Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Single-center analysis of the first 304 living-donor liver transplantations in 3 years.

BACKGROUND/AIMS: Living donor liver transplantations (LDLT) is a definitive treatment for patients with end-stage liver disease (ESLD), especially in the countries with donation problem. Between April 2007 and April 2010, we performed LDLT in 289 patients. Fifteen of the cases required re-transplantations. This study evaluates these 304 consecutive LDLTs donor and recipient outcomes. METHODOLOGY: Complication rates and survival data of the recipients and donors of 304 LDLT cases were analyzed. RESULTS: All donors are alive and well. Overall complication rate was 27%. Early postoperative recipient complication rate was 51%. Most frequent complication was infection. In the long-term there were 57 biliary stricture and 5 chronic bile fistula cases. Chronic and acute rejection attacks developed in 7 and 103 patients, respectively. Hepatic artery thrombosis rate was 8%. One, two and three year survival rates were 82%, 79% and 75%, respectively. Recipient mortality was 25%, mostly due to vascular complications, septic complications, liver dysfunction and chronic rejection. CONCLUSIONS: More than 150 liver tranplantations per year in a single center is a challenge in Turkey, where there is a shortage of deceased donor grafts. LDLT is a safe procedure for donors and effective for ESLD. Improvement in surgical technique would provide better outcomes.

Rare association of solitary necrotic nodule of the liver with rheumatoid arthritis and systemic lupus erythematosus.

Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with uncertain etiology characterized by a "completely necrotic core" and a hyalinized capsule containing elastin fibers (Journal of Clinical Pathology 36:1181-1183, 1983). We report herein a 26-year-old woman with a previous diagnosis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome and no history of malignancy who presented with a complaint of diarrhea of 1-year duration. In the abdominal ultrasound, multiple paraaortic, portocaval, and ileal lymphadenopathies (LAPs) have been found with the largest one being 2 cm in size. The biopsy of the iliac LAP showed reactive nodular hyperplasia. An abdominal CT disclosed an incidental hypoechoic, heterogenous mass sized 27 × 27 mm close to segment VI of the liver. A trucut biopsy of this lesion was made, and clinicopathologic features of the specimen were compatible with a solitary necrotic nodule of the liver. Here, we discuss the diagnosis and the clinical course of this rare entity in light of current literature.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

Liver Transplant and Improvements in Cholesterol Biosynthesis Defects: A Case Report of Smith-Lemli-Opitz Syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic disease characterized by mental retardation and multiple congenital anomalies. The main pathology is the lack of the enzyme 3ß-hydroxysterol Δ7-reductase, which is the last enzymatic step in cholesterol synthesis, ending with a low cholesterol level. Cholesterol is vitally important in cell membranes and myelination of the nervous system. The cholesterol level affects many systems of the body, especially the nervous system. The cause of liver involvement in Smith-Lemli-Opitz syndrome is unclear, and many hypotheses have been suggested. Here, we present the early results of a patient with Smith-Lemli-Opitz syndrome who underwent living-donor liver transplant due to cirrhosis. As a result of liver transplant, normal cholesterol levels were shown, as well as improvements in the patient's neurodevelopment and behavior. Early liver transplant may be considered for patients with a defect of cholesterol biosynthesis, even in the absence of cirrhosis, and may be a future treatment option to prevent risks of neurologic deterioration.

A rare benign laryngeal tumor: angiomyolipoma.

Angiomyolipoma is a mesenchymal neoplasm containing adipose tissue, blood vessels, and smooth muscle fibers. Arising most frequently in the kidney, the tumor may exceptionally be at the head and neck region. The literature has 1 single published report of laryngeal angiomyolipoma, which was resected through laryngofissure. In this study, a 58-year-old man presented with laryngeal angiomyolipoma with swallowing discomfort. The tumor was removed by an endolaryngeal approach.

Effect of leflunomide on liver regeneration after partial hepatectomy in rats.

