Leukocyte recruitment in preterm and term infants

Abstract

Impaired cellular innate immune defense accounts for susceptibility to sepsis and its high morbidity and mortality in preterm infants. Leukocyte recruitment is an integral part of the cellular immune response and follows a well-defined cascade of events from rolling of leukocytes along the endothelium to firm adhesion and finally transmigration which is concerted by a variety of adhesion molecules. Recent analytical advances such as fetal intravital microscopy have granted new insights into ontogenetic regulation and maturation of fetal immune cell recruitment. Understanding the fetal innate immune system is essential for targeted prevention and therapy of premature infants with severe infections or disorders of the immune system. This review gives an overview of the basic principles of leukocyte recruitment, particularly neutrophil trafficking, and its development during early life and highlights technical limitations to our current knowledge.

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Clinical characteristics of synchronous colorectal cancers in Japan

Abstract

Background

Incidence and clinical characteristics of synchronous colorectal cancer (sCRC) patients significantly vary among studies, likely due to differences in surveillance methodology. If remain undetected, sCRC can progress to more advanced stages seriously aggravating patient prognosis. We studied the incidence and clinicopathological characteristics of Japanese patients with sCRCs who underwent surgery for primary CRC and received exhaustive perioperative surveillance.

Methods

We recruited 1005 patients with surgically resected CRCs between January 2007 and December 2011. The associations of clinical and pathological factors with sCRC development were assessed by univariate and multivariate logistic regression.

Results

Eighty-four patients (8.4 %) developed sCRCs, 16 of them (19.0 %) harboring three or more cancers. Companion sCRCs were smaller and earlier stage than the index lesion (P < 0.0001). In multivariate analysis, advanced age (odds ratio (OR) 1.03 per year; P = 0.009) and left colon tumor location (OR 1.78; P = 0.013) are associated with higher risk of sCRCs, particularly in females. Overall survival did not differ between solitary CRC and sCRC (P = 0.62).

Conclusions

Our results highlight the importance of perioperative colonoscopy examination to ensure the absence of sCRCs that, being small and early staged, are more difficult to detect. The incidence of sCRC, and notably of triple or more sCRCs, was higher than previously recognized. Because they are also significantly higher than expected by merely stochastic accumulation of individual cancerous lesions, we suggest that the occurrence of many sCRC reflects a hitherto uncharacterized predisposition condition.

http://ift.tt/2eoK3oy

Clinical characteristics of synchronous colorectal cancers in Japan

Abstract

Background

Incidence and clinical characteristics of synchronous colorectal cancer (sCRC) patients significantly vary among studies, likely due to differences in surveillance methodology. If remain undetected, sCRC can progress to more advanced stages seriously aggravating patient prognosis. We studied the incidence and clinicopathological characteristics of Japanese patients with sCRCs who underwent surgery for primary CRC and received exhaustive perioperative surveillance.

Methods

We recruited 1005 patients with surgically resected CRCs between January 2007 and December 2011. The associations of clinical and pathological factors with sCRC development were assessed by univariate and multivariate logistic regression.

Results

Eighty-four patients (8.4 %) developed sCRCs, 16 of them (19.0 %) harboring three or more cancers. Companion sCRCs were smaller and earlier stage than the index lesion (P < 0.0001). In multivariate analysis, advanced age (odds ratio (OR) 1.03 per year; P = 0.009) and left colon tumor location (OR 1.78; P = 0.013) are associated with higher risk of sCRCs, particularly in females. Overall survival did not differ between solitary CRC and sCRC (P = 0.62).

Conclusions

Our results highlight the importance of perioperative colonoscopy examination to ensure the absence of sCRCs that, being small and early staged, are more difficult to detect. The incidence of sCRC, and notably of triple or more sCRCs, was higher than previously recognized. Because they are also significantly higher than expected by merely stochastic accumulation of individual cancerous lesions, we suggest that the occurrence of many sCRC reflects a hitherto uncharacterized predisposition condition.

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Preventive services use among female survivors of adolescent and young adult cancer

Abstract

Purpose

Examine preventive services utilization among female survivors of adolescent and young adult (AYA) cancer compared with women without cancer in the USA.

Methods

A total of 1017 women diagnosed with cancer at AYA ages (15–39 years) who were at least 5 years since diagnosis were identified from 2008 to 2012 Medical Expenditure Panel Surveys. A comparison group without cancer was matched on age and other characteristics. General preventive services included dental, medical, blood pressure, and cholesterol checkups, and flu shots in the previous year. Cancer-related services included pap smear and mammography. Preventive services and covariates (demographics, socioeconomics, and health status) were compared between groups using χ ² tests. Ordinal logistic regression identified covariates associated with general preventive services use.

Results

Female survivors reported dental checkups less often (57.8 vs. 72.4 %, p < 0.001) than the comparison group and checked their blood pressure (90 vs. 86.7 %, p = 0.045) and cholesterol (67.5 vs. 61.7 %, p = 0.045) more often. No differences were found in flu shots, medical checkups, and cancer-related services. Survivors without insurance were less likely to use general preventive services (odds ratio [OR] = 0.2, 95 % confidence interval [CI] 0.12–0.35, p < 0.001). Older survivors (OR = 3.09, 95 % CI 1.69–5.62, p < 0.001) and those who speak Spanish or other languages at home (OR = 3.19, 95 % CI 1.33–7.67, p = 0.01) were more likely to use general prevention than their counterparts.

Conclusion

Overall, female survivors were as likely as the comparison group to use preventive services, except dental services, blood pressure, and cholesterol checks.

Implications for Cancer Survivors

Survivors may require support to use recommended preventive services more effectively, especially the younger and uninsured who may be at greater risk for underuse.

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Preventive services use among female survivors of adolescent and young adult cancer

Abstract

Purpose

Examine preventive services utilization among female survivors of adolescent and young adult (AYA) cancer compared with women without cancer in the USA.

