Resected case of a double cancer,a hepatocellular carcinoma and a cholangiocellular carcinoma,and their spread to the skin

Combined hepatocellular and cholangiocellular carcinomas are rare. Moreover, double cancer cases of hepatocellular carcinoma and cholangiocellular carcinoma are very rare. This report describes a patient with double cancer. A correct clinical diagnosis was made with successful resection, and cutaneous metastases occurred near the exit site of an abdominal drain after the resection of the tumor. The patient, a 66-year-old man with chronic hepatitis C, was admitted to our hospital because he was suspected of having primary liver cancer. Two liver masses in the anteroinferior segment were detected by using angiography, computed tomography during angiography, and computed tomography during arterioportography. These clinical findings indicated that the tumor in the right lobe was hepatocellular carcinoma. A resection of the S5 subsegmentectomy was performed. One mass was diagnosed histologically as hepatocellular carcinoma, and the other mass was diagnosed as cholangiocellular carcinoma. One year after the operation, the patient palpated a hard subcutaneous nodule 4.0 cm in diameter in the right lower abdominal wall. A subcutaneous tumor was excised, and a histological examination revealed moderately differentiated hepatocellular carcinoma. The patient is currently doing well without further recurrence of hepatocellular carcinoma or cholangiocellular carcinoma, 18 months after subsegmentectomy and six months after excision of the subcutaneous tumor.     

Mucin-producing adenoma associated with pancreas divisum and hepatic hilar carcinoma: An autopsy case

We present the autopsy case of an 82-year-old Japanese woman with a mucin-producing adenoma accompanied by pancreas divisum and a hepatic hilar carcinoma. She had suffered from a cholangiocellular carcinoma at the hepatic hilus for 2 months, which was treated with radiation and chemotherapy. She did not complain of any abdominal pain. Obstructive jaundice deteriorated despite percutaneous transhepatic bile duct drainage, and she died of hepatic insufficiency. At autopsy, a hepatic tumor was confirmed to have caused severe obstructive jaundice. Histological examinations showed moderately to poorly differentiated cholangiocellular adenocarcinoma with squamous metaplasia, probably due to radiation. A yellowish mucinous tumor was found in the head of the pancreas near the minor papilla. It consisted of multiple rice-sized cystic lesions with thin septa. Although it had no capsule, its margin was clear. Neither a wide opening of the major or minor papilla nor mucous drainage was observed. Gross examinations revealed unfused pancreatic ducts. The slightly dilated dorsal duct and a branch of the mildly dilatated ventral duct showed tumor involvement. Histological examinations showed mild atypia of the epithelia, and this pancreatic tumor was diagnosed as branch duct-type mucin-producing adenoma with postradiation dysplasia. The combination of a mucin-producing tumor and pancreas divisum is rare, and this is only the third reported case.     

Nine-Year survivor after resection of cholangiocellular carcinoma with tumor thrombi in the main portal trunk

We report a patient with cholangiocellular carcinoma with tumor thrombi in the main portal trunk who has survived for 9.5 years after hepatic resection. A 57-year-old woman underwent an extended left lobectomy, and resection of the caudate lobe plus the main portal trunk for a liver tumor that had a portal tumor thrombus in the main portal trunk. The portal vein was reconstructed with an autologous vein graft obtained from the external iliac vein. Histological examination of the resected specimen revealed moderately differentiated tubular adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing to the patient's long-term survival are discussed. Aggressive surgical resection can be effective even for such an advanced case of cholangiocellular carcinoma. Received Dec. 9, 1997; accepted Mar. 27, 1998     

Parathyroid hormone-related peptide producing cholangiocellular carcinoma with a marked psammoma formation

Humoral hypercalcemia caused by parathyroid hormone-related peptide (PTHrP), associated with cholangiocellular carcinoma (CCC), has rarely been documented. There have been no reports of CCC associated with extensive calcification of the tumor with psammoma body formation. A 66-year-old man was admitted with a large calcified tumor in the liver detected on an abdominal X-ray. An ultrasound-guided fine needle biopsy specimen of the liver tumor showed evidence of adenocarcinoma. He had hypercalcemia with an elevated PTHrP level. The patient died because of disseminated intravascular coagulation and progressive hepatic failure. A postmortem examination revealed a large poorly differentiated CCC in the liver. Immunohistochemical examination showed the presence of PTHrP-positive tumor cells. The calcified lesion consisted of a number of accumulated psammoma bodies. We present a case of PTHrP producing CCC with a marked psammoma formation.     

