AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal car...AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (展开更多
Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifi...Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.展开更多
The accurate diagnosis of extrahepatic bile duct carcinoma is difficult,even now.When ultrasonography(US)shows dilatation of the bile duct,magnetic resonance cholangiopancreatography followed by endoscopic US(EUS)is t...The accurate diagnosis of extrahepatic bile duct carcinoma is difficult,even now.When ultrasonography(US)shows dilatation of the bile duct,magnetic resonance cholangiopancreatography followed by endoscopic US(EUS)is the next step.When US or EUS shows localized bile duct wall thickening,endoscopic retrograde cholangiopancreatography should be conducted with intraductal US(IDUS)and forceps biopsy.Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity.In patients with papillary type bile duct carcinoma,three biopsies are sufficient.In patients with nodular or infiltrating-type bile duct carcinoma,multiple biopsies are warranted,and IDUS can compensate for the limitations of biopsies.In preoperative staging,the combination of dynamic multidetector low computed tomography(MDCT)and IDUS is useful for evaluating vascular invasion and cancer depth infiltration.However,assessment of lymph nodes metastases is difficult.In resectable cases,assessment of longitudinal cancer spread is important.The combination of IDUS and MDCT is useful for revealing submucosal cancer extension,which is common in hilar cholangiocarcinoma.To estimate the mucosal extenextension,which is common in extrahepatic bile duct carcinoma,the combination of IDUS and cholangioscopy is required.The utility of current peroral cholangioscopy is limited by the maneuverability of the“baby scope”.A new baby scope(10 Fr),called“SpyGlass”has potential,if the image quality can be improved.Since extrahepatic bile duct carcinoma is common in the Far East,many researchers in Japan and Korea contributed these studies,especially,in the evaluation of longitudinal cancer extension.展开更多
PreservaUon of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first successful trial, spleen-preserving distal pancreatectomy with conservation of the splenic artery and v...PreservaUon of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first successful trial, spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis has been performed more frequently. The technique for spleenpreserving distal pancreatectomy with conservation of the splenic artery and vein are outlined. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane. The connective tissue membrane is cut longitudinally above the splenic vein. An important issue is to remove the splenic vein from the body of the pancreas toward the spleen, since a different approach may be very difficult. The pancreas is preferably removed from the splenic artery toward the head of the pancreas itself. This procedure is much easier than removing the pancreas from the vein side. One patient had undergone distal gastrectomy for duodenal ulcer, with reconstruction by Billroth Ⅱ tehcnique. If distal pancreatectomy with splenectomy had been performed for the lesion of the distal pancreas at the time, the residual stomach would also have to be resected. The potential damage done to the patient by reconstruction of the gastrointestinal tract in combination with distal pancreatectomy and splenectomy would have been much greater than with distal pancreatectomy only with preservation of the spleen and residual stomach. Benign lesions as well as low-grade malignancy of the body and tail of the pancreas may be a possible indication for this procedure.展开更多
AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.METHODS:A patient cohort with bile duct strictures...AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.METHODS:A patient cohort with bile duct strictures of unknown etiology was examined by IDUS.Sensitivity,specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery.Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients.IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity,specificity and accuracy rates for T and N stages.The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160,Olympus,Ltd.,Tokyo,Japan).All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines.For IDUS,a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co.,Tokyo,Japan).RESULTS:A total of 397 patients (210 males,187 females,mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included.Two hundred and sixty-four patients were referred to the department of surgery for operative exploration,thus surgical histopathological correlation was available for those patients.Out of 264 patients,174 had malignant disease proven by surgery,in 90 patients benign disease was found.In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan,endoscopic ultrasound or magnetic resonance imaging).Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity,specificity and accuracy ratesof 93.展开更多
Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found i...Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.展开更多
