Carcinoma of the gallbladder. A clinicopathology of 103 patients and a newly proposed staging

Tissue samples from 103 patients with gallbladder carcinoma were examined, using 5-mm stepwise tissue sections. Three pathologic stages were used: Stage I; carcinoma invading not further than the muscle coat of the gallbladder, with or without extension along Rokitansky-Aschoff sinuses in the subserosa (11 cases); Stage II, carcinoma extending to the subserosal fibroadipose tissue of the gallbladder (73 cases); and Stage III: carcinoma invading the adjacent organs such as the duodenum, liver, and colon (19 cases). In the 11 patients with Stage I carcinoma, there was no apparent lymph node metastasis and all remained well for 3 months to 14 years after the initial operation. The cumulative 3-year survival rate of Stage I (100%) was significantly higher than of Stage II (40%) and Stage III (10%) (P less than 0.01, P less than 0.001). The Stage I tumors, therefore, can be defined as early carcinoma of the gallbladder. Dysplastic epithelium was seen in the mucosa adjacent to the malignant lesion in 57% of those with gallbladder carcinoma: 73% in Stage I, 59% in Stage II, and 42% in Stage III. Nine gallbladders had multiple foci of adenocarcinoma in a background of a diffuse dysplasia. Immunohistochemical study for carcinoembryonic antigen and carbohydrate antigen 19-9 resulted in positive staining of the dysplastic epithelial element adjacent to the invasive carcinoma and, in a similar fashion, in the carcinoma itself, thereby indicating a close relation between the epithelial dysplasia and adenocarcinoma of the gallbladder.     

Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder

Postsurgical recurrence at distant sites frequently occurs in pathological tumor stage 2 (pT(2)) carcinoma of the gallbladder even though the carcinoma is limited to the gallbladder wall. Little is known, however, about the molecular events leading to its development and progression. A large body of evidence suggests that cyclooxygenase-2 (COX-2) is up-regulated in carcinoma tissues and plays roles in promoting cell-proliferation, growth and metastasis of carcinoma cells. In the present study, immunohistochemistry was performed to determine the expression levels of COX-2 in the subserosal layer of 33 cases of pT(2) gallbladder carcinoma in which curative resections had been performed and to determine the correlations of the expression levels of COX-2 with mode of recurrence and postsurgical survival. Immunostaining of COX-2 in the epithelia was recognized in more than 80% of normal epithelia, noncancerous pathological lesions of the gallbladder except for intestinal metaplasia and pT(1-4) carcinoma specimens. Intense staining was observed in large percentages of hyperplastic lesions (65%), pT(2) carcinoma specimens (76%) and pT(3) and pT(4) carcinoma specimens (64%) compared to the percentages of normal epithelia and other pathological lesions (0-25%). Intense staining was also observed in the adjacent stroma in pT(2) carcinoma specimens (33%) and in those in pT(3) and pT(4) carcinoma specimens (43%) but only in small percentages of the stroma adjacent to normal epithelia and pathological lesions (0-8%). In situ hybridization confirmed the existence of COX-2 mRNA in both the cancerous epithelia and adjacent stroma of pT(2)-pT(4) carcinomas. In 33 cases of pT(2) carcinoma, distant recurrence, i.e., liver metastasis, was seen in 3 of 9 cases of pT(2) carcinoma (33%, P<0.05) with intense stromal staining in the subserosal layer and in 1 of 24 cases (4%) without intense staining, whereas no significant correlation was found between parameters of pathological malignancies (histological grade, lymphatic permeation, venous permeation and lymph node metastasis) and the intensity of stromal staining in the subserosal layer. The postsurgical survival outcome was significantly poorer in the former than in the latter (p = 0.010). In pT(2) gallbladder carcinoma, upregulation of COX-2 in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT(2) gallbladder carcinoma.     

