Surgery for mixed hepatocellular and cholangiocellular carcinoma.

BACKGROUND/AIMS: Mixed tumors composed of hepatocellular carcinoma and cholangiocellular carcinoma are rare. In this report, the clinicopathologic characteristics and treatment outcome of four patients with mixed hepatocellular and cholangiocellular carcinomas are described. METHODOLOGY: Of 539 patients with primary liver cancer who underwent hepatic resection in our department over a 17-year period, 4 were diagnosed with mixed hepatocellular and cholangiocellular carcinoma. The clinicopathological features and treatment outcomes of these 4 patients were investigated. RESULTS: All 4 patients were positive for hepatitis C virus antibody and had hypervascular tumors. Tumor resection was performed for all patients. Three underwent lymph node dissection. At the time of this study, 1 patient was alive without recurrence 12 months after surgery. The other patients died within 28 months of surgery. CONCLUSIONS: Mixed tumors should be considered in patients with a liver mass and increased serum carcinoembryonic antigen and carbohydrate antigen 19-9 concentrations, a low alpha-fetoprotein concentration, and hypervascularity. The cholangiocellular carcinoma component appears to determine the prognosis.

A surgically treated case of hepatocellular carcinoma with extensive lymph node metastases.

A 62-year-old man with chronic hepatitis C was found to have a hepatic tumor by ultrasonography. Computed tomography of the liver disclosed a tumor 4 cm in diameter occupying the posterior segment and associated with a portal tumor thrombus and enlargement of hilar and paraaortic lymph nodes. At laparotomy multiple nodal metastases were seen involving hilar, hepatoduodenal, common hepatic arterial, and paraaortic nodes. We performed right hepatic lobectomy and systematic lymph node dissection. Histologic examination of both the main tumor and nodal metastases showed poorly-differentiated hepatocellular carcinoma. Severe postoperative ascites persisted for 1 month. Fifteen months after surgery the patient died of multiple intrahepatic and systemic nodal recurrences. Our experience confirms that surgical treatment of hepatocellular carcinoma with nodal metastases is likely to benefit only a few carefully selected patients, since the prognosis is commonly poor and hepatectomy with lymph node dissection carries the risk of severe complications.

Right hepatic lobectomy for recurrent cholangitis after bile duct and hepatic artery injury during laparoscopic cholecystectomy: report of a case.

A patient is reported who required a right hepatic lobectomy for recurrent cholangitis due to injury of the major bile ducts and the right hepatic artery during laparoscopic cholecystectomy. A 39 year-old woman with acute cholecystitis underwent laparoscopic cholecystectomy. A laparotomy was performed due to a bile duct injury at the hepatic bifurcation. After surgery, she suffered from recurrent cholangitis due to inadequate biliary reconstruction. A right hepatic lobectomy and reconstruction of the left hepatic duct was required because of right hepatic lobe atrophy and recurrent cholangitis. After the 2nd operation, she was active and exhibited no evidence of recurrence at 22 months.

Type I allergy to foods in atopic dermatitis. Comparison between RAST-positive and RAST-negative cases.

Radioallergosorbent tests (RASTs) with five common foods were performed in 183 patients with atopic dermatitis. The results showed that about half of the patients had type I allergy to at least one of the five foodstuffs. The RAST results correlated roughly to the severity of dermatitis. In each group of patients with mild, moderate and severe atopic dermatitis, positive RAST reactions to common foods occurred predominantly in patients who had a personal or a family history of respiratory atopy. Positive RASTs were rare in patients with pure atopic dermatitis who had neither personal nor family history of respiratory atopy. It seems likely that type I food allergy occurs predominantly in those patients with atopic dermatitis who have a predisposition to respiratory atopy.

Changes in the seasonal dependence of atopic dermatitis in Japan.

Although it has been generally accepted that seasonal aggravation of skin symptoms is a basic feature of atopic dermatitis, recent studies have suggested a decrease in the seasonal dependence of the dermatosis in European countries over the past several decades. We examined incidence of seasonal deterioration of atopic dermatitis in Japanese subjects. The study population consisted of 682 patients aged 3 to 30 years with atopic dermatitis, who visited our outpatient clinic from August 1998 through July 2000. Of these, 452 (66%) showed a seasonal aggravation of skin symptoms, and 230 (34%) had perennial deterioration. The overall incidences of exacerbation in spring, summer, autumn and winter were 25%, 19%, 11% and 36%, respectively. Further, 358 (52%) showed unpredictable and irregular exacerbations of skin symptoms every few days or weeks. These irregular worsenings were more frequent in patients who showed perennial deterioration than in those with seasonal aggravation. From a comparison of the present results with those reported in the 1960s, it became evident that a real decrease in the incidence of seasonal aggravation of atopic dermatitis has occurred over the past three decades in Japan and that the incidence of summer deterioration has greatly decreased during the same period of time.

Successful treatment of dissemination of hepatocellular carcinoma to the pleura and diaphragm after percutaneous liver biopsy.