Intraductal papillary neoplasm of the bile duct(IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries,it is very ra...Intraductal papillary neoplasm of the bile duct(IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries,it is very rare and the etiology is unknown. In this article,we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-yearold female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB,gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of Pub Med database,we collected 354 IPNB patients reported in 22 articles. In these patients,52.8% were from Japan and 27.7% were from western countries including the United States(11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically,57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically,pancreato-biliary subtype accounted for 41.8%,intestinal 28.0%,gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies,diagnosis of IPNB is still challenging,especially in western countries due to its rarity. Defined clinicopathologic features are in demand for the accurate diagnosis and proper treatment.展开更多
AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliar...AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.展开更多
Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological fe...Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.展开更多
Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no ...Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.展开更多
AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343...AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343 biliary tract tumors resected in our single institution.Demographic characteristics, clinical data, pathology, surgical strategies, and long-term follow-up were analyzed.RESULTS: The mean age of the 19 BT-IPMN cases was 53.8 years(range: 25-74 years).The most common symptom was abdominal pain(15/19; 78.9%), followed by jaundice(7/19; 36.8%).Cholangitis was associated with most(16/19; 84.2%) of the BT-IPMN cases.Macroscopically visible mucin was detected in all 19 patients, based on original surgical reports.The most common abnormal preoperative imaging findings for BT-IPMN were bile duct dilation(19/19; 100%) and intraluminal masses(10/19; 52.6%).Thirteen(68.4%) cases involved the intrahepatic bile duct and hilum.We performed left hepatectomy in 11/19(57.9%), right hepatectomy in 2/19(10.5%), bile duct resection in 4/19(21.1%), and pancreatoduodenectomy in 1/19(5.3%) patients.One(5.3%) patient was biopsied and received a choledochojejunostomy because of multiple tumors involving the right extrahepatic and left intrahepatic bile ducts.Histology showed malignancy in 10/19(52.6%) patients.The overall median survival was 68 mo.The benign cases showed a non-significant trend towards improved survival compared to malignant cases(68 mo vs 48 mo, P = 0.347).The patient without tumor resection died of liver failure 22 mo after palliative surgery.CONCLUSION: BT-IPMN is a rare biliary entity.Complete resection of the tumor is associated with good survival, even in patients with malignant disease.展开更多
In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depend...In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.展开更多
AIM: To elucidate the role of contrast-enhanced endoscopic ultrasonography(CE-EUS) in the diagnosis of branch duct intraductal papillary mucinous neoplasm(BD-IPMN).METHODS: A total of 50 patients diagnosed with BDIPMN...AIM: To elucidate the role of contrast-enhanced endoscopic ultrasonography(CE-EUS) in the diagnosis of branch duct intraductal papillary mucinous neoplasm(BD-IPMN).METHODS: A total of 50 patients diagnosed with BDIPMN by computed tomography(CT) and endoscopic ultrasonography(EUS) at our institute were included in this study. CE-EUS was performed when mural lesions were detected by EUS. The diagnostic accuracy for identifying mural nodules(MNs) was evaluated by CT, EUS, and EUS combined with CE-EUS. In the patients who underwent resection, the accuracy of measuring MN height with each imaging modality was compared. The cut-off values to diagnose malignant BD-IPMNs based on MN height for each imaging modality were determined using receiver operating characteristic curve analysis.RESULTS: Fifteen patients were diagnosed with BD-IPMN with MNs and underwent resection. The remaining 35 patients were diagnosed with BD-IPMN without MNs and underwent follow-up monitoring. The pathological findings revealed 14 cases with MNs and one case without. The accuracy for diagnosing MNs was 92% using CT and 72% using EUS; the diagnostic accuracy increased to 98% when EUS and CE-EUS were combined. The accuracy for measuring MN height significantly improved when using CE-EUS compared with using CT or EUS(median measurement error value, CT: 3.3 mm vs CE-EUS: 0.6 mm, P < 0.05; EUS: 2.1 mm vs CE-EUS: 0.6 mm, P < 0.01). A cut-off value of 8.8 mm for MN height as measured by CE-EUS improved the accuracy of diagnosing malignant BDIPMN to 93%. CONCLUSION: Using CE-EUS to measure MN height provides a highly accurate method for differentiating benign from malignant BD-IPMN.展开更多
