Assessing Key Stakeholders’ Knowledge, Needs, and Preferences for Head and Neck Cancer Survivorship Care Plans

Abstract

Cancer survivorship care plans (SCPs) are endorsed to support quality care for cancer survivors, but uptake is slow. We assessed knowledge, needs, and preferences for SCP content and delivery from a wide variety of stakeholders. We focused SCP content for head and neck cancer as it is a disease prone to long-term side effects requiring management from multiple providers. We conducted telephone-based, qualitative interviews. We purposively sampled head and neck cancer survivors (n = 4), primary care physicians in the community (n = 5), and providers affiliated with a large academic medical center (n = 5) who treat head and neck cancer, cancer specialists (n = 6), and nurse practitioners/supportive care staff (n = 5). Interviews were recorded, transcribed, and analyzed using direct content analysis. Few participants reported personal experience with SCPs, but most supported the concept. Several key themes emerged: (1) perceived ambiguity regarding roles and responsibilities for SCPs, (2) a need to tailor the content and language based on the intended recipient, (3) documentation process should be as automated and streamlined as possible, (4) concerns about using the SCP to coordinate with outside providers, and (5) that SCPs would have added value as a "living document." We also report SCP-related issues that are unique to serving patients diagnosed with head and neck cancer. Effort is needed to tailor SCPs for different recipients and optimize their potential for successful implementation, impact on care outcomes, and sustainability. Many cancer survivors may not receive a SCP as part of routine care. Survivors could engage their health care team by requesting a SCP.

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Assessing Key Stakeholders’ Knowledge, Needs, and Preferences for Head and Neck Cancer Survivorship Care Plans

Abstract

Cancer survivorship care plans (SCPs) are endorsed to support quality care for cancer survivors, but uptake is slow. We assessed knowledge, needs, and preferences for SCP content and delivery from a wide variety of stakeholders. We focused SCP content for head and neck cancer as it is a disease prone to long-term side effects requiring management from multiple providers. We conducted telephone-based, qualitative interviews. We purposively sampled head and neck cancer survivors (n = 4), primary care physicians in the community (n = 5), and providers affiliated with a large academic medical center (n = 5) who treat head and neck cancer, cancer specialists (n = 6), and nurse practitioners/supportive care staff (n = 5). Interviews were recorded, transcribed, and analyzed using direct content analysis. Few participants reported personal experience with SCPs, but most supported the concept. Several key themes emerged: (1) perceived ambiguity regarding roles and responsibilities for SCPs, (2) a need to tailor the content and language based on the intended recipient, (3) documentation process should be as automated and streamlined as possible, (4) concerns about using the SCP to coordinate with outside providers, and (5) that SCPs would have added value as a "living document." We also report SCP-related issues that are unique to serving patients diagnosed with head and neck cancer. Effort is needed to tailor SCPs for different recipients and optimize their potential for successful implementation, impact on care outcomes, and sustainability. Many cancer survivors may not receive a SCP as part of routine care. Survivors could engage their health care team by requesting a SCP.

http://ift.tt/2IeJVlo

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

http://ift.tt/2txSuV0

Reducing X-Ray imaging for proton postmastectomy chest-wall patients

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Estelle Batin, Nicolas Depauw, Rachel B. Jimenez, Shannon MacDonald, Hsiao-Ming Lu




http://ift.tt/2oWTZrm

Renal Cell Carcinoma Brain Metastasis with Pseudoprogression and Radiation Necrosis on Nivolumab after previous treatment with Stereotactic Radiosurgery: an Illustrative Case Report and Review of the Literature

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Gary D. Lewis, Eric Jonasch, Amishi Shah, Gregory N. Fuller, Andrew M. Farach, E. Brian Butler, Bin S. Teh




http://ift.tt/2DiNC5I

Reducing X-Ray imaging for proton postmastectomy chest-wall patients

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Estelle Batin, Nicolas Depauw, Rachel B. Jimenez, Shannon MacDonald, Hsiao-Ming Lu




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Renal Cell Carcinoma Brain Metastasis with Pseudoprogression and Radiation Necrosis on Nivolumab after previous treatment with Stereotactic Radiosurgery: an Illustrative Case Report and Review of the Literature

Publication date: Available online 10 March 2018
Source:Practical Radiation Oncology
Author(s): Gary D. Lewis, Eric Jonasch, Amishi Shah, Gregory N. Fuller, Andrew M. Farach, E. Brian Butler, Bin S. Teh




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Use of extracranial radiation therapy in metastatic melanoma patients receiving immunotherapy

