Intrahepatic Cholangiocarcinoma in Wilson's Disease: A Case Report.

BACKGROUND Wilson's disease is a rare autosomal recessive disorder characterized by excessive accumulation of copper in the liver, brain, and kidneys. Although it affects only approximately 1 in 30 000 individuals, it leads to progressive liver damage and neurological issue. Wilson's disease presents a wide spectrum of clinical manifestations related to hepatic disease, ranging from asymptomatic cases to acute liver failure. The occurrence of hepatobiliary malignancies, including intrahepatic cholangiocarcinoma, is relatively uncommon in Wilson's disease, even among patients with cirrhosis. Only 14 cases have been published so far, including the present report, and its etiology remains unclear. CASE REPORT We report the successful treatment of intrahepatic cholangiocarcinoma in a 39-year-old woman with Wilson's disease. Twenty-two years after being diagnosed with Wilson's disease, intrahepatic cholangiocarcinoma was diagnosed. She had an intrahepatic mass that was found to be a 4.3-cm ill-defined hypodense lesion in liver segment 3/4, with features suggesting infiltrative intrahepatic cholangiocarcinoma rather than hepatocellular carcinoma. Laboratory results showed slightly elevated liver enzymes and tumor markers. There was no evidence of metastasis on chest computed tomography or positron emission tomography, and the tumor was resectable, so surgery was the first-choice treatment option. Left hepatectomy was performed successfully, and the final pathology confirmed adenocarcinoma with clear resection margins. The patient received adjuvant chemotherapy with capecitabine. To date, the patient has been doing well without evidence of recurrence or metastasis. CONCLUSIONS Despite limited knowledge regarding hepatic malignancy in Wilson's disease, it is crucial to prioritize careful monitoring and develop suitable treatment strategies upon diagnosis to achieve favorable outcomes, considering the potential occurrence of intrahepatic cholangiocarcinoma in Wilson's disease.

A Novel Serum Glycobiomarker for Diagnosis and Prognosis of Cholangiocarcinoma Detected by Butea monosperma Agglutinin.

Plant lectins are widely used in medical glycosciences and glycotechnology. Many lectin-based techniques have been applied for the detection of disease-associated glycans and glycoconjugates. In this study, Butea monosperma agglutinin (BMA), a lectin purified from seeds of the medicinal plant Butea monosperma, was used for the detection of cholangiocarcinoma (CCA)-associated glycans. Expression of BMA-binding N-acetyl galactosamine/galactose (GalNAc/Gal)-associated glycan (BMAG) in CCA tissues was determined using BMA lectin histochemistry; the results showed that BMAG was undetectable in normal bile ducts and drastically increased in preneoplastic bile ducts and CCA. The study in hamsters showed that an increase of BMAG was associated with carcinogenesis of CCA. Using an in-house double BMA sandwich enzyme-linked lectin assay, BMAG was highly detected in the sera of CCA patients. The level of serum BMAG in CCA patients (N = 83) was significantly higher than non-CCA controls (N = 287) and it was applicable for diagnosis of CCA with 55.4% sensitivity, 81.9% specificity, and 76.0% accuracy. A high level of serum BMAG (≥82.5 AU/mL) was associated with unfavorable survival of CCA patients; this information suggested the potential of serum BMAG as a poor prognostic indicator of CCA. In summary, BMAG was aberrantly expressed in preneoplastic bile ducts and CCA, it was also highly detected in patient serum which potentially used as a marker for diagnosis and prognostic prediction of CCA.

Cholangiocarcinoma: Diagnosis and Management.

Cholangiocarcinoma is a highly lethal biliary epithelial tumor that is rare in the general population but has increased rates in patients with primary sclerosing cholangitis (PSC). It is heterogenous, and management varies by location. No effective prevention exists, and screening is likely only feasible in PSC. Patients often present in an advanced state with jaundice, weight loss, and cholestatic liver enzymes. Diagnosis requires imaging with magnetic resonance cholangiopancreatography, laboratory testing, and endoscopic retrograde cholangiopancreatography. Potentially curative options include resection and liver transplant with neoadjuvant or adjuvant chemoradiation. Chemotherapy, radiation, and locoregional therapy provide some survival benefit in unresectable disease.

miR-138 mediates sorafenib-induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells.

Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR-138 in tumor tissues is related to the poor prognosis in patients, and that miR-138 mediates sorafenib-induced cell survival in cholangiocarcinoma cells. Moreover, miR-138 negatively regulates SOX4 expression by specifically targeting its 3' untranslated region (3' UTR). As per our results, overexpression of SOX4 reversed sorafenib-induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR-138/SOX4 is involved in sorafinib-mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.

A Serendipitous Find: A Case of Cholangiocarcinoma Identified Incidentally After Acute Liver Injury Due to Cascara sagrada Ingestion.

The use of anthranoid laxatives such as Cascara sagrada can, in rare instances, produce a hepatitis that resolves with discontinuation of the offending supplement. However, the clinical presentation of abdominal pain, jaundice, clay-colored stools, and darkening urine can mimic the presentation of a variety of hepatobiliary illnesses, including cholangiocarcinoma. This case report describes a local patient diagnosed with an extrahepatic cholangiocarcinoma following workup for an acute hepatitis due to ingestion of large quantities of Cascara sagrada.

Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma.

Sclerosing cholangitis (SC) is a rarely reported morbidity secondary to transcatheter arterial chemoembolization (TACE) with bleomycin-iodinated oil (BIO) for liver cavernous hemangioma (LCH). This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO. Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts. Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy. Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy. Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area. Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy. Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC.

[Disappearance of intrahepatic bile duct hepatocellular carcinoma after endoscopic retrograde cholangiopancreatography and transarterial chemoinfusion: a case report].

Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and surgical resection is important for treatment. A 58-year-old man who underwent hepatic resection for HCC 4 years ago and received transarterial chemoembolization (TACE) 2 years after the operation for recurred HCC presented with jaundice. CT scan revealed a tumor in the common bile duct without intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary drainage. Histological examination was compatible with hepatocellular carcinoma. However, the tumor could not be visualized at angiography and thus, only transarterial chemoinfusion was performed without embolization. The tumor had disappeared on follow-up CT scan, and the patient has been disease free for 23 months without evidence of recurrence. Herein, we report a case of intrahepatic bile duct HCC which disappeared after ERCP.

Disappearance of Intrahepatic Bile Duct Hepatocellular Carcinoma after Endoscopic Retrograde Cholangiopancreatography and Transarterial Chemoinfusion: A Case Report / 대한소화기학회지

Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and surgical resection is important for treatment. A 58-year-old man who underwent hepatic resection for HCC 4 years ago and received transarterial chemoembolization (TACE) 2 years after the operation for recurred HCC presented with jaundice. CT scan revealed a tumor in the common bile duct without intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary drainage. Histological examination was compatible with hepatocellular carcinoma. However, the tumor could not be visualized at angiography and thus, only transarterial chemoinfusion was performed without embolization. The tumor had disappeared on follow-up CT scan, and the patient has been disease free for 23 months without evidence of recurrence. Herein, we report a case of intrahepatic bile duct HCC which disappeared after ERCP.

Operative management of cholangiocarcinoma.

Cholangiocarcinomas (CCAs) are rare malignancies that originate from the epithelial cells of the bile ducts. It is the second most-common primary liver cancer after hepatocellular carcinoma. Recent epidemiologic studies have shown that the overall incidence and mortality rates of CCAs are increasing. Diagnosis is often challenging due to the difficulty in getting tissue/cytology for confirmation, and it comprises a combination of cross-imaging, tumor markers, histology, and cholangiography. Surgery involving major resections of liver, bile duct, pancreas, and at times adjacent vessels is the only chance for cure. Evaluation should be focused on the assessment of tumor resectability, hepatic reserve, and patient physiological fitness for major surgery. In patients not fit for major surgery, biliary drainage for jaundice is an appropriate intervention and if there is histologic confirmation of a CCA, palliative therapies focused on local and systemic disease control should be considered. The endeavor to expand the indications for liver transplantation reflects the efforts to provide an effective form of therapy for a previously untreatable disease. A multidisciplinary specialized approach should be the platform for providing the best comprehensive care for these patients.

Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy.

Radiation recall phenomenon is an inflammatory process occurring at sites of previous radiation subsequent to administration of pharmacologic agents. The most common chemotherapeutic agents implicated with radiation recall phenomenon are anthracyclines and taxanes. Skin is the most common site for radiation recall. About 63% of the radiation recall events are reported to manifest as dermatitis. This finding differs from radiation recall due to Gemcitabine, in which approximately 70% cases manifested as inflammation of internal organs or tissues and 30% manifested as dermatitis. Here, we report a case of post-operative peri-ampullary carcinoma who developed radiation recall dermatitis during adjuvant chemotherapy with inj. Gemcitabine and inj. Carboplatin after concurrent chemoradiation with capecitabine.

[Radiological diagnosis and intervention of cholangiocarcinomas (CC)]. / Radiologische Diagnostik und Intervention von Cholangiokarzinomen (CC).

To present current data on diagnosis, indication and different therapy options in patients with cholangiocarcinoma (CC) based on an analysis of the current literature and clinical experience. The diagnostic routine includes laboratory investigations with parameters of cholestasis and also serum tumor markers CA19 - 9 and CEA. After ultrasound for clarifying a tumor and/or dilated bile ducts, contrast-enhanced magnetic resonance imaging (MRI) should be performed with magnetic resonance cholangiography (MRCP). The accuracy (positive predictive value) for diagnosing a CC is 37-84% (depending on the location) for ultrasound, 79-94% for computed tomography (CT), and 95% for MRI and MRCP. An endoscopic retrograde cholangiography (ERCP) can then be planned, especially if biliary drainage or cytological or histological specimen sampling is intended. A curative approach can be achieved by surgical resection, rarely by liver transplantation. However, many patients are not eligible for surgery. In addition to systemic chemotherapy, locoregional therapies such as transarterial chemoembolization (TACE), hepatic arterial infusion (HAI)--also known as chemoperfusion--, drug eluting beads-therapy (DEB) as well as thermoablative procedures, such as laser-induced thermotherapy (LITT), microwave ablation (MWA) and radiofrequency ablation (RFA) can be provided with a palliative intention.

Challenge in differential diagnosis of a liver mass histologically defined as a metastatic lesion from an occult primary intestinal tumour. The importance of clinical findings and the limitations of histology and molecular profiles. A case report.

Differential diagnosis of liver lesion in the absence of proven primary tumor is still a challenge. We experienced a case of an asymptomatic 14 cm lesion of right hemiliver in a 67 year-old man submitted to right hepatectomy in December 2010. One year before the patient underwent to endoscopic removal of a tubular adenoma of the right colon. Preoperative diagnosis was supported by ultrasound, CT scan, PET and liver biopsy. The patient received 6 cycles of preoperative chemotherapy (FOLFOX) with down-staging of the lesion diameter. Immunohistochemistry on the surgical specimen showed positivity for cytokeratins 19 and 20, CEA, MUC-2, negativity for cytokeratin 7 and a-fetoprotein. Moreover, the neoplastic cells showed a focal positivity with lower intensity for MUC-1 and MUC-5AC. The immunohistochemical profile suggested the possibility of a metastatic tumour from the large bowel, without excluding a primitive mucinous cholangiocarcinoma with intestinal phenotype. At 6 months after intervention, the patient was submitted to chemotherapy (FOLFOX). At present he is in good condition, without radiological signs of recurrence. Oncologists must evaluate the possible benefits of further adjuvant treatments based on the differential diagnosis between a primitive or metastatic liver tumour. In conclusion, correct diagnosis of liver masses is mandatory and remains a challenge that can differentiate either follow-up or surgical and adjuvant treatment. Histology and immunohistochemistry must be related to clinical findings as they may not always be sufficient to reach a correct final diagnosis, and can even be confusing. At present, molecular biology cannot be considered a helpful for diagnosis in these cases.

[Cholangiocarcinoma]. / Colangiocarcinoma: Actualización, diagnóstico y terapia.

Cholangiocarcinoma is a malignant lesion of the bile duct epithelium. Its incidence and prevalence are low. It appears from the sixth decade of life and there is slight male predominance. It is most frequently found in the confluence of the hepatic ducts, where it is called hilar cholangiocarcinoma or Klatskin tumor. Its etiology is unknown but there are predisposing conditions and environmental risk factors such as primary sclerosing cholangitis, Caroli's disease, bile duct malformations, industrial toxins and parasitic infections. The classic presentation of cholangiocarcinoma includes jaundice, weight loss and right upper quadrant pain. These, in addition to laboratory exams, endoscopical and imaging procedures, lead to the diagnosis. Hilar cholangiocarcinoma must be distinguished from other malignant or benign causes of biliary obstruction. Cholangiocarcinoma of the distal common bile duct must be differentiated from other periampullary tumors and intrahepatic cholangiocarcinoma can be confused with a hepatocellular carcinoma. Two classifications are used for clinical staging: TNM and Bismuth-Corlette. The best treatment is the complete surgical excision with negative histological margins, although the resectability index is low. The type and size of surgery depends on the location and extent of the tumor. Patients with unresectable tumors can be subjected to palliative procedures such as biliary-enteric bypass, endoscopic or pecutaneous stent placement. Chemotherapy is not effective. Recently, endoscopic phototherapy has emerged as a better alternative for palliative care.

Unresectable cholangiocarcinoma: comparison of survival in biliary stenting alone versus stenting with photodynamic therapy.

BACKGROUND & AIMS: Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis, quality of life, and potentially survival. We compared survival in patients with unresectable cholangiocarcinoma undergoing endoscopic retrograde cholangiopancreatography (ERCP) with PDT and stent placement with a group undergoing ERCP with stent placement alone. METHODS: Forty-eight patients were palliated for unresectable cholangiocarcinoma during a 5-year period. Nineteen were treated with PDT and stents; 29 patients treated with biliary stents alone served as a control group. Multivariate analysis was performed by using Model for End-Stage Liver Disease score, age, treatment by chemotherapy or radiation, and number of ERCP procedures and PDT sessions to detect predictors of survival. RESULTS: Kaplan-Meier analysis demonstrated improved survival in the PDT group compared with the stent only group (16.2 vs 7.4 months, P<.004). Mortality in the PDT group at 3, 6, and 12 months was 0%, 16%, and 56%, respectively. The corresponding mortality in the stent group was 28%, 52%, and 82%, respectively. The difference between the 2 groups was significant at 3 months and 6 months but not at 12 months. Only the number of ERCP procedures and number of PDT sessions were significant on multivariate analysis. Adverse events specific to PDT included 3 patients with skin phototoxicity requiring topical therapy only. CONCLUSIONS: ERCP with PDT seems to increase survival in patients with unresectable cholangiocarcinoma when compared with ERCP alone. It remains to be proved whether this effect is attributable to PDT or the number of ERCP sessions. A prospective randomized multicenter study is required to confirm these data.

Colangiocarcinoma: Actualización, diagnóstico y terapia: [revisón] / Cholangiocarcinoma: [review]

Cholangiocarcinoma is a malignant lesion of the bile duct epithelium. Its incidence and prevalence are low. It appears from the sixth decade of life and there is slight male predominance. It is most frequently found in the confluence of the hepatic ducts, where it is called hilar cholangiocarcinoma or Klatskin tumor. Its etiology is unknown but there are predisposing conditions and environmental risk factors such as primary sclerosing cholangitis, Caroli's disease, bile duct malformations, industrial toxins and parasitic infections. The classic presentation of cholangiocarcinoma includes jaundice, weight loss and right upper quadrant pain. These, in addition to laboratory exams, endoscopical and imaging procedures, lead to the diagnosis. Hilar cholangiocarcinoma must be distinguished from other malignant or benign causes of biliary obstruction. Cholangiocarcinoma of the distal common bile duct must be differentiated from other periampullary tumors and intrahepatic cholangiocarcinoma can be confused with a hepatocellular carcinoma. Two classifications are used for clinical staging: TNM and Bismuth-Corlette. The best treatment is the complete surgical excision with negative histological margins, although the resectability index is low. The type and size of surgery depends on the location and extent of the tumor. Patients with unresectable tumors can be subjected to palliative procedures such as biliary-enteric bypass, endoscopic or pecutaneous stent placement. Chemotherapy is not effective. Recently, endoscopic phototherapy has emerged as a better alternative for palliative care.

[Management of hilar cholangiocarcinoma]. / Prise en charge du cholangiocarcinome hilaire.

Hilar cholangiocarcinoma is a rare disease departing from the biliary convergence. It is primarily revealed by the onset of retention jaundice. Only 20%-30% of patients can undergo resection at diagnosis. The only chance for survival for these patients is R0 resection, which requires hepatectomy associated with resection of the common bile duct and pedicle lymph node removal, whatever the classification of the cholangiocarcinoma. No adjuvant treatment has been shown to be effective to date. Palliative treatment is most often based on implanting a biliary stent. Dynamic phototherapy may be beneficial in these situations. Improvements in survival for selected N0 hilar cholangiocarcinoma may be obtained with neoadjuvant treatment with radiochemotherapy followed by liver transplantation.

[Klatskin tumors--diagnostic and interventional therapy]. / Klatskin-Tumoren--Diagnostik und interventionelle Therapie.

Klatskin tumors are defined as malignant tumors of the bile duct involving the bifurcation and intrahepatic bile ducts. The most common presenting clinical feature, obstructive jaundice, usually occurs with advanced disease. Diagnostic tools currently available are therefore either performed too late or are not able to detect early disease stage. Imaging procedures for diagnosis and staging are ultrasonography, magnetic resonance imaging with cholangiopancreaticography, intravenous bolus-enhanced spiral computed tomography and endoscopic retrograde cholangiopancreaticography. Before initiating any palliative measure, a proper staging and a surgical consultation at a hepatobiliary center is necessary. To assess resectability, additional diagnostic methods like angiography, positron emission tomography, cholangioscopy, endoscopic or intraluminal ultrasonography and finally even explorative laparoscopy may be required. At time of diagnosis only a small percentage of Klatskin tumors is curative resectable. Therefore, palliative treatment options play an important role. Endoprostheses insertion is the method of choice to relieve jaundice. Although it improves quality of life, it does not seem to improve survival time. Definitive evidence for a benefit of additional radio and/or chemotherapy is still missing. Photodynamic therapy, a light therapy, is the first approach leading to an improvement of cholestasis and quality of life as well as to a prolongation of survival time. PDT should therefore be offered to all patients with nonresectable cholangiocarcinoma.

[A case of unresectable hilar cholangiocarcinoma treated with an insertion of biliary stent and herbal medicine obtaining a good quality of life].

An advanced hilar cholangiocarcinoma was poor in prognosis and required a biliary duct drainage tube insertion to prevent jaundice. An endoscopically placed metallic biliary stent is efficient for improving QOL of patients with the disease. This case was of a 65-year-old man. He was admitted to our hospital with obstructive jaundice. Hilar cholangiocarcinoma was diagnosed by computed tomography (CT) and MR cholangiopancreatography (MRCP). Abdominal angiography revealed an unresectable cholangiocarcinoma through the portal vein obstruction and stenosis of the left hepatic artery for tumor invasion. After a second opinion and informed consent, he was inserted a biliary stent (non-covered metallic stent) under an endoscopy. The jaundice was improved further and other laboratory data showed normal results except for tumor markers. After the patient left the hospital, he came to our hospital as an outpatient basis for observation. He was prescribed herbal medicine from the other hospital. Now after ten months since the biliary stent insertion, he has been free from symptoms with normal laboratory data.