Secondary amyloidosis can complicate chronic inflammatory autoimmune diseases. However, the clinical findings of primary amyloidosis may mimic those of primary rheumatologic disorders. We present the case of a 53-year-old woman who presented with dystrophic nail changes, dry eyes, bilateral carpal tunnel syndrome, Raynaud's phenomenon, and high titer positive nucleolar pattern antinuclear antibody. She was initially misdiagnosed as having Undifferentiated Connective Tissue Disease (UCTD). On further workup, she was eventually diagnosed with lambda light chain systemic amyloidosis by abdominal fat pad biopsy. Her symptoms completely resolved after autologous stem cell transplantation. With this case, we would like to highlight the similarities in the clinical features between light chain amyloidosis and rheumatological disorders. We would also like to emphasize the importance of the prompt recognition of the clinical features of amyloidosis which are crucial to triggering appropriate diagnostic procedures, since early diagnosis is a key to improving outcomes in this disease with an otherwise poor prognosis.
http://ift.tt/2grmAz2
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 28 Νοεμβρίου 2016
Systemic Light Chain Amyloidosis Mimicking Rheumatic Disorders
GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment
Abstract
Background
The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms.
Methods
The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell proliferative capability. Apoptotic cell number was measured by flow cytometry. The transwell assay was used to test the cell invasive capability. DNA damage effect was identified by COMET assay and γH2AX expression.
Results
Proliferation of tumor cells treated with GANT61 in combination with TMZ was significantly suppressed compared with those treated with either drug used alone. The combination treatment induced a higher rate of apoptosis, DNA damage and reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT and the Notch1 pathway increased in the cells treated by TMZ treatment. However, GANT61 could abrogated the protein increasing.
Conclusions
GANT61 sensitizes glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT expression and the Notch1 pathway.
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GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment
Abstract
Background
The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms.
Methods
The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell proliferative capability. Apoptotic cell number was measured by flow cytometry. The transwell assay was used to test the cell invasive capability. DNA damage effect was identified by COMET assay and γH2AX expression.
Results
Proliferation of tumor cells treated with GANT61 in combination with TMZ was significantly suppressed compared with those treated with either drug used alone. The combination treatment induced a higher rate of apoptosis, DNA damage and reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT and the Notch1 pathway increased in the cells treated by TMZ treatment. However, GANT61 could abrogated the protein increasing.
Conclusions
GANT61 sensitizes glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT expression and the Notch1 pathway.
http://ift.tt/2fGLFnZ
Can morphological MRI differentiate between primary central nervous system lymphoma and glioblastoma?
Abstract
Background
Primary central nervous system lymphoma (PCNSL) is a rare, aggressive brain neoplasm that accounts for roughly 2-6% of primary brain tumors. In contrast, glioblastoma (GBM) is the most frequent and severe glioma subtype, accounting for approximately 50% of diffuse gliomas. The aim of the present study was to evaluate morphological MRI characteristics in histologically-proven PCNSL and GBM at the time of their initial presentation.
Methods
We retrospectively evaluated standard diagnostic MRI examinations in 54 immunocompetent patients (26 female, 28 male; age 62.6 ± 11.5 years) with histologically-proven PCNSL and 54 GBM subjects (21 female, 33 male; age 59 ± 14 years).
Results
Several significant differences between both infiltrative brain tumors were found. PCNSL lesions enhanced homogenously in 64.8% of cases, while nonhomogeneous enhancement was observed in 98.1% of GBM cases. Necrosis was present in 88.9% of GBM lesions and only 5.6% of PCNSL lesions. PCNSL presented as multiple lesions in 51.9% cases and in 35.2% of GBM cases; however, diffuse infiltrative type of brain involvement was observed only in PCNSL (24.1%). Optic pathways were infiltrated more commonly in PCNSL than in GBM (42.6% vs. 5.6%, respectively, p <0.001). Other cranial nerves were affected in 5.6% of PCNSL, and in none of GBM. Signs of bleeding were rare in PCNSL (5.6%) and common in GBM (44.4%); p < 0.001. Both supratentorial and infratentorial localization was present only in PCNSL (27.7%). Involvement of the basal ganglia was more common in PCNSL (55.6%) than in GBM (18.5%); (p < 0.001). Cerebral cortex was affected significantly more often in GBM (83.3%) than in PCNSL (51.9%); mostly by both enhancing and non-enhancing infiltration.
Conclusion
Routine morphological MRI is capable of differentiating between GBM and PCNSL lesions in many cases at time of initial presentation. A solitary infiltrative supratentorial lesion with nonhomogeneous enhancement and necrosis was typical for GBM. PCNSL presented with multiple lesions that enhanced homogenously or as diffuse infiltrative type of brain involvement, often with basal ganglia and optic pathways affection.
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Can morphological MRI differentiate between primary central nervous system lymphoma and glioblastoma?
Abstract
Background
Primary central nervous system lymphoma (PCNSL) is a rare, aggressive brain neoplasm that accounts for roughly 2-6% of primary brain tumors. In contrast, glioblastoma (GBM) is the most frequent and severe glioma subtype, accounting for approximately 50% of diffuse gliomas. The aim of the present study was to evaluate morphological MRI characteristics in histologically-proven PCNSL and GBM at the time of their initial presentation.
Methods
We retrospectively evaluated standard diagnostic MRI examinations in 54 immunocompetent patients (26 female, 28 male; age 62.6 ± 11.5 years) with histologically-proven PCNSL and 54 GBM subjects (21 female, 33 male; age 59 ± 14 years).
