Τρίτη 15 Μαΐου 2018

Peri-operative therapy for operable gastroesophageal adenocarcinoma; past, present and future

Abstract
Surgery represents the only chance of cure for patients with gastroesophageal adenocarcinoma; however surgery alone does not cure most patients. Over the past decade, several multimodality adjunctive treatments have improved survival for patients with operable gastroesophageal adenocarcinoma who are undergoing surgical resection; these include peri-operative chemotherapy, neoadjuvant chemoradiotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy. More recently, the results of several large randomised trials are leading to a shift in the peri-operative treatment of gastroesophageal cancer, away from anthracycline-based and towards taxane-based chemotherapy regimens. Emerging data supports an increased focus on patients who are at high risk for poor operative outcomes such as R1 resection, and on patients who are at high risk for relapse following surgery such as those with lymph node metastases (N1+). Future developments may include use of fluorodeoxyglucose-positron emission tomography (FDG-PET) to inform a switch to non-cross resistant chemotherapy pre-operatively and substitution of alternative treatments for chemotherapy in high risk postoperative node positive patients. Conversely, in molecularly selected subgroups such as microsatellite unstable gastroesophageal cancer, peri-operative or adjuvant chemotherapy may not be helpful, and treatments such as immunotherapy may be considered. In this review the most up-to-date clinical trials and translational research in the field of operable gastroesophageal cancer are discussed; with a focus on how best to risk stratify patients with operable disease for peri-operative treatment plus surgery, and how novel therapies might be integrated into standard treatments in order to improve survival outcomes in this patient group.

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Developing a novel approach to existential suffering in cancer survivorship through Socratic dialogue

Psycho-Oncology, EarlyView.


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TP53, STK11 and EGFR Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma

Purpose: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. Experimental Design: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and to PD-L1 expression, and a public clinical database was used to validate the results obtained. Results: We showed that distinct combinations of STK11, EGFR and TP53 mutations, were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations (TP53-mut/STK11-EGFR-WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T cell density and PD-L1 expression. In this tumor subtype, pathways related to T cell chemotaxis, immune cell cytotoxicity, and antigen processing were up-regulated. Finally, a prolonged progression-free survival (PFS: HR=0.32; 95% CI, 0.16-0.63, p<0.001) was observed in anti-PD-1 treated patients harboring TP53-mut/STK11-EGFR-WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression. Conclusions: Our study reveals that different combinations of TP53, EGFR and STK11 mutations, together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade.



https://ift.tt/2IoMPba

Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation

Purpose: Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. Experimental Design: In a first-in-patient, IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Results: Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans (P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM (P < 0.05). Conclusions: Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies.



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Phase I Study of CC-486 Alone and in Combination With Carboplatin or nab-paclitaxel in Patients With Relapsed or Refractory Solid Tumors

Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors. Patients and Methods: Part 1 (n=57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, maximum tolerated dose, and recommended part 2 dose (RP2D) of CC-486. In part 2 (n=112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486. Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug-drug interactions. The CC-486 RP2D was determined as 300 mg (once daily, days 1-14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days. Conclusion: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943).



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Combined HDAC and Bromodomain Protein Inhibition Reprograms Tumor Cell Metabolism and elicits Synthetic Lethality in Glioblastoma

Purpose: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. Experimental Design: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. Results: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells.  Transcriptome based GSEA analysis suggests that metabolic reprogramming is involved with synergistic reduction of oxidative and glycolytic pathways in the combination treatment. Extracellular flux analysis confirms that combined HDAC inhibition and BRD inhibition blunts oxidative and glycolytic metabolism of cancer cells, leading to a depletion of intracellular ATP production and total ATP levels. In turn, energy deprivation drives an integrated stress response, originating from the endoplasmic reticulum. This results in an increase in pro-apoptotic Noxa. Aside from Noxa, we encounter a compensatory increase of anti-apoptotic Mcl-1 protein. Pharmacological, utilizing the FDA-approved drug sorafenib, and genetic inhibition of Mcl-1 enhanced the effects of the combination therapy. Finally, we show in orthotopic patient-derived xenografts of GBM, that the combination treatment reduces tumor growth, and that the triple therapy, involving clinically validated compounds, panobinostat, OTX015 and sorafenib further enhances these effects, culminating in a significant regression of tumors in vivo. Conclusion: Overall, these results warrant clinical testing of this novel, efficacious combination therapy.



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Preclinical Antitumor Activity of a Novel Anti-c-KIT Antibody Drug Conjugate against Mutant and Wild Type c-KIT Positive Solid Tumors

Purpose: c-KIT overexpression is well-recognized in cancers such as GIST, SCLC, melanoma, NSCLC and AML. Treatment with the small molecule inhibitors imatinib, sunitinib and regorafenib result in resistance (c-KIT mutant tumors) or limited activity (c-KIT wildtype tumors). We selected an anti-c-KIT ADC approach to evaluate the anti-cancer activity in multiple disease models. Experimental Design: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a non-cleavable linker (SMCC). The activity of the resulting ADC, LOP628, was evaluated in vitro against GIST, SCLC and AML models and in vivo against GIST and SCLC models. Results: LOP628 exhibited potent anti-proliferative activity on c-KIT positive cell lines whereas LMJ729 displayed little to no effect. At exposures predicted to be clinically achievable, LOP628 demonstrated single administration regressions or stasis in GIST and SCLC xenograft models in mice. LOP628 also displayed superior efficacy in an imatinib-resistant GIST model. Further, LOP628 was well-tolerated in monkeys with an adequate therapeutic index several fold above efficacious exposures. Safety findings were consistent with the pharmacodynamic effect of neutropenia due to c-KIT-directed targeting. Additional toxicities were considered off-target and were consistent with DM1, such as effects in the liver and hematopoietic/lymphatic system. Conclusions:The preclinical findings suggest that the c-KIT directed ADC may be a promising therapeutic for the treatment of mutant and wildtype c-KIT positive cancers and supported the clinical evaluation of LOP628 in GIST, AML and SCLC patients.



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HP1{gamma} promotes lung adenocarcinoma by downregulating the transcription-repressive regulators NCOR2 and ZBTB7A

Lung adenocarcinoma (LUAD) is a major form of lung cancer, which is the leading cause of cancer death. Histone methylation reader proteins mediate the effect of histone methylation, a hallmark of epigenetic and transcriptional regulation of gene expression. However, their roles in LUAD are poorly understood. Here our bioinformatic screening and analysis in search of an LUAD-promoting histone methylation reader protein show that heterochromatin protein 1γ (HP1γ; also called CBX3) is among the most frequently overexpressed and amplified histone reader proteins in human LUAD, and that high HP1γ mRNA levels are associated with poor prognosis in LUAD patients. In vivo depletion of HP1γ reduced K-RasG12D-driven LUAD and lengthened survival of mice bearing K-RasG12D-induced LUAD. HP1γ and its binding activity to methylated histone H3 lysine 9 were required for the proliferation, colony formation, and migration of LUAD cells. HP1γ directly repressed expression of the transcription-repressive regulators NCOR2 and ZBTB7A. Knockdown of NCOR2 or ZBTB7A significantly restored defects in proliferation, colony formation, and migration in HP1γ-depleted LUAD cells. Low NCOR2 or ZBTB7A mRNA levels were associated with poor prognosis in LUAD patients and correlated with high HP1γ mRNA levels in LUAD samples. NCOR2 and ZBTB7A downregulated expression of tumor-promoting factors such as ELK1 and AXL, respectively. These findings highlight the importance of HP1γ and its reader activity in LUAD tumorigenesis and reveal a unique LUAD-promoting mechanism in which HP1γ downregulates NCOR2 and ZBTB7A to enhance expression of pro-tumorigenic genes.

https://ift.tt/2GjXFZP

Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anti-Cancer Immunity

Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size. Second, we used that miniaturized device to produce a cellular vaccine that regularly initiated therapeutic anti-melanoma immunity. Third, we individually subtracted key factors from either the immunizing inoculum or the treated animal to ascertain their contribution to the in vivo anti-melanoma response. Platelet-signaled monocyte-to-dendritic cell (DC) differentiation followed by sorting/processing/presentation of tumor antigens derived from internalized apoptotic tumor cells were absolute requirements. As in clinical ECP, immunogenic cell death of tumor cells was finely titrated by DNA cross-linkage mediated by photoactivated 8-methoxypsoralen (8-MOPA). ECP-induced tumor-loaded DC were effective immunotherapeutic agents only if they were spared exposure to 8-MOPA, indicating that healthy DC are required for ECP. Infusion of responder T cells into naïve tumor-challenged mice established the protective role of stimulated T cell anti-tumor immunity. Collectively, these results reveal that selective anti-tumor effects of ECP are initiated by tumor antigen-loaded, ECP-induced DC, which promote potent collaboration between CD4 and CD8 tumor-specific T cells. These mechanistic insights suggest potential therapeutic applicability of ECP to solid tumors in addition to CTCL.