Clinicopathological study of depth of subserosal invasion in patients with pT2 gallbladder carcinoma

BACKGROUND: We examined whether depth of subserosal cancer invasion predicts lymph node involvement and survival in gallbladder carcinoma (GBC) patients with pathologicial subserosal invasion (pT2), to explore which patients benefit from radical second resection among patients with inapparent pT2 tumor. METHODS: Subjects comprised 31 patients with pT2 GBC. Thickness of the subserosal layer and vertical length of carcinoma invasion into the subserosa were measured under microscopy. Depth of subserosal invasion was divided subjectively into three categories: ss1, ss2, and ss3 (invasion of upper, middle, and lower thirds of the subserosal layer, respectively). Relationships between subserosal subclassification, histopathological factors, and prognosis were examined. RESULTS: Subserosal layers were significantly thicker (P < 0.001) in portions with cancer invasion (5.46 +/- 0.68 mm; range 1.0 approximately 13.75 mm) than those without cancer invasion (1.89 +/- 0.16 mm, range, 0.88 approximately 4.50 mm). Depth of carcinoma invasion into subserosa was 4.20 +/- 0.65 mm (range, 0.25 approximately 12.5 mm). Rate of lymphatic permeation, venous permeation, and lymph node involvement significantly increased with deeper subserosal invasion (P = 0.014, P = 0.027, P = 0.018, respectively). Among histopathological factors examined, only subserosal subclassification had a significant correlation with presence or absence of lymph node metastasis. Further, there was a significant correlation (P = 0.043) between the degree of subserosal invasion (ss1, ss2, and ss3) and involved nodal disease (pN0, pN1, and pM1 [lymph]). Although 5-year survival rates, according to the degree of subserosal invasion, tended to decrease with deeper invasion into the subserosal layer (ss1, 83.3%; ss2, 62.5%; ss3, 50.0%), no significant differences were noted. CONCLUSIONS: Pathological characteristics tend to become more aggressive with increasing depth of subserous carcinoma invasion in pT2 GBC. Depth of subserosal invasion is a predictor of presence and degree of lymph node metastasis in pT2 GBC. A sampling biopsy of the para-aortic nodes is recommended for inapparent pT2 GBC patients with subserosal invasion beyond one-thirds of the subserosal layer when they undergo radical second resection.     

Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.

PURPOSE AND EXPERIMENTAL DESIGN: Little is known about the molecular events leading to the development and progression of pathological tumor stage 2 (pT(2)) gallbladder carcinoma. An alteration in the site of O-glycosylation may be associated with malignant behavior of carcinoma cells by modulation of the biological properties of the target mucin. The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation. In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT(2) gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival. RESULTS: The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders. Immunostaining of GalNAc-T3 was recognized in the cancerous epithelia, and the subcellular localization was classified into granular and diffuse types. In the 34 cases of pT(2) carcinoma, the localization of GalNAc-T3 was granular type in 50% and diffuse type in 50% of the cases at the deepest invading sites in the subserosal layer. Postsurgical recurrence was significantly more frequent in cases showing diffuse-type localization of GalNAc-T3 at the deepest invading sites (65%) than in those showing granular-type localization (23%; P < 0.05). Postsurgical survival was significantly poorer in cases showing diffuse-type localization than in those showing granular-type localization (P = 0.033) CONCLUSIONS: In pT(2) gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease. This phenotype may serve as a unique biological feature associated with the malignant behavior.     

Characteristics of gastric carcinoma invading the muscularis propria

BACKGROUND: Although gastric carcinomas invading the muscularis propria (mp) are classified among advanced-stage cancers in Japan, postoperative survival has been reported to approximate that in early gastric carcinoma. Characteristics of gastric carcinomas invading the mp, therefore, were compared to carcinomas invading only the mucosa (m) or submucosa (sm), and to those invading the subserosa (ss) or serosa (se). METHODS: We retrospectively compared clinicopathologic findings, prognosis, and cause of death in patients with gastric carcinoma invading mp to those showing the other levels of invasion. RESULTS: Patients with carcinomas invading the mp had larger tumors and more frequent lymph node and hematogenous metastases than those with carcinomas invading only m or sm. Yet they had smaller tumors and less frequent lymph node or peritoneal metastasis than those with carcinomas invading ss or se. Postoperative survival with tumors invading the mp was intermediate between that with carcinoma invading only m or sm and that with subserosal or serosal invasion. Causes of death with tumors invading muscularis were similar to those with carcinomas invading only m or sm. CONCLUSIONS: Characteristics of gastric carcinoma invading the mp are intermediate between those of early and advanced carcinoma.     

