Cancer by Sfakianakis Alexandros: 12/03/16

Σάββατο 3 Δεκεμβρίου 2016

Delayed diagnosis of a foreign body in the tongue

Nuno Ribeiro Costa, Delfim Duarte, Gustavo Lopes Nov 2, 2016; 2016:201621813-201621813 case-report

http://ift.tt/2fURrHy

Symptomatic enlarged fabella

Filon Agathangelidis, Themistoklis Vampertzis, Erato Gkouliopoulou, Stergios Papastergiou Nov 2, 2016; 2016:201621808-201621808 case-report

http://ift.tt/2h0W9zt

Large schwannoma of the sciatic nerve

Owen Godkin, Prasad Ellanti, Gary O'Toole Nov 2, 2016; 2016:201621771-201621771 case-report

http://ift.tt/2fUVWBO

Rare cause of acute hepatitis: a common energy drink

Jennifer Nicole Harb, Zachary A Taylor, Vikas Khullar, Maryam Sattari Nov 1, 2016; 2016:201621661-201621661 case-report

http://ift.tt/2h12DOU

Possible complication of bee stings and a review of the cardiac effects of bee stings

Prabha Nini Gupta, B Krishna Kumar, Praveen Velappan, M D Sudheer Nov 1, 2016; 2016:201521397-201521397 case-report

http://ift.tt/2fUQVJQ

Chronic lead poisoning in an Iranian opium smoker resident in London

Alex Azizi, Katie Ferguson, Sam Dluzewski, Tajammul Hussain, Martin Klein Nov 1, 2016; 2016:201621596-201621596 case-report

http://ift.tt/2h0Xtma

Severe metallosis following oxidised zirconium wear in total hip arthroplasty

Erato Gkouliopoulou, Filon Agathangelidis, Themistoklis Vampertzis, Thomas Ntovas Oct 31, 2016; 2016:201621802-201621802 case-report

http://ift.tt/2fURG5v

Cocaine-induced very late stent thrombosis

Priyank Shah, Rahul Vasudev, Ahmad Hisham Abuarqoub, Fayez Shamoon Oct 12, 2016; 2016:201621655-201621655 case-report

http://ift.tt/2h0YPNS

Late relapse of progressive multifocal leucoencephalopathy postallogenic transplant in a young patient with CLL

Ana Sanchez-Quintana, Joaquin Brena-Atienza, Carmen Marrero-Santos, Luis Alvarez-Acosta Aug 5, 2013; 2013:201320021-201320021 case-report

http://ift.tt/2gUwvOd

Ovarioleukodystrophy: report of a case with the c.338G>A (p.Arg113His) mutation on exon 3 and the c.896G>A (p.Arg299His) mutation on exon 7 of the EIF2B5 gene

Ibrahim Imam, Jeremy Brown, Philip Lee, P K Thomas, Hadi Manji Mar 24, 2011; 2011:112010355-112010355 case-report

http://ift.tt/2h6EJ93

Palinopsia from a posteriorly placed glioma - an insight into its possible causes

Amad Naseer Khan, Rakesh Sharma, Salema Khalid, David McKean, Richard Armstrong, Christopher Kennard Feb 2, 2011; 2011:82010327-82010327 case-report

http://ift.tt/2gUqMIo

A case of premenopausal breast cancer with symptomatic cerebellar metastasis successfully treated by systemic endocrine therapy alone: relationship to biological features

Abstract

We report a case of premenopausal breast cancer with symptomatic cerebellar metastasis successfully treated by systemic endocrine therapy alone. The patient developed dysarthria, headache, lightheadedness and became difficult to write gradually. The cerebellar tumor was detected by computed tomography (CT) and was suspected hemangioma or hemangioblastoma. The tumor was resected and histologically diagnosed as poorly differentiated adenocarcinoma or squamous cell carcinoma. A whole body CT scan revealed a right thyroid tumor and left breast tumor. Core needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and Ki-67 labeling index 5%. After these examinations, histologically, the resected cerebellar tumor showed the same subtype as the breast tumor, so the final diagnosis was metastatic breast cancer with cerebellar metastasis. The patient subsequently received radiotherapy with the CyberKnife and endocrine therapy without resection of the thyroid tumor. Her medical condition has maintained a good response and stable disease for 7.5 years after the start of treatment. Analysis of four ESR1 mutations showed no mutations in the cerebellar metastatic lesion and breast cancer tissue. Our findings show that these tumors have high hormone responsiveness.

