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Background: Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree., Methods: Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy., Results: Twenty-three patients (5.5%) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P < 0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer., Conclusions: The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.

Background: Multifunctional redox protein human thioredoxin (TRX-1) is reduced by thioredoxin reductase (TRX-R). The aim of the present study was to examine the distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to clarify their usefulness as prognostic factors after surgical resection., Methods: Immunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from 38 patients who underwent surgical resection, and TRX-1/TRX-R localization in relation to outcome was examined., Results: TRX-1 protein levels were significantly higher in GBC samples than in cholecystolithiasis samples (P = 0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in the nucleus in 76% (29/38), with nuclear expression in the invasion front observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of cancer cells and in the invasion front in 28 samples. In all of the samples, the depth of tumour invasion, lymph node metastasis, surgical margin, curability and nuclear expression of TRX-1 in the invasion front were significant prognostic factors by univariate analysis. In 27 selected patients who underwent curative resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the invasion front was a significantly prognostic factor., Conclusion: TRX-1 nuclear expression in the GBC invasion front is a significant prognostic marker. Patients with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour invasion front should be observed carefully even if after curative resection., (© 2012 International Hepato-Pancreato-Biliary Association.)

The aim of this study was to evaluate the results of our series of 90 operations for gallbladder carcinoma according to the Japanese Society of Biliary Surgery (JSBS) classification system and to clarify the appropriate surgical strategy for advanced gallbladder carcinoma based on the depth of primary tumor invasion and lymph node metastasis. Generally, only a surgical resection can achieve a prognostic improvement of the advanced gallbladder carcinoma. The survival of patients with this neoplasm depends strictly on the depth of histological primary tumor invasion and lymph node metastasis. A retrospective analysis was conducted on 90 patients from 1990 to 2004 who underwent a surgical resection of gallbladder carcinoma. The factors influencing survival were examined. Thirty-nine patients with palliative treatment (not resected cases), which was diagnosed as T3 or T4 by preoperative imagings, were also included in this study. The significance of the variables for survival was examined by the Kaplan-Meier method and the log-rank test followed by multivariate analyses using Cox's proportional hazard model. Portal invasion, lymph node metastasis, the surgical margin (+ vs. -) and the final curability (fCurA, B vs. C) were all found to be independent prognostic factors in the multivariate analysis. In pT2 gallbladder carcinoma, a better survival was achieved in an aggressive surgical approach, in order of a S4a+S5 hepatic resection, an extended cholecystectomy and a cholecystectomy. In pT3 and pT4, although radical extended surgery did not provide the opportunity for good survival even after lobectomy of the liver, the survival of patients with curative surgery was statistically better than in those without curative surgery. In addition, the nodal involvement of pN1 to pN2 was better than that with pN3. A S4a+S5 hepatectomy, therefore, appears to be adequate for the treatment of pT2 gallbladder carcinoma. Even in patients with pT3 and pT4 gallbladder carcinoma, long-term survival can be expected by an operation with a tumor-free surgical margin. The role of radical surgery, however, is considered to be limited in patients with pN3 lymph node metastasis.

Background/purpose: The role of aggressive surgery for patients with stage IV gallbladder carcinoma was examined., Methods: Cancers were classified according to the TNM system of the Japanese Society of Biliary Surgery. The survival of 37 patients with stage IV cancer (stage IVa, n = 15; stage IVb, n = 22) treated by surgical resection during the period January 1990 to December 2004 was examined and compared with the survival of 41 patients with stage IV disease not treated by surgical resection during the same period., Results: The postoperative survival rate was significantly better for patients with resected stage IVa cancer than for patients with resected stage IVb disease and for those with nonresected stage IV disease. Survival in patients with N3 lymph node metastasis, liver metastasis, peritoneal dissemination, or vascular invasion was poor, like that in the nonresected group. Surgical resection without residual tumors (curability A and B) yielded a significantly better outcome than that with residual tumor (curability C). There were three 5-year survivors that were treated successfully by curative resection (curability A and B) and all had T4N0 disease., Conclusions: These results suggest that surgical resection significantly improves survival even in patients with stage IV gallbladder carcinoma when N3 metastasis, liver metastasis, peritoneal dissemination, and vascular invasion are absent. Curative resection can be expected to produce long-term survival in selected patients with stage IV gallbladder carcinoma.

