AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 l...AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre-and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non- recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbl展开更多
BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against g...BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Box, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm(3), P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 a展开更多
AIM:To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma(GBCa)according to tumor spread in the subserosal layer. METHODS:A series of 84 patients with GBCa were treated at Saga University Hospital...AIM:To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma(GBCa)according to tumor spread in the subserosal layer. METHODS:A series of 84 patients with GBCa were treated at Saga University Hospital,Japan between April 1989 and October 2008.The tumor stage was graded according to the TNM staging for GBCa from the American Joint Committee on Cancer Manual 6th edition. Tumor staging revealed 30 patients with T2 tumors.T2 GBCa was divided into three groups histologically by the extent of tumor spread in the subserosal layer,using a score of ss minimum(ss min),ss medium(ss med)or ss massive(ss mas). RESULTS:For ss min GBCa,there was no positive pathological factor and patient survival was satisfactory with simple cholecystectomy,with or without extra-he- patic bile duct resection.For ss med GBCa,some pathological factors,h-inf(hepatic infiltration),ly(lymphatic invasion)and n(lymph node metastasis),were positive. For ss mas GBCa,there was a high incidence of positive pathological factors.The patient group with extra-hepatic bile duct resection with D2 lymph node dissection (BDR with D2)and those with S4a5 hepatectomy had significantly better survival rates.CONCLUSION:We suggest that radical surgery is not necessary for ss min GBCa,and partial hepatectomy and BDR are necessary for both ss med and ss mas GBCa.展开更多
BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder(GB),and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms.CASE SUMMARY We report a case of GB neuroendocrine ...BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder(GB),and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms.CASE SUMMARY We report a case of GB neuroendocrine carcinoma(GB-NEC)in a 65-year-old man,who presented with flushing for 2 mo.Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis.Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space.High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space,but distant metastasis was not seen by positron emission tomography.Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC.Because of the functional characteristics of poorly differentiated NEC,en bloc cholecystectomy,resection of hepatic segments IVb and V,pancreaticoduodenectomy,and regional lymphadenectomy were performed.A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data.Ki-67 index was>80%.The patient refused adjuvant therapy and passed away in the 7th month.CONCLUSION Distinctive manifestation combined with imaging helps make correct preoperative diagnosis.Radical surgery and adjuvant chemotherapy might improve prognosis.展开更多
BACKGROUND Gallbladder cancer(GBC)is one of the leading and aggressive cancers in this region of India.It is very difficult to diagnose in the early stage,as it lacks typical early signs and symptoms;thus,the diagnosi...BACKGROUND Gallbladder cancer(GBC)is one of the leading and aggressive cancers in this region of India.It is very difficult to diagnose in the early stage,as it lacks typical early signs and symptoms;thus,the diagnosis is often in the advanced stage,which ultimately leads to a poor 5-year survival outcome.Tumor markers including carbohydrate antigen 19-9(CA 19-9),carcinoembryonic antigen(CEA),CA 125,CA 242,and alpha fetoprotein are used as indicators in the diagnosis and prognosis of GBC.AIM To compare tumor marker levels between GBC and benign GB diseases(GBDs)and to assess the combined use of tumor markers to increase the diagnostic accuracy for GBC.METHODS Patients of either sex aged≥18 years,with suspected GBC(GB polyp,irregular thick GB wall,GB mass,porcelain GB)on the basis of radiological imaging were included in this study.GB wall thickness using ultrasonography and tumor markers CEA,CA 125,CA 19-9,and CA 242 in all patients were recorded.All cases after surgical intervention were divided into two groups,GBC and benign GBD,according to histopathological examination findings.The cases were followed up and clinical findings,radiological findings,and levels of tumor markers were assessed.RESULTS A total of 200 patients were included in this study,of whom 80 patients had GBC and 120 patients had benign GBD.The median(interquartile range)age was 52.0(41.0-60.0)years and the majority of patients(132,66.0%)were women.Tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly elevated in patients with GBC(P<0.001).There was a significant reduction in tumor markers at 3 and 6 mo from baseline(P<0.001).The mean survival of patients with normal and elevated levels of tumor markers CA 125,CA 19-9,and CEA was comparable;however lymph node metastasis and CA 242 expression level were independent prognostic factors.CONCLUSION Serum levels of tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly associated with GBC.However,no significant association was observed between the presence of e展开更多
AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder ...AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. RESULTS: The expression rates of abnormal cyclin Dl in gallbladder carcinoma (68.3%)and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3 and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5(33.3% and 38.8%) (P<0.05), and those in pathologic grades G1(54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r= -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin Dl had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). CONCLUSION: Cyclin Dl may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.展开更多
文摘AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA) 199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre-and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non- recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbl
文摘BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. We previously reported that norcantharidin (NCTD) is useful against growth, proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro. In this study, we further studied the inhibitory effect of NCTD on the growth of xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells. The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5-FU groups which were given different treatments. Tumor growth in terms of size, growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and morphological changes of the xenografted tumors were assessed by flow cytometry and light/electron microscopy. The expression of the cell cycle-related proteins cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Box, and survivin were determined by the streptavidin-biotin complex (SABC) method and RT-PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm(3), P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the NTCD group compared with the control group. The apoptosis rate increased (15.08+/-1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with the control group. The morphological changes of apoptosis such as nuclear shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis bodies in the xenografted tumor cells induced by NCTD were observed by light and electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin proteins/mRNAs decreased significantly, with increased expression of p27 a
文摘AIM:To evaluate the adequacy of surgical treatment of T2 gallbladder carcinoma(GBCa)according to tumor spread in the subserosal layer. METHODS:A series of 84 patients with GBCa were treated at Saga University Hospital,Japan between April 1989 and October 2008.The tumor stage was graded according to the TNM staging for GBCa from the American Joint Committee on Cancer Manual 6th edition. Tumor staging revealed 30 patients with T2 tumors.T2 GBCa was divided into three groups histologically by the extent of tumor spread in the subserosal layer,using a score of ss minimum(ss min),ss medium(ss med)or ss massive(ss mas). RESULTS:For ss min GBCa,there was no positive pathological factor and patient survival was satisfactory with simple cholecystectomy,with or without extra-he- patic bile duct resection.For ss med GBCa,some pathological factors,h-inf(hepatic infiltration),ly(lymphatic invasion)and n(lymph node metastasis),were positive. For ss mas GBCa,there was a high incidence of positive pathological factors.The patient group with extra-hepatic bile duct resection with D2 lymph node dissection (BDR with D2)and those with S4a5 hepatectomy had significantly better survival rates.CONCLUSION:We suggest that radical surgery is not necessary for ss min GBCa,and partial hepatectomy and BDR are necessary for both ss med and ss mas GBCa.
基金Supported by The National Natural Science Foundation of China,No.81572975Key Research and Development Project of Science and Technology Department of Zhejiang,China,No.2015C03053
文摘BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder(GB),and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms.CASE SUMMARY We report a case of GB neuroendocrine carcinoma(GB-NEC)in a 65-year-old man,who presented with flushing for 2 mo.Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis.Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space.High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space,but distant metastasis was not seen by positron emission tomography.Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC.Because of the functional characteristics of poorly differentiated NEC,en bloc cholecystectomy,resection of hepatic segments IVb and V,pancreaticoduodenectomy,and regional lymphadenectomy were performed.A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data.Ki-67 index was>80%.The patient refused adjuvant therapy and passed away in the 7th month.CONCLUSION Distinctive manifestation combined with imaging helps make correct preoperative diagnosis.Radical surgery and adjuvant chemotherapy might improve prognosis.
文摘BACKGROUND Gallbladder cancer(GBC)is one of the leading and aggressive cancers in this region of India.It is very difficult to diagnose in the early stage,as it lacks typical early signs and symptoms;thus,the diagnosis is often in the advanced stage,which ultimately leads to a poor 5-year survival outcome.Tumor markers including carbohydrate antigen 19-9(CA 19-9),carcinoembryonic antigen(CEA),CA 125,CA 242,and alpha fetoprotein are used as indicators in the diagnosis and prognosis of GBC.AIM To compare tumor marker levels between GBC and benign GB diseases(GBDs)and to assess the combined use of tumor markers to increase the diagnostic accuracy for GBC.METHODS Patients of either sex aged≥18 years,with suspected GBC(GB polyp,irregular thick GB wall,GB mass,porcelain GB)on the basis of radiological imaging were included in this study.GB wall thickness using ultrasonography and tumor markers CEA,CA 125,CA 19-9,and CA 242 in all patients were recorded.All cases after surgical intervention were divided into two groups,GBC and benign GBD,according to histopathological examination findings.The cases were followed up and clinical findings,radiological findings,and levels of tumor markers were assessed.RESULTS A total of 200 patients were included in this study,of whom 80 patients had GBC and 120 patients had benign GBD.The median(interquartile range)age was 52.0(41.0-60.0)years and the majority of patients(132,66.0%)were women.Tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly elevated in patients with GBC(P<0.001).There was a significant reduction in tumor markers at 3 and 6 mo from baseline(P<0.001).The mean survival of patients with normal and elevated levels of tumor markers CA 125,CA 19-9,and CEA was comparable;however lymph node metastasis and CA 242 expression level were independent prognostic factors.CONCLUSION Serum levels of tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly associated with GBC.However,no significant association was observed between the presence of e
文摘AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. RESULTS: The expression rates of abnormal cyclin Dl in gallbladder carcinoma (68.3%)and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3 and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5(33.3% and 38.8%) (P<0.05), and those in pathologic grades G1(54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r= -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin Dl had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). CONCLUSION: Cyclin Dl may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.
