Intrahepatic cholangiocarcinoma in Thailand

Intrahepatic cholangiocarcinoma is defined as adenocarcinoma originating from bile ductules and segmental and lobar intrahepatic ducts. Four types of surgical pathology have been identified in the Khon Kaen endemic area in Thailand: peripheral, type I; intermediate, type II; central, type III; and diffuse, type IV. We report our experience with intrahepatic cholangiocarcinoma with emphasis on the surgical pathology, operative procedure, and associated survival time. We reviewed the records of patients treated for cholangiocarcinoma at Srinagarind Hospital from January 1, 1992 to February 28, 1997. There was a total of 411 patients, and 138 were intrahepatic and non-jaundiced. Tumors in the proximity of the gray zone i.e., portal, periportal with jaundice, were excluded. Patient profiles, surgical pathology, operative procedure, postoperative morbidity, and mortality were recorded. The data were analyzed using Kaplan-Meier survival curves. Of the 138 patients with intrahepatic disease who were non-jaundiced, 116 had type I, 10 had type II—III, and 12 had type IV. The wear ages of the patients were: 53.0, SE 9.2 years in type I; 57.1, SE 4.6 years in type II—III, and 50.2, SE 9.2 years in type IV. The male-to-female ratios in the three groups were 1.4 : 1, 1.5 : 1, and 5 : 1, respectively. The mean survival times in the three groups were 556, SE 63 days 374, SE 149 days and 97, SE 35 days. Most of the surgical procedures were tumor excisions (108/138). Right hepatectomy was performed in 63 patients, extended right hepatectomy in 8, left hepatectomy in 18, and extended left hepatectomy in 1. Palliative procedures were performed in the other patients because tumors were in both lobes. The mean survival time was 582 days (SE, 75), for right lobe surgery; 458 days (SE, 89) for left lobe surgery; and 127 days (SE, 58) for the other procedures. Mean survival time was 1039 days (SE, 201) in tumor stage III, 773 days (SE, 123) in stage IVa, and 382 days (SE, 60) in stage IVb. There were no significant differences in survival time according to age or sex. The results of surgery in type I and type II-III were better than the results in type IV. Survival time after right hepatectomy was better than that after left hepatectomy, although without statistical significance, but survival time was significantly better after both operations than after palliative procedures. The results of surgery according to pathological staging showed that survival time in stage III was better than that in either stage IVa or IVb, but only the difference from stage IVb was significant.     

Intrahepatic cholangiocarcinoma in Taiwan

We report our experience of the surgical treatment of intrahepatic cholangiocarcinoma (ICC) in Taiwanese patients. A tota1 of 162 patients with histologically proven ICC were treated of whom 106 (65.4%) had associated hepatolithiasis. Patients with hepatolithiasis were in earlier stages than those without hepatolithiasis. Two-thirds of the patients with hepatolithiasis presented with acute cholangitis, and two-thirds of those without hepatolithiasis presented with hepatomegaly. The rate of hepatic resection was 29.6% (48 of 162), and these rates were 31.1% and 26.8% for the patients with and without hepatolithiasis, respectively. Ninety-three percent of the patients with hepatolithiasis underwent common bile duct exploration, compared with 18% of those without hepatolithiasis. The surgical mortality rates were 3.7% (6/162), for all patients, and 3.8% and 3.6% for patients with and without hepatolithiasis, respectively. The morbidity rate was much higher in the patients with hepatolithiasis (37.7% vs 16.1%). The 1-, 3-, and 5-year survival rates were 35.5%, 20.5%, and 16.5% in the patients with hepatolithiasis and 27.2%, 8.8%, and 7.8% in those without hepatolithiasis. Concomitant hepatolithiasis prevented precise diagnosis preoperatively and precipitated biliary sepsis, which affected resectability and increased postoperative morbidity. Hepatolithiasis per se did not influence long-term survival.     

Intrahepatic cholangiocarcinoma in Korea

We reviewed surgically treated patients with intrahepatic cholangiocarcinoma to evaluate the clinical and pathologic features of intrahepatic cholangiocarcinoma that may affect long-term survival in Korean patients with the disease. Between 1990 and 1997, 28 patients with intrahepatic cholangiocarcinoma underwent laparotomy. Resection was performed in 25 patients, and wedge resection alone in 3 patients. The liver resections consisted of right lobectomy in 5 patients, right trisegmentectomy in 1, left lobectomy in 7, extended left lobectomy in 3, hepatopancreatoduodenectomy in 2, and segmentectomy in 7. Curative resection was performed in 15 patients. Histological sections of all resected specimens were immunohistochemically stained with p53 and Ki-67 monoclonal antibodies to assess the biological behavior of the tumor cells. Cumulative survival rate and clinicopathological factors that may influence the prognosis, including biological markers (p53, Ki-67), were analyzed statistically. Patients who underwent curative resection survived significantly longer than patients who underwent noncurative resection. The median survival time of the patients who underwent curative resection was 24 months (mean, 34 ± 8 months), with 1-, 2-, and 3-year survival rates of 66.6%, 44.4%, and 35.6%, respectively. The median survival time of the patients who underwent noncurative resection was 3 months (mean, 8 ± 3 months), with 1- and 2-year survival rates of 26.7% and 13.4%, respectively. Univariate analysis showed that positive regional lymph nodes correlated significantly with poor outcome (P = 0.004) and that curative resection significantly correlated with better prognosis (P = 0.001). Age, sex, tumor size, degree of cell differentiation, gross type of tumor, and p53 and Ki-67 labeling index were not significantly correlated with outcome. Our findings support the concept that aggressive liver resection, along with regional lymph node dissection, be recommended for long-term survival. The validity of molecular biologic tumor markers (p53, Ki-67) as prognostic factors has not yet been clearly demonstrated.     

Intrahepatic cholangiocarcinoma with sarcomatous transformation: an autopsy case.

We report an adult case of intrahepatic cholangiocarcinoma with remarkable sarcomatous changes. At autopsy a yellowish-white tumor (8 x 6 cm) was found in the left hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor, and all of the daughter nodules examined, showed sarcomatous changes (spindle- or fusiform-shaped and pleomorphic cells). Histologic examination of a whole slice of the main tumor disclosed a focus of adenosquamous carcinoma (cholangiocarcinoma) within the tumor. Frequent transitions between adenosquamous carcinoma areas and sarcomatous areas suggested that sarcomatous transformation occurred in cholangiocarcinoma and then grew to spread rapidly. Immunohistochemically, squamous carcinoma and, to a lesser degree, adenocarcinoma elements were strongly positive for keratin and epithelial membrane antigen, both being also weakly positive in sarcomatous cells, supporting that possibility. Vimentin was positive only in sarcomatous elements. Cholangiocarcinoma should be included in the list of hepatic tumors showing sarcomatous change.     

Intrahepatic cholangiocarcinoma: new insights in pathology

Cholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis. This review focuses on ICC, which is rising in incidence with the emergence of hepatitis C virus (HCV) infection as a risk factor. The authors examined 73 ICC, which were resected at The Mount Sinai Medical Center in New York City, and reviewed the literature. The tumors were categorized into classical and nonclassical ICCs based on histopathology. Classical ICCs (54.8%) were characterized by a tubular, glandular, or nested pattern of growth, were significantly associated with tumor size of more than 5 cm and the absence of underlying liver disease and/or advanced fibrosis. Nonclassical ICCs (45.2%) consisted of tumors with trabecular architecture, tumors that exhibited features of extrahepatic carcinomas, and carcinomas considered to be derived from hepatic progenitor cells, i.e., combined hepatocellular/cholangiocarcinomas and cholangiolocellular carcinomas (ductular type of ICC). They were smaller and often arose in chronic liver disease, mostly HCV infection, and/or with significant fibrosis. The role of immunohistochemistry in the diagnosis of ICC and the importance of the new American Joint Committee on Cancer Staging System for ICC are also discussed.     

Intrahepatic cholangiocarcinoma: indication for transplantation

Background/Purpose. Cholangiocarcinoma (CCC) is a rare malignant tumor of the biliary system with a poor prognosis that frequently presents in advanced unresectable stages. A discussion of the role of liver transplantation (LTx) for intrahepatic (IH)-CCC will be presented, based on a review of the international literature. Methods. A search of the international literature related to the topic was performed in the established online databases and databanks. Only those reports with patient series larger than ten were included. Results. The largest series of patients with IH-CCC (n = 186) was reported in the Data Analysis Booklet of the European Liver Transplant Registry (ELTR), revealing 1-, 3-, 5-, 8-, and 10-year survival rates of 58%, 38%, 29%, 23%, and 21%. Other single-center series had comparable or even worse outcomes. More recent experience identified a certain highly selected group of patients who could benefit from LTx in an otherwise unresectable state of disease. Several single-center studies found tumor stage or size, lymph node involvement, and positive surgical margins/contiguous organ infiltration to be predictors of outcome. The recently published Mayo Clinic protocol uses preoperative chemoirradiation and staging at laparotomy before proceeding to liver transplantation, resulting in an early experience with 100% 1-year survival. Conclusions. Generally speaking, IH-CCC is not a favorable indication for liver transplantation. However, there is a highly selected group of patients with early tumor stages potentially benefitting from LTx. Combination with neoadjuvant chemoirradiation may further improve results after LTx. Living-donation LTx may open new therapeutic possibilities to treat patients at an early stage of disease.     

Intrahepatic cholangiocarcinoma in Hong Kong

We retrospectively analyzed the results of hepatic resection for patients with intrahepatic cholangiocarcinoma managed between December 1966 and January 1998 at the University of Hong Kong Medical Center, Queen Mary Hospital. There were 61 men and 40 women (mean age, 61.8 years). The clinical records of these patients were reviewed. A survival analysis was performed on the group of patients who had undergone hepatic resection. Twenty-one patients were treated conservatively. Non-resective (palliative) operations were performed in 32 patients. The median survivals after conservative management and palliative operation were 2.5 and 3.3 months, respectively. The remaining 48 patients underwent hepatic resection. The overall operative morbidity and mortality rates after hepatic resection were 41.7% and 16.7%, respectively. The median survival after hepatic resection was 16.4 months. The overall 1-, 3-, and 5-year survival rates after hepatic resection were 60.3%, 29.4% and 22.0%, respectively. Lymphatic permeation (P = 0.007) and hilar nodal metastases (P = 0.009) were found to be significantly associated with poor survival after hepatic resection. Hepatic resection is the treatment of choice for intrahepatic cholangiocarcinoma when it is resectable.     

