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A 68-year-old man was admitted to the hospital because of a sensation of fullness in the abdomen and right hypochondralgia. A diagnosis of cystadenocarcinoma of the liver was made by analysis of various diagnosticimagings. Hemigastrectomy and left hepatic lobectomy were performed. Cystadenocarcinoma of the liver is a relatively rare disease, though the case report been increasingly seen in the recent years. As the method of the preoparative diagnosis of the cystadenocarcinoma has not been yet established, we cannot help relying on the comprehensive analysis of various diagnostic imagings. In this case, a preoperative histopathological diagnosis was not made but magnetic resonance imaging (MRI) could offer characteristics of the internal structure of cystadenocarcinoma. MRI can be recommended to qualitative diagnosis of the disease. The classification of cystadenocarcinomas of the liver has been proposed in terms of the pathogenesis. According to the classification, cystadenocarcinoma of the liver in this case is thought to have grown up as an adenocarcinoma from the onset, on the basis of a fact that mucinous cancer cells were noted in the surrounding wall of the cyst.

1991年12月末までに治癒切除の施しえた肝癌263例のうち142例が再発し, これら症例のうち20例 (14%) に再切除が施行された.そこで再切除症例の初回切除時ならびに再切除時の臨床病理的所見を比較検討した.これら20例の再発確認までの平均日数は875日であり, indocyanine green 15分停滞率でみた肝機能は悪化する傾向にあり, 切除術式は縮小化していた.腫瘍径は小さくなる傾向にあるものの, 肝内転移巣, 門脈内腫瘍栓を有し, 多発する傾向にあった.また8例が対側葉に再発していた.これらを肝癌取扱い規約改訂第3版に基づいて肝内転移巣の増大と多中心性再多に分類することを試みたが, 鑑別の困難な症例が多かった.再発肝癌治療として再切除は有効ではあるものの, 再発肝癌の病態はなお不明な点が多い.これらの早急な解明と病態に応じた治療法の確立が肝癌治療成績の向上に必要である.

早期の微小肝細胞癌(肝癌)ならびにその境界病変における門脈血流の関与を検討するため,肝切除の術中あるいは術後に担癌門脈枝より色素を注入し,術後の病理標本上での結節内色素の有無を観察し,被膜形成ならびに分化度との関係を検索した.対象とした14例17結節を病理組織学的に検討したところ被膜形成のない高分化型肝癌は6結節(腫瘍径:10±7mm)であり,全例結節内に門脈域がみられたが,結節内に色素がみられたものは2結節に過ぎなかった.他の11結節のうち中分化型肝癌(29±26mm)は7結節で,被膜を有さない1結節にのみ色素がみられた.なお残りの4結節(34±10mm)は術前治療のため完全壊死に陥っていた.結節内色素の有無は各結節の組織学的分化度より被膜の有無とよりよく相関しており,肝癌の発育過程で被膜が形成されるに伴い腫瘍内門脈血流が低下することが示唆された.

Sixty patients undergoing hepatobiliary surgery were subjected to a bacteriological exploration in terms of postoperative infection and the significance of prophylactic administration of flomoxef (FMOX) was studied. Intravenous administration of FMOX 4g/day was started during surgery and lasted for 7 days. Bacteria in the bile, washing solution used during surgery, and fluid drained from the patients were cultured. Nine of the 60 patients developed infection (infection group). Five patients had intraabdominal infection and the other 4 patients had wound infection. The mean age of the group with infection was higher than that of the group without infection. The proportion of patients who underwent surgery likely to result in contamination by bile or gastrointestinal juice was greater in the infection group. The detection rate of bacteria in the bile from the infection group was higher than that in the other group. Enterococcus, pseudomonas spp., and Staphylococcus epidermidis were cultured from the bile, washing solution, and purulent dischage from patients with infection. In patients with fever (37°C or more) for one week after the operation, the same bacteria were cultured from the drained fluid. Most postoperative infections occurred because of intraoperative or postoperative contamination, and the causative bactaria were not sensitive to Flomoxef.

This paper presents a patient with mucinous cystadenocarcinoma of the bile duct, who was able to undergo radical operation after the extension of the cancer invasion was preoperatively diagnosed by percutaneous transhepatic cholangioscopy (PTCS), with a review of the literature. A 57-year-old woman was admitted to the hospital because of heart burn and general fatigue. On admission, alkaline phosphatase activity was 12.6 KAU, leucine aminopeptidase was 26mu/ml, carcinoembryonic antigen was 7.9ng/ml, and carbohydrate antigen CA19-9 was 71U/ml. Computed tomography and abdominal ultrasonography visualized dilation of the common bile duct and intrahepatic bile ducts. There was a honeycomb-like tumor stain in the area of cholangiectasis in the left lobe of the liver. The patient was treated by PTCD before cholangioscopy was done by the same route. These findings led us to the diagnosis of mucinous cystadenocarcinoam of the bile duct that had spread from the common bile duct to the intrahepatic bile ducts, as seen from the biopsy specimens. Extended lobectomy of the left lobe, resection of the extrahepatic bile ducts except for the right hepatic duct and common bile duct, and lymph node dissection were carried out. The adenocarcinoma was well differentiated and had not invaded the stroma of the liver or the perineural region.

