Inflammatory responses to Opisthorchis viverrini infection in animal models: A comparison between susceptible and nonsusceptible hosts in different anatomical locations.

Background: Inflammation caused by Opisthorchis viverrini infection increases the risk of cholangitis, cholecystitis, and leads to bile duct cancer (cholangiocarcinoma or CCA). However, only certain infected individuals are susceptible to CCA, suggesting the involvement of host factors in cancer development. In addition, there are reports indicating differences in the locations of CCA. Aim: This study aims to investigate cellular inflammatory responses in the common bile duct (CB), intrahepatic bile duct (IHB), and gallbladder (GB) in susceptible and non-susceptible hosts following O. viverrini infection. Methods: Thirty Syrian golden hamsters (a susceptible host) and 30 BALB/c mice (a non-susceptible host) infected with O. viverrini were studied at six time points (five animals per group). Histopathological evaluations were conducted on samples from the IHB, CB, and GB. Inflammatory cell infiltration was quantitatively assessed and compared between groups and time points. Statistical analysis was performed using one-way ANOVA, with a significance level of p < 0.05. Results: Inflammation was significantly more pronounced in the IHB compared to the other two biliary locations. In comparison between susceptible and non-susceptible hosts, the intensity of inflammation was higher in the OV+H group than in the OV+M group (p < 0.05). Conclusion: This study highlights the association between host response to inflammation, tissue location, and host susceptibility, with the IHB showing particular susceptibility to inflammation and pathological changes. These findings contribute to our understanding of the increased risk of CCA in susceptible hosts.

Jaundice caused by primary common bile duct lymphoma of a cat.

A 10-year-old American Shorthair cat presented with anorexia and jaundice, and echogenic evaluation revealed diffuse thickening of the common bile duct (CBD) wall. An exploratory laparotomy was conducted, the lesion was evaluated as difficult to remove, and the cat was euthanized and autopsied. Histologically, round neoplastic cells proliferated in the mucosa of the CBD and infiltrated the hepatic lobe, pancreas, and duodenum. Immunohistochemistry revealed that the neoplastic cells were positive for cytoplasmic-CD3 and granzyme B, and TCR-gamma clonal rearrangement was detected. Based on these findings, the neoplasia was diagnosed as a primary CBD lymphoma originating from cytotoxic T or natural killer cells. To the best of our knowledge, this is the first reported case of feline primary CBD lymphoma. Although rare, lymphoma of the CBD should be considered in cats with jaundice and thickening of the CBD.

Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts.

Background: Individual host susceptibility is believed to be a risk factor in the interaction between the host and the parasite. Since studying time series in humans is limited, animal models are replaced. Aim: This study aims to explore and compare the pattern of inflammatory cell types along the biliary tract and their association with proliferative lesions in the early development of cholangiocarcinoma from susceptible and nonsusceptible animal models. Methods: Thirty male Syrian golden hamsters and 30 BALB/c mice, serving as the susceptible and nonsusceptible animal models, were used in this comparative study. The animals were infected with 50 Opisthorchis viverrini metacercariae via gastric intubation. At days 1, 2, 7, 14, 28, and 56 postinfection (p.i.), five animals were randomly selected from each group and humanely sacrificed. The hepatobiliary tissues were collected and processed for histopathological study. Histochemical and immunohistochemical staining were applied to differentiate the inflammatory cell types. Kruskal-Wallis and Mann-Whitney tests were applied to assess all semi-quantitative and quantitative variables. The correlation between each variable was also analyzed using Spearman rank at a p-value < 0.05. Results: The results demonstrated that mice had different patterns of infiltrating cell types when compared to hamsters. This suggested that the cellular response to the infection in mice occurred earlier than that in hamsters. The response in mice reached its peak at D7 to D14 and then rapidly declined at D28. In contrast, although the inflammatory response in hamsters started slowly, the response reached the peak at D28 and maintained a high level until D56. Significant differences in the number of inflammatory cells between mice and hamsters were seen at D1 (p = 0.047), D7 (p = 0.049), D28 (p = 0.040), and D56 (p < 0.040). Conclusion: The inflammatory responses to O. viverrini infection in the nonsusceptible animal model occurred and declined earlier while the response in the susceptible animal model occurred later in a gradual manner. Both rodents are suitable animal models for the studies of opisthorchiasis susceptibility.

