An epi(c)genetic war: Pathogens, cancer and human genome

Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Deepa Rajagopalan, Sudhakar Jha
Cancer is characterized by inter and intra-heterogeneity and this is also observed in the context of cancers caused by pathogens. Nearly 20% of all cancers are attributable to pathogenic organisms. Pathogenic infections result in deregulation of gene expression both by genetic and epigenetic mechanisms, thereby causing malignant transformation. Another characteristic of pathogen-induced cancers is the occurrence of chronic inflammation due to activation of the innate and adaptive arms of the immune system. This review focuses on the epigenetic changes induced by oncoviruses, parasites, cancer-causing bacteria and 'endogenous pathogens' to trigger host cell proliferation indefinitely as well as the inflammation associated with pathogen-induced cancers. The opportunity of targeting components of both pathogen and host epigenetic machinery to limit tumor progression is also discussed.



https://ift.tt/2GYiJ9q

Nervous system and primary liver cancer

Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Seogsong Jeong, Bo Zheng, Hongyang Wang, Qiang Xia, Lei Chen
Recent advances have found irregular activities of the nervous system-associated factors in the development and progression of primary liver cancer. These factors contributed in the regulation of migration, proliferation, and apoptosis of cancer cells, and took a role in modulating invasion, metastasis, and recurrence after curative treatment. In clinical researches, neural-related factors were found to be significant prognostic factors, suggesting that the interactions between nervous system and primary liver cancer are indispensable in understanding underlying biological mechanisms. Herein, we reviewed up-to-date achievements in this area and the future perspectives of the interactions between the nervous system and primary liver cancer.

Graphical abstract

https://ift.tt/2HzeTor

Protein restriction and cancer

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Jie Yin, Wenkai Ren, Xingguo Huang, Tiejun Li, Yulong Yin
Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.



https://ift.tt/2GYiGKM

ILT4 functions as a potential checkpoint molecule for tumor immunotherapy

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Aiqin Gao, Yuping Sun, Guangyong Peng
Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4 is also enriched in tumor cells and stroma cells in the tumor microenvironment of various malignancies, modulating the biological behaviors of tumor cells and promoting their immune escape. However, the underlying mechanisms responsible for ILT4-mediated tumor development and progression are still poorly understood. In this review, we explore the functional role of ILT4 as a novel checkpoint molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for controlling tumor malignant behaviors, impairing effector anti-tumor immune responses, and sustaining the tumor suppressive microenvironment. We also highlight the potential role of ILT4 as a novel immune checkpoint target for tumor immunotherapy. Improved understanding of these issues is critical for elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues for cancer immunotherapy specifically targeting this novel and alternative checkpoint molecule.



https://ift.tt/2HzeN03

Larotrectinib Has Antitumor Activity in TRK+ Pediatric Solid Tumors [Research Watch]

Larotrectinib achieved a 93% response rate in pediatric patients with TRK fusion–positive tumors.

from Cancer via ola Kala on Inoreader https://ift.tt/2v8Exxy
via IFTTT

The IL15 Superagonist ALT-803 plus Nivolumab Has Antitumor Activity [Research Watch]

Nivolumab in combination with ALT-803 is tolerable and achieves responses in patients with NSCLC.

from Cancer via ola Kala on Inoreader https://ift.tt/2JIayA0
via IFTTT

SLAM-seq Identifies Direct Transcriptional Targets of BRD4 and MYC [Research Watch]

BRD4 activates RNA Pol2–dependent transcription, whereas MYC activates a confined set of target genes.

from Cancer via ola Kala on Inoreader https://ift.tt/2viytms
via IFTTT

Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place [Review]

Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication–transcription collisions, reactive oxygen species, and defective nucleotide metabolism.

Significance: Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress. Cancer Discov; 8(5); 1–19. ©2018 AACR.

from Cancer via ola Kala on Inoreader https://ift.tt/2JM0gyH
via IFTTT

Glioblastoma Stem Cell-Tumor Cell Cross-talk Drives Gliomagenesis [Research Watch]

Reciprocal paracrine signaling between GBM stem cells and GBM cells promotes tumor growth.

from Cancer via ola Kala on Inoreader https://ift.tt/2EKI7xz
via IFTTT

Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers

Background: The European Society for Medical Oncology defines rare cancers as 5 or fewer cases per 100,000 persons/year. For many rare cancers, no standard of care exists, and treatment is often extrapolated. Identifying potentially targetable genomic alterations is a rational approach to improving treatment options. We sought to catalog these mutations in rare tumors and assess their clinical utility. Methods: For this retrospective analysis, we selected rare tumors from a dataset of patients who underwent clinical genomic profiling. Sarcomas were excluded. To index potentially actionable alterations, patients' reports were reviewed for mutations in cancer associated genes and pathways. Respective records were abstracted to appraise the benefit of using a targeted therapy approach. Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials. Results: The 95 patients analyzed had 40 different tumor subtypes, most common being adenoid cystic(13%), cholangiocarcinoma(7%), and metaplastic breast(6%). At least one genomic alteration was identified in 87 patients(92%). The most common identifiable mutations were in TP53(23%), KRAS(10%), PIK3CA(9%), CDKN2A/B(8%), BRAF(7%), MLL(7%), and ARID1A(6%). Thirty-six patients (38%) with 21 different tumors had at least one potentially actionable alteration. Thirteen patients received targeted therapy. Of these, 4 had a partial response, 6 had stable disease, and 3 had progressive disease as the best response. Conclusion: Addition of genomic profiling to management of rare cancers adds a potential line of therapy for cancers that have little or no standard of care. In our analysis, tumors with a BRAF alteration responded well to BRAF inhibitors.

https://ift.tt/2EKHl3w

A short BRCA2-derived cell-penetrating peptide targets RAD51 function and confers hypersensitivity towards PARP inhibition

Under conditions of genotoxic stress, cancer cells strongly rely on efficient DNA repair to survive and proliferate. The human BRCA2 tumor suppressor protein is indispensable for the repair of DNA double-strand breaks by homologous recombination (HR) by virtue of its ability to promote RAD51 loading onto single-stranded DNA. Therefore, blocking the interaction between BRCA2 and RAD51 could significantly improve the efficacy of conventional anti-cancer therapies. However, targeting protein-protein interaction (PPI) interfaces has proven challenging because flat and large PPI surfaces generally do not support binding of small molecule inhibitors. In contrast, peptides are more potent for targeting PPIs but are otherwise difficult to deliver into cells. Here, we report that a synthetic 16-mer peptide derived from the BRC4 repeat motif of BRCA2 is capable of blocking RAD51 binding to BRCA2. Efficient non-cytotoxic cellular uptake of a nona-arginine (R9)-conjugated version of the BRC4 peptide interferes with DNA damage-induced RAD51 foci formation and HR. Moreover, transduction of the BRC4 peptide impairs replication fork protective function of BRCA2 and triggers MRE11-dependent degradation of nascent DNA in response to DNA replication stress. Finally, the BRC4 cell-penetrating peptide (CPP) confers selective hypersensitivity to PARP inhibition in cancer cells but spares non-cancerous cells. Taken together, our data highlight an innovative approach to develop novel peptide-based DNA repair inhibitors and establish BRCA2-derived CPPs as promising anti-cancer agents.

https://ift.tt/2JLkM2H

Efficient gene silencing in brain tumors with hydrophobically modified siRNAs

Glioblastoma (GBM) is the most common and lethal form of primary brain tumor with dismal median and two-year survivals of 14.5 months and 18%, respectively. The paucity of new therapeutic agents stems from the complex biology of a highly adaptable tumor that uses multiple survival and proliferation mechanisms to circumvent current treatment approaches. Here, we investigated the potency of a new generation of small interfering RNAs (siRNAs) to silence gene expression in orthotopic brain tumors generated by transplantation of human glioma stem-like cells (GSCs) in athymic nude mice. We demonstrate that cholesterol-conjugated, nuclease-resistant siRNAs (Chol-hsiRNAs) decrease mRNA and silence luciferase expression by 90% in vitro in GBM neurospheres. Furthermore, Chol-hsiRNAs distribute broadly in brain tumors after a single intratumoral injection, achieving sustained and potent (>45% mRNA and >90% protein) tumor-specific gene silencing. This readily available platform is sequence-independent and can be adapted to target one or more candidate GBM driver genes, providing a straightforward means of modulating GBM biology in vivo.

https://ift.tt/2vfvISO

RAS-MAPK reactivation facilitates acquired resistance in FGFR1-amplified lung cancer and underlies a rationale for upfront FGFR-MEK blockade