A 69-year-old man was admitted to our hospital because of anorexia and weight loss. Abdominal computed tomography showed an irregularly contoured mass in his left renal pelvis. The patient had a remarkable degree of leukocytosis with no obvious focus of infection. An enzyme immunoassay of the serum revealed a remarkably high concentration of granulocyte colony-stimulating factor (G-CSF). The patient died 6 weeks after admission without a resection of the renal pelvic tumor. At autopsy, the tumor involved the pancreas, stomach, and descending colon. The histopathologic diagnosis was squamous cell carcinoma with sarcomatous change. Immunohistochemical staining using anti-G-CSF antibody demonstrated immunoreactivity in the cancer cells. To our knowledge, this is the first case of renal pelvic carcinoma proven to produce G-CSF reported in English.

肝癌切除後の残肝再発には,転移再発ならびに多中心性再発の2種類の様式が考えられている.これら残肝再発の機序を解明する一助として,最近5年間に取り扱った切除肝癌161症例の非癌部肝内結節性病変を再検索した.その結果,161症例中31症例(19%)に術前術中に診断し得なかった結節性病変48結節が検出された.これらを病理組織学的に検討したところ,large regenerative noduleは19結節(40%),adenomatous hyperplasiaは10結節(21%), early HCCは8結節(17%), intrahepatic metas-tasisは8結節(17%)であった.したがって,最近精度の著しく向上した術前画像診断法によっても検出しえない結節性病変が残肝にかなり存在することが推測された.

76歳男性, 約10年前より糖尿病のため経口血糖降下剤を服用.72歳時に軽度の嚥下困難に対して精査を行い, 頸部食道から噴門部直上におよぶ食道真菌症と診断し, 抗真菌薬の投与にて経過観察中であった.3年後の上部消化管造影で, 胃穹窪部の隆起性病変を発見し, 生検で腺癌の診断を得た.開腹所見では腫瘍は噴門部大弯側前壁にあり, 食道胃接合部との間に約3cmの正常粘膜を有していた.そこで腫瘍の口側距離 (OW) を2cmとり, しかも食道胃接合部より1cm遠位側の胃粘膜と小腸とを吻合する胃全摘術を施行した.術後体表に創感染を認めた以外良好に経過した.食道真菌症に胃癌を合併した例 (以下本症) の報告は検索範囲ではなく, 本症に対して胃全摘術後, 真菌症罹患食道との再建術では縫合不全が危惧される.今回は幸運にも罹患食道との吻合を行わずに治癒切除しえたが, 場合により危険度の高い吻合もありえたため本症に対する再建術の2, 3の工夫を考察した.

The liver hanging maneuver is widely used in right lobectomy to resect huge tumors and harvest living donors. The convenience of tape assistance in other types of hepatectomy is not well known.Tape-guiding technique (TGT) was applied in 30 hepatectomies of different type between April 2003 and April 2006. The indications were liver carcinoma in 22 and living-donor in 8. Hepatectomies included right lobectomy, 14; left lobectomy with caudate lobectomy, 8; left lobectomy without caudate lobectomy, 2; lateral segmentectomy, 3; central bisegmentectomy, posterior segmentectomy, and superior dorsal partial resection, 1 each. A tape was placed in front of the inferior vena cava for right hepatectomy and left hepatectomy with caudate lobectomy. In other hepatectomies, the tape was positioned to be the target of parenchymal dissection.TGT was successfully performed in all 30 cases. Tape facilitated dissection by helping the surgeon maintain orientation, and traction on the tape flattened the parenchyma, making it easier to identify and manage vessels and ducts. With an assistant holding the tape, the surgeon's left hand was free, and ligation and suturing was easier and more secure.The TGT is a convenient technique that is applicable to different types of liver resection.

Liver resection for hepatocellular carcinoma in patients with cirrhosis carries risk of major hemorrhage and sometimes requires blood transfusion. We investigated risk factors for massive blood loss during liver resection and indications for storing blood for autologous intraoperative transfusion.We analyzed clinical records of 100 patients with cirrhosis who underwent liver resection for hepatocellular carcinoma. Autologous blood was stored preoperatively for 19 patients.Intraoperative blood loss ranged from 5 to 3000 mL (mean, 640). Liver resection was performed without transfusion in 67 patients and with autologous blood storage in 17 patients not receiving homologous blood. In the other 16 patients, homologous blood was transfused. Univariate analysis identified youth, large tumors (4cm), major hepatectomy, portal tumor involvement, hepatic vein involvement, and prolonged operation time as risk factors for massive blood loss; multivariate analysis identified portal involvement and hepatic vein involvement as independent risk factors. Blood loss exceeded 1000 mL in the 4 transfused group B patients and 3 of the 4 patients had hepatic vein involvement.Portal involvement and hepatic vein involvement were risk factors for massive blood loss during liver resection for hepatocellular carcinoma in patients with cirrhosis. Autologous blood storage is indicated in patients with such risk factors.

