Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation.

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers.

Xanthogranulomatous inflammation of terminal ileum: report of a case with small bowel involvement.

Xanthogranulomatous inflammation is a rare pathological condition most frequently detected in the kidney and gallbladder. Reported herein is a case of xanthogranulomatous inflammation in a 51-year-old male presenting as a mass-forming lesion in the terminal ileum with mucosal ulceration. Diagnostic laparoscopy followed by ileocecectomy was performed due to intra-operative suspicion of carcinoma of appendix. This is a report of the condition involving the terminal ileum with mucosal ulceration and full-thickness involvement of bowel wall which are uncommon features of xanthogranulomatous inflammation in previously reported lower gastro-intestinal tract lesions.

A case of IgG4-related disease manifesting as a spinal epidural mass.

IgG4-related disease is an immune-mediated fibroinflammatory condition. Isolated manifestation in the spine as hypertrophic pachymeningitis is very rare and the mass-like lesion on MRI often mimic tumour or infection. Patients would present with symptoms that result from mass effect or neurovascular compression. Studies showed that serum and CSF IgG4 levels are rarely informative, and therefore, tissue biopsy is crucial for accurate diagnosis. Apart from supporting the diagnosis, MRI is helpful in delineating the extent of disease and follow-up after treatment. A 18F-FDG PET/CT scan is useful in detecting systemic manifestations of IgG4-related disease. Although IgG4-related disease generally responds well to corticosteroid at inflammatory state, relapse is not uncommon. Current treatment strategies for IgG4-related hypertrophic pachymeningitis are high dose corticosteroid therapy and early decompressive surgery to avoid chronic neurological complications. We described a case of a 27-year-old gentleman complaining of lower limb weakness and numbness. MRI showed a mass-like epidural lesion at the thoracic spine causing cord compression. Open biopsy of the epidural mass demonstrated histopathological characteristics of IgG4-related disease. Patient responded well to early surgical decompression of the spinal cord and corticosteroid as evidenced by symptom improvement and resolving mass on subsequent MRI study. However, a follow-up MRI revealed disease recurrence years later.

Hepatic steatosis estimated microscopically versus digital image analysis.

BACKGROUND & AIMS: Evaluate in liver biopsies: (i) interobserver agreement of estimates of fat proportionate area (eFPA) and steatosis grading, (ii) the relationship between steatosis grades and measured fat proportionate area (mFPA, digital image analysis), (iii) the accuracy of eFPA, (iv) to present images to aid standardization and accuracy of eFPA. METHODS: Twenty-one liver biopsies were selected from the Royal Free Hospital (RFH) histopathology archive to represent the full range of histopathological steatosis severity. As many non-overlapping fields of parenchyma as possible were photographed at ×20 objective magnification from the biopsies (n = 651). A total of 15 sample images were selected to represent the range of steatosis seen. Twelve hepatopathologists from 11 sites worldwide independently evaluated the sample images for steatosis grade [normal (none)/mild/moderate/severe], and eFPA (% area of liver parenchyma occupied by fat). RESULTS: The hepatopathologists had good linear correlation between eFPA and mFPA for sample images (r = 0.924, P < .001) and excellent concordance (kappa = 0.91, P < 0.001). Interobserver concordance of steatosis grade showed 'substantial agreement' (kappa = 0.64). There was significant difference between eFPA and mFPA in the sample images for mild, moderate and severe steatosis (P = 0.024, P < 0.001, P < 0.001 respectively): the observers consistently over-estimated the eFPA. CONCLUSION: Hepatopathologists showed 'excellent' interobserver agreement in eFPA and 'substantial' agreement in assigning steatosis grade (precision was high). However, compared with mFPA, eFPA was inaccurate. eFPA systematically exceeds mFPA; generally the overestimation increases with severity of steatosis. Considering that non-invasive technologies for estimating liver fat utilize histopathology as reference, such assessments would benefit from quantitative validation of visually estimated microscopic liver fat percentages.

Hepatolithiasis and the syndrome of recurrent pyogenic cholangitis: clinical, radiologic, and pathologic features.

