BACKGROUND In recent years,increasing evidence of second neoplasms associated with gastrointestinal stromal tumors(GIST)has been found.Numerous case reports,mostly retrospective studies and a few reviews,have been pub...BACKGROUND In recent years,increasing evidence of second neoplasms associated with gastrointestinal stromal tumors(GIST)has been found.Numerous case reports,mostly retrospective studies and a few reviews,have been published.To our knowledge,however,no systematic review or meta-analysis of the existing data has been performed so far.AIM To prepare a compilation,as complete as possible,of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency,localization,and types of GIST-associated neoplasms.METHODS The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary,synchronous,coincident/tumor,neoplasm,and relevant publications were selected by two independent authors.RESULTS Initially,3042 publications were found.After deletion of duplicates,1631 remained,and 130 papers were selected;22 of these were original studies with a minimum of 20 patients,and 108 were case reports.In the 22 selected studies,comprising a total number of 12050 patients,an overall rate of GIST-associated neoplasias of 20%could be calculated.Most second neoplasias were found in the gastrointestinal tract(32%)and in the male and female urogenital tract(30%).The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias.CONCLUSION In this first systematic review,we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias.The question whether there is an underlying causal association will need further investigation.Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.展开更多
Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevan...Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevance in stage Ⅱ/Ⅲ cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However,this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This,however,had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor's behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.展开更多
AIM To test the validity of tumour thickness measurement in distinguishing between the different infiltration depths, especially when the duplication of muscularis mucosae cannot be demarcated clearly. METHODS We re-e...AIM To test the validity of tumour thickness measurement in distinguishing between the different infiltration depths, especially when the duplication of muscularis mucosae cannot be demarcated clearly. METHODS We re-evaluated 100 completely embedded Barrett's adenocarcinomas regarding m-classification, maximum tumour thickness, and muscularis mucosae duplication. For validation, smoothelin staining was performed on a subset of cases. RESULTS The m1-, m2-and m3-classified adenocarcinomasshowed a significant lower tumour thickness compared to the m4-and sm1-classified lesions(P < 0.001). Smoothelin staining determined a clear muscularis mucosae duplication in 64% of the tested samples and enabled the differentiation of the two layers in diffuse and merged splits. CONCLUSION Tumour thickness in early oesophageal adenocarcinoma significantly correlates with the depth of infiltration and demonstrates its worth as an accurate p T classification in non-polypoid lesions. We created a new algorithm, which combines histomorphology with morphometric analyses. It is noteworthy that it facilitates the assessment of mucosal vs submucosal infiltration depth. The smoothelin staining strengthened our results of the tumour thickness evaluation and can be used in cases of doubt.展开更多
Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I...Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.展开更多
文摘BACKGROUND In recent years,increasing evidence of second neoplasms associated with gastrointestinal stromal tumors(GIST)has been found.Numerous case reports,mostly retrospective studies and a few reviews,have been published.To our knowledge,however,no systematic review or meta-analysis of the existing data has been performed so far.AIM To prepare a compilation,as complete as possible,of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency,localization,and types of GIST-associated neoplasms.METHODS The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary,synchronous,coincident/tumor,neoplasm,and relevant publications were selected by two independent authors.RESULTS Initially,3042 publications were found.After deletion of duplicates,1631 remained,and 130 papers were selected;22 of these were original studies with a minimum of 20 patients,and 108 were case reports.In the 22 selected studies,comprising a total number of 12050 patients,an overall rate of GIST-associated neoplasias of 20%could be calculated.Most second neoplasias were found in the gastrointestinal tract(32%)and in the male and female urogenital tract(30%).The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias.CONCLUSION In this first systematic review,we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias.The question whether there is an underlying causal association will need further investigation.Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.
文摘Lymph node staging is of crucial importance for the therapy stratification and prognosis estimation in colon cancer. Beside the detection of metastases,the number of harvested lymph nodes itself has prognostic relevance in stage Ⅱ/Ⅲ cancers. A stage migration effect caused by missed lymph node metastases has been postulated as most likely explanation for that. In order to avoid false negative node staging reporting of at least 12 lymph nodes is recommended. However,this threshold is met only in a minority of cases in daily practice. Due to quality initiatives the situation has improved in the past. This,however,had no influence on staging in several studies. While the numbers of evaluated lymph nodes increased continuously during the last decades the rate of node positive cases remained relatively constant. This fact together with other indications raised doubts that understaging is indeed the correct explanation for the prognostic impact of lymph node harvest. Several authors assume that immune response could play a major role in this context influencing both the lymph node detectability and the tumor's behavior. Further studies addressing this issue are need. Based on the findings the recommendations concerning minimal lymph node numbers and adjuvant chemotherapy should be reconsidered.
文摘AIM To test the validity of tumour thickness measurement in distinguishing between the different infiltration depths, especially when the duplication of muscularis mucosae cannot be demarcated clearly. METHODS We re-evaluated 100 completely embedded Barrett's adenocarcinomas regarding m-classification, maximum tumour thickness, and muscularis mucosae duplication. For validation, smoothelin staining was performed on a subset of cases. RESULTS The m1-, m2-and m3-classified adenocarcinomasshowed a significant lower tumour thickness compared to the m4-and sm1-classified lesions(P < 0.001). Smoothelin staining determined a clear muscularis mucosae duplication in 64% of the tested samples and enabled the differentiation of the two layers in diffuse and merged splits. CONCLUSION Tumour thickness in early oesophageal adenocarcinoma significantly correlates with the depth of infiltration and demonstrates its worth as an accurate p T classification in non-polypoid lesions. We created a new algorithm, which combines histomorphology with morphometric analyses. It is noteworthy that it facilitates the assessment of mucosal vs submucosal infiltration depth. The smoothelin staining strengthened our results of the tumour thickness evaluation and can be used in cases of doubt.
文摘Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.