Biliary strictures present a diagnostic challenge,especially when no etiology can be ascertained after laboratory evaluation,abdominal imaging and endoscopic retrograde cholangiopancreatography(ERCP)sampling.These str...Biliary strictures present a diagnostic challenge,especially when no etiology can be ascertained after laboratory evaluation,abdominal imaging and endoscopic retrograde cholangiopancreatography(ERCP)sampling.These strictures were traditionally classified as indeterminate strictures,although with advances in endoscopic techniques and better understanding of hepato-biliary pathology,more are being correctly diagnosed.The implications of missing a malignancy in patients with biliary strictures—and hence delaying surgery—are grave but a significant number of patients(up to 20%)undergoing surgery for suspected biliary malignancy can have benign pathology.The diagnostic approach to these patients involves detailed history and physical examination and depends on the presence or absence of jaundice,level of obstruction,and presence or absence of a mass lesion.While abdominal imaging helps to find the level of obstruction and provides a‘road map’for further endoscopic investigations,tissue diagnosis is usually needed to make decisions on management.Initially ERCP was the only modality to investigate these strictures but now,with the development of endoscopic ultrasound with fine needle aspiration and the availability of newer techniques such as intraductal ultrasound,single-operator cholangioscopy and confocal laser endomicroscopy,the diagnostic approach to biliary strictures has changed significantly.In this review,we will focus on the decision-making process for patients with biliary strictures and discuss the key decision points that should dictate further diagnostic investigations at each step.展开更多
基金Supported by the National Key Development Programs of West China during the 10th Five-Year Plan Period, No. 2001BA901A44
文摘AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (
文摘Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.
文摘The accurate diagnosis of extrahepatic bile duct carcinoma is difficult,even now.When ultrasonography(US)shows dilatation of the bile duct,magnetic resonance cholangiopancreatography followed by endoscopic US(EUS)is the next step.When US or EUS shows localized bile duct wall thickening,endoscopic retrograde cholangiopancreatography should be conducted with intraductal US(IDUS)and forceps biopsy.Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity.In patients with papillary type bile duct carcinoma,three biopsies are sufficient.In patients with nodular or infiltrating-type bile duct carcinoma,multiple biopsies are warranted,and IDUS can compensate for the limitations of biopsies.In preoperative staging,the combination of dynamic multidetector low computed tomography(MDCT)and IDUS is useful for evaluating vascular invasion and cancer depth infiltration.However,assessment of lymph nodes metastases is difficult.In resectable cases,assessment of longitudinal cancer spread is important.The combination of IDUS and MDCT is useful for revealing submucosal cancer extension,which is common in hilar cholangiocarcinoma.To estimate the mucosal extenextension,which is common in extrahepatic bile duct carcinoma,the combination of IDUS and cholangioscopy is required.The utility of current peroral cholangioscopy is limited by the maneuverability of the“baby scope”.A new baby scope(10 Fr),called“SpyGlass”has potential,if the image quality can be improved.Since extrahepatic bile duct carcinoma is common in the Far East,many researchers in Japan and Korea contributed these studies,especially,in the evaluation of longitudinal cancer extension.
文摘PreservaUon of the spleen at distal pancreatectomy has recently attracted considerable attention. Since our first successful trial, spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for tumors of the pancreas and chronic pancreatitis has been performed more frequently. The technique for spleenpreserving distal pancreatectomy with conservation of the splenic artery and vein are outlined. The splenic vein is identified behind the pancreas and within the thin connective tissue membrane. The connective tissue membrane is cut longitudinally above the splenic vein. An important issue is to remove the splenic vein from the body of the pancreas toward the spleen, since a different approach may be very difficult. The pancreas is preferably removed from the splenic artery toward the head of the pancreas itself. This procedure is much easier than removing the pancreas from the vein side. One patient had undergone distal gastrectomy for duodenal ulcer, with reconstruction by Billroth Ⅱ tehcnique. If distal pancreatectomy with splenectomy had been performed for the lesion of the distal pancreas at the time, the residual stomach would also have to be resected. The potential damage done to the patient by reconstruction of the gastrointestinal tract in combination with distal pancreatectomy and splenectomy would have been much greater than with distal pancreatectomy only with preservation of the spleen and residual stomach. Benign lesions as well as low-grade malignancy of the body and tail of the pancreas may be a possible indication for this procedure.