Methods

A total of 1017 women diagnosed with cancer at AYA ages (15–39 years) who were at least 5 years since diagnosis were identified from 2008 to 2012 Medical Expenditure Panel Surveys. A comparison group without cancer was matched on age and other characteristics. General preventive services included dental, medical, blood pressure, and cholesterol checkups, and flu shots in the previous year. Cancer-related services included pap smear and mammography. Preventive services and covariates (demographics, socioeconomics, and health status) were compared between groups using χ ² tests. Ordinal logistic regression identified covariates associated with general preventive services use.

Results

Female survivors reported dental checkups less often (57.8 vs. 72.4 %, p < 0.001) than the comparison group and checked their blood pressure (90 vs. 86.7 %, p = 0.045) and cholesterol (67.5 vs. 61.7 %, p = 0.045) more often. No differences were found in flu shots, medical checkups, and cancer-related services. Survivors without insurance were less likely to use general preventive services (odds ratio [OR] = 0.2, 95 % confidence interval [CI] 0.12–0.35, p < 0.001). Older survivors (OR = 3.09, 95 % CI 1.69–5.62, p < 0.001) and those who speak Spanish or other languages at home (OR = 3.19, 95 % CI 1.33–7.67, p = 0.01) were more likely to use general prevention than their counterparts.

Conclusion

Overall, female survivors were as likely as the comparison group to use preventive services, except dental services, blood pressure, and cholesterol checks.

Implications for Cancer Survivors

Survivors may require support to use recommended preventive services more effectively, especially the younger and uninsured who may be at greater risk for underuse.

http://ift.tt/2f1nndk

Important Considerations When Determining the Cost-effectiveness of Viscosupplements in the Treatment of Knee Osteoarthritis: Letter to the Editor regarding Rosen, J., Sancheti, P., Fierlinger, A. et al. Adv Ther (2016) 33: 998. doi:10.1007/s12325-016-0331-8

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Response to: Important Considerations When Determining the Cost-effectiveness of Viscosupplements in the Treatment of Knee Osteoarthritis

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Erratum to: miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma

http://ift.tt/2ehdMM8

The long non-coding RNA maternally expressed gene 3 activates p53 and is downregulated in esophageal squamous cell cancer

Abstract

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor survival. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression; hence, lncRNAs are also involved in the development and progression of ESCC. In this study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression of lncRNA, maternally expressed gene 3 (MEG3) in ESCC. Ectopic expression of MEG3 was performed in ESCC cell lines. Proliferation and apoptosis of ESCC cell lines were analyzed after ectopic expression of MEG3. We found MEG3 was significantly downregulated in ESCC tissues compared with normal tissues by qRT-PCR. Low expression of MEG3 was correlated with lymph node metastasis and advanced TNM stages of ESCC patients and indicated shorter survival (HR = 0.471, 95 % CI 0.234–0.950, P = 0.035), which was confirmed by The Cancer Genome Atlas (TCGA) esophageal cancer dataset. DNA-demethylating agent (5-aza-2-deoxy-cytidine (5-aza-CdR)) treatment significantly increased MEG3 expression level in ESCC cells, and TCGA esophageal cancer dataset also showed that DNA methylation of MEG3 predicted survival. Ectopic expression of MEG3 in ESCC cells inhibited cell proliferation, promoted apoptosis, and suppressed metastasis. Further investigation showed enforced expression of MEG3 activated p53 and its target genes by downregulation of mouse double minute 2 homolog (MDM2). Overall, our study indicated that MEG3 expression loss is common in ESCC and MEG3 could activate p53 and predict prognosis in ESCC.

http://ift.tt/2dDdRvX

Important Considerations When Determining the Cost-effectiveness of Viscosupplements in the Treatment of Knee Osteoarthritis: Letter to the Editor regarding Rosen, J., Sancheti, P., Fierlinger, A. et al. Adv Ther (2016) 33: 998. doi:10.1007/s12325-016-0331-8

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Response to: Important Considerations When Determining the Cost-effectiveness of Viscosupplements in the Treatment of Knee Osteoarthritis

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The long non-coding RNA maternally expressed gene 3 activates p53 and is downregulated in esophageal squamous cell cancer

Abstract

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor survival. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression; hence, lncRNAs are also involved in the development and progression of ESCC. In this study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression of lncRNA, maternally expressed gene 3 (MEG3) in ESCC. Ectopic expression of MEG3 was performed in ESCC cell lines. Proliferation and apoptosis of ESCC cell lines were analyzed after ectopic expression of MEG3. We found MEG3 was significantly downregulated in ESCC tissues compared with normal tissues by qRT-PCR. Low expression of MEG3 was correlated with lymph node metastasis and advanced TNM stages of ESCC patients and indicated shorter survival (HR = 0.471, 95 % CI 0.234–0.950, P = 0.035), which was confirmed by The Cancer Genome Atlas (TCGA) esophageal cancer dataset. DNA-demethylating agent (5-aza-2-deoxy-cytidine (5-aza-CdR)) treatment significantly increased MEG3 expression level in ESCC cells, and TCGA esophageal cancer dataset also showed that DNA methylation of MEG3 predicted survival. Ectopic expression of MEG3 in ESCC cells inhibited cell proliferation, promoted apoptosis, and suppressed metastasis. Further investigation showed enforced expression of MEG3 activated p53 and its target genes by downregulation of mouse double minute 2 homolog (MDM2). Overall, our study indicated that MEG3 expression loss is common in ESCC and MEG3 could activate p53 and predict prognosis in ESCC.

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Erratum to: miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma

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Erratum to: miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma

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The long non-coding RNA maternally expressed gene 3 activates p53 and is downregulated in esophageal squamous cell cancer

Abstract

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor survival. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression; hence, lncRNAs are also involved in the development and progression of ESCC. In this study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to investigate expression of lncRNA, maternally expressed gene 3 (MEG3) in ESCC. Ectopic expression of MEG3 was performed in ESCC cell lines. Proliferation and apoptosis of ESCC cell lines were analyzed after ectopic expression of MEG3. We found MEG3 was significantly downregulated in ESCC tissues compared with normal tissues by qRT-PCR. Low expression of MEG3 was correlated with lymph node metastasis and advanced TNM stages of ESCC patients and indicated shorter survival (HR = 0.471, 95 % CI 0.234–0.950, P = 0.035), which was confirmed by The Cancer Genome Atlas (TCGA) esophageal cancer dataset. DNA-demethylating agent (5-aza-2-deoxy-cytidine (5-aza-CdR)) treatment significantly increased MEG3 expression level in ESCC cells, and TCGA esophageal cancer dataset also showed that DNA methylation of MEG3 predicted survival. Ectopic expression of MEG3 in ESCC cells inhibited cell proliferation, promoted apoptosis, and suppressed metastasis. Further investigation showed enforced expression of MEG3 activated p53 and its target genes by downregulation of mouse double minute 2 homolog (MDM2). Overall, our study indicated that MEG3 expression loss is common in ESCC and MEG3 could activate p53 and predict prognosis in ESCC.