Hypothesis: Resection of the gallbladder together with the dilated bile duct is the preferred treatment for pancreaticobiliary maljunction (PBM) with bile duct dilatation, whereas this treatment for PBM without bile duct dilatation is still controversial., Design: Retrospective study of 196 patients from January 1979 to November 2004., Setting: Two university hospitals., Patients: One hundred ninety-six patients with PBM, 152 (78%) with and 44 (22%) without bile duct dilatation, formed the basis of this study., Main Outcome Measures: The effects of cholecystectomy on long-term results in the patients without bile duct dilatation., Results: Significant differences were observed in patients without bile duct dilatation: patients were older, carcinoma of the gallbladder was more prevalent (19 patients [43.2%] without dilatation vs 9 patients [5.9%] with dilatation), and pancreatic cancer and pancreatitis were also more frequent. Most of their gallbladder carcinomas were found at stage IV (63%). The outcome was very poor in stage IV, whereas 5 patients in stage I and II lived for more than 5 years after surgery. Of the 44 patients without bile duct dilatation, 23 with carcinoma of the gallbladder or pancreas died and the other 2 were lost to follow-up. The remaining 19 patients were alive at the study's conclusion after cholecystectomy without bile duct resection. None of them had bile duct carcinoma at the time of surgery or during the mean follow-up period of 9 years after surgery., Conclusions: Prophylactic cholecystectomy without bile duct resection is the best treatment option for patients with PBM without bile duct dilatation. Possible association of gallbladder carcinoma should be kept in mind at the time of treatment of patients with PBM when the bile duct is not dilated.

Background/aims: The outcome of advanced gallbladder carcinoma is dismal despite aggressive surgery. The aim of this study was to evaluate the surgical outcome and prognostic factors for patients with gallbladder carcinoma and to identify patients who may benefit from radical surgery., Methodology: Fifty-six patients who underwent surgical resection of gallbladder carcinoma were retrospectively reviewed. Their tumor markers, operative management, pathological factors and survival were analyzed., Results: The serum carcinoembryonic antigen level was elevated in 9 of 51 patients (18%) with data available as was the serum carbohydrate antigen 19-9 level in 14 of 47 patients (30%). Univariate analysis showed that jaundice, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, the number, size, macroscopic type, and histological grade of the tumor, the depth of tumor invasion (pT), pathological stage, lymph node metastasis (pN), lymphatic invasion, vascular invasion, perineural infiltration, curability of lymph node dissection and surgical margins have prognostic significance for survival. Multivariate analysis revealed jaundice, high histological grade, pT3 or pT4, and surgical margins were independent prognostic factors for survival., Conclusions: Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels are potential predictors and informative for survival. There are still difficulties to treat gallbladder carcinoma infiltrating beyond subserosa or revealing jaundice.

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65-7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.

Objective: Our aim was to evaluate the performance of helical CT as an aid in the preoperative diagnosis of the spread of carcinomas of the gallbladder., Materials and Methods: Two radiologists retrospectively reviewed both hard-copy and soft-copy (on a monitor with multiplanar reconstruction capability) versions of helical CT scans (3-mm collimation and 3-mm reconstruction) of 21 patients who had undergone surgical resection for carcinomas of the gallbladder. The local spread of the disease was evaluated according to the TNM system, and the results were correlated to the pathologic findings. Inter- and intraobserver differences were checked with kappa statistics. Results of the consensus interpretations were used to calculate sensitivity, specificity, and accuracy of helical CT., Results: No significant inter- or intraobserver differences were found in any T category evaluation. The sensitivities of the hard-copy consensus interpretations in the diagnosis of T1, T2, T3, and T4 lesions were 33%, 64%, 80%, and 100%, respectively; specificities of hard-copy interpretations were 94%, 80%, 81%, and 95%, respectively. For soft-copy (monitor) consensus interpretations, the sensitivities for the diagnosis of T1, T2, T3, and T4 lesions were 33%, 73%, 80%, and 100%, respectively; the specificities of soft-copy interpretations were 94%, 80%, 88%, and 95%, respectively. Overall accuracy of the hard-copy interpretation was 83%; the overall accuracy of the soft-copy interpretation was not significantly different-86%., Conclusion: Helical CT provided 83-86% accuracy in the diagnosis of the local extent of carcinomas of the gallbladder, showing acceptable sensitivity and specificity for the T2 and more advanced lesions but poor sensitivity for the T1 lesions. Use of a monitor with multiplanar reconstructions of the CT data did not significantly improve the diagnostic accuracy.

