Video-assisted thoracic lobectomy for lung cancer in Italy: the ‘VATS Group’ Project

Future Oncology Ahead of Print.


http://ift.tt/2exfpqc

Ultrasound, computed tomography or magnetic resonance imaging - which is preferred for acute appendicitis in children? A Meta-analysis

Abstract

Background

There is no established consensus about the relative accuracies of US, CT and MRI in childhood appendicitis.

Objective

To compare, through meta-analysis, the accuracies of US, CT and MRI for clinically suspected acute appendicitis in children.

Materials and methods

PubMed, Embase, Web of Science and the Cochrane Library were searched. After study selection, data extraction and quality assessment, the sensitivity, specificity and the area under the curve of summary receiver operating characteristic were calculated and compared.

Results

Twenty-seven articles including 29 studies met the inclusion criteria, including 19 studies (9,170 patients) of US, 6 studies (928 patients) of CT and 4 studies (990 patients) of MRI. The analysis showed that the area under the receiver operator characteristics curve of MRI (0.995) was a little higher than that of US (0.987) and CT (0.982; P > 0.05).

Conclusion

US, CT and MRI have high diagnostic accuracies of clinically suspected acute appendicitis in children overall with no significant difference.

http://ift.tt/2fqA9NY

Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005–2012

Abstract

Background

Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation.

Objective

To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether ¹⁸F-fluorodeoxyglucose positron emission tomography – computed tomography (¹⁸F-FDG PET-CT) is a major contributor of radiation.

Materials and methods

Twenty Ewing sarcoma patients diagnosed in Norway in 2005–2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient.

Results

The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6–70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2–28) and nuclear medicine for 18 mSv (range: 2–47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%).

Conclusion

There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT.

http://ift.tt/2exc5vc

Imaging in the diagnosis of pediatric urolithiasis

Abstract

Pediatric urolithiasis is an important and increasingly prevalent cause of pediatric morbidity and hospital admission. Ultrasound (US) is the recommended primary imaging modality for suspected urolithiasis in children. There is, however, widespread use of CT as a first-line study for abdominal pain in many institutions involved in pediatric care. The objective of this review is to outline state-of-the-art imaging modalities and methods for diagnosing urolithiasis in children. The pediatric radiologist plays a key role in ensuring that the appropriate imaging modality is performed in the setting of suspected pediatric urolithiasis. Our proposed imaging algorithm starts with US, and describes the optimal technique and indications for the use of CT. We emphasize the importance of improved communication with a greater collaborative approach between pediatric and general radiology departments so children undergo the appropriate imaging evaluation.

http://ift.tt/2fqA0tD

From bench to operating theater: has the time come for a molecular scalpel?

Future Oncology Ahead of Print.


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Outcomes and toxicities in patients treated with definitive focal therapy for primary prostate cancer: systematic review

Future Oncology Ahead of Print.


from Cancer via ola Kala on Inoreader http://ift.tt/2fqASP6
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Video-assisted thoracic lobectomy for lung cancer in Italy: the ‘VATS Group’ Project

Future Oncology Ahead of Print.


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

Ultrasound, computed tomography or magnetic resonance imaging - which is preferred for acute appendicitis in children? A Meta-analysis

Abstract

Background

There is no established consensus about the relative accuracies of US, CT and MRI in childhood appendicitis.

Objective

To compare, through meta-analysis, the accuracies of US, CT and MRI for clinically suspected acute appendicitis in children.

Materials and methods

PubMed, Embase, Web of Science and the Cochrane Library were searched. After study selection, data extraction and quality assessment, the sensitivity, specificity and the area under the curve of summary receiver operating characteristic were calculated and compared.

Results

Twenty-seven articles including 29 studies met the inclusion criteria, including 19 studies (9,170 patients) of US, 6 studies (928 patients) of CT and 4 studies (990 patients) of MRI. The analysis showed that the area under the receiver operator characteristics curve of MRI (0.995) was a little higher than that of US (0.987) and CT (0.982; P > 0.05).

Conclusion

US, CT and MRI have high diagnostic accuracies of clinically suspected acute appendicitis in children overall with no significant difference.

from Cancer via ola Kala on Inoreader http://ift.tt/2fqA9NY
via IFTTT

Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005–2012

Abstract

Background

Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation.

Objective

To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether ¹⁸F-fluorodeoxyglucose positron emission tomography – computed tomography (¹⁸F-FDG PET-CT) is a major contributor of radiation.

Materials and methods

Twenty Ewing sarcoma patients diagnosed in Norway in 2005–2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient.

Results

The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6–70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2–28) and nuclear medicine for 18 mSv (range: 2–47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%).

Conclusion

There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT.

from Cancer via ola Kala on Inoreader http://ift.tt/2exc5vc
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Imaging in the diagnosis of pediatric urolithiasis

Abstract

Pediatric urolithiasis is an important and increasingly prevalent cause of pediatric morbidity and hospital admission. Ultrasound (US) is the recommended primary imaging modality for suspected urolithiasis in children. There is, however, widespread use of CT as a first-line study for abdominal pain in many institutions involved in pediatric care. The objective of this review is to outline state-of-the-art imaging modalities and methods for diagnosing urolithiasis in children. The pediatric radiologist plays a key role in ensuring that the appropriate imaging modality is performed in the setting of suspected pediatric urolithiasis. Our proposed imaging algorithm starts with US, and describes the optimal technique and indications for the use of CT. We emphasize the importance of improved communication with a greater collaborative approach between pediatric and general radiology departments so children undergo the appropriate imaging evaluation.

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Clinicopathological and microbiological findings associated with wounds in Nigerian horses

Abstract

Horses are usually at risk of physical injuries/wounds because of their typical flight and fright temperament. These wounds are readily infected because of the nature of work they do. This study was a 6-month survey of wound infections of horses at the Obollo-Afor Horse Lairage, Udenu Local Government area, Enugu State, Nigeria. Two hundred seven horses were sampled. They were physically examined, and those that had wounds were purposively selected for further study. Blood samples were collected from these horses that had wounds for haematological and serum biochemistry evaluations. Sterile swab sticks were used to collect samples from the wound edges after disinfection for microbiological examination. This showed that out of the 207 horses sampled, 21 had wounds. The horses with wounds had significantly (p < 0.05) higher total leukocyte, band and segmented neutrophil, basophil and monocyte counts, serum alanine aminotransferase activity and globulin levels, than the apparently healthy horses. They also had significantly (p < 0.05) lower serum albumin levels than those without wounds. Staphylococcus aureus was isolated from all the 21 horses with wounds while Escherichia coli were isolated from 19 of them. These two organisms were resistant to commonly used antibiotics (ampicillin, amoxicillin/clavulanic acid combination and tetracycline) but were sensitive to ciprofloxacin, ofloxacin, gentamycin and chloramphenicol. Wound infections in the horses studied were associated with leukocytosis, neutrophilia, monocytosis, basophilia, hypoalbuminemia and hyperglobulinemia, and that Staphylococcus aureus and Escherichia coli were the pathogens associated with wound infections in the horses.