A 76-year-old man, who underwent central bisegmentectomy of the liver, transcatheter arterial chemoembolization, and radiofrequency ablation for chronic hepatitis C virus-related hepatocellular carcinoma (HCC), was found to have a 3 cm mass in the spleen and a 2 cm mass in the liver by computed tomography in January 2003. As both tumors were adjacent, a diagnosis of HCC with splenic infiltration was made. In February 2003, transcatheter arterial chemoembolization and splenic arterial chemo-infusion were performed. However, the splenic tumor increased to 5 cm with slight enhancement on contrast-enhanced computed tomography performed 6 months later, while the hepatic tumor had no enhancement. Limited resection of the liver with splenectomy was performed in October 2003. Macroscopically, the splenic tumor showed infiltrative growth without a capsule while the hepatic tumor showed complete necrosis within its capsule. The splenic tumor was limited to the splenic parenchyma. Histologic examination revealed that the splenic tumor was poorly differentiated HCC, leading to the diagnosis of splenic metastasis. The patient is doing well 17 months after surgery without recurrence. One should perform surgery for splenic metastasis of HCC without hesitation whenever possible.

Bowel injury associated liver surgery is rare but can be fatal if not adequately treated. The contribution of underlying liver disease and previous hepatectomy to bowel injury in hepatectomy for hepatocellular carcinoma is unknown.Clinical records of 531 patients who underwent hepatic resection without combined resection of the biliary tract or intestine for hepatocellular carcinoma during 13 years were reviewed. Differences in incidence of bowel injury according to presence or absence of liver cirrhosis, technique of hepatectomy, and history of hepatectomy were investigated. Outcome after treatment also was reviewed.Bowel injury occurred in 5 patients (0.9%). Previous hepatectomy history was associated with an increased incidence of bowel injury [repeat hepatectomy, 3/91 (3.3%), and first hepatectomy, 2/440 (0.5%), p = 0.038]. Injury was recognized intraoperatively in two patients and postoperatively in three. In the former two patients, the injured bowel was repaired immediately but a fistula still developed in one patient. One patient with a fistula eventually required temporary fecal diversion and eventually limited colectomy. The other three patients were treated by continuous external drainage, but two of them required debridement or colic sleeve resection.Previous hepatectomy increases the risk for bowel injury during hepatectomy. Care must be taken to prevent adhesion to the hepatic cut surface. Careful use of electrocautery to prevent burn injury also should be taken.

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.

Influence of interferon (IFN) therapy on postoperative outcomes in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is still inconclusive. Of 518 patients who underwent hepatic resection for HCV-related HCC, 312 patients with Japan integrated staging score 0-2 were included in this study. Of 50 patients underwent IFN therapy, 29 patients who obtained a normalized alanine aminotransferase (ALT) activity irrespective of disappearance of serum HCV RNA were classified as the response group, while 21 patients were classified as the non-response group because their ALT activities were not normalized and serum HCV RNA persisted. The non-IFN group included 262 patients who had not received IFN therapy. The tumor-free and the overall survival rates for patients in the response group were significantly higher than those in other groups. Only one patient in the response group died of HCC recurrence, and the proportion of deaths associated with liver disease (HCC recurrence or cirrhosis) was significantly lower in the response group than other two groups. IFN therapy can improve postoperative outcomes in patients with HCV-related HCC because of suppression of recurrence and preventing progress of cirrhosis, especially when IFN therapy has controlled their active hepatitis.

Recently, it has been suggested that hepatitis C virus infection plays a role in the pathogenesis of some intrahepatic cholangiocarcinomas (ICC). We describe two patients with small ICC detected after interferon therapy for chronic hepatitis C. Case 1 was diagnosed with ICC by preoperative biopsy and underwent anterior segmentectomy of the liver, while Case 2 was diagnosed with hepatocellular carcinoma preoperatively and the tumor was diagnosed as ICC after biopsy and microwave coagulonecrotic therapy. Both patients are in good health six months and five months, respectively, after operation. It is important to monitor carefully for ICC as well as hepatocellular carcinoma in patients with chronic hepatitis C, even when interferon therapy has been carried out, since the outcome of treatment for small ICC is favorable.

The Japan integrated staging (JIS) score is recognized to be useful in managing hepatocellular carcinoma (HCC). We evaluated the effects of the causative virus in patients stratified by this system.We compared clinicopathologic features, cumulative and tumor-free survival rates, and causes of death between 301 hepatitis C virus-positive patients (HCV group) and 60 hepatitis B virus-positive patients (HBV group).Among patients with low JIS scores (0 or 1), the proportions of patients with high aspartate and alanine aminotranferase activities, moderate-to-severe active hepatitis, and with cirrhosis were significantly higher in the HCV than in the HBV group. Among patients with high JIS scores (2 to 4), the proportion with moderate-to-severe active hepatitis was also significantly higher in the HCV group. In patients with low JIS scores, those in the HCV group had significantly lower tumor-free and cumulative survival rates than those in the HBV group. Although no patient in the HBV group died of causes other than liver disease (HCC or hepatic failure), some patients in the HCV group died of causes other than liver disease. The proportion of patients who died because of HCC recurrence tended to be higher among patients with high JIS scores than among patients with a low JIS score.The effects of viral status on survival outcomes are greatest in patients with JIS scores of 0 or 1.