Background: The current study evaluated whether the sites of liver metastasis from gallbladder carcinoma are correlated with areas of cholecystic venous drainage (CVD) utilizing helical computed tomography (CT) during the injection of contrast medium into the cholecystic artery (cholecystic artery CT)., Methods: Cholecystic artery CT scans were performed in 26 patients with gallbladder carcinoma. Liver metastases were examined retrospectively in these patients on CT, and the sites of liver metastasis and CVD were compared closely. The patients were divided into concurrent (those who had metastasis at the time of cholecystic artery CT), early postoperative metastasis (those who developed metastasis within 6 months after surgery), and late postoperative metastasis (those who developed metastasis more than 6 months after surgery) groups. The frequency of metastasis related to CVD was compared between the three groups., Results: A total of 32 metastases were identified in 11 patients, 21 of which were related to CVD. Six patients were included in the concurrent metastasis group; 18 of 20 tumors were found to be related closely to CVD. There were two patients in the early postoperative metastasis group; all three of the tumors detected were found to be closely related to CVD. Three patients were subclassified as being in the late postoperative metastasis group; none of the nine tumors detected appeared to be in areas associated with CVD., Conclusions: The sites of liver metastases were found to be well correlated with the areas with CVD, particularly in the concurrent and early postoperative metastasis groups. CVD may be a useful marker of potential areas of liver metastasis from gallbladder carcinoma, particularly in patients with early stage metastasis., (Copyright 2001 American Cancer Society.)

Background: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables., Study Design: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model., Results: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%., Conclusions: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.

The role of radical resection in the treatment of gallbladder carcinoma was examined with special reference to lymph node metastasis using two classifications: one proposed by the American Joint Committee on Cancer (AJCC) and the other by the Japanese Society of Biliary Surgery (JSBS). Histologic evaluations for the depth of tumor invasion (T), lymph node metastasis (N), stage, and follow-up for a mean period of 38 months (range 4-185 months) were completed in 52 patients with gallbladder carcinoma who underwent surgical resection from 1982 to 1997. The definition of T was similar in the two classifications. The extent of nodal involvement (N, AJCC; n, JSBS), stage, and survival were examined. In the absence of lymph node metastasis, the 5-year survival rate reached 71%. The 5-year survival rate in patients with involved nodes confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, or along the common hepatic artery (N1 and part of N2 by AJCC; nl and n2 by JSBS) approximated 28%. In contrast, postoperative survival was poor in the presence of more extensive nodal involvement (rest of N2 by AJCC; n3 and n4 by JSBS), with no 2-year survivors. The definition of stage I was the same in both classifications, and all patients in this stage are alive. The 5-year survival rates in stages II and III by the AJCC were 70.7% and 22.4%, respectively, and those by JSBS 61.9% and 23.1%, respectively. Thus the survival rates in stages I to III were essentially similar irrespective of the staging system. Stage IV showed significantly worse survival than stage III by the JSBS classification. In contrast, the differentiation of stage IV from III by the AJCC was not significant because of the better survival in stage IV that contained any T with nodal involvement in the posterosuperior pancreaticoduodenal region and along the common hepatic artery. Radical resection should be considered for patients with stage I to III disease defined by either classification and applied to the tumor invasion up to T3 with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery. The role of radical surgery seems to be limited in patients with more extensive tumor invasion or lymph node metastasis.

Objective: We evaluated the MR imaging features of adenomyomatosis of the gallbladder with particular emphasis on Rokitansky-Aschoff sinuses., Materials and Methods: MR images of 17 patients with histologically proven adenomyomatosis were retrospectively reviewed. The presence of Rokitansky-Aschoff sinuses was evaluated and analyzed; four T2-weighted (fast spin-echo with a surface coil, with or without breath-holding, fast spin-echo with a phased-array coil with breath-holding, and half-Fourier rapid acquisition with relaxation enhancement with breath-holding) and two contrast-enhanced dynamic pulse sequences were studied. These six pulse sequences were separately rated on a 5-point scale by two radiologists for comparison. Interobserver differences were evaluated. Other MR findings were also analyzed., Results: Among the six pulse sequences studied, three T2-weighted with breath-holding sequences were found to be superior to the other three sequences in showing Rokitansky-Aschoff sinuses. In particular, the half-Fourier rapid acquisition with relaxation enhancement was scored the highest by the two observers and received the highest kappa coefficient in our statistical analysis of the scoring. Diffuse-type adenomyomatosis typically showed early mucosal and subsequent serosal enhancement. Localized adenomyomatosis exhibited homogeneous enhancement, showing smooth continuity with the surrounding gallbladder epithelium., Conclusion: MR imaging may be able to provide important information in the diagnosis of adenomyomatosis.