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Targeting the Hsp40/Hsp70 chaperone axis as a novel strategy to treat castration-resistant prostate cancer

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40). Pulldown studies using biotinylated-C86 found Hsp40 present in a multi-protein complex with full-length (FL-) AR, ARv7 and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric heat shock protein 70 (Hsp70) inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor (GR), whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard anti-androgen therapy.

https://ift.tt/2GkVBkx

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers, Published online: 16 May 2018; doi:10.1038/s41416-018-0082-1

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers

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MASAN: a novel staging system for prognosis of patients with oesophageal squamous cell carcinoma

MASAN: a novel staging system for prognosis of patients with oesophageal squamous cell carcinoma

MASAN: a novel staging system for prognosis of patients with oesophageal squamous cell carcinoma, Published online: 16 May 2018; doi:10.1038/s41416-018-0094-x

MASAN: a novel staging system for prognosis of patients with oesophageal squamous cell carcinoma

https://ift.tt/2Ks8JH0

Cancer subtype identification using somatic mutation data

Cancer subtype identification using somatic mutation data

Cancer subtype identification using somatic mutation data, Published online: 16 May 2018; doi:10.1038/s41416-018-0109-7

Cancer subtype identification using somatic mutation data

https://ift.tt/2rKFzMi

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2), Published online: 16 May 2018; doi:10.1038/s41416-018-0087-9

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

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Talimogene Laherparepvec combined with anti-PD-1 based immunotherapy for unresectable stage III-IV melanoma: a case series

Abstract

Background

Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients.

Methods

We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months). Responses of injected (on-target) and uninjected (off-target) lesions were evaluated according to RECIST 2.0.

Results

The overall response rate for on-target lesions was 90%, with 6 patients experiencing a complete response in injected lesions. Two patients had off-target lesions, which were completely resolved after treatment. Blood samples were tested for 3 complete responders and 2 partial responders. CD4:CD8 ratio and frequencies of circulating PD1+ CD4 and CD8 T cells were elevated in complete responders but not partial responders. One patient died due to causes unrelated to melanoma and one patient died of progression of the disease.

Conclusion

Our data suggest that combining checkpoint inhibitor(s) with T-VEC injection may provide a synergistic efficacy for patients with unresectable melanoma. We observed a better overall response rate and complete response rate compared to published studies on similar therapeutic regimens.



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Influence of POLG on Radiosensitivity of Nasopharyngeal Carcinoma Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 4, Page 146-154, May 2018.


https://ift.tt/2jXPNo8

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 4, Page 125-130, May 2018.


https://ift.tt/2InjZ6V

Cancer subtype identification using somatic mutation data



https://ift.tt/2IkuOKL

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers



https://ift.tt/2rL6UNG

MASAN: a novel staging system for prognosis of patients with oesophageal squamous cell carcinoma



https://ift.tt/2L0HmEO

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)



https://ift.tt/2rLyfiH

Sexual orientation differences in outpatient psychiatric treatment and antidepressant usage: evidence from a population-based study of siblings

Abstract

In the past two decades, population-based health surveys have begun including measures of sexual orientation, permitting estimates of sexual orientation disparities in psychiatric morbidity and differences in treatment utilization. The present study takes advantage of the high-quality, comprehensive nationwide health registry data available in Sweden to examine whether psychiatric outpatient treatment for various diagnoses and antidepressant medication usage are greater in sexual minority individuals compared to their siblings. A longitudinal cohort study design was used with a representative random population-based sample in Stockholm, Sweden. Registry-based health record data on all specialized outpatient health care visits and prescription drug use was linked to a sample of 1154 sexual minority individuals from the Stockholm Public Health Cohort and their siblings. The main outcomes were treatment due to psychiatric diagnoses retrieved from nationwide registry-based health records. In analyses accounting for dependency between siblings, gay men/lesbians had a greater likelihood of being treated for mood disorder [adjusted odds ratio (AOR) 1.77; 99% confidence intervals (CI) 1.00, 3.16] and being prescribed antidepressants (AOR 1.51; 99% CI 1.10, 2.07) compared to their siblings. Further, bisexual individuals had a greater likelihood of any outpatient psychiatric treatment (AOR 1.69; 99% CI 1.17, 2.45) and being prescribed antidepressants (AOR 1.48; 99% CI 1.07, 2.05) as well as a greater likelihood of being treated for a mood disorder (AOR 1.98; 99% CI 1.33, 2.95) compared to their siblings. No difference in anxiety or substance use disorder treatment was found between any sexual minority subgroup and their siblings. The potential role of familial confounding in psychiatric disorder treatment was not supported for more than half of the outcomes that were examined. Results suggest that sexual minority individuals are significantly more likely to be treated for certain psychiatric disorders compared to their siblings. Future research is needed to understand mechanisms other than familial factors that might cause the substantial treatment differences based on sexual orientation reported here.



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Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy

Abstract

Purpose

Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer.

Patients and methods

This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis.

Results

The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08–1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR.

Conclusion

Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer.

Trial registration

EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7–11, 2016, Copenhagen, Denmark (oral presentation).



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Influence of age on variation in patterns of care in patients with rectal cancer in Catalonia (Spain)

Abstract

Background

Population ageing is a relevant concern in people diagnosed with rectal cancer. This study evaluates the adherence to clinical practice guidelines (CPGs) and patient outcomes in rectal cancer, with a particular focus on variation according to age.

Methods

This is a multicentre retrospective cohort study of all patients surgically treated for the first time for primary rectal cancer with curative intent in public hospitals in Catalonia during two study periods: first, with data from 2005 to 2007, and then with data from 2011 to 2012. We obtained the study data through a comprehensive review of patients' clinical records. Information on diagnosis, treatment and follow-up was collected and then compared with the relevant CPGs. We then performed a descriptive analysis of the categorical variables followed by a univariate and multivariate logistic regression analysis to calculate the odds ratio. Finally, we calculated the recurrence and death rates per person-year at 2 years' follow-up.

Results

In total, 3770 people were included in this study. The participants aged 70 and under were more likely to receive neoadjuvant therapy than those aged over 80 (2005/2007, 63 vs 17.4% p < 0.001; 2011/2012, 72 vs 41.1% p < 0.001); however, in the second study period there was less imbalance between the two groups in this regard, showing improved administration of neoadjuvant therapy in the elderly. The quality of surgery was suboptimal in a larger proportion of the elderly population, and the choice of surgical technique was dependent to some extent on the age of the participant. Recurrence and survival rates were significantly better in the second study period.

Conclusions

Compared to younger patients, the most elderly were less likely to receive the recommended adjuvant treatment, laparoscopy and total mesorectal excision. However, we observed improved adherence to the recommended treatment regimen in the most elderly participants, resulting in decreased recurrence and increased survival rates in this population.



https://ift.tt/2rHoDX8

Risk factors for near-miss events and safety incidents in pediatric radiation therapy

Factors contributing to safety- or quality-related incidents (e.g. variances) in children are unknown. We identified clinical and RT treatment variables associated with risk for variances in a pediatric cohort.

https://ift.tt/2wJ32Cv

Survivorship Care Plan: We’ve Got the Tool—It’s Time to Fix the Process

Since the release of the Institute of Medicine recommendation for the provision of a survivorship care plan (SCP), considerable emphasis has been placed on the document. While patients report satisfaction in receiving SCPs (1), preparing them is time consuming (2), they are not routinely provided by oncologists (3), and they have little to no effect on outcomes (4,5). Primary care providers (PCPs) find the information useful but want the SCP to be simple, accessible, and timely (6,7). In a national survey, the few PCPs who received SCPs were nine times more likely to discuss survivorship care with their patients (8). Yet despite the proliferation of SCP studies, there is a continuing debate about target populations, measures, and outcomes (9,10).

https://ift.tt/2IJ6T7e

Randomized Trial of the Impact of Empowering Childhood Cancer Survivors With Survivorship Care Plans