Results
Several significant differences between both infiltrative brain tumors were found. PCNSL lesions enhanced homogenously in 64.8% of cases, while nonhomogeneous enhancement was observed in 98.1% of GBM cases. Necrosis was present in 88.9% of GBM lesions and only 5.6% of PCNSL lesions. PCNSL presented as multiple lesions in 51.9% cases and in 35.2% of GBM cases; however, diffuse infiltrative type of brain involvement was observed only in PCNSL (24.1%). Optic pathways were infiltrated more commonly in PCNSL than in GBM (42.6% vs. 5.6%, respectively, p <0.001). Other cranial nerves were affected in 5.6% of PCNSL, and in none of GBM. Signs of bleeding were rare in PCNSL (5.6%) and common in GBM (44.4%); p < 0.001. Both supratentorial and infratentorial localization was present only in PCNSL (27.7%). Involvement of the basal ganglia was more common in PCNSL (55.6%) than in GBM (18.5%); (p < 0.001). Cerebral cortex was affected significantly more often in GBM (83.3%) than in PCNSL (51.9%); mostly by both enhancing and non-enhancing infiltration.
Conclusion
Routine morphological MRI is capable of differentiating between GBM and PCNSL lesions in many cases at time of initial presentation. A solitary infiltrative supratentorial lesion with nonhomogeneous enhancement and necrosis was typical for GBM. PCNSL presented with multiple lesions that enhanced homogenously or as diffuse infiltrative type of brain involvement, often with basal ganglia and optic pathways affection.
http://ift.tt/2grbaeB
Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas
Abstract
Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n = 4) and healthy controls (n = 5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.
http://ift.tt/2gAQBze
Patient-reported neuropathic pain in adolescent and young adult cancer patients
Abstract
Background
Neuropathic pain, a known complication of cancer and its treatments, negatively impacts quality of life. There are limited data using screening tools to aid in the diagnosis of neuropathic pain in cancer patients. Our primary objective was to determine the proportion of adolescent and young adult cancer patients reporting neuropathic pain on a patient-completed, neuropathic pain screening tool.
Procedures
This prospective, cohort study enrolled patients 14–39 years of age who were receiving therapy for primary cancer diagnosis, cancer relapse, or had recently completed treatment. The painDETECT, a patient-completed, neuropathic pain screening tool used down to age 14, was administered a maximum of three times in on-therapy patients and once in off-therapy patients. Provider documentation of neuropathic pain at the corresponding visit was abstracted from the medical record.
Results
Seventy-eight patients participated. Median (interquartile range) age at study enrollment was 18.1 (16–19.4) years and 47% were female. Cancer diagnoses included 41% leukemia, 26% solid tumor, 23% lymphoma, and 10% central nervous system tumor. The proportion of patients reporting neuropathic pain was 26% (95% confidence interval [CI] 16–40%) in on-therapy patients and 11% (95% CI 3–27%) in off-therapy patients. In patients reporting neuropathic pain, only 26% had a clinical diagnosis of neuropathic pain documented in the medical record at the corresponding visit.
Conclusions
Neuropathic pain occurs in one in four adolescents and young adults receiving cancer therapy. Use of screening tools may increase the detection of neuropathic pain in adolescents and young adults receiving cancer therapy and could ultimately improve pain treatment.
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Health-related quality of life and adherence to hydroxyurea in adolescents and young adults with sickle cell disease
Abstract
Background
Complications related to sickle cell disease (SCD) result in significant declines in health-related quality of life (HRQOL). While hydroxyurea reduces SCD complications, adherence remains suboptimal. The study's objectives were to assess the feasibility of Internet-based electronic assessment of HRQOL in SCD clinic and to examine the relationship between HRQOL and hydroxyurea adherence in adolescents and young adults (AYAs) with SCD.
Procedure
A cross-sectional survey was administered on tablets to 34 AYAs (12–22 years old) in a SCD clinic from January through December 2015. Study measures included Patient Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive testing and ©Modified Morisky Adherence Scale 8-items (©MMAS-8).
Results
Participants (59% male, 91% Black) had median age of 13.5 (range 12–18) years. Ninety-one percent completed PROMIS® measures electronically in the clinic, meeting our feasibility criterion of ≥85% completion rate. ©MMAS-8 scores positively correlated with fetal hemoglobin (HbF) (rs = 0.34, P = 0.04) and mean corpuscular volume (MCV) (rs = 0.42, P = 0.01) and inversely correlated with fatigue (rs = –0.45, P = 0.01), depression (rs = –0.3, P = 0.08), and social isolation (rs = –0.78, P = 0.02). Low ©MMAS-8 scores, indicating poor adherence, were associated with worse fatigue (P = 0.001) and trended toward significance for pain (P = 0.07) and depression (P = 0.06). Homozygous hemoglobin S disease patients with low HbF (<16%) had worse social isolation (P = 0.04) and those with low MCV (<102 fl) reported worse fatigue (P = 0.001), pain (P = 0.01), mobility (P = 0.01), and social isolation (P = 0.04).
Conclusions
HRQOL assessment in the SCD clinic is feasible. SCD patients with low hydroxyurea adherence and/or low HbF or MCV levels had worse HRQOL scores, particularly fatigue. Future prospective studies examining the relationship between HRQOL and hydroxyurea adherence are warranted.
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Evaluation of maternal and perinatal characteristics on childhood lymphoma risk: A population-based case-control study
Abstract
Background
Lymphoma is one of the most common pediatric malignancies; however, there are few well-established risk factors. Therefore, we investigated if maternal and perinatal characteristics influenced the risk of childhood lymphoma.
