scholarly journals Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage: A study on 25 cases

2005 ◽  
Vol 11 (46) ◽  
pp. 7384 ◽  
Author(s):  
Jens Krugmann
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 599
Author(s):  
Lazaros Vasilikos ◽  
Kay Hänggi ◽  
Lisanne M. Spilgies ◽  
Samanta Kisele ◽  
Stefanie Rufli ◽  
...  

In this study, we determined whether Smac mimetics play a role in metastasis, specifically in circulation, tumor extravasation and growth in a metastatic site. Reports suggest inducing the degradation of IAPs through use of Smac mimetics, alters the ability of the tumor cell to metastasize. However, a role for the immune or stromal compartment in affecting the ability of tumor cells to metastasize upon loss of IAPs has not been defined. To address this open question, we utilized syngeneic tumor models in a late-stage model of metastasis. Loss of cIAP1 in the endothelial compartment, rather than depletion of cIAP2 or absence of cIAP1 in the hematopoietic compartment, caused reduction of tumor load in the lung. Our results underline the involvement of the endothelium in hindering tumor cell extravasation upon loss of cIAP1, in contrast to the immune compartment. Endothelial specific depletion of cIAP1 did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a decrease in tumor cell extravasation. Surprisingly, lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells, was critical for the extravasation. Using TCGA, we found high LTA mRNA expression correlated with decreased survival in kidney carcinoma and associated with advanced disease stage. Our data suggest that Smac mimetics, targeting cIAP1/2, reduce metastasis to the lung by inhibiting tumor cell extravasation.


1988 ◽  
Vol 6 (1) ◽  
pp. 147-153 ◽  
Author(s):  
K Antman ◽  
R Shemin ◽  
L Ryan ◽  
K Klegar ◽  
R Osteen ◽  
...  

All mesothelioma patients identified by a computer search of pathologic diagnoses at the Dana-Farber Cancer Institute (DFCI) between 1965 and 1985 were the subjects of this analysis. A total of 180 patients were identified, 136 with pleural and 37 with peritoneal mesothelioma. There were five pericardial and two testicular primaries. Of the two decades included in the study, later patients were significantly older, with a more advanced disease stage, and a lower performance status than those accrued early in the study. Factors at diagnosis associated with a significantly prolonged survival for all patients with mesothelioma included a 0 to 1 performance status, absence of chest pain, age less than 50 years, and epithelial histology. Factors at diagnosis associated with prolonged survival for the subset of patients with pleural mesothelioma included epithelial histology, 0 to 1 performance status, the absence of chest pain, an interval of greater than 6 months from onset of symptoms, and treatment with chemotherapy and pleuropneumonectomy. This last result must be interpreted with caution, since this was not a randomized study.


Author(s):  
Pascal Martin ◽  
Gisela E. Hagberg ◽  
Thomas Schultz ◽  
Klaus Harzer ◽  
Uwe Klose ◽  
...  

Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 520-520 ◽  
Author(s):  
ZiYi Lim ◽  
Ronald Brand ◽  
Anja van Biezen ◽  
Jurgen Finke ◽  
Dietger W. Niederwieser ◽  
...  

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with MDS. However, the advanced age of the majority of patients with MDS poses a significant barrier to the success of transplantation. Many of these patients have co-morbidities, or lack a suitable sibling matched donor. While reduced intensity conditioning (RIC) has expanded the scope of allografting to older patients, it remains unclear as to whether it confers an improvement in overall survival in this patient sub-group. Here we report on the results of a retrospective multi-centre analysis of 1385 patients aged 50 years or older with MDS transplanted since 1993. The main variables analysed in this study were donor status (sibling vs unrelated matched), age group (50–60 years vs >60years), disease stage at time of transplantation (early:<5% blasts vs advanced:>5% blasts), type of conditioning regimen (RIC vs standard myeloablative conditioning, SMC), period of transplantation (1993–96, 1997–2000–2001-). There were 1000 matched sibling (72%) and 385 matched unrelated donor transplants (28%). The median age of the cohort was 56 years (range:50–74 years), with 1053 patients (76%) aged 50–60 years and 332 patients (24%) above 60 years. 604 patients(44%) received SMC and 781 patients (56%) received RIC. 189 patients (14%) had RA/RARS, 388 patients (28%) had RAEB, 233 patients(17%) had RAEB-t and 393 patients secondary AML (28%). FAB classification was unavailable for 182 patients (13%). Patients receiving RIC were older (age>60 years: 30% RIC vs 14% SMC, p<0.001), but SMC had a more advanced disease stage at transplant (42% RIC vs 51% SMC). There was no difference in donor type between RIC and SMC (MUD: 28% RIC vs 28% SMC) The estimated cumulative incidence (competing risk model) at 4-years post transplant for TRM decreased from 47%(1993–1996), via 40%(1997–2000) to 35%(2001-); for Relapse Incidence these figures are 29%, 33% and 40% respectively. On multivariate analysis, age >60 years(HR:1.28, 95%CI [1.0–1.6], p=0.04), use of RIC (HR:1.50 95%CI [1.2–1.9], p<0.001) and advanced disease stage at transplantation (HR:1.51, 95%CI [1.2–2.0], p=0.002) were associated with an increased relapse rate; the use of RIC with a lower TRM (HR:0.71, 95%CI [0.57–0.88], p<0.01) and advanced disease stage at transplantation with a higher TRM (HR: 1.4, 95%CI [1.1–1.8], p<0.01) In contrast, donor type did not significantly influence either the 4-year TRM or relapse rates(HR’s 1.12 and 0.94 respectively, both p>0.30). Advanced disease stage at transplantation was the only independent variable associated with an inferior 4-year overall survival(OS)(HR: 1.47, 95%CI [1.2–1.8], p<0.001). In conclusion, disease stage at time of transplantation has an important prognostic impact on outcomes. The use of RIC is associated with higher relapse but lower TRM and comparable OS with SMC in this cohort. While patients aged >60 years had an increased relapse rate, there was no significant difference in OS compared with those aged 50–60 years. The choice of donor did not significantly influence outcomes. Long-term survival can be achieved in a sub-group of older MDS patients, but prospective studies are warranted to improve patient selection and to identify optimal treatment strategies.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15703-e15703
Author(s):  
Zhaohui Jin ◽  
Mindy L. Hartgers ◽  
Cristobal T. Sanhueza ◽  
Benny Johnson ◽  
Christopher R. Shubert ◽  
...  