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Resection of falx and parasagittal meningioma: complication avoidance

Abstract

Falx and parasagittal meningiomas are common locations for meningiomas of the cranial vault. Many of these tumors are now discovered incidentally during cranial imaging for other reasons. Therefore, in the calculation of the risks and benefits of surgery it behooves the surgeon to do all he/she can to avoid surgical complications. This is a heavily experience based article based off the senior author's experience with over 1200 intracranial meningiomas. We present three cases to illustrate some of the decision-making and techniques used to reduce complications in the management of these cases treated with an open operation.

http://ift.tt/2eLt0sr

Surgical resection of fourth ventricular ependymomas: case series and technical nuances

Abstract

Ependymomas are rare neuroepithelial tumors which may arise anywhere along the ventricular system. Tumors arising in the fourth ventricle present unique challenges. Complete tumor resection favors prolonged survival, but may result in inadvertent injury of surrounding neural structures—such as cranial nerve (CN) nuclei. Here, our institutional experience with surgical resection of fourth ventricular ependymomas is described. A single institution, retrospective analysis of consecutive case series of adult surgically resected fourth ventricular ependymomas with the bilateral telovelar approach. Extent of resection, outcomes and postoperative complications are statistically analyzed. From January 2000 to April 2016, 22 fourth ventricular ependymomas underwent surgical resection. Gross total resection was achieved in 18 of 22 cases (82 %). There were six postoperative CN palsies—3 lower CN palsies (IX, X, or XI), 1 CN VII palsy, 1 CN IV palsy, and 1 CN VI palsy. No deaths or cerebellar mutism occurred. Two of 6 CN deficits resolved and the rate of permanent neurologic deficit was 18 %. A CN deficit was not statistically associated with prolonged hospital stay or functional outcome. With exception of one patient, all patients functionally improved or remained unchanged following surgery. Postoperative complications included one wound infection (4.5 %) and four pseudomeningoceles (18 %). The rate of shunt-dependent hydrocephalus was 18 %. Tumors adherence to the fourth ventricular floor is not an absolute contraindication for complete resection. Intraoperative neuro-monitoring is essential, and the development of sustained, but not transient CN activity, and/or hemodynamically significant bradycardia should limit the extent of resection.

http://ift.tt/2eofRXZ

Resection of falx and parasagittal meningioma: complication avoidance

Abstract

Falx and parasagittal meningiomas are common locations for meningiomas of the cranial vault. Many of these tumors are now discovered incidentally during cranial imaging for other reasons. Therefore, in the calculation of the risks and benefits of surgery it behooves the surgeon to do all he/she can to avoid surgical complications. This is a heavily experience based article based off the senior author's experience with over 1200 intracranial meningiomas. We present three cases to illustrate some of the decision-making and techniques used to reduce complications in the management of these cases treated with an open operation.

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Surgical resection of fourth ventricular ependymomas: case series and technical nuances

Abstract

Ependymomas are rare neuroepithelial tumors which may arise anywhere along the ventricular system. Tumors arising in the fourth ventricle present unique challenges. Complete tumor resection favors prolonged survival, but may result in inadvertent injury of surrounding neural structures—such as cranial nerve (CN) nuclei. Here, our institutional experience with surgical resection of fourth ventricular ependymomas is described. A single institution, retrospective analysis of consecutive case series of adult surgically resected fourth ventricular ependymomas with the bilateral telovelar approach. Extent of resection, outcomes and postoperative complications are statistically analyzed. From January 2000 to April 2016, 22 fourth ventricular ependymomas underwent surgical resection. Gross total resection was achieved in 18 of 22 cases (82 %). There were six postoperative CN palsies—3 lower CN palsies (IX, X, or XI), 1 CN VII palsy, 1 CN IV palsy, and 1 CN VI palsy. No deaths or cerebellar mutism occurred. Two of 6 CN deficits resolved and the rate of permanent neurologic deficit was 18 %. A CN deficit was not statistically associated with prolonged hospital stay or functional outcome. With exception of one patient, all patients functionally improved or remained unchanged following surgery. Postoperative complications included one wound infection (4.5 %) and four pseudomeningoceles (18 %). The rate of shunt-dependent hydrocephalus was 18 %. Tumors adherence to the fourth ventricular floor is not an absolute contraindication for complete resection. Intraoperative neuro-monitoring is essential, and the development of sustained, but not transient CN activity, and/or hemodynamically significant bradycardia should limit the extent of resection.

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Modern American scurvy — experience with vitamin C deficiency at a large children’s hospital

Abstract

Background

Until recently scurvy has been viewed in developed countries as a disease of the past. More recently there have been reports of case series of children with scurvy who have had a delayed diagnosis after an extensive diagnostic workup that included imaging. Most of these children have had underlying neurologic conditions such as autism.

Objective

To review the medical records of children diagnosed with vitamin C (ascorbic acid) deficiency based on serum ascorbic acid levels at a large pediatric health care system, to determine imaging findings and utility of imaging in management, and to identify at-risk pediatric populations.

Materials and methods

We retrospectively identified cases of vitamin C deficiency in children tested for serum ascorbic acid levels during the last 5 years. We used the criteria of normal ascorbic acid >23 μmol/L and included children with ascorbic acid levels <23 μmol/L. We evaluated their clinical history, underlying medical condition, imaging studies obtained and imaging findings.