Abstract
Background
A survivorship care plan (SCP), that is, individualized treatment summary and schedule of off-therapy surveillance, will be mandated by January 2019. It is unclear whether SCPs improve adherence to recommended follow-up care in the community. In this trial, we evaluated the impact of randomly assigning childhood cancer survivors to 1) SCPs to be taken to their primary care physician (PCP) to implement or 2) survivorship clinic (SC) on health care quality measures.
Methods
Eligibility included cancer diagnosis younger than age 18 years (2000–2012), cancer free, one or more years off therapy, and no prior survivorship clinic attendance. At 12 months, the random assignment groups were compared (SCP+PCP vs SC) by intent-to-treat analysis with two-sided statistical tests in terms of patient adherence to guideline-recommended surveillance tests (eg, echocardiogram) and number of newly identified late complications of therapy.
Results
From 2011 to 2013, 96 participants (46.9% female, mean age = 15.9 ± 6.1 years) were randomly assigned. Adherence to 14 evaluated guideline-recommended surveillance tests ranged from 0% to 46.9% in the SCP+PCP group (n = 47) and from 50.0% to 86.4% in the SC group (n = 47). Adherence to 10 tests was statistically significantly different between the groups (all P < .05). One mild new late complication was identified in the SCP+PCP group compared with 21 late complications, ranging from mild to severe, identified in 11 patients in the SC group (2.1% vs 23.4% of patients, respectively, P = .003).
Conclusions
Our randomized trial suggests that empowering childhood cancer survivors with SCPs to be implemented by their PCPs is not sufficient to meet consensus follow-up recommendations.

https://ift.tt/2ImxwLL

Influence of POLG on Radiosensitivity of Nasopharyngeal Carcinoma Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 4, Page 146-154, May 2018.


https://ift.tt/2jXPNo8

Antitumor Effect of GO-PEG-DOX Complex on EMT-6 Mouse Breast Cancer Cells

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 4, Page 125-130, May 2018.


https://ift.tt/2InjZ6V

Long non-coding RNA NEAT1 -modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

Abstract

Background

Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of the lipolytic pathway in HCC has not been elucidated.

Methods

We compared levels of adipose triglyceride lipase (ATGL) in human HCC and healthy liver tissues by real time PCR, western blot and immunohistochemistry. We measured diacylglycerol(DAG) and free fatty acid (FFA) levels in HCC cells driven by the NEAT1-ATGL axis and in HCC tissues. We also assessed the effects of ATGL, DAG, FFA, and NEAT1 on HCC cells proliferation in vitro and in an orthotopic xenograft HCC mouse model. We also performed a luciferase reporter assay to investigate the interaction between NEAT1/ATGL and miR-124-3p.

Results

We found that the lipolytic enzyme, ATGL is highly expressed in human HCC tissues and predicts poor prognosis. We also found that high levels of DAG and FFA are present in HCC tissues. Furthermore, the lncRNA-NEAT1 was found to modulate ATGL expression and disrupt lipolysis in HCC cells via ATGL. Notably, ATGL and its products, DAG and FFA, were shown to be responsible for NEAT1-mediated HCC cell growth. NEAT1 regulated ATGL expression by binding miR-124-3p. Additionally, NEAT1 knockdown attenuated HCC cell growth through miR-124-3p/ATGL/DAG+FFA/PPARα signaling.

Conclusion

Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.



https://ift.tt/2InR96m

Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy

Abstract

Purpose

Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer.

Patients and methods

This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis.

Results

The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08–1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR.

Conclusion

Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer.

Trial registration

EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7–11, 2016, Copenhagen, Denmark (oral presentation).



https://ift.tt/2KpE9NZ

Influence of age on variation in patterns of care in patients with rectal cancer in Catalonia (Spain)

Abstract

Background

Population ageing is a relevant concern in people diagnosed with rectal cancer. This study evaluates the adherence to clinical practice guidelines (CPGs) and patient outcomes in rectal cancer, with a particular focus on variation according to age.

Methods

This is a multicentre retrospective cohort study of all patients surgically treated for the first time for primary rectal cancer with curative intent in public hospitals in Catalonia during two study periods: first, with data from 2005 to 2007, and then with data from 2011 to 2012. We obtained the study data through a comprehensive review of patients' clinical records. Information on diagnosis, treatment and follow-up was collected and then compared with the relevant CPGs. We then performed a descriptive analysis of the categorical variables followed by a univariate and multivariate logistic regression analysis to calculate the odds ratio. Finally, we calculated the recurrence and death rates per person-year at 2 years' follow-up.

Results

In total, 3770 people were included in this study. The participants aged 70 and under were more likely to receive neoadjuvant therapy than those aged over 80 (2005/2007, 63 vs 17.4% p < 0.001; 2011/2012, 72 vs 41.1% p < 0.001); however, in the second study period there was less imbalance between the two groups in this regard, showing improved administration of neoadjuvant therapy in the elderly. The quality of surgery was suboptimal in a larger proportion of the elderly population, and the choice of surgical technique was dependent to some extent on the age of the participant. Recurrence and survival rates were significantly better in the second study period.

Conclusions

Compared to younger patients, the most elderly were less likely to receive the recommended adjuvant treatment, laparoscopy and total mesorectal excision. However, we observed improved adherence to the recommended treatment regimen in the most elderly participants, resulting in decreased recurrence and increased survival rates in this population.



https://ift.tt/2rHoDX8

Enhancer of zeste homolog 2 promotes cisplatin resistance by reducing cellular platinum accumulation

Cancer Science, EarlyView.


https://ift.tt/2Kn1vnm

Laparoscopic splenectomy for solitary splenic metastasis in a patient with ovarian cancer with a long disease-free interval: a case report

In general, splenic metastasis of epithelial ovarian cancer is considered a terminal stage resulting in widespread metastasis. Solitary splenic metastasis of epithelial ovarian cancer is rare in patients with ...

https://ift.tt/2Gkxke5

Dengue fever complicated with Guillain-Barré syndrome: a case report and review of the literature

Dengue is an arboviral infection classically presenting with fever, arthralgia, headache, and rashes. It is hyperendemic in Sri Lanka and has a major impact on health. Neurological complications of dengue feve...

https://ift.tt/2rIvC1F

Dexmedetomidine as an adjuvant during general anesthesia



https://ift.tt/2IqZLc8

Molecular drivers of metastatic castrate-resistant prostate cancer: New roads to resistance

.


https://ift.tt/2Iqic0D

Hypoxia-mediated miR-212-3p downregulation enhances progression of intrahepatic cholangiocarcinoma through upregulation of Rab1a

.


https://ift.tt/2k04p6E

LRRC15 is a novel mesenchymal protein and stromal target for antibody-drug conjugates.

Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) as well as on mesenchymal stem cells (MSC). These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) directed against LRRC15 and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard of care therapies. ABBV-085's unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085.

https://ift.tt/2ImtQh2

3D Fibrin Stiffness mediates Dormancy of Tumor-repopulating cells via a Cdc42-driven Tet2 Epigenetic Program

Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2. Tet2 epigenetically activated cell cycle-inhibiting genes p21 and p27 to induce dormancy, but also caused downregulation of integrin β3 to maintain dormancy. This stiffness-mediated dormancy was recapitulated in mouse models for both murine and primary human melanoma TRC. These data identify an epigenetic program directed by mechanics, which drives highly tumorigenic TRC to enter dormancy in a stiff mechanical environment.

https://ift.tt/2KrkaOS

Consensus document on the progression and treatment response criteria in gastroenteropancreatic neuroendocrine tumors

Abstract

Purpose

Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of low incidence neoplasms characterized by a low proliferative activity and slow growth. Their response to targeted therapies is heterogeneous and often does not lead to tumor shrinkage. Thus, evaluation of the therapeutic response should differ from other kind of tumors.

Methods

To answer relevant questions about which techniques are best in the assessment of progression or treatment response a RAND/UCLA-based consensus process was implemented. Relevant clinical questions were listed followed by a systematic search of the literature. The expert panel answered all questions with recommendations, combining available evidence and expert opinion. Recommendations were validated through a questionnaire and a participatory meeting.

Results

Expert recommendations regarding imaging tools for tumor assessment and evaluation of progression were agreed upon. Available imaging techniques were reviewed and recommendations for best patient monitoring practice and the best way to evaluate treatment response were formulated.



https://ift.tt/2IpOQji

Consensus guidelines for the use and interpretation of angiogenesis assays

Abstract

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.



https://ift.tt/2Knc5Lq

Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men

Abstract

Hyperphosphatemia has been associated with increased mortality in chronic kidney disease but the nature of such a relation in the general population is unclear. To investigate the association between phosphate (P) levels and all-cause and cause-specific mortality, we assessed two cohorts from the Rotterdam Study, with follow-up of 14.5 (RS-I) and 10.9 (RS-II) years until January 2012 with availability of fasting phosphate levels. Deaths were classified according to International Classification of Diseases into 7 groups: cardiovascular, cancer, infections, external, dementia, chronic lung diseases and other causes. Sex-stratified Weibull and competing-risks models were adjusted for age, BMI and smoking. Hazard ratios are expressed per 1 mg/dL increase in phosphate levels. The total number of participants included 3731 (RS-I, 2154 women) and 2494 (RS-II, 1361 women) subjects. The main outcome measures were all-cause and cause-specific mortality. A significant positive association was found between phosphate and all-cause mortality in men (pooled HR (95% CI): 1.46 (1.26–1.69)) but not in women (0.90 (0.77–1.05)). In men, higher phosphate increased the risk for cardiovascular mortality (1.66 (1.29–2.14)), other causes (1.67 (1.16–2.40)) and chronic lung disease mortality (1.94 (1.02–3.72)), the latter driven by mortality due to chronic obstructive pulmonary disease (COPD) (4.44 (2.08–9.49)). No relations were found for mortality due to infections, cancer, dementia or external causes. In conclusion, serum P is associated with increased all-cause, cardiovascular and COPD mortality in men but not women. The association with COPD mortality is novel and needs further research on underlying mechanisms.



https://ift.tt/2GhVC8F

Consensus document on the progression and treatment response criteria in gastroenteropancreatic neuroendocrine tumors

Abstract

Purpose

Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of low incidence neoplasms characterized by a low proliferative activity and slow growth. Their response to targeted therapies is heterogeneous and often does not lead to tumor shrinkage. Thus, evaluation of the therapeutic response should differ from other kind of tumors.