An inflammatory polyp of the gallbladder is a rare variant of benign gallbladder polyp. Differentiation between an inflammatory polyp and polypoid gallbladder carcinoma is difficult when the polyp is more than 1 cm in diameter. We report a rare case of a large inflammatory polyp of the gallbladder masquerading as gallbladder carcinoma in a 37-year-old Japanese woman who was incidentally diagnosed with a large gallbladder polyp, measuring 1 cm in diameter, by ultrasonography. She was asymptomatic and physical examination was unremarkable. Abdominal ultrasonography and endoscopic ultrasonography revealed three polypoid lesions in the gallbladder. One lesion was an isoechoic polyp, measuring 15 x 8 mm, showing a nodular surface and located in the fundus of the gallbladder. The other two lesions were hyperechoic polyps, measuring 5 x 5 mm, in the body of the gallbladder. Computed tomography and magnetic resonance imaging revealed marked enhancement of the largest polypoid lesion by dynamic study, and no lymph node enlargement was noted. Endoscopic retrograde cholangiography revealed a 12 x 8 mm polyp with an irregular surface in the fundus of the gallbladder. Superselective angiography of the cystic artery revealed neovascularity and a tumor stain in the fundus of the gallbladder. Cholecystectomy with lymph node dissection was performed. Intraoperative frozen section diagnosis of the largest polyp was an inflammatory polyp of the gallbladder. The other two polyps were cholesterol polyps. Inflammatory polyp should be considered as a differential diagnosis of hypervascular gallbladder polyps that measure more than 1 cm in diameter.

Background: Extended cholecystectomy is the common operation for gallbladder carcinoma. When extended cholecystectomy is performed, the liver bed can be generously resected from the fundus to the body of the gallbladder; however, the thickness of the liver parenchyma to be removed is limited to the neck of the gallbladder. There have been few reports providing convincing data with regard to how thick the liver can be anatomically resected by extended cholecystectomy., Methods: The thickness of the liver tissue actually resected at the time of extended cholecystectomy and that potentially resected by extended cholecystectomy were measured in 24 clinical and 25 autopsy cases, respectively, to assess the anatomical limit of extended cholecystectomy., Results: The mean anatomical distances from the neck of the gallbladder to the right hepatic duct and to the bifurcation of the anterior and posterior branch of the right hepatic duct were only 1.6 and 5.9 mm, respectively. The distance from the gallbladder to the bifurcation of the superior and inferior branch of the right anterior hepatic duct, and to the root of the right anterior inferior hepatic duct were 11.2 mm2, and 12.8 mm3, respectively (123:p < 0.05). The actual width of the liver excised by extended cholecystectomy was 5.2 mm at the neck, 11.7 mm at the body, and 8.1 mm at the fundus of the gallbladder, respectively. These results indicate that the neck of the gallbladder is anatomically close to the hepatic hilum including the right hepatic duct and portal vein., Conclusions: Surgical strategy for gallbladder carcinoma should be considered to rely not only upon the depth of invasion but also upon the site of gallbladder tumor. When gallbladder carcinoma involves the muscle layer or further at the neck of the organ, more extensive hepatectomy than extended cholecystectomy should be considered.

Forty-nine pathologically proven gallbladder lesions were evaluated in 45 patients using dynamic MRI with a spoiled gradient pulse sequence (SPGR), to access the ability of this technique to differentiate benign from malignant gallbladder lesions. The studies were reviewed retrospectively. Signal intensity of the lesions were measured. Twenty-one malignant and 28 benign lesions were classified into three categories: polypoid, diffuse wall thickening, and exophytic. Early and delayed enhancement patterns were evaluated. For the polypoid masses, malignant lesions (n = 9) demonstrated early and prolonged enhancements, whereas benign lesions (n = 14) had early enhancement with subsequent washout (P < .05). For diffuse gallbladder wall thickening, malignant lesions (n = 6) demonstrated early and prolonged enhancement and benign lesions (n = 14) showed relatively slow, prolonged enhancement (P < .05). The exophytic masses (n = 6) all were malignant and demonstrated early and prolonged enhancement. Dynamic MRI can help differentiate benign from malignant gallbladder lesions.