Procedure
Information on cases (n = 374) diagnosed with lymphoma and born in Texas for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10 controls per 1 case for the same period of 1995–2011. Unconditional logistic regression was used to generate unadjusted (OR) and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the following histologic subtypes: Hodgkin (HL), Burkitt (BL), and non-BL non-HLs (non-BL NHLs).
Results
Overall, our findings indicate specific maternal and perinatal characteristics influence childhood lymphoma risk. Mexico-born mothers were more likely to have offspring who developed BL compared to mothers born in the United States (U.S.; aOR: 2.15; 95% CI: 1.06–4.36). Further, mothers who resided at time of delivery in a county on the U.S.-Mexico border were more likely to give birth to offspring who developed non-BL NHL (aOR: 1.72; 95% CI: 1.11–2.67) compared to mothers not living on the U.S.-Mexico border at time of infant birth. Last, infants born large-for-gestational-age experienced a twofold increase in BL risk (aOR: 2.00; 95% CI: 1.10–3.65).
Conclusions
In this population-based assessment, we confirmed previously reported risk predictors of childhood lymphoma, including sex of infant, while highlighting novel risk factors that warrant assessment in future studies.
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Quantifying bias in survival estimates resulting from loss to follow-up among children with lymphoma in Malawi
Abstract
Pediatric lymphoma is common in sub-Saharan Africa, where survival estimates are often based on limited follow-up with incomplete retention, introducing potential for bias. We compared follow-up and overall survival (OS) between passive and active tracing within a prospective cohort of children with lymphoma in Malawi. Median follow-up times were 4.4 months (interquartile range [IQR] 2.0–9.4) and 10.8 months (IQR 6.2–20.6) in passive and active follow-up, respectively. Twelve-month overall survival (OS) was 69% (95% confidence interval [CI] 54–80) in passive and 44% (95% CI 34–54) in active follow-up. Passive follow-up significantly overestimated the OS and underestimated the mortality. Efforts to improve retention in regional studies are needed.
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Patient-reported neuropathic pain in adolescent and young adult cancer patients
Abstract
Background
Neuropathic pain, a known complication of cancer and its treatments, negatively impacts quality of life. There are limited data using screening tools to aid in the diagnosis of neuropathic pain in cancer patients. Our primary objective was to determine the proportion of adolescent and young adult cancer patients reporting neuropathic pain on a patient-completed, neuropathic pain screening tool.
Procedures
This prospective, cohort study enrolled patients 14–39 years of age who were receiving therapy for primary cancer diagnosis, cancer relapse, or had recently completed treatment. The painDETECT, a patient-completed, neuropathic pain screening tool used down to age 14, was administered a maximum of three times in on-therapy patients and once in off-therapy patients. Provider documentation of neuropathic pain at the corresponding visit was abstracted from the medical record.
Results
Seventy-eight patients participated. Median (interquartile range) age at study enrollment was 18.1 (16–19.4) years and 47% were female. Cancer diagnoses included 41% leukemia, 26% solid tumor, 23% lymphoma, and 10% central nervous system tumor. The proportion of patients reporting neuropathic pain was 26% (95% confidence interval [CI] 16–40%) in on-therapy patients and 11% (95% CI 3–27%) in off-therapy patients. In patients reporting neuropathic pain, only 26% had a clinical diagnosis of neuropathic pain documented in the medical record at the corresponding visit.
Conclusions
Neuropathic pain occurs in one in four adolescents and young adults receiving cancer therapy. Use of screening tools may increase the detection of neuropathic pain in adolescents and young adults receiving cancer therapy and could ultimately improve pain treatment.
http://ift.tt/2gDXy0a
Health-related quality of life and adherence to hydroxyurea in adolescents and young adults with sickle cell disease
Abstract
Background
Complications related to sickle cell disease (SCD) result in significant declines in health-related quality of life (HRQOL). While hydroxyurea reduces SCD complications, adherence remains suboptimal. The study's objectives were to assess the feasibility of Internet-based electronic assessment of HRQOL in SCD clinic and to examine the relationship between HRQOL and hydroxyurea adherence in adolescents and young adults (AYAs) with SCD.
Procedure
A cross-sectional survey was administered on tablets to 34 AYAs (12–22 years old) in a SCD clinic from January through December 2015. Study measures included Patient Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive testing and ©Modified Morisky Adherence Scale 8-items (©MMAS-8).
Results
Participants (59% male, 91% Black) had median age of 13.5 (range 12–18) years. Ninety-one percent completed PROMIS® measures electronically in the clinic, meeting our feasibility criterion of ≥85% completion rate. ©MMAS-8 scores positively correlated with fetal hemoglobin (HbF) (rs = 0.34, P = 0.04) and mean corpuscular volume (MCV) (rs = 0.42, P = 0.01) and inversely correlated with fatigue (rs = –0.45, P = 0.01), depression (rs = –0.3, P = 0.08), and social isolation (rs = –0.78, P = 0.02). Low ©MMAS-8 scores, indicating poor adherence, were associated with worse fatigue (P = 0.001) and trended toward significance for pain (P = 0.07) and depression (P = 0.06). Homozygous hemoglobin S disease patients with low HbF (<16%) had worse social isolation (P = 0.04) and those with low MCV (<102 fl) reported worse fatigue (P = 0.001), pain (P = 0.01), mobility (P = 0.01), and social isolation (P = 0.04).