The Fibroblast Growth Factor Receptor (FGFR) kinases are promising therapeutic targets in multiple cancer types including lung and head and neck squamous cell carcinoma, cholangiocarcinoma and bladder cancer. Although several FGFR kinase inhibitors have entered clinical trials, single agent clinical efficacy has been modest and resistance invariably occurs. We therefore conducted a genome-wide functional screen to characterize mechanisms of resistance to FGFR inhibition in a FGFR1-dependent lung cancer cellular model. Our screen identified known resistance drivers, such as MET, and additional novel resistance mediators including members of the neurotrophin receptor pathway (NTRKs), the TAM family of tyrosine kinases (TYRO3, MERTK, AXL) and MAPK pathway, which were further validated in additional FGFR-dependent models. In an orthogonal approach, we generated a large panel of resistant clones by chronic exposure to FGFR inhibitors in FGFR1- and FGFR3-dependent cellular models, and characterized gene expression profiles employing the L1000 platform. Notably, resistant clones had enrichment for NTRK and MAPK signaling pathways. Novel mediators of resistance to FGFR inhibition were found to compensate for FGFR loss in part through reactivation of MAPK pathway. Intriguingly, co-inhibition of FGFR and specific receptor tyrosine kinases identified in our screen was not sufficient to suppress ERK activity or to prevent resistance to FGFR inhibition, suggesting a redundant re-activation of RAS-MAPK pathway. Dual blockade of FGFR and MEK, however, proved to be a more powerful approach in preventing resistance across diverse FGFR-dependencies, and may represent a therapeutic opportunity to achieve durable responses to FGFR inhibition in FGFR-dependent cancers.

https://ift.tt/2JLQ60S

Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity.

https://ift.tt/2vdf9GZ

Induced Telomere Damage to Treat Telomerase Expressing Therapy-Resistant Pediatric Brain Tumors

Brain tumors remain the leading cause of cancer-related deaths in children and often are associated with long-term sequelae among survivors of current therapies. Hence, there is an urgent need to identify actionable targets and to develop more effective therapies. Telomerase and telomeres play important roles in cancer, representing attractive therapeutic targets to treat children with poor-prognosis brain tumors such as diffuse intrinsic pontine glioma (DIPG), high-grade glioma (HGG) and high-risk medulloblastoma (MB). We have previously shown that DIPG, HGG and MB frequently express telomerase activity. Here we show that the telomerase-dependent incorporation of 6-thio-2'deoxyguanosine (6-thio-dG), a telomerase substrate precursor analog, into telomeres leads to telomere dysfunction-induced foci (TIFs) along with extensive genomic DNA damage, cell growth inhibition and cell death of primary stem-like cells derived from patients with DIPG, HGG and MB. Importantly, the effect of 6-thio-dG is persistent even after drug withdrawal. Treatment with 6-thio-dG elicits a sequential activation of ATR and ATM pathways, and induces G2/M arrest. In vivo, treatment of mice bearing MB xenografts with 6-thio-dG delays tumor growth, increases in-tumor TIFs and apoptosis. Furthermore, 6-thio-dG crosses the blood-brain barrier and specifically targets tumor cells in an orthotopic mouse model of DIPG. Together, our findings suggest that 6-thio-dG is a promising novel approach to treat therapy-resistant telomerase-positive pediatric brain tumors.

https://ift.tt/2JJ3vXJ

Photodynamic Therapy Using Indocyanine Green Loaded on Super Carbonate Apatite as Minimally Invasive Cancer Treatment

Minimally invasive treatment is getting more and more important in an aging society. The purpose of this study was to explore the possibility of ICG loaded on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen species (ROS) production and temperature rise were also evaluated to explore the underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature increase after laser irradiation was 27.1°C and 23.1°C in sCA-ICG and ICG, respectively (control DW: 5.7oC). A significant increase in ROS generation was noted in cell cultures treated with sCA-ICG plus irradiation compared to those treated with ICG plus irradiation (P<0.01). Uptake of ICG in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro and in vivo. The fluorescence signals of ICG in the tumor, liver, and kidney faded away in both treatments by 24 h. Finally, the HT29 tumors treated with sCA-ICG followed by irradiation exhibited drastic tumor growth retardation (P<0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts to the other nanoparticles remaining in normal organs for a long time.

https://ift.tt/2vfvFX8

Mechanistic Investigations of Diarrhea Toxicity Induced by anti-HER2/3 Combination Therapy

Combination of targeted therapies is expected to provide superior efficacy in the treatment of cancer either by enhanced anti-tumor activity or by preventing or delaying the development of resistance. Common challenges in developing combination therapies include the potential of additive and aggravated toxicities associated with pharmacologically-related adverse effects. We have recently reported that combination of anti-HER2 and anti-HER3 antibodies, pertuzumab and lumretuzumab, along with paclitaxel chemotherapy in metastatic breast cancer resulted in a high incidence of diarrhea that ultimately limited further clinical development of this combination. Here, we further dissected the diarrhea profile of the various patient dose cohorts and carried out in vitro investigations in human colon cell lines and explants to decipher the contribution and the mechanism of anti-HER2/3 therapeutic antibodies to intestinal epithelium malfunction. Our clinical investigations in patients revealed that while dose reduction of lumretuzumab, omission of pertuzumab loading dose and introduction of a prophylactic anti-diarrheal treatment reduced most severe adverse events, patients still suffered from persistent diarrhea during the treatment. Our in vitro investigations showed that pertuzumab and lumretuzumab combination treatment resulted in up-regulation of chloride channel activity without indication of intestinal barrier disruption. Overall, our findings provide a mechanistic rationale to explore alternative of conventional anti-gut motility using medication targeting chloride channel activity to mitigate diarrhea of HER combination therapies.

https://ift.tt/2JIk4D4

Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers

Background: The European Society for Medical Oncology defines rare cancers as 5 or fewer cases per 100,000 persons/year. For many rare cancers, no standard of care exists, and treatment is often extrapolated. Identifying potentially targetable genomic alterations is a rational approach to improving treatment options. We sought to catalog these mutations in rare tumors and assess their clinical utility. Methods: For this retrospective analysis, we selected rare tumors from a dataset of patients who underwent clinical genomic profiling. Sarcomas were excluded. To index potentially actionable alterations, patients' reports were reviewed for mutations in cancer associated genes and pathways. Respective records were abstracted to appraise the benefit of using a targeted therapy approach. Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials. Results: The 95 patients analyzed had 40 different tumor subtypes, most common being adenoid cystic(13%), cholangiocarcinoma(7%), and metaplastic breast(6%). At least one genomic alteration was identified in 87 patients(92%). The most common identifiable mutations were in TP53(23%), KRAS(10%), PIK3CA(9%), CDKN2A/B(8%), BRAF(7%), MLL(7%), and ARID1A(6%). Thirty-six patients (38%) with 21 different tumors had at least one potentially actionable alteration. Thirteen patients received targeted therapy. Of these, 4 had a partial response, 6 had stable disease, and 3 had progressive disease as the best response. Conclusion: Addition of genomic profiling to management of rare cancers adds a potential line of therapy for cancers that have little or no standard of care. In our analysis, tumors with a BRAF alteration responded well to BRAF inhibitors.

from Cancer via ola Kala on Inoreader https://ift.tt/2EKHl3w
via IFTTT

A short BRCA2-derived cell-penetrating peptide targets RAD51 function and confers hypersensitivity towards PARP inhibition

Under conditions of genotoxic stress, cancer cells strongly rely on efficient DNA repair to survive and proliferate. The human BRCA2 tumor suppressor protein is indispensable for the repair of DNA double-strand breaks by homologous recombination (HR) by virtue of its ability to promote RAD51 loading onto single-stranded DNA. Therefore, blocking the interaction between BRCA2 and RAD51 could significantly improve the efficacy of conventional anti-cancer therapies. However, targeting protein-protein interaction (PPI) interfaces has proven challenging because flat and large PPI surfaces generally do not support binding of small molecule inhibitors. In contrast, peptides are more potent for targeting PPIs but are otherwise difficult to deliver into cells. Here, we report that a synthetic 16-mer peptide derived from the BRC4 repeat motif of BRCA2 is capable of blocking RAD51 binding to BRCA2. Efficient non-cytotoxic cellular uptake of a nona-arginine (R9)-conjugated version of the BRC4 peptide interferes with DNA damage-induced RAD51 foci formation and HR. Moreover, transduction of the BRC4 peptide impairs replication fork protective function of BRCA2 and triggers MRE11-dependent degradation of nascent DNA in response to DNA replication stress. Finally, the BRC4 cell-penetrating peptide (CPP) confers selective hypersensitivity to PARP inhibition in cancer cells but spares non-cancerous cells. Taken together, our data highlight an innovative approach to develop novel peptide-based DNA repair inhibitors and establish BRCA2-derived CPPs as promising anti-cancer agents.

from Cancer via ola Kala on Inoreader https://ift.tt/2JLkM2H
via IFTTT

Efficient gene silencing in brain tumors with hydrophobically modified siRNAs

Glioblastoma (GBM) is the most common and lethal form of primary brain tumor with dismal median and two-year survivals of 14.5 months and 18%, respectively. The paucity of new therapeutic agents stems from the complex biology of a highly adaptable tumor that uses multiple survival and proliferation mechanisms to circumvent current treatment approaches. Here, we investigated the potency of a new generation of small interfering RNAs (siRNAs) to silence gene expression in orthotopic brain tumors generated by transplantation of human glioma stem-like cells (GSCs) in athymic nude mice. We demonstrate that cholesterol-conjugated, nuclease-resistant siRNAs (Chol-hsiRNAs) decrease mRNA and silence luciferase expression by 90% in vitro in GBM neurospheres. Furthermore, Chol-hsiRNAs distribute broadly in brain tumors after a single intratumoral injection, achieving sustained and potent (>45% mRNA and >90% protein) tumor-specific gene silencing. This readily available platform is sequence-independent and can be adapted to target one or more candidate GBM driver genes, providing a straightforward means of modulating GBM biology in vivo.