Primary cholesterol hepatolithiasis associated with cholangiocellular carcinoma: a case report and literature review

Hepatolithiasis associated with cholangiocellular carcinoma is occasionally a calcium bilirubinate stone. Primary cholesterol hepatolithiasis associated with cholangiocellular carcinoma is rare; only 6 cases have been reported in the literature. A 55-year-old man was admitted to our hospital because of an elevated level of carbohydrate antigen 19-9. Various imaging studies demonstrated a mass in the segment VII of the liver. The patient underwent a curative surgical operation. Histopathological examination revealed that it was cholangiocellular carcinoma located in the periphery of the liver. A cholesterol stone was present, encircled by the cholangiocellular carcinoma. Minor inflammatory changes were observed around the stone.     

An unusual growth pattern of a mucin-producing intrahepatic cholangiocellular carcinoma involving the hepatic hilus.

The case of a mucin-producing intrahepatic cholangiocellular carcinoma in a 73 year-old-man is presented. A tumor originating in the right posterior inferior segment of the liver was found to be invading the right posterior and anterior bile ducts, and the hepatic hilus. Extensive superficial spread was observed in the entire posterior segmental bile duct extending to the hepatic hilus. Mucin produced and excreted by the tumor was retained in the common hepatic and common bile duct. The diagnosis in this case was suggested by percutaneous transhepatic aspiration of mucinous bile, and was confirmed by utilizing the techniques of ultrasonography, percutaneous transhepatic cholangiography, computed tomography and angiography. Curative surgery, which included right hepatic lobectomy with total caudate lobectomy and bile duct resection, was performed. Biliary continuity was maintained by left hepaticojejunostomy using a Roux-en-Y jejunal loop. The histological diagnosis was mucin-producing papillary adenocarcinoma originating in the right posterior inferior segment of the liver. Postoperative recovery was very good and the patient has now been enjoying a good active social life for the last 20 months with no signs of tumor recurrence. This case report discusses the unusual growth pattern of a mucin-producing intrahepatic cholangiocellular carcinoma involving the hepatic hilus, and suggests rational surgical treatment.     

Occurrence of hepatocellular and cholangiocellular carcinoma in different hepatic lobes

Separate hepatocellular and cholangiocellular carcinoma (double cancer) in the liver are extremely rare subtypes of primary hepatic carcinomas. We report a case of double primary liver carcinomas that were surgically resected simultaneously. A 66-year-old man was admitted because of elevation of serum levels of alpha-fetoprotein. Abdominal computed tomography and angiography showed two hypervascular masses in S4 and S8 hepatic segments. With the diagnosis of multiple hepatocellular carcinomas, the tumors were surgically resected. Histological examination showed that the tumor in S4 segment was moderately differentiated cholangiocellular carcinoma, the other in S8 segment was trabecular, moderately differentiated hepatocellular carcinoma. Immunohistochemically, a positive staining in carcinoembyonic antigen and cytokeratin 7 supported the diagnosis of cholangiocellular carcinoma for the tumor in S4 segment. The frequency of double cancer in the liver is much lower than mixed or combined cancer (0.1-0.5%). The different epithelial malignant tumors of hepatocellular carcinoma and cholangiocellular carcinoma, which were located in different hepatic lobes and resected simultaneously, has been reported in only two cases including the present case.     

Cholangiocellular Carcinoma Associated with Multiple Liver Cysts

A 46-year-old woman visited our outpatient clinic complaining of dull right hypochondrial pain. Ultrasonography revealed four cysts in the right lobe of the liver. Arteriography and CT could not determine whether these cysts were benign or malignant. Because one of these cysts contained chocolate-colored fluid, amebic abscess was suspected, and the cyst was drained. No amebae were found in the cultured exudate, and fresh bleeding continued; therefore, laparotomy was performed. A tumor was present on the surface of the liver. Right lobectomy was performed. The resected specimen contained one nonepithelialized cyst which was invaded by surrounding cholangiocellular carcinoma and three epithelialized cysts. Preoperative diagnosis of this kind of cholangiocellular carcinoma seems to be very difficult. Recently cholangiocellular carcinoma associated with developmental cysts has been classified as a new entity different from cystadenocarcinoma. Cholangiocarcinoma, which belongs to this group, seems to deserve special attention.     