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A case of premenopausal breast cancer with symptomatic cerebellar metastasis successfully treated by systemic endocrine therapy alone: relationship to biological features

Abstract

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SBRT for centrally localized NSCLC – What is too central?

Current guidelines recommend stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in medically inoperable patients. There are excellent outcome and toxicity data for SBRT of per...

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SBRT for centrally localized NSCLC – What is too central?

Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

Abstract

Background

Approximately 8–15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer.

Methods

In a cross sectional study performed in one reference centre for cancer treatment in São Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA).

Results

Nineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1–2 deleted and exon 5–7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c.5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A).

Conclusions

Among epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost ¾ of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.

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Predicting general and cancer-related distress in women with newly diagnosed breast cancer

Abstract

Background

Psychological distress can impact medical outcomes such as recovery from surgery and experience of side effects during treatment. Identifying the factors that explain variability in distress would guide future interventions aimed at decreasing distress. Two factors that have been implicated in distress are illness perceptions and coping, and are part of the Self-Regulatory Model of Illness Behaviour (SRM). The model suggests that coping mediates the relationship between illness perceptions and distress. Despite this; very little research has assessed this relationship with cancer-related distress, and none have examined women with screen-detected breast cancer. This study is the first to examine the relative contribution of illness perceptions and coping on general and cancer-related distress in women with screen-detected breast cancer.

Methods

Women recently diagnosed with breast cancer (N = 94) who had yet to receive treatment completed measures of illness perceptions (Revised Illness Perception Questionnaire), cancer-specific coping (Mental Adjustment to Cancer Scale), general anxiety and depression (Hospital Anxiety and Depression scale), and cancer-related distress.

Results

Hierarchical regression analyses revealed that medical variables, illness perceptions and coping predicted 50% of the variance in depression, 42% in general anxiety, and 40% in cancer-related distress. Believing in more emotional causes to breast cancer (β = .22, p = .021), more illness identity (β = .25, p = .004), greater anxious preoccupation (β = .23, p = .030), and less fighting spirit (β = −.31, p = .001) predicted greater depression. Greater illness coherence predicted less cancer-related distress (β = −.20, p = .043). Greater anxious preoccupation also led to greater general anxiety (β = .44, p < .001) and cancer-related distress (β = .37, p = .001). Mediation analyses revealed that holding greater beliefs in a chronic timeline, more severe consequences, greater illness identity and less illness coherence increases cancer-specific distress (ps < .001) only if women were also more anxiously preoccupied with their diagnosis.

Conclusions

Screening women for anxious preoccupation may help identify women with screen-detected breast cancer at risk of experiencing high levels of cancer-related distress; whilst illness perceptions and coping could be targeted for use in future interventions to reduce distress.

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Analysing population-based cancer survival – settling the controversies

Abstract

Background

The relative survival field has seen a lot of development in the last decade, resulting in many different and even opposing suggestions on how to approach the analysis.

Methods

We carefully define and explain the differences between the various measures of survival (overall survival, crude mortality, net survival and relative survival ratio) and study their differences using colon and prostate cancer data extracted from the national population-based cancer registry of Slovenia as well as simulated data.

Results

The colon and prostate cancer data demonstrate clearly that when analysing population-based data, it is useful to split the overall mortality in crude probabilities of dying from cancer and from other causes. Complemented by net survival, it provides a complete picture of cancer survival in a given population. But when comparisons of different populations as defined for example by place or time are of interest, our simulated data demonstrate that net survival is the only measure to be used.