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Second-degree atrioventricular block in a diarrheic calf-camel ( Camelus dromedarius )

Abstract

Atrioventricular block (AVB) is a type of heart block in which the conduction between the atria and ventricles of the heart is impaired. The purpose of the present paper is to report the occurrence of second-degree AVB in a diarrheic calf-camel. A 7-day-old female calf-camel (Camelus dromedarius) weighting approximately 50 kg was referred to the veterinary hospital with a 5-day history of diarrhea, prostration, tremors, sternal recumbency, and muscular weakness. Clinical examination revealed increases in rectal temperature (RT 39.9 °C), heart rate (HR 124 beats min⁻¹), and respiratory rate (RR 49 breaths min⁻¹) with hyperemic mucous membranes. Incidentally, in precise cardiac auscultation, the clinicians found out irregularities in the rhythm and recognized the random absence of S₁ and S₂ heart sounds. Moreover, no palpable pulse and jugular pulsation (JP) could be detected during the cardiac irregularities. Other clinical examinations showed no sign of cardiovascular insufficiency such as edema and jugular distension (JD) and no murmur was auscultated. Before the treatment, serum levels of magnesium were significantly lower than the reference values, while the concentration of potassium was significantly higher than the reference value (P < 0.05). Two days after treatment, serum electrolyte levels were within reference ranges. There were no significant differences in the serum levels of other electrolytes (sodium, chloride, calcium, and phosphorous) and all cardiovascular biomarkers (homocysteine, cardiac troponin I, and enzymes such as creatine kinase isoenzyme MB and lactate dehydrogenase) before and 2 days after the treatment (P > 0.05). Based on the cardiovascular examination (observation, palpation, and auscultation), heart block was suspected. ECG recording confirmed the presence of sinus arrhythmia (SA) and heart block including first-degree and Mobitz type 1 (Wenkebach) second-degree. Finally, since the AVB was resolved after correction of serum electrolyte imbalance, it can be suggested that electrolyte disturbance was the main cause of Mobitz I second-degree AVB in the above described diarrheic calf-camel.

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Phase I–II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints

Abstract

This phase I–II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1–16) and alemtuzumab (weeks 5–16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1–29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3–4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67⁺) CD8⁺ T cells was increased at week 4, with further increase in both the CD4⁺ and CD8⁺ subsets (p < 0.01 and <0.05), which was accompanied by significant upregulation of HLA-DR after addition of alemtuzumab. Antigen-experienced cells increased at week 4 as the frequency of effector memory cells increased in the CD8⁺ subset (p < 0.003), while effector cells decreased in both the CD8⁺ and CD4⁺ subsets (p < 0.0001 and p < 0.01). The Th1/Th2 balance was unchanged at week 4 but shifted toward a Th2 profile after combination therapy. At end of treatment, the frequency of Th17 and regulatory T cells was reduced (p < 0.01), naïve T cells decreased, and effector memory T cells increased (p < 0.05 and p < 0.01). Granzyme B⁺ T cells increased at 30-week follow-up (p < 0.05). PD-1 expression was unaffected. In conclusion, low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

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The role of endoplasmic reticulum stress in neurodegenerative disease

Abstract

The endoplasmic reticulum (ER) is an important organelle involved in cellular homeostasis and control of protein quality. Unfolded protein response (UPR) is a cellular response to ER stress and promotes cell survival. Severe or prolonged stress activates apoptosis signaling to trigger cell death. In mammals, the UPR is initiated by three major ER stress sensors, including inositol-requiring transmembrane kinase 1, double-stranded RNA-activated protein kinase-like ER kinase and activating transcription factor 6. UPR dysfunction plays an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, which is characterized by the accumulation and aggregation of misfolded proteins. ER stress mediates the pathogenesis of psychiatric diseases, such as depression, schizophrenia, sleep fragmentation and post-traumatic stress disorder. The role of UPR in the neuropathology of humans, cell lines and animal models, is established. Therefore, inhibition of specific ER mediators may contribute to the treatment and prevention of neurodegeneration. Preclinical studies have shed light on the potential therapeutic strategies. Here, we will review the evidence of UPR activation in neurodegenerative disorders and psychiatric diseases along with the methodology.

http://ift.tt/2fqux6c

Phase I–II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints

Abstract

This phase I–II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1–16) and alemtuzumab (weeks 5–16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1–29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3–4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67⁺) CD8⁺ T cells was increased at week 4, with further increase in both the CD4⁺ and CD8⁺ subsets (p < 0.01 and <0.05), which was accompanied by significant upregulation of HLA-DR after addition of alemtuzumab. Antigen-experienced cells increased at week 4 as the frequency of effector memory cells increased in the CD8⁺ subset (p < 0.003), while effector cells decreased in both the CD8⁺ and CD4⁺ subsets (p < 0.0001 and p < 0.01). The Th1/Th2 balance was unchanged at week 4 but shifted toward a Th2 profile after combination therapy. At end of treatment, the frequency of Th17 and regulatory T cells was reduced (p < 0.01), naïve T cells decreased, and effector memory T cells increased (p < 0.05 and p < 0.01). Granzyme B⁺ T cells increased at 30-week follow-up (p < 0.05). PD-1 expression was unaffected. In conclusion, low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

http://ift.tt/2fqbdG4

Phase I–II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints

Abstract

This phase I–II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1–16) and alemtuzumab (weeks 5–16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1–29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3–4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67⁺) CD8⁺ T cells was increased at week 4, with further increase in both the CD4⁺ and CD8⁺ subsets (p < 0.01 and <0.05), which was accompanied by significant upregulation of HLA-DR after addition of alemtuzumab. Antigen-experienced cells increased at week 4 as the frequency of effector memory cells increased in the CD8⁺ subset (p < 0.003), while effector cells decreased in both the CD8⁺ and CD4⁺ subsets (p < 0.0001 and p < 0.01). The Th1/Th2 balance was unchanged at week 4 but shifted toward a Th2 profile after combination therapy. At end of treatment, the frequency of Th17 and regulatory T cells was reduced (p < 0.01), naïve T cells decreased, and effector memory T cells increased (p < 0.05 and p < 0.01). Granzyme B⁺ T cells increased at 30-week follow-up (p < 0.05). PD-1 expression was unaffected. In conclusion, low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

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Erratum to: Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma

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Erratum to: Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma

http://ift.tt/2en5rV5

Temporal trends in the risk of developing multiple primary cancers: a systematic review

Abstract

Background

Cancer survivors are at risk of developing second and subsequent primary cancers, referred to as multiple primary cancers (MPCs). It is not clear whether the risk of MPCs has increased over recent decades, but increasing use of radiological imaging and potentially harmful effects of certain cancer treatments raise this possibility. A systematic review was undertaken to assess whether there has been a temporal change in the risk of developing MPCs.

Methods

A systematic search to identify population-based studies of MPCs was performed in Medline/PubMed and Embase databases from inception to August 2016. Included studies were those reporting risk of MPCs for all sites combined following a first cancer at any site or a specific site, using standard incidence ratios (SIRs) or equivalent, and with analysis stratified by calendar years.

Results

We identified 28 articles eligible for inclusion, comprising 26 population-based studies and two monographs. MPC incidence was reported in nearly 6.5 million cancer survivors. For all first cancer sites combined, a higher rate of MPCs was reported in more recent than earlier calendar periods in four of the six relevant studies. The SIRs ranged from 1.14 for a first cancer diagnosis in the early 1980s to 1.21–1.46 in the late 1990s in the USA and Australia. Two studies from Italy and France showed no significant difference in SIRs across time periods 1978–2010 and 1989–2004. The remaining 22 studies reported various temporal trends in the risk of developing MPCs after a first cancer at a specific site, but most showed little change.

Conclusion

Overall, the risk of developing MPCs appears to have increased since the 1980s when considering studies of all primary cancer sites combined from the USA and Australia but not from Europe. With the introduction of more routine nuclear medical imaging over the last 15 years, more studies are needed to confirm recent trends of MPC risk in adult cancer survivors.

http://ift.tt/2ex1mAK

Requirement of ABC transporter inhibition and Hoechst 33342 dye deprivation for the assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes

Abstract

Background

Elucidating the precise properties of cancer stem cells (CSCs) is indispensable for the development of effective therapies against tumors, because CSCs are key drivers of tumor development, metastasis and relapse. We previously reported that the Hoechst 33342 dye-low staining side population (SP) method can enrich for CSCs in the C6 glioma cell line, and that the positively stained main population (MP) cells are non-CSCs. Presence of cancer stem-like SP cells is reported in various types of cancer. Although altered cellular energy metabolism is a hallmark of cancer, very little has been studied on the applicability of fluorescent probes for the understanding of CSC energy metabolism.

