Multidetector computed tomography assessment of vascular involvement in perihilar cholangiocarcinoma.

BACKGROUND: In approximately 40% of patients with perihilar cholangiocarcinoma (PHC), the tumor is deemed unresectable at laparotomy, often due to vascular involvement. On imaging, occlusion, narrowing, wall irregularity and >180° tumor-vessel contact have been suggested to predict vascular involvement in patients with PHC. The objective of this study was to correlate computed tomography (CT) findings in PHC with surgical and histopathological results, in order to evaluate the accuracy of currently used CT criteria for vascular involvement. METHODS: Patients with PHC undergoing exploration in a single tertiary center (2015-2018) were included. Tumor-vessel relation of portal vein and hepatic artery on CT were scored by two independent radiologists, blinded for surgical and pathological outcomes. Intraoperative findings were scored by the surgeon in theatre or derived from operation/pathology reports. RESULTS: A total of 42 CT scans were evaluated, resulting in assessment of 115 vessels. Portal vein occlusion, narrowing and presence of an irregular wall on CT corresponded with a positive predictive value (PPV) for involvement of 100%, 83% and 75%, respectively. For the hepatic artery, PPV of occlusion and stenosis was 100%, whilst other criteria had PPV <70%. Combining potential criteria (>180° contact, narrowing, irregularity or occlusion) resulted in PPV, sensitivity and specificity of 85%, 67% and 94%, respectively, for the portal vein and 53%, 40% and 75%, respectively, for the hepatic artery. CONCLUSIONS: Prediction of vascular involvement on CT is more difficult for the hepatic artery than for the portal vein. Suggestion of hepatic artery invasion on imaging, other than occlusion or stenosis, should not preclude surgical exploration.

Resection of the Portal-Superior Mesenteric Vein in Pancreatic Cancer: Pathological Assessment and Recurrence Patterns.

OBJECTIVES: The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). METHODS: This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. RESULTS: In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. CONCLUSIONS: Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.

Quality Assessment of Gallbladder Cancer Pathology Reports: A Dutch Nationwide Study.

Adequate reporting of pathological findings is essential for optimal patient management and to perform high-quality research. The aim of this study was to assess the completeness of pathology reports of gallbladder cancer (GBC) at the nationwide level to assess guideline adherence and make recommendations for improvement. A retrospective population-based cohort of GBC patients diagnosed in the Netherlands from 2000 to 2019 was collected using data from the Dutch Cancer Registry and the nationwide network and registry of histology. Pathology reports were scored on the presence and content of essential and optional items according to the Dutch consensus-based guideline on biliary tract cancer. By histopathological review of cases, we compared findings with the conclusion of the corresponding pathology report. All pathology reports (n = 849) had a narrative, nonstructured format. Overall completeness was low. Information on key prognostic factors, such as tumor side (hepatic vs. serosal), status of cystic duct and liver surgical margins and venous and perineural invasion, was frequently lacking (80%, 23%, 59%, 74% and 74% missing, respectively). Whereas certain items were often missing from the report, they could be retrospectively detected in a substantial proportion of cases during pathology review (n = 738). In conclusion, significant improvements could be made in the reporting of GBC in the Netherlands. Synoptic reporting could greatly enhance the completeness of reports, as already demonstrated for tumor types.

Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course.

BACKGROUND & AIMS: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. METHODS: Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. RESULTS: A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (±SD) age of 45.0 ± 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. CONCLUSIONS: Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines.

Assessment of Imaging Modalities Against Liver Biopsy in Nonalcoholic Fatty Liver Disease: The Amsterdam NAFLD-NASH Cohort.