Conclusions

The choice of the method should be done in two steps: first, one should determine the measure of interest and second, one should choose among the methods that estimate that measure consistently.

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Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

Abstract

Background

Methods

Results

Conclusions

http://ift.tt/2gZemxF

Predicting general and cancer-related distress in women with newly diagnosed breast cancer

Abstract

Background

Methods

Results

Conclusions

http://ift.tt/2fTbshz

Analysing population-based cancer survival – settling the controversies

Abstract

Background

The relative survival field has seen a lot of development in the last decade, resulting in many different and even opposing suggestions on how to approach the analysis.

Methods

Results

Conclusions

The choice of the method should be done in two steps: first, one should determine the measure of interest and second, one should choose among the methods that estimate that measure consistently.

http://ift.tt/2gZfuB4

Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

Publication date: Available online 2 December 2016
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Alejandra Méndez Romero, Fatma Keskin-Cambay, Rob M. van Os, Joost J. Nuyttens, Ben J.M. Heijmen, Jan N.M. IJzermans, Cornelis Verhoef
AimTo investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity.Materials and methodsA cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between December 2002 and December 2013 were eligible for this study. Inclusion criteria were a Karnofsky performance status ≥80% and, according to the multidisciplinary tumor board, ineligibility for surgery or radiofrequency ablation. Exclusion criteria were a lesion size >6cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5Gy or 16.75Gy prescribed at the 65–67% isodose. To analyze local control, CT or MRI scans were acquired during follow-up. Toxicity was scored using the Common Toxicity Criteria Adverse Events v4.0.ResultsA total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5Gy to 32 lesions, and 50.25Gy to 23 lesions. Median follow-up was 26 and 25 months for these two groups. Local control at 2 and 3 years was 74 and 66% in the low dose group while 90 and 81% was reached in the high dose group. No significant difference in local control between the two dose fractionation schemes could be found. Grade 3 toxicity was limited and was not increased in the high dose group.ConclusionsSBRT for colorectal liver metastases offers a high chance of local control at long term. High irradiation doses may contribute to enhance this effect without increasing toxicity.

http://ift.tt/2gzr74R

Histone deacetylase inhibitors deplete myeloid-derived suppressor cells induced by 4T1 mammary tumors in vivo and in vitro

Abstract

Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored. In the present study, we provide the first demonstration that HDACi treatment decreases MDSC accumulation in the spleen, blood and tumor bed but increases the proportion of T cells (particularly the frequency of IFN-γ- or perforin-producing CD8⁺ T cells) in BALB/C mice with 4T1 mammary tumors. In addition, HDACi exposure of bone marrow (BM) cells significantly eliminated the MDSC population induced by GM-CSF or the tumor burden in vitro, which was further demonstrated as functionally important to relieve the inhibitory effect of MDSC-enriched BM cells on T cell proliferation. Mechanistically, HDACi increased the apoptosis of Gr-1⁺ cells (almost MDSC) compared with that of Gr-1⁻ cells, which was abrogated by the ROS scavenger N-acetylcysteine, suggesting that the HDACi-induced increase in MDSC apoptosis due to increased intracellular ROS might partially account for the observed depletion of MDSC. These findings suggest that the elimination of MDSC using an HDACi may contribute to the overall anti-tumor properties of these agents, highlighting a novel property of HDACi as potent MDSC-targeting agents, which may be used to enhance the efficacy of immunotherapeutic regimens.

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Histone deacetylase inhibitors deplete myeloid-derived suppressor cells induced by 4T1 mammary tumors in vivo and in vitro

Abstract

http://ift.tt/2gza8Q4

Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature

Abstract

Background

Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar.

Case presentation

In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m², biweekly administration), the death of the patient disease occurred 1 month later.