Primary hepatothiasis (HL) and recurrent pyogenic cholangitis (RPC) are two terms describing the different aspects of the same disease, with HL emphasizing the pathologic changes and RPC emphasizing the clinical presentation and suppurative inflammation. It is predominantly a disease of the Far East. In the 1960s, it was the third most common cause of emergency abdominal surgery at a university hospital in Hong Kong. Thereafter, its incidence has decreased considerably, possibly due to improved standards of living and Westernized diet. Clinically, patients may present acutely with recurrent bacterial cholangitis and its possible complications, such as liver abscess and septicemic shock, or with chronic complications, such as cholangiocarcinoma. Pathologically, it is characterized by pigmented calcium bilirubinate stones within dilated intrahepatic bile ducts featuring chronic inflammation, mural fibrosis, and proliferation of peribiliary glands, without extrahepatic biliary obstruction. Episodes of suppurative inflammation cumulate in sclerosing cholangitis of peripheral ducts and parenchymal fibrosis resulting from collapse and scarring. Mass-forming inflammatory pseudotumor and neoplasms like intraductal papillary neoplasms and cholangiocarcinoma are increasingly recognized complications. Modern imaging techniques allow definitive diagnosis, accurate assessment for treatment planning, and detection of complications. A multidisciplinary team approach (interventional endoscopist, interventional radiologist, hepatobiliary surgeon, and intensivists) is important for optimal patient outcome.

Primary hepatolithiasis, recurrent pyogenic cholangitis, and oriental cholangiohepatitis: a tale of 3 countries.

Primary hepatolithiasis (HL), recurrent pyogenic cholangitis, and oriental cholangiohepatitis are terms commonly used in Japan, Hong Kong, and Korea respectively, and describing the different aspects of the same disease, with "HL" indicating the pathologic changes, "recurrent pyogenic cholangitis" emphasizing the clinical presentation and suppurative inflammation, and "oriental cholangiohepatitis" highlighting its ethnic preference and mysterious nature. HL is predominantly a disease of the far east and shows great regional differences in the incidence and the type of intrahepatic stones. Pathologically, it is characterized by pigmented calcium bilirubinate stones within dilated intrahepatic bile ducts featuring chronic inflammation, mural fibrosis, and proliferation of peribiliary glands, without extrahepatic biliary obstruction. Episodes of suppurative inflammation cumulate in sclerosing cholangitis in peripheral ducts and parenchymal fibrosis from scarring and collapse. Mass-forming inflammatory pseudotumor and neoplasms-like intraductal papillary neoplasms and cholangiocarcinoma are increasingly recognized complications. Bacterial infection and dietary factors are believed to be important in the formation of pigment stones within intrahepatic bile ducts, whereas parasitic infestation is likely coincidental. With improvement of environmental conditions and westernization of diet, the incidence of pigment stones has decreased. At the same time, cholesterol stones with milder clinical manifestations and pathologic changes are increasingly recognized, and for which stone dissolution therapy can be considered. Understanding the underlying pathology avoids confusion with other diseases more prevalent in the western world, and allows correct selection of the appropriate treatment.

Dejian mind-body intervention on depressive mood of community-dwelling adults: a randomized controlled trial.

The present study evaluated the effectiveness of a short-term mind-body intervention program on improving the depressive mood of an adult community sample. Forty adult volunteers with various degrees of depressive mood were randomly assigned to the experimental group (Dejian Mind-Body Intervention, DMBI) and control group (Cognitive-Behavioral Therapy, CBT). For each group, a total of four 90-min weekly sessions were conducted. Treatment-related changes were measured using the Beck Depression Inventory (BDI-II), an electroencephalographic indicator of positive affect (i.e., prefrontal activation asymmetry), and self-report ratings on physical health. Results indicated that both the DMBI and the CBT group demonstrated significant reduction in depressive mood. However, among individuals with moderate to severe depressive mood at baseline, only those in the DMBI but not the CBT group showed significant reduction in depressive mood. Besides, only the DMBI group demonstrated a significant increase in prefrontal activation asymmetry, suggesting increase in positive affect. While most psychological therapies for depressive mood normally take several months to show treatment effect, the present findings provided initial data suggesting that the DMBI was effective in improving depressive mood of community adults after 1 month of training.

ERp57 is up-regulated in free fatty acids-induced steatotic L-02 cells and human nonalcoholic fatty livers.

Pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not clear. In this study we aimed to identify proteins involved in NAFLD development in free fatty acids (FFA)-induced hepatosteatotic cells and in human liver biopsies. Steatosis was induced by incubating a normal human hepatocyte-derived cell line L-02 with FFA. Differentially expressed proteins in the steatotic cells were analyzed by two-dimensional gel electrophoresis-based proteomics. Involvement of one of the up-regulated proteins in steatosis was characterized using the RNA interference approach with the steatotic cells. Protein expression levels in liver biopsies of patients with NAFLD were assessed by immunohistochemistry. Proteomic analysis of L-02 steatotic cells revealed the up-regulation of ERp57, a condition not previously implicated in NAFLD. Knockdown of ERp57 expression with siRNA significantly reduced fat accumulation in the steatotic cells. ERp57 expression was detected in 16 out of 17 patient biopsies and correlated with inflammation grades or fibrosis stages, while in 5 normal biopsies ERp57 expression was not detectable in hepatocytes. In conclusion, ERp57 was up-regulated in FFA-induced steatotic hepatic cells and in NAFLD patient livers and demonstrated steatotic properties in cultured cells. Further investigations are warranted to verify the involvement of ERp57 in NAFLD development.