Results

We identified 32 children with vitamin C deficiency. All of these children had underlying medical conditions, most commonly iron overload from multiple transfusions related to sickle cell anemia or thalassemia (20), neurologic disorders (4) and bone marrow transplant/chemotherapy (3). No cases of scurvy from dietary deficiency in otherwise normal children were identified. All except two children had multiple imaging studies, primarily related to their underlying conditions. Three of these children had extensive imaging workups related to diffuse musculoskeletal pain. Imaging findings included ill-defined sclerotic and lucent metaphyseal bands (mainly at the knee) on radiography and MRI studies that showed diffuse increased T2-weighted signal in the bilateral lower-extremity long-bone metaphyses, periosteal reaction and adjacent soft-tissue edema.

Conclusion

Vitamin C deficiency is not uncommon in large pediatric health care facilities, and it is frequently missed on clinical evaluation and diagnostic imaging. At-risk populations include those with iron overload, neurologic conditions and history of chemotherapy. Scurvy related to dietary deficiency in otherwise normal children was not encountered. When characteristic MRI findings are seen, particularly in children with a predisposing condition for vitamin C deficiency, scurvy should be considered and a serum ascorbic acid level checked to potentially confirm a diagnosis prior to further invasive tests.

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Modern American scurvy — experience with vitamin C deficiency at a large children’s hospital

Abstract

Background

Until recently scurvy has been viewed in developed countries as a disease of the past. More recently there have been reports of case series of children with scurvy who have had a delayed diagnosis after an extensive diagnostic workup that included imaging. Most of these children have had underlying neurologic conditions such as autism.

Objective

To review the medical records of children diagnosed with vitamin C (ascorbic acid) deficiency based on serum ascorbic acid levels at a large pediatric health care system, to determine imaging findings and utility of imaging in management, and to identify at-risk pediatric populations.

Materials and methods

We retrospectively identified cases of vitamin C deficiency in children tested for serum ascorbic acid levels during the last 5 years. We used the criteria of normal ascorbic acid >23 μmol/L and included children with ascorbic acid levels <23 μmol/L. We evaluated their clinical history, underlying medical condition, imaging studies obtained and imaging findings.

Results

We identified 32 children with vitamin C deficiency. All of these children had underlying medical conditions, most commonly iron overload from multiple transfusions related to sickle cell anemia or thalassemia (20), neurologic disorders (4) and bone marrow transplant/chemotherapy (3). No cases of scurvy from dietary deficiency in otherwise normal children were identified. All except two children had multiple imaging studies, primarily related to their underlying conditions. Three of these children had extensive imaging workups related to diffuse musculoskeletal pain. Imaging findings included ill-defined sclerotic and lucent metaphyseal bands (mainly at the knee) on radiography and MRI studies that showed diffuse increased T2-weighted signal in the bilateral lower-extremity long-bone metaphyses, periosteal reaction and adjacent soft-tissue edema.

Conclusion

Vitamin C deficiency is not uncommon in large pediatric health care facilities, and it is frequently missed on clinical evaluation and diagnostic imaging. At-risk populations include those with iron overload, neurologic conditions and history of chemotherapy. Scurvy related to dietary deficiency in otherwise normal children was not encountered. When characteristic MRI findings are seen, particularly in children with a predisposing condition for vitamin C deficiency, scurvy should be considered and a serum ascorbic acid level checked to potentially confirm a diagnosis prior to further invasive tests.

http://ift.tt/2eLnZAb

Diagnostic yield of cytopathology in evaluating pericardial effusions: Clinicopathologic analysis of 419 specimens

BACKGROUND

Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited.

METHODS

Relevant records of all pericardial effusions from January 2008 to September 2014 were examined and compared with pericardial biopsy results when performed. Discrepant cases were reviewed to determine the cause of the disagreement.

RESULTS

In total, 419 pericardial effusion specimens obtained from 364 patients were examined. Cytologic diagnostic categories included: negative for malignancy (332 specimens; 79%), equivocal (25 specimens; 6%), and positive (62 specimens from 51 patients; 15%). Forty-seven patients who had positive effusions were known to have malignancy. The most common primary malignancies were breast (39.3%) and lung (39.3%) cancers in women and lung cancer (47.4%) in men. A concurrent pericardial biopsy was performed in 46% of patients. Excluding equivocal cytologic diagnoses, cytology and biopsy were concordant in 153 of 173 paired samples (88.4%). The sensitivity of cytology in diagnosing malignancy was 92.1% compared with 55.3% for pericardial biopsy.

CONCLUSIONS

Cytologic examination has significant diagnostic utility in the evaluation of pericardial effusions and exhibits a lower false-negative rate compared with pericardial biopsy. Submission of pericardial biopsy alongside effusion cytology is associated with increased sensitivity for detecting malignancy and may be especially useful in the setting of low-volume pericardial effusion. Cancer Cytopathol 2016. © 2016 American Cancer Society.

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Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution

BACKGROUND

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined.

METHODS

Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013.

RESULTS

Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years.

CONCLUSIONS

To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2016. © 2016 American Cancer Society.

http://ift.tt/2eLlWvY

Diagnostic yield of cytopathology in evaluating pericardial effusions: Clinicopathologic analysis of 419 specimens

BACKGROUND

Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited.

METHODS

Relevant records of all pericardial effusions from January 2008 to September 2014 were examined and compared with pericardial biopsy results when performed. Discrepant cases were reviewed to determine the cause of the disagreement.

RESULTS

In total, 419 pericardial effusion specimens obtained from 364 patients were examined. Cytologic diagnostic categories included: negative for malignancy (332 specimens; 79%), equivocal (25 specimens; 6%), and positive (62 specimens from 51 patients; 15%). Forty-seven patients who had positive effusions were known to have malignancy. The most common primary malignancies were breast (39.3%) and lung (39.3%) cancers in women and lung cancer (47.4%) in men. A concurrent pericardial biopsy was performed in 46% of patients. Excluding equivocal cytologic diagnoses, cytology and biopsy were concordant in 153 of 173 paired samples (88.4%). The sensitivity of cytology in diagnosing malignancy was 92.1% compared with 55.3% for pericardial biopsy.