Methods

To answer relevant questions about which techniques are best in the assessment of progression or treatment response a RAND/UCLA-based consensus process was implemented. Relevant clinical questions were listed followed by a systematic search of the literature. The expert panel answered all questions with recommendations, combining available evidence and expert opinion. Recommendations were validated through a questionnaire and a participatory meeting.

Results

Expert recommendations regarding imaging tools for tumor assessment and evaluation of progression were agreed upon. Available imaging techniques were reviewed and recommendations for best patient monitoring practice and the best way to evaluate treatment response were formulated.



https://ift.tt/2IpOQji

Primo software as a tool for Monte Carlo simulations of intensity modulated radiotherapy: a feasibility study

IMRT provides higher dose conformation to the target and dose sparing to surrounding tissues than 3DCRT. Monte Carlo method in Medical Physics is not a novelty to approach dosimetric problems. A new PENELOPE b...

https://ift.tt/2IG7vKZ

Evaluation of target dose inhomogeneity in breast cancer treatment due to tissue elemental differences

Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues.

https://ift.tt/2Ip5lfn

Comparison of the peripheral antinociceptive effect of somatostatin with bupivacaine and morphine in the rodent postoperative pain model

BACKGROUND AND OBJECTIVES Infiltration of surgical wound with local anaesthetics attenuate postoperative pain. However, side effects can also occur. Somatostatin (SST) and its analogues like octreotide reportedly reduce peripheral sensitisation. The current study evaluates peripherally mediated antinociceptive effect of SST in a rat model of postoperative pain. This was compared with bupivacaine and morphine under identical experimental conditions. DESIGN Randomised vehicle-controlled blind study. SETTING Pain research laboratory, All India Institute of Medical Sciences, New Delhi from February 2014 to July 2017. EXPERIMENTAL SUBJECT Rodent hind paw incision model. INTERVENTIONS Sprague-Dawley rats were subjected to incision and one of the following drugs administered into the open wound once by a micropipette: SST (10, 30 or 100 μg), bupivacaine (3, 10, 30, 50 or 100 μg) or morphine (100 μg). Antinociceptive effect of SST was further evaluated for its reversibility, site of action, effect on spinal c-fos expression and blood glucose level. The site of action of morphine was also investigated. MAIN OUTCOME MEASURE Nociception was estimated by nonevoked (guarding behaviour) and evoked (mechanical allodynia and thermal hyperalgesia) pain behaviours between 2 h and days 4 to 7. RESULTS Nociception was maximum 2 h after incision. SST (10 to 100 μg) significantly attenuated guarding behaviour between 2 h and day 2. A delayed inhibitory effect was observed on allodynia. Bupivacaine (10 to 100 μg doses) similarly decreased guarding score up to day 2 though evoked pain behaviours were relatively unaffected. In contrast, morphine produced a potent but transient inhibitory effect on guarding score at 2 h, which was mediated by both peripheral and central opioid receptors. The antinociceptive effect of SST was peripherally mediated by type 2 receptors and was associated with decreased c-fos staining. Blood glucose level was unaltered. CONCLUSION Guarding behaviour, which likely represents pain-at-rest following surgery, was attenuated by both bupivacaine and SST to comparable extents. This novel peripherally mediated antinociceptive effect of SST needs further evaluation. Correspondence to Subrata Basu Ray, Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India Tel: +91 11 26593453; fax: +91 11 26588641; e-mail: raysb48@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

https://ift.tt/2wFdE5q

Post SABCS local therapy and radiology

Summary

This year there were three interesting oral presentations and several posters presenting important new data regarding local therapy (surgery and radiotherapy) as well as radiological aspects. This minireview is a personal view of the clinically most relevant data in this respect with the following conclusions: A micrometastasis is no indication for axillary dissection. The number of involved sentinel lymph nodes predicts non-sentinel lymph node metastasis and should be taken into account regarding omitting axillary dissection. Neoadjuvant chemotherapy reduces the risk of non-sentinel lymph node metastasis. A 2 mm margin shows an optimal rate of local recurrences after breast conservation. The question of the correct definition for an R0 resection after neoadjuvant therapy remains open. We should omit radiotherapy for women with low risk ductal carcinoma in situ (DCIS) below 2.5 cm in size and pT1a G1 after breast conservation. Risk of finding invasive cancer after having a B3 biopsy is very low depending on the type of lesion, thus, questioning the surgical approach of some of these entities. The use of magnetic resonance imaging is a standard procedure before and after neoadjuvant therapy. Data regarding correlation between complete radiologic response (rCR) with pathologic complete response (pCR) and real tumor size are rare. For women with micrometastases or isolated tumor cells in the sentinel node postmastectomy radiotherapy has little benefit. After neoadjuvant therapy only women with ypN2 had a significant benefit of postmastectomy radiotherapy for local, disease-free and overall survival.



https://ift.tt/2wEZEIN

Hermes



https://ift.tt/2rHZJqd

Current status of wrist imaging in juvenile idiopathic arthritis

Abstract

Wrist involvement occurs in about one-quarter of patients diagnosed with juvenile idiopathic arthritis (JIA), increasing to 40% 5 years after diagnosis. The imaging appearances, both for active inflammation and permanent change, differ from those seen in adult rheumatoid arthritis; therefore, a child-specific approach is crucial for correct assessment. In this review article, we provide an update on the current status for imaging wrist JIA, with a focus on evidence-based practice.



https://ift.tt/2rJqtGS

Imaging of temporomandibular joint abnormalities in juvenile idiopathic arthritis with a focus on developing a magnetic resonance imaging protocol

Abstract

Inflammation and damage in the temporomandibular joint (TMJ) often develop without clinical symptoms but can lead to severe facial growth abnormalities and impaired health-related quality of life, making early diagnosis of TMJ changes crucial to identify. Inflammatory and osteochondral changes detectable through magnetic resonance imaging (MRI) occur in TMJs of approximately 40% of children with juvenile idiopathic arthritis (JIA), and no other imaging modality or physical method of examination can reliably detect these changes. Therefore contrast-enhanced MRI is the diagnostic standard for diagnosis and interval monitoring of JIA. However the specific usage of MRI for TMJ arthritis is not standardized at present. There is a recognized need for a consensus effort toward standardization of an imaging protocol with required and optional sequences to improve detection of pathological changes and shorten study time. Such a consensus imaging protocol is important for providing maximum information with minimally necessary sequences in a way that allows inter-site comparison of results of clinical trials and improved clinical management. In this paper we describe the challenges of TMJ imaging and present expert-panel consensus suggestions for a standardized TMJ MRI protocol.



https://ift.tt/2GhUWQO

Detecting inflammation in inflammatory bowel disease — how does ultrasound compare to magnetic resonance enterography using standardised scoring systems?

Abstract

Background

Magnetic resonance enterography (MRE) is the current gold standard for imaging in inflammatory bowel disease, but ultrasound (US) is a potential alternative.

Objective

To determine whether US is as good as MRE for the detecting inflamed bowel, using a combined consensus score as the reference standard.

Materials and methods

We conducted a retrospective cohort study in children and adolescents <18 years with inflammatory bowel disease (IBD) at a tertiary and quaternary centre. We included children who underwent MRE and US within 4 weeks. We scored MRE using the London score and US using a score adapted from the METRIC (MR Enterography or Ultrasound in Crohn's Disease) trial. Four gastroenterologists assessed an independent clinical consensus score. A combined consensus score using the imaging and clinical scores was agreed upon and used as the reference standard to compare MRE with US.