Conclusions
HRQOL assessment in the SCD clinic is feasible. SCD patients with low hydroxyurea adherence and/or low HbF or MCV levels had worse HRQOL scores, particularly fatigue. Future prospective studies examining the relationship between HRQOL and hydroxyurea adherence are warranted.
http://ift.tt/2gQECOz
Evaluation of maternal and perinatal characteristics on childhood lymphoma risk: A population-based case-control study
Abstract
Background
Lymphoma is one of the most common pediatric malignancies; however, there are few well-established risk factors. Therefore, we investigated if maternal and perinatal characteristics influenced the risk of childhood lymphoma.
Procedure
Information on cases (n = 374) diagnosed with lymphoma and born in Texas for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10 controls per 1 case for the same period of 1995–2011. Unconditional logistic regression was used to generate unadjusted (OR) and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the following histologic subtypes: Hodgkin (HL), Burkitt (BL), and non-BL non-HLs (non-BL NHLs).
Results
Overall, our findings indicate specific maternal and perinatal characteristics influence childhood lymphoma risk. Mexico-born mothers were more likely to have offspring who developed BL compared to mothers born in the United States (U.S.; aOR: 2.15; 95% CI: 1.06–4.36). Further, mothers who resided at time of delivery in a county on the U.S.-Mexico border were more likely to give birth to offspring who developed non-BL NHL (aOR: 1.72; 95% CI: 1.11–2.67) compared to mothers not living on the U.S.-Mexico border at time of infant birth. Last, infants born large-for-gestational-age experienced a twofold increase in BL risk (aOR: 2.00; 95% CI: 1.10–3.65).
Conclusions
In this population-based assessment, we confirmed previously reported risk predictors of childhood lymphoma, including sex of infant, while highlighting novel risk factors that warrant assessment in future studies.
http://ift.tt/2gDRGns
Quantifying bias in survival estimates resulting from loss to follow-up among children with lymphoma in Malawi
Abstract
Pediatric lymphoma is common in sub-Saharan Africa, where survival estimates are often based on limited follow-up with incomplete retention, introducing potential for bias. We compared follow-up and overall survival (OS) between passive and active tracing within a prospective cohort of children with lymphoma in Malawi. Median follow-up times were 4.4 months (interquartile range [IQR] 2.0–9.4) and 10.8 months (IQR 6.2–20.6) in passive and active follow-up, respectively. Twelve-month overall survival (OS) was 69% (95% confidence interval [CI] 54–80) in passive and 44% (95% CI 34–54) in active follow-up. Passive follow-up significantly overestimated the OS and underestimated the mortality. Efforts to improve retention in regional studies are needed.
http://ift.tt/2gQGWoJ
Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric cancer
Abstract
Background
The role of type I collagen, composed of collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2), has been studied in several cancers. However, the expression of COL1A1 and COL1A2 in malignant, premalignant, and normal gastric tissues and their clinical significances in gastric cancer have not been elucidated.
Methods
Real-time quantitative PCR was performed in 55 malignant, 27 premalignant, and 19 normal tissues to measure COL1A1 and COL1A2 messenger RNA (mRNA) expression, and the correlations between COL1A1 and COL1A2 expression and clinicopathological parameters and patients' survival rate were analyzed.
Results
We found that COL1A1 mRNA expression was significantly upregulated in premalignant and malignant tissues than in normal tissues, whereas COL1A2 mRNA expression was significantly higher in malignant tissues than in premalignant and normal tissues. Moreover, COL1A1 expression was unrelated to clinicopathological parameters, while COL1A2 expression was positively related to tumor size and depth of invasion. Besides, higher COL1A1 and COL1A2 expression levels were related to lower overall survival.
Conclusions
We find that COL1A1 might have its potential as a monitoring factor to screen early gastric cancer, and COL1A1 and COL1A2 might predict poor clinical outcomes in gastric cancer patients.
http://ift.tt/2gr66ag
Surgical treatment of recurrent urachal carcinoma with liver metastasis: a case report and literature review
Abstract
Background
Urachal carcinoma is a rare malignancy with poor prognosis due to late presentation of the disease and its aggressiveness. Surgery remains the mainstay of therapy even in cases of disease recurrence. To the best of our knowledge, this is the first report of salvage surgery in the case of urachal carcinoma with liver metastasis.
Case presentation
The patient was a young woman who suffered from locally advanced urachal carcinoma treated with en-bloc cystectomy, hysterectomy with bilateral adnexectomy, partial resection of the sigmoid colon, and partial resection of the rectus abdominis muscle with the fascia, skin, and umbilicus. Adjuvant chemotherapy with paclitaxel and carboplatin was applied. Two years after the treatment, she was diagnosed with a single liver metastasis and a local pelvic recurrence. In a two-step operation, the patient underwent right hemihepatectomy as well as resection of pelvic recurrence site and adjuvant chemotherapy with gemcitabine. Due to the disease progression, a complete resection of the lesions was not achieved and the response to chemotherapy was poor. The patient died of the disease after a year.
Conclusions
Surgery is the first line of treatment for urachal carcinoma and should be always considered as an option in cases of disease recurrence. Radical initial surgical management, close patient surveillance, and prompt treatment of disease relapse may all contribute to prolonging patient's survival.
http://ift.tt/2fL5iP3
Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric cancer
Abstract
Background
The role of type I collagen, composed of collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2), has been studied in several cancers. However, the expression of COL1A1 and COL1A2 in malignant, premalignant, and normal gastric tissues and their clinical significances in gastric cancer have not been elucidated.