Conclusions

Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules.

http://ift.tt/2gRMIGu

Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature

Abstract

Background

Case presentation

Conclusions

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Does the TNM classification of solitary internal mammary lymph node metastases in breast cancer still apply?

Abstract

Purpose

TNM classification of solitary internal mammary lymph node metastases (IMLNMs) in breast cancer varies depending on their method of detection: sentinel lymph node biopsy (pN1b) or clinical examination including radiological and/or physical examination (pN2b). This study aimed to evaluate whether there is a difference in prognosis between both groups.

Methods

Data of all patients diagnosed with primary invasive epithelial breast cancer between 2005 and 2008 were obtained from the Netherlands Cancer Registry. Patients with IMLNMs were divided in groups according to their pN1b and pN2b status. The main outcome measures disease-free survival (DFS) after 5 years and overall survival (OS) after 8 years were analyzed using Kaplan–Meier survival analysis. Cox regression analysis was used to determine independent predictors for DFS and OS.

Results

A total of 73 patients with pN1b status and 28 patients with pN2b status were included. DFS rate was 74.1% in the pN1b group compared to 85.0% in the pN2b group (p = 0.211). Regarding OS, 20.5% (pN1b) and 25.0% (pN2b) of the patients deceased within 8 years of follow-up (p = 0.589). In multivariable cox regression analysis, nodal status was not statistically significant for DFS (HR 0.29 [95% CI 0.04–2.33], p = 0.244) or OS (HR 1.04 [95% CI 0.37–2.89], p = 0.947).

Conclusions

Although the TNM classification considers pN1b and pN2b to be distinct prognostic entities, we did not observe any prognostic differences between these groups. Therefore, solitary IMLNMs may be regarded as a single category in the future and revision of TNM classification should be considered.

http://ift.tt/2gSSK7g

Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians

Abstract

Background

Triple-negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC.

Methods

Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data.

Results

1104 patients were identified, of which 178 had TNBC. TNBC was more frequent in African Americans than Caucasians (33.3 vs 14.9%). Although more African Americans than Caucasians overall were classified as basal-like from PAM50 gene expression (34.8 vs 16.1%), no differences in the TNBC cohort were observed. Median tumor somatic mutation counts were higher in African Americans versus Caucasians (39.5 vs 34), but no racial differences in the mutation counts in TNBC were observed. Somatic mutation analysis revealed racial differences in specific high prevalence genes in all patients (TP53 46% in African Americans vs 27% in Caucasians; PIK3CA 23% in African Americans vs 34% in Caucasians; and MLL3 12% in African Americans vs 6% in Caucasians). TNBC patients did not have any specific high prevalence genes associated with racial differences. There were no racial differences in gene expression patterns in selected genes involved in breast cancer biology. Overall, African Americans had shorter TTP and worse DFS. Racial differences in clinical outcomes were not observed in TNBC.

Conclusion

The mutational landscape of TNBC is similar between African Americans and Caucasians. The higher frequency of TNBC in African Americans is therefore not associated with a different genomic profile of commonly established tumor regulatory pathway genes. Other modifiable factors may exist that contribute to the racial disparity in TNBC.

http://ift.tt/2h53hz3

Fatigue reduction diet in breast cancer survivors: a pilot randomized clinical trial

Abstract

Purpose

Fatigue is a prevalent and burdensome effect of breast cancer. Fatigue has been linked to chronic inflammation, and diets high in antioxidant nutrients have been associated with lesser prevalence and severity of fatigue. Studies are needed, however, to test if antioxidant-rich diets could improve fatigue.

Methods

Pilot, randomized, trial conducted between January 2014 and April 2015, to investigate if a 3-month diet rich in fruit, vegetables, whole grains, and omega-3 fatty acid-rich foods, named the fatigue reduction diet (FRD), improved fatigue and sleep compared to an attention control, named the general health curriculum (GHC). 30 stage 0 to III breast cancer survivors, who had completed cancer treatments, were randomized: 15 receiving the FRD and 15 the GHC. Primary outcome was change in fatigue, as measured by the brief fatigue Inventory, from baseline to 3 months analyzed using linear mixed models. Secondary analyses were changes in sleep quality, serum carotenoids, and fatty acids.

