AIM： To evaluate the role of positron emission tomography using 18F-fluorodeoxyglucose （FDG-PET） in the surgical management of patients with pancreatic cancer, including the diagnosis, staging, and selection of pat...AIM： To evaluate the role of positron emission tomography using 18F-fluorodeoxyglucose （FDG-PET） in the surgical management of patients with pancreatic cancer, including the diagnosis, staging, and selection of patients for the subsequent surgical treatment. METHODS： This study involved 53 patients with proven primary pancreatic cancer. The sensitivity of diagnosing the primary cancer was examined for FDG-PET CT, cytological examination of the bile or pancreatic juice, and the serum levels of carcinoembrionic antigens （CEA） and carbohydrate antigen 19-9 （CA29-9）. Next, the accuracy of staging was compared between FDG-PET and CT. Finally, FDG-PET was analyzed semiquantitatively using the standard uptake value （SUV）. The impact of the SUV on patient management was evaluated by examining the correlations between the SUV and the histological findings of cancer. RESULTS： The sensitivity of FDG-PET, CT, cytological examination of the bile or pancreatic juice, and the serum levels of CEA and CA19-9 were 92.5%, 88.7%, 46.4%, 37.7% and 69.8%, respectively. In staging, FDG-PET was superior to CT only in diagnosing distant disease （bone metastasis）. For local staging, the sensitivity of CT was better than that of FDG-PEr. The SUV did not correlate with the pTNM stage, grades, invasions to the vessels and nerve, or with the size of the tumor. However, there was a statistically significant difference （4.6 ± 2.9 vs 7.8 ± 4.5, P = 0.024） in the SUV between patients with respectable and unresectable disease. CONCLUSION： FDG-PET is thus considered to be useful in the diagnosis of pancreatic cancer. However, regarding the staging of the disease, FDG-PET is not considered to be a sufficiently accurate diagnostic modality. Although the SUV does not correlate with the patho-histological prognostic factors, it may be useful in selecting patients who should undergo subsequent surgical treatment.展开更多
Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic opti...Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA(ct DNA) could provide diagnostic information. In this review, we provide an overview of the current status of bloodbased tests for diagnosis of pancreatic cancer and the potential utility of ct DNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ct DNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.展开更多
Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis...Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.展开更多
BACKGROUND Bile duct cancer constitutes gallbladder cancer(GBC),intrahepatic cholangiocarcinoma(ICA),and extrahepatic cholangiocarcinoma(ECA).These three entities show morphological and immunohistochemical resemblance...BACKGROUND Bile duct cancer constitutes gallbladder cancer(GBC),intrahepatic cholangiocarcinoma(ICA),and extrahepatic cholangiocarcinoma(ECA).These three entities show morphological and immunohistochemical resemblance so that it is difficult to differentiate between primary ICA and liver metastasis of GBC,which sometimes becomes a point of discussion in clinical practice.Although these cancers demonstrate significant differences in their mutational landscape,several reports demonstrated shared genomic alteration in paired primary and metastatic site aids in distinguishing metastatic recurrence from second primary cancers.CASE SUMMARY We present a 73-year-old female patient who underwent curative resection for GBC harboring epidermal growth factor receptor 2(ERBB2)activating mutation on next-generation sequencing(NGS)-based genomic testing.One year later,a hepatic lesion was observed on follow-up imaging and she underwent surgical resection for a pathological diagnosis.The histological findings of the hepatic lesion were similar to those of the primary lesion.Additionally,using NGS panel testing,the hepatic lesion was found to have ERBB2 activating mutation,which is the identical mutation detected in the sequencing result of the primary site.ERBB2 activating mutation occurs more frequently in GBC than ICA and ECA.Therefore,in the present case,we think this molecular finding potentiated the diagnosis of the liver mass toward a metastatic recurrence.Additionally,this patient underwent HER2-targeted treatment with lapatinib in combination with capecitabin and obtained clinical benefit.CONCLUSION This case illustrated NGS panel usefulness in distinguishing GBC recurrence from second primary cancer and HER2-targeted agent efficacy on ERBB2 mutated GBC.展开更多
Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations ...Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.展开更多