from Cancer via ola Kala on Inoreader https://ift.tt/2vfvISO
via IFTTT

RAS-MAPK reactivation facilitates acquired resistance in FGFR1-amplified lung cancer and underlies a rationale for upfront FGFR-MEK blockade

The Fibroblast Growth Factor Receptor (FGFR) kinases are promising therapeutic targets in multiple cancer types including lung and head and neck squamous cell carcinoma, cholangiocarcinoma and bladder cancer. Although several FGFR kinase inhibitors have entered clinical trials, single agent clinical efficacy has been modest and resistance invariably occurs. We therefore conducted a genome-wide functional screen to characterize mechanisms of resistance to FGFR inhibition in a FGFR1-dependent lung cancer cellular model. Our screen identified known resistance drivers, such as MET, and additional novel resistance mediators including members of the neurotrophin receptor pathway (NTRKs), the TAM family of tyrosine kinases (TYRO3, MERTK, AXL) and MAPK pathway, which were further validated in additional FGFR-dependent models. In an orthogonal approach, we generated a large panel of resistant clones by chronic exposure to FGFR inhibitors in FGFR1- and FGFR3-dependent cellular models, and characterized gene expression profiles employing the L1000 platform. Notably, resistant clones had enrichment for NTRK and MAPK signaling pathways. Novel mediators of resistance to FGFR inhibition were found to compensate for FGFR loss in part through reactivation of MAPK pathway. Intriguingly, co-inhibition of FGFR and specific receptor tyrosine kinases identified in our screen was not sufficient to suppress ERK activity or to prevent resistance to FGFR inhibition, suggesting a redundant re-activation of RAS-MAPK pathway. Dual blockade of FGFR and MEK, however, proved to be a more powerful approach in preventing resistance across diverse FGFR-dependencies, and may represent a therapeutic opportunity to achieve durable responses to FGFR inhibition in FGFR-dependent cancers.

from Cancer via ola Kala on Inoreader https://ift.tt/2JLQ60S
via IFTTT

Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fc receptor (FcR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity.

from Cancer via ola Kala on Inoreader https://ift.tt/2vdf9GZ
via IFTTT

Induced Telomere Damage to Treat Telomerase Expressing Therapy-Resistant Pediatric Brain Tumors

Brain tumors remain the leading cause of cancer-related deaths in children and often are associated with long-term sequelae among survivors of current therapies. Hence, there is an urgent need to identify actionable targets and to develop more effective therapies. Telomerase and telomeres play important roles in cancer, representing attractive therapeutic targets to treat children with poor-prognosis brain tumors such as diffuse intrinsic pontine glioma (DIPG), high-grade glioma (HGG) and high-risk medulloblastoma (MB). We have previously shown that DIPG, HGG and MB frequently express telomerase activity. Here we show that the telomerase-dependent incorporation of 6-thio-2'deoxyguanosine (6-thio-dG), a telomerase substrate precursor analog, into telomeres leads to telomere dysfunction-induced foci (TIFs) along with extensive genomic DNA damage, cell growth inhibition and cell death of primary stem-like cells derived from patients with DIPG, HGG and MB. Importantly, the effect of 6-thio-dG is persistent even after drug withdrawal. Treatment with 6-thio-dG elicits a sequential activation of ATR and ATM pathways, and induces G2/M arrest. In vivo, treatment of mice bearing MB xenografts with 6-thio-dG delays tumor growth, increases in-tumor TIFs and apoptosis. Furthermore, 6-thio-dG crosses the blood-brain barrier and specifically targets tumor cells in an orthotopic mouse model of DIPG. Together, our findings suggest that 6-thio-dG is a promising novel approach to treat therapy-resistant telomerase-positive pediatric brain tumors.

from Cancer via ola Kala on Inoreader https://ift.tt/2JJ3vXJ
via IFTTT

Photodynamic Therapy Using Indocyanine Green Loaded on Super Carbonate Apatite as Minimally Invasive Cancer Treatment

Minimally invasive treatment is getting more and more important in an aging society. The purpose of this study was to explore the possibility of ICG loaded on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen species (ROS) production and temperature rise were also evaluated to explore the underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature increase after laser irradiation was 27.1°C and 23.1°C in sCA-ICG and ICG, respectively (control DW: 5.7oC). A significant increase in ROS generation was noted in cell cultures treated with sCA-ICG plus irradiation compared to those treated with ICG plus irradiation (P<0.01). Uptake of ICG in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro and in vivo. The fluorescence signals of ICG in the tumor, liver, and kidney faded away in both treatments by 24 h. Finally, the HT29 tumors treated with sCA-ICG followed by irradiation exhibited drastic tumor growth retardation (P<0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts to the other nanoparticles remaining in normal organs for a long time.

from Cancer via ola Kala on Inoreader https://ift.tt/2vfvFX8
via IFTTT

Mechanistic Investigations of Diarrhea Toxicity Induced by anti-HER2/3 Combination Therapy

Combination of targeted therapies is expected to provide superior efficacy in the treatment of cancer either by enhanced anti-tumor activity or by preventing or delaying the development of resistance. Common challenges in developing combination therapies include the potential of additive and aggravated toxicities associated with pharmacologically-related adverse effects. We have recently reported that combination of anti-HER2 and anti-HER3 antibodies, pertuzumab and lumretuzumab, along with paclitaxel chemotherapy in metastatic breast cancer resulted in a high incidence of diarrhea that ultimately limited further clinical development of this combination. Here, we further dissected the diarrhea profile of the various patient dose cohorts and carried out in vitro investigations in human colon cell lines and explants to decipher the contribution and the mechanism of anti-HER2/3 therapeutic antibodies to intestinal epithelium malfunction. Our clinical investigations in patients revealed that while dose reduction of lumretuzumab, omission of pertuzumab loading dose and introduction of a prophylactic anti-diarrheal treatment reduced most severe adverse events, patients still suffered from persistent diarrhea during the treatment. Our in vitro investigations showed that pertuzumab and lumretuzumab combination treatment resulted in up-regulation of chloride channel activity without indication of intestinal barrier disruption. Overall, our findings provide a mechanistic rationale to explore alternative of conventional anti-gut motility using medication targeting chloride channel activity to mitigate diarrhea of HER combination therapies.

from Cancer via ola Kala on Inoreader https://ift.tt/2JIk4D4
via IFTTT

Resistance to Antibody-Drug Conȷugates

Antibody–drug conjugates (ADC) are multicomponent molecules constituted by an antibody covalently linked to a potent cytotoxic agent. ADCs combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent. At present, four ADCs have been approved and over 60 are being explored in clinical trials. Despite their effectiveness, resistance to these drugs unfortunately occurs. Efforts to understand the bases underlying such resistance are being carried out with the final purpose of counteracting them. In this review, we report described mechanisms of resistance to ADCs used in the clinic along with other potential ones that may contribute to resistance acquisition. We also discuss strategies to overcome resistance to ADCs. Cancer Res; 1–7. ©2018 AACR.

https://ift.tt/2JJ4F5v

Resistance to Antibody-Drug Conȷugates

Antibody–drug conjugates (ADC) are multicomponent molecules constituted by an antibody covalently linked to a potent cytotoxic agent. ADCs combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent. At present, four ADCs have been approved and over 60 are being explored in clinical trials. Despite their effectiveness, resistance to these drugs unfortunately occurs. Efforts to understand the bases underlying such resistance are being carried out with the final purpose of counteracting them. In this review, we report described mechanisms of resistance to ADCs used in the clinic along with other potential ones that may contribute to resistance acquisition. We also discuss strategies to overcome resistance to ADCs. Cancer Res; 1–7. ©2018 AACR.

from Cancer via ola Kala on Inoreader https://ift.tt/2JJ4F5v
via IFTTT

Mitotic Exit dysfunction through the deregulation of APC/C characterizes cisplatin resistant state in epithelial ovarian cancer

Purpose: Acquired resistance to cisplatin is a major barrier to success in treatment of various cancers and understanding mitotic mechanisms unique to cisplatin resistant cancer cells can provide the basis for developing novel mitotic targeted therapies aimed at eradicating these cells. Experimental Design: Using cisplatin resistant models derived from primary patient epithelial ovarian cancer (EOC) cells, we have explored the status of mitotic exit mechanisms in cisplatin resistant cells. Results: We have uncovered an unexpected role of long-term cisplatin treatment in inducing mitotic exit vulnerability characterized by increased spindle checkpoint activity and functional dependency on Polo-like kinase 1 (PLK1) for mitotic exit in the presence of Anaphase Promoting Complex/Cyclosome (APC/C) dysfunction in a cisplatin resistant state. Accordingly, PLK1 inhibition decreased the survival of cisplatin resistant cells in-vitro and in-vivo, and exacerbated spindle checkpoint response in these cells. APC/C ^CDC20 inhibition increased sensitivity to pharmacologic PLK1 inhibition further confirming the existence of APC/C dysfunction cisplatin resistant cells. In addition, we uncovered that resistance to Volasertib, PLK1 inhibitor, is due to maintenance of cells with low PLK1 expression. Accordingly, stable PLK1 downregulation in cisplatin resistant cells induced tolerance to Volasertib. Conclusions: We provide the first evidence of APC/C dysfunction in cisplatin resistant state, suggesting that understanding APC/C functions in cisplatin resistant state could provide basis for developing novel mitotic exit based therapies to eradicate cisplatin resistant cancer cells. Our results also show that PLK1 down-regulation could underlie emergence of resistance to PLK1 targeted therapies in cancers.