Methods

The metabolic status of C6 SP and MP cells are evaluated by CellROX, MitoTracker Green (MTG) and JC-1 for cellular oxidative stress, mitochondrial amount, and mitochondrial membrane potential, respectively.

Results

SP cells were found to exhibit significantly lower fluorescent intensities of CellROX and MTG than MP cells. However, inhibition of ATP binding cassette (ABC) transporters by verapamil enhanced the intensities of these probes in SP cells to the levels similar to those in MP cells, indicating that SP cells expel the probes outside of the cells through ABC transporters. Next, SP cells were stained with JC-1 dye which exhibits membrane potential dependent accumulation in mitochondrial matrix, followed by formation of aggregates. The mitochondrial membrane potential indicated by the aggregates of JC-1 was 5.0-fold lower in SP cells than MP cells. Inhibition of ABC transporters enhanced the fluorescent intensities of the JC-1 aggregates in both SP and MP cells, the former of which was still 2.2-fold lower than the latter. This higher JC-1 signal in MP cells was further found to be due to the Hoechst 33342 dye existing in MP cells. When SP and MP cells were recultured to deprive the intracellular Hoechst 33342 dye and then stained with JC-1 in the presence of verapamil, the intensities of JC-1 aggregates in such SP and MP cells became comparable.

Conclusion

Inhibiting ABC transporters and depriving Hoechst 33342 dye are required for the accurate assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes.

http://ift.tt/2ex3YyR

LPA receptor 1 mediates LPA-induced ovarian cancer metastasis: an in vitro and in vivo study

Abstract

Background

The facts that LPA is present at high concentration in ovarian cancer patients' ascites and it may serve as a stimulator to cell migration, implicate the role of LPA in the ovarian cancer metastasis. Since LPA mediates various biological functions through its interaction with LPA receptors, we aim to investigate the correlation between the expression of LPA receptors and the metastasis of ovarian cancer.

Methods

To test whether the LPA responsiveness correlated with the metastatic capability of ovarian cancer cells, we performed LPA induced invasion assay and peritoneal metastatic colonization assay with a panel of established human ovarian cancer cell lines. The expression of LPAR1-3 in different ovarian cancer lines was examined by qRT-PCR. We also tested the effects of LPAR1 inhibition or overexpression on ovarian cancer cell's invasiveness. To confirm our laboratory results, we detected LPARs expression in specimens from 52 ovarian cancer patients by qRT-PCR and immunohistochemistry.

Results

Thirteen ovarian cancer cells were enrolled in the invasion assay. Ovarian cancer cell lines which responded well to LPA-induced invasion, also displayed good capability for metastatic colonization. On the contrary, cell lines with poor LPA responsiveness showed inferior metastatic potential in peritoneal colonization assay. High expression level of LPAR1 was detected in all of the metastatic ovarian cancer cell lines. T-test showed that LPAR1, not LPAR2 or LPAR3, expression was significantly higher in the metastatic cell lines than in the non-metastatic cell lines (P = 0.003). Furthermore, silencing LPAR1 alone could significantly reduce LPA-induced invasion (P < 0.001). Finally, we analyzed the correlation between the LPARs expression and clinicopathological features of the clinical cases. It indicated that LPAR1 expression rate increased significantly along with the more advanced stages (stage I: 16.67 %; II 50.00 %; III: 75.00 %; and IV: 100.00 %; P = 0.003). Besides that, LPAR1 expression was detected in all the 13 cases with abdominal metastasis more than 2 cm, 10 cases with retroperitoneal lymph node metastasis and 6 cases with hepatic metastasis. Moreover, the expression rate of LPAR2 significantly increased in ovarian cancer than in normal specimens (P = 0.039). LPAR3 expression showed the same trend as LPAR2, though the difference is not statistically significant (P = 0.275). Besides that LPAR2 and LPAR3 expression increased along with poorer differentiation (P = 0.002, P = 0.034, respectively).

Conclusions

Metastatic capability of ovarian cancer cells correlated well with their responsiveness to LPA for cell invasion. LPAR1 acts as the main mediator responsible for LPA-stimulated ovarian cancer cell invasion. LPAR2 and LPAR3 might play an role in carcinogenesis of ovarian cancer.

http://ift.tt/2fqkez6

A consultation training program for physicians for communication about complementary medicine with breast cancer patients: a prospective, multi-center, cluster-randomized, mixed-method pilot study

Abstract

Background

The aim was to develop and evaluate a training program for physicians for communicating with breast cancer patients about complementary medicine (CM).

Methods

In a cluster-randomized pilot trial eight breast cancer centers (two physicians per center) were randomized to either a complementary communication training program (9 h e-learning + 20 h on-site skills training) or to a control group without training. Each physician was asked to consult ten patients for whom he or she is not the physician in charge. We used mixed methods: Quantitative outcomes included physicians' assessments (empathy, complexity of consultation, knowledge transfer) and patients' assessments (satisfaction, empathy, knowledge transfer). For qualitative analyses, 15 (eight in the training and seven in the control group) videotaped consultations were analyzed based on grounded theory, and separate focus groups with the physicians of both groups were conducted.

Results

A total of 137 patients were included. Although cluster-randomized, physicians in the two groups differed. Those in the training group were younger (33.4 ± 8.9 vs. 40.0 ± 8.5 years) and had less work experience (5.4 ± 8.9 vs. 11.1 ± 7.4 years). Patient satisfaction with the CM consultation was relatively high on a scale from 0 to 24 and was comparable in the two groups (training group: 19.4 ± 4.6; control group 20.5 ± 4.1). The qualitative findings showed that physicians structured majority of consultations as taught during the training. Comparing only the younger and less CM experienced physicians, those trained in CM communication felt more confident discussing CM-related topics than those without training.

Conclusion

A CM communication-training program might be especially beneficial for physicians with less consulting experience when communicating about CM-related issues. A larger trial using more suitable quantitative outcomes needs to confirm this.

Trial registration

ClinicalTrials.gov: NCT02223091, date of registration: 7 February 2014.

http://ift.tt/2fqgsWi

The expression pattern of matrix-producing tumor stroma is of prognostic importance in breast cancer

Abstract

Background

There are several indications that the composition of the tumor stroma can contribute to the malignancy of a tumor. Here we utilized expression data sets to identify metagenes that may serve as surrogate marker for the extent of matrix production and vascularization of a tumor and to characterize prognostic molecular components of the stroma.

Methods

TCGA data sets from six cancer forms, two breast cancer microarray sets and one mRNA data set of xenografted tumors were downloaded. Using the mean correlation as distance measure compact clusters with genes representing extracellular matrix production (ECM metagene) and vascularization (endothelial metagene) were defined. Explorative Cox modeling was used to identify prognostic stromal gene sets.

Results

Clustering of stromal genes in six cancer data sets resulted in metagenes, each containing three genes, representing matrix production and vascularization. The ECM metagene was associated with poor prognosis in renal clear cell carcinoma and in lung adenocarcinoma but not in other cancers investigated. Explorative Cox modeling using gene pairs identified gene sets that in multivariate models were prognostic in breast cancer. This was validated in two microarray sets. Two notable genes are TCF4 and P4HA3 which were included in the sets associated with positive and negative prognosis, respectively. Data from laser-microdissected tumors, a xenografted tumor data set and from correlation analyses demonstrate the stroma specificity of the genes.