PURPOSE: Partial hepatectomy (PH) can be an inevitable surgical therapy in some conditions, such as hepatic malignancies, trauma or partial liver transplantation. Its capacity for regeneration distinguishes the liver from other essential organs. Regeneration is a complex process involving growth factors, cytokines, transcription factors, hormones, and oxidative stress products. In the event of ineffective or total absent liver regeneration, the life threatening picture of acute liver failure may supervene. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and antiinflammatory agent against autoimmune disease, on hepatic regeneration after PH in Wistar Albino rats. METHODS: Thirty-five Wistar albino rats were divided into five groups: group 1, control; group 2, sham; group 3, drug control (was treated with leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH, approximately 70% of the rat liver was surgically removed under general anesthesia. On postoperative day 3, all rats were humanely killed. Catalase (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were determined in remnant liver tissue. Inflammatory process and liver regeneration were evaluated with H&E and KI67, respectively. RESULTS: The tissue levels of MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was significantly improved by the treatment with leflunomide. Histopathologically the enhancement of the liver parenchymal regeneration in the group 5 was significantly greater than the group 4. CONCLUSION: The findings imply that oxidative stress products play a preventive role in liver regeneration after PH and leflunomide ameliorates the regeneration probably by the radical scavenging and antioxidant activities.

Endoscopic ultrasound-guided liver biopsy using a 20-gauge fine needle biopsy needle with the wet-heparinized suction technique.

OBJECTIVES: The primary aim of this study was to evaluate the histological adequacy of the liver tissue specimens obtained with a 20-gauge fine-needle biopsy needle and the secondary aim was to test the safety endoscopic ultrasound-guided liver biopsy with a 20-gauge fine-needle biopsy needle with the wet-heparinized suction technique. METHODS: Forty patients who underwent endoscopic ultrasound-guided liver biopsy were included in the study. A 20-gauge fine-needle biopsy needle was used with the wet-heparinized suction technique to make one pass each from the left and the right lobe. Histologic characteristics of the specimens were evaluated, and patients were observed after the procedure in order to intervene in case of an adverse event. RESULTS: The median longest core fragment was 22 mm from the left lobe [first quartile-third quartile 20-25 mm, interquartile range (IQR) 5 mm], and 20 mm (first quartile-third quartile 17-22 mm, IQR 5 mm) from the right lobe. The median cumulative core length per patient was 103 mm (91-108 mm, IQR 17 mm). The median cumulative number of complete portal triads per patient was 69.50 (52.25-82.25, IQR 30). The rate of diagnostic yield was 100%. Post-biopsy self-limiting abdominal pain was reported in two patients (5%). The most common histologic diagnosis was fatty liver disease (25%). CONCLUSION: Endoscopic ultrasound-guided liver biopsy with the wet-heparinized suction technique using a 20-gauge fine-needle biopsy needle is a safe alternative method in clinical practice.

Successful treatment of pediatric post-liver transplant Kaposi`s sarcoma with paclitaxel.

BACKGROUND: Kaposi`s sarcoma (KS) is a complication of immunosuppressive therapy for transplant recipients. Unlike adult recipients, KS in pediatric organ transplantation is quite rare. Treatment is usually withdrawal of immunosuppression; non-responders often receive chemotherapy. CASE: We have reported a child with post-liver transplant visceral KS which has progressed despite withdrawal of immunosuppressive therapy, who has been treated with Paclitaxel for three weeks. KS has regressed completely after four cycles of Paclitaxel. CONCLUSION: Paclitaxel should be considered as an effective first line treatment option for patients with posttransplant KS.

Expression of matrix metalloproteinases in gallbladder carcinoma and their significance in carcinogenesis.

The correlation between matrix metalloproteinase (MMP)-2, MMP-9, and MMP-14 expression on the prognostic parameters of gallbladder carcinoma (GBC) and their role in carcinogenesis were evaluated. Carcinomas of the gallbladder (n=20) and chronic cholecystitis (n=10) were studied for the expression of MMP-2, MMP-9, and MMP-14 by immunohistochemistry. In all of the cases, metaplastic and dysplastic epithelial alterations, and (in GBC histologic type, grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, and lymph node involvement were noted. MMP-2, MMP-9, MMP-14 were expressed in tumor epithelium in 9 (45%), 20 (100%), and 20 (100%) of the cases, respectively. MMP stromal expression including muscle layer, vascular endothelium, fibroblasts, and lymphoid cells were detected in all cases. MMP-2 was not expressed in normal, metaplastic, and dysplastic epithelia. In contrast, MMP-9 and MMP-14 immunoreactivities were present in antral-type metaplastic areas as moderate (grade 2) and strong in dysplastic epithelia (grade 3). Only in mucinous-type GBC was the expression of the MMPs lower than in the other types. No significant correlation was detected with the grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, or lymph node involvement. These data suggest that MMP-9 and MMP-14 overexpression may have an important role in tumorigenesis. MMP-2, MMP-9, and MMP-14 were expressed in GBC epithelium but also the expression in the stromal component may be essential for the malignant potential of GBC.