from Cancer via ola Kala on Inoreader https://ift.tt/2IS8jIZ
via IFTTT

Mitotic Exit dysfunction through the deregulation of APC/C characterizes cisplatin resistant state in epithelial ovarian cancer

Purpose: Acquired resistance to cisplatin is a major barrier to success in treatment of various cancers and understanding mitotic mechanisms unique to cisplatin resistant cancer cells can provide the basis for developing novel mitotic targeted therapies aimed at eradicating these cells. Experimental Design: Using cisplatin resistant models derived from primary patient epithelial ovarian cancer (EOC) cells, we have explored the status of mitotic exit mechanisms in cisplatin resistant cells. Results: We have uncovered an unexpected role of long-term cisplatin treatment in inducing mitotic exit vulnerability characterized by increased spindle checkpoint activity and functional dependency on Polo-like kinase 1 (PLK1) for mitotic exit in the presence of Anaphase Promoting Complex/Cyclosome (APC/C) dysfunction in a cisplatin resistant state. Accordingly, PLK1 inhibition decreased the survival of cisplatin resistant cells in-vitro and in-vivo, and exacerbated spindle checkpoint response in these cells. APC/C ^CDC20 inhibition increased sensitivity to pharmacologic PLK1 inhibition further confirming the existence of APC/C dysfunction cisplatin resistant cells. In addition, we uncovered that resistance to Volasertib, PLK1 inhibitor, is due to maintenance of cells with low PLK1 expression. Accordingly, stable PLK1 downregulation in cisplatin resistant cells induced tolerance to Volasertib. Conclusions: We provide the first evidence of APC/C dysfunction in cisplatin resistant state, suggesting that understanding APC/C functions in cisplatin resistant state could provide basis for developing novel mitotic exit based therapies to eradicate cisplatin resistant cancer cells. Our results also show that PLK1 down-regulation could underlie emergence of resistance to PLK1 targeted therapies in cancers.

https://ift.tt/2IS8jIZ

Evaluating the Training of Chinese-Speaking Community Health Workers to Implement a Small-Group Intervention Promoting Mammography

Abstract

This study evaluated the training of Chinese American Community Health Workers (CHWs) to implement a small-group mammography video and discussion program as part of a randomized controlled trial that had the goal to increase adherence to mammography screening guidelines among Chinese American women. A total of 26 Chinese American CHWs in the metropolitan Washington DC area, Southern California, and New York City participated in a 4-h training workshop and completed surveys before and after the workshop to assess their knowledge regarding mammography screening guidelines and human subjects protection rules. The results showed significantly increased knowledge of mammography screening guidelines and human subjects protection rules (both p < 0.01) after the training. CHWs were also trained to lead a discussion of the video, including screening benefits and misconceptions. Forty-three audio recordings of discussions led by 13 active CHWs were transcribed and qualitatively analyzed to assess implementation fidelity. Ten out of 13 active CHWs fully addressed about 3 of the 5 benefit items, and 11 out of 13 CHWs fully addressed more than 5 of the 9 misconception items. Chinese CHWs can be trained to implement research-based intervention programs. However, a one-time training resulted in moderate adherence to the discussion protocol. Ongoing or repeat trainings throughout the intervention period may be needed to enhance implementation fidelity.

from Cancer via ola Kala on Inoreader https://ift.tt/2quQwB3
via IFTTT

Evaluating the Training of Chinese-Speaking Community Health Workers to Implement a Small-Group Intervention Promoting Mammography

Abstract

This study evaluated the training of Chinese American Community Health Workers (CHWs) to implement a small-group mammography video and discussion program as part of a randomized controlled trial that had the goal to increase adherence to mammography screening guidelines among Chinese American women. A total of 26 Chinese American CHWs in the metropolitan Washington DC area, Southern California, and New York City participated in a 4-h training workshop and completed surveys before and after the workshop to assess their knowledge regarding mammography screening guidelines and human subjects protection rules. The results showed significantly increased knowledge of mammography screening guidelines and human subjects protection rules (both p < 0.01) after the training. CHWs were also trained to lead a discussion of the video, including screening benefits and misconceptions. Forty-three audio recordings of discussions led by 13 active CHWs were transcribed and qualitatively analyzed to assess implementation fidelity. Ten out of 13 active CHWs fully addressed about 3 of the 5 benefit items, and 11 out of 13 CHWs fully addressed more than 5 of the 9 misconception items. Chinese CHWs can be trained to implement research-based intervention programs. However, a one-time training resulted in moderate adherence to the discussion protocol. Ongoing or repeat trainings throughout the intervention period may be needed to enhance implementation fidelity.

https://ift.tt/2quQwB3

Severe perineal lacerations after vaginal delivery: are they an anesthesiologist's problem?

Purpose of review Perineal tears or lacerations are common occurrences after vaginal delivery. Understanding the degree of severity of these tears and the immediate and long-term complications of severe perineal lacerations can assist anesthesiologists with the management of these patients in the immediate postpartum period. Recent findings Severe perineal lacerations have a high degree of association with postpartum depression. The presence of neuraxial labor analgesia decreases the odds of severe perineal lacerations. Summary Neuraxial labor analgesia does not directly predispose parturients to the development of perineal lacerations, and may even be protective against these injuries. Correspondence to Feyce Peralta, MD, 251 E. Huron St. F5-704, Chicago, IL 60611, USA. Tel: +1 312 472 3585; e-mail: feyce.peralta@northwestern.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2HkBd7p

Clinical pearls part 3: anaesthetic management of abnormally invasive placentation

Purpose of review Abnormal placentation is a clinical condition seen increasingly in the pregnant population. It is associated with significant morbidity and mortality, which may be mitigated through robust multidisciplinary care for these patients. The role of maternal critical care for these patients has largely been ignored in the literature. Recent findings Advances in pharmacological management of bleeding with recent publications of large multicentre trials in addition to new technologies in the management of massive obstetric haemorrhage (MOH) have revolutionized the management of abnormal placentation. These include the use of tranexamic acid, interventional radiology, cell saver technology, and point-of-care coagulation tests. The role of maternal critical care for the optimization of postoperative complications and physiological derangements has not been considered widely in the literature. This article summarizes the current evidence for interventions and suggests a protocol for the management of these high-risk patients. Summary A robust protocol outlining the key elements of the management of placenta accreta, including optimizing postoperative care, should be in place to promote desired outcomes. Correspondence to Dr Vinod Patil, Consultant Obstetric Anaesthetist, Department of Anesthesiology, Queens Hospital, BHR University Hospital NHS Trust Romford, Romford RM7 0AG, UK. Tel: 44 1708503727; e-mail: Vinodpatiluk@gmail.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2vcE7pX

Impact of intra-operative fluid and noradrenaline administration on early postoperative renal function after cystectomy and urinary diversion: A retrospective observational cohort study

BACKGROUND The use of noradrenaline to enable a restrictive approach to intra-operative fluid therapy to avoid salt and water overload has gained increasing acceptance. However, concerns have been raised about the impact of this approach on renal function. OBJECTIVES To identify risk factors for acute kidney injury (AKI) in patients undergoing cystectomy with urinary diversion and determine whether administration of noradrenaline and intra-operative hydration regimens affect early postoperative renal function. DESIGN Retrospective observational cohort study. SETTING University hospital, from 2007 to 2016. PATIENTS A total of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those with incomplete data and having pre-operative haemodialysis were excluded. MAIN OUTCOME MEASURES AKI was defined as a serum creatinine increase of more than 50% over 72 postoperative hours. Multiple logistic regression analysis was performed to model the association between risk factors and AKI. RESULTS Postoperative AKI was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI, 1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01 to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P = 0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097). Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16 [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION Noradrenaline administration did not increase the risk for AKI. A too restrictive approach to administration of crystalloids was associated with an increased risk for AKI, particularly in older patients, those receiving antihypertensive medication, and those whose surgery was prolonged. As AKI was associated with longer hospital stay and increased postoperative morbidity, these observations should be taken into account to improve outcome when addressing peri-operative fluid management. TRIAL REGISTRATION Not applicable. Correspondence to Patrick Y. Wuethrich, MD, Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland Tel: +41 316322725; fax: +41 316320554; e-mail: patrick.wuethrich@insel.ch © 2018 European Society of Anaesthesiology

https://ift.tt/2v9py6Q

Treatment outcomes of patients with spinal metastases derived from hepatocellular carcinoma

Abstract

Background

The prognosis of hepatocellular carcinoma (HCC) used to be poor, but it has recently improved, which has meant that clinicians have greater opportunity to treat spinal metastases and the associated epidural spinal cord compression. However, there have been few systematic functional studies about HCC-derived spinal metastases. The treatment outcomes of surgical treatment for HCC-derived metastatic spinal tumors were investigated.