Conclusions

It is possible to construct ECM and endothelial metagenes common for several cancer forms. The molecular composition of matrix-producing cells, rather than the extent of matrix production seem to be important for breast cancer prognosis.

http://ift.tt/2fqofDy

Pancreatic resection for intraductal papillary mucinous neoplasm– a thirteen-year single center experience

Abstract

Background

The purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma.

Methods

A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma.

Results

Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 – 87), median in hospital stay is 23 days (range 7 – 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 – 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001).

Conclusions

Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient.

http://ift.tt/2ex0yMd

Estimating long-term clinical effectiveness and cost-effectiveness of HPV 16/18 vaccine in China

Abstract

Background

Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China.

Methods

A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China.

Results

Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8–119) in urban; and remained cost-effective when the vaccine cost ranged 630–1,700 CNY (US$ 100–270) in rural and 750–1,900 CNY (US$ 119–302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust.

Conclusions

In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden.

http://ift.tt/2fqmyWJ

Planning TTFields treatment using the NovoTAL system-clinical case series beyond the use of MRI contrast enhancement

Abstract

Background

Gliomas are the most common primary brain tumors in adults and invariably carry a poor prognosis. Recent clinical studies have demonstrated the safety and compelling survival benefit when tumor treating fields (TTFields) are added to temozolomide for patients with newly diagnosed glioblastoma. TTFields are low-intensity, intermediate frequency (200 kHz) alternating electric fields, delivered directly to a patient's brain through the local application of non-invasive transducer arrays. Experimental simulations have demonstrated that TTFields distribute in a non-uniform manner within the brain. To ensure patients receive the maximal therapeutic level of TTFields at the site of their tumor, tumor burden is mapped and an optimal array layout is personalized using the NovoTAL software. The NovoTAL software utilizes magnetic resonance imaging (MRI) measurements for head size and tumor location obtained from axial and coronal T1 postcontrast sequences to determine the optimal paired transducer array configuration that will deliver the maximal field intensity at the site of the tumor. In clinical practice, physicians planning treatment with TTFields may determine that disease activity is more accurately represented in noncontrast-enhancing sequences. Here we present and discuss a series of 8 cases where a treating physician has utilized non-contrast enhancement and advanced imaging to inform TTFields treatment planning based on a clinical evaluation of where a patient is believed to have active tumor. This case series is, to our knowledge, the first report of this kind in the literature.

Case presentations

All patients presented with gliomas (grades 2–4) and ranged in age from 49 to 65 years; 5 were male and 3, female. Each patient had previously received standard therapy including surgery, radiation therapy and/or chemotherapy prior to initiation of TTFields. The majority had progressed on prior therapy. A standard pre- and postcontrast MRI scan was acquired and used for TTFields treatment planning.

Conclusion

This paper details important approaches for integrating clinical considerations, nonmeasurable disease and advanced imaging into the treatment planning workflow for TTFields. As TTFields become integrated into standard care pathways for glioblastoma, this case series demonstrates that treatment planning beyond the extent of contrast enhancement is clinically feasible and should be prospectively compared to standard treatment planning in a clinical trial setting, in order to determine the impact on patient outcomes.

http://ift.tt/2ex074B

Requirement of ABC transporter inhibition and Hoechst 33342 dye deprivation for the assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes

Abstract

Background

Elucidating the precise properties of cancer stem cells (CSCs) is indispensable for the development of effective therapies against tumors, because CSCs are key drivers of tumor development, metastasis and relapse. We previously reported that the Hoechst 33342 dye-low staining side population (SP) method can enrich for CSCs in the C6 glioma cell line, and that the positively stained main population (MP) cells are non-CSCs. Presence of cancer stem-like SP cells is reported in various types of cancer. Although altered cellular energy metabolism is a hallmark of cancer, very little has been studied on the applicability of fluorescent probes for the understanding of CSC energy metabolism.

Methods

The metabolic status of C6 SP and MP cells are evaluated by CellROX, MitoTracker Green (MTG) and JC-1 for cellular oxidative stress, mitochondrial amount, and mitochondrial membrane potential, respectively.

Results

SP cells were found to exhibit significantly lower fluorescent intensities of CellROX and MTG than MP cells. However, inhibition of ATP binding cassette (ABC) transporters by verapamil enhanced the intensities of these probes in SP cells to the levels similar to those in MP cells, indicating that SP cells expel the probes outside of the cells through ABC transporters. Next, SP cells were stained with JC-1 dye which exhibits membrane potential dependent accumulation in mitochondrial matrix, followed by formation of aggregates. The mitochondrial membrane potential indicated by the aggregates of JC-1 was 5.0-fold lower in SP cells than MP cells. Inhibition of ABC transporters enhanced the fluorescent intensities of the JC-1 aggregates in both SP and MP cells, the former of which was still 2.2-fold lower than the latter. This higher JC-1 signal in MP cells was further found to be due to the Hoechst 33342 dye existing in MP cells. When SP and MP cells were recultured to deprive the intracellular Hoechst 33342 dye and then stained with JC-1 in the presence of verapamil, the intensities of JC-1 aggregates in such SP and MP cells became comparable.

Conclusion

Inhibiting ABC transporters and depriving Hoechst 33342 dye are required for the accurate assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes.

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LPA receptor 1 mediates LPA-induced ovarian cancer metastasis: an in vitro and in vivo study

Abstract

Background

The facts that LPA is present at high concentration in ovarian cancer patients' ascites and it may serve as a stimulator to cell migration, implicate the role of LPA in the ovarian cancer metastasis. Since LPA mediates various biological functions through its interaction with LPA receptors, we aim to investigate the correlation between the expression of LPA receptors and the metastasis of ovarian cancer.

Methods

To test whether the LPA responsiveness correlated with the metastatic capability of ovarian cancer cells, we performed LPA induced invasion assay and peritoneal metastatic colonization assay with a panel of established human ovarian cancer cell lines. The expression of LPAR1-3 in different ovarian cancer lines was examined by qRT-PCR. We also tested the effects of LPAR1 inhibition or overexpression on ovarian cancer cell's invasiveness. To confirm our laboratory results, we detected LPARs expression in specimens from 52 ovarian cancer patients by qRT-PCR and immunohistochemistry.

Results

Thirteen ovarian cancer cells were enrolled in the invasion assay. Ovarian cancer cell lines which responded well to LPA-induced invasion, also displayed good capability for metastatic colonization. On the contrary, cell lines with poor LPA responsiveness showed inferior metastatic potential in peritoneal colonization assay. High expression level of LPAR1 was detected in all of the metastatic ovarian cancer cell lines. T-test showed that LPAR1, not LPAR2 or LPAR3, expression was significantly higher in the metastatic cell lines than in the non-metastatic cell lines (P = 0.003). Furthermore, silencing LPAR1 alone could significantly reduce LPA-induced invasion (P < 0.001). Finally, we analyzed the correlation between the LPARs expression and clinicopathological features of the clinical cases. It indicated that LPAR1 expression rate increased significantly along with the more advanced stages (stage I: 16.67 %; II 50.00 %; III: 75.00 %; and IV: 100.00 %; P = 0.003). Besides that, LPAR1 expression was detected in all the 13 cases with abdominal metastasis more than 2 cm, 10 cases with retroperitoneal lymph node metastasis and 6 cases with hepatic metastasis. Moreover, the expression rate of LPAR2 significantly increased in ovarian cancer than in normal specimens (P = 0.039). LPAR3 expression showed the same trend as LPAR2, though the difference is not statistically significant (P = 0.275). Besides that LPAR2 and LPAR3 expression increased along with poorer differentiation (P = 0.002, P = 0.034, respectively).

Conclusions

Metastatic capability of ovarian cancer cells correlated well with their responsiveness to LPA for cell invasion. LPAR1 acts as the main mediator responsible for LPA-stimulated ovarian cancer cell invasion. LPAR2 and LPAR3 might play an role in carcinogenesis of ovarian cancer.