Results

We included 53 children. At a whole-patient level, MRE scores were 2% higher than US scores. We used Lin coefficient to assess inter-observer variability. The repeatability of MRE scores was poor (Lin 0.6). Agreement for US scoring was substantial (Lin 0.95). There was a significant positive correlation between MRE and clinical consensus scores (Spearman's rho = 0.598, P=0.0053) and US and clinical consensus scores (Spearman's rho = 0.657, P=0.0016).

Conclusion

US detects as much clinically significant bowel disease as MRE. It is possible that MRE overestimates the presence of disease when using a scoring system. This study demonstrates the feasibility of using a clinical consensus reference standard in paediatric IBD imaging studies.



https://ift.tt/2rGaQQA

Juvenile idiopathic arthritis - the role of imaging from a rheumatologist’s perspective

Abstract

Alongside recent advances in treatment strategies for juvenile idiopathic arthritis (JIA), paediatric rheumatologists have taken increasing interest in the use of imaging. Magnetic resonance imaging (MRI) and musculoskeletal ultrasound, by providing more detailed information on disease activity than clinical examination and conventional radiography (CR), have become helpful diagnostic and managerial tools. The growing skeleton, however, with changing appearances over time, is still challenging in the establishment of valid scoring systems for pathological changes. Defining child- and age-specific reference standards is therefore a highly prioritized issue. The aim of this article is to raise awareness among radiologists of the substantial role that imaging can play to optimize the management of JIA patients and to describe the state-of-the-art validation process of imaging as an outcome measure. A closer collaboration between radiologists and pediatric rheumatologists is crucial to define a scheduled workflow for imaging in JIA.



https://ift.tt/2rJp1UN

Herman Grossman, MD, MS (1924–2018)



https://ift.tt/2GgKWHt

Diagnostic role of strain imaging in atypical myocarditis by echocardiography and cardiac MRI

Abstract

Background

The diagnosis of myocarditis presenting as isolated acute chest pain with elevated troponins but normal systolic function is challenging with significant drawbacks even for the gold-standard endomyocardial biopsy.

Objective

This study aimed to evaluate the diagnostic role of strain imaging by echocardiography and cardiac MRI in these patients.

Materials and methods

This was a retrospective review of children with cardiac MRI for acute chest pain with elevated troponins compared to normal controls. Echocardiographic fractional shortening, ejection fraction, speckle-tracking-derived peak longitudinal, radial, and circumferential strain were compared to cardiac MRI ejection fraction, T2 imaging, late gadolinium enhancement, speckle-tracking-derived peak longitudinal strain, radial strain, and circumferential strain.

Results

Group 1 included 10 subjects diagnosed with myocarditis, 9 (90%) males with a median age of 15.5 years (range: 14-17 years) compared with 10 age-matched controls in group 2. All subjects in group 1 had late gadolinium enhancement consistent with myocarditis and troponin ranged from 2.5 to >30 ng/ml. Electrocardiogram changes included ST segment elevation in 6 and abnormal Q waves in 1. Qualitative echocardiographic function was normal in both groups and mean fractional shortening was similar (35±6% in group 1 vs. 34±4% in group 2, P=0.70). Left ventricle ejection fraction by cardiac MRI, however, was lower in group 1 (52±9%) compared to group 2 at (59±4%) (P=0.03). Cardiac MRI derived strain was lower in group 1 vs. group 2 for speckle-tracking-derived peak longitudinal strain (-12.8±2.8% vs. -17.1±1.5%, P=0.001), circumferential strain (-12.3±3.8% vs. -15.8±1.2%, P=0.020) and radial strain (13.6±3.7% vs. 17.2±3.2%, P=0.040). Echocardiography derived strain was also lower in group 1 vs. group 2 for speckle-tracking-derived peak longitudinal strain (-15.6±3.9% vs. -20.8±2.2%, P<0.002), circumferential strain (-16±3% vs. -19.8±1.9%, P<0.003) and radial strain (17.3±6.1% vs. 24.8±6.3%, P=0.010).

Conclusion

In previously asymptomatic children, myocarditis can present with symptoms of acute chest pain suspicious for coronary ischemia. Cardiac MRI and echocardiographic strain imaging are noninvasive, radiation-free tests of immense diagnostic utility in these situations. Long-term studies are needed to assess prognostic significance of these findings.



https://ift.tt/2L2Km3v

Update on imaging in juvenile idiopathic arthritis



https://ift.tt/2GjxBhs

Pediatric Radiology Continuing Medical Education Activity



https://ift.tt/2rGPjHm

Imaging of the hip in juvenile idiopathic arthritis

Abstract

Hip involvement is common and estimated to occur in approximately 35–63% of children with juvenile idiopathic arthritis (JIA). It is more prevalent in the aggressive systemic subtypes, with irreversible changes occurring as early as within 5 years of diagnosis. Whilst clinical parameters and joint examination can be useful for assessing disease severity, subclinical disease is known to exist and delayed treatment may herald a lifetime of disability and pain. Early recognition of JIA changes is therefore crucial in determining treatment options. Validated scoring systems in the radiologic assessment of the hip for clinical drug trials may inform treatment outcomes, although robust tools for analysis are still lacking. This review article details the modalities utilised for imaging the hip in children with JIA with particular efforts focused upon reliability and validity in their assessment of joint disease. We conclude with a short literature review on the potential future techniques being developed for hip joint imaging in JIA.



https://ift.tt/2GguRBH

Imaging of the knee in juvenile idiopathic arthritis

Abstract

In juvenile idiopathic arthritis (JIA), imaging is increasingly used in clinical practice. In this paper we discuss imaging of the knee, the clinically most commonly affected joint in JIA. In the last decade, a number of important steps have been made in the development of imaging outcome measures in children with JIA knee involvement. Ultrasound is undergoing a fast validation process, which should be accomplished within the next few years. The validation processes of MRI as an imaging biomarker for clinical trials in the JIA knee are at an advanced stage, with important data available on the feasibility, reliability and validity of the Juvenile Arthritis MRI Scoring system. Moreover, both US and MRI data are emerging on the normal appearance of the growing knee joint.



https://ift.tt/2GgJapX

Joint-preserving palliative surgery using self-locking screws of intramedullary nail and percutaneous cementoplasty for proximal humeral metastasis in the advanced cancer patients

Abstract

Background

We introduced a palliative joint-preserving surgery using proximal self-locking screws of intramedullary (IM) nail and percutaneous cementoplasty (PC) in patients with proximal humeral metastases, including the head and neck, and evaluated the outcome of the surgical method.

Methods

Twenty-three patients (mean age = 63.0 ± 11.8 years, M:F = 14:9) had IM nailing with a self-locking screw system and PC for the treatment of humeral head and neck metastases. Usually, three proximal locking screws were inserted after IM nailing, and 20.9 ± 8.0 ml of polymethylmethacrylate (PMMA) bone cement was injected in the perimetal osteolytic area.

Results

Regional anesthesia with interscalene block was performed in 87.0% (20/23), and the duration of surgery (from anesthesia to awakening) was approximately 40–55 min. Red blood cell was not transfused intra- and/or postoperatively in 65.2% (15/23). The localized preoperative pain (visual analog scale (VAS), 8.2 ± 3.1) was gradually decreased at postoperative 1 week (VAS, 4.9 ± 2.1) and at 6 weeks (VAS, 2.9 ± 2.1) (P < 0.001). Among nine patients who underwent F-18-FDG PET/CT, the proximal humeral metastasis around PC showed improved, stable, and aggravated states in five (55.6%), three (33.3%), and one patient (11.1%), respectively. Meanwhile, 88.8% (8/9) of patients showed aggravation at the naive bone metastasis area.

Conclusion

The selection of the self-locking screw type of the IM nail and PC was helpful in preventing fixation failure for joint-preserving palliative surgery in the proximal humeral metastasis.



https://ift.tt/2IlVGpE

Evaluation of target dose inhomogeneity in breast cancer treatment due to tissue elemental differences

Abstract

Background

Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues.

Methods

CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV_lob and CTV_fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed.

Results

From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions.

Conclusion

Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.



https://ift.tt/2GgcrkB

Primo software as a tool for Monte Carlo simulations of intensity modulated radiotherapy: a feasibility study

Abstract

Background

IMRT provides higher dose conformation to the target and dose sparing to surrounding tissues than 3DCRT. Monte Carlo method in Medical Physics is not a novelty to approach dosimetric problems. A new PENELOPE based code named PRIMO recently was published. The most intriguing features of PRIMO are the user-friendly approach, the stand-alone property and the built-in definition of different linear accelerators models. Nevertheless, IMRT simulations are not yet implemented.

Methods

A Varian Trilogy with a Millennium120 MLC and a Varian Novalis with 120HD MLC were studied. A RW3 multi-slab phantom was irradiated with Gafchromic films inserted between slabs. An Expression 10000XL scanner (Seiko Epson Corp., Nagano, Japan) was used to digitalize the films. PTW-Verisoft software using the global Gamma Function (2%, 2 mm) was used to compare simulated and experimental results.