The Assessment of Hepatosteatosis in Living-Donor Liver Transplant: Comparison of Liver Attenuation Index and Histopathologic Results.

OBJECTIVES: The purpose of the study was to determine the diagnostic value of computed tomography densitometry in the quantification of hepatosteatosis. MATERIALS AND METHODS: Fifty-one potential liver donors, ranging in age from 19 to 52 years (mean age: 32.4 years ± 10.2), participated in the study. The mean hepatic attenuation and mean splenic attenuation were determined using regions of interest measurements. The difference between the mean hepatic attenuation and mean splenic attenuation (or liver attenuation index), with liver attenuation index = mean hepatic attenuation - mean splenic attenuation were calculated. Computed tomography densitometric parameters were correlated with histopathologic results. RESULTS: From the histopathologic analysis, the degree of macrovesicular hepatosteatosis was 0% to 8% (mean: 1.1% ± 2%). Seven donors (13.7%) had a degree of macrovesicular steatosis of > 5%, and 12 donors (23.5%) had ≥ 2%. Of the 29 normal donors with histopathologic verification, computed tomography densitometry predicted ≤ 5% of the hepatosteatosis in 27 donors, and ≤ 2% hepatosteatosis in 2 subjects. The liver attenuation index was significantly correlated to the histopathologic results. The mathematical relation between liver attenuation index and the degree of histopathologic hepatosteatosis was calculated using the least-squares methods, which provided quadratic polynomials. CONCLUSIONS: Computed tomography densitometry is a rapid, robust, noninvasive technique for the assessment of hepatosteatosis. When used in conjunction with clinically stable reference measurements of spleen, the density measurements of liver correctly predicted the presence of fatty infiltration with significant sensitivity (77%) and specificity (75%). This technique, which was refined during the course of our liver transplant program, minimizes the need for highly invasive percutaneous liver biopsies.

The effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats.

OBJECTIVE: This study evaluates the effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats. METHODS: Fifty-six male Wistar rats were divided into four groups. Group 1 underwent tracheal anastomosis. Group 2 underwent radiation therapy followed by tracheal anastomosis. Group 3 underwent radiation therapy followed by tracheal anastomosis and received granulocyte colony-stimulating factor. Group 4 underwent sham radiation therapy followed by sham tracheal anastomosis. At 10 days following radiation therapy, the trachea was dissected for histopathological, mechanical and biochemical evaluation. RESULTS: Median scores for inflammation were three points for Group 1, two points for Group 2, two points for Group 3 and one point for Group 4. Median scores for angiogenesis were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for connective tissue regeneration were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for epithelial regeneration were two points for Group 1, one point for Group 2, one point for Group 3 and one point for Group 4. Mean anastomotic bursting pressures were 853 mmHg for Group 1, 293 mmHg for Group 2, 417 mmHg for Group 3 and 966 mmHg for Group 4. Mean hydroxyproline concentrations were 159 microg/mg for Group 1, 177 microg/mg for Group 2, 120 microg/mg for Group 3 and 117 microg/mg for Group 4. CONCLUSIONS: This study suggests that granulocyte colony-stimulating factor contributes to the healing of tracheal anastomosis following radiation therapy through improved connective tissue regeneration.

A giant solitary schwannoma of the arm mimicking cyst hydatid.

We present a 77-year-old female with a size of 9.5×9×7 cm3 giant schwannoma of musculocutaneous nerve volarly located in midarm, which was misdiagnosed as cyst hydatid on ultrasonographic and magnetic resonance image examination. There was not any neurologic sequele after the operation. In case of the similarity of their clinical and radiological findings, schwannoma should be included in the differential diagnosis of hydatid cysts especially in endemic countries.

Protective effect of melatonin against oxidative stress on adhesion formation in the rat cecum and uterine horn model.

This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) and the effect of melatonin on these metabolites in a postoperative intraperitoneal adhesion formation model in rats. Thirty adult female Wistar albino rats were subjected to standardized lesions by cecal and uterine horn abrasion and were randomly divided into three groups. Control rats were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin before closure and for 10 consecutive days intraperitoneally after surgery. Rats in the sham operation group underwent a surgical procedure similar to the other groups however the peritoneal abrasion was not performed. On postoperative day 10 relaparatomy was performed. After the assessment of the adhesions, the rats in each group were sacrificed and peritoneal tissues were harvested to determine the tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the melatonin group were significantly lower than that of control and sham group (p<0.01 and p<0.02, respectively). Tissue levels of MDA and NO were significantly lower in the melatonin treated rats when compared with control and sham groups. The levels of GSH in the melatonin treated rats were significantly higher than those of control and sham groups (p<0.01). The results demonstrate that in this experimental model, intraperitoneal administration of melatonin decreases the extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH levels.

Osteofibrous dysplasia-like adamantinoma in a 3-month-old male infant: a case report.

We report a case of a very rarely seen osteofibrous dysplasia-like adamantinoma (OFDLA) of the lower leg in a 3-month-old male infant, making it the youngest case in the literature. OFDLA is typically regarded as a benign lesion; however, due to its convertibility into classical adamantinoma, it is recommended to evaluate it as a pre-malignant lesion. After OFDLA diagnosis with biopsy, our case underwent surgical resection and reconstruction with a large allograft. Patient experienced good outcomes and did not experience any local relapse in the 3-year follow-up.

Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn.

PURPOSE: To evaluate the effects of resveratrol and bevacizumab on experimental corneal neovascularization. METHOD: A corneal alkali burn was performed in 62 eyes of 31 male white Vienna rabbits. Resveratrol (group 1), dimethyl sulfoxide (group 2), bevacizumab (group 3) and 0.9% NaCl (group 4) were administered to both eyes of the rabbits by subconjunctival injection for 7 days. Corneal photos were taken at 15 days after alkali injury. Inflammatory index scores and neovascularization areas were calculated. RESULTS: In bevacizumab group both inflammatory index scores and the calculation of the corneal neovascularization area was significantly less than the groups. CONCLUSION: The subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model. No effect of resveratrol to the corneal neovascularization on experimental model of the corneal alkali burn was seen at the doses of usage.

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus (PMME) comprises only 0.1-0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ultrasonography findings and management of a PMME case.

Beneficial effects of aminoguanidine on skin flap survival in diabetic rats.

Random flaps in DM patients have poor reliability for wound coverage, and flap loss remains a complex challenge. The protective effects of aminoguanidine (AG) administration on the survival of dorsal random flaps and oxidative stress were studied in diabetic rats. Two months after the onset of DM, dorsal McFarlane flaps were raised. Forty rats were divided into four groups: (1) control, (2) AG, (3) DM, and (4) DM + AG groups. Flap viability, determined with the planimetric method, and free-radical measurements were investigated. In addition, HbA1c and blood glucose levels, body weight measurements, and histopathological examinations were evaluated. The mean flap necrotic areas (%) in Groups I to IV were 50.9 ± 13.0, 32.9 ± 12.5, 65.2 ± 11.5, and 43.5 ± 14.7, respectively. The malondialdehyde (MDA) and nitric oxide (NO) levels were higher in the DM group than in the nondiabetic group, while the reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity were reduced as a result of flap injury. In the diabetic and nondiabetic groups, AG administration significantly reduced the MDA and NO levels and significantly increased GSH content and SOD enzyme activity. We concluded that AG plays an important role in preventing random pattern flap necrosis.

Ocular surface and dry eye in Graves' disease.