Clinical significance of wall invasion pattern of subserosa-invasive gallbladder carcinoma

We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox's proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.     

Expression of MUC1 mucins in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder.

The overall outcome of pT(2) gallbladder carcinoma has not been favorable. Postsurgical recurrence at distant sites occurs in some cases, although the carcinoma was limited to the gallbladder wall. A high level expression of MUC1 mucins with sialylated carbohydrates (sialylated MUC1 mucins) is correlated with poor survival in intrahepatic bile duct carcinoma. In the present study, immunohistochemistry was performed to determine the expression level of sialylated MUC1 mucins, detected by a monoclonal antibody, MY.1E12, in 31 cases of pT(2) gallbladder carcinoma on which curative resections had been performed and to determine the correlation of the expression level of MY.1E12-reactive-MUC1 mucin with mode of recurrence and postsurgical survival. Immunostainings of the MUC1 mucin were recognized in different types of noncancerous pathological epithelia of the gallbladder except for intestinal metaplasia and cancerous epithelia. Immunohistochemical localization was classified into apical, cytoplasmic, and stromal types based on the predominant cellular distribution of MY.1E12-reactive-MUC1 mucin. In 31 cases of pT(2) carcinoma, the localization was apical type in 64%, cytoplasmic type in 71%, and stromal type in 48% of the cases at the deepest invading sites in the subserosal layer. Distant recurrences, i.e., peritoneal dissemination in 8 patients and liver metastasis in 3 patients, were seen in 8 (53%) of 15 cases of pT(2) carcinoma that had > or =10% of the cancerous epithelia showing stromal localization of the MUC1 mucin at the deepest invading sites and in 2 (12%) of 16 cases that had <10% of those showing the stromal localization. The postsurgical survival outcome was significantly poorer in the former than in the latter (P = 0.044). In pT(2) gallbladder carcinoma, the presence of MY.1E12-reactive-MUC1 mucin in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT(2) gallbladder carcinoma.     

Width of serosal invasion and prognosis in advanced human gastric cancer with special reference to the mode of tumor invasion

We studied the influence of the width of serosal invasion on the prognosis, in relation to the mode of invasion, in 142 patients who had curative resection for gastric carcinoma that invaded beyond the muscularis propria. The mode of invasion was classified into infiltrative and expanding types. Average diameter of tumor at the serosal or subserosal layer for the infiltrative type was 4.2 +/- 3.2 cm, a value significantly greater than that of 2.5 +/- 2.0 cm for the expanding type (P less than 0.01). The 5-year survival rate of patients with the infiltrative type carcinoma was significantly lower (36.8%) than that with the expanding type carcinoma (50.0%) (P less than 0.05). In the infiltrative type, the survival time of patients with a serosal invasion exceeding 2 cm was significantly shorter than when the serosal invasion was less than 2 cm (P less than 0.05). In the expanding type, however, the prognosis was good until the width of serosal invasion extended to 4 cm or greater. The difference in survival according to the width of serosal invasion did not always depend on the incidence of positive lymph nodes in both types of carcinomas. Therefore, influence of the width of serosal invasion on the prognosis for advanced gastric carcinomas differs between infiltrative and expanding types.     