Cystadenocarcinoma of the intrahepatic bile duct in a dog.

A 14-year-old spayed female Shih-Tzu was referred to the Veterinary Medical Teaching Hospital of Konkuk University for evaluation of an abdominal mass. In diagnostic imaging, two large cystic masses were identified. The affected liver lobes were surgically resected, and the specimens were submitted for histopathological evaluation and immunohistochemical staining. The two cystic lesions were diagnosed as biliary cystadenocarcinoma (BCAC). Recurrence and regional invasion were identified on ultrasonography 36 days postoperatively. The patient died on postoperative day 271. To the best of our knowledge, previously reported case studies of BCAC in dogs presented limited clinical information. In this report, we present a detailed picture comprising a range of clinical information and histopathological examination of BCAC in a dog.

Clinical, diagnostic, and pathologic features and surgical outcomes of combined hepatocellular-cholangiocarcinoma in dogs: 14 cases (2009-2021).

OBJECTIVE: To describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine combined hepatocellular-cholangiocarcinoma (cHCC-CCA). ANIMALS: 14 privately owned dogs that underwent surgical treatment. PROCEDURES: The medical records, including signalment, clinical signs, blood test, urine analysis, computed tomography (CT) findings, intraoperative findings, and pathological findings, were retrospectively reviewed in the dogs with cHCC-CCA. RESULTS: Of 306 dogs that underwent surgical removal of hepatic masses, 14 dogs (4.6%) were pathologically confirmed to have cHCC-CCA. Median age and body weight were 11.3 years and 7.3 kg, respectively. There were no specific clinicopathological findings for cHCC-CCA. CT revealed a massive hepatic mass in all dogs and the inclusion of cyst-like lesions within the mass in 13 dogs. Intrahepatic metastases were found at time of surgery in 2 dogs (14.3%). Of the residual 12 dogs, 1 dog showed postoperative formation of intrahepatic nodules suggestive of metastases and another had intrahepatic and pulmonary nodules and a forelimb skin mass, suggesting postoperative metastases. The median survival time of the patients with cHCC-CCA was 700 days (range, 10 to 869 days) after surgery. CLINICAL RELEVANCE: To the authors' knowledge, this is the first study to describe the clinical, diagnostic, and pathological features and postoperative prognosis of canine cHCC-CCA. The clinical and diagnostic features of canine cHCC-CCA might be more similar to those of HCC rather than to those of CCA, but the preoperative diagnosis differentiating between HCC and cHCC-CCA was challenging. Our study suggests that the postoperative prognosis of canine patients with cHCC-CCA is similar to that of dogs with HCC.

Metastatic cholangiocarcinoma mimicking tuberculosis in a cow.

Here we describe a metastatic hepatic cholangiocarcinoma (cholangiocellular carcinoma) in a 14-y-old Beefmaster cow that was euthanized because of depression and progressive weight loss. Gross changes included coalescing, white-to-yellow, firm-to-hard nodules with central areas of necrosis and mineralization that effaced much of the hepatic parenchyma, omentum, mesentery, ruminal serosa, and diaphragm. A fresh sample of a hepatic nodule was submitted for a modified acid-fast (MAF) stain during autopsy to rule out tuberculosis. The MAF stain was inconclusive, and the sample was subsequently submitted for a PCR assay for Mycobacterium spp. Histologically, all nodules consisted of a neoplastic proliferation of epithelial cells surrounded by extensive areas of desmoplasia, consistent with a metastatic cholangiocarcinoma. PCR for Mycobacterium spp. was negative. Although the histologic diagnosis in our case was metastatic hepatic cholangiocarcinoma, gross changes were strikingly similar to those described in cases of tuberculosis, highlighting the need to remain vigilant in the identification of zoonotic and suspected foreign animal diseases during autopsy to protect human health.

Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms.