PURPOSE: To evaluate the tear function tests and the ocular surface damage in Graves' disease (GD) patients either with or without thyroid associated orbitopathy (TAO). METHODS: Forty-two eyes of 21 randomly selected patients with GD, and 30 eyes of 15 healthy subjects were included in this prospective study. The presence of TAO was evaluated clinically. The palpebral fissure height, degree of proptosis, ocular surface disease index (OSDI), Schirmer tear test, tear break-up time (TBUT), and conjunctival impression cytology were assessed. The results were first compared between the patient and the control groups. Results were then compared between the patients with TAO (group I) and without TAO (group II). RESULTS: The mean OSDI score in the patient group was 44.79 ± 11.83 and it was 21.17 ± 9.89 in the control group (p = 0.001). The mean Schirmer tear test score was 14.4 ± 8.32 mm and 24.9 ± 3.57 mm in the patient and control group, respectively (p = 0.001). The mean TBUT in the patient group was 7.1 sec. In the control group it was significantly increased to 10 sec (p = 0.003). The mean proptosis and interpalpebral distance did not show any difference between the GD patients and controls (p > 0.05). The patients with GD showed significant ocular surface damage in which 75.71% had grade 2-3 squamous metaplasia in temporal interpalpebral conjunctiva. Twenty-four (57%) eyes composed group I. There were no differences in the mean OSDI score, Schirmer tear test score, TBUT, and the amount of ocular surface damage between group I and group II (p > 0.05). CONCLUSIONS: Dry eye findings and the ocular surface damage in GD were most likely associated with the ocular surface inflammation. Before the development of the classic findings of TAO, ocular surface inflammation can be the only presenting clinical sign in GD.

The expression of matrix metalloproteinases in intrahepatic cholangiocarcinoma, hilar (Klatskin tumor), middle and distal extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma: role of matrix metalloproteinases in tumor progression and prognosis.

BACKGROUND/AIMS: Carcinomas of the biliary tree are rare tumors of the gastrointestinal tract, with an increasing incidence in recent years. Biliary neoplasms are classified into intra- and extrahepatic cholangiocarcinoma (Klatskin tumor, middle and distal extrahepatic tumors), gallbladder adenocarcinoma, and ampullary carcinoma. We aimed to determine the expression profile of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-14 in the biliary neoplasms classified according to their localization and the relation with the prognosis. METHODS: Ten gallbladder adenocarcinoma, 8 distal bile duct carcinomas (distal cholangiocarcinoma), 8 Klatskin tumors, 8 intrahepatic cholangiocarcinomas and 10 ampullary carcinomas were included in the study. The immunohistochemical expression of MMP-2, MMP-9 and MMP-14 was detected in the nontumoral, metaplastic, dysplastic and tumoral epithelia. The tumor differentiation, angiolymphatic and perineural invasion of the tumor, and presence of lymph node and distant metastasis were determined. Survey of the patients was noted from the patient follow-up data. RESULTS: The nontumoral epithelia of the gallbladder, intrahepatic ducts, and Klatskin tumor did not express MMP-2. MMP-2 expression was detected in the distal part of the biliary ducts, in 75% (6/18) of cases and in the nontumoral epithelia of the ampullary region in 50% (5/10) of cases. The metaplastic and dysplastic epithelia were positively stained in all of the gallbladder adenocarcinoma, distal cholangiocarcinoma and ampullary tumors. In the intrahepatic cholangiocarcinoma, the hepatocytes were positively stained but the infiltrative tumors were spared. Klatskin tumors were also not stained with MMP-2. The gallbladder adenocarcinoma, distal cholangiocarcinoma and ampullary carcinomas expressed MMP-2 in 30%, 37% and 40% of the cases, respectively. MMP-9 and MMP-14 were expressed in normal, metaplastic, and dysplastic epithelium and tumoral cells in all of the cases of the groups. Expressions of MMPs were higher in subjects with neural invasion, but there was no correlation between MMP expression and tumor differentiation or angiolymphatic invasion. CONCLUSIONS: When tumors of the biliary system are divided as intrahepatic and extrahepatic cholangiocarcinomas, MMP-2 expression was present in the extrahepatic cholangiocarcinomas including gallbladder carcinomas. Like the intrahepatic cholangiocarcinoma, Klatskin tumors also did not express MMP-2. This can be related with its characteristic growth pattern. MMP-9 and MMP- 14 were present in metaplasia, dysplasia carcinoma sequence in all of the bile tract tumors, suggesting that MMPs play an important role in carcinogenesis. The higher expression of the MMPs with neural invasion suggests the significant role of those tumors in the invasion activity.