Paired donor interchange to avoid ABO-incompatible living donor liver transplantation.

We report an emergency paired donor interchange living donor liver transplant performed on January 13, 2009. The 4 operations (2 liver transplants) were performed simultaneously. The aim was to avoid 2 ABO-incompatible liver transplants. One recipient in acute liver failure underwent transplantation in a high-urgency situation. The abdomen of the other recipient had severe adhesions from previous spontaneous bacterial peritonitis that rendered the recipient operation almost impossible. The ethical and logistical issues are discussed. Approaches adopted in anticipation of potential adverse outcomes are explained in view of the higher donor and recipient mortality and morbidity rates in comparison with kidney transplantation.

Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement.

Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice.

Bioavailable testosterone is associated with a reduced risk of amnestic mild cognitive impairment in older men.

OBJECTIVE: We investigated the risk of amnestic mild cognitive impairment (aMCI) in relation to serum bioavailable (BT) and total testosterone (TT) levels in older men. DESIGN, SETTING AND SUBJECTS: A cross-sectional study in an ambulatory setting, with older men aged 55-93 years with normal cognition, aMCI and Alzheimer's disease (AD). MEASUREMENTS: Morning serum BT and TT levels were determined. AD was diagnosed by the Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and aMCI by the Petersen criteria. RESULTS: We recruited 203 Chinese older men (48 aMCI, 66 AD and 89 with normal cognition). Mean serum BT, but not TT, levels were significantly lower in the aMCI (mean BT +/- SEM 1.06 +/- 0.10 nmol/l) and AD (0.99 +/- 0.08 nmol/l) groups than in the normal controls (1.82 +/- 0.12 nmol/l) (P < 0.001, one-way anova) with no significant difference between the aMCI and AD groups. After adjustment for education, age and apolipoprotein E (apoE) genotype, logistic regression analyses showed that the serum BT level [adjusted odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.32-0.85] was an independent protective factor for aMCI. For the combined outcome of aMCI and AD, the serum BT level was an independent protective factor but age and apoE epsilon4 were independent risk factors. There was no interaction between BT and age. CONCLUSIONS: In older men, serum BT, but not TT, levels were associated with a lower risk of aMCI and AD.

Calcification of a hydrophilic acrylic intraocular lens: clinicopathological report.

A 72-year-old man who had phacoemulsification with implantation of an Akreos Adapt Advanced Optics (AO) IOL in the left eye complained of blurring vision 4 months postoperatively. Multiple fine white granules were found within the IOL. Intraocular lens exchange was performed at 7 months, and the explanted IOL was sent for histopathological analysis. Diffuse fine white granules were seen within the explanted IOL material just beneath the surface; they were stained positive by alizarin red and the von Kossa method. Scanning electron microscopy confirmed the presence of calcium deposits in the IOL material. Blood and aqueous were drawn from the patient for biochemical analysis, and the results were normal. We believe this is the first clinicopathological report of calcification of the Akreos Adapt AO IOL.

Acute-on-chronic liver failure 2018: a need for (urgent) liver biopsy?

INTRODUCTION: 'Acute-on-Chronic-Liver Failure (ACLF)' entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis.

Biliary Adenofibroma of Liver: Morphology, Tumor Genetics, and Outcomes in 6 Cases.

Biliary adenofibroma is a rare primary hepatic neoplasm, recognized in the World Health Organization classification, although only 14 cases have been reported to date. This series includes extended follow-up from 2 of the early case reports and 4 novel cases. Clinical history and histology were reviewed in all 6 cases. Tumor DNA was analyzed for point mutations by multiplex polymerase chain reaction and copy number alterations by array comparative genomic hybridization. The patients included 4 females and 2 males presenting between 46 and 83 years of age, with tumors ranging from 7 to 16 cm in diameter. The tumors had similar morphology, with tubules and cysts lined mainly by bland to mildly atypical cuboidal epithelium embedded in fibrous stroma. Multiplex polymerase chain reaction did not identify mutations in 4 tumors tested. Three tumors tested by array comparative genomic hybridization showed chromosomal copy number alterations, including 1 with amplifications of CCND1 and ERBB2. Three patients underwent resection with no recurrence at 21, 20, and 3 years of follow-up. One patient is alive after 14 months with no resection. Two patients with margin-positive resections had local recurrence at 1 and 6 years after surgery. No patient had distant metastasis. The distinct morphology and multiple clonal cytogenetic alterations in biliary adenofibromas indicate that the lesions are neoplastic. Amplifications of CCND1 and ERBB2 are not typical of benign neoplasms, and suggest that these tumors may have the ability to behave aggressively. However, the clinical outcomes in these patients suggest the neoplasms are only slowly progressive.