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Temporal trends in the risk of developing multiple primary cancers: a systematic review

Abstract

Background

Cancer survivors are at risk of developing second and subsequent primary cancers, referred to as multiple primary cancers (MPCs). It is not clear whether the risk of MPCs has increased over recent decades, but increasing use of radiological imaging and potentially harmful effects of certain cancer treatments raise this possibility. A systematic review was undertaken to assess whether there has been a temporal change in the risk of developing MPCs.

Methods

A systematic search to identify population-based studies of MPCs was performed in Medline/PubMed and Embase databases from inception to August 2016. Included studies were those reporting risk of MPCs for all sites combined following a first cancer at any site or a specific site, using standard incidence ratios (SIRs) or equivalent, and with analysis stratified by calendar years.

Results

We identified 28 articles eligible for inclusion, comprising 26 population-based studies and two monographs. MPC incidence was reported in nearly 6.5 million cancer survivors. For all first cancer sites combined, a higher rate of MPCs was reported in more recent than earlier calendar periods in four of the six relevant studies. The SIRs ranged from 1.14 for a first cancer diagnosis in the early 1980s to 1.21–1.46 in the late 1990s in the USA and Australia. Two studies from Italy and France showed no significant difference in SIRs across time periods 1978–2010 and 1989–2004. The remaining 22 studies reported various temporal trends in the risk of developing MPCs after a first cancer at a specific site, but most showed little change.

Conclusion

Overall, the risk of developing MPCs appears to have increased since the 1980s when considering studies of all primary cancer sites combined from the USA and Australia but not from Europe. With the introduction of more routine nuclear medical imaging over the last 15 years, more studies are needed to confirm recent trends of MPC risk in adult cancer survivors.

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A consultation training program for physicians for communication about complementary medicine with breast cancer patients: a prospective, multi-center, cluster-randomized, mixed-method pilot study

Abstract

Background

The aim was to develop and evaluate a training program for physicians for communicating with breast cancer patients about complementary medicine (CM).

Methods

In a cluster-randomized pilot trial eight breast cancer centers (two physicians per center) were randomized to either a complementary communication training program (9 h e-learning + 20 h on-site skills training) or to a control group without training. Each physician was asked to consult ten patients for whom he or she is not the physician in charge. We used mixed methods: Quantitative outcomes included physicians' assessments (empathy, complexity of consultation, knowledge transfer) and patients' assessments (satisfaction, empathy, knowledge transfer). For qualitative analyses, 15 (eight in the training and seven in the control group) videotaped consultations were analyzed based on grounded theory, and separate focus groups with the physicians of both groups were conducted.

Results

A total of 137 patients were included. Although cluster-randomized, physicians in the two groups differed. Those in the training group were younger (33.4 ± 8.9 vs. 40.0 ± 8.5 years) and had less work experience (5.4 ± 8.9 vs. 11.1 ± 7.4 years). Patient satisfaction with the CM consultation was relatively high on a scale from 0 to 24 and was comparable in the two groups (training group: 19.4 ± 4.6; control group 20.5 ± 4.1). The qualitative findings showed that physicians structured majority of consultations as taught during the training. Comparing only the younger and less CM experienced physicians, those trained in CM communication felt more confident discussing CM-related topics than those without training.

Conclusion

A CM communication-training program might be especially beneficial for physicians with less consulting experience when communicating about CM-related issues. A larger trial using more suitable quantitative outcomes needs to confirm this.

Trial registration

ClinicalTrials.gov: NCT02223091, date of registration: 7 February 2014.

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The expression pattern of matrix-producing tumor stroma is of prognostic importance in breast cancer

Abstract

Background

There are several indications that the composition of the tumor stroma can contribute to the malignancy of a tumor. Here we utilized expression data sets to identify metagenes that may serve as surrogate marker for the extent of matrix production and vascularization of a tumor and to characterize prognostic molecular components of the stroma.

Methods

TCGA data sets from six cancer forms, two breast cancer microarray sets and one mRNA data set of xenografted tumors were downloaded. Using the mean correlation as distance measure compact clusters with genes representing extracellular matrix production (ECM metagene) and vascularization (endothelial metagene) were defined. Explorative Cox modeling was used to identify prognostic stromal gene sets.

Results

Clustering of stromal genes in six cancer data sets resulted in metagenes, each containing three genes, representing matrix production and vascularization. The ECM metagene was associated with poor prognosis in renal clear cell carcinoma and in lung adenocarcinoma but not in other cancers investigated. Explorative Cox modeling using gene pairs identified gene sets that in multivariate models were prognostic in breast cancer. This was validated in two microarray sets. Two notable genes are TCF4 and P4HA3 which were included in the sets associated with positive and negative prognosis, respectively. Data from laser-microdissected tumors, a xenografted tumor data set and from correlation analyses demonstrate the stroma specificity of the genes.

Conclusions

It is possible to construct ECM and endothelial metagenes common for several cancer forms. The molecular composition of matrix-producing cells, rather than the extent of matrix production seem to be important for breast cancer prognosis.

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Pancreatic resection for intraductal papillary mucinous neoplasm– a thirteen-year single center experience

Abstract

Background

The purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma.

Methods

A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma.

Results

Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n = 30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n = 3). Median intensive care stay is three days (range 1 – 87), median in hospital stay is 23 days (range 7 – 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 – 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001).

Conclusions

Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient.

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Estimating long-term clinical effectiveness and cost-effectiveness of HPV 16/18 vaccine in China

Abstract

Background

Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China.

Methods

A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China.

Results

Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8–119) in urban; and remained cost-effective when the vaccine cost ranged 630–1,700 CNY (US$ 100–270) in rural and 750–1,900 CNY (US$ 119–302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust.

Conclusions

In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden.

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Planning TTFields treatment using the NovoTAL system-clinical case series beyond the use of MRI contrast enhancement

Abstract

Background

Gliomas are the most common primary brain tumors in adults and invariably carry a poor prognosis. Recent clinical studies have demonstrated the safety and compelling survival benefit when tumor treating fields (TTFields) are added to temozolomide for patients with newly diagnosed glioblastoma. TTFields are low-intensity, intermediate frequency (200 kHz) alternating electric fields, delivered directly to a patient's brain through the local application of non-invasive transducer arrays. Experimental simulations have demonstrated that TTFields distribute in a non-uniform manner within the brain. To ensure patients receive the maximal therapeutic level of TTFields at the site of their tumor, tumor burden is mapped and an optimal array layout is personalized using the NovoTAL software. The NovoTAL software utilizes magnetic resonance imaging (MRI) measurements for head size and tumor location obtained from axial and coronal T1 postcontrast sequences to determine the optimal paired transducer array configuration that will deliver the maximal field intensity at the site of the tumor. In clinical practice, physicians planning treatment with TTFields may determine that disease activity is more accurately represented in noncontrast-enhancing sequences. Here we present and discuss a series of 8 cases where a treating physician has utilized non-contrast enhancement and advanced imaging to inform TTFields treatment planning based on a clinical evaluation of where a patient is believed to have active tumor. This case series is, to our knowledge, the first report of this kind in the literature.

Case presentations

All patients presented with gliomas (grades 2–4) and ranged in age from 49 to 65 years; 5 were male and 3, female. Each patient had previously received standard therapy including surgery, radiation therapy and/or chemotherapy prior to initiation of TTFields. The majority had progressed on prior therapy. A standard pre- and postcontrast MRI scan was acquired and used for TTFields treatment planning.

Conclusion

This paper details important approaches for integrating clinical considerations, nonmeasurable disease and advanced imaging into the treatment planning workflow for TTFields. As TTFields become integrated into standard care pathways for glioblastoma, this case series demonstrates that treatment planning beyond the extent of contrast enhancement is clinically feasible and should be prospectively compared to standard treatment planning in a clinical trial setting, in order to determine the impact on patient outcomes.

