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The objective of this study was to determine how thoracic surgeons manage intraoperative esophagectomy positive margins and how these decisions may relate to overall survival and progression-free survival in esophageal cancer. A survey was sent to thoracic surgeons to understand the management of intraoperative positive esophagectomy margins. Primary data at two high-volume esophageal cancer institutions from 1994 to 2017 were retrospectively reviewed to identify patients who had intraoperative positive frozen section margins during esophagectomy. Patient characteristics and survival data were collected and analyzed. Overall survival and progression-free survival were assessed using a Cox model. Eighty-five percent of thoracic surgeons responding to a survey reported the utilization of frozen pathologic evaluation during esophagectomy with attempts at re-resection to achieve negative margin. Our esophagectomy database identified 94 patients with intraoperative positive margins. Of those re-resected (n = 67, 63%), 44 patients (46.8%) were converted to R0 resections. overall survival was improved for patients in the R0 group (13 months) vs R+ group (3.4 months, P =.04). Progression-free survival was also improved between the R0 group (8.6 months) and the R+ group (2.2 months, P =.03). In a multivariable analysis for progression-free survival, margin status was an independent predictor of survival (hazard ratio 3.13, P =.03). From a thoracic surgery survey, 85% of surgeons use intraoperative frozen section margin analysis to guide surgical decision making during an esophagectomy. Analyzing patients with a positive margin discovered during esophagectomy suggests that esophageal cancer patients who can undergo re-resection to a negative margin have increased progression-free survival. The final margin appears to be related to progression-free survival. [ABSTRACT FROM AUTHOR]

Diagnostic tools for nonalcoholic fatty liver disease (NAFLD) detection and prognostication are limited, with histology remaining the criterion standard. We evaluated the feasibility and safety of EUS-guided liver biopsy (EUS-LB) sampling in NAFLD staging. In a prospective cohort of NAFLD patients with steatohepatitis and early liver fibrosis based on magnetic resonance elastography (MRE), EUS-LB sampling procedures were performed using a 22-gauge fork-tip core biopsy needle. Samples were evaluated by a blinded pathologist. Total aggregate sample length (TASL), number of complete portal triads, ability to calculate NAFLD activity score, ability to stage liver fibrosis, and ability to provide enough core liver tissue for lipidomics analysis were evaluated. Performance of EUS-LB sampling was compared with MRE. Forty-one EUS-LB samples were obtained. The median TASL was 2.4 cm (interquartile range, 2.00-2.75). The median number of complete portal triads per TASL was 26 (interquartile range, 7-62). Of the samples, 100% were adequate to convey NAFLD activity score and fibrosis stage. All samples provided enough core liver tissue to allow the application of lipidomics testing. A significant positive linear association between EUS-LB sampling–detected fibrosis and MRE-detected fibrosis was observed (r =.469, P <.005). Compared with MRE, EUS-LB sampling established early fibrosis in 13 cases that MRE classified as normal. EUS-LB sampling–related adverse events occurred in 7% and were restricted to postprocedural pain. EUS-LB sampling is a viable technique for full NAFLD evaluation and may be superior to MRE in establishing the diagnosis of nonalcoholic steatohepatitis with early fibrosis. (Clinical trial registration number: NCT02880189.) [ABSTRACT FROM AUTHOR]

Summary Hepatoblastoma is the most frequent malignant hepatic tumor in children. Expression of high mobility group AT-hook 2, an architectural nuclear factor and marker for hepatic progenitor cells, has not been studied in detail in hepatocellular neoplasms. Immunohistochemical stains using antibodies against high mobility group AT-hook 2, β-catenin, glypican-3, p53, and Ki-67 were performed in 15 hepatoblastomas, 15 fibrolamellar hepatocellular carcinomas, 34 hepatocellular carcinomas (12, ≤30 years old; 22, >30 years old), and 22 hepatic adenomas. High mobility group AT-hook 2 was expressed in all 15 hepatoblastomas, including all fetal and embryonal components, significantly higher than in 41.7% (5/12) of hepatocellular carcinomas of 30 years or younger (P = .001) and in 9% (2/22) of hepatocellular carcinomas of older than 30 years (P < .001). Aberrant β-catenin expression was detected in 80% (12/15) of hepatoblastomas, 41.6% (5/12) of hepatocellular carcinomas of 30 years or younger, and 18.2% (4/22) of hepatocellular carcinomas of older than 30 years. All 15 fibrolamellar hepatocellular carcinomas and 22 hepatic adenomas were negative for high mobility group AT-hook 2 or β-catenin. High mobility group AT-hook 2 and β-catenin expression correlated positively (P = .017; τ = 0.522) in 34 hepatocellular carcinomas. β-Catenin and glypican-3 exhibited a distinct spatial distribution within hepatoblastomas; glypican-3 was more frequently expressed in fetal components (P = .007), whereas β-catenin tended to be more frequently expressed in embryonal components (P = .062). In conclusion, high mobility group AT-hook 2 is expressed in all hepatoblastomas and could be used as a sensitive marker in their diagnosis. High mobility group AT-hook 2 was also expressed in a subset of hepatocellular carcinomas in association with β-catenin expression; this might represent a subtype of hepatocellular carcinoma with hepatic progenitor cell differentiation. [ABSTRACT FROM AUTHOR]