Results

From baseline to 3-month fatigue improved by 44 ± 39% in FRD compared to 8 ± 34% in GHC (p = 0.01); sleep quality improved by 2.5 ± 3.3 points in FRD, and diminished by 0.9 ± 2.3 in GHC (p = 0.03); serum total carotenoids (p < 0.01), β-cryptoxanthin (p = 0.02), lutein (p = 0.05), zeaxanthin (p = 0.01), lycopene (p = 0.05), omega-3 fatty acids (p < 0.01), and ratio of omega-3:omega-6 fatty acids (p = 0.02) were significantly increased, and percent saturated fatty acids were decreased (p = 0.04) in FRD; γ-tocopherol was significantly increased in GHC (p = 0.03), and there was a significant visit by group difference for α-carotene between the study groups (p = 0.05).

Conclusions

The FRD intervention improved fatigue and sleep in breast cancer survivors compared to the GHC. FRD diet could provide a non-toxic treatment strategy for persistent fatigue.

http://ift.tt/2gSUOMu

Prognostic significance of the lymphocyte-to-monocyte ratio and the tumor-infiltrating lymphocyte to tumor-associated macrophage ratio in patients with stage T3N0M0 esophageal squamous cell carcinoma

Abstract

Purpose

We assessed the prognostic significance of, and the relationship between, the pretreatment lymphocyte-to-monocyte ratio (LMR) and the TILs/tumor-associated macrophages (TAMs) ratio, in patients with esophageal squamous cell carcinoma (ESCC) of pathological stage T3N0M0 (pT3N0M0).

Methods

A total of 220 newly diagnosed ESCC patients of stage pT3N0M0 who had not undergone neoadjuvant therapy were included. Densities of CD8+ TILs, CD4+ TILs, CD45RO+ TILs, and CD68+ TAMs were assessed by immunohistochemical staining of tissue microarray cores from all 220 pT3N0M0 ESCC patients (who underwent radical resection). Hematological biomarkers including lymphocyte and monocyte counts were obtained from routine preoperative blood test data, and the LMR and TILs/TAMs ratios calculated. Cutoff finder for survival prediction was plotted to find out the optimal cutoff point for each parameter.

Results

The LMR and TILs/TAMs ratios were interrelated. On univariate analyses of data from the entire cohort, the LMR, CD45RO/CD68 ratio, and CD8/CD68 ratio were significantly associated with both OS and disease-free survival. Only the CD45RO/CD68 ratio was independently prognostic of survival on multivariate analysis.

Conclusions

The prognostic significance of the CD45RO/CD68 ratio was higher than that of the LMR. The CD45RO/CD68 ratio is a useful independent prognostic marker in patients with pT3N0M0 ESCC who have undergone complete resection without neoadjuvant therapy.

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Prognostic significance of the lymphocyte-to-monocyte ratio and the tumor-infiltrating lymphocyte to tumor-associated macrophage ratio in patients with stage T3N0M0 esophageal squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusions

http://ift.tt/2gM3kwk

Long-term benefit of sunitinib in patients with metastatic renal cell carcinoma in Latin America: retrospective analysis of patient clinical characteristics

http://ift.tt/2gkQjJm

Prognostic significance of the lymphocyte-to-monocyte ratio and the tumor-infiltrating lymphocyte to tumor-associated macrophage ratio in patients with stage T3N0M0 esophageal squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusions

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Comparison of different concepts for interpretation of chromosomal aberrations in urothelial cells detected by fluorescence in situ hybridization

Abstract

Purpose

Urine fluorescence in situ hybridization (FISH) has become a broadly used marker for noninvasive detection of bladder cancer (BC). However, it has been discussed whether the interpretation algorithm proposed by the manufacturer could be improved. Aim of the present study was to compare alternative evaluation strategies of FISH for detection of BC.