BACKGROUND: Noninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD. PURPOSE: To examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores. STUDY TYPE: Prospective, cohort. POPULATION: Thirty-seven patients with NAFLD. FIELD STRENGTH/SEQUENCE: Multiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi-echo stimulated-echo acquisition mode, magnitude-based and three-point Dixon using a two-dimensional multi-echo gradient echo, MR elastography (MRE) using a generalized multishot gradient-recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single-shot echo-planar sequence. ASSESSMENT: Histological steatosis grades were compared to proton density fat fraction measured by MRS (PDFFMRS ), magnitude-based MRI (PDFFMRI-M ), and three-point Dixon (PDFFDixon ), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH). STATISTICAL TESTS: Spearman's rank test, Kruskal-Wallis test, Dunn's post-hoc test with Holm-Bonferroni P-value adjustment, receiver operating characteristic curve analysis. A P-value <0.05 was considered statistically significant. RESULTS: Histological steatosis grade correlated significantly with PDFFMRS (rs  = 0.66, P < 0.001), PDFFMRI-M (rs  = 0.68, P < 0.001), and PDFFDixon (rs  = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (rs  = 0.55, P < 0.001, rs  = -0.40, P = 0.016, rs  = -0.37, P = 0.027, respectively) and fibrosis (rs  = 0.55, P < 0.001, rs  = -0.46, P = 0.0051; rs  = -0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area-under-the-curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively). DATA CONCLUSION: Multiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: 2.

Surgical management and pathological assessment of pancreatoduodenectomy with venous resection: an international survey among surgeons and pathologists.

BACKGROUND: The aim of this survey was to gain insights in the current surgical management and pathological assessment of pancreatoduodenectomy with portal-superior mesenteric vein resection (VR). METHODS: A systematic literature search was performed to identify international expert surgeons (N = 150) and pathologists (N = 40) who published relevant studies between 2009 and 2019. These experts and Dutch surgeons (N = 17) and pathologists (N = 20) were approached to complete an online survey. RESULTS: Overall, 76 (46%) surgeons and 37 (62%) pathologists completed the survey. Most surgeons (71%) estimated that preoperative imaging corresponded correctly with intraoperative findings of venous involvement in 50-75% of patients. An increased complication risk following VR was expected by 55% of surgeons, mainly after Type 4 (segmental resection-venous conduit anastomosis). Most surgeons (61%) preferred Type 3 (segmental resection-primary anastomosis). Most surgeons (75%) always perform the VR themselves. Standard postoperative imaging for patency control was performed by 54% of surgeons and 39% adjusted thromboprophylaxis following VR. Most pathologists (76%) always assessed tumor infiltration in the resected vein and only 54% of pathologists always assess the resection margins of the vein itself. Variation in assessment of tumor infiltration depth was observed. CONCLUSION: This international survey showed variation in the surgical management and pathological assessment of pancreatoduodenectomy with venous involvement. This highlights the lack of evidence and emphasizes the need for research on imaging modalities to improve patient selection for VR, surgical techniques, postoperative management and standardization of the pathological assessment.

Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.

Overtreatment of Nonneoplastic Gallbladder Polyps due to Inadequate Routine Ultrasound Assessment.

BACKGROUND: The primary aim was to assess the diagnostic accuracy of routine ultrasound assessment for gallbladder polyps. The secondary aim was to identify the characteristics that differentiate neoplastic polyps from nonneoplastic polyps. METHODS: A total of 156 patients with histopathologically proven gallbladder polyps in 4 Dutch hospitals between 2003 and 2013 were included. Sensitivity and specificity of ultrasound for polyp size, number of polyps, and polyp type were assessed using histopathological findings as a reference standard. In addition, diagnostic accuracy of sonographic size ≥1 cm for neoplasia was assessed. Subgroup analysis for patients with polyps as primary indication for cholecystectomy was performed. The sonographic polyp characteristics on preoperative routine ultrasound were described. RESULTS: Fifty-six percent of gallbladder polyps were preoperatively identified on ultrasound, of which 31% were neoplastic. Sensitivity and specificity of ultrasound to estimate polyp size were 93 and 43% (subgroup; 92 and 33%). Sensitivity and specificity of sonographic polyp size ≥1 cm for neoplasia were 86 and 32% (subgroup; 94 and 26%). No specific sonographic characteristics for neoplastic polyps could be established due to lack of reporting. CONCLUSION: Routine ultrasound assessment of polyps is associated with overestimation of polyp size and low specificity of sonographic size ≥1 cm for neoplasia, which contributes to surgical overtreatment of nonneoplastic polyps.

Scintigraphic liver function and transient elastography in the assessment of patients with resectable hepatocellular carcinoma.

BACKGROUND: Hepatobiliary scintigraphy (HBS) is used to quantify total and regional liver function. Transient elastography (TE) provides a non-invasive alternative to percutaneous biopsy to assess liver fibrosis and cirrhosis. This study aims to determine the correlation between HBS and histopathology of liver parenchyma, and to compare these with TE in patients with resectable hepatocellular carcinoma (HCC). METHODS: Patients who underwent surgery for HCC between 2000 and 2016 after preoperative HBS were included. Non-tumorous liver tissue was evaluated for inflammation, steatosis, ballooning, siderosis and fibrosis. Correlation analysis was performed between HBS results and histopathological scoring. These were also compared with TE and surgical outcomes. RESULTS: 71 patients underwent preoperative HBS of whom 24 also had TE. HBS correlated with portal and lobular inflammation as well as fibrosis. TE correlated with portal and lobular inflammation, ballooning and fibrosis. A significant correlation was found between HBS and TE. No association was found with overall postoperative morbidity and mortality. CONCLUSION: HBS and TE show a moderate to strong correlation. HBS and TE share discriminatory features of histopathological scoring and show a weak to moderate correlation with hepatic inflammation and fibrosis.

Dilemmas for the pathologist in the oncologic assessment of pancreatoduodenectomy specimens : An overview of different grossing approaches and the relevance of the histopathological characteristics in the oncologic assessment of pancreatoduodenectomy specimens.

A pancreatoduodenectomy specimen is complex, and there is much debate on how it is best approached by the pathologist. In this review, we provide an overview of topics relevant for current clinical practice in terms of gross dissection, and macro- and microscopic assessment of the pancreatoduodenectomy specimen with a suspicion of suspected pancreatic cancer. Tumor origin, tumor size, degree of differentiation, lymph node status, and resection margin status are universally accepted as prognostic for survival. However, different guidelines diverge on important issues, such as the diagnostic criteria for evaluating the completeness of resection. The macroscopic assessment of the site of origin in periampullary tumors and cystic lesions is influenced by the grossing method. Bi-sectioning of the head of the pancreas may offer an advantage in this respect, as this method allows for optimal visualization of the periampullary area. However, a head-to-head comparison of the assessment of clinically relevant parameters, using axial slicing versus bi-sectioning, is not available yet and the gold standard to compare both techniques prospectively might be subject of debate. Further studies are required to validate the various dissection protocols used for pancreatoduodenectomy specimens and their specific value in the assessment of pathological parameters relevant for prognosis.

A comparative study of diagnostic scoring systems for autoimmune pancreatitis.

OBJECTIVE: Several diagnostic scoring systems for autoimmune pancreatitis (AIP) have been proposed including the Asian, HISORt (Histology, Imaging, Serology, Other organ involvement and Response to therapy), and International Consensus Diagnostic Criteria (ICDC), which have been compared by a few studies. We evaluated the diagnostic performance of these criteria in patients diagnosed with AIP between May 1992 and August 2011. METHODS: Scoring systems were applied retrospectively using data obtained in the initial evaluation period, before pancreatic resection was performed. RESULTS: One hundred fourteen cases with AIP were included. Eighty-two percent met the diagnostic criteria for AIP according to either the Asian, HISORt, or ICDC criteria. Only 33% met the Asian criteria, probably mainly related to a low rate of diagnostic pancreatography. In 18%, all scoring systems failed to confirm the diagnosis, even though these patients were considered to have a firm diagnosis of AIP. CONCLUSIONS: In this cohort of AIP patients, the 3 major diagnostic scoring systems for AIP proved to be complementary rather than overlapping. Our data indicate that one-fifth of our AIP patients do not meet any of these scoring systems. The ICDC, Asian, and HISORt criteria should be considered as useful clinical tools but not as criterion standard for the diagnosis.

Comparison of macroscopic pathology measurements with magnetic resonance imaging and assessment of microscopic pathology extension for colorectal liver metastases.

PURPOSE: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. METHODS AND MATERIALS: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. RESULTS: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r(s) = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r(s) = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r(s) = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r(s) = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. CONCLUSIONS: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.