Cancer by Sfakianakis Alexandros: 05/05/17

Παρασκευή 5 Μαΐου 2017

Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

Abstract

The fourth edition of the World Health Organization (WHO) classification of endocrine tumours contains substantial new findings for the adrenal tumours. The tumours are presented in two chapters labelled as "Tumours of the adrenal cortex" and "Tumours of the adrenal medulla and extra-adrenal paraganglia." Tumours of the adrenal cortex are classified as cortical carcinoma, cortical adenoma, sex cord stromal tumours, adenomatoid tumour, mesenchymal and stromal tumours (myelolipoma and schwannoma), haematological tumours, and secondary tumours. Amongst them, schwannoma and haematological tumours are newly documented. The major updates in adrenal cortical lesions are noted in the genetics of the cortical carcinoma and cortical adenoma based on the data from The Cancer Genome Atlas (TCGA). Also, a system for differentiation of oncocytoma from oncocytic cortical carcinoma is adopted. Tumours of the adrenal medulla and extra-adrenal paraganglia comprise pheochromocytoma, paraganglioma (head and neck paraganglioma and sympathetic paraganglioma), neuroblastic tumours (neuroblastoma, nodular ganglioneuroblastoma, intermixed ganglioneuroblastoma, and ganglioneuroma), composite pheochromocytoma, and composite paraganglioma. In this group, neuroblastic tumours are newly included in the classification. The clinical features, histology, associated pathologies, genetics, and predictive factors of pheochromocytoma and paraganglioma are the main changes introduced in this chapter of WHO classification of endocrine tumours. The term "metastatic pheochromocytoma/paraganglioma" is used to replace "malignant pheochromocytoma/paraganglioma." Also, composite pheochromocytoma and composite paraganglioma are now documented in separate sections instead of one. Overall, the new classification incorporated new data on pathology, clinical behaviour, and genetics of the adrenal tumours that are important for current management of patients with these tumours.

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Role of DNA methylation in the dietary restriction mediated cellular memory

Abstract

An important facet of dietary restriction (DR) that has been largely overlooked is that DR can have early effects that create a cellular memory, which persists even when DR is discontinued. The goal of this study was to determine if DNA methylation played a role in the cellular memory of DR by examining the effect of short-term DR on gene expression and DNA methylation and determining if the changes in expression and DNA methylation persist when DR is discontinued and mice returned to ad libitum (AL) feeding. We show that DR can induce substantial changes in gene expression within 1 month of its implementation in various tissues, and more interestingly, ~19–50% of these changes in gene expression persist across the tissues even when DR is discontinued. We then determined whether DR induced changes in DNA methylation in the promoter of three candidate genes identified from our gene expression analysis (Pomc, Hsph1, and Nts1) that correlated with the changes in the expression of these genes. Decreased methylation at three specific CG sites in the promoter of the Nts1 gene encompassing the distal consensus AP-1 site was correlated with increased Nts1 expression. Both the promoter hypomethylation and increased Nts1 expression persisted even after DR was discontinued and mice fed AL, supporting our hypothesis that DNA methylation could play a role in the memory effect of DR. The changes in DNA methylation in the Nts1 gene are likely to occur in intestinal stem cells and could play a role in preserving the intestinal stem cell pool in DR mice.

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Chemotherapy may eradicate ductal carcinoma in situ (DCIS) but not the associated microcalcifications

Publication date: Available online 4 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Hadassah Goldberg, Judith Zandbank, Varda Kent, Mia Leonov-Polak, Alejandro Livoff, Anna Chernihovsky, Michal Guindy, Ella Evron
IntroductionWe studied the effect of neoadjuvant chemotherapy (NAC)±trastuzumab on the ductal carcinoma in situ (DCIS) component in patients with locally advanced breast cancer who achieved pathological complete response (pCR).MethodsThe diagnostic biopsies of 92 consecutive breast cancer patients that were treated with neoadjuvant chemotherapy (NAC)±trastuzumab were evaluated for the presence of DCIS. Upon completion of NAC, the surgical specimens were evaluated for complete eradication of both the invasive and noninvasive cancer in the breast.The pretreatment mammograms were evaluated for the presence of microcalcifications and compared to the mammograms that were obtained upon completion of therapy prior to surgery.ResultsThirty of 92 patients (33%) had a substantial component of DCIS in the pretreatment biopsy. Thirty nine patients (42%) achieved pCR: 22 (56%) following NAC+trastuzumab, 17 (32%) following chemotherapy only. Ten of 30 patients (33%) with DCIS component achieved pCR: 4 received chemotherapy only, in 6 trastuzumab was added. Multiple microcalcifications on the pretreatment mammograms were observed in 3 of 10 patients with DCIS who achieved pCR. No reduction in the area of calcifications was observed following NAC.ConclusionsDCIS may be completely eradicated by NAC±trastuzumab. However, associated microcalcificatios probably persist. Patients with locally advanced breast cancer with substantial DCIS may still opt for NAC and breast conservation as the DCIS component may respond and even completely disappear following NAC. Residual widespread microcalcificatios after NAC do not necessarily indicate residual cancer. Larger studies are needed to direct the surgical management of these patients.

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Results after Surgical Treatment of Liver Metastases in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Carcinomas

Publication date: Available online 4 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Renate B. Galleberg, Ulrich Knigge, Eva Tiensuu Janson, Lene Weber Vestermark, Sven-Petter Haugvik, Morten Ladekarl, Seppo W. Langer, Henning Grønbæk, Pia Österlund, Geir Olav Hjortland, Jörg Assmus, Laura Tang, Aurel Perren, Halfdan Sorbye
BackgroundGastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC.Methods32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 >20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analyses for the entire cohort and for subgroups.ResultsMedian OS after resection/RFA of liver metastases was 35.9 months (95%-CI: 20.6–51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95%-CI: 3.9-13). Four patients (13%) were disease-free after five years. Two patients had well-differentiated morphology (NET G3) and 20 patients (63%) had Ki-67≥55%. A Ki-67<55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA.ConclusionThis study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.

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Contextual determinants of participation in cervical cancer screening in France, 2010

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Mélanie Araujo, Jeanna-Eve Franck, Emmanuelle Cadot, Arnaud Gautier, Pierre Chauvin, Laurent Rigal, Virginie Ringa, Gwenn Menvielle
BackgroundSome contextual factors associated with participation in cervical cancer screening are reported in the literature, but few studies have examined their combined effect. Our objective was to assess the role of contextual characteristics, separately and in combination, in participation in cervical cancer screening in France.MethodsMarginal Poisson regression models – taking into account the correlation between women in a given commune – were conducted using data from the Baromètre Santé 2010 survey. The characteristics of the commune of residence of the women studied were the potential spatial accessibility to general practitioners (GP) and gynecologists, the agglomeration category, and the socioeconomic level.ResultsThe analyses were performed in 3380 women, 88.2% of whom were up to date with their cervical cancer screening. Once the individual characteristics were taken into account, the screening participation rate was similar in all the communes, with the exception of those with poor access to a gynecologist and good access to a GP, where the rate was 6% lower (95%CI: 0.5–11%) than in the communes with good access to both GP and gynecologist. The same association with accessibility was observed in small agglomerations. Compared to women living in the more advantaged communes, the screening participation rate was 8% (2–12%) lower in those living in the more disadvantaged ones, except when accessibility to both types of physician was high.DiscussionWe observed an association between potential spatial accessibility to care in women's residential communities and their cervical cancer screening practices, in particular in small agglomerations, rural communes, and more disadvantaged communes.