Methods
Real-time quantitative PCR was performed in 55 malignant, 27 premalignant, and 19 normal tissues to measure COL1A1 and COL1A2 messenger RNA (mRNA) expression, and the correlations between COL1A1 and COL1A2 expression and clinicopathological parameters and patients' survival rate were analyzed.
Results
We found that COL1A1 mRNA expression was significantly upregulated in premalignant and malignant tissues than in normal tissues, whereas COL1A2 mRNA expression was significantly higher in malignant tissues than in premalignant and normal tissues. Moreover, COL1A1 expression was unrelated to clinicopathological parameters, while COL1A2 expression was positively related to tumor size and depth of invasion. Besides, higher COL1A1 and COL1A2 expression levels were related to lower overall survival.
Conclusions
We find that COL1A1 might have its potential as a monitoring factor to screen early gastric cancer, and COL1A1 and COL1A2 might predict poor clinical outcomes in gastric cancer patients.
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Surgical treatment of recurrent urachal carcinoma with liver metastasis: a case report and literature review
Abstract
Background
Urachal carcinoma is a rare malignancy with poor prognosis due to late presentation of the disease and its aggressiveness. Surgery remains the mainstay of therapy even in cases of disease recurrence. To the best of our knowledge, this is the first report of salvage surgery in the case of urachal carcinoma with liver metastasis.
Case presentation
The patient was a young woman who suffered from locally advanced urachal carcinoma treated with en-bloc cystectomy, hysterectomy with bilateral adnexectomy, partial resection of the sigmoid colon, and partial resection of the rectus abdominis muscle with the fascia, skin, and umbilicus. Adjuvant chemotherapy with paclitaxel and carboplatin was applied. Two years after the treatment, she was diagnosed with a single liver metastasis and a local pelvic recurrence. In a two-step operation, the patient underwent right hemihepatectomy as well as resection of pelvic recurrence site and adjuvant chemotherapy with gemcitabine. Due to the disease progression, a complete resection of the lesions was not achieved and the response to chemotherapy was poor. The patient died of the disease after a year.
Conclusions
Surgery is the first line of treatment for urachal carcinoma and should be always considered as an option in cases of disease recurrence. Radical initial surgical management, close patient surveillance, and prompt treatment of disease relapse may all contribute to prolonging patient's survival.
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Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK). Activation of receptor shedding by mechanical cues, hypoxia, radiation, and phosphosignaling offers insight into mechanisms of drug resistance. This particularly holds for kinase inhibitors targeting BRAF (such as vemurafenib and dabrafenib) and MEK (such as trametinib and cobimetinib), along with direct sheddase inhibitors. Receptor proteolysis can be detected in patient fluids and is especially relevant in melanoma, glioblastoma, lung cancer, and triple-negative breast cancer where RTK substrates, MAPK signaling, and ADAMs are frequently dysregulated. Translatable strategies to exploit receptor shedding include combination kinase inhibitor regimens, recombinant decoy receptors based on endogenous counterparts, and potentially immunotherapy.
http://ift.tt/2fw6h7c
Molecular Pathways: Deciphering Mechanisms of Resistance to Macrophage-Targeted Therapies
Tumor-associated macrophages (TAMs) are a major cellular component of numerous tumor types. TAM-targeted therapies include depletion strategies, inhibiting their effector functions, or reprogramming towards an anti-tumorigenic phenotype, with varying degrees of efficacy. Here we review preclinical and clinical strategies to target macrophages in cancer, and discuss potential explanations for why some strategies are effective while other approaches have shown limited success.
http://ift.tt/2fGDHeN
Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK). Activation of receptor shedding by mechanical cues, hypoxia, radiation, and phosphosignaling offers insight into mechanisms of drug resistance. This particularly holds for kinase inhibitors targeting BRAF (such as vemurafenib and dabrafenib) and MEK (such as trametinib and cobimetinib), along with direct sheddase inhibitors. Receptor proteolysis can be detected in patient fluids and is especially relevant in melanoma, glioblastoma, lung cancer, and triple-negative breast cancer where RTK substrates, MAPK signaling, and ADAMs are frequently dysregulated. Translatable strategies to exploit receptor shedding include combination kinase inhibitor regimens, recombinant decoy receptors based on endogenous counterparts, and potentially immunotherapy.
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Molecular Pathways: Deciphering Mechanisms of Resistance to Macrophage-Targeted Therapies
Tumor-associated macrophages (TAMs) are a major cellular component of numerous tumor types. TAM-targeted therapies include depletion strategies, inhibiting their effector functions, or reprogramming towards an anti-tumorigenic phenotype, with varying degrees of efficacy. Here we review preclinical and clinical strategies to target macrophages in cancer, and discuss potential explanations for why some strategies are effective while other approaches have shown limited success.
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Mesothelial cells create a novel tissue niche that facilitates gastric cancer invasion
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells. Mutual attraction between cancer cells and PMC accelerated tumor invasion in the gastric wall, and PMC led cancer cell invasion in disseminated tumors within the abdominal wall and diaphragm. Addition of the carboxyl terminus of Dickkopf-1 attenuated directional invasion of PMC toward cancer cells both in vitro and in the gastric wall in vivo. PMC was sensitive to the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF), as ALDH activity is elevated in PMC. Wnt3a upregulated ALDH, and addition of DSF inhibited the invasive properties of PMC, while DSF pretreatment suppressed gastric infiltration of PMC and subserosal invasion by cancer cells. Our results suggest that stabilization of PMC may become an effective therapy for the prevention of local invasion and metastasis of gastric cancer.