Mucinous tumors of the ovary. A clinicopathologic study of 70 cases

Seventy cases of mucinous ovarian tumor were reviewed. All patients were followed for a minimum of 5 years. Clinicopathologically, three groups were defined: (1) mucinous cystadenoma, which demonstrated no nuclear stratification and no stromal invasion (15 cases); (2) mucinous tumor of uncertain malignant potential, which was characterized by nuclear stratification of two to three layers and no stromal invasion (21 cases); and (3) mucinous carcinoma, which showed stromal invasion and/or nuclear stratification in excess of three layers (34 cases; 15 with invasion, 19 without). All patients with mucinous cystadenomas remained tumor-free after initial surgery. Two patients with mucinous tumors of uncertain malignant potential died of tumor at 55 and 72 months, respectively, whereas 18 with mucinous carcinomas died after intervals ranging from 2 to 71 months. All mucinous tumors of uncertain malignant potential were Stage I at presentation. Twenty-one mucinous carcinomas were Stage I (six tumor deaths), one was Stage II (tumor death), ten were Stage III (nine tumor deaths), one was Stage IV (tumor death), and one was of uncertain stage (tumor death). Patients with mucinous carcinomas having stromal invasion demonstrated poorer survival (10 of 15 dead) than those with mucinous carcinomas lacking this finding (8 of 19 dead); however, stromal invasion was related to higher stage (5 with invasion Stage I; 16 without invasion Stage I).     

Relation of the serosal invasion mode to a recurrence in advanced gastric carcinomas

Discussed are the attributable factors affecting the type of carcinomatous recurrence seen in 126 patients who had been operated on for their gastric carcinomas from 1979 to 1982 and who later showed a macroscopically positive serosal invasion (S0) and a histologically ss alpha approximately se invasion and required a curative resection. Forty-six percent of the patients with an ss beta approximately se invasion had a peritoneal recurrence, 21% a liver recurrence, and 33% a recurrence of some other type, whereas those with ss alpha had no such recurrence. Peritoneal recurrence tended to increase with the increase in the length of the serosal invasion and its rates were: one third in serosal invasions of less than 3 cm, one third in invasions of 3 approximately 6 cm and another third in invasions of over 6 cm. The smaller ratio of submucosal length to subserosal length, especially when less than 1.0, meant a greater frequency of peritoneal recurrence. The histologic characteristics of carcinomas that developed a peritoneal recurrence were poorly differentiated, contained INF alpha and had weaker cellular cohesion, whereas those that developed a liver metastasis were well differentiated carcinomas, contained INF beta and had a tighter cellular cohesion.     

A hepatocellular carcinoma with lymph node metastasis and invasion into the gallbladder: preoperative difficulty ruling out a gallbladder carcinoma

We present a case of resected hepatocellular carcinoma (HCC) which invaded the gallbladder with a metastasis to a lymph node. It was extremely difficult to make a differential diagnosis between HCC and gallbladder cancer preoperatively. A 68-year old man was admitted to hospital with complaint of a fever. Ultrasonography (US) and CT scan showed a mass, growing invasively from the gallbladder bed of the liver (S4) to the lumen of the gallbladder. A selective arteriography showed the mass stained by the cholecystic artery, internal branch of the left hepatic artery, and frontal branch of the right hepatic artery. Endoscopic retrograde cholangiopancreatography (ERCP) showed the non-visualized gallbladder, a constriction of the common hepatic duct with suspicion of metastatic lymph nodes in the hepatoduodenal ligament. The tumor markers were: alpha-fet-protein 13175 ng/ml, PIVKA-II 26200 mAU/ml and CA19-9 0.0 U/ml. Both HBs antigen and HCV antibody were negative. We performed cholecystectomy with en-block resection of the anterior and middle inferior segment of the liver, the common bile duct and a part of the transverse colon, with dissection of the lymph nodes. The tumor, 8 cm in diameter, was brown colored without a capsule, growing diffusely in the liver, to the inside of the gallbladder and the transverse colon. Histopathological inspection of the specimen revealed moderately differentiated hepatocellular carcinoma with a metastatic lymph node along the common hepatic artery. TNM classification was IVB phase [T3,N0,M1 (LYM,OTH)]. There are only 3 previous cases of HCC reported with invasion into the gallbladder. At most 2.2% of the resected cases of HCC had metastatic lymph nodes at resection, while it was as high as 20-50% of the autopsy cases. Operation on such an invasive HCC case should consider lymph node metastasis.     