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Benefits of omitting primary site radiotherapy after TORS: Only time will tell

Publication date: Available online 4 November 2016
Source:Practical Radiation Oncology
Author(s): Eric Ojerholm, J. Nicholas Lukens, Peter H. Ahn, Geoffrey Geiger, Samuel Swisher-McClure, Jason Newman, Ara Chalian, Gregory Weinstein, Bert W. O'Malley, Roger Cohen, Alexander Lin




http://ift.tt/2flwggY

Coexistence of inversion 16 in chronic myeloid leukaemia in blast crisis

Abstract

Chronic myeloid leukaemia (CML) is consistently associated with the BCR-ABL1 fusion gene located on the derivative chromosome 22 (Philadelphia chromosome, Ph + ve) as a result of a t(9;22)(q34;q11.2) translocation. We describe a 36-year-old male in blast phase CML presenting with acute myelomonocytic leukaemia and eosinophilia. Five months after initial disease diagnosis and despite being treated with standard imatinib therapy (400 mg daily) conventional cytogenetic analysis (CCA) demonstrated the evolution of a chromosome 16 pericentric inversion (inv(16)(p13q22)) within the already Ph + ve cells. Bone marrow aspiration and biopsy revealed 60% blasts, positive for CD34, HLADR, CD33 and CD13. Fluorescence in situ hybridization (FISH) and reverse transcription–polymerase chain reaction (RT-PCR) confirmed presence of a CBFβ-MHY11 rearrangement whilst next generation sequencing (NGS) detected an E255K point mutation within the BCR-ABL1 tyrosine kinase domain. Neither the CBFβ-MHY11 rearrangement nor the E225K point mutation were present at diagnosis. The patient received a combination of daunorubicin (60 mg/m²) and cytarabine (100 mg/m²) and had his tyrosine kinase inhibitor (TKI) changed to nilotinib before undergoing a male unrelated donor (MUD) stem cell transplant (SCT). The t(9;22) and inv(16) rearrangements persisted at day 100 post MUD SCT and his TKI was further switched to dasatinib. The patient presented with pleural effusions and had subsequent CNS relapse and passed away from relapsed disease and infective complications, 19-month post MUD allograft.

http://ift.tt/2eIsIl5

Benefits of omitting primary site radiotherapy after TORS: Only time will tell

Publication date: Available online 4 November 2016
Source:Practical Radiation Oncology
Author(s): Eric Ojerholm, J. Nicholas Lukens, Peter H. Ahn, Geoffrey Geiger, Samuel Swisher-McClure, Jason Newman, Ara Chalian, Gregory Weinstein, Bert W. O'Malley, Roger Cohen, Alexander Lin




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CDK4 in lung, and head and neck cancers in old age: evaluation as a biomarker

Abstract

Background

Cyclin dependent kinases (CDK) are key factors in promoting the initiation and development of tumors. These kinases are important for maintenance of mitochondrial biogenesis and imbalance in their expression in old age may lead to the oxidative stress. Lung cancer (LC), and head and neck squamous cell carcinoma (HNSCC) are two very prominent cancers in older Indians. Both the cancers are showing increasing trend in older population. The present study assessed serum concentration of one of the kinases; CDK4 in older LC and HNSCC patients.

Methods

The study included 100 subjects each of LC and HNSCC; and older subjects without cancer or any major health problems as controls. Serum CDK4 concentration was estimated using real-time label-free Surface plasmon resonance (SPR) and was verified by western blot.

Results

Significant elevation in serum CDK4 was observed in cases with LC and HNSCC compared to controls. HNSCC patients with higher CDK4 expression had distinctly shorter survival than patients with comparatively lower CDK4 expression. No such difference was observed in LC patients. The germ line mutation study of this gene in Exon-2 was performed and none was observed among cases and controls.

Conclusion

It can be concluded that older patients with HNSCC and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice.

http://ift.tt/2eI09V1

SEOM clinical guidelines for the management of germ cell testicular cancer (2016)

Abstract

Testicular cancer represents the most common malignancy in males aged 15–34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3–4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

http://ift.tt/2e9CAIs

CDK4 in lung, and head and neck cancers in old age: evaluation as a biomarker

Abstract

Background

Cyclin dependent kinases (CDK) are key factors in promoting the initiation and development of tumors. These kinases are important for maintenance of mitochondrial biogenesis and imbalance in their expression in old age may lead to the oxidative stress. Lung cancer (LC), and head and neck squamous cell carcinoma (HNSCC) are two very prominent cancers in older Indians. Both the cancers are showing increasing trend in older population. The present study assessed serum concentration of one of the kinases; CDK4 in older LC and HNSCC patients.

Methods

The study included 100 subjects each of LC and HNSCC; and older subjects without cancer or any major health problems as controls. Serum CDK4 concentration was estimated using real-time label-free Surface plasmon resonance (SPR) and was verified by western blot.

Results

Significant elevation in serum CDK4 was observed in cases with LC and HNSCC compared to controls. HNSCC patients with higher CDK4 expression had distinctly shorter survival than patients with comparatively lower CDK4 expression. No such difference was observed in LC patients. The germ line mutation study of this gene in Exon-2 was performed and none was observed among cases and controls.

Conclusion

It can be concluded that older patients with HNSCC and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice.

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SEOM clinical guidelines for the management of germ cell testicular cancer (2016)

Abstract

Testicular cancer represents the most common malignancy in males aged 15–34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3–4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

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Contributors

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4





http://ift.tt/2fkYg1A

The Patient with Multimorbidities: Does 1 + 1 Always Simply Equal 2?

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Lee A. Fleisher




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Medically Complex Patients

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Robert B. Schonberger, Stanley H. Rosenbaum




http://ift.tt/2fkWvRX

Medically Complex Patients

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Robert B. Schonberger, Stanley H. Rosenbaum




http://ift.tt/2fE1wJl

Anesthetic Management of the Adult Patient with Concomitant Cardiac and Pulmonary Disease

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Misty A. Radosevich, Daniel R. Brown

Teaser

Several common diseases of the cardiac and pulmonary systems and the interactions of the two in disease and anesthetic management are discussed. Management of these disease processes in isolation is reviewed and how the management of one organ system impacts another is then explored. For example, in a patient with acute lung injury and right heart failure, lung-protective ventilation may directly conflict with strategies to minimize right heart afterload. Such challenging clinical scenarios require appreciation of each disease entity, their appropriate management, and the balance between competing priorities.


http://ift.tt/2fkZBWp

Anesthesia for the Patient with Concomitant Hepatic and Renal Impairment

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Tricia E. Brentjens, Ryan Chadha

Teaser

Hepatic and renal disease are common comorbidities in patients presenting for intermediate- and high-risk surgery. With the evolution of perioperative medicine, anesthesiologists are encountering more patients who have significant hepatic and renal disease, both acute and chronic in nature. It is important that anesthesiologists have an in-depth understanding of the physiologic derangements seen with hepatic and renal disease to evaluate and manage these patients appropriately. Perioperative management requires an understanding of the physiologic perturbations associated with each disease process. This article elucidates the goals in the management and treatment of this complex patient population.


http://ift.tt/2fE2DIM

Coexisting Cardiac and Hematologic Disorders

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Jordan E. Goldhammer, Benjamin A. Kohl

Teaser

Patients with concomitant cardiac and hematologic disorders presenting for noncardiac surgery are challenging. Anemic patients with cardiac disease should be approached in a methodical fashion. Transfusion triggers and target should be based on underlying symptomatology. The approach to anticoagulation management in patients with artificial heart valves, cardiac devices, or severe heart failure in the operative setting must encompass a complete understanding of the rationale of a patient's therapy as well as calculate the risk of changing this regimen. This article focuses common disorders and discusses strategies to optimize care in patients with coexisting cardiac and hematologic disease.