基金Supported by A research fellowship from the Faculty of Medicine,Westf lische Wilhelms-Universit t Münster
文摘AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.METHODS:A patient cohort with bile duct strictures of unknown etiology was examined by IDUS.Sensitivity,specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery.Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients.IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity,specificity and accuracy rates for T and N stages.The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160,Olympus,Ltd.,Tokyo,Japan).All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines.For IDUS,a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co.,Tokyo,Japan).RESULTS:A total of 397 patients (210 males,187 females,mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included.Two hundred and sixty-four patients were referred to the department of surgery for operative exploration,thus surgical histopathological correlation was available for those patients.Out of 264 patients,174 had malignant disease proven by surgery,in 90 patients benign disease was found.In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan,endoscopic ultrasound or magnetic resonance imaging).Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity,specificity and accuracy ratesof 93.
基金Supported by The National Natural Science Foundation of China,No.30970623 and No.31071137International Science and Technology Cooperation Projects,No.2010DFA31840 and No.2010DFB33720+1 种基金Program for New Century Excellent Talents in University,No.NCET-11-0288Beijing Natural Science Foundation,No.5112030
文摘Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.
文摘Intraductal papillary neoplasm of the bile duct(IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries,it is very rare and the etiology is unknown. In this article,we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-yearold female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB,gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of Pub Med database,we collected 354 IPNB patients reported in 22 articles. In these patients,52.8% were from Japan and 27.7% were from western countries including the United States(11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically,57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically,pancreato-biliary subtype accounted for 41.8%,intestinal 28.0%,gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies,diagnosis of IPNB is still challenging,especially in western countries due to its rarity. Defined clinicopathologic features are in demand for the accurate diagnosis and proper treatment.
文摘目的对全胰切除术的疗效进行评价。方法对2003年4月至2006年6月21例接受全胰切除术的患者的临床资料进行回顾性分析。结果 21例行全胰切除术的患者中1例联合横结肠切除,1例联合全胃切除,9例行门静脉-肠系膜上静脉部分切除端端吻合术,9例行门静脉-肠系膜上静脉部分切除人造血管间置术,其中联合腹腔干切除8例,联合腹腔干、肝固有动脉切除4例,联合腹腔干、肝总动脉切除和肠系膜上动脉部分切除端端重建1例。12例(57.1%)发生术后并发症;5例(23.8%)术后30 d 内死亡。术后每日胰岛素用量18～28 U,均能较好地控制血糖。生活质量较术前有明显提高。16例获得随访,中位生存期为9.2个月(1.2～13.0个月),其中胰腺导管癌中位生存期为7个月(1.2～9.0个月),侵袭性导管内乳头状黏液性肿瘤中位生存期为11.3个月(10.0～13.0个月)。结论全胰切除术不提高生存期,而并发症和手术死亡率增加,但可改善生活质量,可作为胰管内乳头状黏液性肿瘤的手术选择,对胰腺导管腺癌则必须考虑手术的必要性。全胰切除术后糖尿病是可控的。
文摘AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.
文摘Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.
文摘Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.