http://ift.tt/2fvZnia
Mesothelial cells create a novel tissue niche that facilitates gastric cancer invasion
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells. Mutual attraction between cancer cells and PMC accelerated tumor invasion in the gastric wall, and PMC led cancer cell invasion in disseminated tumors within the abdominal wall and diaphragm. Addition of the carboxyl terminus of Dickkopf-1 attenuated directional invasion of PMC toward cancer cells both in vitro and in the gastric wall in vivo. PMC was sensitive to the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF), as ALDH activity is elevated in PMC. Wnt3a upregulated ALDH, and addition of DSF inhibited the invasive properties of PMC, while DSF pretreatment suppressed gastric infiltration of PMC and subserosal invasion by cancer cells. Our results suggest that stabilization of PMC may become an effective therapy for the prevention of local invasion and metastasis of gastric cancer.
from Cancer via ola Kala on Inoreader http://ift.tt/2fvZnia
via IFTTT
18 F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation
Abstract
Purpose
Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.
Methods
Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.
Results
Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT's sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n = 4), pulmonary fungal infection (n = 1), histoplasmosis (n = 1), cutaneous abscess (n = 1), inflammatory disorder (sacroiliitis) (n = 1), lymphoma (n = 3) and NSCLC (n = 3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.
Conclusions
FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.
http://ift.tt/2gAxky0
18 F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation
Abstract
Purpose
Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.
Methods
Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.
Results
Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT's sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n = 4), pulmonary fungal infection (n = 1), histoplasmosis (n = 1), cutaneous abscess (n = 1), inflammatory disorder (sacroiliitis) (n = 1), lymphoma (n = 3) and NSCLC (n = 3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.
Conclusions
FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.
from Cancer via ola Kala on Inoreader http://ift.tt/2gAxky0
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When the Patient Believes That the Organs Are Destroyed: Manifestation of Cotard’s Syndrome
Cotard's Syndrome (CS) is a rare clinical event described for the first time in 1880 by the neurologist and psychiatrist Jules Cotard and characterized by negation delusions (or nihilists). Immortality and hypochondriac delusions are also typical. Nowadays, it is known that CS can be associated with many neuropsychiatric conditions. In this article, we describe the case of a patient that believed not having more organs and having the body deformed and whose CS was associated with a bigger depressive disorder. Although the electroconvulsive therapy is the most described treatment modality in the literature, the reported case had therapeutic success with association of imipramine and risperidone.
http://ift.tt/2gOcagj
Volar Locking Plate Breakage after Nonunion of a Distal Radius Osteotomy
We report a 38-year-old male with a nonunion followed by plate breakage after volar plating of a distal radius osteotomy. Volar locking plates have added a new approach to the treatment of distal radius malunions, due to a lower morbidity of the surgical approach and the strength of the final construction, allowing early mobilization and return to function. Conclusion. Plate breakage is an uncommon complication of volar locking plate fixation. To our knowledge, few cases have been described after a distal radius fracture and no case has been described after a distal radius corrective osteotomy. In the present case, plate breakage appears to have occurred as a result of a combination of multiple factors as the large corrective lengthening osteotomy, the use of demineralized bone matrix instead of bone graft, and the inappropriate fixation technique as an unfilled screw on the osteotomy site, rather than the choice of plate.
http://ift.tt/2gBt2Us
SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016)
Abstract
Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDM2jd
via IFTTT
SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016)
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
from Cancer via ola Kala on Inoreader http://ift.tt/2gxxRRi
via IFTTT
Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients
Abstract
Purpose
Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.
Methods/patients
Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.
Results
1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.
Conclusion
We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDRQt2
via IFTTT
SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)
Abstract
Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
from Cancer via ola Kala on Inoreader http://ift.tt/2gxF7MS
via IFTTT
SEOM Clinical Guideline for bone metastases from solid tumours (2016)
Abstract
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDSiY7
via IFTTT
SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016)
Abstract
Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
http://ift.tt/2fDM2jd
SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016)
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
http://ift.tt/2gxxRRi
Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients
Abstract
Purpose
Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.
Methods/patients
Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.
Results
1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.
Conclusion
We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.
http://ift.tt/2fDRQt2
SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)
Abstract
Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
http://ift.tt/2gxF7MS
SEOM Clinical Guideline for bone metastases from solid tumours (2016)
Abstract
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
http://ift.tt/2fDSiY7
SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016)
Abstract
Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDM2jd
via IFTTT
SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016)
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
from Cancer via ola Kala on Inoreader http://ift.tt/2gxxRRi
via IFTTT
Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients
Abstract
Purpose
Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.
Methods/patients
Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.
Results
1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.
Conclusion
We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDRQt2
via IFTTT
SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)
Abstract
Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
from Cancer via ola Kala on Inoreader http://ift.tt/2gxF7MS
via IFTTT
SEOM Clinical Guideline for bone metastases from solid tumours (2016)
Abstract
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
from Cancer via ola Kala on Inoreader http://ift.tt/2fDSiY7
via IFTTT
SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016)
Abstract
Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
http://ift.tt/2fDM2jd
SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016)
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
http://ift.tt/2gxxRRi
Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients
Abstract
Purpose
Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.
Methods/patients
Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.
Results
1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.
Conclusion
We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.
http://ift.tt/2fDRQt2
SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)
Abstract
Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
http://ift.tt/2gxF7MS
SEOM Clinical Guideline for bone metastases from solid tumours (2016)
Abstract
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
http://ift.tt/2fDSiY7
Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer
Abstract
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein-coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin-like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets.