Methods

We included 1048 patients suspicious for BC, who underwent urine FISH examination before cystoscopy (diagnostic cohort). Herefrom, we selected 122 patients (prognostic cohort) with a history of non-muscle-invasive BC who were cystoscopically tumor free and received FISH analysis ahead of a follow-up period of 24 months. FISH results were interpreted by the algorithms of UroVysion™, Bubendorf et al. and Zellweger et al.

Results

In the diagnostic cohort, 228 patients (21.8%) had BC at time of evaluation; in the prognostic cohort 39 patients (32.0%) experienced tumor recurrence. Alterations in chromosome 3, 7 and 17 correlated with the presence of BC. Relative loss of 9p21 was associated with BC and higher risk for progression. The evaluation strategy proposed by Zellweger et al. showed highest accuracy of all FISH assessments. Performance of evaluation strategies differed in voided urine samples and samples obtained after mechanical manipulation.

Conclusions

The performance of FISH in BC diagnosis strongly depends on the interpretation criteria. Alternative evaluation methods partly show superior diagnostic performance compared to the manufacturer's algorithm. The introduction of specific cutoffs for tetraploid cells improves specificity. Further modifications of the interpretation algorithm of the Urovysion^® FISH assay have the potential to positively affect the value of this test in diagnosis and surveillance of BC.

http://ift.tt/2fW2Emk

Comparison of different concepts for interpretation of chromosomal aberrations in urothelial cells detected by fluorescence in situ hybridization

Abstract

Purpose

Methods

Results

Conclusions

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BCOR Upregulation in a Poorly Differentiated Synovial Sarcoma with SS18L1-SSX1 Fusion – A Pathologic and Molecular Pitfall

ABSTRACT

The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH which were misinterpreted as a URCS with BCOR gene rearrangements. The tumor had an unusual clinical presentation arising as an intraneural tumor in the ankle of a 29-year-old female. The tumor displayed a mixture of fascicular spindle cells and undifferentiated round cell components. FISH studies showed no SS18 gene abnormality; however, RNA sequencing identified a fusion transcript involving SS18L1 (a paralog gene of SS18 at 20q13.33) and SSX1. Further FISH testing validated rearrangements in SSX1 and SS18L1 genes, in addition to complex structural abnormalities of the Xp11.22-4 region. This is the second reported SS case harboring an SS18L1-SSX1 alternative fusion variant, similarly occurring in association with a large nerve. The lack of SS18 gene rearrangements by FISH corroborated with the BCOR overexpression at both mRNA and protein level may result in diagnostic pitfalls with URCS with BCOR gene abnormalities. Our results further suggest that BCOR upregulation is emerging as a common downstream pathway for SS with either typical SS18-SSX transcript or with rare fusion variants, such as SS18L1-SSX. This article is protected by copyright. All rights reserved.

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BCOR Upregulation in a Poorly Differentiated Synovial Sarcoma with SS18L1-SSX1 Fusion – A Pathologic and Molecular Pitfall

ABSTRACT

http://ift.tt/2gLV8wa

Early treatment response to transcatheter arterial chemoembolization is associated with time to the development of extrahepatic metastasis and overall survival in intermediate-stage hepatocellular carcinoma

Abstract

Purpose

Transcatheter arterial chemoembolization (TACE) is the treatment of choice for intermediate-stage hepatocellular carcinoma (HCC). The absence of an early response to TACE might indicate alternative therapeutic strategies early in the course of the disease, thus improving outcomes. Therefore, our purpose was to identify the relationship between treatment response after two sessions of TACE and the time to the development of extrahepatic metastasis and overall survival.

Methods

In total, 108 treatment-naïve intermediate-stage HCC patients who received at least two consecutive sessions of TACE as the first-line treatment were analyzed.