基金Supported by The Research Special Fund for Public Welfare Industry of Health,No.201202007
文摘AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343 biliary tract tumors resected in our single institution.Demographic characteristics, clinical data, pathology, surgical strategies, and long-term follow-up were analyzed.RESULTS: The mean age of the 19 BT-IPMN cases was 53.8 years(range: 25-74 years).The most common symptom was abdominal pain(15/19; 78.9%), followed by jaundice(7/19; 36.8%).Cholangitis was associated with most(16/19; 84.2%) of the BT-IPMN cases.Macroscopically visible mucin was detected in all 19 patients, based on original surgical reports.The most common abnormal preoperative imaging findings for BT-IPMN were bile duct dilation(19/19; 100%) and intraluminal masses(10/19; 52.6%).Thirteen(68.4%) cases involved the intrahepatic bile duct and hilum.We performed left hepatectomy in 11/19(57.9%), right hepatectomy in 2/19(10.5%), bile duct resection in 4/19(21.1%), and pancreatoduodenectomy in 1/19(5.3%) patients.One(5.3%) patient was biopsied and received a choledochojejunostomy because of multiple tumors involving the right extrahepatic and left intrahepatic bile ducts.Histology showed malignancy in 10/19(52.6%) patients.The overall median survival was 68 mo.The benign cases showed a non-significant trend towards improved survival compared to malignant cases(68 mo vs 48 mo, P = 0.347).The patient without tumor resection died of liver failure 22 mo after palliative surgery.CONCLUSION: BT-IPMN is a rare biliary entity.Complete resection of the tumor is associated with good survival, even in patients with malignant disease.
文摘In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.
文摘AIM: To elucidate the role of contrast-enhanced endoscopic ultrasonography(CE-EUS) in the diagnosis of branch duct intraductal papillary mucinous neoplasm(BD-IPMN).METHODS: A total of 50 patients diagnosed with BDIPMN by computed tomography(CT) and endoscopic ultrasonography(EUS) at our institute were included in this study. CE-EUS was performed when mural lesions were detected by EUS. The diagnostic accuracy for identifying mural nodules(MNs) was evaluated by CT, EUS, and EUS combined with CE-EUS. In the patients who underwent resection, the accuracy of measuring MN height with each imaging modality was compared. The cut-off values to diagnose malignant BD-IPMNs based on MN height for each imaging modality were determined using receiver operating characteristic curve analysis.RESULTS: Fifteen patients were diagnosed with BD-IPMN with MNs and underwent resection. The remaining 35 patients were diagnosed with BD-IPMN without MNs and underwent follow-up monitoring. The pathological findings revealed 14 cases with MNs and one case without. The accuracy for diagnosing MNs was 92% using CT and 72% using EUS; the diagnostic accuracy increased to 98% when EUS and CE-EUS were combined. The accuracy for measuring MN height significantly improved when using CE-EUS compared with using CT or EUS(median measurement error value, CT: 3.3 mm vs CE-EUS: 0.6 mm, P < 0.05; EUS: 2.1 mm vs CE-EUS: 0.6 mm, P < 0.01). A cut-off value of 8.8 mm for MN height as measured by CE-EUS improved the accuracy of diagnosing malignant BDIPMN to 93%. CONCLUSION: Using CE-EUS to measure MN height provides a highly accurate method for differentiating benign from malignant BD-IPMN.
文摘Biliary strictures present a diagnostic challenge,especially when no etiology can be ascertained after laboratory evaluation,abdominal imaging and endoscopic retrograde cholangiopancreatography(ERCP)sampling.These strictures were traditionally classified as indeterminate strictures,although with advances in endoscopic techniques and better understanding of hepato-biliary pathology,more are being correctly diagnosed.The implications of missing a malignancy in patients with biliary strictures—and hence delaying surgery—are grave but a significant number of patients(up to 20%)undergoing surgery for suspected biliary malignancy can have benign pathology.The diagnostic approach to these patients involves detailed history and physical examination and depends on the presence or absence of jaundice,level of obstruction,and presence or absence of a mass lesion.While abdominal imaging helps to find the level of obstruction and provides a‘road map’for further endoscopic investigations,tissue diagnosis is usually needed to make decisions on management.Initially ERCP was the only modality to investigate these strictures but now,with the development of endoscopic ultrasound with fine needle aspiration and the availability of newer techniques such as intraductal ultrasound,single-operator cholangioscopy and confocal laser endomicroscopy,the diagnostic approach to biliary strictures has changed significantly.In this review,we will focus on the decision-making process for patients with biliary strictures and discuss the key decision points that should dictate further diagnostic investigations at each step.
