Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gas...Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.展开更多
A case of esophageal carcinoma exclusively composed of adenocarcinoma simulating an esophageal gland duct in a 61-year-old man is presented. The tumor arose as a slightly elevated lesion in the middle intrathoracic es...A case of esophageal carcinoma exclusively composed of adenocarcinoma simulating an esophageal gland duct in a 61-year-old man is presented. The tumor arose as a slightly elevated lesion in the middle intrathoracic esophagus. It was almost completely overlaid with nonneoplastic stratified squamous epithelial cells. Beneath the overlying surface epithelium, an adenocarcinoma that was bilayered in structure diffusely invaded both the mucosal and submucosal layers. Although the tumor consisted exclusively of adenocarcinomatous cells, a keratinizing squamous cell carcinoma component was focally observed. The invasive carcinoma was focally continuous with the small area of the surface squamous epithelial layer, which was confirmed to be neoplastic by immunohistochemistry. Morphological and immunohistochemical examinations suggested that the adenocarcinomatous component arose from the esophageal surface epithelium and clearly differentiated into an esophageal gland duct. It is important to consider the possibility of this type of adenocarcinoma when diagnosing a ductal or glandular lesion of the esophagus in small biopsy specimens.展开更多
To examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett’s mucosa, dysplasia and esophageal adenocarcinoma (EA).METHODSSlides were stained with TGR5 antibody. The staining intensity was scored a...To examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett’s mucosa, dysplasia and esophageal adenocarcinoma (EA).METHODSSlides were stained with TGR5 antibody. The staining intensity was scored as 1+, 2+ and 3+. The extent of staining (percentage of cells staining) was scored as follows: 1+, 1%-10%, 2+, 11%-50%, 3+, 51%-100%. A combined score of intensity and extent was calculated and categorized as negative, weak, moderate and strong staining. TGR5 mRNA was measured by real time PCR.RESULTSWe found that levels of TGR5 mRNA were significantly increased in Barrett’s dysplastic cell line CP-D and EA cell line SK-GT-4, when compared with Barrett’s cell line CP-A. Moderate to strong TGR5 staining was significantly higher in high-grade dysplasia and EA cases than in Barrett’s esophagus (BE) or in low-grade dysplasia. Moderate to strong staining was slightly higher in low-grade dysplasia than in BE mucosa, but there is no statistical significance. TGR5 staining had no significant difference between high-grade dysplasia and EA. In addition, TGR5 staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis.CONCLUSIONWe conclude that TGR5 immunostaining was much stronger in high-grade dysplasia and EA than in BE mucosa or low-grade dysplasia and that its staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. TGR5 might be a potential marker for the progression from BE to high-grade dysplasia and EA.展开更多
Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a res...Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a result of tumor recurrence.We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the recent trials of novel agents that attempt to target these pathways.There are many trials underway with the aim of improving survival in oesophageal cancer.Currently,phase 2 and 3 trials are focused on MAP kinase inhibition,either through inhibition of growth factor receptors or signal transducer proteins.In order to avoid tumor resistance,it appears to be clear that targeted therapy will be needed to combat the multiple signalling pathways that are in operation in oesophageal adenocarcinomas.This may be achievable in the future with the advent of gene signatures and a combinatorial approach.展开更多
In the last thirty years, the incidence of primary esophageal adenocarcinoma has increased steadily and now they account for 30% to 50% of esophageal carcinomas in western countries. In the mean time, adenocarcinomas ...In the last thirty years, the incidence of primary esophageal adenocarcinoma has increased steadily and now they account for 30% to 50% of esophageal carcinomas in western countries. In the mean time, adenocarcinomas at the esophagogastric junction have also increased, though less prominently. In this report, the natural history of these tumors is presented.展开更多
Endoscopic mucosal resection is indicated in limited esophageal carcinomas with in?ltration of the mucosa. As submucosal cancer is combined with a rate of lymph node metastasis in up to 30% mucosectomy is not the proc...Endoscopic mucosal resection is indicated in limited esophageal carcinomas with in?ltration of the mucosa. As submucosal cancer is combined with a rate of lymph node metastasis in up to 30% mucosectomy is not the procedure of choice. The main techniques of endoscopic mucosal resection are the “suck and cut” technique using a cap on the endoscope or a ligation device to create a pseudocroup of the carcinoma. Submucosal injection of saline or other solutions is recommended prior to diathermic mucosectomy in order to reduce the risk of perforation or haemorrhage. The long term results of endoscopic mucosal resection show tumor speci?c 5 year survival rates of about 97% especially if the indication is restricted to m1 and m2 mucosal carcinomas.展开更多