Background: An accurate frozen section diagnosis is important when deciding the surgical strategy against a gallbladder tumor intraoperatively. Little has been reported on the accuracy of frozen section diagnosis of the gallbladder., Patients and Methods: In a total of 86 consecutive patients with gallbladder tumor, the accuracy of the frozen section diagnosis was examined. There were 32 patients with polypoid lesions and 54 with nonpolypoid tumors., Results: The frozen tissue diagnosis and final diagnosis were identical in 82 of the 86 cases, that is, benign in 65 and malignant in 17. The other four cases had different diagnoses, that is, conversion from benign to malignant in two and from malignant to benign in two. The overall accuracy of frozen diagnosis was 95.3% (97.0% for benign and 94.7% for malignant). In 32 polypoid lesions, the accuracy of frozen section diagnosis was 91% (93% for benign; 89% for malignant). In 54 nonpolypoid lesions, the accuracy of diagnosis was 98% (100% for benign; 93% for malignant). The diagnosis of depth of invasion was identical only in 7 (70%) of the 10 carcinoma cases examined, while it was diverse in the remaining 3, that is, conversion from adenocarcinoma invading the subserosa to that limiting to the mucosa in one, from carcinoma within the mucosa to that infiltrating the muscle coat in one, and from carcinoma affecting the muscle layer to that invading the subserosa in the other. Alterations of frozen section diagnosis about being benign or malignant and about the depth of invasion were encountered in seven patients, five of whom had a polypoid tumor., Conclusions: The intraoperative frozen tissue diagnosis is fairly reliable as to whether lesions are malignant or benign; however, accuracy is low in patients with polypoid lesions of the gallbladder. Also, frozen section diagnosis does not reliably measure the depth of invasion of gallbladder carcinoma.

Xanthogranulomatous cholecystitis (XC) is occasionally difficult to differentiate from gallbladder cancer and mandates efforts to avoid extensive operations. We studied the clinical factors to differentiate XC from cancer. Subjects were a consecutive series of 10 patients with XC and 10 with carcinoma, all of whom radiologically showed thickened gallbladder walls. As opposed to cancer, XC was typified by invisible gallbladders on cholangiography (1), the presence of cholelithiasis (P = 0.01) (2), and, intraoperatively, an aspirate of pus or nothing (P < 0.01) (3). To diagnose XC against gallbladder cancer, (1) and (2) in combination and (3) demonstrated an accuracy of 82.4% and 85.0 per cent, respectively. Clinically, XC can be distinguished from gallbladder cancer by cholangiography, calculous findings, and a gallbladder aspirate of pus or nothing.

Background: The clinical course of patients with carcinoma of the gallbladder depends on the depth of tumour invasion. This study was conducted to clarify the prognostic factors affecting survival and appropriate surgical strategy based on depth of invasion of gallbladder carcinoma according to the pathological tumour node metastasis (pTNM) classification., Methods: A total of 70 patients who underwent surgical resection were reviewed retrospectively with regard to the type of operation, histopathological findings of the resected gallbladder carcinoma and clinical follow-up after operation., Results: Twelve patients with pT1 gallbladder carcinoma fared favourably following cholecystectomy or extended cholecystectomy. In 13 of 26 patients with pT2 gallbladder carcinoma, lymph node metastasis was evident: pN1 in eight and pN2 in five. The 3-year survival rate of patients with pT2 gallbladder carcinoma was 28 per cent after cholecystectomy, 91 per cent after extended cholecystectomy and 67 per cent after hepatectomy. In 21 of 28 patients with pT3 or pT4 gallbladder carcinoma, surgical margins were affected by malignant cells. The 1-year survival rate of patients with pT3 or pT4 gallbladder carcinoma was 24 per cent, even after hepatectomy. Significant prognostic factors were age, macroscopic type, histological grade, depth of invasion, lymph node metastasis, pathological stage, lymphatic invasion, venous invasion, perineural invasion and involved surgical margins., Conclusion: Cholecystectomy was adequate for pT1 gallbladder carcinoma. Extended cholecystectomy or hepatectomy with extrahepatic bile duct resection and lymph node dissection (pN1 and pN2) were justified for pT2 gallbladder carcinoma. The survival of patients with more advanced gallbladder carcinoma remains dismal.