Pathological and immunohistochemical aspects of primary hepatobiliary neoplasms in cats / Aspectos patológicos e imuno-histoquímicos de neoplasias hepatobiliares primárias em gatos

Primary hepatobiliary neoplasms (PHN) are uncommon in cats, and originate in hepatocytes, intra- and extrahepatic bile ducts, mesenchymal cells, and cells of neuroendocrine origin. The aim of this study was to determine the frequency of PHN in cats diagnosed in the metropolitan region of Porto Alegre (RS), Brazil, for a period of 17 years, determining their epidemiological, anatomopathological and immunohistochemical aspects. Necropsy reports of 2.090 cats were analyzed, 125 were diagnosed with primary hepatobiliary diseases, of which 15 were cases of PHN, representing 12% of the specific hepatobiliary conditions and 0.7% of the necropsies. All PHN were malignant, of which 93.3% had epithelial origin and 6.7% presented mesenchymal origin. Cholangiocarcinoma was the most commonly diagnosed neoplasm, followed by hepatocellular carcinoma and hemangiosarcoma. In general, cats with no defined breed were the most affected. Concerning sex, 60% were females and 40% males. Age ranged from five to 18 years, with a mean age of 10.5 years (median of ten years). Grossly, cholangiocarcinoma and hemangiosarcoma were multinodular and hepatocellular carcinoma was massive. Microscopically, cholangiocarcinomas were arranged in acini and ducts, whereas hepatocellular carcinomas were arranged in solid sheets or trabeculae. On immunohistochemistry, cholangiocarcinomas, hepatocellular carcinomas, and hemangiosarcomas were positive for the antibodies CK 7, Hep Par-1, and vimentin and von Willebrand factor, respectively.(AU)

Neoplasias hepatobiliares primárias (NHP) são incomuns em gatos e se originam de hepatócitos, células dos ductos biliares intra e extra-hepáticos, células mesenquimais e ainda células de origem neuroendócrina. O objetivo do trabalho foi determinar a frequência das NHP em gatos diagnosticados na Região Metropolitana de Porto Alegre, no período de 17 anos, abordando seus aspectos epidemiológicos, anatomopatológicos e imuno-histoquímicos (IHQ). Foram analisados os laudos de necropsia de 2.090 gatos sendo que 125 foram diagnosticados com doenças hepatobiliares primárias, destes 15 foram casos de NHP, representando 12% das condições hepatobiliares específicas e 0,7% do total de necropsias. Todos os diagnósticos de NHP eram malignos, destes 93,3% apresentaram origem epitelial e 6,7% mesenquimal. Colangiocarcinoma foi a neoplasia mais diagnosticada, seguido do carcinoma hepatocelular e hemangiossarcoma. De uma maneira geral, os gatos sem raça definida foram os mais acometidos. Em relação ao sexo 60% eram fêmeas e 40% machos. A idade variou de cinco a 18 anos, com a idade média de 10,5 anos (mediana de 10 anos). Macroscopicamente o colangiocarcinoma e hemangiossarcoma eram multinodulares, e o carcinoma hepatocelular, maciço. À histologia, houve predomínio do arranjo acinar e ductal nos colangiocarcinomas e sólido, no carcinoma hepatocelular. Na IHQ os colangiocarcinomas foram reativos para CK 7, carcinoma hepatocelular para Hep Par-1 e hemangiossarcoma para vimentina e fator de von Willebrand.(AU)

Contrast-enhanced ultrasonography features of hepatobiliary neoplasms in cats.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) features of primary hepatobiliary neoplasms have been reported in dogs but no information is available in cats. METHODS: Qualitative and quantitative features of bile duct adenomas (BDAs, n=20), bile duct carcinomas (BDCs, n=16), and hepatocellular carcinomas (HCCs, n=8) are described in 44 cats. RESULTS: There was an overlap in CEUS qualitative features between different histotypes, both in wash-in and wash-out phases. Distinction between different neoplasms based only on the CEUS qualitative features was not possible. At peak of enhancement, the BDAs, BDCs and HCCs showed a large range of echogenicities, from hypoenhancement to hyperenhancement, in comparison to the liver parenchyma. Eight of 20 BDAs showed inhomogeneous hyperenhancement during wash-in, which is a feature reported as typical of malignant lesions in dogs. BDC had a significantly faster wash-in compared with both BDA and HCC but the diagnostic accuracy of all the included quantitative variables was only moderate. No significant differences in the wash-out quantitative features of BDA and BDC were evident. CONCLUSION: There is poor evidence that CEUS may be used to distinguish between different primary hepatobiliary neoplasms in cats.

