of progression from PanIN states (1, 2, and 3) to PDAC and the time between PanIN onset and PDAC (dwell time). We evaluated a hypothetical intervention to test for and treat PanIN 3 lesions to estimate the potential benefits from PanIN detection. RESULTS: We estimated the lifetime probability of progressing from PanIN 1 to PDAC to be 1.5% (men), 1.3% (women). Progression from PanIN 1 to PDAC took 33.6 years and 35.3 years, respectively, and from PanIN 3 to PDAC took 11.3 years and 12.3 years. A hypothetical test for PanIN 3 detection and treatment could provide a maximum, average life expectancy gain of 40 days. CONCLUSIONS: Our modeling analysis estimates PanINs have a relatively indolent course to PDAC, supporting the feasibility of potential future early detection strategies.

Dynamics of oxygen and carbon dioxide in rhizospheres of Lobelia dortmanna - a planar optode study of belowground gas exchange between plants and sediment.

Root-mediated CO2 uptake, O2 release and their effects on O2 and CO2 dynamics in the rhizosphere of Lobelia dortmanna were investigated. Novel planar optode technology, imaging CO2 and O2 distribution around single roots, provided insights into the spatiotemporal patterns of gas exchange between roots, sediment and microbial community. In light, O2 release and CO2 uptake were pronounced, resulting in a distinct oxygenated zone (radius: c. 3 mm) and a CO2 -depleted zone (radius: c. 2 mm) around roots. Simultaneously, however, microbial CO2 production was stimulated within a larger zone around the roots (radius: c. 10 mm). This gave rise to a distinct pattern with a CO2 minimum at the root surface and a CO2 maximum c. 2 mm away from the root. In darkness, CO2 uptake ceased, and the CO2 -depleted zone disappeared within 2 h. By contrast, the oxygenated root zone remained even after 8 h, but diminished markedly over time. A tight coupling between photosynthetic processes and the spatiotemporal dynamics of O2 and CO2 in the rhizosphere of Lobelia was demonstrated, and we suggest that O2 -induced stimulation of the microbial community in the sediment increases the supply of inorganic carbon for photosynthesis by building up a CO2 reservoir in the rhizosphere.

Image-Guided Percutaneous Omental and Mesenteric Biopsy: Assessment of Technical Success Rate and Diagnostic Yield.

PURPOSE: To assess biopsy technique, technical success rate, and diagnostic yield of image-guided percutaneous biopsy of omental and mesenteric lesions. MATERIALS AND METHODS: This retrospective study included 186 patients (89 men, 97 women; mean [SD] age, 63 [13.8] y) who underwent percutaneous image-guided biopsy of omentum and mesentery between March 2007 and August 2015. Biopsies were performed with computed tomography (CT) (n = 172) or ultrasound (US) (n = 14) guidance using coaxial technique yielding core and fine-needle aspiration (FNA) specimens. Biopsy results were classified as diagnostic (neoplastic or nonneoplastic) or nondiagnostic based on histopathology and cytology. Technical success rate and diagnostic yield of omental and mesenteric lesions were calculated. RESULTS: There were 186 image-guided percutaneous biopsies of omental (n = 95) and mesenteric (n = 91) lesions performed. Technical success rate was 99.5% for all biopsies, 100% for omental biopsies, and 98.9% for mesenteric biopsies. Overall sensitivity was 95.5%, specificity was 100%, negative predictive value was 78.3%, and positive predictive value was 100%, which was comparable for omental and mesenteric biopsies. Core biopsies had higher diagnostic yields compared with FNA: 98.4% versus 84% overall, 99% versus 88% for omental biopsies, and 97.7% versus 80% for mesenteric biopsies. Spearman rank correlation showed no correlation between lesion size and diagnostic yield (P = .14) and lesion depth and diagnostic yield (P = .29) for both groups. There were 5 complications. CONCLUSIONS: Image-guided percutaneous omental and mesenteric biopsies have high technical success rates and diagnostic yield regardless of lesion size or depth from the skin for both omental and mesenteric specimens.

Bayesian nonparametric statistics: A new toolkit for discovery in cancer research.