A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonanc...A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonance imaging revealed an elongated mass in the retrotracheal region of the lower neck with extension to the posterior mediastinum. Partial tumor resection and histopathological evaluation revealed a WHO type B2 thymoma. Adjuvant radiation and chemotherapy were subsequently administered resulting in complete tumor regression. To our knowledge, this is the first report of ectopic retrotracheal thymoma with clinical and imaging manifestations mimicking those for esophageal submucosal tumor.展开更多
Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world.Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing intere...Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world.Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle.A large international effort has led to the development of a large number of inhibitors,which target cell cycle kinases,including cyclin-dependent kinases,Aurora kinases and polo-like kinase.Initial phase Ⅰ/Ⅱ trials in solid tumors have often demonstrated only modest clinical benefits of monotherapy.This may relate in part to a failure to identify the patient populations that will gain the most clinical benefit.Newer compounds lacking the side effect profile of first-generation compounds may show utility as adjunctive treatments targeted to an individual's predicted response to treatment.展开更多
AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE...AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE). METHODS: Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients' samples (81%). Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ (n = 8), type Ⅱ (n = 12), type Ⅲ (n = 9), and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage (lymph-node involvement), histological type (papillary, signet-ring cell, tubular), state of differentiation (good, moderate, poor), and survival (≤24 or ≥24 mo). RESULTS: In adenocarcinomas, the activity of α-mannosidase (AMAN), cathepsin B (CB) and dipeptidyl-peptidase Ⅰ (DPP Ⅰ) increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were significantly higher than of those who survived for 2 years or more. CONCLUSION: Adenocarcinomas of the GEJ form a homogenous group from a tumor-biochemical aspect, and differ from the biochemical characteristics of squamous cell carcinomas of the LTE on many points. When adenocarcinomas of the GEJs are examined at the preoperative phase, the ratio of the performed AMAN, CB, and DPP Ⅰ enzymatic activity of the tissue sample from the tumor and adjacent intact mucosa within 2 cm of the tumor may have a prognostic value even in the preoperative examination period, and may indicate that ranking of these patients into the neo-adjuvant treatment group should be considered.展开更多
OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected ...OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected from 1,526 thoracicesophageal and cardiac carcinoma patients who were admitted inthe Fourth Hospital of Hebei Medical University during a periodfrom January 1996 to December 2004,were randomly selectedand an Access Database of the patient's information was set up.Eight clinico-pathologic factors,including the patient's age,tumorlocation and size,pathological classification,the depth of tumorinvasion,vascular tumor embolus (VTE),the state of surroundingorgan encroachment and the status of tumor residues,wereidentified.A correlation between these factors and metastases wasstatistically analyzed using SPSS13.0 software.RESULTS Lymph node metastatic sites from esophagealcarcinomas included the thoracic and abdominal cavity.Lymphnode metastasis from the superior esophageal carcinomasmainly occurred in the neck and thoracic cavity.There was atwo-way lymph node metastasis in the patients with the middleesophageal carcinoma.The inferior esophageal carcinomas mainlymetastasized to the paraesophageal,paragastric cardia,and leftgastric artery lymph nodes.The rate and degree of the metastasisfrom the inferior esophageal carcinomas were significantly highercompared to those of the superior and the middle esophagealcarcinomas (P<0.0125).The degree of abdominal lymph node metastasis fromcarcinomas of the gastric cardia was significantly higher comparedwith that of esophageal carcinomas.In the group with carcinomaof the gastric cardia,the rate and degree of the lymph nodemetastases in the paragastric cardia and left gastric artery weresignificantly higher compared to the group with esophagealcarcinoma (P<0.05).Paraesophageal lymph node metastasis fromcarcinomas of the gastric