CONCLUSIONS

Cytologic examination has significant diagnostic utility in the evaluation of pericardial effusions and exhibits a lower false-negative rate compared with pericardial biopsy. Submission of pericardial biopsy alongside effusion cytology is associated with increased sensitivity for detecting malignancy and may be especially useful in the setting of low-volume pericardial effusion. Cancer Cytopathol 2016. © 2016 American Cancer Society.

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Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution

BACKGROUND

The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined.

METHODS

Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013.

RESULTS

Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years.

CONCLUSIONS

To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2016. © 2016 American Cancer Society.

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Spotlight on the relevance of mtDNA in cancer

Abstract

The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer. Cybrid studies support that mtDNA mutations are relevant and exert their effect through a modification of OXPHOS function and ROS production. However, there is still much controversy regarding the clinical relevance of mtDNA mutations. New studies should focus more on OXPHOS dysfunction associated with a specific mutational signature rather than the presence of mutations in the mtDNA.

http://ift.tt/2eomwnA

Spotlight on the relevance of mtDNA in cancer

Abstract

The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer. Cybrid studies support that mtDNA mutations are relevant and exert their effect through a modification of OXPHOS function and ROS production. However, there is still much controversy regarding the clinical relevance of mtDNA mutations. New studies should focus more on OXPHOS dysfunction associated with a specific mutational signature rather than the presence of mutations in the mtDNA.

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Paraneoplastic neurological complications of breast cancer

Abstract

Breast cancer is the most frequent cause of cancer of women in much of the world. In countries with screening programs, breast cancer is often detected before clinical symptoms are apparent, but occasionally the occurrence of a paraneoplastic syndrome precedes the identification of cancer. In breast cancer, there are known to be paraneoplastic endocrine syndromes and neurologic syndromes. The neurologic syndromes are often hard to identify and treat. The neurologic syndromes associated with breast cancer include cerebellar degeneration, sensorimotor neuropathy, retinopathy, stiff-persons syndrome, encephalitis, and opsoclonus–myoclonus. Most of these are mediated by antibodies against known neural antigens, although some cases appear to be mediated by non-humoral mechanisms. Treatments differ depending upon the syndrome type and etiology. Outcomes also vary depending upon duration of disease, the treatments used and the responsiveness of the underlying cancer. A thorough review of the published literature is provided along with recommendations for management and future research.

http://ift.tt/2eLhvkA

Paraneoplastic neurological complications of breast cancer

Abstract

Breast cancer is the most frequent cause of cancer of women in much of the world. In countries with screening programs, breast cancer is often detected before clinical symptoms are apparent, but occasionally the occurrence of a paraneoplastic syndrome precedes the identification of cancer. In breast cancer, there are known to be paraneoplastic endocrine syndromes and neurologic syndromes. The neurologic syndromes are often hard to identify and treat. The neurologic syndromes associated with breast cancer include cerebellar degeneration, sensorimotor neuropathy, retinopathy, stiff-persons syndrome, encephalitis, and opsoclonus–myoclonus. Most of these are mediated by antibodies against known neural antigens, although some cases appear to be mediated by non-humoral mechanisms. Treatments differ depending upon the syndrome type and etiology. Outcomes also vary depending upon duration of disease, the treatments used and the responsiveness of the underlying cancer. A thorough review of the published literature is provided along with recommendations for management and future research.

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Primary aortoduodenal fistula: a rare entity with lethal effects

Primary aortoduodenal fistula (ADF) is a rare but morbid diagnosis. Here, we present the case of a patient with a primary ADF that resulted in mortality. Despite multiple attempts at radiographic and endoscopic diagnosis, the fistula did not declare itself until the patient exsanguinated. Given the morbidity associated with ADF and the imperfection of associated diagnostic studies, a high index of suspicion is required to make a timely diagnosis.

http://ift.tt/2dPxXl1

Lung lobar collapse as the first manifestation of pulmonary epithelioid haemangioendothelioma diagnosed with fibreoptic bronchoscopy

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare tumour of endothelial origin that usually occurs in the lung and liver. It usually presents as bilateral multiple nodular lesions. We report a middle-aged woman with a unique presentation of PEH with lung lobar collapse. The diagnosis was made with fibreoptic bronchoscopy rather than video-assisted thoracoscopy. Clinicians and pathologists should be aware of rare conditions that can present as lung lobar collapse.

http://ift.tt/2eKriWR

Piperacillin-induced mild haemolytic anaemia in a 44-year-old patient with cystic fibrosis

Piperacillin–tazobactam is an antipseudomonal antibiotic frequently used in patients with cystic fibrosis (CF) to treat pulmonary exacerbations. Drug-induced immune haemolytic anaemia is a rare complication during treatment with piperacillin. So far, piperacillin-induced immune haemolytic anaemia (PIHA) is regarded as an acute and severe haemolytic anaemia resulting into life-threatening events. Here we report on a patient with mild PIHA, which did not result in any clinical symptoms or necessity for treatment. To the best of our knowledge, this is the first case report of PIHA without an acute severe haemolytic anaemia. Further research is needed to clarify if this case is a solitary clinical manifestation of PIHA or if mild clinical courses of PIHA might be under-reported. Cases of PIHA have been largely reported in patients with CF. This unequal distribution maybe due to the frequent administration of piperacillin for pulmonary exacerbation in patients with CF or due to CF-related cofactors of yet unknown aetiology.

http://ift.tt/2dPy3Jq

Self-disembowelment during delirium tremens: why early diagnosis is vital

Delirium tremens is a serious yet treatable complication of alcohol withdrawal. Timely diagnosis is critical as there are well-established treatment regimens that provide symptomatic relief within hours to days. We report the case of a 34-year-old man with an undisclosed history of alcohol dependency. He presented with paranoid beliefs and was transferred to a psychiatric inpatient unit with suspected schizophrenia. Classic features of delirium tremens such as sympathetic overdrive and visual hallucinations were not salient features of his presentation. Within 24 hours of admission, he sustained major self-inflicted abdominal stab wounds and extracted a metre of small bowel as a result of command hallucinations. The possibility of delirium tremens was raised by the receiving trauma team and he responded rapidly to benzodiazepines. Emergency jejunal reanastomosis was successful. This case highlights the fact that delirium tremens may present atypically and that associated command hallucinations can confer grave risks.