Methods

The post-treatment survival period and pain, paralysis, and disturbance of activities of daily living (ADL) were investigated in 60 patients (surgery 25, conservative treatment 35).

Results

The mean post-treatment survival period was 7.4 ± 8.2 months (range 0.3–36 months). Univariate analysis indicated that the following factors influenced survival: the patient's general condition, presence/absence of major internal organ metastasis, serum albumin level, Child–Pugh classification, surgical treatment for spinal metastasis, and bone-modifying agent treatment. In the multivariate analysis of these 6 items, 3 significant factors were extracted: the patient's general condition, the serum albumin level, and bone-modifying agent treatment. Pain significantly improved in both groups (p < 0.001). Paralysis did not change significantly in the surgical group (p = 0.575), but it was significantly aggravated in the conservative treatment group (p = 0.047). The ADL abilities of the surgical group improved significantly (p < 0.001).

Conclusion

Most patients exhibited poor survival. In the conservative treatment group, paralysis was significantly aggravated, and little improvement was seen in the patients' ADL abilities. In the surgical group, the patients' ADL abilities improved significantly, but their paralysis did not. Therefore, surgery should be actively performed for HCC-derived spinal metastasis whenever it is indicated.

from Cancer via ola Kala on Inoreader https://ift.tt/2JKyGlu
via IFTTT

Hemoglobinopathies—genetically diverse, clinically complex, and globally relevant

Summary

Hemoglobinopathies represent the most frequent monogenic disorders worldwide. Migration during recent years led to a profoundly increasing number of patients in countries where the indigenous population has not been affected. This short review will give an overview on etiology, pathogenesis, clinical features, diagnostics, and treatment of the most relevant hemoglobinopathies, i.e., the thalassemias and sickle cell disease.

from Cancer via ola Kala on Inoreader https://ift.tt/2GWsTLR
via IFTTT

Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie

Publication date: Available online 12 April 2018
Source:Cancer/Radiothérapie
Author(s): Y. Brahimi, D. Antoni, R. Srour, F. Proust, H. Cebula, A. Labani, G. Noël




from Cancer via ola Kala on Inoreader https://ift.tt/2IUgnsV
via IFTTT

Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review

Publication date: Available online 12 April 2018
Source:Cancer/Radiothérapie
Author(s): C. Demoor-Goldschmidt, M.-A. Mahé, S. Supiot
Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment.



from Cancer via ola Kala on Inoreader https://ift.tt/2HkGnAo
via IFTTT

Unusual occurrence reporting system: Sharing a ten years experience from a tertiary care JCIA accredited university hospital

Publication date: Available online 13 April 2018
Source:Cancer/Radiothérapie
Author(s): A. Hussain, Y. Khan, N. Ali, A.Q. Jangda, S. Siddiqui, W. Muhammad, Z. Khan, A.N. Abbasi, L. Rehman, A. Yousuf
PurposeIdentifying a true measure of safety is challenging in radiation oncology. A culture of unusual reporting may however be used as an indirect measure for it. The purpose of this study is to share our experience of unusual occurrence reporting system, established in the Radiation Oncology section since 2006, the first of this nature in Pakistan.Materials and methodsData is collected over the last ten years. An in-house online reporting system has been developed for reporting unusual events. All the reported events are evaluated retrospectively. The stage of unusual occurrence along the radiation therapy process, possible causes, severity and preventive measures taken are discussed.ResultsAnalysis of the 501 unusual occurrences reported over the last ten years has shown a substantial decrease in the number of significant mistakes observed. Of the total, 57 % unusual occurrences have been reported by radiation therapy technologists, including treatment preparation processes. Oversight is supposed to be the most common cause for unusual occurrences.ConclusionsThe ten years experience with reporting and documenting of unusual occurrences resulted in a safety culture where every individual is willing to share any type of incident with a free well. Our experience at the Aga Khan University Hospital (AKUH) shows that the major reason for the occurrence of incidents was oversight. The majority of unusual occurrences were reported by radiation therapy technologists, as expected, since they handle the bulk of the treatment planning process.



from Cancer via ola Kala on Inoreader https://ift.tt/2IObC3Z
via IFTTT

Treatment outcomes of patients with spinal metastases derived from hepatocellular carcinoma

Abstract

Background

The prognosis of hepatocellular carcinoma (HCC) used to be poor, but it has recently improved, which has meant that clinicians have greater opportunity to treat spinal metastases and the associated epidural spinal cord compression. However, there have been few systematic functional studies about HCC-derived spinal metastases. The treatment outcomes of surgical treatment for HCC-derived metastatic spinal tumors were investigated.

Methods

The post-treatment survival period and pain, paralysis, and disturbance of activities of daily living (ADL) were investigated in 60 patients (surgery 25, conservative treatment 35).

Results

The mean post-treatment survival period was 7.4 ± 8.2 months (range 0.3–36 months). Univariate analysis indicated that the following factors influenced survival: the patient's general condition, presence/absence of major internal organ metastasis, serum albumin level, Child–Pugh classification, surgical treatment for spinal metastasis, and bone-modifying agent treatment. In the multivariate analysis of these 6 items, 3 significant factors were extracted: the patient's general condition, the serum albumin level, and bone-modifying agent treatment. Pain significantly improved in both groups (p < 0.001). Paralysis did not change significantly in the surgical group (p = 0.575), but it was significantly aggravated in the conservative treatment group (p = 0.047). The ADL abilities of the surgical group improved significantly (p < 0.001).

Conclusion

Most patients exhibited poor survival. In the conservative treatment group, paralysis was significantly aggravated, and little improvement was seen in the patients' ADL abilities. In the surgical group, the patients' ADL abilities improved significantly, but their paralysis did not. Therefore, surgery should be actively performed for HCC-derived spinal metastasis whenever it is indicated.

https://ift.tt/2JKyGlu

Hemoglobinopathies—genetically diverse, clinically complex, and globally relevant

Summary

Hemoglobinopathies represent the most frequent monogenic disorders worldwide. Migration during recent years led to a profoundly increasing number of patients in countries where the indigenous population has not been affected. This short review will give an overview on etiology, pathogenesis, clinical features, diagnostics, and treatment of the most relevant hemoglobinopathies, i.e., the thalassemias and sickle cell disease.

https://ift.tt/2GWsTLR

Méningiomes de la base du crâne : efficacité et tolérance clinique, efficacité radiologique et cinétique tumorale après radiothérapie

Publication date: Available online 12 April 2018
Source:Cancer/Radiothérapie
Author(s): Y. Brahimi, D. Antoni, R. Srour, F. Proust, H. Cebula, A. Labani, G. Noël




https://ift.tt/2IUgnsV

Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review

Publication date: Available online 12 April 2018
Source:Cancer/Radiothérapie
Author(s): C. Demoor-Goldschmidt, M.-A. Mahé, S. Supiot
Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment.



https://ift.tt/2HkGnAo

Unusual occurrence reporting system: Sharing a ten years experience from a tertiary care JCIA accredited university hospital

Publication date: Available online 13 April 2018
Source:Cancer/Radiothérapie
Author(s): A. Hussain, Y. Khan, N. Ali, A.Q. Jangda, S. Siddiqui, W. Muhammad, Z. Khan, A.N. Abbasi, L. Rehman, A. Yousuf
PurposeIdentifying a true measure of safety is challenging in radiation oncology. A culture of unusual reporting may however be used as an indirect measure for it. The purpose of this study is to share our experience of unusual occurrence reporting system, established in the Radiation Oncology section since 2006, the first of this nature in Pakistan.Materials and methodsData is collected over the last ten years. An in-house online reporting system has been developed for reporting unusual events. All the reported events are evaluated retrospectively. The stage of unusual occurrence along the radiation therapy process, possible causes, severity and preventive measures taken are discussed.ResultsAnalysis of the 501 unusual occurrences reported over the last ten years has shown a substantial decrease in the number of significant mistakes observed. Of the total, 57 % unusual occurrences have been reported by radiation therapy technologists, including treatment preparation processes. Oversight is supposed to be the most common cause for unusual occurrences.ConclusionsThe ten years experience with reporting and documenting of unusual occurrences resulted in a safety culture where every individual is willing to share any type of incident with a free well. Our experience at the Aga Khan University Hospital (AKUH) shows that the major reason for the occurrence of incidents was oversight. The majority of unusual occurrences were reported by radiation therapy technologists, as expected, since they handle the bulk of the treatment planning process.



https://ift.tt/2IObC3Z

Calendar

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5





https://ift.tt/2HxPPy0

Omitting radiotherapy in women ≥ 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe

Publication date: Available online 13 April 2018
Source:European Journal of Surgical Oncology
Author(s): Åsa Wickberg, Göran Liljegren, Fredrika Killander, Henrik Lindman, Judith Bjöhle, Michael Carlberg, Carl Blomqvist, Johan Ahlgren, Kenneth Villman
PurposeThe aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET).Patients and MethodsEligibility criteria were: consecutive patients with age ≥ 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival.ResultsBetween 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65 to 90).After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1 %) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%).ConclusionBCS and ET without RT seem to be a safe treatment option in women ≥ 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors.