cardia in the thoracic cavity frequentlyoccurred,too,and the degree of the metastasis was similar to thatof esophageal carcinoma.There was no significant difference inthe rate and degree of the paraesophageal lymph-node metastasisbetween the group with carcinoma of the gastric cardia comparedto those with esophageal carcinoma (P>0.05).Multifactoriallogistic regression analysis showed that the tumor size,depth oftumor encroachment,VTE,and tumor residues could all bringabout obvious impact on lymph-node metastases (P<0.05).CONCLUSION Lymph node metastasis from superioresophageal carcinomas mainly occurs in the neck and thoraciccavity.The middle esophageal carcinomas presented a two-waylymph-node metastasis (both the upwards and the downwards),and the lymph node metastasis from inferior esophagealcarcinomas mainly occurred in the thoracic and abdominal cavities.The metastases of carcinoma of the gastriccardia were most commonly found in the abdominalcavity,with frequent paraesophageal lymph-nodemetastasis.The sufficient attention should be paidto neck lymph node clearance in cases of esophagealcarcinoma.What is of the greatest concern is theclearance of the left gastric artery lymph nodes,andalso in cases of gastric cardia carcinoma,clearance,the paraesophageal lymph nodes.With an increasein the tumor size and depth of tumor encroachment,and occurrence of VTE and tumor residual cells,therisk of lymph node metastasis is significantly raised (P<0.05).展开更多
Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired ...Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening,surveillance and management of Barrett's oesophagus,however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance,and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features,smoking,gender,obesity,ethnicity,patient age,biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.展开更多
AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies ev...AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies(n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate(AIR) of progression to HGD and or EAC was 10.35%(95%CI: 7.56-13.13) and progression to EAC was 5.18%(95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65%(95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42%(95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63%(95%CI: 13.98-43.27). CONCLUSION When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.展开更多
文摘Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.
文摘A case of esophageal carcinoma exclusively composed of adenocarcinoma simulating an esophageal gland duct in a 61-year-old man is presented. The tumor arose as a slightly elevated lesion in the middle intrathoracic esophagus. It was almost completely overlaid with nonneoplastic stratified squamous epithelial cells. Beneath the overlying surface epithelium, an adenocarcinoma that was bilayered in structure diffusely invaded both the mucosal and submucosal layers. Although the tumor consisted exclusively of adenocarcinomatous cells, a keratinizing squamous cell carcinoma component was focally observed. The invasive carcinoma was focally continuous with the small area of the surface squamous epithelial layer, which was confirmed to be neoplastic by immunohistochemistry. Morphological and immunohistochemical examinations suggested that the adenocarcinomatous component arose from the esophageal surface epithelium and clearly differentiated into an esophageal gland duct. It is important to consider the possibility of this type of adenocarcinoma when diagnosing a ductal or glandular lesion of the esophagus in small biopsy specimens.
文摘To examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett’s mucosa, dysplasia and esophageal adenocarcinoma (EA).METHODSSlides were stained with TGR5 antibody. The staining intensity was scored as 1+, 2+ and 3+. The extent of staining (percentage of cells staining) was scored as follows: 1+, 1%-10%, 2+, 11%-50%, 3+, 51%-100%. A combined score of intensity and extent was calculated and categorized as negative, weak, moderate and strong staining. TGR5 mRNA was measured by real time PCR.RESULTSWe found that levels of TGR5 mRNA were significantly increased in Barrett’s dysplastic cell line CP-D and EA cell line SK-GT-4, when compared with Barrett’s cell line CP-A. Moderate to strong TGR5 staining was significantly higher in high-grade dysplasia and EA cases than in Barrett’s esophagus (BE) or in low-grade dysplasia. Moderate to strong staining was slightly higher in low-grade dysplasia than in BE mucosa, but there is no statistical significance. TGR5 staining had no significant difference between high-grade dysplasia and EA. In addition, TGR5 staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis.CONCLUSIONWe conclude that TGR5 immunostaining was much stronger in high-grade dysplasia and EA than in BE mucosa or low-grade dysplasia and that its staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. TGR5 might be a potential marker for the progression from BE to high-grade dysplasia and EA.