http://ift.tt/2eKripP

Hoarse voice: a rare presentation of tuberculosis lymphadenitis

A man aged 37 years from Indian descent presented to an inner city London hospital with hoarseness of voice, fatigue, night sweats and a 2 kg weight loss. Laryngoscopy demonstrated a left vocal fold palsy. Extensive investigations were undertaken with disseminated malignancy being primarily investigated. CT/MRI scanning showed non-specific necrotic mediastinal lymph nodes. Tuberculin skin testing, cytology and PCR were eventually undergone. Tests yielded results consistent with tuberculosis (TB) infection and the patient was started on standard TB treatment protocol, with excellent results. TB infection can result in multiple atypical presentations of disease, including hoarseness of voice secondary to vocal cord paralysis. This is a rare but important presentation for community clinician's to consider, especially in populations where TB is epidemiologically thought to be prevalent.

http://ift.tt/2dPvSFE

MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition

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http://ift.tt/2eKsD03

MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition

.


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Recurring Facial Erythema in an Infant

Causes of facial rashes and erythema in infants are many but rarely only happen during feeding times which are commonly and sometimes wrongly attributed to food allergy. There is a rare condition called Auriculotemporal nerve syndrome that is characterized by recurrent episodes of gustatory facial flushing and sweating along the cutaneous distribution of Auriculotemporal nerve: the so-called Frey syndrome. This condition is most frequently observed in adults usually after parotid surgery. It is rare in children and is mostly attributed to forceps assisted delivery. It can also be misinterpreted as food allergy. Here we report a case of an infant with Frey syndrome without any history of perinatal trauma, which was considered initially as food allergy and highlights the importance of distinguishing it from food allergy.

http://ift.tt/2eKNwcJ

Is routine abdominal drainage necessary after liver resection?

Abstract

Purpose

Prophylactic abdominal drainage is performed routinely after liver resection in many centers. The aim of this study was to examine the safety and validity of liver resection without abdominal drainage and to clarify whether routine abdominal drainage after liver resection is necessary.

Methods

Patients who underwent elective liver resection without bilio-enteric anastomosis between July, 2006 and June, 2012 were divided into two groups, based on whether surgery was performed before or after, we adopted the no-drain strategy. The "former group" comprised 256 patients operated on between July, 2006 and June, 2009 and the "latter group" comprised 218 patients operated between July, 2009 and June, 2012. We compared the postoperative complications, percutaneous drainage, and postoperative hospital stay between the groups, retrospectively.

Results

There were no significant differences in the rates of postoperative bleeding, intraabdominal infection, or bile leakage between the groups. Drain insertion after liver resection did not reduce the rate of percutaneous drainage. Postoperative hospital stay was significantly shorter in the latter group.

Conclusion

Routine abdominal drainage is unnecessary after liver resection without bilio-enteric anastomosis.

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Is routine abdominal drainage necessary after liver resection?

Abstract

Purpose

Prophylactic abdominal drainage is performed routinely after liver resection in many centers. The aim of this study was to examine the safety and validity of liver resection without abdominal drainage and to clarify whether routine abdominal drainage after liver resection is necessary.

Methods

Patients who underwent elective liver resection without bilio-enteric anastomosis between July, 2006 and June, 2012 were divided into two groups, based on whether surgery was performed before or after, we adopted the no-drain strategy. The "former group" comprised 256 patients operated on between July, 2006 and June, 2009 and the "latter group" comprised 218 patients operated between July, 2009 and June, 2012. We compared the postoperative complications, percutaneous drainage, and postoperative hospital stay between the groups, retrospectively.

Results

There were no significant differences in the rates of postoperative bleeding, intraabdominal infection, or bile leakage between the groups. Drain insertion after liver resection did not reduce the rate of percutaneous drainage. Postoperative hospital stay was significantly shorter in the latter group.

Conclusion

Routine abdominal drainage is unnecessary after liver resection without bilio-enteric anastomosis.

http://ift.tt/2eDMbod

Corrigendum to “Recurrent Syncope Associated with Lung Cancer”

http://ift.tt/2egxRT5

Functional and therapeutic relevance of hepatocyte growth factor/c-MET signaling in synovial sarcoma

Abstract

Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis and thus novel therapeutic strategies for SS are urgently required. In the present study, we investigated functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS.

Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS.

Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors.

This article is protected by copyright. All rights reserved.

http://ift.tt/2dD2ajT

Functional and therapeutic relevance of hepatocyte growth factor/c-MET signaling in synovial sarcoma

Abstract

Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis and thus novel therapeutic strategies for SS are urgently required. In the present study, we investigated functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS.

Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS.

Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors.

This article is protected by copyright. All rights reserved.

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Chemotherapy decisions and patient experience with the recurrence score assay for early-stage breast cancer

BACKGROUND

The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor–positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making.

METHODS

This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%). Women reported chemotherapy recommendations, the receipt of chemotherapy, testing experiences, and decision satisfaction. Registries linked the tumor data, RS, and surveys. Regression models examined factors associated with chemotherapy recommendations and receipt by the RS and subgroups.

RESULTS

There were 1527 patients with stage I/II, estrogen receptor/progesterone receptor–positive, human epidermal growth factor 2–negative disease: 778 received an RS (62.6% of patients with node-negative, favorable disease, 24.3% of patients with node-negative, unfavorable disease, and 13.0% of patients with node-positive disease; P < .001). Overall, 47.2% of the patients received a recommendation against chemotherapy, and 40.5% received a recommendation for it. RS results correlated with recommendations: nearly all patients with high scores (31-100) received a chemotherapy recommendation (86.9%-96.5% across clinical subgroups), whereas the majority of the patients with low-risk results (0-18) received a recommendation against it (65.9%-78.2% across subgroups). Most patients with high RSs received chemotherapy (87.0%, 91.1%, and 100% across subgroups), whereas few patients with low scores received it (2.9%, 9.5%, and 26.6% across subgroups). There were no substantial racial/ethnic differences in testing or treatment. Women were largely satisfied with the RS and chemotherapy decisions.