http://ift.tt/2fkW6it

Surgical Critical Care for the Patient with Sepsis and Multiple Organ Dysfunction

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Gary J. Kaml, Kimberly A. Davis

Teaser

Sepsis and multiple organ dysfunction syndrome (MODS) is common in the surgical intensive care unit. Sepsis involves infection and the patient's immune response. Timely recognition of sepsis and swift application of evidence-based interventions is critical to the success of therapy. This article reviews the nature of the septic process, existing definitions of sepsis, and current evidence-based treatment strategies for sepsis and MODS. An improved understanding of the process of sepsis and its relation to MODS has resulted in clinical definitions and scoring systems that allow for the quantification of disease severity and guidelines for treatment.


http://ift.tt/2fE23ee

Anesthesia for Patients with Concomitant Cardiac and Renal Dysfunction

Publication date: December 2016
Source:Anesthesiology Clinics, Volume 34, Issue 4
Author(s): Radwan Safa, Nicholas Sadovnikoff

Teaser

Renal disease and cardiovascular disease are commonly encountered in the same patient. The dynamic interactions between renal disease and cardiovascular disease have an impact on perioperative management. Renal failure is an independent risk factor for cardiovascular disease and the link between the two disease states remains to be fully elucidated.


http://ift.tt/2fl1GRO

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials

ABSTRACT

Immune checkpoint inhibition therapy has benefited people and shown powerful anti-tumor activity during the past several years. Nivolumab, a fully human IgG4 monoclonal antibody against PD-1, is a widely-studied immune checkpoint inhibitor for the treatment of cancers. To assess the safety and efficacy of nivolumab, we analyzed 27 clinical trials on nivolumab. Results showed that the summary risks of all grade adverse effects (AEs) and grade ≥3 AEs were 0.65 and 0.12. The rate of nivolumab-related death was 0.25%. The most common any grade AEs were fatigue (25.1%), rush (13.0%), pruritus (12.5%), diarrhea (12.1%), nausea (11.8%) and asthenia (10.4%). The most common grade ≥3 AEs were hypophosphatemia (only 2.3%) and lymphopenia (only 2.1%). The pooled objective response rate (ORR), 6-month progression-free survival (PFS) rate and 1-year overall survival (OS) rate were 0.26, 0.40 and 0.52, respectively. The odds ratio of ORR between PD-L1 positive and negative was 2.34 (95% CI 1.77-3.10, P <0.0001). The odds ratios of ORR, 6-month PFS rate and 1-year OS rate between nivolumab and chemotherapeutics were 2.77 (95% CI 1.69-4.56, P <0.0001), 1.97 (95% CI 1.02-3.81, P = 0.04) and 1.87 (95% CI 1.46-2.40, P <0.0001), respectively. In conclusion, nivolumab has durable outcomes with tolerable AEs and drug-related deaths in cancer patients. Nivolumab monotherapy has better treatment response compared to chemotherapy, whereas chemotherapeutics have significantly higher risk of adverse effects than nivolumab. This article is protected by copyright. All rights reserved.

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The plasma membrane Ca2+ pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells

Abstract

Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca²⁺ signaling is a well-known regulator of tumor progression, the crosstalk between Ca²⁺ signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca²⁺ ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi. The MEK inhibitor selumetinib – similarly to that of the BRAF-specific inhibitor - also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. The increased abundance of PMCA4b in the plasma membrane enhances [Ca²⁺]_i clearance from cells after Ca²⁺ entry. Moreover we show that both vemurafenib treatment and PMCA4b overexpression induce marked inhibition of migration of BRAF mutant melanoma cells. Importantly, reduced migration of PMCA4b expressing BRAF mutant cells is associated with a marked decrease in their metastatic potential in vivo. Taken together, our data reveal an important crosstalk between Ca²⁺ signaling and the MAPK pathway through the regulation of PMCA4b expression and suggest that PMCA4b is a previously unrecognized metastasis suppressor. This article is protected by copyright. All rights reserved.

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Nutlin-3a selects for cells harbouring TP53 mutations

Abstract

TP53 mutations occur in half of all human tumours. Mutagen-induced or spontaneous TP53 mutagenesis can be studied in vitro using the human TP53 knock-in (Hupki) mouse embryo fibroblast (HUF) immortalisation assay (HIMA). TP53 mutations arise in up to 30% of mutagen-treated, immortalised HUFs; however, mutants are not identified until TP53 sequence analysis following immortalisation (2–5 months) and much effort is expended maintaining TP53-WT cultures. In order to improve the selectivity of the HIMA for HUFs harbouring TP53 mutations, we explored the use of Nutlin-3a, an MDM2 inhibitor that leads to stabilisation and activation of wild-type (WT) p53. First, we treated previously established immortal HUF lines carrying WT or mutated TP53 with Nutlin-3a to examine the effect on cell growth and p53 activation. Nutlin-3a induced the p53 pathway in TP53-WT HUFs and inhibited cell growth, whereas most TP53-mutated HUFs were resistant to Nutlin-3a. We then assessed whether Nutlin-3a treatment could discriminate between TP53-WT and TP53-mutated cells during the HIMA (n=72 cultures). As immortal clones emerged from senescent cultures, each was treated with 10 µM Nutlin-3a for 5 days and observed for sensitivity or resistance. TP53 was subsequently sequenced from all immortalised clones. We found that all Nutlin-3a-resistant clones harboured TP53 mutations, which were diverse in position and functional impact, while all but one of the Nutlin-3a-sensitive clones were TP53-WT. These data suggest that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. This article is protected by copyright. All rights reserved.

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Lifecourse Socioeconomic Status and Cancer-Related Risk Factors: Analysis of the WHO study on Global Ageing and Adult Health (SAGE)

ABSTRACT

Few studies have examined cancer-related risk factors in relation to SES across the lifecourse in low to middle income countries. This analysis focuses on adult women in India, China, Mexico, Russia and South Africa, and examines the association between individual, parental and lifecourse SES with smoking, alcohol, BMI, nutrition and physical activity. Data on 22,283 women aged 18 years and older were obtained from the 2007 WHO Study on Global Aging and Adult Health (SAGE). Overall, 34% of women had no formal education, 73% had mothers with no formal education and 73% of women had low lifecourse SES. Low SES women were almost 4 times more likely to exceed alcohol use guidelines (OR: 3.86, 95% CI: 1.23-12.10), and 68% more likely to smoke (OR: 1.68, 95% CI: 1.01-2.80) compared with higher SES. Women with low SES mothers and fathers were more likely to have poor nutrition (Mothers OR: 1.59, 95% CI: 1.17-2.16; Fathers OR: 1.33, 95% CI: 1.11-1.59) and more likely to smoke (Mothers OR: 1.46, 95% CI: 1.15-1.87; Fathers OR: 2.17, 95% CI: 1.80-2.63) compared with those with high SES parents. Women with stable low lifecourse SES were more likely to smoke (OR: 2.55, 95% CI: 1.47-4.43), while those with declining lifecourse SES were more likely to exceed alcohol use guidelines (OR: 3.63, 95% CI: 1.07-12.34). Cancer-related risk factors varied significantly by lifecourse SES, suggesting that cancer prevention strategies will need to be tailored to specific sub-groups in order to be most effective. This article is protected by copyright. All rights reserved.

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In response to: Letter to the Editor by Kilbreath et al

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The effects of neoadjuvant therapy on morbidity and mortality of esophagectomy for esophageal cancer: American college of surgeons national surgical quality improvement program (ACS–NSQIP) 2005–2012

Objective

This study used a multi-center database to evaluate the impact of neoadjuvant therapy on the 30-day morbidity and mortality following esophagectomy for esophageal cancer.

