One hundred two consecutive hepatobiliary resections for perihilar cholangiocarcinoma with zero mortality.

OBJECTIVE: To analyze the short-term surgical outcome of hepatobiliary resections for perihilar cholangiocarcinoma in the last 5 years. SUMMARY BACKGROUND DATA: Hepatobiliary resection for perihilar cholangiocarcinoma remains a technically demanding procedure, calling for a high level of expertise in biliary and hepatic surgery, and is still associated with significant morbidity or mortality. METHODS: Between 2000 and 2004, we surgically treated 102 consecutive patients with perihilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization (for right-sided and extended left-sided resections), and major hepatobiliary resection. The data on all of the patients were analyzed retrospectively to identify the factors that might significantly affect the postoperative mortality and morbidity. RESULTS: There were no cases of in-hospital mortality or postoperative liver failure. Major complications were encountered in 7 patients (6.9%), and the overall morbidity rate was 50%. Reoperation was required in 2 patients (2%). The overall median length of postoperative hospital stay was 26 days (range, 13-119 days). Univariate analysis in relation to the postoperative morbidity showed significant differences in the preoperative occurrence of segmental cholangitis or cholecystitis (P = 0.015), the severity of postoperative hyperbilirubinemia (P < 0.001), and the total amount of fresh frozen plasma administered (P = 0.002). Multivariate analysis revealed a single independent significant predictive factor for postoperative morbidity, namely, preoperative cholangitis or cholecystitis (odds ratio, 9.08; 95% confidence interval, 1.05-78.56, P = 0.045). CONCLUSIONS: Our experience indicates that hepatobiliary resections for perihilar cholangiocarcinoma can be conducted safely, without a single case of postoperative liver failure or mortality. Occurrence of preoperative cholangitis or cholecystitis is a significant indicator for morbidity of major hepatobiliary resection.

A solid pseudopapillary tumor arising from the greater omentum followed by multiple metastases with increasing malignant potential.

Solid pseudopapillary tumor is a rare, indolent neoplasm almost exclusively seen in the pancreas. We describe an unusual case of solid pseudopapillary tumor arising in the greater omentum of a 45-year-old man with subsequent multiple liver metastases and peritoneal dissemination. The patient underwent a total of ten laparotomies and died of unresectable disease 8 years after the initial presentation. Microscopically, the primary tumor and the relapsed tumors consistently exhibited identical growth patterns, which were characterized by solid sheets intermingling with pseudopapillary arrangements of uniformly small cells. Immunohistochemical staining was diffusely positive for vimentin and focally positive for alpha-1-antitrypsin. These features were compatible with those of conventional pancreatic solid pseudopapillary tumors. We also performed quantitative evaluation of Ki-67 immunoreactivity and mitotic figures, which indicated malignant transformation of this extremely rare tumor. This is the first detailed report of solid pseudopapillary tumor arising outside the pancreas complicated by repetitive liver metastases and peritoneal carcinomatosis, suggesting the existence of a more lethal subgroup of tumors.

Prognostic factors of surgical resection in middle and distal bile duct cancer: an analysis of 55 patients concerning the significance of ductal and radial margins.

BACKGROUND: The surgical outcome of middle and/or distal bile duct cancer remains unsatisfactory. Although the resectional margin is known to be a predictive factor, the prognostic significance of a positive ductal margin and other radial margin has never been evaluated independently. METHODS: The clinicopathologic data of 55 patients who had undergone surgical resection for middle and/or distal bile duct cancer between 1987 and 2003 were reviewed retrospectively. The surgical procedures consisted of pancreatoduodenectomy in 42 patients (76%), extrahepatic bile duct resection in 8 patients (15%), major hemihepatectomy (Hx) in 3 patients (5%), and pancreatoduodenectomy plus Hx in 2 patients (4%). In all the patients, intraoperative diagnosis of the ductal margins was performed using frozen sections. Twenty-one clinicopathologic factors, including the status of the ductal margins and of other radial margins, were evaluated using univariate and multivariate analyses. RESULTS: The overall 5-year survival rate and the median survival time were 24% and 38 months, respectively. There were 4 (7%) postoperative deaths. Fifteen of the remaining 51 patients (29%) were determined to have positive hepatic-side ductal margins during operation, and 14 of them underwent additional resection of the bile duct (1.6[range, 1-3] times, on average). As a result, hepatic-side ductal margin (hm) and duodenal-side ductal margin were found to be positive in 6 and 0 patients on the final pathologic analysis, respectively. Two of the 6 patients (33%) with positive hm have developed ductal recurrence so far, but the status of hm was not found to be a significant predictor. The depth of neoplastic invasion into the bile duct wall, pancreatic invasion, radial margin, and blood transfusion were significant prognostic factors by the univariate analysis. Multivariate analysis revealed that the depth of neoplastic invasion and blood transfusion were the independent prognostic factors. CONCLUSIONS: In the treatment of middle and distal bile duct cancer, it is of importance to secure a negative radial margin, although it may be less beneficial to obtain a negative hm. Surgeons should make efforts to obtain negative radial margins and to avoid blood transfusion.