CONCLUSIONS

Oncologists use the RS to personalize treatment, even for those with node-positive disease. High satisfaction and an absence of disparities in testing and treatment suggest that precision-medicine advances have improved systemic breast cancer treatment. Cancer 2016. © 2016 American Cancer Society.

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Chemotherapy decisions and patient experience with the recurrence score assay for early-stage breast cancer

BACKGROUND

The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor–positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making.

METHODS

This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%). Women reported chemotherapy recommendations, the receipt of chemotherapy, testing experiences, and decision satisfaction. Registries linked the tumor data, RS, and surveys. Regression models examined factors associated with chemotherapy recommendations and receipt by the RS and subgroups.

RESULTS

There were 1527 patients with stage I/II, estrogen receptor/progesterone receptor–positive, human epidermal growth factor 2–negative disease: 778 received an RS (62.6% of patients with node-negative, favorable disease, 24.3% of patients with node-negative, unfavorable disease, and 13.0% of patients with node-positive disease; P < .001). Overall, 47.2% of the patients received a recommendation against chemotherapy, and 40.5% received a recommendation for it. RS results correlated with recommendations: nearly all patients with high scores (31-100) received a chemotherapy recommendation (86.9%-96.5% across clinical subgroups), whereas the majority of the patients with low-risk results (0-18) received a recommendation against it (65.9%-78.2% across subgroups). Most patients with high RSs received chemotherapy (87.0%, 91.1%, and 100% across subgroups), whereas few patients with low scores received it (2.9%, 9.5%, and 26.6% across subgroups). There were no substantial racial/ethnic differences in testing or treatment. Women were largely satisfied with the RS and chemotherapy decisions.

CONCLUSIONS

Oncologists use the RS to personalize treatment, even for those with node-positive disease. High satisfaction and an absence of disparities in testing and treatment suggest that precision-medicine advances have improved systemic breast cancer treatment. Cancer 2016. © 2016 American Cancer Society.

http://ift.tt/2exVwSm

Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells

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SUSD2 expression in high-grade serous ovarian cancer correlates with increased patient survival and defective mesothelial clearance

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GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth

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Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells

http://ift.tt/2e3GjTJ

SUSD2 expression in high-grade serous ovarian cancer correlates with increased patient survival and defective mesothelial clearance

http://ift.tt/2e3G8bh

GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth

http://ift.tt/2e3F338

Minimally Invasive Treatment of Mirizzi Syndrome, a Rare Cause of Cholestasis in Childhood

Mirizzi syndrome is the compressive blockage of the cystic or choledochal duct caused by a biliary stone occupying the cystic canal or Hartmann's pouch. This occurrence is rare and, in English literature, three cases defined in children have been observed. In order to draw attention to this rare occurrence, we preferred a 14-year-old male patient with Mirizzi syndrome. In this case, ERCP was performed preoperatively and the diagnosis was carried out with the help of clear visualisation and identification of the tissue structures as well as the stent placed in bile duct; so we protected the patient from the possible iatrogenic injury occurring during surgery.

http://ift.tt/2e2UmsP

MiR-17-5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21

Abstract

MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay. A nude mice xenograft model was used to verify the tumor growth in vivo. MiR-17-5p was overexpressed, whereas the expression of p21 was downregulated in NPC cell lines and tissues. The miR-17-5p expression level was inversely correlated with the p21 mRNA level in NPC samples. Furthermore, analysis of 2^−ΔΔCt value in 81 NPC patients suggested that the elevated expression level of miR-17-5p or the downregulated expression level of p21 was significantly correlated with tumor size (T classification) and tumor stage, and Kaplan–Meier survival analysis revealed a correlation between miR-17-5p or p21 expression level and overall survival times in 81 NPC patients. MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of NPC and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of nasopharyngeal carcinoma (NPC) and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

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Positioning of second-line treatment for advanced gastric and gastroesophageal junction adenocarcinoma

Abstract

Tumors of the upper gastrointestinal tract are increasing in incidence; yet, approaches to the treatment of advanced gastric and/or gastroesophageal junction cancer vary widely, with no internationally agreed first-line regimens. Recent clinical trials have shown that second-line treatment is now possible for selected patients with advanced disease, and current data suggest that the combination of ramucirumab plus paclitaxel may become a standard of care in the second-line setting for metastatic gastric cancer. Several prognostic factors have been identified for overall survival in the second-line setting; this emphasizes the need for careful sequencing of all treatments to ensure that individual patients receive optimum care. This article reviews published data on the treatment of advanced gastric cancer, with a particular emphasis on second-line chemotherapy, and suggests treatment sequences based on current understanding.

The possibility of effective second-line treatment for patients with advanced gastric cancer increases the need for careful decision-making in first-line therapy. Treatment sequencing should be based on current evidence and should aim to improve the chances of benefit from second-line treatment.

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Touch imprint cytology with massively parallel sequencing (TIC-seq): a simple and rapid method to snapshot genetic alterations in tumors

Abstract

Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors. We prepared FFPE tissues and TIC specimens from tumors in nine lung cancer patients and one patient with breast cancer. We found that the quality and quantity of TIC DNA was higher than that of FFPE DNA, which requires microdissection to enrich DNA from target tissues. Targeted sequencing using a next-generation sequencer obtained sufficient sequence data using TIC DNA. Most (92%) somatic mutations in lung primary tumors were found to be consistent between TIC and FFPE DNA. We also applied TIC DNA to primary and metastatic tumor tissues to analyze tumor heterogeneity in a breast cancer patient, and showed that common and distinct mutations among primary and metastatic sites could be classified into two distinct histological subtypes. TIC-seq is an alternative and feasible method to analyze genomic alterations in tumors by simply touching the cut surface of specimens to slides.

In this study, we evaluated touch imprint cytology with massively parallel sequencing (touch imprint cytology [TIC]-seq) as an improved method for the genetic analysis of cancer patients. Our findings provide clear evidence that TIC-seq is a more robust and efficient method than FFPE-derived DNA analysis for the detection of somatic mutations in cancer, and capture intratumoral heterogeneity among primary and metastatic sites. TIC-seq has potential application for small-volume samples obtained by a number of standard clinical approaches, thus enabling more rapid diagnosis and treatment.