Cholangiocarcinoma in a Free-Ranging Eurasian Brown Bear (Ursus arctos arctos) from Northern Spain.

A hepatic cholangiocarcinoma with metastases in the gallbladder, left elbow joint, adrenal glands, and lungs was observed in a female 21-yr-old free-ranging Eurasian brown bear (Ursus arctos arctos) found in the Principality of Asturias (northern Spain). Gross and histopathologic findings are described.

Combined hepatocellular-cholangiocarcinoma in a cow.

We examined a 10-year-old cow in which about half of the liver was displaced by malignant tissue consisting of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Cytokeratin (CK) 18 and 7 were expressed in the latter. Metastasis was present in the hepatic, pancreaticoduodenal and mediastinal lymph nodes, where malignant cells had hepatocellular features, but more pleomorphic and atypical than in the primary lesion. Areas composed solely of CC cells or less-differentiated HCC cells were observed. In contrast, well-differentiated HCC cells were almost always admixed with the other two types, and may have had the ability to transform into CC cells and to dedifferentiate into less-differentiated cells. This report suggests that CK18 is an excellent marker for biliary differentiation in cattle.

Primary intrahepatic squamous cell carcinoma in a sika deer.

A white nodule was detected in the liver of a wild female sika deer. The nodule was histologically diagnosed as squamous cell carcinoma (SCC), and it transitioned into a hyperplastic and chronically inflamed intrahepatic bile duct showing Fasciola infection. Therefore, the tumor was demonstrated to have originated from the biliary epithelium of the intrahepatic bile duct. Hyperplastic and chronic inflammatory changes of the biliary epithelium might have contributed the carcinogenesis of the present case, as proposed in human primary intrahepatic SCC cases. To the best of our knowledge, this is the first reported case of primary intrahepatic SCC in an animal.

Findings of contrast-enhanced ultrasonography with Sonazoid for cholangiocellular adenoma in three dogs.

Contrast-enhanced ultrasonography (CEUS) is useful to distinguish benign and malignant focal liver lesions in dogs. Cholangiocellular adenoma is an extremely rare benign tumor in dogs and has not been examined using CEUS with Sonazoid. The aim of this study was to describe findings of CEUS with Sonazoid in three dogs with cholangiocellular adenoma. All three dogs showed contrast defects in the Kupffer phase and these findings mimicked malignant neoplasia during the Kupffer phase. Moreover, all dogs showed early washout and hypoechoic lesions relative to the surrounding normal liver parenchyma in the portal phase. To our knowledge, this is the first study to report that CEUS findings of cholangiocellular adenoma with Sonazoid mimicked malignancy in three dogs.

Hypercalcemia of Malignancy in a Dog Diagnosed With Cholangiocellular Carcinoma.

A 4-year-old, neutered male Golden Retriever was presented with a 1-week history of weight loss, polyuria, and polydipsia. The diagnostic workup showed an increased ionized calcium concentration, mild increase in serum creatinine and urea concentration, and severe hyperlipasemia. A complete abdominal ultrasound revealed multiple hepatic nodules. A cytological diagnosis of malignant epithelial neoplasia, highly suggestive of bile duct adenocarcinoma was made. In order to confirm the presumptive diagnosis of hypercalcemia of malignancy due to the presence of a hepatic neoplasia, serum parathormone-related peptide concentration was measured, and the result revealed an increased concentration. The dog was hospitalized and received supportive treatments consisting of intravenous furosemide and fluid therapy. After ruling out lymphoma and hypoadrenocorticism, oral prednisone was initiated and ionized calcium concentration decreased gradually down to normal concentration after 7 days of hospitalization. Chemotherapy with intravenous epirubicin was initiated based on the cytological diagnosis. One month after diagnosis and due to the worsening of its clinical condition, the dog was humanely euthanized. Postmortem examination confirmed a cholangiocellular carcinoma. To our knowledge, this is the first report of malignant hypercalcemia associated with cholangiocellular carcinoma in a dog.