Many commonly used statistical methods for data analysis or clinical trial design rely on incorrect assumptions or assume an over-simplified framework that ignores important information. Such statistical practices may lead to incorrect conclusions about treatment effects or clinical trial designs that are impractical or that do not accurately reflect the investigator's goals. Bayesian nonparametric (BNP) models and methods are a very flexible new class of statistical tools that can overcome such limitations. This is because BNP models can accurately approximate any distribution or function and can accommodate a broad range of statistical problems, including density estimation, regression, survival analysis, graphical modeling, neural networks, classification, clustering, population models, forecasting and prediction, spatiotemporal models, and causal inference. This paper describes 3 illustrative applications of BNP methods, including a randomized clinical trial to compare treatments for intraoperative air leaks after pulmonary resection, estimating survival time with different multi-stage chemotherapy regimes for acute leukemia, and evaluating joint effects of targeted treatment and an intermediate biological outcome on progression-free survival time in prostate cancer.

Long-Term Outcomes Following Percutaneous Cholecystostomy Tube Placement for Treatment of Acute Calculous Cholecystitis.

INTRODUCTION: Percutaneous cholecystostomy tube (PCT) placement is considered a safe alternative to cholecystectomy for the treatment of acute calculous cholecystitis (ACC), but data regarding long-term outcomes following PCT are limited. METHODS: We retrospectively reviewed our institutional experience of patients undergoing PCT for ACC between 1997 and 2015. Recurrent biliary events were defined as cholecystitis, cholangitis, or gallstone pancreatitis. RESULTS: PCT was placed for 288 patients with ACC. Mean age and age-adjusted Charlson comorbidity index were 72 ± 15 years and 5.3 ± 2.4, respectively. Following PCT placement, 91% of patients successfully resolved their episode of ACC. PCT dysfunction occurred in 132 patients (46%), with 80 patients (28%) requiring re-intervention, while 7% developed procedure-related complications. Interval cholecystectomy reduced the risk of recurrent biliary events to 7% from 21% (p = 0.002). Cholecystectomy was completed laparoscopically in 45% of patients receiving an interval operation vs. 22% of those undergoing urgent surgery for PCT failure or recurrent biliary event (p = 0.03). CONCLUSIONS: PCT placement is a highly successful treatment for acute calculous cholecystitis and is associated with low complication rate, but high rate of tube dysfunction requiring frequent re-intervention. Interval cholecystectomy is associated with a decreased likelihood of recurrent biliary events and increased likelihood of successful laparoscopic completion.

High-Content Biopsies Facilitate Molecular Analyses and Do Not Increase Complication Rates in Patients With Advanced Solid Tumors.

PURPOSE: Precision oncology relies on frequent pathologic, molecular, and genomic assessments of tumor tissue to guide treatment selection, evaluate pharmacodynamic effects of novel agents, and determine drug resistance mechanisms. Newer forms of analyses such as drug screens in cell lines and patient-derived xenografts demand increasing amounts of tissue material. It remains unknown how the need for serial biopsies with large numbers of tumor cores relates to tissue yields and biopsy complication rates. MATERIALS AND METHODS: In this study, we performed a retrospective analysis of 199 focal liver biopsies performed in 143 patients in the setting of oncologic research protocols (research biopsy group) over a 4-year period at a single-intervention oncology service. Practice patterns and complication rates were compared with those related to 1,522 consecutive biopsies performed in 1,154 patients in whom two cores were obtained for standard clinical management of patients (standard biopsy). RESULTS: In the research biopsy group, 1,100 tissue cores (average, 5.5 cores per procedure) were harvested and distributed to trial sponsors, internal research laboratories, and pathology services. The complication rate in this cohort was 0.5% for major complications (one of 199) and 1.0% for minor complications managed conservatively (two of 199). In the standard biopsy control group, major complications were observed in 1.4% of procedures (22 of 1,522) and minor complications in 0.2% (three of 1,522). These complication rates were not statistically different. CONCLUSION: Harvesting extra tissue cores through coaxial needles during focal liver biopsies does not increase complication rates and yields valuable tissue for additional experimental testing.