Multistep and multicentric development of hepatocellular carcinoma: histological analysis of 980 resected nodules.

BACKGROUND/AIMS: Histological observations support the concept of multistep and multicentric development of hepatocellular carcinoma (HCC) in cases of chronic liver disease. However, the relationship between the incidence of such a modality of development of HCC and the type of background liver disease has not been fully investigated. METHODS: A total of 980 HCC nodules resected from 664 patients were analyzed. Multistep HCC was defined as well differentiated HCC containing the portal tracts (early HCC), or the presence of early HCC-like areas in the periphery of the nodule. In cases with multiple nodules, if the smaller nodule showed the features of multistep HCC, or if each nodule showed a distinct histology, the case was defined to have multicentric HCC. RESULTS: Of the 980 nodules, 369 (37.7%) met the criteria of multistep HCC. Of the 664 patients, 177 (26.7%) had multiple nodules that met the criteria of multicentric HCC. Both the incidences of multistep and multicentric HCC were significantly higher in HCV-Ab-positive cases than in HBs-Ag-positive cases (46.0 vs. 19.1%, P<0.001 and 34.1 vs. 16.5%, P=0.005, respectively). CONCLUSIONS: Multistep and multicentric HCC develops most frequently in patients with HCV infection.

Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who showed early massive disease recurrence due to hematogenous intrahepatic metastasis after curative resection had a poor prognosis. The authors previously reported that Akt phosphorylation was correlated with hematogenous intrahepatic metastasis, using HCC cell lines. METHODS: The authors analyzed clinicopathologic features and the status of selected biologic markers, including phosphorylated Akt, to identify risk factors for early disease recurrence and poor prognosis in HCC. In the current series, 49 postoperative patients developed intrahepatic disease recurrence within 6 months (Group 1) and 86 patients remained disease recurrence free > 3 years after resection (Group 2). Group 1 was further divided into 2 subgroups: 19 patients who died of disease recurrence within a year after resection (Group 1A) and 27 patients who survived > 1 year (Group 1B). RESULTS: Using univariate analysis, the risk factors for early disease recurrence were tumor size, macroscopic classification, tumor differentiation, microscopic capsule infiltration, microscopic portal vein (MPV) invasion, microscopic intrahepatic metastasis (MIM), and positive immunostaining for phosphorylated Akt, Ki-67, and p53 (P < 0.05). The risk factors for poor prognosis were the number of intrahepatic metastases, tumor differentiation, and positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05). Multivariate analysis revealed that the risk factors for early disease recurrence were MPV invasion, MIM, and positive immunostaining for phosphorylated Akt, and that the risk factors for poor prognosis were positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05). CONCLUSIONS: The current clinical study showed the critical involvement of Akt phosphorylation in the aggressiveness of HCC. The potential benefits of surgery should be assessed carefully in patients with any of these risk factors.

Successful outcome after resection of pancreatic cancer with a solitary hepatic metastasis.

The presence of hepatic metastasis in pancreatic cancer has generally been considered to be a contraindication for surgery. However, the present case survived seven years after concomitant resection of pancreatic cancer and hepatic metastasis. This shows that hepatic metastasis may be a strong predictor of poor survival, but not a determinant of noncurability. Surgical resection may be an option for highly selected patients with pancreatic cancer complicated with hepatic metastasis.

Intrahepatic cholangiocarcinoma: macroscopic type and stage classification.

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

Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases.

BACKGROUND: Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer, the clinicopathological features of which have rarely been reported in detail. The aim of this study was to clarify the characteristics of cHCC-CC in comparison with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS: The clinicopathological features of 26 cHCC-CC patients, who were surgically treated, were reviewed by comparing them with the features of patients suffering from ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). RESULTS: The cHCC-CC patients showed greater similarity with HCC patients than with CC patients with regard to male/female ratio, status of hepatitis viral infection, serum alpha-fetoprotein (AFP) level, and non-tumor liver histology. The disease stage of the cHCC-CC patients was more advanced than that of either the HCC or CC patients. The cHCC-CC tumors were significantly more invasive to the portal vein than the HCC tumors and were comparable to the CC tumors. The overall 3-, 5-, and 10-year survival rates and the median survival times (95% confidence interval) were 34.6%, 23.1%, 11.5% and 1.8 (0.7-3.0) years for cHCC-CC patients, 86.7%, 66.2%, 46.8% and 4.6 (4.3-5.0) years for HCC patients, and 68.5%, 32.3%, 23.9% and 1.9 (1.1-2.7) years for CC patients, respectively. Survival of patients with cHCC-CC was significantly poorer than that of HCC or CC patients. Among the 26 patients, six survived for >5 years. CONCLUSIONS: In most cases, cHCC-CC seems to be a variant of ordinary HCC with cholangiocellular features, rather than a true intermediate disease entity between HCC and CC. The surgical approach is recommended for selected patients with cHCC-CC.

IHPBA concordant classification of primary liver cancer: working group report.

The working group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association(IHPBA) examined conventional staging systems and decided to establish a new staging system that depended on macroscopic findings after liver resection. The TNM/International Union Against Cancer (UICC) classification has been widely used but is too complicated. Vauthey and colleagues, and the Liver Cancer Study Group of Japan (LCSGJ) have proposed new simplified classifications. These are compared and discussed. The IHPBA working group proposed a new classification, as follows. T factor. 1. Solitary 2. No more than 2 cm 3. No vascular invasion to portal vein, hepatic vein, and bile duct T1 meets all of the above three requirements.T2 meets two of the three requirements.T3 meets one of the three requirements.T4 does not meet any requirements. Stage: I T1N0M0 II T2N0M0 III T3N0M0IV A T4N0M0 Any TN1M0 IV B Any T/N, M1 The survival curves of each stage were separated clearly (P < 0.0001). The staging system is easy to remember and easy to use. We hope this staging system will be generally used in future.

Satellite lesions in patients with small hepatocellular carcinoma with reference to clinicopathologic features.

BACKGROUND: It is not rare to find satellite lesions in patients with small hepatocellular carcinoma (HCC). The purpose of this study was to elucidate the factors associated with satellite lesions in these patients. METHODS: We investigated the prevalence of satellite lesions, the relationship of clinicopathologic factors to satellite lesions, and the distance from the main tumor to the satellite lesion in 149 patients. Patients, who had a solitary HCC of 3.0 cm or less in diameter but no satellite lesions on preoperative imaging procedures, underwent potentially curative resection. The main tumors were macroscopically classified into four groups: early HCC, a vaguely nodular type showing preservation of the preexisting liver structure; single nodular type; single nodular type with extranodular growth; and confluent multinodular type. RESULTS: Of 149 resected specimens, 28 (19%) showed satellite lesions. Of the clinicopathologic factors investigated, the macroscopic type and tumor differentiation were significantly associated with the prevalence of satellite lesions. Both the single nodular type with extranodular growth and the confluent multinodular type showed satellite lesions more frequently than the early HCC and the single nodular type. A significantly higher prevalence of satellite lesions was observed in poorly differentiated HCC than in well and moderately differentiated HCC. The satellite lesions were located 0.5 cm or less from the main tumor in 8 (33%) specimens, 0.6-1.0 cm in 12 (50%), and 1.1-2.0 cm in 4 (17%). No identifiable factors were significantly related to the distance from the main tumor to the satellite lesion. However, all satellite lesions located more than 1.0 cm from the main tumor coexisted with poorly differentiated HCC, which were the single nodular type with extranodular growth or the confluent multinodular type. CONCLUSION: In the single nodular type with extranodular growth, confluent multinodular type, and poorly differentiated HCC, extensive treatment achieving a large safety margin and/or frequent posttreatment follow-up examinations may be needed because of the high prevalence of satellite lesions.

Preoperative portal embolization in patients with hepatocellular carcinoma.

The factors that contribute to the effect of portal vein embolization before hepatectomy for hepatocellular carcinoma are unclear. Sixty-six patients with hepatocellular carcinoma were enrolled in the study. Changes in liver function, portal vein pressure, and liver volume after embolization were examined. A multiple linear regression analysis was performed to identify factors that independently contributed to the effects of portal vein embolization. The acceptable volume ratio of the remnant liver was calculated from liver function and compared with the volume ratio of the non-embolized liver. No postoperative deaths were observed after portal vein embolization or hepatectomy. Serum total bilirubin and prothrombin time did not change significantly after portal vein embolization. In patients who underwent arterial embolization before portal vein embolization, aminotransferase levels increased significantly. The only factor that could significantly predict the atrophy effects of portal vein embolization was previous arterial embolization. The volume ratio of the non-embolized liver was smaller than the acceptable volume ratio of the remnant liver in 18 of 40 patients and increased over the acceptable volume ratio in all cases after portal vein embolization. Portal vein embolization induced atrophy or hypertrophy of the embolized or non-embolized liver sufficiently, even when the liver was dysfunctional or cirrhotic. The atrophy effects were significant, especially when arterial embolization had been performed before portal vein embolization.