The objective of this study was to determine histopathologic factors that influence the failure or success of extended cholecystectomy and more aggressive surgery to attain long-term survival in patients with advanced carcinoma of the gallbladder. Of 46 patients with carcinoma of the gallbladder who had undergone surgical resection, 36 had advanced carcinoma invading to or beyond the subserosal layer. Among these 36 patients were 10 long-term survivors (> 5 years) and 11 short-term survivors who died of recurrence (< 37 months) after extended cholecystectomy or more extensive surgery. Factors were compared between the two groups. Significant factors observed in the long-term survivors were the depth of invasion limited to the subserosal layer (p < 0.05), hepatic infiltration < 5 mm (p < 0.01), histologic grade of papillary or well differentiated adenocarcinoma (p < 0.01), absent or minimal venous, lymphatic, and perineural invasion (p < 0.01), and lymph node metastasis limited to the hepatoduodenal ligament (p < 0.05). It was concluded that the patients with subserosal invasion have a hope for long-term survival by extended cholecystectomy or more aggressive surgery when hepatic infiltration and venous, lymphatic, and perineural invasion are absent or minimal, the histologic grade is papillary or well differentiated adenocarcinoma, and lymph node metastasis is limited to the hepatoduodenal ligament.

Objective: To assess the usefulness of laparoscopic cholecystectomy for unsuspected and suspected gallbladder carcinoma., Design: Retrospective review with a mean follow-up of 27 months, ranging from 1 to 47 months., Setting: University hospital and 8 affiliated hospitals., Patients: Of 2616 laparoscopic cholecystectomies performed over 4 years, 24 gallbladder carcinomas were treated by laparoscopic cholecystectomy and retrospectively reviewed., Results: The clinical course depended on the histopathologic depth of invasion of gallbladder carcinoma. All 6 cases of pathologic tumor (pT) stage in situ (pTis) gallbladder carcinoma and 2 cases of pT1 gallbladder carcinoma showed no invasion to the lymphatic, venous, or perineural spaces, and these 8 patients were all doing well from 2 to 19 months (mean, 11 months) after laparoscopic cholecystectomy. Sixteen cases of pT2 or pT3 gallbladder carcinoma invaded the subserosal layer or the liver, and 5 of the 16 patients were dead of liver dysfunction, abdominal wound recurrence, or liver metastasis 5 days and 7, 12, 15, and 18 months after operation, although additional resection of the liver bed with lymph node dissection was performed after laparoscopic cholecystectomy in 4 of these 5 patients. Abdominal wall recurrence in the absence of distant metastasis was present in 3 (19%) of the 16 patients with pT2 or pT3 gallbladder carcinoma due to inoculation of cancer cells in the abdominal stab wounds where the gallbladder or laparoscope was removed., Conclusions: Gallbladder carcinoma at the pTis or pT1 stage removed laparoscopically needs no other treatment. We recommend that the gallbladder be removed by vinyl bag and port sites be excised or washed with normal saline to prevent port site recurrence in patients with laparoscopic cholecystectomy for pT2 or pT3 carcinoma.

Anomalous pancreaticobiliary ductal junction (APBDJ) can be defined as the junction between the choledochus and the pancreatic duct outside of the duodenalwall and beyond the influence of the sphincter of Oddi. The frequency of APDBJ has been reported to be 2-3% of patients examined with ERCP. The significance of APBDJ has been recognized as an etiological factor developing congenital choledochal dilatation (CCD) and biliary tarct carcinoma because most patients with CCD present with APBDJ and 23% of patients with APBDJ have biliary tract carcinoma in the Japanese nationwide study. Of the patients with APBDJ, approximately 80% are associated with CCD and the remaining 20% are not. The occurrence rate of biliary tract carcinoma has been reported to be 3-18% (9% in ours) in the former group, while it reaches 33-54% or even more in the latter. The origin of biliary tract carcinoma is either the gallbladder or extrehepatic bile duct in most patients with CCD, whereas the gallbladder is in patients without CCD. We advocate the excision of the extrahepatic dilated bile duct together with the gallbladder in patients with CCD and cholecystectomy for patients with APBDJ without CCD at the time of diagnosis. The necessity of prophylatic hepatectomy in patients with type IVA CCD and of prophylactic resection of the extrahepatic bile duct in patients without CCD need further analyses to draw the final conclusion. Careful follow-up is recommended against the liver, biliary tract and pancreas even after surgery.

