AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular ca...AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule. CONCLUSION: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.展开更多
AIM:To study the effects of cytokeratin 17(CK17) on sodium iodate(NalO_3) induced rat retinal pigment epithelium(RPE) degeneration,laser induced rat choroidal neovascularization(CNV),and oxidative stress of human reti...AIM:To study the effects of cytokeratin 17(CK17) on sodium iodate(NalO_3) induced rat retinal pigment epithelium(RPE) degeneration,laser induced rat choroidal neovascularization(CNV),and oxidative stress of human retinal pigment epithelium cells(ARPE-19) and human umbilical vein endothelial cell(HUVEC).· METHODS:Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups,10 rats in control group treated with solvent alone;10 rats in NalO_3 group treated with solvent and 35 mg/kg NalO_3 injection through hypoglossal vein and 10 rats in CK17+NalO_3group treated with 1%CK17 eye drop 3 times a day for1 wk before and 4wk after NalO_3 injection.RPE function was measured with c-wave of electroretinogram(ERG).Another 20 rats were randomly divided into 2 groups.Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1%CK17 eye drop before same as above;10 rats in control were received Nd:YAG and treated with solvent.The development of choroidal neovascularization(CNV) was determined by fundus fluorescein angiography(FFA) performed on 4wk after laser.Methylthiazoly tetrazolium(MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro.· RESULTS:Four weeks after NalO_3 injection,the cwave amplitude of ERG was 0.393±0.02 V in the control group,0.184 ±0.018 V in NalO_3 group and 0.3±0.01 V in CK17+NalO_3 group.There was a significant reversal of the c-wave by CK17 as compared to NalO_3 group(P<0.01).Four weeks after laser,the size of the CNV lesion was2.57±0.27 mm^2 in control group and 1.64±0.08 mm_2 in CK17 group.The lesion size significantly diminished in CK17 group(P<0.01).The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 μg/mL and enhanced the injury in HUVECs at different concentrations.CONCLUSION:CK17 can significantly protect RPE from NalO_3 induced degeneration in vivo and in vitro and also could reverse the various oxidants induced injuries in vitro.It inhibits the development of CNV in rat model,interfered with vascular endothelial cell proliferation in vitro.展开更多
Background: We used transcatheter arterial infusion chemotherapy (TAI) for patients with T1G3 and greater than T2 bladder cancer, which was diagnosed after extensive and deep transurethral resection of bladder tumor (...Background: We used transcatheter arterial infusion chemotherapy (TAI) for patients with T1G3 and greater than T2 bladder cancer, which was diagnosed after extensive and deep transurethral resection of bladder tumor (TUR-BT), and we investigated the utility of serum cytokeratin 19 fragment (CYFRA) as a predictive factor of the response to therapy. Material and Methods: From November 2001 to November 2010, 56 patients (46 males and 10 females) with pathologically confirmed T1 G3 or greater than T2 bladder cancer after TUR-BT underwent two courses of TAI of cisplatin, methotrexate and doxorubicin as neoadjuvant setting. Then, patients underwent evaluation TUR-BT. Thereafter, the bladder was preserved in patients with superficial or undetectable tumors on TUR-BT. Advanced cases and residual bladder tumor cases were treated with total cystectomy or systemic chemotherapy. CYFRA levels were measured before and after performing TAI. Results: With this therapy, the 5-year survival rate was 85.7% in pT1G3, 82.3% in pT2, and 66.6% in greater than pT3 cases. Bladder preservation with no recurrence was observed in 58.7% of the patients. Grade III adverse events included leucopenia (6/56 patients: 10.7%). Serum CYFRA levels significantly decreased with treatment (in 4/6 patients with elevated CYFRA levels). Conclusion: These results suggest that although total cystictomy is usually indicated for T1G3 bladder cancers, bladder preservation and control of micrometastases can be achieved by performing TAI after extensive and deep TUR-BT. Our results also suggest the utility of monitoring serum CYFRA to assess the response to therapy.展开更多
The histological specificities of 4 monoclonal antibodies against cytokeratins (HK2, HK5, K174 and K27) were investigated in various kinds of human and rat tissues with ABC immunohistochemical technique. K174 was show...The histological specificities of 4 monoclonal antibodies against cytokeratins (HK2, HK5, K174 and K27) were investigated in various kinds of human and rat tissues with ABC immunohistochemical technique. K174 was shown to have the same recognition spectrum with a polyclonal antibody (RAK1) to epidermal keratin. HK2 and HK5 were similar except the difference in reaction with stratified squqmous epithelium. K27 could only label the suprabasal layers of the squamous epithelium, and could be used as a marker of cornified or cornifying epithelium. This study provided a sound basis for the use of this group of antibodies in the subtyping of different epithelial tissues and the tumors originating from them.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive te...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.展开更多