Glypican-3 (GPC3) is a plasma membrane-bound proteoglycan that can be overexpressed in certain malignancies but has been particularly linked to hepatocellular carcinoma (HCC). GPC3 is currently used as an immunohistochemical marker for HCC, but its expression in epithelial neoplasms of the gastrointestinal (GI) tract and pancreas, a common source of liver metastasis, has not been studied in detail. In this study, we examined GPC3 immunoreactivity in 98 neoplasms of the GI tract including 30 adenocarcinomas (ADCA), 29 squamous cell carcinomas (esophageal and anal), and 39 neuroendocrine carcinomas, and 60 neoplasms of the pancreas including 22 ADCA, 26 pancreatic neuroendocrine neoplasms, and 12 pancreatic acinar cell carcinomas. Two control groups of 32 HCCs and 16 intrahepatic cholangiocarcinomas were also stained with GPC3. Although most (7/12, 58.5%) acinar cell carcinomas were GPC3 positive, pancreatic ADCA and neuroendocrine neoplasms were GPC3 negative. In addition, 27.5%, (8/29) of squamous cell carcinomas, 20% (6/30) of ADCA, and 2.5% (1/39) of neuroendocrine carcinomas of the GI tract were immunoreactive for GPC3. HCC was positive for GPC3 in 75% (24/32) of cases but cholangiocarcinoma was negative. While significant correlation between GPC3 positivity and poor differentiation was observed in HCC only, GPC3 expression did not correlate with tumor size. In conclusion, 14% of GI tract and pancreatic carcinomas/ neoplasms (particularly pancreatic acinar cell carcinoma) can express GPC3 by immunohistochemistry. As these tumors commonly metastasize to the liver, this offers a potential pitfall in differentiating between HCC and metastatic carcinoma when evaluating tumors involving the liver. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: We sought to test the hypothesis that transcatheter hepatic artery delivery of dilute gadolinium (Gd) in rabbits can be monitored in real-time using magnetic resonance imaging (MRI). Materials and Methods: Catheters (2F) were inserted via a femoral access into the hepatic arteries of six New Zealand White rabbits under radiographic guidance. After transfer to a 1.5-T MRI scanner, 26 separate hepatic artery injections of 2 mL of 4% Gd and 14 sham injections were performed. Real-time imaging of all injections was acquired using two-dimensional projection inversion recovery-gradient echo. Films of these 40 injections, as well as 10 random repeats, were independently reviewed in a randomized, blinded fashion by two Certificate of Added Qualification–certified interventional radiologists. Observers reported (i) if Gd injection occurred and (ii) if so, the location of delivery. For each observer, we compared sensitivity/specificity for real-time visualization of contrast injection and accuracy of injection localization. Interobserver and intraobserver variability was assessed using the κ statistic. X-ray digital subtraction angiography was the gold standard for all MRI studies. Results: Both observers had a sensitivity of 100% and a specificity of 93%. Accuracy for intrahepatic contrast delivery was 77% for both observers. Accuracy for extrahepatic delivery was 92% and 96%, respectively. Both interobserver and intraobserver agreement was outstanding. Conclusions: In rabbits, MRI allows for accurate real-time monitoring of transcatheter hepatic artery delivery of contrast agent. Localization accuracy is higher outside the liver than within the liver. These results can be used as a baseline reference for comparing the accuracy of delivery of Gd-tagged therapies in the future. [Copyright &y& Elsevier]

PURPOSE: Yttrium 90 radioembolization is a transcatheter therapy for unresectable hepatocellular carcinoma (HCC) that delivers internal radiation to tumors. In contrast to the usual method of lobar regional delivery, catheter-directed computed tomographic (CT) angiography was investigated as a potentially useful technique to evaluate the administration of segmental90Y tumor radiation doses superselectively without significantly altering liver function or Child-Pugh classification. MATERIALS AND METHODS: Fourteen patients underwent 90Y therapy for unresectable HCC. After standard angiographic placement of a 3-F microcatheter in a segmental hepatic artery supplying the tumor, each patient underwent CT angiography with use of segmental hepatic artery injection of iodinated contrast agent to confirm segmental perfusion and delineate segmental liver volume. 90Y was later injected into the same segmental artery. Target dose was calculated according to infused 90Y activity and targeted hepatic volume with standard lobar volume (before CT angiography) versus segmental liver volume (after CT angiography). The Wilcoxon signed-rank test (α0.05) was used to compare the estimated 90Y dose before CT angiography with the actual 90Y dose after CT angiography, as well as changes in serum bilirubin level and Child-Pugh classification as a result of treatment. RESULTS: The mean estimated tumor dose before CT angiography (SD) was 100 Gy±43 (range, 35–169 Gy). The mean actual tumor dose after CT angiography was 348 Gy±204 (range, 105–857 Gy), which was significantly greater (P < .001). The mean bilirubin level before treatment was 1.0 mg/dL ±0.97 (range, 0.2–4.0 mg/dL), whereas the mean bilirubin level after treatment was 1.3 mg/dL ±0.85 (range, 0.5–3.8 mg/dL). This difference, although statistically significant (P=.03), was not clinically important. Thirteen of 14 patients had no change in Child-Pugh class. CONCLUSION: CT angiography can be used to delineate the blood supply and volume to a targeted hepatic segment, allowing superselective90Y radioembolization. This approach significantly increases effective 90Y tumor radiation dose without clinically altering liver function or Child-Pugh class. [Copyright &y& Elsevier]