Methods

The NSQIP database was queried for 2005–2012 for patients, who had esophagectomy for esophageal cancer. Patients were divided into two groups: neoadjuvant therapy and esophagectomy only.

Results

The neoadjuvant group had a lower rates of sepsis (8% vs. 13%, unadjusted P = 0.004) and acute renal failure (0.4% vs. 2%, unadjusted P = 0.01), and a higher rate of pulmonary embolism (PE) (3% vs. 1%, unadjusted P = 0.04). The adjusted odds of PE for patients, who received neoadjuvant therapy were 2.8 times the odds of PE for patients in the esophagectomy group, controlling for BMI. The association with renal failure was not significant, when one adjusted for race. There was no difference in the rates of reoperation, readmission, stroke, cardiac arrest, MI, surgical site and deep organ infections, anastomosis failure, blood transfusions, DVT, septic shock, pneumonia, UTI, respiratory failure, and 30-day mortality between the two groups.

Conclusions

We conclude that neoadjuvant therapy followed by esophagectomy for esophageal cancer does not have a negative impact on 30-day mortality. Neoadjuvant therapy is associated with increased odds of PE. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Real-time confocal laser endomicroscopic evaluation of primary liver cancer based on human liver autofluorescence

Background

Confocal laser endomicroscopy (CLE) is available for real-time microscopic examination. This study aims to evaluate the usefulness of intraoperative CLE examination as a modality to evaluate surgical margins in surgery for primary liver cancer.

Methods

A probe-based CLE system (Cellvizio 100, Mauna Kea Technologies, Paris, France) was used. The subjects comprised seven specimens obtained from six patients with primary liver cancer in November 2015. The probe was manually attached to the surfaces of specimens, and images were collected without external fluorophores. CLE images were compared with hematoxylin and eosin-stained slides. Fluorescence intensity (FI) values of the CLE images were assessed using luminance-analyzing software.

Results

CLE examination visualized non-cancerous regions in the background liver as regular structures with high fluorescence because of human liver autofluorescence. Conversely, hepatocellular carcinoma and intrahepatic cholangiocarcinoma were depicted as irregular structures with low fluorescence. The median FI values of the non-cancerous regions and the cancerous regions were 104 (79.8–156) and 74.9 (60.6–106), respectively, and were significantly different (P = 0.031).

Conclusions

The probe-based CLE enables real-time differentiation of cancerous regions from non-cancerous tissues in surgical specimens because of human liver autofluorescence. CLE can be used to confirm negative surgical margins in the operating room. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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A novel “shrug technique” for totally implantable venous access devices via the external jugular vein: A consecutive series of 254 patients

Background

The external jugular vein (EJV) approach for totally implantable venous access devices (TIVADs) is safe. However, the success rate is unsatisfactory because of the difficulty in catheterization due to the acute angle between the EJV and the subclavian vein (SCV). A novel "shrug technique" to overcome this difficulty was developed, and its efficacy was assessed in a consecutive case series.

Methods

TIVAD placement was performed via the EJV cut-down approach. "Shrug technique," a simple way to straighten the EJV–SVC angle by shrugging the patient's shoulder, was applied to facilitate the passage of the guidewire and sheath-introducer when there was acute angulation between the EJV and SCV.

Results

A total of 254 patients underwent TIVAD implantation by the EJV cut-down approach. The "shrug technique" was applied in 51 cases (20%), and catheterization was successful in all cases. Thus, TIVAD implantation was successfully completed in all 254 cases (100%) in a single operative setting. The median operating time was 38 [IQR 30–45] min. Eleven complications (4%) were observed, but none of them were EJV-specific.

Conclusion

The "shrug technique" is simple but very useful to achieve a higher success rate and safer insertion of TIVADs from the EJV. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Outcomes of patients with hepatocellular carcinoma are determined in multidisciplinary team meetings

Background and Objectives

To analyze overall survival (OS) rates for the three curative treatments of hepatocellular carcinoma (HCC) on an intention-to-treat (ITT) basis.

Methods

Cohort study based on data from a multidisciplinary team meeting (MDT) dedicated to HCC. From 2006 to 2013, we included every patient with newly diagnosed HCC, for whom curative treatment (liver transplantation (LT), radiofrequency ablation (RFA), surgical resection (SR)) was decided upon.

Results

We included 387 consecutive patients. LT was decided in 136 cases, RFA in 131 cases, SR in 120 cases. Sixty-six percent of patients received the planned treatment. Five-year OS on an ITT basis were: 35% for the LT-group, 32% for the RFA-group, 34% for the SR-group (P = 0.77). In multivariate analyses, the main negative prognostic factors were not following the MDT decision (HR: 0.39, CI95% [0.27–0.54], P < 0.001), elevated alpha-fetoprotein level (HR: 0.63, CI95% [0.45–0.87], P = 0.005), being outside the Milan criteria (HR: 0.45, CI95% [0.31–0.65], P < 0.001). When curative treatment was performed, per-protocol 5-year OS were 64% for LT, 34% for RFA, 40% for SR.

Conclusion

On an ITT basis, OS was similar whatever the type of curative treatment chosen in MDT. Negative prognostic factors were not following the MDT decision, elevated alpha-fetoprotein, being outside the Milan criteria. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Utilization of pre-operative imaging for colon cancer: A population-based study

Objective

To assess the use of pre-operative imaging for colon cancer and to identify factors associated with utilization in routine clinical practice.

Methods

This population-based, retrospective cohort study used a random sample of 25% of colon cancer patients treated with surgery in the province of Ontario (2002–2008). Pre-operative imaging (<16 weeks from surgery) of the chest, abdomen-pelvis was identified. Modified poisson regression was used to analyze factors associated with practice patterns.

Results

Of the 7,249 included patients, 48% had pre-operative imaging (CT abdomen and imaging of the chest) in keeping with guideline recommendations. The rate of guideline concordant pre-operative imaging increased over time: 64% in the most recent study period (2006–2008) versus 31% (2002–2004); P < 0.001. Variables associated with use of chest imaging: Age, co-morbidity, surgeon volume, and geographic region; no association with gender, hospital volume, or socio-economic status. Variables associated with use of abdomen imaging: Hospital volume and geographic region; no association with age, gender, comorbidity, socio-economic status, or surgeon volume.

Conclusion

In clinical practice, the majority of patients were not receiving pre-operative imaging that was in line with clinical practice guidelines; however, use increased over time indicating a possible association with dissemination of clinical practice guidelines. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Bioimpedance spectroscopy does have a valid and evidence-based role in detection and monitoring of lymphoedema

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Cancers, Vol. 8, Pages 100: TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts

The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue. These results demonstrated a 44-fold decrease in TGFBR3 mRNA in tumor stroma in comparison to control tissue. We investigated publicly available databases, and have identified that TGFBR3 mRNA levels are decreased in tumor stroma. We next investigated fibroblast cell lines derived from cancerous and normal breast tissue and found that in addition to mRNA levels, TβRIII protein levels were significantly reduced. Having previously identified that cancer-associated fibroblasts secrete greater levels of tumor promoting cytokines, we investigated the consequences of soluble-TβRIII (sTβRIII) on fibroblasts. Fibroblast conditioned medium was analyzed for 102 human secreted cytokines and distinct changes in response to sTβRIII were observed. Next, we used the fibroblast-conditioned medium to stimulate human monocyte cell line THP-1. These results indicate a distinct transcriptional response depending on sTβRIII treatment and whether it was derived from normal or cancerous breast tissue. We conclude that the effect of TβRIII has distinct roles not only in cancer-associated fibroblasts but that sTβRIII has distinct paracrine functions in the tumor microenvironment.

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