Introduction:Although many studies have shown the vast potential of circulating tumor cells(CTCs)detection in cancer diagnosis and prognosis,our understanding of their clinical significance is still far from complete....Introduction:Although many studies have shown the vast potential of circulating tumor cells(CTCs)detection in cancer diagnosis and prognosis,our understanding of their clinical significance is still far from complete.A major obstacle arises from the lack of well-established tumor or tissue-specific markers to detect CTCs by immunocytochemical staining after immunomagnetic enrichment(IE).Methods:We have established the utility of cytokeratin 20(CK20),a gastrointestinal tract specific marker,for the specific detection and identification of colorectal cancer(CRC)CTCs.This breakthrough was successfully validated in spike-in experiments using CRC cell line models followed by a pilot study which recruited 32 metastatic CRC patients,25 benign colorectal diseases patients and 27 normal subjects.Results:CK20-positive CTCs were detected in 90%metastatic CRC patients but not in benign colorectal diseases patients and normal subjects using this refined assay.Conclusions:These impressive results have laid the foundation for further development of CK20-positive CTCs as a promising marker in diagnosis,prognostication and treatment monitoring of metastatic CRC.展开更多
Background: Benign prostate hyperplasia (BPH) is the most common benign disease of the human prostate. The comparison between global versus local changes in spatial patterns of pathological lesions provoked a growing ...Background: Benign prostate hyperplasia (BPH) is the most common benign disease of the human prostate. The comparison between global versus local changes in spatial patterns of pathological lesions provoked a growing interest in some fields such as neuropathology. To date, there is little data on this subject in prostatic pathology. Given the interest of local parameters to distinguish between normal and pathological structures, the present study will apply first and second order stereological tools to find out if the cytokeratin18 (ck18) immunoexpression shows relevant local changes in BPH compared to normal prostate, independently if global estimates were similar in both groups. Methods: To verify if the global and local changes in immuno-expression of ck18 are relevant to ascertain differences between normal (CTR) and BPH cases, the following parameters will be applied: Volume fraction of epithelium immunostained for ck18 (VV ck18), both in global and local estimates;dispersion indices of VV ck18;estimates of local variance of VV ck18 (positional and of scale) using wavelet analysis;and lacunarity analysis to measure the tissue heterogeneity. Then, the set of values from the parameters studied that show significant differences between CTR and BPH will be employed to perform stepwise linear discriminant analyses to determine if locally estimated parameters were able to classify accurately the cases in CTR and BPH groups. Results and Conclusions: The findings of the present study indicate that changes in the expression of ck18 by the hyperplastic prostatic epithelium are not homogeneous. This limits the use of a single biopsy based markers to predict biological behavior in BPH. On the other hand, the local changes in the expression of ck18 are more evident in terms of VV ck18 and its local variability, whereas other parameters that are useful in other pathologies, such as lacunarity, are less relevant In prostatic hyperplasia.展开更多
文摘AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule. CONCLUSION: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.
文摘AIM:To study the effects of cytokeratin 17(CK17) on sodium iodate(NalO_3) induced rat retinal pigment epithelium(RPE) degeneration,laser induced rat choroidal neovascularization(CNV),and oxidative stress of human retinal pigment epithelium cells(ARPE-19) and human umbilical vein endothelial cell(HUVEC).· METHODS:Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups,10 rats in control group treated with solvent alone;10 rats in NalO_3 group treated with solvent and 35 mg/kg NalO_3 injection through hypoglossal vein and 10 rats in CK17+NalO_3group treated with 1%CK17 eye drop 3 times a day for1 wk before and 4wk after NalO_3 injection.RPE function was measured with c-wave of electroretinogram(ERG).Another 20 rats were randomly divided into 2 groups.Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1%CK17 eye drop before same as above;10 rats in control were received Nd:YAG and treated with solvent.The development of choroidal neovascularization(CNV) was determined by fundus fluorescein angiography(FFA) performed on 4wk after laser.Methylthiazoly tetrazolium(MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro.· RESULTS:Four weeks after NalO_3 injection,the cwave amplitude of ERG was 0.393±0.02 V in the control group,0.184 ±0.018 V in NalO_3 group and 0.3±0.01 V in CK17+NalO_3 group.There was a significant reversal of the c-wave by CK17 as compared to NalO_3 group(P<0.01).Four weeks after laser,the size of the CNV lesion was2.57±0.27 mm^2 in control group and 1.64±0.08 mm_2 in CK17 group.The lesion size significantly diminished in CK17 group(P<0.01).The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 μg/mL and enhanced the injury in HUVECs at different concentrations.CONCLUSION:CK17 can significantly protect RPE from NalO_3 induced degeneration in vivo and in vitro and also could reverse the various oxidants induced injuries in vitro.It inhibits the development of CNV in rat model,interfered with vascular endothelial cell proliferation in vitro.