The primary beam parameters were adjusted to best match reference data previously obtained in a water phantom. Static MLC simulations were performed to validate the MLC models in use. Two Dynamic IMRT preliminary tests were performed with leaves moving with constant and variable speed. A further test of an in phantom delivery of a real IMRT field allowed simulating a clinical-like MLC modulation.

Results

Simulated PDD, X- and Y-profiles in reference conditions showed respectively 100.0%, 100.0% and 99.4% of Gamma points < 1 (2%, 2 mm). Static MLC simulations showed 100.0% of Gamma points < 1 with the 120HD MLC and 99.1% with the Millennium compared with the scanned images.

The fixed speed test showed 99.5 and 98.9% of Gamma points < 1 respectively with two different MLC configuration-sampling algorithms when the 120HD MLC was used. The higher modulation MLC motion simulation showed 99.1% of Gamma points < 1 with respect to the experimental. This result depends on the number of the fields to reproduce the MLC motion, as well as calculation time. The clinical-like simulation showed 96.2% of Gamma points < 1 using the same analysis conditions.

Conclusions

The numerical model of the Varian Trilogy and Novalis in the PRIMO software was validated. The algorithms to simulate MLC motion were considered reliable. A clinical-like procedure was successfully simulated.



https://ift.tt/2rFMQgs

Molecular features in young vs elderly breast cancer patients and the impacts on survival disparities by age at diagnosis

Cancer Medicine, EarlyView.


https://ift.tt/2KmbI3K

On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B

Cancer Medicine, EarlyView.


https://ift.tt/2IhNz1x

Systematic analyses of a novel lncRNA‐associated signature as the prognostic biomarker for Hepatocellular Carcinoma

Cancer Medicine, EarlyView.


https://ift.tt/2wJb0LX

Lactoferricin B reverses cisplatin resistance in head and neck squamous cell carcinoma cells through targeting PD‐L1

Cancer Medicine, EarlyView.


https://ift.tt/2rDmbkj

Predictive impact of the inflammation‐based indices in colorectal cancer patients with adjuvant chemotherapy

Cancer Medicine, EarlyView.


https://ift.tt/2wKeVbg

Immediate breast reconstruction for women having inflammatory breast cancer in the United States

Cancer Medicine, EarlyView.


https://ift.tt/2rFRw62

Evaluation of the ThroLy score for the prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies in clinical practice

Cancer Medicine, EarlyView.


https://ift.tt/2wCMoEq

Paediatric osteofibrous dysplasia-like adamantinoma with classical radiological findings

Description  

A 16-year-old girl presented with a 1-month history of a painful lump on the right tibia. There was no history of trauma; she had no medical conditions and was physically active. On examination, she had a diffuse bony lump in the middle third of the right tibia with some localised tenderness. There was no neurovascular deficit and no bony masses were present elsewhere.

Plain radiograph of the right leg (figure 1) showed a well-circumscribed, slightly expansile, mixed sclerotic and lytic lesion of the anterior diaphysis of the right tibia. The sclerosis and lysis were seen as a multilocular 'soap bubble' appearance. No aggressive features including periosteal reaction or soft-tissue abnormality were present. A subsequent MRI scan confirmed the presence of an extensive lesion involving the anterior cortex of the midshaft of the right tibia, extending a vertical distance of 20 cm. The lesion appeared confined to...



https://ift.tt/2rHToej

Case of drug-induced interstitial lung disease secondary to adalimumab

We report a rare case of drug-induced intestinal lung disease (ILD) secondary to adalimumab, a tumour necrosis factor alpha-receptor blocker. A 52-year-old smoker with ankylosing spondylitis, treated with adalimumab, presented with progressive breathlessness. A high resolution CT chest demonstrated predominantly upper-zone patchy ground glass changes and small bilateral pleural effusions. Bronchoscopy and bronchoalveolar lavage showed no evidence of infection or malignant cells and an echocardiogram was normal. The working diagnosis was that of possible adalimumab-induced ILD. Adalimumab was subsequently stopped. The patient's breathlessness and cough improved on cessation of the drug. A further CT chest several months later showed resolution of the ground glass changes. Adalimumab-induced ILD is rare. We review the literature surrounding this and discuss the diagnostic challenges. This case highlights the importance of considering the possibility of drug-induced lung disease in patients taking adalimumab.



https://ift.tt/2wQXbv5

Endoscopic diagnosis of a goblet cell carcinoid tumour of the appendix

Primary malignancies of the appendix are rare. Of these, less than 5% are goblet cell carcinoid (GCC) tumours. The majority of GCC present with findings of acute appendicitis or advanced peritoneal spread. We describe a rare presentation of GCC as subtle mucosal abnormality of the appendiceal orifice seen on colonoscopy performed for iron-deficiency anaemia. Biopsies were interpreted as adenocarcinoma; however, final surgical pathology confirmed GCC of the appendix with caecal involvement. The patient recovered well from surgery, anaemia resolved and follow-up did not show metastatic disease.



https://ift.tt/2rFLKRS

A mysterious postoperative rash

This case report describes the development of a rash in a patient admitted with large bowel obstruction secondary to carcinoma of the sigmoid colon. The patient underwent a Hartmann's procedure and right hemicolectomy for a metastatic deposit at the terminal ileum. On postoperative day 3, the patient developed a bullous haemorrhagic rash on the thighs, flanks and abdomen, associated with a sharp drop in platelet count. Suspicion of heparin-induced skin necrosis was raised, and prophylactic enoxaparin was switched to fondaparinux. Skin biopsy results later confirmed the diagnosis. Clinical suspicion of heparin-induced skin necrosis is essential and should prompt a switch between prophylactic agents, in order to prevent potentiation of this life-threatening side effect.



https://ift.tt/2wL10So

Non-operative management of an isolated lateral collateral ligament injury in an adolescent patient and review of the literature

We present a rare case of isolated traumatic pure ligamentous rupture of the lateral collateral ligament of the knee in an adolescent high-level footballer managed non-operatively with a good functional outcome and return to sport in 4 months.



https://ift.tt/2rHTnHh

10-year-old with concha bullosa pyogenic mucocele

A 10-year-old girl presented with episodes of migraine. A nasal mass was found randomly during work-up. Interpreted as an osteoma, the mass was removed during endoscopic surgery. However, the histopathological examination turned out to be a pyomucocele in the right middle turbinate, which is an extremely rare yet benign condition in children.



https://ift.tt/2Kn9HEm

Inflammatory myofibroblastic tumour: an unusual presentation including small bowel obstruction and palpable abdominal mass

A 41-year-old man with no medical history presented with 2 weeks of nausea, vomiting, a new palpable abdominal mass, constipation and a 14kgweight loss. On admission, CT abdomen and pelvis demonstrated a 6.9x3.7 cm soft-tissue abdominal mass deep to and invading the lower anterior abdominal wall with tethering of the urinary bladder and potential involvement of the urachus. Subsequently, a biopsy demonstrated a low-grade spindle cell neoplasm compatible with inflammatory myofibroblastic tumour with immunostain positive for smooth muscle actin and desmin and negative for CD21, CD117, DOG-1, TKE-1, mdm2, CD34 and ALK. One week following admission, he underwent en bloc excision of the mass including abdominal wall (umbilicus, portions of rectus sheath and muscle), bladder dome, right colon and a segment of small bowel. Final pathology of the mass confirmed an inflammatory myofibroblastic tumour, and his postoperative course was uneventful.



https://ift.tt/2rGVZp0

Second-look laparostomy for perforated gangrenous gastric volvulus to prevent total gastrectomy

A 42-year-old Caucasian woman presented to the emergency department with severe upper abdominal pain and vomiting. Clinically, she was septic, and abdominal examination suggested peritonitis. Following immediate resuscitation, the patient was stabilised and underwent urgent contrast-enhanced CT of the abdomen and pelvis. This revealed a mesenteroaxial gastric volvulus with traction on the mesentery and a small volume of free fluid. She underwent laparotomy revealing gangrenous gastric fundus perforation complicated by persistent intraoperative hypotension. This mandated a damage-control approach for the patient's safety entailing a limited-sleeve gastrectomy and laparostomy formation. Stabilisation in the intensive care unit allowed for a safer return to the operating room. On second look 24 hours later, previously ischaemic non-viable-looking portions of the stomach had recovered their blood supply. The patient was discharged 31 days postoperatively after recovering from the operations, postoperative wound infections and pleural effusions.



https://ift.tt/2Kn9z7Q

Thoracic Empyema as Rare Complication of an Appendicular Mass: A Case Study and Review of the Literature