Carcinoma detection at the breast examination center of Harlem

BACKGROUND: Breast carcinoma is one of the leading causes of excess mortality rates in Harlem, an inner-city neighborhood with the highest mortality rates and worst life expectancy in New York City. This study reports the results of a breast carcinoma screening and diagnostic program in Harlem. METHODS: Retrospective review was performed of a database of 49,750 visits to the Breast Examination Center of Harlem from 1995 to 2000. During this period, 181 breast carcinomas were diagnosed in 178 women. The medical records of these 178 women were reviewed to determine the method of detection, stage, and treatment. RESULTS: Among these women, 89% were black or Hispanic, 45% had no medical insurance, and 38% had incomes below federal poverty guidelines. Breast carcinoma stage, known for 167 carcinomas, was Stage 0 in 38 (23%), Stage I in 38 (23%), Stage II in 63 (38%), Stage III in 24 (14%), and Stage IV in 4 (2%). Fifty-six cases (34%) were minimal breast carcinomas. Of 181 breast carcinomas, 122 (67%) were palpable and 59 (33%) were nonpalpable, detected only by mammography in asymptomatic women. Nonpalpable, as opposed to palpable, breast carcinomas were significantly more likely to be ductal carcinoma in situ (30 of 55 [54%] vs. 8 of 112 [7%], P < 0.0000001) or minimal breast carcinoma (39 of 55 [71%] vs. 17 of 112 [15%], P = 0.0000001) and were more likely to be treated with breast-conserving surgery (47 of 56 [84%] vs. 76 of 110 [69%], P < 0.04). CONCLUSIONS: A breast carcinoma screening and diagnostic program has been established in Harlem, a traditionally underserved area in New York City. Early, curable breast carcinomas were detected but outreach remains a challenge, particularly for the uninsured.     

Gallbladder carcinomas with a single lymph node involvement behind biliary tract -two resected cases

Case 1 was an 85-year-old man, who was pointed out a gallbladder tumor by screening CT scan after bladder cancer. The tumor was arisen in the gallbladder body, 1 .5 cm in diameter. He underwent a radical surgery; the gallbladder-bed was resected with more than 1 cm margin, and lymphadenectomy was done preserving biliary tract. Pathologically his tumor was papillary adenocarcinoma suspected to invade to the liver-bed minimally. A lymph node involvement was solitary located at right side of hepatoduodenal ligament (behind biliary tract). Case 2 was a 73-year-old man who was pathologically diagnosed to be advanced gallbladder carcinoma after laparoscopic cholecystectomy. CT scan and MRI revealed a mass sized 2 cm in diameter, at the gallbladder-bed, and PET exam showed a hot spot at this site only. Therefore, he underwent a radical surgery like case 1. Pathologically the tumor was moderately differentiated adenocarcinoma, and a lymph node involvement was solitary and located behind a biliary tract. Both patients have been recurrent free for more than 22 months and 15 months, respectively. Two lymphatic drainage routes have been suggested, one is the route which runs right side of hepatoduodenal ligament, another runs via left side of the ligament, along hepatic artery. Our two cases are considered to be solitary metastatic cases along the right side route. A clinical case of solitary node positive seems to be known for its relatively good prognosis. In order to justify our cases, we need a longer follow-up period, or we should have more cases to be experienced.     

Direct biliopancreatoduodenal invasion by hepatocellular carcinoma: report of the first resected case and review of the literature

A rare resected case of hepatocellular carcinoma (HCC) invading the duodenum, the common bile duct (CBD), the gallbladder, and the pancreas is described. A 63-year-old man presented with a painful upper abdominal mass. Radiologic findings showed a 25-cm liver tumor arising from segment IV with an invasive extension to the hepatoduodenal ligament and pancreatoduodenal region, with a single intrahepatic metastasis. The patient successfully underwent a left hepatectomy in conjunction with a pylorus-preserving pancreatoduodenectomy (PD). As an unusual procedure, liver parenchymal transection was followed by PD to explore tumor resectability, because the overhanging liver mass precluded full hepatoduodenal ligament dissection. He was discharged without surgical complications, being free from antianalgesics, which had been used preoperatively. The main tumor was histologically diagnosed to be a poorly differentiated HCC with sarcomatous change invading the duodenum, the CBD, the gallbladder, and the pancreas. Unfortunately, aggressive hepatic and nodal recurrence, which was resistant to salvage chemotherapy, caused the patient’s death at 8 months postoperatively. This is the first documented case of HCC with biliopancreatoduodenal invasion resected by hepatopancreatoduodenectomy. Literature review suggests a significant role of resection in selected patients with HCC with contiguous gastrointestinal tract invasion, particularly when the HCCs are naive without any forms of previous treatment. However, further surgical and nonsurgical experience is necessary to determine the oncological validity of aggressive surgery for HCC invading the biliopancreatoduodenal region.     