Results

The median follow-up duration was 28.5 months. Extrahepatic metastasis developed in 32 patients (29.6%). Patient age >60 years (P = 0.027), alpha-fetoprotein (AFP) >200 ng/ml (P = 0.039), and objective response after two TACE treatments (P = 0.001) were the predictive factors for time to the development of metastasis. The median survival time for the patients who achieved objective response after two sessions of TACE was 45.9 and 14.4 months for the patients who failed to achieve objective response (P = 0.0001). Objective response after two TACE treatments (P = 0.0001) and the occurrence of extrahepatic metastasis (P = 0.002) were associated with overall survival.

Conclusions

Early objective tumor response after two sessions of TACE was associated with prolonged time to metastasis and improved survival. Therefore, surveillance for metastasis should be performed more frequently when an objective response is not obtained after two sessions of TACE and in younger intermediate-stage HCC patients with high AFP levels.

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Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway

Abstract

Background

The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.

Patients and methods

A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.

Results

The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3–4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3–4 AEs. High AUC_0–24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS.

Conclusions

Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC.

ClinicalTrials.gov identifier

NCT02090153

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Early treatment response to transcatheter arterial chemoembolization is associated with time to the development of extrahepatic metastasis and overall survival in intermediate-stage hepatocellular carcinoma

Abstract

Purpose

Methods

In total, 108 treatment-naïve intermediate-stage HCC patients who received at least two consecutive sessions of TACE as the first-line treatment were analyzed.

Results

Conclusions

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Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway

Abstract

Background

Patients and methods

Results

Conclusions

Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC.

ClinicalTrials.gov identifier

NCT02090153

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Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival

Abstract

To identify genetic variants involved in prognosis of cutaneous melanoma (CM), we investigated associations of single nucleotide polymorphisms (SNPs) of genes in the integrin signaling pathway with CM survival by re-analyzing a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center (MDACC), and then validated significant SNPs in another GWAS from Harvard University. In the MDACC study, 1,148 SNPs were significantly associated with CM-specific survival (CMSS) (P ≤ 0.050 and false-positive report probability ≤ 0.20), and nine SNPs were validated in the Harvard study (P ≤ 0.050). Among these, three independent SNPs (i.e., DOCK1 rs11018104 T>A, rs35748949 C>T and PAK2 rs1718404 C>T) showed a predictive role in CMSS, with an effect-allele attributed adjusted hazards ratio [adjHR of 1.50 (95% confidence interval (CI) = 1.18-1.90, P = 7.46E-04), 1.53 (1.18-1.97, 1.18E-03) and 0.58 (0.45-0.76, 5.60E-05), respectively]. Haplotype analysis revealed that a haplotype carrying two risk alleles A-T in DOCK1 was associated with the poorest survival in both MDACC (adjHR=1.73, 95% CI = 1.19-2.50, P = 0.004) and Harvard (adjHR = 1.95, 95% CI=1.14-3.33, P = 0.010) studies. In addition, patients with an increasing number of unfavorable genotypes (NUGs) for these three SNPs had a poorer survival. Incorporating NUGs with clinical variables showed a significantly improved ability to classify CMSS (AUC increased from 86.8% to 88.6%, P = 0.031). Genetic variants in the integrin signaling pathway may independently or jointly modulate the survival of CM patients. Further large, prospective studies are needed to validate these findings. This article is protected by copyright. All rights reserved.

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Examining temporal effects on cancer risk in the International Nuclear Workers' Study (INWORKS)

ABSTRACT

The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma.

Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies. This article is protected by copyright. All rights reserved.

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TUC.338 promotes invasion and metastasis in colorectal cancer

Abstract

Ultraconserved regions (UCRs) are non-protein coding gene sequences that are strictly conserved across among different species. Emerging evidence demonstrates that transcribed ultraconserved regions (TUCRs) encoding noncoding RNAs serve as regulators of gene expression. In recent decades, increasing evidence implicates the involvement of UCRs in carcinogenesis. The role of TUC.338 in cervical cancers was an oncogene in previous studies. Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) markedly inhibited cell migration and invasion in SW480 and HCT116 colorectal cancer cell lines. TIMP-1 was demonstrated to be negatively regulated by TUC.338 at the posttranscriptional level, via a specific target site within the 3' untranslated region by dual-luciferase reporter assay. The expression of TIMP-1 was also observed to inversely correlate with TUC.338 expression in CRC tissues. Over-expression of TIMP-1 with migRI-TIMP-1-GFP inhibited CRC cell migration and invasion and down-regulates MMP9, resembling that of TUC.338-siRNA. Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion. This article is protected by copyright. All rights reserved.

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Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD-1 antibodies

Abstract

A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the impact of blocking PD-1 on cytokine expression and on progression of lesions to cancer. The results of this study show increased production of IL-2 and the inflammatory cytokines IL-6, IL-17 and TNF-α by spleen cells of lesion-bearing mice that were treated with PD-1 antibody for one week compared to cytokine production by spleen cells of lesion-bearing mice treated with control antibody. Production of IFN-γ increased at 3 weeks of PD-1 antibody treatment, although production of the other Th1 and inflammatory mediators declined. By 5 weeks, levels of these cytokines declined for both control and PD-1 antibody-treated mice. Flow cytometric analysis for IFN-γ-expressing cells showed shifts in CD4⁺ cells expressing IFN-γ consistent with the changes in cytokine secretion. Whether or not treatment generated reactivity to lesions or HNSCC was determined. Spleen cells from PD-1 antibody-treated mice were stimulated by lysates of premalignant lesion and HNSCC tongue tissues to produce increased levels of Th1 and select inflammatory cytokines early in the course of PD-1 antibody treatment. However, with continued treatment, reactivity to lesion and HNSCC lysates declined. Analysis of clinical response to treatment suggested an early delay in lesion progression but, with continued treatment, lesions in PD-1 antibody-treated mice progressed to the same degree as in control antibody-treated mice. Overall, these results show an early beneficial response to PD-1 antibody treatment, which then fails with continued treatment and lesion progression. This article is protected by copyright. All rights reserved.

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Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival

Abstract

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Examining temporal effects on cancer risk in the International Nuclear Workers' Study (INWORKS)

ABSTRACT

from Cancer via ola Kala on Inoreader http://ift.tt/2gLuK5t
via IFTTT

TUC.338 promotes invasion and metastasis in colorectal cancer

Abstract

from Cancer via ola Kala on Inoreader http://ift.tt/2g3ICcR
via IFTTT

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD-1 antibodies

Abstract

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via IFTTT

Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery

Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis.

Methods

Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis. Expression of different cathepsins (CTS-B, -D, -F, -G, -K, -L, -O, and -S) was determined by quantitative RT-PCR and immunohistochemistry. The hand-held cathepsin-based fluorescent imaging system was used to detect peritoneal xenografts derived from human colon cancer cells (HT29, LoVo and HCT116) in nu/nu mice.

Results

While the expression levels of CTS-B, -D, -L, and -S could be higher in peritoneal tumors than normal peritoneum with a median (range) of 6.1 (2.9–25.8), 2.0 (1.0–15.8), 1.4 (0.8–7.0), and 2.1 (1.6–13.9) folds by quantitative RT-PCR, respectively, CTS-B was consistently the major contributor of the overall cathepsin expression in appendiceal and colonic peritoneal tumors, including adenocarcinomas and low-grade appendiceal mucinous neoplasms. Using peritoneal xenograft mouse models, small barely visible colonic peritoneal tumors (<2.5 mm in maximum diameter) could be detected by the hand-held cathepsin-based fluorescent imaging system.

Conclusions

Because cathepsin expression is higher in peritoneal tumors than underlying peritoneum, the hand-held cathepsin-based fluorescent imaging system could be useful for intraoperative detection of microscopic peritoneal metastasis during CRS-HIPEC and clinical trial is warranted.

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