A 64-year-old man with a 9.0 cm benign hepatic cyst near the hepatic hilum presented with obstructive jaundice caused by the compression of the hepatic ducts. The cyst was aspirated percutaneously, and minocycline hydrochloride was instilled as a sclerosant through a catheter inserted into the cyst. The cyst gradually became smaller, relieving the obstructive jaundice. There were no complications or side-effects. The instillation of minocycline hydrochloride is a useful alternative to ethanol instillation for treating benign hepatic cysts, even when the cyst is causing obstructive jaundice.

Clinicopathologic variables favoring recurrence after hepatic resection for intrahepatic cholangiocarcinoma showing intraductal growth remain unclear. We investigated various clinicopathologic features in three patients who underwent resection for this type of intrahepatic cholangiocarcinoma. All underwent extended left hepatectomy plus resection of the caudate lobe and lymph node dissection. Lymph nodes showed no pathologic involvement. Although no cancer cells were seen in the mucosal layer by intraoperative pathologic examination at the bile duct stump in any patient, pathologic examination of resected specimens showed cancer cells invading beyond the mucosal layer in connective tissues surrounding the bile duct stump (interstitial invasion) of the Glisson's sheath in 2 patients. One of them died of cancer recurrence near the bile duct stump, while the third patient, without interstitial invasion, has survived for 10.6 years. In the intraductal growth type of intrahepatic cholangiocarcinoma, absence of cancer cells should be confirmed by intraoperative pathologic examination of not only the mucosal layer of the bile duct but also the connective tissue surrounding the bile duct, since interstitial invasion may be a risk factor for cancer recurrence.

Background: Although hepatitis C virus (HCV) infection is a possible pathogenetic factor for intrahepatic cholangiocarcinoma (ICC), clinicopathologic features of ICC patients with HCV infection remain unclear. Patients and Methods: Of 50 patients with ICC treated, 19 were infected with HCV (HCV-positive group) and 38 underwent surgical treatment. Clinicopathologic features and postoperative outcome were compared between patients with and without HCV infection. Results: In 15 patients in the HCV-positive group, ICC was detected during follow-up for chronic hepatitis C. The proportion of patients who underwent curative resection was significantly higher in the HCV-positive than in the HCV-negative group, and tumors were significantly smaller in the HCV-positive than in the HCV-negative group. In the HCV-positive group, tumors were significantly smaller in patients who were followed up for chronic hepatitis C than in patients who were not followed up. Although cumulative survival rates did not differ significantly between groups, prognoses of patients with small ICC were significantly better than those with large ICC. Conclusion: Follow-up for patients with chronic hepatitis C by imaging series at regular intervals is important and provides the possibility to detect a small ICC as well as a hepatocellular carcinoma. Resection should be guided by liver function and the tumor stage in patients with HCV-associated ICC.

Although intractable pleural effusion is a well-known complication after liver resection, risk factors for this condition have not been established.Records of 254 patients who underwent liver resection for hepatocellular carcinoma between January 1994 and December 2002 were reviewed. Postoperative pleural effusion that required thoracentesis or continuous drainage with or without pleurodesis was defined as intractable. Variables evaluated as risk factors included demographic factors, presence of cirrhosis, routine preoperative laboratory data, serum concentration of type IV collagen 7S domain (7S collagen), Child-Pugh class, preoperative interventions, including transcatheter arterial embolization (TAE), operative procedure, intraoperative blood loss, histology of noncancerous hepatic parenchyma, and major postoperative complications.Postoperative intractable pleural effusion developed in 15 (5.9%) patients. Serum concentration of 7S collagen, preoperative transcatheter arterial embolization (TAE), and liver resection that included segments 7 and/or 8 were independent risk factors on multivariate analysis. In patients with high concentration of 7S collagen (or = 8.0 ng/mL), the incidence of the complication was significantly lower in patients who had not undergone TAE than in those who had undergone TAE.An increase in serum 7S collagen concentration (or = 8.0 ng/mL) and preoperative TAE are independent and preoperative risk factors for the development of intractable pleural effusion after liver resection for HCC. Preoperative TAE should be avoided when possible in patients whose serum 7S collagen concentration isor = 8.0 ng/mL.

Although some gallbladder carcinomas are immunoreactive for c-Kit, the reasons for the c-Kit expression and its clinicopathologic implications are unknown.We investigated the prevalence of c-Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c-Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM-based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c-Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma.Cytoplasmic immunostaining for c-Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c-Kit positivity; however, there were no significant differences in the incidence of c-Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c-Kit-positive gallbladder carcinoma compared with c-Kit-negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19.Gallbladder carcinomas positive for c-Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.