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Contextual determinants of participation in cervical cancer screening in France, 2010

Foreword

Publication date: Available online 5 May 2017
Source:Surgical Oncology Clinics of North America
Author(s): Nicholas J. Petrelli

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Individual training at the undergraduate level to promote competence in breaking bad news in oncology

Abstract

Objective

Training medical students in breaking bad news (BBN) in oncology may be key to improve patient care in an area where many physicians tend to be uncomfortable. Given the lack of evidence in the literature, this study aimed to assess empirically the impact of two teaching strategies to prepare students for the task of BBN in oncology: one-to-one simulated patient (SP) training with individual feedback (intervention group) vs. small-group SP training with collective feedback (comparison group).

Methods

Fourth-year students (N = 236) were randomly assigned to the intervention or comparison group. SP videotaped interviews were analyzed with respect to: BBN communication performance, rated using the Calgary-Cambridge checklist of teaching objectives for BBN; verbal interaction behaviors, coded with the Roter Interaction Analysis System; and seven nonverbal behaviors.

Results

Students in the intervention group scored significantly higher after than before the training on the overall evaluation of the interview (P < .001) as well as on process skills (P < .001); they also obtained significantly higher scores compared to students in the comparison group on the overall evaluation of the interview (P < .001) and on process skills (P < .001).

Conclusions

This study supports an individualized BBN teaching strategy, and contributes to efforts to find the best way to train and reach the largest number of future physicians to improve communication competences in oncology.

http://ift.tt/2pffr82

Mindfulness-Based Cognitive Therapy (MBCT) is Cost-Effective Compared to a Wait-List Control for Persistent Pain in Women Treated for Primary Breast Cancer - Results from a Randomized Controlled Trial

Abstract

Objective

To investigate the cost-effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) com- pared to a wait-list control group for pain in women treated for breast cancer.

Methods

A total of 129 women were randomly allocated to MBCT or a wait-list control group. The primary outcome was the Minimal Clinically Important Difference (MCID) on pain intensity (>2 point reduction on an 11-point Numeric Rating Scale). Analyses were conducted from the healthcare system perspective and included data on healthcare utilization and pain medication retrieved from national registries for the period from baseline (T1) to 6 months post-intervention (T4). Bootstrap simulations were used to estimate confidence intervals for the incremental cost and effect measures, and Cost-Effectiveness Acceptability Curves (CEAC). In sensitivity analyses, we replaced dropouts with last-observation-carried-forward and tested consequences of higher costs of the intervention.

Results

The intervention cost was 240€ per participant. The average total cost from T1-T4 in the MBCT group was 1706€ compared with 2436€ in the control group (mean difference: 729€, p = 0.07). More women in the MBCT group (N:19/36; 52.8%) than in the control group (N:14/48; 29.2%) achieved a MCID in pain intensity (OR = 2.71, p = 0.03). The MBCT was cost-effective with a probability of 85%, and remained cost-effective with a probability of 70-82% when smaller effect and higher MBCT costs were assumed.

Conclusions

Our results suggest that MBCT is a cost-effective pain intervention for women treated for breast cancer. Future studies could include utility measures, indirect costs, and active control groups to increase the generalizability and pragmatic value of the results.

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Individual training at the undergraduate level to promote competence in breaking bad news in oncology

Abstract

Objective

Methods

Results

Conclusions

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Mindfulness-Based Cognitive Therapy (MBCT) is Cost-Effective Compared to a Wait-List Control for Persistent Pain in Women Treated for Primary Breast Cancer - Results from a Randomized Controlled Trial

Abstract

Objective

To investigate the cost-effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) com- pared to a wait-list control group for pain in women treated for breast cancer.

Methods

Results

Conclusions

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Preoperative chemoradiotherapy for rectal cancer and impact on outcomes – A population-based study

Preoperative (chemo)radiotherapy ((C)RT) for rectal cancer is, in Norway, restricted to patients with cT4-stage or threatened circumferential resection margin. This nationwide population-based study assessed the use of preoperative (C)RT in Norway and its impact on treatment outcomes.

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Mothers with breast cancer: A mixed-method systematic review on the impact on the parent-child relationship

Abstract

Objective

To systematically review and integrate the findings from quantitative and qualitative studies on parenting and parent-child relationships in families where mothers had Breast Cancer (BC).

Methods

Ten different databases were searched from inception to January 2016. All authors assessed these data independently. Full-text, peer-reviewed articles exploring parenting and/or mother-child relationships in families where the mother had BC, regardless of cancer stage, were considered for inclusion. PRISMA guidelines were followed.

Results

From 116 studies, 23 were deemed eligible for inclusion. Five of them were quantitative, 15 were qualitative, and one study used a mixed-method approach. Most studies analysed the mother's perceptions about the experience of having BC in parenting and in the parent-child relationship. The majority of studies explored experiences and perspectives on the parent-child relationship in mothers with minor children, although a minority of studies included adult children. Additionally, a few studies (17%) addressed perceptions and experiences of women with advanced stage cancer. Three main themes were found: priorities and concerns of patients; decision-making processes about sharing the diagnosis with their children; and mother-child relationship and parenting after mother's diagnosis.

Conclusions

Findings indicated that the diagnosis of BC is accompanied by an array of challenges that affect parental roles and parenting. Further studies are needed in order to explore these issues more sensitively. For now, however, the evidence suggests that the families of women with BC, and particularly the women themselves, may benefit from informal and formal support aimed at helping them cope effectively with this challenging life event.

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Mothers with breast cancer: A mixed-method systematic review on the impact on the parent-child relationship

Abstract

Objective

To systematically review and integrate the findings from quantitative and qualitative studies on parenting and parent-child relationships in families where mothers had Breast Cancer (BC).

Methods

Results

Conclusions

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Correction to: Cancer Biother Radiopharm 2017;32(3):101–110

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.

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Correction to: Cancer Biother Radiopharm 2017;32(3):101–110

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.

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Population-based assessment of racial/ethnic differences in utilization of radical cystectomy for patients diagnosed with bladder cancer

Abstract

Purpose

Radical cystectomy is a surgical treatment for recurrent non-muscle-invasive and muscle-invasive bladder cancer; however, many patients may not receive this treatment.

Methods

A total of 27,578 patients diagnosed with clinical stage I–IV bladder cancer from 1 January 2007 to 31 December 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry database. We used multivariable regression analyses to identify factors predicting the use of radical cystectomy and pelvic lymph node dissection. Cox proportional hazards models were used to analyze survival outcomes.