BACKGROUND/AIM: Treatment for dissemination of hepatocellular carcinoma to the pleura and diaphragm following percutaneous needle biopsy has not been established. METHODS: The case of a 57-year-old man who underwent percutaneous needle biopsy for liver tumor is presented. RESULTS: Ten months after resection of the tumor (moderately differentiated hepatocellular carcinoma), masses in the right pleural cavity and on the diaphragm were detected by computed tomography. Resections of the masses with surrounding tissue and the diaphragm and wedge resection of the right lung were performed. A wide range of the pleura and the diaphragm was coagulated with an argon beam coagulator. The patient is in good health without recurrence 4 years after the operation. CONCLUSION: Aggressive surgical treatment should be considered for patients with dissemination of hepatocellular carcinoma by needle biopsy when the lesions are limited.

Resectable pleomorphic giant cell carcinoma of the pancreas.

We present a 72-yr-old woman who underwent surgical resection of a large pancreatic tumor. On preoperative imaging, an intratumoral cavity containing necrotic tissue was noted, mimicking the appearance of a cystic tumor. There was no invasion of adjacent organs nor distant metastasis, and histopathologic examination revealed the tumor to be a giant cell carcinoma. Postoperatively, the patient has been followed for 1.5 yr without evidence of recurrence. Giant cell carcinoma generally is associated with a poor prognosis, and patients usually die within months despite intensive multimodality therapy. Some patients with giant cell carcinomas, however, achieve long-term survival when invasion of adjacent organs and distant metastases are absent. Surgical resection is the appropriate treatment for tumors with these favorable characteristics.

Histologic factors affecting prognosis following hepatectomy for intrahepatic cholangiocarcinoma.

Long-term survival following hepatectomy for intrahepatic cholangiocarcinoma has been poor, and specific factors influencing survival are unclear. In a retrospective study we sought to determine prognostic factors related to survival in these patients. In 28 patients who underwent hepatic resection for intrahepatic cholangiocarcinoma, we investigated the relations of several histologic factors to patient survival by univariate and multivariate analyses. No deaths occurred during the first 30 days. Median and mean survival times following hepatectomy were 409 and 935 days, respectively. The respective survival rates at 1, 3, and 5 years were 57%, 27%, and 27%. Resection margin status, intrahepatic metastasis, lymph node involvement, and lymphatic invasion were significant predictors of outcome. In a multivariate analysis using the Cox proportional hazards model, only lymphatic invasion independently predicted survival. Curative resection with clear margins was found to prolong survival after surgery. Hepatectomy for intrahepatic cholangiocarcinoma without lymphatic invasion offers hope for long-term survival.

Clinicopathological factors predicting outcome after resection of mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with intrahepatic cholangiocarcinoma differs according to macroscopic type. The identification of clinical and pathological features that predict outcome in patients with mass-forming intrahepatic cholangiocarcinoma is required in order to determine optimal surgical strategies for patients with this type of tumour. METHODS: The details of 35 patients with resected mass-forming intrahepatic cholangiocarcinomas were analysed retrospectively. Univariate analysis of potential prognostic factors was performed. RESULTS: The cumulative survival rate at 1, 3 and 5 years after operation was 58, 33 and 33 per cent respectively. Patients with stage II tumours had a better outcome than those with advanced stage tumours. By univariate analysis, lymphatic invasion, lymph node metastasis, intrahepatic satellite lesions and microscopic resection margin involvement were found to be highly significant variables and were identified as possible risk factors for a poor outcome after operation. CONCLUSION: When frozen-section examination of lymph nodes reveals negative nodal metastasis, extensive anatomical hepatic resection is indicated for mass-forming intrahepatic cholangiocarcinomas. Intraoperative frozen-section examination of the resection margin to confirm the absence of cancer cells is recommended.

Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer.

Using an electrochemiluminescence immunoassay, CYFRA 21-1 concentrations were measured in sera from 187 patients with primary liver cancer (164 with hepatocellular carcinoma (HCC) and 23 with intrahepatic cholangiocarcinoma (ICC)) and 87 patients with benign liver diseases. Concentrations of CYFRA 21-1 were significantly higher in patients with ICC (5.0; interquartile range 3.1-10.7 ng ml(-1)) than in those with benign liver disease (1.4; 1.0-1.9; Mann-Whitney U-test, P<0.0001) or HCC (1.7; 1.1-2.7; Mann-Whitney U-test, P<0.0001). Using cutoff values selected for 95% specificity in the benign group (3.0 ng ml(-1)), CYFRA 21-1 showed higher sensitivity for ICC (87.0%) than three commonly used markers including alpha-fetoprotein (17.4%), carcinoembryonic antigen (34.8%), and carbohydrate antigen 19-9 (60.9%). Serum CYFRA 21-1 increased in ICC from stages I/II to IV (Kruskal-Wallis test, P=0.0102). CYFRA 21-1 concentration increased with extent of local invasion, but not nodal status. Serum CYFRA 21-1 represents a useful diagnostic test for ICC that offers high sensitivity. CYFRA 21-1 reflected differences in tumour burden, suggesting applicability to staging and follow-up.

Spontaneous regression of a large hepatocellular carcinoma with portal vein tumor thrombi: report of a case.