https://ift.tt/2EKfCjA

Follow-up after curative treatment for oral squamous cell carcinoma. A critical appraisal of the guidelines and a review of the literature

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): M.T. Brands, P.A. Brennan, A.L.M. Verbeek, M.A.W. Merkx, S.M.E. Geurts
The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC).There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong).Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC.To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen.



https://ift.tt/2JJ64Jt

Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): L. Max Almond, Alessandro Gronchi, Dirk Strauss, Mariam Jafri, Samuel Ford, Anant Desai
Extended surgery remains the mainstay of treatment in retroperitoneal sarcoma, although conflicting data exist on the benefit of neoadjuvant and adjuvant therapies, particularly with regard to tumour grade and histological type. Experience of radiotherapy and chemotherapy in extremity soft tissue sarcoma can inform treatment strategies, however these data cannot be universally extrapolated to the retroperitoneum where disease biology and anatomical considerations are different. The present review sets a historical context before discussing recent evidence and on-going multi-centre trials in retroperitoneal sarcoma. Promising data on histologically- and molecularly-targeted chemotherapy are discussed and the need for centralisation of retroperitoneal sarcoma services in order to facilitate large international collaborative trials is emphasised.



https://ift.tt/2EKfCQC

Clinical and pathological features of “small” GIST (≤2 cm). What is their prognostic value?

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Juan Ángel Fernández, Álvaro Jesús Gómez-Ruiz, Vicente Olivares, Belén Ferri, Maria Dolores Frutos, Teresa Soria, Pedro José Gil, Gloria Torres, Pascual Parrilla
IntroductionSmall GIST (<2 cm) are tumors whose biological behavior is benign and frequently involutes. Despite their increasing incidence, few studies have addressed the characteristics of these GIST. The aim of this work is to clarify the management of this entity.Patients and methodThe characteristics of ≤2 cm GIST were initially described, and then compared with those >2 cm. This series comprises 104 patients and they were divided according to tumor size in 4 groups: tumors which are ≤2 cm (group 1, G1), >2 and ≤ 5 cm (G2), >5 and ≤ 10 cm (G3) and >10 cm (G4).Results and discussionMost of small GIST were asymptomatic and incidental, and were located in the stomach. There is an association between patients with associated tumors and asymptomatic GIST. A high overall mortality rate of up to 40% is observed being disease-specific mortality 4.5%. The disease-specific mortality increases proportionally with size. The overall survival (OS) at 5 years are lower for both <2 cm (61%) and >10 cm (53%) than the rest (85–91%). When analyzing the impact of tumor association on <2 cm GIST, we observed that the OS of patients with non-associated tumors was much higher than in the associated ones (90% vs 32% at 5 years, respectively), while no differences were observed in the disease specific survival.ConclusionsSmall GIST are tumors that are very often incidentally discovered in the course of complementary examinations. Its prognosis is very good, but it depends on the associated tumor.



https://ift.tt/2JJ5Odt

Editorial Board

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5





https://ift.tt/2HxaYbM

Generalized cardiovascular disease on a preoperative CT scan is predictive for anastomotic leakage after esophagectomy

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Alicia S. Borggreve, Lucas Goense, Peter S.N. van Rossum, Richard van Hillegersberg, Pim A. de Jong, Jelle P. Ruurda
BackgroundRecent studies demonstrated that calcification of arteries supplying the gastric tube is associated with anastomotic leakage after esophagectomy. However, it remains unclear whether this association only derives from local flow limitations, or generalized vascular disease as well. The purpose of this study was to determine whether calcification throughout the entire cardiovascular system is associated with anastomotic leakage.MethodsConsecutive patients who underwent an esophagectomy with gastric tube reconstruction and cervical anastomosis for esophageal cancer were analyzed. Diagnostic CT images were scored for the presence of arterial calcification on 10 locations based on a visual grading system. The association with anastomotic leakage was studied using logistic regression analysis.ResultsA total of 406 patients were included for analysis of whom 104 developed anastomotic leakage (25.6%). Presence of calcification in the coronary arteries (minor calcification: 36.5% leakage; no calcification: 18.1%, p = .001), supra-aortic arteries (minor calcification: 30.9% leakage; major calcification: 35.3%; no calcification: 16.1%, p = .007 and p < .001, respectively) and thoracic aorta (major calcification: 33.3% leakage; no calcification: 19.4%, p = .011) was associated with leakage. In multivariable analysis, minor calcification of the coronary arteries (OR 2.29, 95% CI: 1.28–4.12, p = .005) and calcification of the supra-aortic arteries (OR 2.48, 95% CI: 1.30–4.74, p = .006 for minor calcification and OR 2.72, 95% CI: 1.49–4.99, p = .001 for major calcification) remained independently associated with leakage.ConclusionsCalcification of the coronary and supra-aortic arteries on routine CT are predictive of cervical anastomotic leakage after esophagectomy. These results suggest that generalized cardiovascular disease is a strong indicator for the risk of leakage.



https://ift.tt/2GY82DI

Poor performance in incremental shuttle walk and cardiopulmonary exercise testing predicts poor overall survival for patients undergoing esophago-gastric resection

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Jessica Whibley, Christopher J. Peters, Laura J. Halliday, Asif M. Chaudry, William H. Allum
IntroductionEsophageal and gastric cancer have a poor prognosis and surgical intervention is associated with considerable morbidity, highlighting the need for careful preoperative assessment. The Incremental Shuttle Walk Test (ISWT) and Cardiopulmonary exercise testing (CPET) can assess preoperative fitness. This study aims to investigate their correlation with both postoperative respiratory complications and overall survival.Patients and methodsPatients were identified who underwent esophageal or gastric resections for cancer between 2010 and 2014 and had ISWT and/or CPET assessments. Tumor differentiation, stage, postoperative respiratory complications, and outcome were documented and then correlated with the results of the preoperative fitness assessments.ResultsNeither the ISWT result, anaerobic threshold (AT) nor VO2 Max correlated well with perioperative complications. However, ISWT (p < 0.001), AT (p < 0.001) and VO2 Max (p < 0.001) all correlated strongly with overall survival. No patient with a score of less than 350 m on ISWT survived beyond 3 years. In a subset of patients with ISWT results both pre and post chemotherapy (n = 49), those that had an improvement in result had a 19% incidence of post-operative respiratory complications compared to 45% where the result did not change or declined, though due to small numbers this only approached significance (p = 0.08).ConclusionISWT and CPET can be useful preoperative tools to predict overall survival for patients undergoing esophago-gastric resection. Furthermore, patients that improve their functional status during chemotherapy seem to do better than those where it remains static or declines.



https://ift.tt/2GYHVN9

Surgical morbidity and mortality after neoadjuvant chemotherapy in the CRITICS gastric cancer trial

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Y.H.M. Claassen, H.H. Hartgrink, J.L. Dikken, W.O. de Steur, J.W. van Sandick, N.C.T. van Grieken, A. Cats, A.K. Trip, E.P.M. Jansen, W.M. Meershoek-Klein Kranenbarg, J.P.B.M. Braak, H. Putter, M.I. van Berge Henegouwen, M. Verheij, C.J.H. van de Velde
BackgroundIn order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity.MethodsPatients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications.ResultsBetween 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038).ConclusionCompared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection.



https://ift.tt/2EIm5M1

Development of a risk-scoring system to evaluate the serosal invasion for macroscopic serosal invasion positive gastric cancer patients

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Peng-liang Wang, Jin-yu Huang, Zhi Zhu, Bao-cheng Gong, Han-wei Huang, Shi-jie Duan, Hui-mian Xu, Fu-nan Liu
BackgroundThe status of serosal invasion is often discordance between pathological and intraoperative evaluation. Our study sought to develop a risk-scoring system (RSS) to predict the probability of pT4a for macroscopic serosal invasion (MSI) positive patients and reevaluate the serosal invasion status.Patients and MethodsA total of 1301 pT3/pT4a gastric cancer patients with curative surgery were reviewed. We constructed the RSS to predict the probability of pT4a and assigned MSI-positive patients into different risk groups based on the risk scores. The prognostic significance of these risk groups was also evaluated.ResultsUnivariate and multivariate analyses identified that tumor location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI-positive patients in high-risk group had similar survival with pT4a patients. We incorporated these two groups into one stage and proposed a novel revised-T stage. Two-step multivariate analyses indicated that the revised-T stage showed better prediction ability for prognosis and peritoneal recurrence assessment than original pT stage and MSI status.ConclusionsIn our present study, we developed a RSS to predict the probability of pT4a for MSI-positive patients. Based on our RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI-positive patients in clinical practice. Future studies should include other preoperative predictors to improve the clinical utility of our model.



https://ift.tt/2HxjkjF

Preoperative predictors of high and low axillary nodal burden in Z0011 eligible breast cancer patients with a positive lymph node needle biopsy result