Objective: To assess the indications for, and limitations of, extended cholecystectomy in the treatment of carcinoma of the gall bladder. DESIGN. Retrospective study., Setting: University hospital, Japan., Subjects: 23 Patients who were operated on for carcinoma of the gall bladder, 1982-92 out of the total of 73 who presented to our department with the disease., Interventions: Extended cholecystectomy with en bloc lymph node dissection with or without resection of the extrahepatic bile duct, or hepatic resection, or pancreaticoduodenectomy, or a combination., Main Outcome Measures: Outcome related to TNM classification., Results: 7 Patients had stage I or II disease, and their cumulative five year survival rates (including one censored death) were 67% and 100%, respectively; 9 patients had stage III disease and of these 2/4 patients with T3N1 tumours died of their cancer, but the remaining 7 were alive a mean of 58 months later (though there was one censored death). Of the 7 with stage IV disease all but one were dead within 16 months despite more extensive surgery. The cumulative five year survival was 92% in patients with stage I, II and III (except T3N1 tumours)., Conclusion: Extended cholecystectomy with or without resection of the extrahepatic bile duct is indicated for patients with stage I, II, or III (except T3N1) tumours of the gall bladder.

Anomalous pancreaticobiliary ductal junction (APBDJ) is considered to be a factor developing carcinoma of the biliary tract. However, the difference in clinical significance of APBDJ between patients associated with choledochal cyst and those without cyst with special reference to the malignant potential of the gallbladder has been little studied. Of 1,325 patients examined with direct cholangiography, 29 patients were found to have APBDJ of whom 21 patients were associated with choledochal cyst while eight were not. Their associated hepatobiliary diseases were clinicopathologically examined and compared. The frequencies of carcinoma of the gallbladder in patients without choledochal cyst and in those with cyst were 50% and 5%, respectively, the difference being significant (p < 0.05). This frequency did not depend upon the type of APBDJ. None of the patients with gallbladder carcinoma had gallstones. The overall frequencies of carcinoma of the biliary tract (gallbladder and bile duct) were 14% in patients with cyst and 50% in those without cyst. All were gallbladder carcinoma in the latter group. We conclude that the gallbladder is under the condition with significantly greater malignant potential in patients with APBDJ especially in cases not associated with choledochal cyst. Prophylactic cholecystectomy and excision of cyst if associated should be indicated for patients with APBDJ.

Background: After the development of hepatobiliary imaging modalities and surgical procedures, we reappraised the effect of surgical treatment on the prognosis of gallbladder carcinoma., Methods: Records of 32 patients with gallbladder carcinoma who underwent surgical resection between 1982 and 1992 were examined according to the pTNM staging system, and patients' prognoses were analyzed in relation to pathologic staging and surgical procedures., Results: The standard operative procedure was extended cholecystectomy (cholecystectomy plus hepatic resection [wedge or anatomic segmentectomy] plus en bloc lymph node dissection) with or without extrahepatic bile duct resection, and this was performed in 63% of cases. The actual 5-year survival rate of patients whose postoperative period was more than 5 years was 53%. The standard operative procedure gave satisfactory results for nine patients with stage I or II disease because all except two patients who died of other diseases were still alive more than 3 years after operation and there were five (56%) 5-year survivors. At stage III with pN1a lymph node metastasis, 50% of patients survived more than 5 years. However, in patients with pN1b or distant organ metastases, none survived more than 3 years even after more aggressive operation including hepatectomy plus pancreatoduodenectomy., Conclusions: Complete removal of microscopic spread to the liver, bile duct, and lymph nodes is a great advantage to patients with gallbladder carcinoma at stages I and II and to those at stage III even in the presence of lymph node metastasis in the hepatoduodenal ligament.

Of 716 consecutive patients who underwent cholecystectomy, forty-four patients had preoperatively defined polypoid lesions of the gallbladder. Of these 44, 32 patients had benign polypoid lesion and the other 12 had carcinoma of the gallbladder. The aim of the present study was to evaluate the precise differentiating factors between the malignant and benign polypoid lesions and to examine the outcome of patients with polypoid carcinoma after radical surgery. The patients' sex, symptoms and the presence of gallstones were not significantly different between patients with carcinoma and those with benign polypoid lesion. However, the size (> 10 mm), number of polypoid lesion (single) and patients' age (> or = 60-yr-old) were the significant indicators of carcinoma. All but one patient with carcinoma underwent surgery and ten of twelve patients are alive at present with a mean of 6 years after surgery. The maximal size of the lesion was closely associated with the depth of invasion and carcinomas confined to the mucosal or proper muscle layer were free from lymph node metastasis. We concluded that carcinoma is highly suspected when the size of the polypoid lesion is over 10 mm, when the polypoid lesion is solitary and patient's age is over 60 years. The detection of the malignant polypoid lesion results in satisfactory outcome after surgery.