Results

A total of 1,693 (6.1%) patients with bladder cancer underwent radical cystectomy. Most patients (92.4%) who underwent radical cystectomy also underwent pelvic lymph node dissection. When compared with white patients, non-Hispanic blacks were less likely to undergo a radical cystectomy [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. Moreover, recent year of surgery 2013 versus 2007 (OR 2.32, 95% CI 1.90–2.83, p < 0.001), greater percentage of college education ≥36.3 versus <21.3% (OR 1.23, 95% CI 1.04–1.44, p = 0.013), Midwest versus West (OR 1.64, 95% CI 1.39–1.94, p < 0.001), and more advanced clinical stage III versus I (OR 29.1, 95% CI 23.9–35.3, p < 0.001) were associated with increased use of radical cystectomy. Overall survival was improved for patients who underwent radical cystectomy compared with those who did not undergo a radical cystectomy (hazard ratio 0.88, 95% CI 0.80–0.97, p = 0.008).

Conclusion

There is significant underutilization of radical cystectomy in patients across all age groups diagnosed with bladder cancer, especially among older, non-Hispanic black patients.

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Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE, France)

Abstract

Purpose

To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT.

Methods

We pooled data from two French national population-based case–control studies with similar designs conducted in 2003–2004 and 2010–2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin.

Results

No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74).

Conclusion

We found some evidence of a weak association between paternal smoking in the year before the child's birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes.

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Population-based assessment of racial/ethnic differences in utilization of radical cystectomy for patients diagnosed with bladder cancer

Abstract

Purpose

Radical cystectomy is a surgical treatment for recurrent non-muscle-invasive and muscle-invasive bladder cancer; however, many patients may not receive this treatment.

Methods

Results

Conclusion

There is significant underutilization of radical cystectomy in patients across all age groups diagnosed with bladder cancer, especially among older, non-Hispanic black patients.

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Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE, France)

Abstract

Purpose

To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT.

Methods

Results

Conclusion

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Poppers retinopathy

Joshua Luis Mar 7, 2016; 2016:bcr2016214442-bcr2016214442 case-report

http://ift.tt/2p5BlQ9

Cutaneous and pleural involvement in a patient with multiple myeloma

Olfa Saidane Oct 5, 2015; 2015:bcr2015211197-bcr2015211197 case-report

http://ift.tt/2qMGZmE

Potential involvement of Campylobacter curvus and Haemophilus parainfluenzae in preterm birth

George Louis Mendz Oct 1, 2014; 2014:bcr2014205282-bcr2014205282 case-report

http://ift.tt/2p58qvA

Use of ticagrelor in human pregnancy, the first experience

Marjan Verbruggen Nov 25, 2015; 2015:bcr2015212217-bcr2015212217 case-report

http://ift.tt/2qMqnvf

Pleural effusion caused by a malpositioned umbilical venous catheter in a neonate

Thangaraj Abiramalatha Oct 30, 2015; 2015:bcr2015212705-bcr2015212705 case-report

http://ift.tt/2p5j6dj

Molecular detection of Schizophyllum commune in a case of allergic fungal rhinosinusitis

Prashant Gupta May 24, 2015; 2015:bcr2015209955-bcr2015209955 case-report

http://ift.tt/2p5JDaz

Steroid unresponsive anti-NMDA receptor encephalitis during pregnancy successfully treated with plasmapheresis

Lokesh Shahani Apr 29, 2015; 2015:bcr2014208823-bcr2014208823 case-report

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Actinomyces meyeri brain abscess following dental extraction

U Clancy Apr 13, 2015; 2015:bcr2014207548-bcr2014207548 case-report

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Rothia aeria: a great mimicker of the Nocardia species

Takeshi Saraya Dec 3, 2014; 2014:bcr2014206349-bcr2014206349 case-report

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Maxillary sinusitis with pulmonary tuberculosis

Rashmi Upadhyay Aug 1, 2014; 2014:bcr2014203952-bcr2014203952 case-report

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Calvarial and cutaneous metastasis as the primary presentation of a renal cell carcinoma

Tarun Jindal May 19, 2014; 2014:bcr2013202830-bcr2013202830 case-report

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Fatal Bipolaris spicifera infection in an immunosuppressed child

Carlos G Teran Feb 3, 2014; 2014:bcr2013009703-bcr2013009703 case-report

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Subcutaneous endometriosis: a rare cause of deep dyspareunia

Aruna Nigam Jan 6, 2014; 2014:bcr2013202230-bcr2013202230 case-report

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Quetiapine-induced manic episode: a paradox for contemplation

Sundar Gnanavel Dec 4, 2013; 2013:bcr2013201761-bcr2013201761 case-report

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Enterobius vermicularis infection of the ovary

George Powell Oct 31, 2013; 2013:bcr2013201146-bcr2013201146 case-report

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Heterotopic ossification of the elbows in a major petrol burn

Shahriar Raj Zaman Aug 27, 2012; 2012:bcr0320126027-bcr0320126027 case-report

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Primary disseminated extrahepatic abdominal hydatid cyst: a rare disease

Jitendra Kumar Kushwaha May 30, 2012; 2012:bcr0220125808-bcr0220125808 case-report

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Autoimmune pernicious anaemia as a cause of collapse, heart failure and marked panyctopaenia in a young patient

Justin Carey May 8, 2012; 2012:bcr0120125576-bcr0120125576 case-report

http://ift.tt/2qMpumg

Still dizzy after all these years: a 90-year-old woman with a 54-year history of dizziness

Alina Smirnova Sep 15, 2011; 2011:bcr0520114247-bcr0520114247 case-report

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Cardiac arrhythmias associated with umbilical venous catheterisation in neonates

Gerdina Verheij Jun 21, 2009; 2009:bcr0420091778-bcr0420091778 case-report

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Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Gladys Blandino, Marina Guenzi, Liliana Belgioia, Elisabetta Bonzano, Elena Configliacco, Elena Tornari, Francesca Cavagnetto, Davide Bosetti, Alessandra Fozza, Daniele Friedman, Renzo Corvò
BackgroundThe present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program.Materials and methodsFrom October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3–50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS).ResultsWith a median follow up of 47 months (range 10–78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively.ConclusionAlthough we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

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Evaluating the performance of TG-43 protocol in esophageal HDR brachytherapy viewpoint to trachea inhomogeneity

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Seyed Mohsen Hosseini Daghigh, Hamid Reza Baghani, Seyed Mahmoud Reza Aghamiri, Seyed Rabi Mahdavi
AimThe aim of this study is to evaluate the effect of air within trachea on dose calculations of esophageal HDR brachytherapy treatment planning.BackgroundDose calculations in esophageal HDR brachytherapy treatment planning systems are greatly based on TG-43 protocol which in all materials are considered to be water equivalent.Materials and methodsA cylindrical PMMA phantom with a tube in the center (neck equivalent phantom) accompanied by Flexitron HDR brachytherapy system was used in this study. Brachytherapy applicators with various diameters were placed inside the esophageal tube and EDR2 film was used for dosimetry. The absorbed dose by reference point of esophageal HDR brachytherapy and anterior wall of trachea were measured and compared with those calculated by Flexiplan treatment planning system.ResultsBased on the performed statistical analysis (t-test) with 95% confidence level (t-value >1.96), there was a meaningful difference between the results of film dosimetry and treatment planning at all of the points understudy.ConclusionThe meaningful difference between the results of film dosimetry and treatment planning indicates that the trachea inhomogeneity has a considerable effect on dose calculations of Flexiplan treatment planning software featuring the TG-43 dose calculation algorithm. This mismatch can affect the accuracy of performed treatment plan and irradiation.