Despite improvements in the preoperative assessment of liver function and advances in surgical techniques, liver resection for hepatocellular carcinoma still holds a risk for postoperative hepatic failure, especially in patients with cirrhosis. Physiologic characteristics in patients with cirrhosis include hyperdynamic state of the systemic circulation, decrease in hepatic blood flow, portal hypertension, metabolic disorders, dysfunction of the reticuloendothelial system, and thrombocytopenia. Surgical stress including massive bleeding, disturbance of hepatic circulation, and infection are risk factors for postoperative hepatic failure. The risk of hepatic failure also correlates with the severity of active hepatitis and the degree of hepatic fibrosis. To prevent postoperative hepatic failure, dopamine, prostaglandin, and hydrocortisone have been used. Although various treatments including plasma exchange have been tried in hepatic failure, the results have often been unsatisfactory. Careful preoperative evaluation of the hepatic functional reserve and the severity of active hepatitis, and adequate selection of surgical method are important to prevent postoperative hepatic failure.

Sporadic cases of hepatocellular carcinoma (HCC) originating from nonalcoholic steatohepatitis (NASH) have recently been reported. Thus, we investigated the prevalence of NASH in patients with HCC. A review of the clinical records of 481 patients who underwent liver resection for HCC in our department between January 1991 and December 2003 revealed only two (0.4%) patients with HCC associated with NASH. Both of these patients had noninsulin-dependent diabetes mellitus, and neither had a history of alcohol consumption or blood transfusion. All serologic markers for hepatitis B and C viruses were negative. Histological examination of the noncancerous hepatic tissue revealed NASH with moderate hepatic fibrosis in one patient and cirrhosis in the other. Thus, clinical follow-up and screening for HCC should be done for patients with hepatic fibrosis caused by NASH, even though this form of hepatitis is an uncommon cause of HCC.

We investigated the clinical and virologic findings in hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis C virus antibody (anti-HCV)-negative patients with hepatocellular carcinoma (HCC) to investigate the role of previous or occult hepatitis B virus (HBV) infections in the development of HCC. We examined sera and HCC samples from 40 HBsAg-negative and anti-HCV-negative patients. Sera were tested for some viral markers, and genomic DNA was extracted from the HCC samples. HBx RNA was also extracted from the HCC and amplified by a polymerase chain reaction with reverse transcription (RT-PCR). Hepatocellular carcinomas from five patients with anti-HBc (group 1, 25 patients) and nine patients without anti-HBc (group 2, 15 patients) were examined for HBx RNA. HBx RNA was detected in four of the five HCC samples from group 1 and in four of the nine HCC samples from group 2. These findings suggested that previous or occult hepatitis B virus infection is common in HBsAg-negative and anti-HCV-negative patients with HCC.

A 71-year-old woman was admitted to our hospital with obstructive jaundice. Magnetic resonance cholangiography revealed a 9-cm spindle-shaped tumor in the common bile duct. Laboratory examination noted a high concentration of total serum bilirubin. Although the serum concentration of carcinoembryonic antigen was within normal limits, the serum concentration of carbohydrate antigen 19-9 was elevated. We diagnosed the lesion as an extrahepatic bile duct cancer and performed a laparotomy. The anterior wall of the common bile duct was incised, and the tumor was found to have a small base in only the posterior wall of the duct, and spread within the duct was from the common hepatic duct to the intrapancreatic bile duct. Bile duct resection, cholecystectomy with lymphadenectomy and hepaticojejunostomy were performed. Frozen sections of the proximal and distal surgical margins of the bile duct were free of cancer. Macroscopically, the lesion was an expansive polypoid tumor measuring 9x3cm in diameter arising from a 5-mm base. Histologic examination revealed that the tumor was a well-differentiated tubular adenocarcinoma that had infiltrated the fibromuscular layer at its base. Longitudinal spread was more extensive hepatopetally than hepatofugally. The patient is alive and well without any complaints 8 months after surgery.

Hypothesizing that combined hepatocellular and intrahepatic cholangiocellular carcinoma originates from hepatic stem cells, we conducted a series of immunohistochemical studies using hepatic stem cell markers to better understand the origin of the tumor. Specially, we investigated 15 combined tumors confirmed to be immunoreactive to anti-hepatocyte paraffin 1, and anti-cytokeratin 7 and 19 antibodies. Macroscopic investigation revealed cancer cells morphologically intermediate between neoplastic hepatocytes and cholangiocytes (combined tumor with intermediate morphology) in 11 of 15 tumors. The remaining four tumors lacking these cells were considered ordinary combined tumors. We used 20 hepatocellular carcinomas and 10 cholangiocarcinomas as controls. Immunohistochemical analysis was performed using stem cell markers (c-kit and CD34). Of the 15 combined tumors, 8 stained for c-kit (2 of the 4 ordinary tumors and 6 of the 11 intermediate morphologic tumors). Both of the tumor cell types in both of the ordinary combined tumors stained for c-kit. The c-kit staining was present in cells of all three morphologic types, including the intermediate cells, in all six of the intermediate combined tumors. None of the cells in the combined tumors showed immunoreactivity for CD34. None of the 30 control tumors expressed CD 34 or c-kit. The present study suggests that combined hepatocellular and intrahepatic cholangiocellular carcinomas originate not from a hepatic stem cell, but from a hepatic precursor cell, such as the canal of Hering cell. Alternatively, these tumors might show up-regulation of c-kit in relation to angiogenesis.

Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotrans-ferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% Cl, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan.