Explore the patterns of use of extracranial radiation therapy (RT) in metastatic melanoma patients receiving immunotherapy, its potential association with OS, the impact of the site and timing of RT on clinical outcomes when combined with immunotherapy.

http://ift.tt/2p98FTB

Dose dependence of accelerated repopulation in head and neck cancer: Supporting evidence and clinical implications

Accelerated repopulation (AR) can compromise tumor control after conventional radiotherapy for fast-growing tumors. Standard AR models assume it begins at a fixed time, with repopulation rates independent of the number of clonogens killed. We investigate the validity and significance of an alternative model where onset-time and rate of AR depend on the number of clonogens killed, and thus on dose and dose-fractionation.

http://ift.tt/2IkiZRd

Disparities in Oral Cancer Awareness: a Population Survey in Tehran, Iran

Abstract

Oral cancer is a life-threatening disease with low survival rates, especially when diagnosed in an advanced stage. Lack of awareness about this cancer among the population is proposed as a possible reason for this diagnostic delay. The aim of this study was to evaluate oral cancer awareness, as well as the association of this with sociodemographic status in Tehran. In this cross-sectional population-based survey, 1800 self-administered questionnaires (collecting sociodemographic data, questions regarding oral cancer awareness and the source of information) were distributed through multistage stratified random sampling. Scores for questions ranged from 0 to 4, and totals were summed. The outcome of question responses was also analyzed separately. In total, 1312 questionnaires were available for analysis, from 788 females and 489 males (37.8 ± 9.02 years). Only 30% of the respondents were aware of oral cancer. The average score for awareness was 1.09 ± 1.6 with no significant differences between age groups and genders. Almost 6.5% of participants had complete awareness about oral cancer. A significant difference was found between mean scores in different levels of education and occupation (p = 0.0001). From 585 responses to the "source of information" question, "public media" was the most important source (almost 50%). Only 2% mentioned "dentists" as a source of information. This study indicated an alarming lack of oral cancer awareness and literacy in Tehran, Iran. Dentists should be obliged to practice their pivotal role in informing the public about oral cancer.

http://ift.tt/2tyZh0J

Disparities in Oral Cancer Awareness: a Population Survey in Tehran, Iran

Abstract

Oral cancer is a life-threatening disease with low survival rates, especially when diagnosed in an advanced stage. Lack of awareness about this cancer among the population is proposed as a possible reason for this diagnostic delay. The aim of this study was to evaluate oral cancer awareness, as well as the association of this with sociodemographic status in Tehran. In this cross-sectional population-based survey, 1800 self-administered questionnaires (collecting sociodemographic data, questions regarding oral cancer awareness and the source of information) were distributed through multistage stratified random sampling. Scores for questions ranged from 0 to 4, and totals were summed. The outcome of question responses was also analyzed separately. In total, 1312 questionnaires were available for analysis, from 788 females and 489 males (37.8 ± 9.02 years). Only 30% of the respondents were aware of oral cancer. The average score for awareness was 1.09 ± 1.6 with no significant differences between age groups and genders. Almost 6.5% of participants had complete awareness about oral cancer. A significant difference was found between mean scores in different levels of education and occupation (p = 0.0001). From 585 responses to the "source of information" question, "public media" was the most important source (almost 50%). Only 2% mentioned "dentists" as a source of information. This study indicated an alarming lack of oral cancer awareness and literacy in Tehran, Iran. Dentists should be obliged to practice their pivotal role in informing the public about oral cancer.

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The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: a classic and Bayesian meta-analysis

Publication date: Available online 9 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Domenico Ciliberto, Nicoletta Staropoli, Francesca Caglioti, Silvia Chiellino, Antonella Ierardi, Rossana Ingargiola, Cirino Botta, Mariamena Arbitrio, Pierpaolo Correale, Pierfrancesco Tassone, Pierosandro Tagliaferri
BackgroundAt present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients.MethodsA systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled using the random-effect model for pair-wise meta-analyses and bayesan model for network meta-analysis (NMA).ResultsEight studies with a total of 2518 individuals were included in the meta-analyses. Pooled analyses for subgroups stratified by type of schedule and tumor location demonstrated that anti-EGFR + doublet had the best OS when compared to doublet ± bevacizumab (0.767; 95%CI, 0.695–0.846; P < .0001). This benefit is limited to LSCC when compared to a doublet-based schedule and doublet + bevacizumab (HRs, 0.692; 95%CI, 0.596–0.804; P < .001; 0.706; 95%CI, 0.584–0.854; P < .001; respectively). No significant differences are detected in PFS, whereas the cetuximab-based regimens showed the highest ORR and TR. In NMA our ranking showed the best performance for FOLFOX + panitumumab.ConclusionsOur study indicates that FOLFOX + panitumumab has the major probability to provide an improvement of survival with a good safety profile in patients with RAS WT mCRC with an added value from selection based on sidedness.



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The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: a classic and Bayesian meta-analysis

Publication date: Available online 9 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Domenico Ciliberto, Nicoletta Staropoli, Francesca Caglioti, Silvia Chiellino, Antonella Ierardi, Rossana Ingargiola, Cirino Botta, Mariamena Arbitrio, Pierpaolo Correale, Pierfrancesco Tassone, Pierosandro Tagliaferri
BackgroundAt present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients.MethodsA systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled using the random-effect model for pair-wise meta-analyses and bayesan model for network meta-analysis (NMA).ResultsEight studies with a total of 2518 individuals were included in the meta-analyses. Pooled analyses for subgroups stratified by type of schedule and tumor location demonstrated that anti-EGFR + doublet had the best OS when compared to doublet ± bevacizumab (0.767; 95%CI, 0.695–0.846; P < .0001). This benefit is limited to LSCC when compared to a doublet-based schedule and doublet + bevacizumab (HRs, 0.692; 95%CI, 0.596–0.804; P < .001; 0.706; 95%CI, 0.584–0.854; P < .001; respectively). No significant differences are detected in PFS, whereas the cetuximab-based regimens showed the highest ORR and TR. In NMA our ranking showed the best performance for FOLFOX + panitumumab.ConclusionsOur study indicates that FOLFOX + panitumumab has the major probability to provide an improvement of survival with a good safety profile in patients with RAS WT mCRC with an added value from selection based on sidedness.



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Réirradiation des tumeurs de la tête et du cou : volumes cibles, évolutions techniques et perspectives

Publication date: Available online 7 February 2018
Source:Cancer/Radiothérapie
Author(s): R. Kinj, K. Bénézery, C. Florescu, B. Gery, J.L. Habrand, J. Thariat
Les tumeurs malignes de la tête et du cou ont un profil de récidive avant tout locorégional, la plupart des décès résultent de cette progression. L'optimisation de la réirradiation en situation de récidive, est un objectif majeur pour ces patients. Une recherche extensive a été réalisée à l'aide du moteur de recherche PubMed pour retrouver les publications traitant de cette thématique. Les premiers essais de réirradiation de la sphère ORL remontent aux années 1980 et les premiers par radiothérapie conformationnelle avec modulation d'intensité (RCMI) à la fin des années 1990. Comparée à la radiothérapie conformationnelle tridimensionnelle, la modulation d'intensité améliore les résultats cliniques et réduit la toxicité. Dans les séries de RCMI, associées ou non à une chimiothérapie concomitante, le taux de contrôle locorégional obtenu à 2 ans était de l'ordre de 45 à 65 % et celui de survie globale de 15 à 60 % selon les facteurs pronostiques. La survenue de toxicité aiguë de grade 3 était de l'ordre de 10 à 30 % des cas et celle de toxicité tardive de grade 3 de l'ordre de 15 à 50 %. Dans une population sélectionnée à faible volume tumoral, une réirradiation stéréotaxique de dose minimale de 35Gy donnait des résultats du même ordre qu'après RCMI. La réirradiation de tumeurs ORL par protons est encore peu évaluée du fait d'une accessibilité réduite à la technique. Le taux de toxicité semble inférieur à celui habituellement constaté après traitement par photons. Cependant, nous ne disposons pas d'un suivi assez long. Cette technique reste réservée aux protocoles de recherche et représente une perspective d'avenir dans ces situations.Malignant tumors of the head and neck have a predominantly regional recurrence pattern, with most deaths resulting from this progression. Optimization of re-radiation in recurrence setting is a major objective for these patients. Extensive research has been carried out with the PubMed search engine to find publications dealing with this topic. The first attempts to reirradiate the ORL sphere date back to the 1980s and the first to be performed by intensity modulation conformational radiotherapy (IMRT) date back to the late 1990s. Compared to 3 dimensional conformal radiotherapy, IMRT improves clinical outcomes and reduces toxicity. In IMRT series, associated or not with concomitant chemotherapy, the locoregional control obtained at 2 years was of the order of 45 to 65% and the overall survival of 15 to 60%, depending on predictive factors. Grade 3 acute toxicity occurred on the order of 10 to 30% and late-grade 3 toxicity on the order of 15 to 50%. In a selected population with low volumes tumors, stereotactic re-irradiation at a minimum dose of 35Gy obtained outcome comparable to IMRT. Re-irradiation of head and neck tumors by proton therapy is rare. The toxicity rate appears to be lower than that usually seen after photon therapy. However, we do not have a long follow-up. This technique therefore remains reserved for search protocols and represents a future perspective in these situations.



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Réirradiation des tumeurs de la tête et du cou : volumes cibles, évolutions techniques et perspectives

Publication date: Available online 7 February 2018
Source:Cancer/Radiothérapie
Author(s): R. Kinj, K. Bénézery, C. Florescu, B. Gery, J.L. Habrand, J. Thariat
Les tumeurs malignes de la tête et du cou ont un profil de récidive avant tout locorégional, la plupart des décès résultent de cette progression. L'optimisation de la réirradiation en situation de récidive, est un objectif majeur pour ces patients. Une recherche extensive a été réalisée à l'aide du moteur de recherche PubMed pour retrouver les publications traitant de cette thématique. Les premiers essais de réirradiation de la sphère ORL remontent aux années 1980 et les premiers par radiothérapie conformationnelle avec modulation d'intensité (RCMI) à la fin des années 1990. Comparée à la radiothérapie conformationnelle tridimensionnelle, la modulation d'intensité améliore les résultats cliniques et réduit la toxicité. Dans les séries de RCMI, associées ou non à une chimiothérapie concomitante, le taux de contrôle locorégional obtenu à 2 ans était de l'ordre de 45 à 65 % et celui de survie globale de 15 à 60 % selon les facteurs pronostiques. La survenue de toxicité aiguë de grade 3 était de l'ordre de 10 à 30 % des cas et celle de toxicité tardive de grade 3 de l'ordre de 15 à 50 %. Dans une population sélectionnée à faible volume tumoral, une réirradiation stéréotaxique de dose minimale de 35Gy donnait des résultats du même ordre qu'après RCMI. La réirradiation de tumeurs ORL par protons est encore peu évaluée du fait d'une accessibilité réduite à la technique. Le taux de toxicité semble inférieur à celui habituellement constaté après traitement par photons. Cependant, nous ne disposons pas d'un suivi assez long. Cette technique reste réservée aux protocoles de recherche et représente une perspective d'avenir dans ces situations.Malignant tumors of the head and neck have a predominantly regional recurrence pattern, with most deaths resulting from this progression. Optimization of re-radiation in recurrence setting is a major objective for these patients. Extensive research has been carried out with the PubMed search engine to find publications dealing with this topic. The first attempts to reirradiate the ORL sphere date back to the 1980s and the first to be performed by intensity modulation conformational radiotherapy (IMRT) date back to the late 1990s. Compared to 3 dimensional conformal radiotherapy, IMRT improves clinical outcomes and reduces toxicity. In IMRT series, associated or not with concomitant chemotherapy, the locoregional control obtained at 2 years was of the order of 45 to 65% and the overall survival of 15 to 60%, depending on predictive factors. Grade 3 acute toxicity occurred on the order of 10 to 30% and late-grade 3 toxicity on the order of 15 to 50%. In a selected population with low volumes tumors, stereotactic re-irradiation at a minimum dose of 35Gy obtained outcome comparable to IMRT. Re-irradiation of head and neck tumors by proton therapy is rare. The toxicity rate appears to be lower than that usually seen after photon therapy. However, we do not have a long follow-up. This technique therefore remains reserved for search protocols and represents a future perspective in these situations.



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Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis.

Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis.

Curr Cancer Drug Targets. 2018 Mar 08;:

Authors: Passiglia F, Rizzo S, Rolfo C, Galvano A, Bronte E, Incorvaia L, Listi A, Barraco N, Castiglia M, Calo V, Bazan V, Russo A

Abstract
BACKGROUND: Recent studies evaluated the diagnostic accuracy of circulating tumor DNA (ctDNA) in the detection of epidermal growth factor receptor (EGFR) mutations from plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue genotyping. However it is less clear if the location of metastatic site may influence the ability to identify EGFR mutations in plasma.
OBJECTIVE: This pooled analysis aims to evaluate the association between the metastatic site location and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients.
METHODS: Data from all published studies, evaluating the sensitivity of plasma-based EGFR-mutation testing, stratified by metastatic site location (extrathoracic (M1b) vs intrathoracic (M1a)) were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the ctDNA analysis sensitivity, according to metastatic site location.
RESULTS: A total of ten studies, with 1425 patients, were eligible. Pooled analysis showed that the sensitivity of ctDNA-based EGFR-mutation testing is significantly higher in patients with M1b vs M1a disease (OR: 5.09; 95% CIs: 2.93 - 8.84). A significant association was observed for both EGFR-activating (OR: 4.30, 95% CI: 2.35-7.88) and resistant T790M mutations (OR: 11.89, 95% CI: 1.45-97.22), regardless of the use of digital-PCR (OR: 5.85, 95% CI: 3.56-9.60) or non-digital PCR technologies (OR: 2.96, 95% CI: 2.24-3.91).
CONCLUSIONS: These data suggest that the location of metastatic sites significantly influences the diagnostic accuracy of ctDNA analysis in detecting EGFR mutations in NSCLC patients.

PMID: 29521235 [PubMed - as supplied by publisher]

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Noxa: Role in Cancer Pathogenesis and Treatment.

Noxa: Role in Cancer Pathogenesis and Treatment.

Curr Cancer Drug Targets. 2018 Mar 07;:

Authors: Morsi RZ, Hage-Sleiman R, Kobeissy H, Dbaibo G

Abstract
The B-cell lymphoma 2 (Bcl-2) family proteins play an important role in regulating apoptosis, or programmed cell death, in response to several extracellular and intracellular signals. These proteins are either pro-apoptotic or anti-apoptotic. The pro-apoptotic Noxa is a Bcl-2 family protein that belongs to a subclass of BH3-only proteins. Noxa induces apoptosis via p53-dependent and/or p53-independent mechanisms. While Noxa may play a limited role in apoptosis, it is a crucial player that interacts with several proteins in the apoptosis pathway, highlighting its importance in the pathogenesis and treatment of certain cancers. In this review, we will elucidate the mechanisms by which Noxa regulates apoptosis and review the roles of chemotherapeutic drugs in relation to Noxa.

PMID: 29521234 [PubMed - as supplied by publisher]

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Parp Inhibitors for the Treatment of Ovarian Cancer.

Parp Inhibitors for the Treatment of Ovarian Cancer.

Curr Cancer Drug Targets. 2018 Mar 07;:

Authors: Cortesi L, Toss A, Cucinotto I

Abstract
The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer. Mutations in one of the BRCA genes result in impaired homologous-recombination DNA repair, which causes genetic abnormalities that promote carcinogenesis. Interestingly, this defect has been exploited by the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors to provide specific cancer cell cytotoxicity. Particularly, the inhibition of PARP in BRCA-mutation carriers leads to the persistence of DNA damage usually repaired by the homologous-recombination system, resulting in cell cycle arrest and thus apoptosis. Despite the mechanism of action, an activity of PARP inhibitors was also observed in "BRCAness" ovarian tumors, and in BRCA-related tumors other than ovarian, suggesting that these agents may be active regardless of BRCA mutation status or site of origin. This review aims to describe the principal evidence that led to the development and the study of PARP inhibitors and to discuss their main implications in our daily clinical practice.

PMID: 29521233 [PubMed - as supplied by publisher]

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Role of miR-193a in cancer: complexity and factors control the pattern of its expression.

Role of miR-193a in cancer: complexity and factors control the pattern of its expression.

Curr Cancer Drug Targets. 2018 Mar 07;:

Authors: Mamoori A, Gopalan V, Lam AK

Abstract
BACKGROUND: There is emerging data suggest that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers.
OBJECTIVE: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature.
METHOD: All the literature concerning miR-193a in cancer in PubMed are analysed.
RESULTS: Several studies proved the association of miR-193a expression patterns with cancer's stages, grades, response to the chemotherapy and even patient survival. Also, miR-193a can be used to differentiate some types of cancer. In cancer, miR-193a can act as a tumour suppressor gene or as an oncogene. Till now, several genetic factors (MAX, RXR α, XB130, P63, P73, AEG-1, HIFs, EGFR, Drosha, DGCR8, Dicer) and epigenetic factors (DNA methylation and long non-coding RNAs) were predicted to control miR-193a expression. They have fundamental effects on its biological behaviour in different types of cancers.
CONCLUSION: miR-193a has significant roles in cancer and can be targeted in the future for cancer therapy by better understanding to the factors that control it's biological behaviour.

PMID: 29521232 [PubMed - as supplied by publisher]

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Spinal meningioma, aortic aneurysms and the missing link of observation: the anchoring heuristic approach

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition.

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Radiomics and Deep Learning in Clinical Imaging: What Should We Do?

http://ift.tt/2txl3lx

C-Myc-dependent repression of two oncogenic miRNA clusters contributes to triptolide-induced cell death in hepatocellular carcinoma cells

Triptolide is a structurally unique diterpene triepoxide with potent antitumor activity. However,the effect and mechanism of triptolide on hepatocellular carcinoma (HCC) is not well studied.

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Radiomics and Deep Learning in Clinical Imaging: What Should We Do?

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Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome

Abstract

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

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Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report

There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading trans...

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Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome

Abstract

Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.

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Patterns of pathologically confirmed metastasis to bone in Near East population

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Abdallah Flaifel, Farah Tabaja, Sami Bannoura, Asif Loya, Sajid Mushtaq, Ibrahim Khalifeh
BackgroundMetastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly.MethodsA total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded.ResultsOut of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations.ConclusionThe patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis.



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Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Rebecca Nash, Kevin C. Ward, Ahmedin Jemal, David E. Sandberg, Vin Tangpricha, Michael Goodman
BackgroundTransgender people and persons with disorders of sex development (DSD) are two separate categories of gender minorities, each characterized by unique cancer risk factors. Although cancer registry data typically include only two categories of sex, registrars have the option of indicating that a patient is transgender or has a DSD.MethodsData for primary cancer cases in 46 states and the District of Columbia were obtained from the North American Association of Central Cancer Registries (NAACCR) database for the period 1995–2013. The distributions of primary sites and categories of cancers with shared risk factors were examined separately for transgender and DSD patients and compared to the corresponding distributions in male and female cancer patients. Proportional incidence ratios were calculated by dividing the number of observed cases by the number of expected cases. Expected cases were calculated based on the age- and year of diagnosis-specific proportions of cases in each cancer category observed among male and female patients.ResultsTransgender patients have significantly elevated proportional incidence ratios (95% confidence intervals) for viral infection induced cancers compared to either males (2.3; 2.0–2.7) or females (3.3; 2.8–3.7). Adult DSD cancer patients have a similar distribution of primary sites compared to male or female patients but DSD children with cancer have ten times more cases of testicular malignancies than expected (95% confidence interval: 4.7–20).ConclusionThe proportions of certain primary sites and categories of malignancies among transgender and DSD cancer patients are different from the proportions observed for male or female patients.



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Patterns of pathologically confirmed metastasis to bone in Near East population

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Abdallah Flaifel, Farah Tabaja, Sami Bannoura, Asif Loya, Sajid Mushtaq, Ibrahim Khalifeh
BackgroundMetastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly.MethodsA total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded.ResultsOut of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations.ConclusionThe patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis.



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Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Rebecca Nash, Kevin C. Ward, Ahmedin Jemal, David E. Sandberg, Vin Tangpricha, Michael Goodman
BackgroundTransgender people and persons with disorders of sex development (DSD) are two separate categories of gender minorities, each characterized by unique cancer risk factors. Although cancer registry data typically include only two categories of sex, registrars have the option of indicating that a patient is transgender or has a DSD.MethodsData for primary cancer cases in 46 states and the District of Columbia were obtained from the North American Association of Central Cancer Registries (NAACCR) database for the period 1995–2013. The distributions of primary sites and categories of cancers with shared risk factors were examined separately for transgender and DSD patients and compared to the corresponding distributions in male and female cancer patients. Proportional incidence ratios were calculated by dividing the number of observed cases by the number of expected cases. Expected cases were calculated based on the age- and year of diagnosis-specific proportions of cases in each cancer category observed among male and female patients.ResultsTransgender patients have significantly elevated proportional incidence ratios (95% confidence intervals) for viral infection induced cancers compared to either males (2.3; 2.0–2.7) or females (3.3; 2.8–3.7). Adult DSD cancer patients have a similar distribution of primary sites compared to male or female patients but DSD children with cancer have ten times more cases of testicular malignancies than expected (95% confidence interval: 4.7–20).ConclusionThe proportions of certain primary sites and categories of malignancies among transgender and DSD cancer patients are different from the proportions observed for male or female patients.



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Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy, Published online: 09 March 2018; doi:10.1038/s41416-018-0005-1

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

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Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy, Published online: 09 March 2018; doi:10.1038/s41416-018-0005-1

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

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Cell Cycle Markers in the Evaluation of Bladder Cancer

Abstract

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

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Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas

Abstract

A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-d-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-d-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects. Immunocytochemistry was carried out on Grade IV astrocytomas to determine the cellular location of SGLT proteins within the tumors. Me-4FDG retention was pronounced in astrocytomas in dramatic contrast to the lack of uptake into the normal brain, resulting in a high signal-to-noise ratio. Macroscopically, the distribution of Me-4FDG within the tumors overlapped with that of 2-FDG uptake and tumor definition using contrast-enhanced MRI images. Microscopically, the SGLT2 protein was found to be expressed in neoplastic glioblastoma cells and endothelial cells of the proliferating microvasculature. This preliminary study shows that Me-4FDG is a highly sensitive probe for visualization of high-grade astrocytomas by PET. The distribution of Me-4FDG within tumors overlapped that for 2-FDG, but the absence of background brain Me-4FDG resulted in superior imaging sensitivity. Furthermore, the presence of SGLT2 protein in astrocytoma cells and the proliferating microvasculature may offer a novel therapy using the SGLT2 inhibitors already approved by the FDA to treat type 2 diabetes mellitus.

http://ift.tt/2p7EMmC

Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas

Abstract

A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-d-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-d-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects. Immunocytochemistry was carried out on Grade IV astrocytomas to determine the cellular location of SGLT proteins within the tumors. Me-4FDG retention was pronounced in astrocytomas in dramatic contrast to the lack of uptake into the normal brain, resulting in a high signal-to-noise ratio. Macroscopically, the distribution of Me-4FDG within the tumors overlapped with that of 2-FDG uptake and tumor definition using contrast-enhanced MRI images. Microscopically, the SGLT2 protein was found to be expressed in neoplastic glioblastoma cells and endothelial cells of the proliferating microvasculature. This preliminary study shows that Me-4FDG is a highly sensitive probe for visualization of high-grade astrocytomas by PET. The distribution of Me-4FDG within tumors overlapped that for 2-FDG, but the absence of background brain Me-4FDG resulted in superior imaging sensitivity. Furthermore, the presence of SGLT2 protein in astrocytoma cells and the proliferating microvasculature may offer a novel therapy using the SGLT2 inhibitors already approved by the FDA to treat type 2 diabetes mellitus.

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Cell Cycle Markers in the Evaluation of Bladder Cancer

Abstract

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

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Cancer screening policy in Hungary

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Author's reply to: Cancer screening policy in Hungary

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Caspase-3 regulates the migration, invasion, and metastasis of colon cancer cells

Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared with parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug, and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastases. This article is protected by copyright. All rights reserved.

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Cancer screening policy in Hungary

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Author's reply to: Cancer screening policy in Hungary

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Associations between Statin Use and Risk of Non-Hodgkin Lymphomas by Subtype

Abstract

Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear.

We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence, and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income, and use of other medications.

Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR=0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR=0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR=0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration- or dose-response relationships were observed.

Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms. This article is protected by copyright. All rights reserved.

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Caspase-3 regulates the migration, invasion, and metastasis of colon cancer cells

Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared with parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug, and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastases. This article is protected by copyright. All rights reserved.

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Case-series of paraneoplastic Cushing syndrome in small-cell lung cancer

Summary

The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential.

Learning points:

Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.

Distinguish between occult and severe ectopic Cushing syndrome and etiology.

Providing the adequate treatment of the primary tumor as well as for the cortisol excess.

Prognosis depends on the differentiation and type of the primary malignancy.

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Correction to: Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer

Following the publication from the original article, it came to our attention that we unintentionally neglected to acknowledge some text overlap with previous publications.

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Correction to: Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer

Following the publication from the original article, it came to our attention that we unintentionally neglected to acknowledge some text overlap with previous publications.

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Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

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Lifestyle factors, cardiovascular disease and all-cause mortality in middle-aged and elderly women: a systematic review and meta-analysis

Abstract

Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15–4.52) for CHD incidence, 2.09 (95% CI 1.51–2.89) for stroke incidence, 2.76 (95% CI 1.62–4.71) for CVD mortality and 2.22 (95% CI 1.92–2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67–0.80) for overall CVD, 0.71 (95% CI 0.67–0.75) for CHD, 0.77 (95% CI 0.70–0.85) for stroke, 0.70 (95% CI 0.58–0.84) for CVD mortality and 0.71 (95% CI 0.65–0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56–0.91) for CHD, 0.63 (95% CI 0.57–0.71) for CVD mortality and 0.80 (95% CI 0.76–0.84) for all-cause mortality. For women with BMI 30–35 kg/m² the risk was 1.67 (95% CI 1.24–2.25) for CHD and 2.3 (95% CI 1.56–3.40) for CVD mortality, compared to normal weight. Each 5 kg/m² increase in BMI was associated with 24% (95% CI 16–33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.

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Lactate gap as a tool in identifying ethylene glycol poisoning

Ethylene glycol toxicity is a known cause of anion gap metabolic acidosis, with the presence of an osmolar gap and the right clinical context suggesting to the diagnosis. Rapid recognition and early treatment is crucial. Unfortunately, ethylene glycol levels are not readily available and must be performed at a reference laboratory. We present a case where recognising the significance of the 'lactate gap' assisted in identifying ethylene glycol poisoning.

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Pancytopenia: a rare complication of Graves disease

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

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Renocolic fistula secondary to urothelial carcinoma

A 77-year-old man presented with watery, bloody diarrhoea, symptomatic anaemia and signs of sepsis. He was well known to our unit with a history of extensive low-grade urothelial carcinoma involving a solitary kidney. CT performed on admission demonstrated a new finding of renocolic fistula. Due to his multiple medical and surgical comorbidities conservative management was elected. He passed away after 1 year of follow-up.

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The novel use of botulinum toxin A for the treatment of Raynauds phenomenon in the toes

Raynaud's phenomenon is a vasospastic disorder of the digital vessels triggered by exposure to cold or stress. It is most commonly observed in the hands, but also frequently affects the toes. We present three cases of patients with severe Raynaud's phenomenon in the toes, secondary to scleroderma. The diagnosis of Raynaud's syndrome and scleroderma was established according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria. Patients were treated with 10 units of botulinum toxin injected into each foot. Two millilitres was injected into the base of each toe in both the left and right feet. Six weeks postinjection into the toes, patients reported an improvement of cold intolerance, colour change and frequency and severity of Raynaud's attacks. The effects were reported to last up to 5 months. To our knowledge, these are the first reported cases of the treatment of Raynaud's phenomenon in the toes with botulinum toxin A.

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Atrial myxoma presenting as infective endocarditis

A 23-year-old Asian student presented to our service with a 1-month history of fever, weight loss of 10 kg, night sweats, fatigue and general malaise. He was previously well with no significant medical or family history. He had a low-grade pyrexia and cardiac auscultation revealed a diastolic murmur consistent with 'tumour plop'. He had no sequelae of endocarditis. He had low-grade pyrexia of 37.7°C, and ECG showed sinus tachycardia at 130 bpm. He had raised inflammatory markers and was started on broad spectrum antibiotics. Blood cultures grew Streptococcus viridans twice. Transthoracic and transo-oesophageal echocardiography revealed a large mobile mass attached to the interatrial septum, suspicious for atrial myxoma, flopping into the left ventricle but not causing left ventricular outflow tract obstruction. All valves looked normal in appearance. He was treated with antibiotics for 2 weeks until inflammatory markers normalised. The patient was referred for cardiothoracic surgery where a large atrial myxoma (5 cmx3 cm) was excised just superior to the mitral valve. It had areas of necrosis and was colonised with S. viridans. He had an unremarkable postoperative course and made a complete recovery.

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Rare case of thoracic endometriosis presenting with lung nodules and pneumothorax

We present the case of a 34-year-old Nigerian woman who was referred to the Respiratory team with a 12-month history of breathlessness. She was concurrently being investigated for an abdominal mass and rectal and vaginal bleeding. Consequently, she underwent cross-sectional imaging of her chest, abdomen and pelvis, revealing a small right-sided pneumothorax and right lower lobe pleural-based lesion. Shortly thereafter, she was admitted to the hospital with chest pain and required chest drain insertion. This partially treated her pneumothorax but she required referral to a cardiothoracic centre for definitive diagnosis and to manage her non-resolving pneumothorax. Biopsies from the video-assisted thoracoscopic surgery confirmed the very rare diagnosis of thoracic endometriosis.

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Spontaneous renal infarct heralding bowel ischaemia in an adult male: lessons to learn from a rare clinical association

Spontaneous renal artery dissection (SRAD) is a rare entity with less than 200 cases reported in literature. It usually affects middle-aged men and the clinical presentation is non-specific. Many times it is associated with conditions such as hypertension, fibromuscular dysplasia or vasculitides. We report the case of a patient who initially had renal infarct due to SRAD and then progressed to have bowel ischaemia. The renal infarct preceded bowel ischaemia in this patient and to the best of our knowledge this is the first such association reported in literature. Our report emphasises the point that whenever this condition is diagnosed in a patient one should be vigilant for other vascular disorders.

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