Introduction. Thoracic empyema is an infrequent complication of appendicitis that has rarely been reported in the literature. Case Presentation and Review of the Literature. The case of a 11-year-old boy who was admitted for medical management of an appendicular mass is presented. His clinical course was complicated by the development of an appendicular abscess and an extensive right-sided empyema. A comprehensive review of the literature was conducted including the most representative cases. The data were collected and analyzed by two independent investigators. Ten cases were found. Most patients were young individuals (mean age: 25.1 years; male : female ratio: 0.5). Risk factors for thoracic empyema included pregnancy (10%) and age (60%). The most frequent organisms isolated were Escherichia coli, Bacteroides spp., and Klebsiella spp. The survival rate was 100%. Conclusion. Thoracic empyema should be considered a potential cause of respiratory distress in patients with appendicitis. Furthermore, the abdomen should be carefully evaluated as a source of infection in patients with thoracic empyema without an underlying lung disease.

https://ift.tt/2rHBSqt

Phase I/II study on kilovoltage surface brachytherapy in conjunctival cancer: preliminary results

Gustavo R Sarria, Gustavo J Sarria, Paola Fuentes Rivera, Mayer Zaharia, Solón Serpa and Mario Buitrago

https://ift.tt/2IGuo0M

A novel nomogram individually predicting disease-specific survival after D2 gastrectomy for advanced gastric cancer

Abstract

Background

Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients.

Methods

A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets.

Results

The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.82 vs. 0.74; P < 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C-index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P < 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate.

Conclusions

The established nomogram was able to predict 3-, 5-, and 10-year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.



https://ift.tt/2IoY9j9

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons

Abstract

Background

The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC.

Results

The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker's staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC.

Conclusions

Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.



https://ift.tt/2Kl7TM7

Small bowel lymphoma presenting as inguinal hernia: case report and literature review

Abstract

Background

Inguinal hernia is one of the most common benign pathologies that primarily affects men. Primary gastrointestinal non-Hodgkin's lymphoma (PGI NHL) is the most common type of extranodal lymphoma. This study reports a rare case in which these two conditions co-exist.

Case presentation

An 85-year-old male complained of bowel movement pattern change, abdominal distension and loss of weight, without vomiting but with nausea. A computed tomographic scan of the abdomen showed a small bowel obstruction caused by a migration of a small bowel loop in the right inguinal canal, with a clinically non-reducible inguinal hernia. The patient underwent surgery. The histopathological report showed small bowel large B cell non-Hodgkin's lymphoma.

Conclusion

When the diagnosis of the contents of an inguinal hernia is not well-established, surgery should be performed as soon as possible to ensure the cure of the disease and the correct diagnosis of the contents.



https://ift.tt/2jYHU1S

Epidemiological trends in the diagnosis of melanoma in a Southern European population: analysis of a large database from a tertiary referral center

The aim of this study was to present the epidemiological, clinicopathological, and treatment characteristics of patients diagnosed and treated in a tertiary referral center and to analyze independent factors associated with these characteristics. In this cohort study, epidemiological, clinicopathological, and treatment characteristics of 1461 consecutive melanoma patients diagnosed and treated in a tertiary referral center in 1987–2015 were prospectively collected in a registry. All patients underwent resection of their melanoma lesion. Multiple logistic regression analysis was used to examine independent correlations between characteristics. Internal validation of these correlations was performed by the bootstrap method. The median age of the patients was 53 years. Female sex had a slight predominance, whereas the majority were of Southern European origin. Superficial spreading melanoma was associated with younger age (P

https://ift.tt/2L2QLvS

Dual role of Par‐4 in abrogation of EMT and switching on Mesenchymal to Epithelial Transition (MET) in metastatic pancreatic cancer cells

Molecular Carcinogenesis, EarlyView.


https://ift.tt/2IjXekc

Achieving Full Neurological Recovery in Snakebite using Best Supportive Care

A 29-year-old woman presented to a community hospital in Sierra Leone 2 hours after being bitten by an unknown snake. On arrival, she was agitated though alert, however deteriorated into respiratory arrest. There was no local availability of antivenom. The patient remained in respiratory arrest undergoing best supportive care in a low-resource setting for 2 hours 55 minutes before returning to spontaneous ventilation. She went on to make a full neurological recovery. Though spontaneous recovery following snakebite envenoming is rare, this case showcases that good communication and basic manoeuvres can have a hugely positive impact on patient outcome. Alongside this, it highlights the need for staff and community engagement and implementation of local protocols in order to improve confidence and achieve consistent practice.



https://ift.tt/2KnFncB

Early prosthetic valve endocarditis after transcatheter aortic valve implantation using St Jude Medical Portico valve

An 87-year-old woman presented to the emergency department with a 2-week history of progressively worsening shortness of breath, fever and generalised myalgia. She underwent a transcatheter Portico aortic valve implantation for severe symptomatic aortic stenosis 3 months prior to this presentation. Examination revealed a temperature of 40°C and a systolic murmur in the aortic area. Inflammatory markers were elevated, and blood cultures were positive for methicillin-sensitive Staphylococcus aureus. A possible diagnosis of infective endocarditis was made as one major and one minor criterion in the modified Duke criteria were fulfilled. Subsequent transoesophageal echocardiography (TOE) demonstrated vegetation attached to the prosthetic valve stent frame at the level of the left ventricular outflow tract. She was started on a prolonged course of intravenous antibiotics, and follow-up TOE, 4 weeks later, confirmed resolution of the vegetation. She was discharged home after prolonged hospital stay.



https://ift.tt/2rJa5pG

Penetrating trauma causing cerebrospinal fluid leak without nerve root damage

A 19-year-old man with a stab injury to the lower back presented with no focal neurology or haemodynamic instability. He complained of a headache that was improved by lying flat and underwent imaging to look for damage to local structures. He was found to have air in his intraspinal space. Initially this case was managed conservatively; however, 2 weeks after discharge, he presented with cerebrospinal fluid leak from his wound. This was managed with neurosurgical intervention and watertight closure of fascia. There were no further complications.



https://ift.tt/2KkMMcA

Role of dynamic MRI in occult cervical canal stenosis

Description

A 61-year-old elderly man presented to us with complaints of neck pain radiating to bilateral upper limbs with associated tingling and numbness of all four limbs since 8 months. He also had difficulty in walking and performing fine motor activities with his hands. On examination, he had spasticity of all four limbs, with exaggerated reflexes and power of 4/5 in his limbs. On evaluation with a static MRI of the cervical spine, a T2 cord signal hyperintensity was found at the C3–4 junction with no compression noted in sagittal and axial MRI sections. A dynamic X-ray of the cervical spine showed grade 1 listhesis of C3–4 (figure 1). Dynamic MRI of the spine was done with flexion and extension, which clearly demonstrated canal stenosis at the C3–4 junction with both anterior compression and posterior buckling of the ligamentum flavum (LF) on extension and significant reduction of the...



https://ift.tt/2IhpOqn

Unexplained bruising: a developing story

We present the case of a 10-month-old male infant who presented to accident and emergency with unexplained bruising of the ear. Initial blood tests showed no clotting or platelet abnormalities and non-accidental injury investigation commenced. He was subsequently reviewed by the dermatology team who suggested the diagnosis of acute haemorrhagic oedema of infancy presumably triggered by a viral or bacterial infection, and the clinical findings fit this diagnosis.



https://ift.tt/2wHdAC0

Not so mass effect? Finding of a remarkable 'incidentaloma in a teenager with neurofibromatosis

A 13-year-old boy with neurofibromatosis type 1 presented to the emergency department twice in a fortnight with moderate intermittent abdominal pain, radiating to the back and associated with nausea and vomiting. He examined as a well child with a soft abdomen and minimal tenderness. A history of constipation was identified but he failed to respond to a trial of laxatives. Subsequent ultrasound abdomen demonstrated a large mass surrounding the porta hepatis. MRI further characterised a focal, non-aggressive lesion extending from his liver, encapsulating his pancreas, portal vessels and laterally displacing his spleen and left kidney. Biopsy performed at a specialist cancer treatment hospital of our reference later confirmed this to be a benign neurofibroma of a size not previously reported in the literature. He will be managed conservatively with surveillance imaging and the potential for chemotherapy should the lesion continue to grow.



https://ift.tt/2rJ9TXu

Atopic dermatitis complicated by severe impetigo in a Syrian refugee infant

We present the case of a 3-month-old infant with atopic dermatitis who developed severe impetigo. The child was born to Syrian refugees shortly after they arrived in Canada. The case demonstrates the rapid and nearly complete resolution of dramatic skin findings after a course of hydrocortisone ointment and oral antibiotics with adjuvant measures. For resettled refugees, access to family physicians and local language proficiency are common barriers that negatively impact their health and healthcare. We discuss some aspects of how the healthcare model in one Canadian city addresses these issues in the context of this case. The case also raises questions about the burden of dermatological conditions in refugees while in transit and in countries of resettlement. The few reports that exist suggest that some conditions may be relatively common and that the epidemiology warrants additional investigation.



https://ift.tt/2Kok4HS

Prosopometamorphopsia secondary to a left splenium of the corpus callosum infarct

Description 

A 67-year-old right-handed woman with a medical history of coronary artery disease, hyperlipidaemia, hypertension and diabetes mellitus presented with seeing peoples' faces distorted on the left side. When she saw faces in person or watched images of people on television, she noted the left eye on faces appeared to be moving to the side and upwards. She did not see any distortion when looking at her own face in a mirror or when looking at photographs of faces. She had no difficulty recognising faces and nothing other than faces appeared distorted to her. Her neurological examination was normal. Her ophthalmological examination was also unremarkable. Brain MRI performed 2 months after symptom development showed a subacute infarct in the left aspect of the splenium of the corpus callosum (figure 1A).

Figure 1

(A) Diffusion-weighted MRI imaging 2 months after onset of prosopometamorphopsia showing a...



https://ift.tt/2Iiutse

Numb chin syndrome: an ominous sign of mandibular metastasis

A 51-year-old woman a known case of stage 2 breast carcinoma in 2006 and underwent left mastectomy performed in the same year presented with bilateral lower limb pain suggestive of spinal pathology, and left chin numbness, both of 2 weeks' duration. Examination revealed left mandibular hypoesthesia without any other sign or symptoms. Orthopantomogram was unremarkable apart from mild alveolar bone expansion at tooth 36 area, which was extracted 3 months earlier. Subsequently, a full-body positron emission tomography contrast enhanced computer tomography revealed hypermetabolic lesions of her axial (excluding skull) and appendicular skeleton. In the head and neck region, left mandibular foramen and oropharynx bilaterally showed increased metabolism suggestive of tumour metastasis. The diagnosis was numb chin syndrome secondary to mandibular metastasis. Apart from supportive treatment, she was started on palliative chemotherapy and radiotherapy. At the time of discharge, there were no active complaints other than the aforementioned hypoesthesia.



https://ift.tt/2Kr1NKi

Necrotising scleritis, keratitis and uveitis in primary antiphospholipid syndrome

Ocular manifestations of antiphospholipid syndrome typically include thromboembolic and neuro-ophthalmic complications. In this report we present a case of inflammation of the ocular coats in a patient diagnosed with antiphospholipid syndrome 16 years prior. We discuss management of the case and the possible aetiology of the rare association.



https://ift.tt/2IierhN

Spontaneous closure of branchial sinus of the pyriform fossa

Management of third and fourth branchial cleft anomalies are similar. These anomalies should be suspected in a child with recurrent low-anterior neck abscess. Investigations in the form of cross-sectional studies and examination of the pharynx under anaesthesia will facilitate diagnosis and resolution of abscess. Spontaneous closure of the pyriform sinus can occur following conservative management with antibiotic treatment and abscess drainage. This emphasise the role of second-look prior to implementing endoscopic cauterisation or surgery.



https://ift.tt/2Kr1LCa

Medically managed coronary artery aneurysm without concomitant stenosis

Coronary artery aneurysms (CAAs) are relatively rare with an incidence varying from 1.4% to 5.3% of patients undergoing coronary angiography. Studies suggest that management of CAA can be guided by the absence or presence of significant coronary artery stenosis, with most concluding that CAA associated with stenosis of ≥70% should be managed surgically or with percutaneous intervention. However, given the paucity of cases described in the literature and lack of randomised control trials, no consensus exists on the natural history, prognosis or management of CAAs without significant concomitant stenosis. We present a case of medically managed atherosclerotic CAA without significant stenosis that was found to no longer be present on coronary angiography performed 11 years after initial diagnosis.



https://ift.tt/2rHCWuy

Palatal tremor as a manifestation of posterior circulation haemorrhagic stroke

Description

Palatal tremor (previously called palatal myoclonus) is an extremely rare movement disorder characterised by involuntary, rhythmic contractions of the palatal muscles. Due to its rarity, this cryptic neurological finding is practically challenging to discover, and often missed by clinicians unless specifically looked for during physical examination.

Palatal tremor was first described by Politzer in 1862. Its prevalence data are lacking in the literature, with only a few hundred cases reported. The most notable pathological change is hypertrophic degeneration of the inferior olivary nuclei, which are presumed to be the pacemaker of symptomatic palatal tremor. The rhythmic inferior olivary activity is transmitted to the brainstem reticular centres controlling bulbar and limb functions.1

Two forms of palatal tremor have been described: essential and symptomatic. The aetiology of essential palatal tremor remains unclear. It can be idiopathic or psychogenic, but without any focal lesions on brain imaging. In essential palatal...



https://ift.tt/2IhprMv

Sudden hemichorea and frontal lobe syndrome: a rare presentation of unbalanced polycythaemia vera

Polycythaemia vera (PV) is an haematological neoplasm that frequently presents neurological symptoms. However, chorea is a rare complication of this disease, occurring in less than 5% of the patients. Cognitive impairment related to PV unbalanced is also a rare complication, and it can improve with proper treatment. We present a 96-year-old-man with acute-onset hemichorea and frontal lobe syndrome with no vascular pathology in the basal ganglia or frontal region. A clear relationship was observed between the onset of involuntary movements and the cognitive impairment and worsening of haematological parameters in the patient. After causal and symptomatic treatment, the patient's clinical status improved. In the elderly, PV must be considered as a cause of acute chorea and sudden cognitive impairment, as early diagnosis leads to effective treatment and prevention of complications.



https://ift.tt/2wG1oBr

Large bowel obstruction in a 27-year-old woman caused by a sigmoid faecal bolus

A 27-year-old woman presented to the emergency department with a 24-hour history of severe left iliac fossa pain associated with vomiting. She reported a history of ovarian cysts and was provisionally diagnosed with a ruptured ovarian cyst and admitted under the obstetrics and gynaecology team for further investigation. 24 hours later, she became haemodynamically unstable with increasing abdominal distention and developed a metabolic acidosis. A CT scan revealed large bowel obstruction (LBO) secondary to a faecal bolus in the sigmoid colon with appearances suggestive of adult-onset Hirschsprung's disease. She underwent an emergency laparotomy and decompressive transverse colotomy and was admitted to the intensive care unit overnight. After discharge, she presented again with small bowel obstruction (SBO) which resolved with conservative management. A follow-up colonoscopy and biopsies showed no anatomical abnormalities to account for the LBO and were inconclusive for Hirschsprung's disease.



https://ift.tt/2IkJMAN

Systemic sclerosis: severe pulmonary arterial hypertension and pericardial effusion at diagnosis

A 51-year-old female patient with a recent hospital admission reported to the emergency room (ER) with progressive worsening of fatigue, dyspnoea and chest discomfort. She had been recently admitted and discharged with the diagnosis of pericarditis and medicated with non-steroidal anti-inflammatory drugs and diuretics. She returned to the ER with persisting symptoms. Echocardiography was repeated and showed signs of elevated right ventricular systolic pressure and a slightly increased moderate/severe pericardial effusion without signs of cardiac tamponade. The patient was admitted and further evaluation confirmed an underlying case of advanced systemic sclerosis with skin, vascular, pulmonary and cardiac involvement. The patient was referred to specialised consults in autoimmune pathology and pulmonary arterial hypertension. She was started on bosentan and corticosteroids, presenting a favourable clinical evolution although symptoms of exertional dyspnoea persist.



https://ift.tt/2KpH6hE

Correction: A 74-year-old woman with dyspnoea and a mass in the right atrium

Rijlaarsdam MA, van Boven WJ, Planken RN, et al. A 74-year-old woman with dyspnoea and a mass in the right atrium. BMJ Case Reports 2018; doi:10.1136/bcr-2017-222261.

In the published paper, the correct figure 4 should have been:

Furthermore, the acknowledgement section was missing; it should have been as follows:

The authors would like to thank our colleagues in the Academic Medical Centre, Amsterdam (NL) for their support in describing the clinical course and the various diagnostic modalities/images: W.E.M. Kok MD PhD (department of cardiology), S.M. Boekholdt MD PhD (department of cardiology), R. Britstra MD PhD (department of Pathology) and A.H.G. Driessen MD PhD (department of cardio-thoracic surgery). We thank our colleagues from the Rode Kruis Hospital, Beverwijk (NL) for providing details about the initial presentation and management of this patient (M.A.C. Koole MD & R. Kist MPA).



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