We investigated the correlation between vascular endothelial growth factor (VEGF) and CD44 expression in hepatocellular carcinoma (HCC) and the frequency of extrahepatic metastasis, in order to evaluate the influence of vascular growth and adhesion molecules in facilitation of distant metastasis.We obtained materials from primary lesions of HCC with no extrahepatic metastasis (control group) and primary lesions and metastatic lesions with extrahepatic metastasis (metastasis group). Immunohistochemical staining was performed using anti-human CD44v3 monoclonal antibodies and anti-human VEGF ab-3 monoclonal antibodies. Although pathological parameters such as tumor size, differentiation, capsule formation, and vascular invasion were analyzed, there was no marked difference among the groups.Percentages of nodules with VEGF-positive tumor and sinusoidal cells were low in primary lesions of the control and metastasis groups, while high in metastatic lesions in the metastasis group. On the other hand, percentages of nodules with CD44-positive tumor and sinusoidal cells were low in primary lesions of the control group, while high in primary lesions and metastatic lesions of the metastasis group.The present study demonstrated that CD44 expression in primary lesions is related to a higher frequency of extrahepatic metastasis, suggesting that this is a clinicopathologically useful parameter in predicting the occurrence of distant metastasis.

Although percutaneous trans-hepatic portal vein embolization (PTPE) expands the candidate pool for hepatectomy in patients with hepatobiliary malignancies, the role of PTPE in patients with active hepatitis or cirrhosis has yet to be determined.Records of patients who underwent PTPE of the right portal vein between 1984 and April 2001 were reviewed retrospectively. To determine the indication for PTPE and subsequent hepatectomy, clinical variables, including serum concentrations of hyaluronic acid (HA), procollagen type III peptide (P-III-P), and the 7S domain of type IV collagen (7S-IV), were compared between patients who underwent right hepatectomy (group A; n=44) and the other patients (group B; n=17).The scores for prediction of postoperative liver failure (prediction score) and serum HA and P-III-P concentrations were different in the two groups. Thirteen of 30 patients (43%) whose prediction score was more than 50, the limit of the hepatectomy without PTPE, successfully underwent right hepatectomy following PTPE. The resectability ratios increased to 75% and 100%, when the HA concentration wasor = 100mg/L and the P-III-P concentrationor = 0.7/mL.Serum HA and P-III-P concentrations are useful guidelines for identifying candidates for right hepatectomy following PTPE.

A number of reports on limy bile have been published but obstructive jaundice due to limy bile is quite rare. We report a case of obstructive jaundice due to limy bile and review 26 cases of limy bile diagnosed in our institution.A 39-year-old woman was admitted to our hospital with epigastric pain and jaundice. Abdominal ultrasonography and computed tomography revealed limy bile in the common bile duct and a gallbladder stone with biliary obstruction. Percutaneous transhepatic biliary drainage was performed. The limy bile drained out through the catheter over a few weeks. Cholecystectomy and choledochotomy with choledocholithotomy were subsequently performed.The strategy for managing patients with limy bile is individualized based on symptoms, the clinical conditions, and the location of the limy bile, and any associated biliary stones or lesions causing cystic duct obstruction.

A 40-year-old Japanese woman, who previously had undergone choledocho-jejunostomy in childhood for a congenital choledocal cyst, presented with right-sided chest pain. Computed tomography and ultrasonography demonstrated a right pleural effusion and a 10-cm unilocular hepatic cystic lesion with no solid component. These findings suggested a non-neoplastic cyst or cystadenoma. However, intracystic fluid aspirated had high concentrations of carbohydrate antigen 19-9 and carcinoembryonic antigen. Cytology of the pleural effusion demonstrated malignant cells. During exploratory laparo- and thoracotomy, a hepatic cystadenocarcinoma with invasion of the diaphragm and pleural dissemination was discovered. This case demonstrates that malignancy should be ruled out when a patient with an intrahepatic unilocular cystic lesion presents with atypical symptoms and findings, such as chest pain, pleural effusion, and high serum concentration of tumor markers. We believe that intrahepatic cystic lesions should be approached aggressively, including the use of exploratory laparotomy/laparoscopy to be certain that cancer is not present.

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.

Serum concentrations of the 7S fragment of type IV collagen (7S collagen), amino-terminal propeptide of type III procollagen (PIIIP), and hyaluronic acid (HA) have been reported to serve as serologic markers of liver fibrosis in hepatitis and cirrhosis. We investigated whether these fibrosis markers reliably reflect histologic changes in the livers of patients with hepatocellular carcinoma.Subjects included 165 patients undergoing liver resection for hepatocellular carcinoma. Most were seropositive for chronic hepatitis B or C. Histopathologic changes in liver tissue resected with the tumor were scored according to Knodell's histologic activity index. Serum was sampled for assays shortly before surgery.Significant correlations were found between hepatitis activity score and 7S collagen, PIIIP, and HA. Concentrations of 7S collagen differed significantly between activity grades, but differences were not significant for PIIIP or HA. Significant correlations were found between fibrosis staging score and all these three markers. When patients were divided according to activity grade, 7S collagen showed stronger correlation with fibrosis staging score than did PIIIP or HA.The 7S collagen fragment correlated more strongly than PIIIP or HA with stage and activity grade in patients with hepatocellular carcinoma. However, overlapping of results between histologically defined groups appeared to limit clinical diagnostic usefulness of all markers in individual patients.