Diagnosis and treatment of cholangiocellular carcinoma of the liver

Of the 239 patients with primary liver cancer treated in our department over the last 13 years, 27 had cholangiocellular carcinoma, and 4 cystic adenocarcinoma of the liver. In this paper, the diagnosis and treatment of cholangiocellular carcinoma was reviewed and discussed. Twenty-four (88.9%) of the 27 patients with cholangiocellular carcinoma underwent surgery and 16 (66.7%) had hepatic resection. There were no operative deaths. None with hilar type cancer survived more than 2 years but in the case of the peripheral type the one-year cumulative survival rate after hepatectomy was 63.6%, the 3- and 5-year rates were both 33.9%. Two cases survived more than 5 years. One was a 69-year-old female who died of tumor recurrence 5 years and 6 months after hepatectomy; the other a 61-year-old female who is still alive and well, without recurrence, 10 years and 5 months after right trisegmentectomy. Although the cholangiocellular carcinoma in our series were in the advanced stages, good results were obtained by hepatic resection with multimodal treatment.     

Diffuse and psammomatous calcification in intestinal type gastric carcinoma: report of two cases with literature review

Psammoma bodies are round, concentrically laminated calcospherites ranging from 5 to 100 μm in diameter. They may indicate certain types of tumors including papillary carcinoma of the thyroid, meningioma and papillary serous tumors of the ovary, and to a lesser extent may be found in leiomyomas and angiomas of the gastrointestinal tract. Dystrophic calcification is uncommon in gastric cancer and displays either diffuse or psammomatous pattern. Diffuse type calcification is generally seen within the pools of mucin in advanced mucinous adenocarcinoma. Conversely, psammomatous calcification is associated with non-mucinproducing carcinomas and detected not only within the carcinomatous glandular lumina but also in the stroma. Total gastrectomy specimens of a 74-year-old male and a 54-year-old female with moderately differentiated intestinal type adenocarcinomas revealed diffuse and psammomatous calcification, respectively. Although diffuse type calcification is well-documented, to date it has not been reported in non-mucin-producing intestinal gastric carcinoma. Moreover, the psammomatous type is exceptionally rare, and only six such cases have been reported in the literature; the current patient represents the seventh case.     

Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas.

BACKGROUND/AIMS: Patients with advanced unresectable hepatobiliary carcinomas have a dismal prognosis. The efficacy of systemic chemotherapy in these patients is negligible and often, in particular in patients with hepatocellular carcinomas, the toxicity of chemotherapy outweighs the potential palliative effect of antineoplastic agents. Gemcitabine is a new anticancer agent with a mild toxicity profile, which has demonstrated antineoplastic activity in many solid tumors. Therefore we investigated the effect of gemcitabine in patients with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a phase II study. METHODOLOGY: Twenty-three patients with cholangiocellular carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the study. Eighteen of the 20 patients with hepatocellular carcinomas had liver cirrhosis. Gemcitabine was administered once weekly over 30 min for 3 consecutive weeks out of every 4 weeks. Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle. Disease status was assessed every 4 weeks. RESULTS: Overall the regimen was well tolerated. The median number of gemcitabine administration was 15 (range, 3-37) in the group of patients with cholangiocellular carcinomas and 7.6 (range, 3-21) in the group of patients with hepatocellular carcinomas. In the group of patients with hepatocellular carcinomas thrombocytopenia was the most frequent side effect (30% grade 3/4). Among the patients with cholangiocellular carcinomas nausea and neutropenia were the most commonly observed side effects. The overall response rate of hepatocellular carcinomas was only 5% and chemotherapy generally did not improve the tumor symptoms of the patients in this group. In contrast, in the group of cholangiocellular carcinomas, seven patients achieved a partial response (overall response rate 30%). Eleven patients with cholangiocellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment. Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight. CONCLUSIONS: Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies. In contrast, palliative chemotherapy with gemcitabine cannot be recommended in patients with hepatocellular carcinoma and liver cirrhosis.     

Epithelioid hemangioendothelioma of the liver

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor and is difficult to differentiate from cholangiocellular carcinoma or metastatic liver tumor on image diagnosis. A case of curatively resected EH of the liver is reported. A 48-year-old woman was admitted because she had a mass in the liver. Cholangiocellular carcinoma was suspected preoperatively. Right trisegmentectomy of the liver, combined with bile duct resection and portal vein resection and reconstruction, was performed. Characteristic macro- and microscopic findings of the resected specimen revealed EH of the liver. The patient has survived for more than 6 years without recurrence. Because of the tendency of EH of the liver to appear in multiple or scattered forms, only 12 cases of resection for EH have been reported.     