基金Supported by UK National Institute of Health Research/Cancer Research Network (UK NIHR/UKCRN) and Research and Development Department of Wrightington Wigan and Leigh NHS Foundation Trust (to Ang YS)R Keld WrightingtonWigan and Leigh NHS Foundation Trust Cancer Therapy Fund(to Keld RR,in part)
文摘Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a result of tumor recurrence.We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the recent trials of novel agents that attempt to target these pathways.There are many trials underway with the aim of improving survival in oesophageal cancer.Currently,phase 2 and 3 trials are focused on MAP kinase inhibition,either through inhibition of growth factor receptors or signal transducer proteins.In order to avoid tumor resistance,it appears to be clear that targeted therapy will be needed to combat the multiple signalling pathways that are in operation in oesophageal adenocarcinomas.This may be achievable in the future with the advent of gene signatures and a combinatorial approach.
文摘In the last thirty years, the incidence of primary esophageal adenocarcinoma has increased steadily and now they account for 30% to 50% of esophageal carcinomas in western countries. In the mean time, adenocarcinomas at the esophagogastric junction have also increased, though less prominently. In this report, the natural history of these tumors is presented.
文摘Endoscopic mucosal resection is indicated in limited esophageal carcinomas with in?ltration of the mucosa. As submucosal cancer is combined with a rate of lymph node metastasis in up to 30% mucosectomy is not the procedure of choice. The main techniques of endoscopic mucosal resection are the “suck and cut” technique using a cap on the endoscope or a ligation device to create a pseudocroup of the carcinoma. Submucosal injection of saline or other solutions is recommended prior to diathermic mucosectomy in order to reduce the risk of perforation or haemorrhage. The long term results of endoscopic mucosal resection show tumor speci?c 5 year survival rates of about 97% especially if the indication is restricted to m1 and m2 mucosal carcinomas.
文摘A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonance imaging revealed an elongated mass in the retrotracheal region of the lower neck with extension to the posterior mediastinum. Partial tumor resection and histopathological evaluation revealed a WHO type B2 thymoma. Adjuvant radiation and chemotherapy were subsequently administered resulting in complete tumor regression. To our knowledge, this is the first report of ectopic retrotracheal thymoma with clinical and imaging manifestations mimicking those for esophageal submucosal tumor.
基金Supported by UK National Institute of Health Research/Cancer Research Network and Research and Development Department of Wrightington Wigan and Leigh NHS Foundation Trust (to Ang YS)Wrightington Wigan and Leigh NHS Foundation Trust Cancer Therapy Fund (to Dibb M)
文摘Esophageal adenocarcinoma is a major cause of cancer death in men in the developed world.Continuing poor outcomes with conventional therapies that predominantly target apoptosis pathways have lead to increasing interest in treatments that target the cell cycle.A large international effort has led to the development of a large number of inhibitors,which target cell cycle kinases,including cyclin-dependent kinases,Aurora kinases and polo-like kinase.Initial phase Ⅰ/Ⅱ trials in solid tumors have often demonstrated only modest clinical benefits of monotherapy.This may relate in part to a failure to identify the patient populations that will gain the most clinical benefit.Newer compounds lacking the side effect profile of first-generation compounds may show utility as adjunctive treatments targeted to an individual's predicted response to treatment.
文摘AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE). METHODS: Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients' samples (81%). Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ (n = 8), type Ⅱ (n = 12), type Ⅲ (n = 9), and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage (lymph-node involvement), histological type (papillary, signet-ring cell, tubular), state of differentiation (good, moderate, poor), and survival (≤24 or ≥24 mo). RESULTS: In adenocarcinomas, the activity of α-mannosidase (AMAN), cathepsin B (CB) and dipeptidyl-peptidase Ⅰ (DPP Ⅰ) increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were significantly higher than of those who survived for 2 years or more. CONCLUSION: Adenocarcinomas of the GEJ form a homogenous group from a tumor-biochemical aspect, and differ from the biochemical characteristics of squamous cell carcinomas of the LTE on many points. When adenocarcinomas of the GEJs are examined at the preoperative phase, the ratio of the performed AMAN, CB, and DPP Ⅰ enzymatic activity of the tissue sample from the tumor and adjacent intact mucosa within 2 cm of the tumor may have a prognostic value even in the preoperative examination period, and may indicate that ranking of these patients into the neo-adjuvant treatment group should be considered.
基金This work was supported by a grant from the Hebei Provincial Program for Subjects with High Scholarship and Creative Research Potential
文摘OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected from 1,526 thoracicesophageal and cardiac carcinoma patients who were admitted inthe Fourth Hospital of Hebei Medical University during a periodfrom January 1996 to December 2004,were randomly selectedand an Access Database of the patient's information was set up.Eight clinico-pathologic factors,including the patient's age,tumorlocation and size,pathological classification,the depth of tumorinvasion,vascular tumor embolus (VTE),the state of surroundingorgan encroachment and the status of tumor residues,wereidentified.A correlation between these factors and metastases wasstatistically analyzed using SPSS13.0 software.RESULTS Lymph node metastatic sites from esophagealcarcinomas included the thoracic and abdominal cavity.Lymphnode metastasis from the superior esophageal carcinomasmainly occurred in the neck and thoracic cavity.There was atwo-way lymph node metastasis in the patients with the middleesophageal carcinoma.The inferior esophageal carcinomas mainlymetastasized to the paraesophageal,paragastric cardia,and leftgastric artery lymph nodes.The rate and degree of the metastasisfrom the inferior esophageal carcinomas were significantly highercompared to those of the superior and the middle esophagealcarcinomas (P<0.0125).The degree of abdominal lymph node metastasis fromcarcinomas of the gastric cardia was significantly higher comparedwith that of esophageal carcinomas.In the group with carcinomaof the gastric cardia,the rate and degree of the lymph nodemetastases in the paragastric cardia and left gastric artery weresignificantly higher compared to the group with esophagealcarcinoma (P<0.05).Paraesophageal lymph node metastasis fromcarcinomas of the gastric cardia in the thoracic cavity frequentlyoccurred,too,and the degree of the metastasis was similar to thatof esophageal carcinoma.There was no significant difference inthe rate and degree of the paraesophageal lymph-node metastasisbetween the group with carcinoma of the gastric cardia comparedto those with esophageal carcinoma (P>0.05).Multifactoriallogistic regression analysis showed that the tumor size,depth oftumor encroachment,VTE,and tumor residues could all bringabout obvious impact on lymph-node metastases (P<0.05).CONCLUSION Lymph node metastasis from superioresophageal carcinomas mainly occurs in the neck and thoraciccavity.The middle esophageal carcinomas presented a two-waylymph-node metastasis (both the upwards and the downwards),and the lymph node metastasis from inferior esophagealcarcinomas mainly occurred in the thoracic and abdominal cavities.The metastases of carcinoma of the gastriccardia were most commonly found in the abdominalcavity,with frequent paraesophageal lymph-nodemetastasis.The sufficient attention should be paidto neck lymph node clearance in cases of esophagealcarcinoma.What is of the greatest concern is theclearance of the left gastric artery lymph nodes,andalso in cases of gastric cardia carcinoma,clearance,the paraesophageal lymph nodes.With an increasein the tumor size and depth of tumor encroachment,and occurrence of VTE and tumor residual cells,therisk of lymph node metastasis is significantly raised (P<0.05).
文摘Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening,surveillance and management of Barrett's oesophagus,however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance,and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features,smoking,gender,obesity,ethnicity,patient age,biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.
文摘AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies(n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate(AIR) of progression to HGD and or EAC was 10.35%(95%CI: 7.56-13.13) and progression to EAC was 5.18%(95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65%(95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42%(95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63%(95%CI: 13.98-43.27). CONCLUSION When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.