Feline hepatobiliary neoplasia and mistaken age.

A cat, thought to be 5 years old, and with reduced appetite and weight loss, was presented for dental cleaning and extractions. Bile duct origin hepatic carcinoma was diagnosed. The progression of iris degeneration, dental disease, histological renal lesions, spondylosis, and hepatobiliary neoplasia suggest this cat was closer to 10 years old.

Néoplasie hépatobiliaire féline et âge erroné. Un chat, que l'on croyait âgé de 5 ans et qui souffrait d'une diminution d'appétit et d'une perte de poids, a été présenté pour un nettoyage des dents et une extraction dentaire. Un carcinome hépatique de la voie biliaire principale a été diagnostiqué. La progression de la dégénérescence de l'iris, la maladie dentaire, les lésions rénales histologiques, la spondylose et la néoplasie hépatobiliaire suggèrent que ce chat était probablement âgé d'environ 10 ans.(Traduit par Isabelle Vallières).

Imaging diagnosis-hypoglycemia associated with cholangiocarcinoma and peritoneal carcinomatosis in a horse.

An 8-year-old Thoroughbred mare presented for decreased appetite, ataxia, and weakness. Abdominal ultrasound revealed a large volume of anechoic fluid along with multiple masses involving the spleen, liver, and diaphragm. Pleural fluid was identified via ultrasonography and thoracic radiography. Thoracic radiographs also identified pulmonary interstitial nodules, an undulant dorsal diaphragmatic margin and enlargement of tracheobronchial lymph nodes. Clinical signs of weakness and mild seizures were concurrent with hypoglycemic episodes. The final diagnosis was cholangiocarcinoma with extensive metastasis. Clinical signs of weakness, ataxia, and seizures were attributed to a paraneoplastic syndrome of tumor-associated hypoglycemia that has been infrequently reported in horses.

[Sonographic findings in two miniature goats with metastatic bile duct carcinoma]. / Sonographische Befunde bei zwei Zwergziegen mit metastasierendem Gallengangskarzinom.

This case study describes 2 miniature goats with metastatic bile duct carcinoma. The main clinical sign was a pear-shaped abdomen due to abdominal distension in case 1 and stranguria and pollakiuria in case 2. Liver enzyme activity was markedly elevated in both goats, and ultrasonographic examination showed multiple round echoic structures that were partly surrounded by a hypoechoic zone. A tentative diagnosis of liver tumour was made based on the sonographic findings, and a final diagnosis of intrahepatic bile duct carcinoma was made post mortem.

Intrahepatic cholangiocarcinoma in a captive meerkat (Suricata suricatta).

A 9-yr-old male meerkat (Suricata suricatta) living in captivity, with a history of anorexia, lethargy, and weight loss, was examined postmortem. Physical examination revealed poor body condition, dehydration, and icteric mucous membranes. Macroscopically, white to yellowish, multinodulated masses were found protruding from the liver. These multinodular masses were also observed in all lobes of the lungs and the mediastinal lymph nodes. Microscopic examination revealed tumors with well-circumscribed, atypical proliferating cuboidal to columnar bile duct epithelial layers arranged in solid sheets and papillary patterns. The neoplastic masses were separated by dense fibrous connective tissues and invaded the normal parenchyma. Periodic acid-Schiff-positive material was occasionally found within the lumen of tubuloacinar structures. Immunohistochemical labeling revealed that neoplastic cells were intensely positive for pan-cytokeratin, but negative for vimentin. Based on the macroscopic and microscopic findings, intrahepatic cholangiocarcinoma was diagnosed. This is the first report describing cholangiocarcinoma in a meerkat.