A case of cholangiolocellular carcinoma asynchronously developing 3 years after the resection of hepatocellular carcinoma

Cholangiolocellular carcinoma (CLC) is a rare malignant primary liver tumor, categorized as a subtype of cholangiocellular carcinoma. CLC is considered to originate from hepatic progenitor cells, and sometimes accompanies a component of cholangiocellular carcinoma and/or hepatocellular carcinoma (HCC). We report herein a case of a 53-year-old Japanese male with CLC occurring asynchronously after a resection of HCC. At the age of 50, the patient underwent a first hepatectomy due to HCC, followed by intrahepatic recurrence. At 53, a new type of hepatic tumor was detected. Dynamic computed tomography revealed a multinodular enhanced tumor in the hepatic arterial phase, and an iso-density tumor in the portal venous and delayed phases. Living donor liver transplantation was performed for the treatment of this liver tumor because of his poor liver function. Histological findings confirmed the diagnosis of CLC. Nineteen months after the liver transplantation, bone metastasis of CLC was detected. Although the preoperative diagnosis of CLC is difficult in general, CLC should be considered as a differential diagnosis when a tumor with atypical image findings for HCC is observed after the resection of HCC. Once the diagnosis of CLC is made, postoperative surveillance of the patient must be performed, including the bone.     

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy： Report of a case and a review of the literature

Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.     

A mixed hepatocellular carcinoma and cholangiocarcinoma: dual expression of biliary-type cytokeratin and hepatocyte specific marker

A 5-cm lesion in the right hepatic lobe was detected in a 61-year-old man with chronic hepatitis C by ultrasonography. Contrast-enhanced computed tomography showed a low-density lesion with wide peripheral enhancement. Hepatic angiography revealed that the tumor had partial hypervascularity. Although serum concentrations of alpha-fetoprotein and carcinoembryonic antigen were within normal limits, an elevated concentration of carcinohydrate antigen 19-9 was detected in serum. A definitive diagnosis was not made although we strongly suspected mixed hepatocellular carcinoma and cholangiocarcinoma. Since intraoperative frozen-section examination revealed adenocarcinoma, a right hepatic lobectomy with regional lymph node dissection was performed. A histologic diagnosis of mixed hepatocellular carcinoma and cholangiocarcinoma was made because the hepatic tumor consisted of components of both hepatocellular carcinoma and cholangiocellular carcinoma, with a transitional area. Additionally, immunohistochemical examination revealed that some tumor cells in the transitional area were immunoreactive for both cytokeratin 19 and hepatocyte paraffin 1.     

Surgically treated cases of mixed hepatocellular carcinoma and cholangiocarcinoma

The mixed type of combined hepatocellular carcinoma and cholangiocarcinoma is particularly rare. Hepatic resection was performed for two patients with mixed hepatocellular carcinoma and cholangiocarcinoma. In case 1, a 55-year-old Japanese man was found to have a hepatic tumor on ultrasonography. Since ultrasonically-guided needle biopsy revealed that the tumor was poorly differentiated hepatocellular carcinoma, the patient underwent a limited hepatic resection. Histologic and immunohistochemical examination revealed that the tumor had elements of both hepatocellular carcinoma and cholangiocarcinoma. Six months after surgery, the patient died of systemic recurrences. In case 2, a 58-year-old man was found by ultrasonography to have a hepatic tumor occupying the entire right hepatic lobe. Computed tomography revealed that the tumor had a portal tumor thrombus. The diagnosis of hepatocellular carcinoma was made because of a markedly elevated serum alpha-fetoprotein concentration, and a right hepatic lobectomy was performed. Histologic and immunohistochemical examination confirmed that the lesion was mixed hepatocellular and cholangiocellular carcinoma. The patient died of multiple recurrent tumors in the remnant liver 3 months after surgery. Surgical control of mixed hepatocellular carcinoma and cholangiocarcinoma is difficult.     

p53 protein expression in intraductal papillary mucinous tumors (IPMT) of the pancreas as an indicator of tumor malignancy

BACKGROUND/AIMS: Intraductal papillary mucinous tumors, as a cystic disease in the pancreas, clinically has a more indolent and favorable course than invasive ductal pancreas carcinoma. However, some cases of intraductal papillary mucinous tumors show invasive and rapid progression like ductal pancreas carcinoma and the prognosis of such patients is sometimes poor. In the current study, we carried out immunohistochemical staining of intraductal papillary mucinous tumor tissues for p53 and investigated whether positive staining indicates tumor malignancies and has a prognostic value for intraductal papillary mucinous tumors. METHODOLOGY: Nineteen (19) patients who underwent pancreatic resection under the diagnosis of intraductal papillary mucinous tumors at the Chiba University Hospital between April 1992 and December 1996 were studied. We performed immunohistochemical staining of p53 as well as of PCNA, Ki-67 and Bcl-2 using their respective antibodies. Pathological findings revealed that 9 cases were intraductal papillary adenoma, 9 were intraductal papillary adenocarcinoma, and one was invasive ductal papillary adenocarcinoma. RESULTS: p53 expression could only be detected in the 1 case with invasive ductal papillary adenocarcinoma. Significant association could not be found between histological features and immunohistochemical staining of PCNA, Ki-67 and Bcl-2. CONCLUSIONS: p53 protein expression could be detected after progression to invasive type of intraductal papillary mucinous tumors. The present results demonstrate that p53 expression might be an indicator of invasive progression in intraductal papillary mucinous tumors, and might represent a surgical indicator of intraductal papillary mucinous tumors.     