Publication date: Available online 12 April 2018
Source:European Journal of Surgical Oncology
Author(s): Geok-Hoon Lim, Vidya S. Upadhyaya, Hannah Angela Acosta, Jayne Michelley Adolfo Lim, John C. Allen, Lester Chee Hao Leong
BackgroundZ0011 trial showed that early breast cancer patients with low axillary nodal burden, may be spared an axillary lymph node dissection with no survival compromise. Axillary lymph node dissection can be reserved for patients with a high axillary nodal burden. We aim to determine the preoperative factors that could distinguish between low and high axillary nodal burden in Z0011 eligible patients with a needle biopsy proven metastatic node.MethodPatients who fulfilled Z0011 trial criteria with a positive lymph node needle biopsy and had axillary lymph node dissection (ALND) were recruited. These patients were classified into low and high nodal burden subgroups, defined as having 1-2 and ≥3 metastatic lymph nodes, respectively. The clinical, radiological and pathological features between the 2 subgroups were compared.Results70 (40%) and 105 (60%) patients had low and high nodal burden respectively. The high nodal burden subgroup was more likely to have on ultrasound ≥3 abnormal lymph nodes (37.14% versus 4.29%) (P<.0001) and maximum cortical thickness >4mm (31.43% versus 10.0%) (P=0.0036). Multivariate analysis revealed abnormal lymph nodes ≥3 to have an odds ratio of 20.72 (95% CI 5.91-72.65) P<.0001.Conclusion≥3 abnormal lymph nodes on ultrasound was the most significant predictor of high nodal burden subgroup in Z0011 eligible patients with a positive lymph node needle biopsy. This information could allow this subgroup to proceed to an upfront ALND and avoid the need of a sentinel lymph node biopsy in the post Z0011 trial era.



https://ift.tt/2GWwYvt

The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Ryoichi Miyamoto, Satoshi Inagawa, Naoki Sano, Sosuke Tadano, Shinya Adachi, Masayoshi Yamamoto
BackgroundThe preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic marker for gastric cancer patients. However, the utility of the NLR in predicting short-term outcomes in gastric cancer patients remains unclear. Here, we investigated whether the preoperative NLR is a predictor of short-term outcomes in gastric cancer patients.MethodsWe retrospectively evaluated 154 consecutive gastric cancer patients. We compared the perioperative outcomes and median survival times (MSTs). In particular, for stage II/III (UICC, 7th edition) gastric cancer patients, we compared median disease-free survival time (MDFST) between the low- and high-NLR groups.ResultsBetween the low-NLR group (n = 110) and the high-NLR group (n = 44), significant differences were observed in perioperative outcomes, including postoperative complications (3 (2.7%) vs. 5 (11.3%); p = 0.015), intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusions (0 vs. 3 (6.8%); p = 0.042). MSTs and MDFSTs were also significantly different (812 vs. 594 days, p = 0.04; and 848 vs. 475 days, p = 0.03, respectively). Multivariate analysis identified the NLR (hazard ratio [HR], 2.015; p = 0.004), Glasgow Prognostic Score (GPS) (HR, 1.533; p = 0.012), and presence of stage III/IV disease (HR, 5.488; p < 0.001), preoperative symptoms (HR, 3.412; p = 0.008), or postoperative complications (HR, 2.698; p < 0.001) as independent prognostic factors.ConclusionsWe suggest that the preoperative NLR is an additional useful predictor of both long-term and short-term outcomes in gastric cancer patients.



https://ift.tt/2HzL0nY

Role of neoadjuvant chemoradiotherapy in clinical T2N0M0 esophageal cancer: A population-based cohort study

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Lucas Goense, Els Visser, Nadia Haj Mohammad, Stella Mook, Rob H.A. Verhoeven, Gert J. Meijer, Peter S.N. van Rossum, Jelle P. Ruurda, Richard van Hillegersberg
BackgroundThe aim of this population-based cohort study was to determine whether the addition of neoadjuvant chemoradiotherapy (nCRT) to surgery is associated with improved pathologic outcomes and survival in patients with cT2N0M0 esophageal cancer.MethodsPatients who underwent nCRT followed by surgery or surgery alone for cT2N0M0 esophageal cancer were identified from The Netherlands Cancer Registry database (2005–2014). Accuracy of clinical staging was assessed using the resection specimen as gold standard. After propensity score matching, influences of both treatment strategies on radical resection (R0) rates and overall survival were compared.ResultsIn total 533 patients were included; 353 underwent nCRT followed by surgery and 180 underwent surgery alone. In the nCRT group 32% of patients achieved a pathologic complete response. Clinical understaging was observed in 62% of the patients in the surgery alone group based on pT-stage (n = 30, 27%), pN-stage (n = 26, 23%), or both (n = 55, 50%). Propensity score matching resulted in 78 patients who underwent nCRT plus surgery versus 78 who underwent surgery alone. In the nCRT group radical resections were more frequently observed (99% vs. 89% p = 0.031) and resulted in improved 5-year overall survival (46% vs. 33%, p = 0.017).ConclusionIn this population-based study, clinical staging of cT2N0M0 esophageal cancer was highly inaccurate. Compared to surgery alone, neoadjuvant chemoradiotherapy was associated with higher radical resection rates and improved overall survival.



https://ift.tt/2HwEH4w

The effect of being informed on receiving immediate breast reconstruction in breast cancer patients

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): K.M. de Ligt, A.C.M. van Bommel, K. Schreuder, J.H. Maduro, M.T.F.D. Vrancken Peeters, M.A.M. Mureau, S. Siesling
IntroductionIn previous research from the NABON breast cancer audit, observed hospital variation in immediate breast reconstruction (IBR) rates in the Netherlands could not be fully explained by tumour, patient, and hospital factors. The process of information provision and decision-making may also contribute to the observed variation; the objective of the current study was to give insight in the underlying decision-making process for IBR and to determine the effect of being informed about IBR on receiving IBR.MethodsA total of 502 patients with IBR and 716 without IBR treated at twenty-nine hospitals were invited to complete an online questionnaire on obtained information and decision-making regarding IBR. The effect of being informed about IBR on receiving IBR was determined by logistic regression analysis.ResultsResponses from five hundred and ten patients (n = 229 IBR, n = 281 without IBR) were analysed. Patients with IBR compared to patients without reconstruction showed a difference in patient, tumour, treatment (including radiotherapy), and hospital characteristics. Patients with IBR were more often informed about IBR as a treatment option (99% vs 73%), they discussed (dis)advantages more often with their physician (86% vs 68%), and they were more often involved in shared decision-making (91% vs 67%) compared to patients without IBR. Multivariate logistic regression analysis, corrected for confounders, showed that being informed about IBR increased the odds for receiving IBR fourteen times (p < 0.001).ConclusionsThe positive effect of being informed about IBR on receiving IBR stresses the importance of treatment information in the decision-making process for IBR.



https://ift.tt/2GWwqFV

Optimisation of breast MRI compatibility after sentinel node biopsy with paramagnetic tracers

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Andreas Karakatsanis, Christine Obondo, Shahin Abdsaleh, Abdi-Fatah Hersi, Staffan Eriksson, Fredrik Wärnberg




https://ift.tt/2HwgdZ7

High expression of MMP-9 is associated with better prognosis in extrahepatic bile duct cancer patients

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Younghee Park, Kyubo Kim, Jin Ho Paik, Eui Kyu Chie, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh
PurposeTo evaluate the prognostic value of matrix metalloproteinase-9 (MMP-9) in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy.MethodsBetween January 2000 and August 2006, patients who underwent complete resection followed by adjuvant radiotherapy for EHBD cancer were enrolled in this study. The expression of MMP-9 was assessed with immunohistochemical staining. The prognostic values of the MMP-9 expression and other clinicopathologic factors were evaluated in univariate and multivariate analyses.ResultsSixty-six patients were included in this study. All received radiotherapy with a median dose of 40 Gy (range, 40–56), and 61 patients received concomitant fluoropyrimidine chemotherapy. MMP-9 was highly expressed in 33 patients (50.0%). MMP-9 expression was significantly associated with locoregional recurrence-free survival (LRRFS) and overall survival (OS) but not with distant metastasis-free survival (DMFS). The 5-year LRRFS and OS rates were 50.8% versus 86.5% (p = .0281), and 23.3% versus 68.1% (p = .0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, tumor location was associated with DMFS and OS (p = .0292 and .0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p = .0277 and .0060, respectively). Based on multivariate analysis for OS, tumor location was the only significant prognostic factor (p = .0021), while MMP-9 expression showed marginal significance (p = .0633).ConclusionMMP-9 expression is a useful prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy.



https://ift.tt/2GY75v8

Announcements

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5





https://ift.tt/2HAduy4

Enucleation of pancreatic solid pseudopapillary neoplasm: Short-term and long-term outcomes from a 7-year large single-center experience