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Progress in the clinical detection of heterogeneity in breast cancer

Abstract

Breast cancer is currently the most common form of cancer and the second-leading cause of death from cancer in women. Though considerable progress has been made in the treatment of breast cancer, the heterogeneity of tumors (both inter- and intratumor) remains a considerable diagnostic and prognostic challenge. From clinical observation to genetic mutations, the history of understanding the heterogeneity of breast cancer is lengthy and detailed. Effectively detecting heterogeneity in breast cancer is important during treatment. Various methods of depicting this heterogeneity are now available and include genetic, pathologic, and imaging analysis. These methods allow characterization of the heterogeneity of breast cancer on a genetic level, providing greater insight during the process of establishing an effective therapeutic plan. This study reviews how the understanding of tumor heterogeneity in breast cancer evolved, and further summarizes recent advances in the detection and monitoring of this heterogeneity in patients with breast cancer.

We summarized recent progress in clinical detection of breast cancer heterogeneity from different level (including genes, cells and tissues, and clinical features).

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via IFTTT

MiR-17-5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21

Abstract

MicroRNAs (miRNAs) may act as either tumor suppressors or oncogenes in various types of cancers. Previous studies have indicated that miR-17-5p is involved in the initiation and development of human tumors. However, its mechanism and function in nasopharyngeal carcinoma (NPC) remain largely unclear. In this study, we evaluated the expression profiles of miR-17-5p and p21 in NPC cell lines and tissues by quantitative real-time PCR (qRT-PCR). For the analysis, we have established a stable overexpression or depletion of miR-17-5p NPC cell lines for analyzing the effects of cell proliferation by MTT, colony formation, and cell cycle assay. A nude mice xenograft model was used to verify the tumor growth in vivo. MiR-17-5p was overexpressed, whereas the expression of p21 was downregulated in NPC cell lines and tissues. The miR-17-5p expression level was inversely correlated with the p21 mRNA level in NPC samples. Furthermore, analysis of 2^−ΔΔCt value in 81 NPC patients suggested that the elevated expression level of miR-17-5p or the downregulated expression level of p21 was significantly correlated with tumor size (T classification) and tumor stage, and Kaplan–Meier survival analysis revealed a correlation between miR-17-5p or p21 expression level and overall survival times in 81 NPC patients. MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of NPC and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

MiR-17-5p promoted cell growth in vivo and in vitro by directly targeting p21. Our results indicate that miR-17-5p can promote the occurrence of nasopharyngeal carcinoma (NPC) and it may serve as a potential novel diagnostic maker or therapeutic target for NPC in the future.

http://ift.tt/2eJMVaU

Positioning of second-line treatment for advanced gastric and gastroesophageal junction adenocarcinoma

Abstract

Tumors of the upper gastrointestinal tract are increasing in incidence; yet, approaches to the treatment of advanced gastric and/or gastroesophageal junction cancer vary widely, with no internationally agreed first-line regimens. Recent clinical trials have shown that second-line treatment is now possible for selected patients with advanced disease, and current data suggest that the combination of ramucirumab plus paclitaxel may become a standard of care in the second-line setting for metastatic gastric cancer. Several prognostic factors have been identified for overall survival in the second-line setting; this emphasizes the need for careful sequencing of all treatments to ensure that individual patients receive optimum care. This article reviews published data on the treatment of advanced gastric cancer, with a particular emphasis on second-line chemotherapy, and suggests treatment sequences based on current understanding.

The possibility of effective second-line treatment for patients with advanced gastric cancer increases the need for careful decision-making in first-line therapy. Treatment sequencing should be based on current evidence and should aim to improve the chances of benefit from second-line treatment.

http://ift.tt/2emy7B4

Touch imprint cytology with massively parallel sequencing (TIC-seq): a simple and rapid method to snapshot genetic alterations in tumors

Abstract

Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors. We prepared FFPE tissues and TIC specimens from tumors in nine lung cancer patients and one patient with breast cancer. We found that the quality and quantity of TIC DNA was higher than that of FFPE DNA, which requires microdissection to enrich DNA from target tissues. Targeted sequencing using a next-generation sequencer obtained sufficient sequence data using TIC DNA. Most (92%) somatic mutations in lung primary tumors were found to be consistent between TIC and FFPE DNA. We also applied TIC DNA to primary and metastatic tumor tissues to analyze tumor heterogeneity in a breast cancer patient, and showed that common and distinct mutations among primary and metastatic sites could be classified into two distinct histological subtypes. TIC-seq is an alternative and feasible method to analyze genomic alterations in tumors by simply touching the cut surface of specimens to slides.

In this study, we evaluated touch imprint cytology with massively parallel sequencing (touch imprint cytology [TIC]-seq) as an improved method for the genetic analysis of cancer patients. Our findings provide clear evidence that TIC-seq is a more robust and efficient method than FFPE-derived DNA analysis for the detection of somatic mutations in cancer, and capture intratumoral heterogeneity among primary and metastatic sites. TIC-seq has potential application for small-volume samples obtained by a number of standard clinical approaches, thus enabling more rapid diagnosis and treatment.

http://ift.tt/2eJLgSL

Progress in the clinical detection of heterogeneity in breast cancer

Abstract

Breast cancer is currently the most common form of cancer and the second-leading cause of death from cancer in women. Though considerable progress has been made in the treatment of breast cancer, the heterogeneity of tumors (both inter- and intratumor) remains a considerable diagnostic and prognostic challenge. From clinical observation to genetic mutations, the history of understanding the heterogeneity of breast cancer is lengthy and detailed. Effectively detecting heterogeneity in breast cancer is important during treatment. Various methods of depicting this heterogeneity are now available and include genetic, pathologic, and imaging analysis. These methods allow characterization of the heterogeneity of breast cancer on a genetic level, providing greater insight during the process of establishing an effective therapeutic plan. This study reviews how the understanding of tumor heterogeneity in breast cancer evolved, and further summarizes recent advances in the detection and monitoring of this heterogeneity in patients with breast cancer.

We summarized recent progress in clinical detection of breast cancer heterogeneity from different level (including genes, cells and tissues, and clinical features).

http://ift.tt/2emvlvC