This is the first report of the genomic profile of Borrmann type IV gastric cancer. We found that muscle RAS oncogene homolog (MRAS) is recurrently mutated in Borrmann type IV gastric cancer. We also detected IGF1R gene amplification and that it was correlated with high levels of mRNA and protein expression.
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via IFTTT
GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
Abstract
Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow-up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.
GPX3 methylation was identified in 15% myelodysplastic syndrome (MDS) patients, and was associated with adverse prognosis. GPX3 methylation density was significantly increased during the progression from MDS to sAML in follow-up patients.
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DLL4 overexpression increases gastric cancer stem/progenitor cell self-renewal ability and correlates with poor clinical outcome via Notch-1 signaling pathway activation
Abstract
Gastric cancer is one of the most common malignant diseases, and poses a serious threat to the quality of human life. Gastric cancer stem/progenitor cells (GCSPCs) have critical effects on tumor formation, affecting specific features of self-renewal and differentiation and playing a critical role in metastasis. The Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed. After DLL4 silencing in selected gastric cancer cell lines, the expression of GCSPC markers and colony formation ability were analyzed and the self-renewal and differentiation capacities of the cells were evaluated. The relationship between DLL4 levels and Notch-1 signaling pathway effector amounts was assessed via Western blotting and immunofluorescence. Finally, the tumor formation ability of the gastric cancer cells was evaluated with different levels of DLL4 and multiple cell densities in vivo. Our results indicate that DLL4 expression is associated with TNM stage and cancer metastasis, with high amounts of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal ability of GCSPCs and increased their multidifferentiation capacity, resulting in reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening invasion ability and resistance to 5-FU chemotherapy. In vivo, DLL4 silencing inhibited the tumor formation ability of GCSPCs. In conclusion, DLL4 affects GCSPC stemness, altering their pathological behavior. DLL4 silencing inhibits GCSPC metastatic potential both in vitro and in vivo by impeding Notch-1 signaling pathway activation, indicating that DLL4 may be a new potential therapeutic target.
DLL4 expression is associated with TNM stage and cancer metastasis, with high amounts of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal ability of GCSPCs and increased their multidifferentiation capacity, resulting in reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening invasion ability, and resistance to 5-FU chemotherapy.
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Marijuana use and inpatient outcomes among hospitalized patients: analysis of the nationwide inpatient sample database
Abstract
The purpose of this paper is to examine the relationship between marijuana use and health outcomes among hospitalized patients, including those hospitalized with a diagnosis of cancer. A total of 387,608 current marijuana users were identified based on ICD-9 codes for marijuana use among hospitalized patients in the Nationwide Inpatient Sample database between 2007 and 2011. Logistic regression analysis was performed to determine the association between marijuana use and heart failure, cardiac disease, stroke, and in-hospital mortality. All models were adjusted for age, gender, race, residential income, insurance, residential region, pain, and number of comorbidities. Among hospitalized patients, marijuana use was associated with a 60% increased odds of stroke (OR: 1.60, 95% CI: 1.44–1.77) compared with non-users, but significantly reduced odds of heart failure (OR: 0.78, 95% CI: 0.75–0.82), cardiac disease (OR: 0.86, 95% CI: 0.82–0.91), or in-hospital mortality (OR: 0.41, 95% CI: 0.38–0.44). Among cancer patients, odds of in-hospital mortality was significantly reduced among marijuana users compared with non-users (OR: 0.44, 95% CI: 0.35–0.55). Hospitalized marijuana users were more likely to experience a stroke compared with non-users, but less likely to experience in-hospital mortality. Prospective studies will be needed to better characterize the health effects of marijuana use, especially among older, sicker, and/or hospitalized patients. In the meantime, conversations regarding marijuana use/misuse may be warranted in the clinical setting in order for patients and healthcare providers to adequately weigh the anticipated benefits of marijuana use with potentially significant health risks.
In view of the rapidly increased use of marijuana in the general population. There is significant interest in examining the health effects of marijuana use among adults in general, but more importantly among those with health conditions or chronic diseases. In this study we examined the relationships between marijuana use and health outcomes among hospitalized patients, including hospitalized patients with and without a diagnosis of cancer.
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Does radiotherapy still have a role in unresected biliary tract cancer?
Abstract
The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7–9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1–11.3) months among those who received radiation, conditional on having survived 4 months. In patients who received chemotherapy (n = 1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70–0.97, P = 0.02). In patients who did not receive chemotherapy (n = 1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91–1.30, P = 0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time.
The benefits of radiotherapy for elderly patients with inoperable biliary tract cancer remain unclear due to the lack of randomized data given the rarity of this cancer. Using the SEER-Medicare database, we found that the use of radiotherapy has declined over time, and is influenced by tumor, patient, and socioeconomic factors, and that any survival benefit with radiotherapy is confined to those patients who received concurrent chemotherapy.
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Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting outcome of patients with glioblastoma
Abstract
Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this "cloudy" enhancement during radio-chemotherapy and its impact on patients' progression-free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and with sequences to quantify T1 before radiation, and at 6-week intervals during radio-chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy-enhancing compartment and evaluated the impact of their therapy-related volume change upon PFS. In ∆qT1 maps cloudy-enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy-enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing area of GBM is a new observation which is only visually detectable with qT1-mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio-chemotherapy.
Quantitative T1 subtraction maps uncover a cloudy-enhancing compartment that is not detected in conventional MRI and has prognostic value for patients with glioblastoma.
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Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer
Abstract
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein-coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin-like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets.
This is the first report of the genomic profile of Borrmann type IV gastric cancer. We found that muscle RAS oncogene homolog (MRAS) is recurrently mutated in Borrmann type IV gastric cancer. We also detected IGF1R gene amplification and that it was correlated with high levels of mRNA and protein expression.
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GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
Abstract
Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow-up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.
GPX3 methylation was identified in 15% myelodysplastic syndrome (MDS) patients, and was associated with adverse prognosis. GPX3 methylation density was significantly increased during the progression from MDS to sAML in follow-up patients.
http://ift.tt/2gn04at
DLL4 overexpression increases gastric cancer stem/progenitor cell self-renewal ability and correlates with poor clinical outcome via Notch-1 signaling pathway activation
Abstract
Gastric cancer is one of the most common malignant diseases, and poses a serious threat to the quality of human life. Gastric cancer stem/progenitor cells (GCSPCs) have critical effects on tumor formation, affecting specific features of self-renewal and differentiation and playing a critical role in metastasis. The Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed. After DLL4 silencing in selected gastric cancer cell lines, the expression of GCSPC markers and colony formation ability were analyzed and the self-renewal and differentiation capacities of the cells were evaluated. The relationship between DLL4 levels and Notch-1 signaling pathway effector amounts was assessed via Western blotting and immunofluorescence. Finally, the tumor formation ability of the gastric cancer cells was evaluated with different levels of DLL4 and multiple cell densities in vivo. Our results indicate that DLL4 expression is associated with TNM stage and cancer metastasis, with high amounts of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal ability of GCSPCs and increased their multidifferentiation capacity, resulting in reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening invasion ability and resistance to 5-FU chemotherapy. In vivo, DLL4 silencing inhibited the tumor formation ability of GCSPCs. In conclusion, DLL4 affects GCSPC stemness, altering their pathological behavior. DLL4 silencing inhibits GCSPC metastatic potential both in vitro and in vivo by impeding Notch-1 signaling pathway activation, indicating that DLL4 may be a new potential therapeutic target.
DLL4 expression is associated with TNM stage and cancer metastasis, with high amounts of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal ability of GCSPCs and increased their multidifferentiation capacity, resulting in reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening invasion ability, and resistance to 5-FU chemotherapy.
http://ift.tt/2gn2pSO
Marijuana use and inpatient outcomes among hospitalized patients: analysis of the nationwide inpatient sample database
Abstract
The purpose of this paper is to examine the relationship between marijuana use and health outcomes among hospitalized patients, including those hospitalized with a diagnosis of cancer. A total of 387,608 current marijuana users were identified based on ICD-9 codes for marijuana use among hospitalized patients in the Nationwide Inpatient Sample database between 2007 and 2011. Logistic regression analysis was performed to determine the association between marijuana use and heart failure, cardiac disease, stroke, and in-hospital mortality. All models were adjusted for age, gender, race, residential income, insurance, residential region, pain, and number of comorbidities. Among hospitalized patients, marijuana use was associated with a 60% increased odds of stroke (OR: 1.60, 95% CI: 1.44–1.77) compared with non-users, but significantly reduced odds of heart failure (OR: 0.78, 95% CI: 0.75–0.82), cardiac disease (OR: 0.86, 95% CI: 0.82–0.91), or in-hospital mortality (OR: 0.41, 95% CI: 0.38–0.44). Among cancer patients, odds of in-hospital mortality was significantly reduced among marijuana users compared with non-users (OR: 0.44, 95% CI: 0.35–0.55). Hospitalized marijuana users were more likely to experience a stroke compared with non-users, but less likely to experience in-hospital mortality. Prospective studies will be needed to better characterize the health effects of marijuana use, especially among older, sicker, and/or hospitalized patients. In the meantime, conversations regarding marijuana use/misuse may be warranted in the clinical setting in order for patients and healthcare providers to adequately weigh the anticipated benefits of marijuana use with potentially significant health risks.
In view of the rapidly increased use of marijuana in the general population. There is significant interest in examining the health effects of marijuana use among adults in general, but more importantly among those with health conditions or chronic diseases. In this study we examined the relationships between marijuana use and health outcomes among hospitalized patients, including hospitalized patients with and without a diagnosis of cancer.
http://ift.tt/2fHGQxY
Does radiotherapy still have a role in unresected biliary tract cancer?
Abstract
The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7–9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1–11.3) months among those who received radiation, conditional on having survived 4 months. In patients who received chemotherapy (n = 1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70–0.97, P = 0.02). In patients who did not receive chemotherapy (n = 1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91–1.30, P = 0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time.
The benefits of radiotherapy for elderly patients with inoperable biliary tract cancer remain unclear due to the lack of randomized data given the rarity of this cancer. Using the SEER-Medicare database, we found that the use of radiotherapy has declined over time, and is influenced by tumor, patient, and socioeconomic factors, and that any survival benefit with radiotherapy is confined to those patients who received concurrent chemotherapy.
http://ift.tt/2gn4m1C
Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting outcome of patients with glioblastoma
Abstract
Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this "cloudy" enhancement during radio-chemotherapy and its impact on patients' progression-free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and with sequences to quantify T1 before radiation, and at 6-week intervals during radio-chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy-enhancing compartment and evaluated the impact of their therapy-related volume change upon PFS. In ∆qT1 maps cloudy-enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy-enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing area of GBM is a new observation which is only visually detectable with qT1-mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio-chemotherapy.
Quantitative T1 subtraction maps uncover a cloudy-enhancing compartment that is not detected in conventional MRI and has prognostic value for patients with glioblastoma.
http://ift.tt/2fHJ1S2