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Effect of tumor amplitude and frequency on 4D modeling of Vero4DRT system

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Hideharu Miura, Shuichi Ozawa, Masahiro Hayata, Shintaro Tsuda, Kiyoshi Yamada, Yasushi Nagata
BackgroundAn important issue in indirect dynamic tumor tracking with the Vero4DRT system is the accuracy of the model predictions of the internal target position based on surrogate infrared (IR) marker measurement. We investigated the predictive uncertainty of 4D modeling using an external IR marker, focusing on the effect of the target and surrogate amplitudes and periods.MethodsA programmable respiratory motion table was used to simulate breathing induced organ motion. Sinusoidal motion sequences were produced by a dynamic phantom with different amplitudes and periods. To investigate the 4D modeling error, the following amplitudes (peak-to-peak: 10–40mm) and periods (2–8s) were considered. The 95th percentile 4D modeling error (4D-E95%) between the detected and predicted target position (μ+2SD) was calculated to investigate the 4D modeling error.Results4D-E95% was linearly related to the target motion amplitude with a coefficient of determination R²=0.99 and ranged from 0.21 to 0.88mm. The 4D modeling error ranged from 1.49 to 0.14mm and gradually decreased with increasing target motion period.ConclusionsWe analyzed the predictive error in 4D modeling and the error due to the amplitude and period of target. 4D modeling error substantially increased with increasing amplitude and decreasing period of the target motion.

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Spironolactone ameliorates the cardiovascular toxicity induced by concomitant trastuzumab and thoracic radiotherapy

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Guler Yavas, Esin Celik, Cagdas Yavas, Cagdas Elsurer, Rengin Elsurer Afsar
AimWe aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity of concomitant use of radiotherapy (RT) and trastuzumab (T).BackgroundS, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S ameliorates anthracycline -induced cardiotoxicity, there is no data regarding to effect of S on both T and radiation-induced cardiotoxicity.Materials/MethodsEighty rats were divided into eight groups: group (G) 1 was defined as control group. G2, G3 and G4 were RT, S and T groups respectively. G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. Rats were sacrificed at 6th hour; 21st and 100th days after RT. Heart and thoracic aorta samples were taken for microscopical examination.ResultsCardiac inflammation and fibrosis scores and; TGF-β expression were not significantly different within study groups at 6th hour and 21st days of RT. By 100th days of RT fibrosis scores and TGF-β expression in cardiac samples were significantly different between study groups (p values were 0.004 and 0.002 respectively). Pair-wise comparisons revealed that both cardiac fibrosis scores and TGF-β expression levels were higher in G5 when compared to G8 (p values were 0.046 and 0.028 respectively). Moreover the TGF-β expression was higher in G5 when compared to G2 (p=0.046). We could not demonstrate any significant differences with respect to inflammation, fibrosis and TGF-β expression in thoracic aorta samples between study groups.ConclusionsAlthough S had a protective effect on cardiac tissue it had no protective effect on thoracic aorta when administered with RT+T.

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Validation of the liver mean dose in terms of the biological effective dose for the prevention of radiation-induced liver damage

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Hiroshi Doi, Norihisa Masai, Kenji Uemoto, Osamu Suzuki, Hiroya Shiomi, Daisaku Tatsumi, Ryoong-Jin Oh
AimThe purpose of this study was to determine the optimal mean liver biologically effective dose (BED) to prevent radiation-induced liver disease (RILD) in stereotactic body radiation therapy (SBRT).BackgroundThe actual mean doses appropriate for liver irradiation in modern radiotherapy techniques have not been adequately investigated, although SBRT is sometimes alternatively performed using fractionated regimens.Materials and methodsSBRT treatment plans for liver tumors in 50 patients were analyzed. All distributions of the physical doses were transformed to BED2 using the linear-quadratic model. The relationship between physical doses and the BED2 for the liver were then analyzed, as was the relationship between the mean BED2 for the liver and the planning target volume (PTV).ResultsA significantly positive correlation was observed between the mean physical dose for the background liver and the mean BED2 for the whole liver (P<0.0001, r=0.9558). Using the LQ model, a mean BED2 of 73 and 16Gy for the whole liver corresponded to the hepatic tolerable mean physical dose of 21 and 6Gy for Child–Pugh A- and B-classified patients, respectively. Additionally, the PTV values were positively correlated with the BEDs for the whole liver (P<0.0001, r=0.8600), and the background liver (P<0.0001, r=0.7854).ConclusionA mean BED2 of 73 and 16Gy for the whole liver appeared appropriate to prevent RILD in patients with Child–Pugh classes A and B, respectively. The mean BED2 for the liver correlated well with the PTV.

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Neoadjuvant chemoradiotherapy of the rectal carcinoma – The correlation between the findings on the restaging multiparametric 3T MRI scanning and the surgical findings

Publication date: July–August 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 4
Author(s): Radovan Vojtíšek, Eva Korčáková, Jan Mařan, Ondřej Šorejs, Jindřich Fínek
AimTo figure out how to correlate the findings on functional MRI and carried out after neoadjuvant CRT of rectal carcinoma with final histology after surgery.BackgroundNeoadjuvant CRT is the standard treatment of locally advanced rectal carcinoma. Its use leads to the downstaging of the disease and in 15–42% of patients even to the detection of pCR after TME. The use of functional MRI improves the sensitivity and specificity of pCR detection up to 52–64% and 89–98%, respectively.Materials and methodsBetween January 2013 and June 2016, 67 patients suffering from histologically proven locally advanced rectal cancer underwent neoadjuvant RT or CRT. We selected for further investigation only patients (33 patients) who underwent pelvic staging and restaging using multiparametric imaging on 3T MRI scanner. We compared the findings on functional MRI after neoadjuvant CRT with final histology after surgery.ResultsIn 15 patients pathologic staging of primary tumor differed from expected staging assessed according to preoperative MRI. In 5 patients pathologic complete remission was achieved. In none of these 5 patients pCR was predicted using preoperative MRI. Sensitivity and specificity of MRI in predicting pCR were 0% and 96%. Accuracy of MRI in predicting pT and pN was 79% and 74%.ConclusionsWe have verified that the use of neoadjuvant CRT in the treatment of locally advanced rectal carcinoma leads to a possible achievement of pCR. But in our group of patients this was not predictable nor was it with the use of multiparametric 3T MRI.

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Comparison of Outcomes with Hand-sewn Versus Stapler Closure of Pancreatic Stump in Distal Pancreatectomy

Aim: The optimal method for pancreatic stump closure to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP), remains controversial though DP is still the only curative treatment for pancreatic cancer and other malignancies located on pancreatic body or tail. Patients and Methods: A total of 44 patients who consecutively underwent open DP were retrospectively analyzed, dividing them into two groups: group H (hand-sewn; n=24) and group S (stapler closure; n=20). Results: POPFs were encountered in 5 (21%) and 11 (55%) patients in groups H and S, respectively (p=0.02). POPFs of Clavien–Dindo grade IIIa or above were observed in two (8%) and seven (35%) patients in groups H and S, respectively (p=0.03). Conclusion: When indicating stapler closure, caution should be exercised for pancreatic consistency and thickness, device and cartridge type, and pancreatic duct ligation to more effectively control POPF rates.

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Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer

Aim: We assessed the efficacy and toxicity of salvage radiotherapy for solitary metachronous bone metastasis (SMBM) in patients with breast cancer. Patients and Methods: We retrospectively analyzed 17 patients with SMBM who were treated with salvage radiotherapy. First failure was detected as SMBM in all patients. Salvage radiotherapy using three-dimensional treatment planning was performed at a median total dose of 50 Gy. Median daily dose was 2.0 Gy. Results: Median follow-up was 40 months. Local recurrence of SMBM was noted in only two patients. The 3-year overall survival, progression-free survival, and local control rates were 93%, 51%, and 85%, respectively. Median overall and progression-free survival were 74 and 30 months, respectively. Toxicities were mild, and bone fractures were not observed. Conclusion: Salvage radiotherapy for SMBM was able to achieve higher local control rates without severe toxicity, as well as to provide longer progression-free survival; therefore, this may be an effective modality.

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Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

Background/Aim: Prognoses of patients receiving radio-chemotherapy with 5-fluorouracil (5-FU) and cisplatin for unresectable esophageal cancer may be improved with the addition of cetuximab. This phase I study aimed to define the maximum tolerated dose of 5-FU when combined with cisplatin, cetuximab and radiotherapy. Patients and Methods: Treatment included 59.4 Gy of radiotherapy concurrently with two courses of cisplatin (20 mg/m², d1-4) and 5-FU (dose level 0: 500 mg/m², dose level 1: 750 mg/m², d1-4; dose level 2: 1,000 mg/m², d1-4), followed by two courses of chemotherapy. Cetuximab was given for 14 weeks (400 mg/m² loading dose followed by 250 mg/m² weekly). Results: At dose level 1 (n=3) and 2 (n=3), no patient experienced a dose-limiting toxicity. Minor treatment modifications were due to organization or request by physicians/patients. At dose level 2, only five grade 3 adverse events occurred. Conclusion: Dose level 2 appears safe and is used in a subsequent randomized phase II study.

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Dose Escalation Improves Outcome in Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer

Aim: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for pulmonary metastasis from colorectal cancer. Patients and Methods: Data for 104 lesions from 93 patients who underwent SBRT for pulmonary oligometastases from colorectal cancer at ten Institutions were retrospectively analyzed. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: The median calculated biological effective dose using the linear-quadratic model with α/β of 10 Gy (BED10) was 105.6 Gy. Adjuvant chemotherapy after SBRT was performed in 47 patients. The median observation period was 28 months. The 3- and 5-year local control rates were 65.2% and 56.2%, respectively. The 3- and 5-year overall survival rates were 55.9% and 42.7%, respectively. Only two patients had grade 3 radiation pneumonitis. In multivariate analysis for local control, primary site, age, adjuvant chemotherapy after SBRT and BED10 were selected as prognostic factors. Conclusion: Dose escalation and adjuvant chemotherapy might improve local control in SBRT for pulmonary oligometastases from colorectal cancer.

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Initial Experience with Nab-Paclitaxel for Patients with Advanced Gastric Cancer: Safety and Efficacy

Background: Taxane-based chemotherapy is useful for peritoneal dissemination control in advanced/recurrent gastric cancer; however, insufficient relative dose intensity (RDI) may preclude disease control achievement. Nab-paclitaxel, with high tumour permeability, is a promising second- or later-line treatment. Patients and Methods: We retrospectively evaluated the clinical safety and efficacy of nab-paclitaxel for advanced/recurrent gastric cancer patients treated between April 2013 and December 2015. The response rate, RDI and survival outcomes were assessed. Results: Of 14 evaluated patients, 4 achieved partial response. Overall response and the disease control rates were 28.5% and 64.2%, respectively. Nine patients developed peritoneal metastasis; their overall response and disease control rate were 22.2% and 66.6%. Patients with high RDI (≥80%) showed longer progression-free and overall survival than those with low RDI (≤80%) (11.8 vs. 4.0 months, p=0.02; and 14.3 vs. 8.2 months, p=0.03, respectively). Conclusion: Nab-paclitaxel, at an RDI ≥80%, was safe and beneficial for these patients.

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Simplified Comorbidity Score and Eastern Cooperative Oncology Group Performance Score Predicts Survival in Patients Receiving Organ-preserving Treatment for Bladder Cancer

Background/Aim: This study investigated three comorbidity scales and the Eastern Cooperative Oncology Group performance score (ECOG-PS) for survival in patients receiving local irradiation for bladder cancer. Patients and Methods: Sixty-four patients receiving organ-preserving radio-chemotherapy or radiotherapy for urinary bladder cancer were retrospectively evaluated. Charlson Comorbidity Index (CCI), Simplified Comorbidity Score (SCS), Age-Adjusted Charlson Comorbidity Index (AAC) and ECOG-PS were analyzed for associations with survival. Results: Patients with a SCS of 0-7 points had a significantly better survival than those with 8-18 points (p=0.018). Five-year survival rates were 64% and 32%, respectively. Patients with ECOG-PS of 0-1 had a significantly better 5-year survival than patients with ECOG-PS of 2-3 (64% vs. 0%, p<0.001). For CCI (p=0.16) and AAC (p=0.49), a significant association with survival was not observed. Conclusion: SCS and ECOG-PS were significantly associated with survival in patients irradiated for bladder cancer and can help estimate the prognoses of these patients.

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Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence - A Phase II Study

Aim: To evaluate feasibility and safety of neoadjuvant chemotherapy with capecitabine, oxaliplatin and bevacizumab followed by concomitant standard chemoradiation and surgical resection in patients with high-risk locally advanced rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI)-defined high-risk cT3/4 rectal cancer patients were treated with 3 cycles of neoadjuvant chemotherapy with capecitabine (1,000 mg/m² twice daily days 1-14, 22-35, 43-56), oxaliplatin (130 mg/sqm on days 1, 22, 43) and bevacizumab (7.5 mg/kg on days 1, 22, 43) followed by capecitabine (825 mg/m² twice daily on radiotherapy days week 1-4) concomitantly with radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks) and surgical resection by total mesorectal excision. Feasibility, safety, response rate and postoperative morbidity were evaluated. Results: Twenty-five patients were recruited. Median age was 62 years (range=24-78 years) and all patients had Eastern Cooperation Oncology Group (ECOG) performance status 0. From all patients, 79.2% finished neoadjuvant chemotherapy. Twenty patients underwent surgery. Pathologic complete remission rate, R0 resection and T-downstaging were achieved in 25%, 95% and 54.2% of the "intention to treat" (ITT) patients. The most common grade 3 adverse events (AEs) during neoadjuvant chemotherapy were diarrhea (16.6%) and mucositis (12.5%). In one patient, a grade 4 acute renal failure occurred (4.2%). During chemoradiation, skin reactions (5.3%) were the most common grade 3 AEs. Two major perioperative complications required re-intervention. Conclusion: Neoadjuvant chemotherapy with bevacizumab, capecitabine and oxaliplatin followed by concomitant standard chemoradiation is feasible in patients with high-risk locally advanced rectal cancer (LARC) and resulted in complete pathologic remission (pCR) rate of 25% and neoadjuvant chemotherapy completion rate of 80%.

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Importance of Preoperative Knowledge of the Biomarker HE4 in Early-stage Endometrial Cancer Regarding Surgical Management

Aim: To analyze the utility of HE4 assessment in preoperative management of patients with early-stage endometrial cancer for stratification into low-risk and high-risk groups. Patients and Methods: The following data were prospectively collected from patients operated for endometrial cancer from 05/2012 till 9/2016; age, HE4, CA125, expert ultrasound examination of the pelvis, histotype, grade, FIGO stage. Results: In total, 124 patients were enrolled. A cut-off of ≥113 pmol/l HE4 demonstrated 40.3% sensitivity and 83.9% specificity for detection of high-risk patients. Correlations of HE4 with age (p<0.001), depth of myometrial invasion (p=0.001), clinical stage of the disease according to ultrasound - T1a vs. T1b (63.6 pmol/l vs. 110.6 pmol/l, p<0.001) were found. However, no correlation of HE4 with lymph node invasion (p=0.07) and tumor grade (p=0.212) was identified. Conclusion: HE4 levels correspond to clinical and FIGO stage of the disease. The sensitivity and specificity does not reach the transvaginal ultrasound results in preoperative assessment of the extent of the disease. Combination of HE4 with ultrasound does not improve the stratification of patients into low-risk and high-risk groups. Preoperative assessment of HE4 is useful providing no imaging method is available.

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PD-L1 Expression in Patients with Non-small Cell Lung Cancer

Aim: The aim of this study was to evaluate whether irradiation induces the expression of tumor programed cell death ligand 1 (PD-L1) in patients with non-small cell lung cancer (NSCLC). Patients and Methods: Seventeen patients with NSCLC who received chemoradiotherapy and underwent tumor resection and six patients whose pre-treatment biopsy specimens were available, were analyzed by immunohistochemistry for PD-L1 expression between September 2011 and June 2016 at the Institute of Biomedical Research and Innovation Hospital. Results: Among six patients for which pre-irradiation biopsy samples were available, the H-score for PD-L1 was reduced after irradiation following staining with two different antibody clones (SP28-8 and SP142). A PD-L1 H-score >5 with SP28-8 antibody (hazard ratio=6.46; 95% confidence interval=1.209-34.53; p=0.029) was a significant negative factor for duration of progression-free survival after curative operation or chemoradiation. Conclusion: We showed that tumor PD-L1 expression decreased in patients with NSCLC who received chemoradiotherapy and radiation resistance might be due to pre-treatment PD-L1 expression.

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Predictive Independent Factors for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy

Aim: The aim of this study was to investigate the prognostic factors associated with extrahepatic metastasis of primary hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively analyzed 559 patients with HCC who underwent curative hepatectomy. We divided the patients into no recurrence (NoR), intrahepatic early recurrence (IHER), intrahepatic late recurrence (IHLR), and extrahepatic recurrence (EHR) groups. We compared the non-metastatic group (IHLR and NoR) with the metastatic group (IHER and EHR) and also compared IHER with EHR to determine risk factors for EHR. Results: There were 252, 163, 109, and 35 patients with NoR, IHER, IHLR, and EHR, respectively. For the EHR group, the independent risk factor was vascular invasion. The EHR group had better liver function and worse tumor factors. Conclusion: Vascular invasion is predictive of extrahepatic metastasis of HCC.

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Genome-wide Expression Profiling (with Focus on the Galectin Network) in Tumor, Transition Zone and Normal Tissue of Head and Neck Cancer: Marked Differences Between Individual Patients and the Site of Specimen Origin

Background/Aim: Expression profiling was performed to delineate and characterize the impact of malignancy by comparing tissues from three sites of head and neck cancer of each patient, also determining interindividual variability. Materials and Methods: Genome-wide analysis was carried out covering the expression of 25,832 genes with quantification for each site of seven patients with tonsillar or oropharyngeal squamous cell carcinoma. Immunohistochemical analysis was performed for adhesion/growth-regulatory galectins, three pro-inflammatory chemo- and cytokines and keratins. Results: Up- and down-regulation was found for 281 (tumor vs. normal) and 276 genes (transition zone vs. normal), respectively. The profile of the transition zone had its own features, with similarity to the tumor. Galectins were affected in a network manner, with differential regulation and interindividual variability between patients, also true for keratins and the chemo- and cytokines. Conclusion: These results underline special features at each site of specimen origin as well as the importance of analyzing galectins as a network and of defining the expression status of the individual patient prior to reaching clinically relevant conclusions.

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Are Corrupted Non-dysplastic Colonic Crypts the First Histological Event in Experimental Colonic Carcinogenesis?

Background: The colonic crypts in rats replicate by symmetric fission at the base of the crypts, and proceeds upwards, to generate two separate identical crypts. Recently, anomalous crypts (called corrupted colonic crypts, CCCs) were found in the colonic mucosa of Sprague-Dawley rats treated with the carcinogen dimethylhydrazine. Here it was investigated whether CCCs develop in the colonic mucosa of another rat strain, treated with a different carcinogen. Materials and Methods: Archived Swiss-roll colon sections from 25 male Fisher-344 rats treated with the mutagen 2-amino-6-methyldipyrido imidazole (GLU1) were reviewed. Non-dysplastic and dysplastic CCCs were regarded as those exhibiting asymmetric fission, asymmetric lateral sprouting/lateral fission, basal dilatations, or spatial aberrations of the normal (vertical) axis. Colonic adenomas were found in three out of the 25 specimens. Results: In the entire colonic mucosa of the 25 GLU1-treated rats, 130 non-dysplastic CCCs were recorded amongst 357 non-dysplastic crypts with fission (36.4%). The mean number of non-dysplastic CCCs per animal was 5.2 (range=2-12). These numbers only mirror events taking place at a particular time (i.e. at sacrifice). Considering the high cell production rate of the colonic crypts, the actual number of CCCs/rat occurring during the usual mucosal turnover time of 72 hours might be substantial. In the three adenoma specimens, non-dysplastic CCCs were found underneath CCCs with dysplasia. Discussion and Conclusion: For many years, the development of crypt dysplasia and adenoma have been considered the initial histological events in colonic carcinogenesis. This study demonstrates that non-dysplastic CCCs also develop in GLU 1-treated Fisher-344 rats. Non-dysplastic CCCs were found underneath CCCs with dysplasia. Non-dysplastic CCCs might act as scaffolds at the time of top-down cell replacement/transformation of the crypts by dysplastic cells. It is submitted that non-dysplastic CCCs might be the initial histological recordable event in experimental colonic carcinogenesis.

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Griseofulvin Efficiently Induces Apoptosis in In Vitro Treatment of Lymphoma and Multiple Myeloma

Background/Aim: Recent innovations in the development of systemic and targeted therapies have improved survival and quality of life in multiple myeloma (MM) patients. However, in most cases, this hematological malignancy of monoclonal B-lymphocytes remains incurable. Exaggerated Wnt/β-catenin signaling has been demonstrated in lymphoma and MM, therefore targeting related signaling molecules might represent a promising therapy approach. Griseofulvin, a widely used antifungal drug, is chemically related to other known Wnt-inhibitors and we recently demonstrated its potent in vivo efficacy in a murine myeloma model. Materials and Methods: The anti-tumor apoptotic effect of griseofulvin at doses ranging from 0.1-200 μM was investigated on a total of ten human and two murine myeloma/lymphoma cell lines, as determined by 3'3-dihexyloxacarbocyanine iodide (DiOC6) and propidium iodide (PI) staining in flow cytometry. Results: Griseofulvin significantly induced apoptosis in all investigated myeloma and lymphoma cell lines in a dose-dependent manner, while healthy control cells were less sensitive. Conclusion: Given the known safety profile and apoptosis induction at low effective doses, our data warrant further in vitro and in vivo studies utilizing griseofulvin as a potential therapy agent for MM and lymphoma.

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The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

Background/Aim: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCs). We investigated the expression of these markers and their clinical significance in lung adenocarcinoma. Materials and Methods: An immunohistochemical analysis of ALDH1A1 and CD133 expression of 92 lung adenocarcinomas was performed. The association between the expression of both markers and cancer-related death and recurrence was determined. Results: Cancer-related death and tumor recurrence were observed in 15 and 17 cases, respectively. The expression of CD133, but not ALDHA1A, was significantly associated with poorer overall survival (p<0.0001) and shorter disease-free interval (DFI) (p<0.0001). Multivariate analysis revealed that double negativity was independently associated with increased survival (hazard ratio(HR)=16.1, p=0.0004) and a longer DFI (HR=9.5, p=0.0007). Conclusion: We propose that as a functional marker, ALDH1A1 positivity may influence the viability of CSCs. The findings suggest that it is important to evaluate the expression of both markers.

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Erratum

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Intraoperative Local Ablative Therapies Combined with Surgery for the Treatment of Bilobar Colorectal Liver Metastases

Aim: To investigate the role of intraoperative local ablation techniques (LATs) in bilobar colorectal liver metastases (bCRLM). Patients and Methods: Among patients who underwent LAT for CRLM between 2005 and 2015, we selected 33 patients with bilobar disease submitted to thermal ablation alone or associated to liver resection. Primary end-point was complete local response at one month (CLR). Secondary end-points were morbidity, mortality, disease-free survival (DFS), local tumor recurrence (LTR) and long-term survival. Results: CLR was observed in 100% of cases, while LTR occurred in 8 cases (22%). DFS at 1, 3 and 5 years was 37%, 5% and 5%. Overall survival (OS), in the same interval, was 95%, 49% and 26%. Univariate analysis found a significant correlation between LTR and tumor size (11% ≤20 mm vs. 50% >20 mm; p=0.009). Conclusion: LAT is an effective adjuvant strategy in bCRLM for nodules within 20 mm diameter.

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Erratum

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Relationship Between Circulating Tumor Cells and Annexin A2 in Early Breast Cancer Patients

Background/Aim: Annexin A2 (ANXA2) is a phospholipid-binding protein involved in fibrinolysis, cell proliferation, migration and metastatic dissemination. Circulating tumor cells (CTCs) are cells responsible for tumor dissemination and have a prognostic value in several types of cancers including breast cancer. Previously, we found correlation between CTCs and activation of coagulation. This study aimed to correlate CTCs with ANXA2 expression on CTCs, tumor cells and tumor associated stroma in primary breast cancer (PBC) patients. Patients and Methods: This prospective study included 101 PBC patients treated by primary surgery. CTCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay for the expression of epithelial (CK19) or epithelial-mesenchymal transition (EMT) genes [TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1)]. ANXA2 expression on CTCs was detected by qRT-PCR, while expression of ANXA2 in tumor specimen was evaluated by immunohistochemistry and expressed by a weighted histoscore, evaluating both the percentage of positive cells and the intensity of membrane and cytoplasmic staining. Results of hormone receptors, HER2 status, B-cell lymphoma 2 (bcl-2) protein expression and protein p53 were reported as either positive or negative on histopathology report without further quantification. Results: CTCs were detected in 24.8% patients. Patients with epithelial CTCs had a significantly higher ANXA2 expression on CTCs than those of patients without CTCs (p=0.01). There was no association between CTCs and ANXA2 protein expression in tumor cells. However, patients, whom CTCs with EMT phenotype were detected in, had higher ANXA2 expression in tumor stroma when compared to those with absent EMT CTCs (p=0.04). Hormone-negative tumors had significantly higher ANXA2 expression in tumor cells compared to hormone-positive tumors (p=0.03). Similarly, tumors without bcl-2 protein expression had higher tumor levels of ANXA2 compared to tumor cells that were bcl-2 positive (p=0.05). Conclusion: ANXA2 stromal expression might play a key role in aggressive tumor phenotype associated with increased EMT CTCs release, however, other factors beyond ANXA2 are responsible for coagulation activation mediated by CTCs in breast cancer patients.

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EGFR T790M Detection in Circulating Tumor DNA from Non-small Cell Lung Cancer Patients Using the PNA-LNA Clamp Method

Aim: To evaluate the utility of plasma circulating tumor DNA (ctDNA) using the peptide nucleic acid-locked nucleic acid (PNA-LNA) clamp method to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients who had progressed under treatment with EGFR-tyrosine kinase inhibitors (TKIs). Patients and Methods: Blood samples were collected from patients with EGFR mutation-positive NSCLC who had progressed on EGFR-TKIs between March 2016 and August 2016 at the Kyoto University Hospital. Extracted ctDNA was analyzed using the PNA-LNA clamp method. In eligible patients, tissue re-biopsy was also performed and EGFR mutation status was compared between tissue and plasma samples. Results: Thirty-one patients were enrolled in this study. Known activating EGFR mutations and the T790M mutation were detected in 18 (58%) and 5 patients (16%), respectively. Twenty-five patients underwent tissue re-biopsy. Adequate samples for mutation analysis were obtained from 21 patients and 10 patients were found to be tissue T790M-positive. Among these 10 patients, 4 patients were positive for T790M in plasma ctDNA (sensitivity 40% and specificity 100%). All patients with T790M-positive plasma ctDNA responded to osimertinib. Conclusion: Sensitivity of the PNA-LNA clamp method in detecting the plasma EGFR T790M mutation was moderate with elevated, however, specificity. Plasma EGFR T790M testing may be adequate for the initial step; however, tissue re-biopsy should be considered for plasma T790M-negative patients because of its high false-negative rate.

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Significance of the Preoperative CONUT Score in Predicting Postoperative Disease-free and Overall Survival in Patients with Lung Adenocarcinoma with Obstructive Lung Disease

Background: The usefulness of the controlling nutritional status (CONUT) score for preoperative nutritional assessment has been reported in resected colorectal and esophageal cancer, but not in lung cancer with obstructive lung disease. Patients and Methods: We retrospectively reviewed 109 patients with adenocarcinoma with obstructive pulmonary disease. We set 1 as the cut-off value for the CONUT score and classified patients into high (≥1) and low (0) CONUT groups. Results: Among 109 patients, 35 (32.1%) had low CONUT scores, and 74 (67.8%) had high CONUT scores. The high-CONUT group was significantly associated with a lower body mass index (p=0.025) and wild-type epidermal growth factor receptor mutation status (p=0.011). A multivariate analysis showed that the CONUT score was independently associated with disease-free and overall survival. Conclusion: The results of this study suggest that the CONUT score was an independent prognostic factor for disease-free and overall survival in patients with lung adenocarcinoma with obstructive lung disease.

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Dose Escalation Improves Outcome in Stereotactic Body Radiotherapy for Pulmonary Oligometastases from Colorectal Cancer

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Phase I Study of Definitive Radio-chemotherapy with Cisplatin, 5-Fluorouracil and Cetuximab for Unresectable Locally Advanced Esophageal Cancer

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Initial Experience with Nab-Paclitaxel for Patients with Advanced Gastric Cancer: Safety and Efficacy

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Simplified Comorbidity Score and Eastern Cooperative Oncology Group Performance Score Predicts Survival in Patients Receiving Organ-preserving Treatment for Bladder Cancer

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Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence - A Phase II Study

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Importance of Preoperative Knowledge of the Biomarker HE4 in Early-stage Endometrial Cancer Regarding Surgical Management

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Comparison of Outcomes with Hand-sewn Versus Stapler Closure of Pancreatic Stump in Distal Pancreatectomy

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Predictive Independent Factors for Extrahepatic Metastasis of Hepatocellular Carcinoma Following Curative Hepatectomy

http://ift.tt/2qB9CXf

PD-L1 Expression in Patients with Non-small Cell Lung Cancer

http://ift.tt/2pOVEhW

Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer

http://ift.tt/2qB3nCY

Genome-wide Expression Profiling (with Focus on the Galectin Network) in Tumor, Transition Zone and Normal Tissue of Head and Neck Cancer: Marked Differences Between Individual Patients and the Site of Specimen Origin

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Are Corrupted Non-dysplastic Colonic Crypts the First Histological Event in Experimental Colonic Carcinogenesis?

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Griseofulvin Efficiently Induces Apoptosis in In Vitro Treatment of Lymphoma and Multiple Myeloma

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The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

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Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer

Abstract

Purpose

Abdominal lymph node (ALN) recurrence in gastric cancer (GC) is rare and usually unresectable. We investigated the effects of integration of radiotherapy (RT) and chemotherapy against ALN recurrence in GC.

Methods

We retrospectively categorized GC patients with ALN recurrence treated between 2005 and 2013 into two groups: those treated with integration of RT and chemotherapy (RCT) and those who received systemic chemotherapy only (CT). The median follow-up period after ALN recurrence for all patients was 20 months.

Results

Of 53 patients, 31 and 22 were in the RCT and CT groups, respectively. Isolated distant failure (DF; 35.5%) without local progression (LP) was the dominant pattern of failure (POF) in the RCT group (median DF-free period, 26 months). LP followed by DF (31.8%) was the dominant POF in the CT group; LP (median LP-free period, 8 months) occurred 10 months earlier than DF (median DF-free period, 18 months). RCT patients had significantly longer median progression-free survival (PFS) compared to CT patients (25 vs. 8 months; P = 0.021). On multivariate analysis, treatment (CT vs. RCT) was an independent prognostic factor for PFS (hazard ratio 2.085; 95% confidence interval 1.073–4.050; P = 0.013).

Conclusions

Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

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Integration of radiotherapy and chemotherapy for abdominal lymph node recurrence in gastric cancer

Abstract

Purpose

Methods

Results

Conclusions

Integration of RT and chemotherapy achieved long-term local control and prolonged PFS in GC patients with ALN recurrence. Local RT is feasible for treating isolated ALN recurrences.

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Down-regulated miRs specifically correlate with non-cardial gastric cancers and Lauren's classification system

Background and Objectives

Gastric cancers are usually characterized using Lauren's classification into intestinal and diffuse types. We previously documented the down-modulation of miR31, miR148a, miR204, and miR375 in gastric cancers. We aimed this manuscript to investigate these miRs with the end-points of diagnosis, Lauren's classification and prognosis.

Methods

A total of 117 resected non-cardial adenocarcinomas were evaluated for miRs' expressions. The performance of miRs' expressions for cancer diagnosis was tested using ROC curves. Logistic regression was conducted with the end-point of Lauren's classification. Kaplan-Meier and Cox analyses were performed for OS, DFS, and DSS. miRs' targets were reviewed using PRISMA method and BCL-2 was further investigated in cell lines.

Results

ROC curves documented that miRs' down-modulation was significant in differentiating cancer versus normal tissues. Diffuse type cancers were associated with female sex, young age, and miR375 higher expression. We confirmed BCL-2 as a miR204 target. However, survival analyses confirmed the pathologic criteria (advanced stages, LNR, and low LNH) as the significant variables correlated to worse prognosis.

Conclusions

The down-modulation of miR31, miR148a, miR204, and miR375 is significantly associated with non-cardial gastric cancers and miR375 is specifically linked to Lauren's classification. Nevertheless, standard pathological features display as the independent variables associated with worse prognosis.

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Translating the 2-dimensional mammogram into a 3-dimensional breast: Identifying factors that influence the movement of pre-operatively placed wire

Background: Pre-operative measurements from the skin to a wire-localized breast lesion can differ from operating room measurements. This study was designed to measure the discrepancies and study factors that may contribute to wire movement.

Methods: Prospective data were collected on patients who underwent wire localization lumpectomy. Clip and hook location, breast size, density, and direction of wire placement were the main focus of the analysis.

Results: Wire movement was more likely with longer distance from skin to hook or clip, larger breast size (especially if "fatty"), longer time between wire placement and surgery start time, and medial wire placement in larger breast. Age, body mass index, presence of mass, malignant diagnosis, tumor grade, and clip distance to the chest wall were not associated with wire movement. A longer distance from skin to hook correlated with larger specimen volume.

Conclusions: Translation of the lesion location from a 2-dimensional mammogram into 3-dimensional breasts is sometimes discrepant because of movement of the localizing wire. Breast size, distance of skin to clip or hook, and wire exit site in larger breasts have a significant impact on wire movement. This information may guide the surgeon's skin incision and extent of excision.

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Kocher maneuver to facilitate cytoreduction within the foramen of Winslow

A potential site for incomplete cytoreduction in patients with peritoneal metastases is the foramen of Winslow, especially the posterior aspect of the hepatoduodenal ligament. The Kocher maneuver can be used to rotate the duodenum, head of pancreas, and portal structures 180°. In so doing, the foramen of Winslow is clearly exposed for peritonectomy. Residual tumor at this site is a prominent cause of unnecessary treatment failure in the management of patients with mucinous appendiceal neoplasms.

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Multi-disciplinary management of locally advanced pancreatic cancer with irreversible electroporation

The essential diagnosis for LAPC is based on high-quality cross-sectional imaging, which demonstrates tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and non-thermal ablation modalities. This review will present the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer.

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Down-regulated miRs specifically correlate with non-cardial gastric cancers and Lauren's classification system

Background and Objectives

Methods

Results

Conclusions

from Cancer via ola Kala on Inoreader http://ift.tt/2q7LPP8
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Translating the 2-dimensional mammogram into a 3-dimensional breast: Identifying factors that influence the movement of pre-operatively placed wire

from Cancer via ola Kala on Inoreader http://ift.tt/2pOD09C
via IFTTT