We report two cases of benign biliary strictures managed by metallic stent placement because the patients refused surgical repair. One patient is a 67-year-old man who had a stricture of the right hepatic duct and a bile leak following a cholecystectomy. The second patient is a 50-year-old man who had a stricture of the left hepatic duct following a right hepatic lobectomy for hepatolithiasis. For treatment of these bile duct strictures, a Gianturco-Rosch Z stent was placed in the former case and a Wallstent in the latter. Luminal patency of the stent was maintained for 7 years in the former case but in the latter, luminal stenosis of the stent was induced soon after placement. However, in the former, bile stasis in the left hepatic duct system, which emptied into the side of the stent, gradually developed without signs or symptoms of cholangitis or biliary obstruction. Therefore, the use of metallic stents for benign biliary stricture remains controversial. However, if metallic stent placement is the only therapeutic option, it is necessary to maintain bile flow not only through the stent but also in the bile ducts which flow into the side of the stent.

Primary sclerosing cholangitis is an uncommon chronic hepatobiliary disorder, and the definitive surgical treatment for symptomatic primary sclerosing cholangitis is liver transplantation. Although some cases with primary sclerosing cholangitis treated with hepaticojejunostomy or partial hepatectomy have been reported, the indications for these procedures and their long-term results have not been well defined or studied. We present three patients with segmental primary sclerosing cholangitis, and discuss the indication of surgical treatment for primary sclerosing cholangitis excluding liver transplantation. Three patients with segmental primary sclerosing cholangitis of the common bile duct and the hepatic ducts were treated by hepaticojejunostomy with partial resection of the common bile duct. We investigated clinical features such as angiography, cholangiography, and surgical treatment outcomes. It was difficult to differentiate primary sclerosing cholangitis from a cholangioma preoperatively, despite the use of cytology, angiography, and cholangiography. Two of the three patients were preoperatively suspected to have cholangioma. Segmental primary sclerosing cholangitis was diagnosed operatively. All patients were treated hepaticojejunostomy and achieved long-term survival. Although liver transplantation is the treatment of choice for primary sclerosing cholangitis, in cases of segmental primary sclerosing cholangitis, local resection of the involved structures may be curative. Resection of a discrete lesion may provide many years of survival with a good quality of life, in some cases obviating the need for liver transplantation.

Liver transplantation in patients with end-stage hepatolithiasis is complicated by the high incidence of the suppurative cholangitis and systemic infection. A 43-year-old Korean-Japanese woman with hepatolithiasis, biliary cirrhosis, suppurative cholangitis, and biliary-bronchial fistula underwent living-related liver transplantation (LRLT) using a right lobe graft of her sister. The risk of infection was minimized by preoperative percutaneous transhepatic biliary drainage initiated 2 months before transplantation. The native liver was resected en bloc with the extrahepatic bile ducts and the infected section of the right hemidiaphragm. Opportunistic infection was prevented by limiting antimicrobial therapy to the interval from preoperative day 3 to postoperative day 4. Immunosuppressive agents were given below standard dose. The postoperative course following LRLT was uncomplicated, and hepatic function was good. Careful management of infection and adequate graft size are essential for successful LRLT in patients with end-stage hepatolithiasis.

We investigated correlations between laboratory test results and multicentric development of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in 202 patients who underwent liver resection. Two types of HCC were considered to meet multicentricity criteria: in one, at least one tumor was well-differentiated, with at least one other being less differentiated; in the other, all tumors included well-differentiated HCC with or without less differentiated components. Forty-five patients had multicentric HCC. Platelet counts were lower in patients with multicentric HCC than in others. Serum concentrations of type IV collagen 7s domain and alpha-fetoprotein, histologic hepatitis activity score, and histologic hepatic fibrosis score were higher in patients with multicentric HCC. By multiple logistic regression analysis, low platelet count was an independent risk factor for multicentric HCC. The proportion of patients with multicentric HCC was significantly higher among patients with low platelet counts (below 10(5)/mm(3)) than in patients with a higher count. Thus, HCC patients with a platelet count below 10(5)/mm(3) may require particularly careful examination for multicentricity.

Ornithine decarboxylase activity, a rate-limiting enzyme in polyamine biosynthesis, is correlated with the degree of malignancy of hepatocellular carcinoma. We investigated the relationship between polyamine metabolism in hepatocellular carcinoma tissues and the recurrence after resection of hepatocellular carcinoma.The subjects were 49 patients who underwent liver resection for hepatocellular carcinoma. The relationship between ornithine decarboxylase activity and polyamine concentration in hepatocellular carcinoma tissues and the pathologic findings or recurrence after the operation was studied.The prevalences of moderately or poorly differentiated hepatocellular carcinoma, portal invasion, and intrahepatic metastasis were higher in patients with a high ornithine decarboxylase activity (or = 100 pmol putrescine/h/mg protein) than in patients with a low ornithine decarboxylase activity (100 pmol putrescine/h/mg protein). The tumor-free survival rate was significantly lower in patients with a high ornithine decarboxylase activity than in patients with a low ornithine decarboxylase activity (p=0.0394). The tumor-free survival rate was significantly lower in patients with a high spermidine concentration (or = 80 nmol/mg protein) than in patients with a low spermidine concentration (80 nmol/mg protein, p = 0.0454).A high ornithine decarboxylase activity and a high spermidine concentration of hepatocellular carcinoma were risk factors for recurrence after resection of hepatocellular carcinoma.