Intrahepatic cholangiocarcinoma: macroscopic type and stage classification

The Liver Cancer Study Group of Japan established a classification of macroscopic type and the TNM staging of intrahepatic cholangiocarcinoma (ICC). With the observation of more than 240 resected cases of ICC, three fundamental types were established. They were: (1) mass-forming (MF) type, (2) periductal-infiltrating (PI) type, and (3) intraductal growth (IG) type. The MF type forms a definite mass, located in the liver parenchyma. The PI type is defined as ICC which extends mainly longitudinally along the bile duct, often resulting in dilatation of the peripheral bile duct. The IG type proliferates toward the lumen of the bile duct papillarily or like a tumor thrombus. The TNM classification of ICC was then designed, using 136 cases of the MF type resected curatively between 1990 and 1996 at member institutes. Univariate and multivariate analyses showed: (1) tumor 2?cm or less, (2) single nodule, and (3) no vascular and serous membrane invasion as prognostic factors. T factors were defined as follows: T1 is an ICC that meets all requirements of factors (1), (2), and (3); T2 meets two of the three requirements, T3 meets one of the three requirements and T4 meets none of the three requirements. Our data did not support the idea that the hepatoduodenal lymph node is regional. The N factors were defined as N0 no lymph node metastasis; and N1, positive at any nodes. Thus, the stages of ICC were defined as stage I, T1N0M0; stage II, T2N0M0; stage III, T3N0M0; stage IVA, T4N0M0 or any TN1M0; and stage IVB, any T any NM1.     

Intrahepatic cholangiocarcinoma: current management and emerging therapies

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify ‘target-able’ molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients.

Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies.

Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.     

Case Report: Intrahepatic cholangiocarcinoma with rhabdoid transformation

Sarcomatous transformation is found in approximately 5% of patients with intrahepatic cholangiocarcinoma. According to previous reports, sarcomatous cholangiocarcinomas are composed of spindle-shaped cells and/or multinucleated giant cells. Usually, vimentin is expressed by these sarcomatoid cells. We report a case of intrahepatic cholangiocarcinoma with an element of rhabdoid cells that occurred in a 61-year-old woman admitted for back pain. Various imaging techniques demonstrated multiple liver masses. Histologically, these tumours formed in both sarcomatous and ordinary tubular adenocarcinomatous areas. The sarcomatoid areas were occupied mainly by loosely arranged, eosinophilic rhabdoid cells, which expressed both keratin and vimentin. These findings suggest that rhabdoid cells may occur in an undifferentiated stage of cholangiocarcinoma and possess a strong tendency to metastasize.     

Kartagener's syndrome and rheumatoid arthritis: an unusual association

We report the case of a 66-year-old caucasian woman affected by Kartagener’s syndrome (KS), a genetically transmitted disorder characterised by situs viscerum inversus, bronchiectasis and sinusitis, who also developed rheumatoid arthritis (RA). The impaired mucociliary function typical of KS caused recurrent paranasal sinus and lung infections, as shown by CT scans of the sinuses and chest. The coexistence of KS and RA in our patient was probably accidental. Given the small number of patients in whom an association of the two disorders has been described, it is impossible to establish whether KS might play a role in the pathogenesis of RA. Received: 9 March 2000 / Accepted: 22 January 2001     

Coexisting relapsing polychondritis and sarcoidosis: an unusual association

Relapsing polychondritis is an episodic and progressive systemic inflammatory disease characterized by auricular chondritis, polyarthritis, nasal and respiratory tract chondritis. About 30% of the patients have additional autoimmune and or hematological diseases, most frequently systemic vasculitis, rheumatoid arthritis, myelodysplastic syndromes or systemic lupus erythematosus. So far, only one case of coexisting relapsing polychondritis and sarcoidosis in a patient with AIDS has been reported. We describe here a case of sarcoidosis and relapsing polychondritis in an immunocompetent patient. Physicians should be aware of this possible association.     

Well-differentiated peripheral cholangiocarcinoma with an unusual clinical course.

A patient with an unresectable well-differentiated bile duct tumor who survived for 15 yr after biopsy diagnosis is presented. Histologic examination of the tumor revealed bland features of bile duct adenoma despite extensive spread within the liver. Over its subsequent course, the tumor progressively replaced the liver, achieving huge size, although there was no evidence of metastases until shortly before the patient's death. This clinical course was very unusual for either bile duct adenoma or cholangiocarcinoma, but would be more characteristic of another tumor of intrahepatic bile duct origin, the biliary cystadenoma. However, this latter diagnosis was excluded with both gross and microscopic pathologic criteria. Evidence is presented to support classification of this tumor as an unusual varient of peripheral cholangiocarcinoma which requires correlation of the clinical and pathologic findings for correst diagnosis.