Evolution of carcinoma in the extrahepatic bile ducts

The histopathology of 43 cases of carcinoma in the extrahepatic bile ducts was reported. All four cases of noninfiltrating carcinoma were papillary or polypoid in gross shape. Only one of the eight cases of papillary or polypoid cancers penetrated beyond the fibromuscular layer of the bile ducts, while most cases of nodular or flat cancers spread deeper than the fibromuscular layer. Adenomatous residue was found in 9 (21.4%) of the total 43 cases, and was particularly frequent in papillary or polypoid cancers (6 [75.0%] of 8 cases). It is likely that early cancers were usually polypoid or papillary in gross shape and that most carcinomas arose from a pre-existing adenoma. Carcinoma associated with a choledochal cyst was found in two cases. Multiple carcinomas were seen in one case. Three cases of carcinoma in the extrahepatic bile ducts were associated with carcinoma of the gallbladder.     

Laparoscopic bile duct resection with lymph node dissection for gallbladder cancer diagnosed after laparoscopic cholecystectomy

IntroductionLaparoscopic reoperation of postoperatively diagnosed gallbladder cancer is a technically challenging procedure due to inflammatory adhesion or fibrosis around the hepatoduodenal ligament and gallbladder bed [1,2]. Here we describe a technique for laparoscopic bile duct resection with lymph node dissection in a patient with cystic duct cancer diagnosed after laparoscopic cholecystectomy.VideoA 73-year-old woman presented with postoperatively diagnosed gallbladder cancer. She underwent laparoscopic cholecystectomy to treat symptomatic gallbladder stones at another hospital, 2 months earlier. Postoperative pathology revealed a 0.9 × 0.7 cm, T2 lesion of adenosquamous carcinoma located at the cystic duct. The cystic duct margin showed high-grade dysplasia. We planned to perform laparoscopic bile duct resection with lymph node dissection. After adhesiolysis to expose the hepatoduodenal ligament, the lymph nodes were dissected around the retropancreatic area, hepatoduodenal ligament, and common hepatic artery in an en bloc fashion. Combined segmental resection of the bile duct, including the fibrotic scar around the cystic duct stump, was completed with negative resection margins. Retrocolic choledochojejunostomy and side-to-side jejunojejunostomy were then performed intracorporeally.ResultsThe operation time was 195 minutes and the estimated intraoperative blood loss was minimal. The postoperative pathologic report revealed no residual tumor tissue and negative resection margins. Lymph node metastasis was found in one of eight retrieved lymph nodes. The patient was discharged on postoperative day 4 with no postoperative complications.Conclusion.Laparoscopic radical surgery involving bile duct resection and lymph node dissection can be safely performed in patients with postoperatively diagnosed gallbladder cancer.     

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human gallbladder lesions

The aim of this study was to investigate the expression of platelet-derived endothelial growth factor (PD-ECGF) in human gallbladder carcinomas to elucidate its role in angiogenesis and tumour progression. To this end, 56 archival surgical specimens of gallbladder lesions were examined for PD-ECGF/thymidine phosphorylase (TP) expression by immunohistochemistry and the PD-ECGF/TP protein level was assessed in five fresh specimens of gallbladder carcinoma by enzyme-linked immunosorbent assay (ELISA). Hyperplastic epithelial cells and adenoma cells showed no or faint staining with PD-ECGF/TP. Out of 43 gallbladder carcinomas, 27 (63%) showed moderate to strong immunoreactivity in the cytoplasm and nuclei of the tumour cells. PD-ECGF/TP immunoreactivity in stromal infiltrating cells was detected in 43% (3/7) hyperplasias, 17% (1/6) adenomas and 86% (37/43) carcinomas. PD-ECGF/TP protein levels in carcinoma tissues were higher than those in corresponding normal mucosa. PD-ECGF/TP expression did not correlate with angiogenesis, but significantly correlated with depth of invasion, lymph node metastasis, and tumour stage. These results overall suggest that PD-ECGF/TP produced by both cancer cells and infiltrating cells is associated with tumour progression in human gallbladder carcinoma.     