Obese patients with nonalcoholic steatohepatitis (NASH) are at risk for cirrhosis if significant weight loss is not achieved. The single fluid-filled intragastric balloon (IGB) induces meaningful weight loss and might be used in NASH treatment. We performed an open-label prospective study to evaluate the effects of IGB placement on metabolic and histologic features of NASH. Twenty-one patients with early hepatic fibrosis (81% female; mean age, 54 years; average body mass index, 44 kg/m2) underwent magnetic resonance elastography (MRE) and endoscopic ultrasound with core liver biopsy collection at time IGB placement and removal at a single center from October 2016 through March 2018. The primary outcome measure was the changes in liver histology parameters after IGB, including change in nonalcoholic fatty liver disease activity score (NAS) and fibrosis score. We also evaluated changes in weight, body mass index, waist to hip ratio, aminotransaminases, fasting levels of lipids, fasting glucose, glycosylated hemoglobin, and MRE-detected liver stiffness. Six months after IGB, patients' mean total body weight loss was 11.7% ± 7.7%, with significant reductions in HbA1c (1.3% ± 0.5%) (P =.02). Waist circumference decreased by 14.4 ± 2.2 cm (P =.001). NAS improved in 18 of 20 patients (90%), with a median decrease of 3 points (range, 1–4 points); 16 of 20 patients (80%) had improvements of 2 points or more. Fibrosis improved by 1.17 stages in 15% of patients, and MRE-detected fibrosis improved by 1.5 stages in 10 of 20 patients (50%). Half of patients reached endpoints approved by the Food and Drug Administration of for NASH resolution and fibrosis improvement. Percent total body weight loss did not correlate with reductions in NAS or fibrosis. Other than post-procedural pain (in 5% of patients), no serious adverse events were reported. In a prospective study, IGB facilitated significant metabolic and histologic improvements in NASH. IGB appears to be safe and effective for NASH management when combined with a prescribed diet and exercise program. ClinicalTrials.gov no: NCT02880189 [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm. [ABSTRACT FROM AUTHOR]

Purpose To characterize the MRI appearance of inflammatory hepatic adenomas using hepatobiliary contrast agents. Materials and methods MRI was performed using hepatobiliary contrast agents (3 with gadobenate dimeglumine and 24 with gadoxetic acid) in 27 patients with immunohistochemistry-confirmed diagnosis of inflammatory hepatic adenoma. The appearance of the lesions on T2 and diffusion-weighted images, pre-gadolinium T1-weighted images, dynamic post-gadolinium images, and hepatobiliary phase images was assessed. Results Seven lesions (26%) showed predominant hyperenhancement on hepatobiliary phase images in comparison with adjacent hepatic parenchyma: 1 lesion showed diffuse, mildly heterogeneous hyperenhancement, and the remaining 6 lesions showed peripheral hyperenhancement and central hypoenhancement. Twenty lesions (74%) were predominantly hypoenhancing compared to adjacent liver on hepatobiliary phase images. Nine lesions showed a pattern of peripheral hyperenhancement and central hypoenhancement on hepatobiliary phase images; in 6 of these lesions a majority of the mass appeared hyperenhancing, while the remaining 3 lesions showed predominant hypoenhancement. Conclusions This investigation shows that a significant percentage of inflammatory hepatic adenomas appear isointense or hyperintense in comparison to adjacent normal liver on hepatobiliary phase images, and therefore this feature should not be used to distinguish hepatic adenomas from focal nodular hyperplasia without additional supporting evidence. [ABSTRACT FROM AUTHOR]

Background The 7th edition of the American Joint Committee on Cancer ( AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma ( ICC). The present study attempted to investigate the validity of these findings. Methods A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan- Meier estimates and log-rank tests. Results A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m2 (range: 17-46 kg/m2). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes ( P < 0.001). A negative resection margin was associated with improved survival ( P < 0.001). Conclusions The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC. [ABSTRACT FROM AUTHOR]