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Xing Wang, Yong-Hua Chen, Chun-lu Tan, Hao Zhang, Jun-jie Xiong, Hong-yu Chen, Neng-wen Ke, Xu-Bao Liu
BackgroundEnucleation is increasingly used for pancreatic solid pseudopapillary neoplasm (SPN) to preserve function of the pancreas. The data was limited due to rarity of this low-grade neoplasm. We sought to describe the indications, operative technique, short and long-term outcomes after enucleation with largest series of enucleated SPNs.MethodsData collected retrospectively from 110 patients with SPN who underwent pancreatectomy between 2009 and 2016 in our institution were reviewed. Thirty-one patients underwent enucleation were identified for analysis, and compared with the 70 patients underwent conventional pancreatic resection.ResultsOf the 31 patients, 27 (87.1%) were women, and the mean age was 29.8 years (range, 11–49 years). Enucleated SPNs were mostly located in the head/uncinate process of the pancreas (38.7%). Overall morbidity was 25.8%, mainly due to POPF (19.4%), and severe morbidity was only 6.5% with no death. Compared with conventional pancreatic resection, enucleation had a shorter duration of surgery (P < 0.001), less blood loss (P < 0.001), lower rate of exocrine insufficiency (P = 0.033) and comparable morbidity (P = 1), with no increased risk of tumor recurrence (P = 1). The rate of endocrine insufficiency after enucleation seemed lower (Nil vs. 4.5%, P = 0.55).ConclusionsEnucleation of SPN of the pancreas appears to be feasible and safe for preserving exocrine and endocrine function of the gland. Enucleation with negative surgical margin seems adequate with no increased risk of tumor recurrence. Enucleation could be seriously considered as an alternative to conventional resection for this frequently young population.



https://ift.tt/2GV4FgZ

Electrochemotherapy as treatment option for hepatocellular carcinoma, a prospective pilot study

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): Mihajlo Djokic, Maja Cemazar, Peter Popovic, Bor Kos, Rok Dezman, Masa Bosnjak, Martina Niksic Zakelj, Damijan Miklavcic, Stojan Potrc, Borut Stabuc, Ales Tomazic, Gregor Sersa, Blaz Trotovsek
Background and objectivesElectrochemotherapy provides non-thermal ablation of cutaneous as well as deep seated tumors. Based on positive results of the treatment of colorectal liver metastases, we conducted a prospective pilot study on hepatocellular carcinomas with the aim of testing the feasibility, safety and effectiveness of electrochemotherapy.Patients and methodsElectrochemotherapy with bleomycin was performed on 17 hepatocellular carcinomas in 10 patients using a previously established protocol. The procedure was performed during open surgery and the patients were followed for median 20.5 months.ResultsElectrochemotherapy was feasible for all 17 lesions, and no treatment-related adverse events or major post-operative complications were observed. The median size of the treated lesions was 24 mm (range 8–41 mm), located either centrally, i.e., near the major hepatic vessels, or peripherally. The complete response rate at 3–6 months was 80% per patient and 88% per treated lesion.ConclusionsElectrochemotherapy of hepatocellular carcinoma proved to be a feasible and safe treatment in all 10 patients included in this study. To evaluate the effectiveness of this method, longer observation period is needed; however the results at medium observation time of 20.5 months after treatment are encouraging, in 15 out of 17 lesions complete response was obtained. Electrochemotherapy is predominantly applicable in patients with impaired liver function due to liver cirrhosis and/or with lesions where a high-risk operation is needed to achieve curative intent, given the intra/perioperative risk for high morbidity and mortality.



https://ift.tt/2HwJJ0O

Low skeletal muscle mass outperforms the Charlson Comorbidity Index in risk prediction in patients undergoing pancreatic resections

Publication date: May 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 5
Author(s): D. Wagner, K. Marsoner, A. Tomberger, J. Haybaeck, J. Haas, G. Werkgartner, H. Cerwenka, H. Bacher, H.J. Mischinger, P. Kornprat
IntroductionLow skeletal muscle mass is a known predictor of morbidity and mortality in patients undergoing major pancreatic surgeries. We sought to combine low skeletal muscle mass with established risk predictors to improve their prognostic capacity for postoperative outcome and morbidity.MethodsAs established parameters to predict preoperative mortality risk for patients, the ASA classification and the Charlson Comorbidity Index (CCI) were used. The Hounsfield Units Average Calculation (HUAC) was measured to define low skeletal muscle mass in 424 patients undergoing pancreatic resections for malignancies. Patients in the lowest sex-adjusted quartile for HUAC were defined as having low skeletal muscle mass (muscle wasting). Multivariable Cox regression analysis was utilized to identify preoperative risk factors associated with postoperative morbidity.ResultsMedian patient age was 63 years (19–87), 47.9% patients were male, and half the cohort had multiple comorbidities (Charlson Comorbidity Index [CCI]>6, 63.2%), 30-day mortality was 5.8% (n = 25). Median HUAC was 19.78 HU (IQR: 15.94–23.54) with 145 patients (34.2%) having low skeletal muscle mass. Preoperative frailty defined by low skeletal muscle mass was associated with an increased risk for postoperative complications (OR 1.55, CI 95% 0.98–2.45, p = 0.014), and a higher 30-day mortality (HR 5.17, CI 95% 1.57–16.69, p = 0.004). With an AUC of 0.85 HUAC showed the highest predictability for 30-day mortality (CI 95% 0.78–0.91, p = 0.0001). Patients with CCI ≥6 and low skeletal muscle mass defined by the HUAC had a 9.78 higher risk of dying in the immediate postoperative phase (HR 9.78, CI 95% 2.98–12.2, p = 0.0001).ConclusionLow skeletal muscle mass predicts postoperative mortality and complications best and it should be incorporated to conventional risk scores to identify high risk patients.



https://ift.tt/2GYd3MS

Primary sarcomatoid urothelial carcinoma of the ureter: a case report and review of the literature

Abstract

Background

Sarcomatoid urothelial carcinoma is a very dangerous malignant tumour derived from the epithelium. Primary sarcomatoid carcinoma of the ureter is extremely rare in clinical practice. The prognosis of this kind of disease is really poor, and there is still not a diagnosis standard in the world.

Case presentation

An 82-year-old female patient who had intermittent waist pain without any other symptoms, had diagnosed as urothelial cancer on computerised tomography urography. Considering the patient's age and quality of life, we made a preserving kidneys resection of the local tumour. The tumour was composed of sarcomatous and carcinomatous elements, and immunohistochemical examination showed that tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and GATA3 markers. There were no complications after 1-hour surgery. After 3 months, there was no signs of recurrence and metastasis.

Conclusion

This case was a patient with sacomatoid urothelial carcinoma. Through a transurethral resection with laser, the patient recovered well, and there was no sign of any recurrence of the tumour after 3 months. With the development of technology and science, more and more cancerous patients' living quality and survival rate were improved. Maybe it is essential for urologists and scientists to entirely understand the characteristics of the sarcomatoid urothelial carcinoma and make a better clinical guideline.

from Cancer via ola Kala on Inoreader https://ift.tt/2HzETQH
via IFTTT

Meningeal carcinomatosis: three case-reports

Abstract

Background

Meningeal carcinomatosis (MC) is characterized by diffuse infiltration of tumor cells in meninges. There is no tumor mass in the brain and parenchyma of the spinal cord. MC is divided into primary and metastatic types. MC cases were previously diagnosed postoperatively or at autopsy. Recent advances in spinal abbreviation cytology and imaging have led to increase in number of reported cases. In this study, we discuss the manifestations of MC patients based on magnetic resonance imaging (MRI) findings, as well as the correlation between the manifestations and pathology.

Case presentation

MC was confirmed in all three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic resonance imaging. Due to different primary diseases, the patients had specific imaging manifestations.

Conclusion

Enhanced MRI examination is extremely sensitive for detecting abnormalities in meninges, which plays a very important role in the diagnosis of MC. Since meninges of some MC patients cannot be enhanced, the enhanced MRI examination cannot be replaced by conventional cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast agents, which could provide higher lesion conspicuity and enhances lesion detection, there may be some more choices to improve the detection rate of MC patients and prolong their survival lifetime.

from Cancer via ola Kala on Inoreader https://ift.tt/2GUZwFH
via IFTTT

Primary sarcomatoid urothelial carcinoma of the ureter: a case report and review of the literature

Abstract

Background

Sarcomatoid urothelial carcinoma is a very dangerous malignant tumour derived from the epithelium. Primary sarcomatoid carcinoma of the ureter is extremely rare in clinical practice. The prognosis of this kind of disease is really poor, and there is still not a diagnosis standard in the world.

Case presentation

An 82-year-old female patient who had intermittent waist pain without any other symptoms, had diagnosed as urothelial cancer on computerised tomography urography. Considering the patient's age and quality of life, we made a preserving kidneys resection of the local tumour. The tumour was composed of sarcomatous and carcinomatous elements, and immunohistochemical examination showed that tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and GATA3 markers. There were no complications after 1-hour surgery. After 3 months, there was no signs of recurrence and metastasis.

Conclusion

This case was a patient with sacomatoid urothelial carcinoma. Through a transurethral resection with laser, the patient recovered well, and there was no sign of any recurrence of the tumour after 3 months. With the development of technology and science, more and more cancerous patients' living quality and survival rate were improved. Maybe it is essential for urologists and scientists to entirely understand the characteristics of the sarcomatoid urothelial carcinoma and make a better clinical guideline.

https://ift.tt/2HzETQH