Proliferative, infiltrative, and metastatic activities in colorectal tumors assessed by MIB-1 antibody

MIB-1 antibody staining discriminates the cells in phases other than G0 of the cell cycle. The current study examined the proliferative activity assessed by MIB-1 antibody in colorectal adenoma, primary lesions of colorectal carcinoma (CRC) to investigate the relation between the histologic atypia, the proliferative, infiltrative, and metastatic activities. The MIB-1 antibody positive rate was immunohistologically determined in primary lesions in 311 patients, 22 having adenoma or carcinoma in situ, 207 invasive CRC without distant metastasis, and 82 invasive CRC with distant metastasis. The MIB-1 antibody positive rate was significantly higher in cases of adenoma with severe atypia and carcinoma in situ, showing a close relation between histologic atypia and proliferative activity. Among invasive CRC, the positive rate in poorly differentiated adenocarcinoma and mucinous carcinoma is significantly lower than in well differentiated and moderately differentiated adenocarcinomas. The positive rate was significantly lower in carcinomas with subserosa or deeper invasion than in carcinomas with submucosa or muscularis propria invasion, showing no distinct relation between the proliferative activity and the infiltrative activity. The positive rate of primary lesion was significantly lower in cases with metachronous liver or lung metastasis than in synchronous cases, indicating that metachronous hematogenous metastasis occurs even in cancers with low proliferative activity. The MIB-1 antibody positive rate showed a close relation between histologic atypia and proliferative activity in mucosal colorectal tumors although its relation with infiltrative activity was unclear in invasive CRC. It was apparent that metachronous hematogenous cancer metastasis might take place even in cases with low proliferative activity.     

Skp2、p27Kip1在胆囊癌组织中的表达及其临床意义

目的探讨Skp2、p27Kip1在胆囊癌及癌旁组织中的表达情况及与其临床病理特征的关系。方法采用免疫组织化学PV6000二步法,检测Skp2、p27Kip1在78例胆囊癌及癌旁组织中的表达情况,并应用SPSS13.0统计软件分析2种生物指标与胆囊癌临床参数的关系。结果 Skp2与p27Kip1在胆囊癌中的阳性表达率分别为59.0%和39.7%,在癌旁组织中为25.0%和70.0%,胆囊癌中Skp2、p27Kip1阳性表达率均高于胆囊癌旁组织(P均<0.05)。Skp2表达与Nevin分期、分化程度及坏死情况相关,Nevin分期高、分化程度低及伴有坏死的患者Skp2表达高(P均<0.05)。p27Kip1阳性表达与患者Nevin分期、神经侵犯及坏死情况呈负相关性,Nevin分期早、无神经侵犯或不伴坏死患者p27Kip1表达水平高(P均<0.05)。相关性检验显示Skp2与p27Kip1两者间无相关性(P>0.05)。结论 Skp2、p27Kip1均与胆囊癌的发生发展有一定关系,可能成为胆囊癌新的临床诊断和监测预后的指标.     

Characteristics of early carcinoma of the gallbladder--clinico-pathological study

53 early carcinomas of the gallbladder in 46 cases were studied. They were surgically resected and limited to the proper muscle layer and/or Rokitansky-Aschoff sinus. 19 percent of them were pointed out by preoperative examination, and 34 percent during the operation. Finally, 85 percent of them were macroscopically with formalin-fixed materials. 53 carcinomas were composed of 14 protruded type carcinomas (26%) and 39 superficial type ones (74%). 21 tumors (40%) were pure flat (II b) type carcinomas and 17 (32%) were tumors having flat (II b) area. In the latter, flat (II b) area spread widely in the carcinoma lesion. The early carcinomas had areas of 0.01 to 80 cm2 (average 16.1 cm2). 29 percent of them occupied wider area than the half of the resected gallbladder.