文摘Background: We used transcatheter arterial infusion chemotherapy (TAI) for patients with T1G3 and greater than T2 bladder cancer, which was diagnosed after extensive and deep transurethral resection of bladder tumor (TUR-BT), and we investigated the utility of serum cytokeratin 19 fragment (CYFRA) as a predictive factor of the response to therapy. Material and Methods: From November 2001 to November 2010, 56 patients (46 males and 10 females) with pathologically confirmed T1 G3 or greater than T2 bladder cancer after TUR-BT underwent two courses of TAI of cisplatin, methotrexate and doxorubicin as neoadjuvant setting. Then, patients underwent evaluation TUR-BT. Thereafter, the bladder was preserved in patients with superficial or undetectable tumors on TUR-BT. Advanced cases and residual bladder tumor cases were treated with total cystectomy or systemic chemotherapy. CYFRA levels were measured before and after performing TAI. Results: With this therapy, the 5-year survival rate was 85.7% in pT1G3, 82.3% in pT2, and 66.6% in greater than pT3 cases. Bladder preservation with no recurrence was observed in 58.7% of the patients. Grade III adverse events included leucopenia (6/56 patients: 10.7%). Serum CYFRA levels significantly decreased with treatment (in 4/6 patients with elevated CYFRA levels). Conclusion: These results suggest that although total cystictomy is usually indicated for T1G3 bladder cancers, bladder preservation and control of micrometastases can be achieved by performing TAI after extensive and deep TUR-BT. Our results also suggest the utility of monitoring serum CYFRA to assess the response to therapy.
文摘The histological specificities of 4 monoclonal antibodies against cytokeratins (HK2, HK5, K174 and K27) were investigated in various kinds of human and rat tissues with ABC immunohistochemical technique. K174 was shown to have the same recognition spectrum with a polyclonal antibody (RAK1) to epidermal keratin. HK2 and HK5 were similar except the difference in reaction with stratified squqmous epithelium. K27 could only label the suprabasal layers of the squamous epithelium, and could be used as a marker of cornified or cornifying epithelium. This study provided a sound basis for the use of this group of antibodies in the subtyping of different epithelial tissues and the tumors originating from them.
基金the Canadian Donation and Transplantation Research Program of the Canadian Society of Transplantation(grant competition 2014)Sebastiani G is supported by a Senior Salary Award from Fonds de la Recherche en Santédu Quebéc(FRQS)(No.#296306).
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.
文摘Introduction:Although many studies have shown the vast potential of circulating tumor cells(CTCs)detection in cancer diagnosis and prognosis,our understanding of their clinical significance is still far from complete.A major obstacle arises from the lack of well-established tumor or tissue-specific markers to detect CTCs by immunocytochemical staining after immunomagnetic enrichment(IE).Methods:We have established the utility of cytokeratin 20(CK20),a gastrointestinal tract specific marker,for the specific detection and identification of colorectal cancer(CRC)CTCs.This breakthrough was successfully validated in spike-in experiments using CRC cell line models followed by a pilot study which recruited 32 metastatic CRC patients,25 benign colorectal diseases patients and 27 normal subjects.Results:CK20-positive CTCs were detected in 90%metastatic CRC patients but not in benign colorectal diseases patients and normal subjects using this refined assay.Conclusions:These impressive results have laid the foundation for further development of CK20-positive CTCs as a promising marker in diagnosis,prognostication and treatment monitoring of metastatic CRC.
文摘Background: Benign prostate hyperplasia (BPH) is the most common benign disease of the human prostate. The comparison between global versus local changes in spatial patterns of pathological lesions provoked a growing interest in some fields such as neuropathology. To date, there is little data on this subject in prostatic pathology. Given the interest of local parameters to distinguish between normal and pathological structures, the present study will apply first and second order stereological tools to find out if the cytokeratin18 (ck18) immunoexpression shows relevant local changes in BPH compared to normal prostate, independently if global estimates were similar in both groups. Methods: To verify if the global and local changes in immuno-expression of ck18 are relevant to ascertain differences between normal (CTR) and BPH cases, the following parameters will be applied: Volume fraction of epithelium immunostained for ck18 (VV ck18), both in global and local estimates;dispersion indices of VV ck18;estimates of local variance of VV ck18 (positional and of scale) using wavelet analysis;and lacunarity analysis to measure the tissue heterogeneity. Then, the set of values from the parameters studied that show significant differences between CTR and BPH will be employed to perform stepwise linear discriminant analyses to determine if locally estimated parameters were able to classify accurately the cases in CTR and BPH groups. Results and Conclusions: The findings of the present study indicate that changes in the expression of ck18 by the hyperplastic prostatic epithelium are not homogeneous. This limits the use of a single biopsy based markers to predict biological behavior in BPH. On the other hand, the local changes in the expression of ck18 are more evident in terms of VV ck18 and its local variability, whereas other parameters that are useful in other pathologies, such as lacunarity, are less relevant In prostatic hyperplasia.