A 65-year-old man with chronic hepatitis C showed a markedly elevated serum alpha-fetoprotein concentration. Computed tomography revealed a huge tumor occupying the entire right hepatic lobe. Three months later, the tumor regressed spontaneously from 12 cm to 7 cm in diameter without any medical treatment. A right hepatic lobectomy was performed 4 months after the initial diagnosis. The main tumor, located in the posterior inferior segment, was completely necrotic, and had a thick fibrous capsule. Many inflammatory cells had also infiltrated into the tumor. Only a small portion of a tumor thrombus in the portal vein and one of three intrahepatic metastases contained viable cancer cells. The tumor was found to be poorly differentiated hepatocellular carcinoma. Tumor regression may have been caused by a disturbance in hepatic circulation associated with the portal vein thrombus.

Pleural dissemination as a complication of preoperative percutaneous transhepatic biliary drainage for hilar cholangiocarcinoma: report of a case.

One potential risk of percutaneous transhepatic biliary drainage is tumor seeding along the catheter tract. A 57-year-old woman with obstructive jaundice due to hilar cholangiocarcinoma underwent an extended left hepatic lobectomy, a regional lymph node dissection, and a right hepaticojejunostomy 2 weeks after percutaneous transhepatic biliary drainage. Multiple right pleural masses were found on a chest radiogram 14 months after the operation. No recurrent lesions were detected in the abdominal cavity. A right panpleuropneumonectomy was performed; however, the patient died of respiratory failure due to tumor recurrence 9 months after the second operation. Preoperative percutaneous transhepatich biliary drainage was considered to have resulted in pleural implantation.

The clinical significance of lymph node metastases in patients undergoing surgery for hepatocellular carcinoma.

The frequency of lymph node (LN) metastasis in patients undergoing surgery for hepatocellular carcinoma (HCC) has rarely been studied. We evaluated the clinicopathologic characteristics and outcomes of six patients with nodal metastases from HCC among a total of 504 patients who underwent hepatic resection for HCC in our department over a 16-year period. The nodal metastases were diagnosed preoperatively in two patients. The average diameter of the resected tumors was 7.8 cm and all were confirmed as poorly differentiated HCC. All of the six patients had intrahepatic metastatic nodules and five also had portal vein invasion. One patient underwent limited resection, and the other five underwent bisegmentectomy. All of the regional LNs were removed in one patient, while only enlarged LNs were removed in the other five. One patient died of postoperative liver failure and the others all died later of intrahepatic or nodal recurrence. Our findings suggest that the prognosis of patients with nodal metastasis from HCC is generally poor, even if hepatic resection with regional LN dissection is performed.

Surgical management of synchronous hepatocellular carcinoma and gastric cancer.

BACKGROUND/AIMS: The improvement of diagnostic modalities and operative techniques has resulted in prolonged survival for cancer patients, but has also led to the diagnosis of an increasing number of patients with synchronous hepatocellular carcinoma (HCC) and extrahepatic primary cancer. It is necessary to determine the optimal surgical strategies for synchronous HCC and gastric cancer. METHODS: In this retrospective study, clinicopathologic findings, diagnostic methods, treatment and outcome were reviewed in 13 patients who underwent curative surgery for synchronous HCC and gastric cancer. RESULTS: Twelve of the 13 patients were men older than 60 years. All patients had chronic hepatic disease, and hepatitis viral infection was detected in 9 patients. Examinations of the esophagus to search for esophageal varices before liver resection for HCC, and imaging studies to rule out liver metastasis before gastrectomy for gastric cancer can lead to the incidental finding of a synchronous carcinoma. The most frequent postoperative complication was massive ascites, which occurred in 4 patients who underwent lymph node dissection, 1 of whom died of perioperative hepatic failure. HCC recurred in 7 patients, 4 of whom died of their disease; only 1 patient died of recurrence of gastric cancer. CONCLUSION: Careful follow-up for recurrence of HCC is necessary because the most common cause of death in patients with synchronous carcinoma is recurrence of HCC.

A pancreatic anaplastic carcinoma of spindle-cell form.

A 56-yr-old man with complaint of abdominal pain and body weight loss was admitted to our hospital. Contrast-enhanced computed tomography on admission revealed a pancreatic tumor. Contrast-enhanced computed tomography 1 m.o. after admission revealed rapid growth of this tumor. We performed exploratory laparotomy with only a needle biopsy of the unresectable tumor because of extensive spread, including liver metastases. Further histological and immunohistochemical examination revealed that both the pancreatic tumor and the hepatic metastases featured malignant spindle-shaped cells. Despite radiotherapy, the patient died 40 d after laparotomy.

Relationship of the microvascular type to the tumor size, arterialization and dedifferentiation of human hepatocellular carcinoma.

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty-eight HCCs with a diameter of 10 - 140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid-containing hepatic stellate cells. Well-, moderately and poorly differentiated HCCs displayed sinusoidal / intermediate / capillary types, intermediate / capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well-differentiated (and probably moderately differentiated) HCCs. Furthermore, well-differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well-differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well-differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.