Instability of clonality in gastric lymphoid infiltrates: a study with emphasis on serial biopsies.

The evolution of low-grade B-cell mucosa-associated lymphoid-tissue (MALT) lymphoma of the stomach is a multistage process, reflected in the histologic continuum from Helicobacter pylori-chronic gastritis, to low-grade and high-grade lymphoma. Interestingly, in daily gastric biopsy sign-out, the authors observed that some biopsies showed monoclonality on polymerase chain reaction (PCR) even though there were no definite histologic features of malignancy and vice versa. To address the question, the authors studied the endoscopic gastric biopsies at first presentation of 46 patients to examine any clonality differences among various histologic patterns within the spectrum of MALT lymphoma evolution. The gastric biopsies were reviewed histologically and graded according to the Wotherspoon-Isaacson histologic scoring system from grade 0 (normal) to grade 5 (MALT lymphoma). The clonality of cases in each grade was determined by performing nested PCR for immunoglobulin heavy chain (IgH) gene rearrangement using FR2/JH and FR3/JH primer sets. The monoclonality rates among different grades were as follows: grade 2, 6.3% (1 of 16); grade 3, 27.3% (3 of 11); grade 4, 83.3% (5 of 6); grade 5, 69.2% (9 of 13). Statistically significant difference of monoclonality rate is demonstrated in histologic grade 4 versus grades 2 and 3, and grade 5 versus grade 2 (P < 0.05, Fisher exact test). The authors went on to examine the progress of disease by following up the clinical status, histologic changes, and clonality fluctuation of these cases. Four of the 8 patients with monoclonality on PCR, but no definite lymphoma at first presentation later progressed to frank MALT lymphoma. Our study shows that, during the progression to MALT lymphoma, there is an instability of clonality. Clonality can fluctuate between polyclonality, oligoclonality, and monoclonality, none of which defines an irreversible stage for progression to MALT lymphoma. Monoclonality is a risk factor for development of MALT lymphoma. Those cases with dense gastric mucosal lymphoid infiltrate (without definite MALT lymphoma) and monoclonality on PCR need to be closely monitored and Helicobacter infection promptly treated if present. In combination with clinicohistologic examination, PCR can serve as a complementary tool in arriving at a definite diagnosis of MALT lymphoma in cases with borderline histologic features.

Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer.

AIM: The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC). METHOD: Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS, PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival. RESULT: Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the genes tested, only KRAS mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup of patients who received cetuximab-based therapy in the first-line setting, KRAS mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi-square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant cases was too small to allow any statistical analysis. CONCLUSION: The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with reports from non-Asian populations, and KRAS mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.

Beyond "cirrhosis": a proposal from the International Liver Pathology Study Group.

"Cirrhosis" is a morphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.

Inter- and intra-observer concordance of cyberpathology in twenty-five cases.

To study the feasibility of anatomical pathology consultation in cyberspace (cyberpathology) and to determine inter- and intra-observer concordance. Twenty-five consecutive cytology and histopathology cases are photographed using a digital camera placed against the eyepiece, and uploaded to an image-server in the Internet. Participants view the images, rate their confidence, and provide a diagnosis. They then view the original glass slides and provide a final diagnosis. The diagnoses are compared for inter- and intra-observer concordance. Participants are confident of their diagnoses based on viewing images on the Internet. The intra-observer concordance exceeds 95% individually, and 96% overall. Inter-observer concordance was 100% in a subset of cases. Cyberpathology as described is both available and affordable and is a valid alternative to slide-based anatomic pathology consultation.

Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria.

Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN) were proposed using the livers of patients with hepatolithiasis. We report herein an international interobserver agreement study on the diagnosis of biliary non-invasive neoplastic lesions with the goal to obtain a consensus on the terminology and grading. Seventeen pathologists from the United States, Europe and Asia participated in this study. They shared a digital file containing histological pictures of 30 foci of non-invasive neoplastic lesions selected from the biliary system of patients suffering from primary sclerosing cholangitis, choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN was classified into three categories based on the degree of atypia: BilIN-1, BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of BilIN and the three-grade classification system. Interobserver agreement on the diagnosis was moderate (kappa-value=0.45). On the basis of the suggestions and opinions obtained from the 17 participants, the original criteria for BilIN were revised. We now propose a new consensus classification of BilIN that may assist in allowing a more uniform terminology for the diagnosis of biliary non-invasive neoplastic lesions. This classification should help to advance clinical and research applications.