文摘AIM： To evaluate the role of positron emission tomography using 18F-fluorodeoxyglucose （FDG-PET） in the surgical management of patients with pancreatic cancer, including the diagnosis, staging, and selection of patients for the subsequent surgical treatment. METHODS： This study involved 53 patients with proven primary pancreatic cancer. The sensitivity of diagnosing the primary cancer was examined for FDG-PET CT, cytological examination of the bile or pancreatic juice, and the serum levels of carcinoembrionic antigens （CEA） and carbohydrate antigen 19-9 （CA29-9）. Next, the accuracy of staging was compared between FDG-PET and CT. Finally, FDG-PET was analyzed semiquantitatively using the standard uptake value （SUV）. The impact of the SUV on patient management was evaluated by examining the correlations between the SUV and the histological findings of cancer. RESULTS： The sensitivity of FDG-PET, CT, cytological examination of the bile or pancreatic juice, and the serum levels of CEA and CA19-9 were 92.5%, 88.7%, 46.4%, 37.7% and 69.8%, respectively. In staging, FDG-PET was superior to CT only in diagnosing distant disease （bone metastasis）. For local staging, the sensitivity of CT was better than that of FDG-PEr. The SUV did not correlate with the pTNM stage, grades, invasions to the vessels and nerve, or with the size of the tumor. However, there was a statistically significant difference （4.6 ± 2.9 vs 7.8 ± 4.5, P = 0.024） in the SUV between patients with respectable and unresectable disease. CONCLUSION： FDG-PET is thus considered to be useful in the diagnosis of pancreatic cancer. However, regarding the staging of the disease, FDG-PET is not considered to be a sufficiently accurate diagnostic modality. Although the SUV does not correlate with the patho-histological prognostic factors, it may be useful in selecting patients who should undergo subsequent surgical treatment.
文摘Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA(ct DNA) could provide diagnostic information. In this review, we provide an overview of the current status of bloodbased tests for diagnosis of pancreatic cancer and the potential utility of ct DNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ct DNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.
文摘Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.
文摘BACKGROUND Bile duct cancer constitutes gallbladder cancer(GBC),intrahepatic cholangiocarcinoma(ICA),and extrahepatic cholangiocarcinoma(ECA).These three entities show morphological and immunohistochemical resemblance so that it is difficult to differentiate between primary ICA and liver metastasis of GBC,which sometimes becomes a point of discussion in clinical practice.Although these cancers demonstrate significant differences in their mutational landscape,several reports demonstrated shared genomic alteration in paired primary and metastatic site aids in distinguishing metastatic recurrence from second primary cancers.CASE SUMMARY We present a 73-year-old female patient who underwent curative resection for GBC harboring epidermal growth factor receptor 2(ERBB2)activating mutation on next-generation sequencing(NGS)-based genomic testing.One year later,a hepatic lesion was observed on follow-up imaging and she underwent surgical resection for a pathological diagnosis.The histological findings of the hepatic lesion were similar to those of the primary lesion.Additionally,using NGS panel testing,the hepatic lesion was found to have ERBB2 activating mutation,which is the identical mutation detected in the sequencing result of the primary site.ERBB2 activating mutation occurs more frequently in GBC than ICA and ECA.Therefore,in the present case,we think this molecular finding potentiated the diagnosis of the liver mass toward a metastatic recurrence.Additionally,this patient underwent HER2-targeted treatment with lapatinib in combination with capecitabin and obtained clinical benefit.CONCLUSION This case illustrated NGS panel usefulness in distinguishing GBC recurrence from second primary cancer and HER2-targeted agent efficacy on ERBB2 mutated GBC.
基金Grants-in Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan,No.26870874 to Takai E and No.25134719 to Yachida Sthe National Cancer Center Research and Development Fund(25-A-3 to Takai E and Yachida S)+5 种基金the Takeda Science Foundation(Yachida S)the Uehara Memorial Foundation(Yachida S)the Mochida Memorial Foundation for Medical and Pharmaceutical Research(Yachida S)the Medical Research Encouragement Prize of the Japan Medical Association(Yachida S)the Pancreas Research Foundation of Japan(Yachida S)Princess Takamatsu Cancer Research Fund(Yachida S)
文摘Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.