We investigated the clinicopathologic characteristics of and outcome after treatment for small intrahepatic cholangiocarcinomas of mass-forming type (3 cm or smaller) in nine patients to study appropriate treatment. In seven of the nine patients, the cancer was detected during follow-up for hepatitis C virus-related disease. One patient was seropositive for anti-hepatitis B core antibody alone. One patient had alcoholic cirrhosis. Three patients also had hepatocellular carcinoma. Seven patients underwent liver resection and two other patients underwent microwave coagulation therapy. In the resection specimens, no vascular or lymphatic invasion, or invasion of perineural spaces, was evident pathologically. No patient had intrahepatic metastasis or lymph node metastasis; all had hepatic fibrosis. Lung metastases developed after surgery in one patient whose surgical margin was positive for cancer. In one patient with both type of carcinoma, the hepatocellular carcinoma recurred. Screening for not only hepatocellular carcinoma but also intrahepatic cholangiocarcinoma is necessary in patients with hepatic fibrosis, especially those infected with hepatitis C virus. For small intrahepatic cholangiocarcinomas of mass-forming type located peripherally in the liver, partial resection or ablation therapy with care to obtain a negative surgical margin may be appropriate.

The prognosis of hepatocellular carcinoma originating from the caudate lobe (caudate HCC) is generally poor, and surgical treatment for caudate HCC is difficult to perform due to the location. We postulate that a combination of surgical resection and transcatheter arterial embolization improves the prognosis, and that operative procedure is straightforward. We examined three cases of large solitary caudate HCC. Three patients (a 68-year-old woman, 65-year-old man, and 71-year-old man) with caudate HCC and viral chronic hepatitis were treated with preoperative transcatheter arterial embolization and partial resection of the caudate lobe. After transcatheter arterial embolization, the solitary hepatocellular carcinomas decreased in size (9 to 6, 10 to 8, and 7 to 5 cm in diameter, respectively) which simplified surgical resection (1120, 3010, and 2110 cc blood loss; 4.5, 7, and 7 hours of operative time, respectively). All the hepatocellular carcinomas were poorly differentiated, and had infiltrated microscopically into the portal vein. The outcome was satisfactory (18, 16, and 10 months after the operation, two cases were alive, and one dead, respectively). The combination of preoperative transcatheter arterial embolization and partial resection for caudate HCC, especially large solitary caudate HCC, works well as a multimodal therapy.

We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B.Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome.The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors.Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.

An aberrant hepatic artery arising from the dorsal pancreatic artery is extremely rare, although the arterial blood supply to the liver is variable. A 56-year-old Japanese man was admitted to our hospital with a lesion in the right hepatic lobe. Serum concentrations of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were within the reference range. Abdominal arteriography showed a hypervascular lesion measuring 3.0 cm in diameter in the right hepatic lobe. The left hepatic artery, the middle hepatic artery, and the anterior branch of the right hepatic artery were derived from the common hepatic artery, while the posterior branch originated from the dorsal pancreatic artery. Computed tomography performed during arteriography via the common hepatic artery showed an arterial perfusion defect in the posterior segment of the right hepatic lobe and enhancement of the ventral portion of the tumor, while the dorsal portion was not enhanced. However, the dorsal portion of the tumor was enhanced when arteriography was performed via the dorsal pancreatic artery. A limited hepatic resection was performed. Histologically, the tumor was a moderately differentiated hepatocellular carcinoma with a thick trabecular pattern.

Many institutions apply the indications for living-related liver transplantation in patients with hepatocellular carcinoma based on the Milan criteria, which state that transplantation is not indicated when more than three foci of disease are present. However, the relationship between the number of foci identified preoperatively and the number detected on pathologic examination of the surgical specimen is unknown. The case of a 66-year-old Japanese woman with cirrhosis secondary to type C viral hepatitis who developed hepatic failure secondary to multifocal hepatocellular carcinoma is presented. Three foci of hepatocellular carcinoma were identified radiologically preoperatively. Following successful living-related liver transplantation, pathologic examination of the surgical specimen revealed that six foci of hepatocellular carcinoma and one dysplastic nodule were present. Although the number of foci of hepatocellular carcinoma is a predictor of recurrence and3 is a relative contraindication to transplantation, lesions undetected radiologically (such as dynamic computed tomography) are unlikely to have metastatic or invasive potential because they have yet to evolve a capillary blood supply and still receive their nutrition via hepatic sinusoids on immunohistochemical and radiological findings. Foci of hepatocellular carcinoma undetected preoperatively are unlikely to effect prognosis when total hepatectomy is performed in the context of living-related liver transplantation.

Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(-), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)- CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness.