Yoshio Shirai

Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage

BACKGROUND The role of surgery in the treatment of gallbladder carcinoma (GBC) is controversial. The outcome after prospective radical surgery for GBC is discussed on the basis of the TNM stage of the tumor. METHODS One hundred six patients who had undergone radical surgery were selected. The standard radical procedure consisted of a cholecystectomy accompanied by lymph node dissection, wedge resection of the liver, and resection of the extrahepatic bile ducts. The stage was determined by pathologic examination of resected specimens. RESULTS Lymph node metastases were identified in no patients with T1 tumors (n = 15), 48% of patients with T2 tumors (n = 46), 72% of patients with T3 tumors (n = 25), and 80% of patients with T4 tumors (n = 20). One patient died within 30 days after radical surgery (mortality rate, 0.9%). There were 35 5-year survivors including 11 patients with nodal involvement, 10 with stage I tumors, 13 with stage II tumors, 10 with stage III tumors, and 2 with stage IV tumors. The cumulative 5-year survival rate in patients with stage I tumors was 91% (n = 15), 85% in patients with stage II tumors (n = 24), 40% in patients with stage III tumors (n = 28), and 19% in patients with stage IV tumors (n = 39). In patients with stage III and IV tumors the 5-year survival rate was 52% after curative resection (n = 35). This was significantly better than the 5% 5-year survival rate after a noncurative resection (n = 32). CONCLUSIONS The presence of lymph node metastases is strongly influenced by the depth of invasion of the primary tumor. Accurate determination of the TNM stage is essential in comparing surgical results, predicting patient outcome, and planning additional treatment. Standard radical surgery contributes to patient survival and is recommended in patients with advanced GBC.

Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder

Specimens from 3197 consecutive and unselected cholecystectomies performed during a 6‐year period were studied. Adenomyomatosis of the gallbladder was defined as a lesion characterized by a thickened wall that consisted of Rokitansky‐Aschoff sinuses surrounded by proliferated fibromuscular tissue. Adenomyomatosis was found in 279 specimens and classified as one of three types: segmental, fundal, or diffuse. Segmental adenomyomatosis was found in 188 specimens; gallbladder cancer (GBC) developed in 12 (6.4%) of the patients with segmental type adenomyomatosis. GBC developed in the mucosa of the fundal compartment distal to the annular stricture of the segmental type adenomyomatosis in all 12 of these patients. Conversely, GBC developed in 93 (3.1%) of the other 3009 patients (those with fundal alone, diffuse, or no adenomyomatosis). The prevalence of GBC in patients with segmental adenomyomatosis was significantly (P < 0.025) higher than that of patients without segmental adenomyomatosis. Clinicians should be aware that segmental adenomyomatosis often coexists with GBC.

Radical second resection provides survival benefit for patients with T2 gallbladder carcinoma first discovered after laparoscopic cholecystectomy

Port site recurrence or peritoneal seeding is a fatal complication following laparoscopic cholecystectomy for gallbladder carcinoma. The aims of this retrospective analysis were to determine the association of gallbladder perforation during laparoscopic cholecystectomy with port site/peritoneal recurrence and to determine the role of radical second resection in the management of gallbladder carcinoma first diagnosed after laparoscopic cholecystectomy. A total of 28 patients undergoing laparoscopic cholecystectomy for gallbladder carcinoma were analyzed, of whom 10 had a radical second resection. Five patients had recurrences; port site/peritoneum recurrence in 3 and distant metastasis in 2. The incidence of port site/peritoneal recurrence was higher in patients with gallbladder perforation (3/7, 43%) than in those without (0/21, 0%) (p = 0.011). The outcome after laparoscopic cholecystectomy was worse in 7 patients with gallbladder perforation (cumulative 5-year survival of 43%) than in those without (cumulative 5-year survival of 100%) (p <0.001). Among 13 patients with a pT2 tumor, the outcome after radical second resection (cumulative 5-year survival of 100%) was better than that after laparoscopic cholecystectomy alone (cumulative 5-year survival of 50%) (p = 0.039), although there was no survival benefit of radical second resection in the 15 patients with a pT1 tumor (p = 0.65). In conclusion, gallbladder perforation during laparoscopic cholecystectomy is associated with port site/peritoneal recurrence and worse patient survival. Radical second resection may be beneficial for patients with pT2 gallbladder carcinoma first discovered after laparoscopic cholecystectomy.

Simultaneous detection of colorectal carcinoma liver and lung metastases does not warrant resection

BACKGROUND Recent evidence suggests that metastasectomy is efficacious for selected patients with hepatic and pulmonary metastases from a colorectal primary. The aim of this study was to identify a subgroup of patients who best benefit from hepatic and pulmonary metastasectomy among those with colorectal carcinoma metastases. STUDY DESIGN We analyzed retrospectively a total of 136 patients who underwent resection of hepatic or pulmonary metastases of colorectal origin at Niigata University Medical Hospital between 1982 and 2000. The median follow-up period was 94 months. Eighty-four patients underwent hepatectomy alone, 25 underwent pulmonary resection alone, and 27 underwent both hepatic and pulmonary resection. The 27 patients undergoing hepatic and pulmonary resection were divided into two groups: 17 patients with sequentially detected hepatic and pulmonary metastases and 10 patients with simultaneously detected metastases. Survival time was determined from the date of initial metastasectomy. Differences in cumulative survival were evaluated using the log-rank test. Sixteen factors were assessed for their influence on the survival of the 27 patients undergoing resection of hepatic and pulmonary metastases; univariate and multivariate analyses were used in this evaluation. RESULTS Patient survival after hepatic and pulmonary resection was comparable with that after hepatectomy alone (p = 0.536) and that after pulmonary resection alone (p = 0.294). Among the 27 patients undergoing hepatic and pulmonary resection, the outcomes after resection were significantly better in patients with sequentially detected metastases (cumulative 5-year survival of 44%) than in those with simultaneously detected ones (cumulative 5-year survival of 0%) (p < 0.001). On multivariate analysis sequential detection of hepatic and pulmonary metastases was the strongest independent favorable prognostic factor (p <0.001). CONCLUSIONS Patients with sequentially detected hepatic and pulmonary metastases from a colorectal primary are good candidates for aggressive metastasectomy. Simultaneous detection of these metastases does not warrant resection.

Spread of gallbladder carcinoma: CT evaluation with pathologic correlation

Abstract.Background: To assess the accuracy of computed tomographic (CT) imaging in the detection of spread and staging of gallbladder carcinoma. Methods: CT findings of spread of gallbladder carcinoma in 59 Japanese patients who underwent radical surgery were correlated retrospectively with pathologic findings. Results: The incidence of histologically proven nodal involvement was 54% (32 patients) and the most common spread of gallbladder carcinoma. The sensitivities in CT detection of N1 and N2 nodal involvement were 36% and 47%, respectively; positive predictive values were 94% and 92%, respectively. Direct extension to the liver, extrahepatic bile duct, and gastrointestinal tract or pancreas were histologically confirmed in 24, 18, and five patients. The sensitivities in the CT detection of direct spread to the liver of less than 2 cm, more than 2 cm, the extrahepatic bile duct, and the gastrointestinal tract or pancreas were 65%, 100%, 50%, and 57%, respectively; positive predictive values were 77%, 100%, 90%, and 100%, respectively. The incidence of liver metastases and involvement of interaortocaval nodes were 7% and 16%, respectively. The sensitivities in CT detection of liver metastases and involvement of interaortocaval nodes were 75% and 21%, respectively; positive predictive values were 100% and 86%, respectively. CT could not detect direct spread to omentum and peritoneal seedings. Conclusion: For detecting the spread of gallbladder carcinoma, CT imaging has low to moderate sensitivity; however, CT imaging can help in determining resectability and in planning the treatment, especially in advanced-stage gallbladder carcinoma, because of a high positive predictive value.

Combined pancreaticoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma

The objective of this study was to evaluate the efficacy of combined pancreaticoduodenectomy and hepatectomy for the treatment of patients with locally advanced gallbladder carcinoma.

Depth of Subserosal Invasion Predicts Long-Term Survival After Resection in Patients With T2 Gallbladder Carcinoma

AbstractBackground: This study aimed to identify a subgroup of patients with inapparent T2 gallbladder carcinoma who may be best suited for radical second resection. Methods: A retrospective analysis was conducted of 126 patients with pathologic stage T2 (pT2) gallbladder carcinoma (51 with clinically evident tumor and 75 with inapparent tumor). Depth of subserosal invasion was measured histologically in each gallbladder specimen. The median follow-up period was 113 months. Results: In all 126 patients, depth of subserosal invasion was the strongest independent prognostic factor by univariate (P < .0001) and multivariate (relative risk, 9.27; P < .0001) analyses. Among the 75 patients with inapparent tumor, the outcome after resection was significantly better in patients who had undergone radical second resection than in patients who had undergone cholecystectomy alone (P = .0006). When depth of subserosal invasion was divided into ≤2 vs. >2 mm, the effectiveness of radical second resection remained only in patients with subserosal invasion >2 mm (P = .0004). Conclusions:Depth of subserosal invasion best predicts postresectional long-term survival of pT2 gallbladder carcinoma patients. Among patients with inapparent pT2 tumors, those with subserosal invasion >2 mm are good candidates for radical second resection.Background: This study aimed to identify a subgroup of patients with inapparent T2 gallbladder carcinoma who may be best suited for radical second resection. Methods: A retrospective analysis was conducted of 126 patients with pathologic stage T2 (pT2) gallbladder carcinoma (51 with clinically evident tumor and 75 with inapparent tumor). Depth of subserosal invasion was measured histologically in each gallbladder specimen. The median follow-up period was 113 months. Results: In all 126 patients, depth of subserosal invasion was the strongest independent prognostic factor by univariate (P < .0001) and multivariate (relative risk, 9.27; P < .0001) analyses. Among the 75 patients with inapparent tumor, the outcome after resection was significantly better in patients who had undergone radical second resection than in patients who had undergone cholecystectomy alone (P = .0006). When depth of subserosal invasion was divided into ≤2 vs. >2 mm, the effectiveness of radical second resection remained only in patients with subserosal invasion >2 mm (P = .0004). Conclusions:Depth of subserosal invasion best predicts postresectional long-term survival of pT2 gallbladder carcinoma patients. Among patients with inapparent pT2 tumors, those with subserosal invasion >2 mm are good candidates for radical second resection.

Preoperative predictors of vascular invasion in hepatocellular carcinoma

AIMS Vascular invasion is an established adverse prognostic factor in hepatocellular carcinoma (HCC). The aim of the current study was to identify the preoperative predictors of vascular invasion in patients undergoing partial hepatectomy for HCC. METHODS A retrospective analysis of 227 consecutive patients who underwent partial hepatectomy for HCC was conducted. Vascular invasion was defined as gross or microscopic involvement of the vessels (portal vein or hepatic vein) within the peritumoral liver tissue. RESULTS Seventy-six (33%) patients had vascular invasion. Among the preoperative factors, only the tumour size (relative risk, 16.78; p<0.01) and the serum alpha-fetoprotein (AFP) level (relative risk, 3.57; p<0.01) independently predicted vascular invasion. As the tumour size increased, the incidence of vascular invasion increased: < or =2 cm, 3%; 2.1-3 cm, 20%; 3.1-5 cm, 38%; and > 5 cm, 65%. The incidence of vascular invasion was 32% in patients with serum AFP levels < or =1000 ng/mL, compared to 61% in patients with higher serum AFP levels (p<0.01). Patients with both tumours >5 cm and serum AFP levels >1000 ng/mL had an 82% incidence of vascular invasion. CONCLUSIONS The tumour size and serum AFP level, alone or in combination, are useful in predicting the presence or absence of vascular invasion before hepatectomy for HCC.

Risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts

The aim of this study was to elucidate the risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts.

Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence

BACKGROUND & AIMS The activating receptor natural killer group 2, member D (NKG2D) and its ligands play a crucial role in immune response to tumors. NKG2D ligand expression in tumors has been shown to be associated with tumor eradication and superior patient survival, but the involvement of NKG2D ligands in the immune response against hepatocellular carcinoma (HCC) still remains to be elucidated. METHODS We investigated the expression of NKG2D ligands in HCC tissues collected from 54 patients and HCC cell lines. We also examined the proteasome expression and the effect of inhibition of proteasome activity on NKG2D ligand expression in HCC tissues and cell lines. RESULTS In dysplastic nodules (DN), well-differentiated (well-HCC), and moderately-differentiated HCCs (mod-HCC), UL16-binding protein (ULBP) 1 was expressed predominantly in tumor cells, but not in poorly-differentiated HCCs (poor-HCC). Remarkably, recurrence-free survival of patients with ULBP1-negative HCC was significantly shorter than that of patients with ULBP1-positive HCC (p=0.006). Cox regression analysis revealed that loss of ULBP1 expression was an independent predictor of early recurrence (p=0.008). We confirmed that ULBP1 was expressed in the well- and mod-HCC cell lines, but not in the poor-HCC cell line KYN-2. However, inhibition of proteasome activity resulted in significant up-regulation of ULBP1 expression in KYN-2. Moreover, we found that 20S proteasome expression was more abundant in KYN-2 than that in the well- and mod-HCC cell lines. CONCLUSIONS ULBP1 is prevalently expressed in DN to mod-HCC, but loss of its expression correlates with tumor progression and early recurrence.