One hundred and twenty-four patients with bile duct carcinoma treated during 16 years were analysed retrospectively for multiple biliary tract carcinoma. Sixty-two cases had undergone a cholecystectomy either as part of a pancreaticoduodenectomy or a bile duct resection or as part of an internal drainage procedure. Three (5%) were found to have an incidental separate carcinoma of the gall-bladder. The discontinuity between the two sites of cancer was histologically confirmed. Clinical concern was that approximately 5% of patients with bile duct carcinoma had a synchronous carcinoma of the gall-bladder. Thus, careful examination of the entire biliary tract including the gall-bladder is necessary at the time of curative surgery for bile duct carcinoma.

We have previously shown that an anomalous pancreaticobiliary ductal junction (APBDJ) is a risk factor for developing carcinoma of the gallbladder. However, the incidence of APBDJ in patients with primary carcinoma of the gallbladder has been little examined. Of 53 consecutive patients with gallbladder carcinoma, 37 patients had a direct cholangiography to allow satisfactory evaluation of the pancreaticobiliary ductal junction. Eleven per cent of these 37 patients had an associated APBDJ, which was significantly higher than the reported incidence of APBDJ in human (2%). Two of these four patients were associated with choledochal cyst and the other two were not. The main clinical differences in patients with gallbladder carcinoma associated with APBDJ and those without APBDJ were that the mean age of the former group was lower by about 10 years than the latter, and none had gallstones in the former while 54 per cent had gallstones in the latter group. The results show that APBDJ is a risk factor for developing carcinoma of the gallbladder earlier, and factors other than gallstone are more causative in patients with APBDJ. The frequent association with APBDJ should be kept in mind at the time of surgical treatment of the primary gallbladder carcinoma.

A clinicopathologic study of 40 cases of carcinoma of the gallbladder is presented. Twenty-six cases resected were assessed retrospectively with respect to the operative procedures employed and the results based on the pathologic findings from the resected specimens. The relationship between clinical features, macroscopic forms of tumor, histological types, liver invasion, and lymph node metastasis were investigated. Papillary, papillary infiltrative and nodular forms were classified as either papillary adenocarcinoma or well-differentiated tubular adenocarcinoma and invasion of the liver and lymph node metastasis were rare. Frequent lymph node metastasis was encountered in the nodular infiltrative form and invasion of the liver was frequently present in the infiltrative form. Invasion of the liver, lymph node metastasis, and the presence of gallstones were less frequent in papillary adenocarcinoma. In contrast, moderately-differentiated tubular adenocarcinoma frequently had lymph node metastasis. Invasion of the liver and lymph node metastasis were, however, present regardless of the histologic types and were more related to the extent of subserosal involvement present. A female preponderance was noted in poorly-differentiated adenocarcinoma. The main reasons for surgery being limited to exploratory laparotomy only or palliative procedures included carcinoma infiltration into the hepatoduodenal ligament, carcinoma extension to the neighboring structures, multiple liver metastases, peritoneal dissemination, large liver invasion, and multiple metastases to the paraaortic lymph nodes.

Among 26 patients with gallbladder carcinoma, 11 resected cases were studied retrospectively with respect to the preoperative imaging techniques and the operative procedures employed. Ultrasonography, endoscopic ultrasonography, and computed tomography were valuable in detecting gallbladder carcinoma preoperatively while direct cholangiography and angiography were helpful in designing operative strategy. The ultrasonographic findings were: a polypoid (fungating) mass protruding into the gallbladder lumen in 45%, abnormal thickening of the gallbladder wall in 18%, and a mass in the gallbladder invading adjacent organs in 18% of cases. Approximately 80% was diagnosed preoperatively by ultrasonography. Correct diagnosis was made by computed tomography in 60% of the cases. Endoscopic ultrasonography offered valuable information on the depth of tumor invasion. Direct cholangiography and angiography were useful in assessing the extent of the tumor spread. Recent advances in hepatobiliary imaging techniques, especially ultrasonography and computed tomography, contributed greatly to the detection and evaluation of gallbladder carcinoma at an early and resectable stage.