An autopsy case of pulmonary metastasis of cholangiocellular carcinoma associated with marked fibrotic change of the lungs]

An autopsy case of pulmonary metastasis of cholangiocellular carcinoma is presented. A 44-year-old woman was admitted to our hospital because of dyspnea, general fatigue and a sense of abdominal fullness on February 5, 1990. In November 1986, at an other hospital, she had been diagnosed as having diffuse metastatic lung tumor and multiple bone metastases, by transbronchial lung biopsy and other examinations. During the clinical course, she was not received chest irradiation and chemotherapy which induced fibrotic change of lungs. Chest X-ray film on December 21, 1986 showed diffuse nodular shadows in both lung fields. Chest X-ray film on February 4, 1990 showed diffuse reticular shadows with marked shrinkage of lung fields. She died two months after admission. The primary site of the carcinoma was not determined clinically, but was revealed by autopsy to be cholangiocellular carcinoma of the liver, with generalized metastasis. Microscopic findings of the autopsied lung showed markedly increased connective tissue around bronchi and blood vessels, in areas where microtubular adenocarcinoma was scattered. This is a very rare case of pulmonary metastasis of cholangiocellular carcinoma, associated with marked fibrotic change of the lungs during about 3.5 years. To our knowledge, this is the first reported case.     

胰腺囊腺瘤与囊腺癌39例的CT影像学特征

目的 探讨胰腺囊腺瘤与囊腺癌的CT影像学特征.方法 回顾性分析经过病理证实的21例浆液性囊腺瘤、12例黏液性囊腺瘤、6例黏液性囊腺癌的CT影像学资料,分析肿瘤部位、单(多)囊、最大囊直径、囊壁特征、囊内分隔、肿瘤边界、肿瘤与胰管关系等影像学征象.结果 21例浆液性囊腺瘤中17例位于胰头颈部,5例位于胰体尾部,其中1例为多发;均为多囊,平均最大囊直径为1.8 cm;4例囊壁或分隔有钙化,7例分隔可见软组织成分;10例胰管轻度增宽.12例黏液性囊腺瘤中6例位于胰头颈部,6例位于胰体尾部;4例为多囊,平均最大囊直径为4.5 cm;1例分隔可见钙化,6例囊壁可见软组织成分;2例胰管扩张,3例胰管轻度增宽.6例黏液性囊腺癌中5例位于胰体尾部,1例位于胰头颈部;4例为多囊,平均最大囊直径为5.1 cm;1例分隔可见钙化,5例囊壁可见软组织成分;1例胰管扩张,1例胰管轻度增宽.所有病灶与胰管均不相通,增强后病灶软组织成分及分隔均有不同程度强化.结论 胰腺囊腺瘤与囊腺癌的CT表现具有一定的特征性,但对于少数不典型表现病例,诊断仍存在困难.     

35例原发性十二指肠癌的诊断及治疗分析

目的总结原发性十二指肠癌的诊治经验,提高其诊治水平。方法回顾分析2001年1月～2007年12月我院经内镜及手术确诊的35例原发性十二指肠癌患者的临床资料。结果本组病例肿瘤位于十二指肠球部6例;十二指肠降部26例;十二指肠水平部3例。其中乳头状腺癌8例、管状腺癌23例、黏液腺癌2例,类癌1例,恶性间质瘤1例。胃镜确诊率为77.4%;上消化道钡餐造影确诊率为52.4%。CT确诊率为46.7%;B超确诊率为10.3%;MRCP确诊率为6.9%。行胰十二指肠切除术22例,十二指肠乳头切除、乳头成形术6例,胃空肠吻合术3例,单纯肿物切除术1例,姑息性旁路手术2例。结论原发性十二指肠癌发病部位以十二指肠降部尤其乳头周围部为多,病理以腺癌为主;本病诊断首选内镜检查,其次是十二指肠气钡双重造影;手术切除尤其是胰十二指肠切除术是最常用、最可靠的治疗方法。