e15703 Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG > = 1), old age ( > = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p < 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score > = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ruolan Xia ◽  
Yuwen Zhou ◽  
Yuqing Wang ◽  
Jiaming Yuan ◽  
Xuelei Ma

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignant tumor, accounting for only 0.17–15% of gastric cancers. Patients are often diagnosed at an advanced disease stage, and their symptoms are similar to conventional gastric cancer (CGC) without specific clinical manifestation. Morphologically, HAC has identical morphology and immunophenotype compared to hepatocellular carcinoma (HCC). This is considered to be an underestimation in diagnosis due to its rare incidence, and no consensus is reached regarding therapy. HAS generally presents with more aggressive behavior and worse prognosis than CGC. The present review summarizes the current literature and relevant knowledge to elaborate on the epidemic, potential mechanisms, clinical manifestations, diagnosis, management, and prognosis to help clinicians accurately diagnose and treat this malignant tumor.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1994-1994 ◽  
Author(s):  
ZiYi Lim ◽  
Murugaiyan Thanigaikumar ◽  
Shreyans Gandhi ◽  
Laurence Pearce ◽  
Michelle Kenyon ◽  
...  

Abstract The use of IV busulphan (Bu) has reported improved bioavailability with lower variability of busulphan plasma levels, and may reduce the effects of transplant related toxicity particularly in the context of myeloablative regimens. In contrast, there is limited data avaliable on the use of IV Bu in the setting of reduced conditioning (RIC) regimens. We retrospectively analysed data from 163 consecutive patients treated at our centre for myeloid malignancies (AML n=78, MDS/MPD n=73, CML n= 12) using RIC HSCT, and evaluated the engraftment and chimerism kinetics as well as the early transplant outcomes between patients receiving either IV or oral Bu. Patients received fludarabine (30mg/m2 × 5 days), alemtuzumab (20mg × 5 days) and either oral Bu (4mg/kg × 2 days) or IV Bu (3.2mg/kg × 2 days). 84 consecutive patients received oral Bu up to Jan 2004. Thereafter, 79 consecutive patients received IV Bu. The median age of the cohort was 53 years(range: 19–72). 50 patients received stem cells from HLA-matched sibling donor, and 113 from a volunteer unrelated donor. 128 patients received PBSC and 35 received BM stem cells. 64 patients had early disease vs 99 advanced disease (advance disease defined as AML &gt; CR1, CML &gt; CP1, MDS with RAEB or AML with multilineage dysplasia). Median follow-up was 1531 days (range: 853–1987) for the oral Bu group and 551 days (range: 228–1072) for the IV Bu group. There was no difference between groups in terms of recipient age, stem cell dose/source, donor type, prior therapies or disease type. However, patients receiving IV Bu had more advanced disease compared with oral Bu (70% vs 52%, p=0.03). There was no significant difference in the median time to neutrophil and platelet regeneration between groups. In contrast lymphoid(CD3) engraftment was significantly delayed in the IV Bu group, with 35% vs 53%(p=0.04) recipients achieving full donor chimerism(FDC) at day 30, and 32% vs 51%(p=0.03) at day 100. The cumulative incidence of acute GvHD was lower in the IV Bu group 18% vs 29%(p=0.04), with no difference in the cummulative incidence of chronic GvHD between groups. Early(1-year) transplant-related mortality (TRM) was higher in the oral Bu group(TRM:: 25%vs13%, p=0.07) with a significantly lower overall survival(60%vs79%, p=0.02) primarily as a result of death from GvHD and related infection complications. There was no significant difference in relapse incidence at 1 year between cohorts(IV Bu 27% vs oral Bu 23%, p=0.84). On multivariate analysis, the type of conditioning regimen had no effect on the overall transplant outcomes. Attainment of CD3 FDC at day 30(HR: 2.14, 95%CI: 1.26–3.63, p&lt;0.01) and advanced disease stage(HR:2.62, 95%CI: 1.41–4.89, p&lt;0.01) were the only significant variables associated with a poorer OS. In contrast, the presence of CD3 mixed donor chimerism at day 30(HR:2.70, 95%CI: 1.24–5.90, p=0.01) was the only independent variable associated with improved TRM. Advanced disease stage was the only independent predictor of disease relapse(HR:2.34, 95%CI: 1.17–4.66, p=0.02). In summary, RIC HSCT with IV busulphan is a safe and well tolerated regimen. When compared with oral Bu, use of IV Bu as part of an FBC regimen is associated with delayed attainment of CD3 FDC, and is associated with a corresponding lower incidence of acute GvHD and early complications.


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