Volumetric-Based Analysis of In-Vivo and Ex-Vivo Quantita-tive MR Diffusion Parameters in Pancreatic Adenocarcinoma: Correlation with Pathologic Findings
Imaging biomarkers are needed to assess modifications in pancreatic adenocarcinoma (PA) induced by stroma-targeted therapies. The study investigates correlations between quantitative diffusion parameters obtained in vivo and ex vivo with a tumour volumetric approach and quantitative pathologic findings including fibrosis, vascular and total nuclear densities in PA
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Intrafraction variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Intrafraction variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including D99 and D95 for Internal Target Volume (ITV) and Gross Tumor Volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution. In this study, we found that intrafraction motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. This phenomenon was compromised when 3-dimensional space distribution was considered. This result may provide a prospective reference for target dose degradation due to intrafraction motion during lung SBRT treatment.
Secondary Malignancy after Treatment of Prostate Cancer. Radical Prostatectom...asclepiuspdfs
Background: This study aims to determine whether the treatment of locally confined prostate cancer (PCa) with external radiotherapy (EBRT) increases the risk to develop secondary malignancies (SM) compared to radical prostatectomy (RPE). Materials and Methods: Data from patients who were treated curatively with RPE or EBRT from 2010 to 2018 and who did not have distant metastases, previous malignancy, or previous treatment with radiotherapy or chemotherapy at the time of diagnosis were reviewed to determine the incidence of SM over a median follow-up period of 47 months (range 12–96 months). Regression models were used to correlate the clinicopathological factors with the incidence of SM.
The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant
breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response.
From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant
chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion
sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest
(ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria)
and pathological response (assessed using Mandard’s classification).
Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evaluated
the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values
obtained with the two different methods of ROI placement were 1.11 and 1.02 · 10)3 mm2 ⁄ seconds. Mean post-treatment
ADC values were 1.40 and 1.35 · 10)3 mm2 ⁄ seconds, respectively. A significant inverse correlation between mean ADC
increase and Mandard’s classifications was observed for both the methods of ADC measurements. Diagnostic performance
analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method
(accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides superior
evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological
MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional
works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to
tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from
nonresponder patients.
This study aimed to compare the overall and disease specific survivals of patients who underwent laparoscopic and open resection of colorectal cancer in a high volume tertiary center.
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Intrafraction variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan
Dosimetric Consequences of Intrafraction Variation of Tumor Motion in Lung St...semualkaira
The purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during Stereotactic Body Radiotherapy (SBRT) for lung cancer. Intensity-Modulated Radiation Therapy (IMRT) plans were designed based on Average Computed Tomography (AVG CT) utilizing the Planning Target Volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Intrafraction variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including D99 and D95 for Internal Target Volume (ITV) and Gross Tumor Volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution. In this study, we found that intrafraction motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. This phenomenon was compromised when 3-dimensional space distribution was considered. This result may provide a prospective reference for target dose degradation due to intrafraction motion during lung SBRT treatment.
Secondary Malignancy after Treatment of Prostate Cancer. Radical Prostatectom...asclepiuspdfs
Background: This study aims to determine whether the treatment of locally confined prostate cancer (PCa) with external radiotherapy (EBRT) increases the risk to develop secondary malignancies (SM) compared to radical prostatectomy (RPE). Materials and Methods: Data from patients who were treated curatively with RPE or EBRT from 2010 to 2018 and who did not have distant metastases, previous malignancy, or previous treatment with radiotherapy or chemotherapy at the time of diagnosis were reviewed to determine the incidence of SM over a median follow-up period of 47 months (range 12–96 months). Regression models were used to correlate the clinicopathological factors with the incidence of SM.
The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant
breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response.
From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant
chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion
sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest
(ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria)
and pathological response (assessed using Mandard’s classification).
Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evaluated
the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values
obtained with the two different methods of ROI placement were 1.11 and 1.02 · 10)3 mm2 ⁄ seconds. Mean post-treatment
ADC values were 1.40 and 1.35 · 10)3 mm2 ⁄ seconds, respectively. A significant inverse correlation between mean ADC
increase and Mandard’s classifications was observed for both the methods of ADC measurements. Diagnostic performance
analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method
(accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides superior
evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological
MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional
works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to
tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from
nonresponder patients.
This study aimed to compare the overall and disease specific survivals of patients who underwent laparoscopic and open resection of colorectal cancer in a high volume tertiary center.
Anemia is a common condition of cancer patients. This is because cancers cause inflammation that decrease red blood cell production. In addition, many chemotherapies are myelosuppressive, meaning they slow down the production of new blood cells by the bone marrow.
Drug Repurposing: Recent Advancements, Challenges, and Future Therapeutics fo...JohnJulie1
Cancer is a prime public health burden that accounts for approximately 9.9 million deaths worldwide. Despite recent advances in treatment regimen and huge capital investment in the pharmaceutical sector, there has been little success in improving the chances of survival of cancer patients.
Abnormal Sodium and Chlorine Level Is Associated With Prognosis of Lung Cance...JohnJulie1
The imbalance of sodium and chloride ions occurs frequently in patients with lung cancer. However, the correlation between ion concentration change and patients prognosis have not been studied thoroughly. Our research will fill the gap, especially for high ion concentration.
Diagnostic Accuracy of Raised Platelet to Lymphocyte Ratio in Predicting Heli...JohnJulie1
Helicobacter Pylori (HP) infection is prevalent among patients with dyspepsia in developing countries with low socioeconomic status. The gold standard investigation is invasive method gastric biopsy through upper GI endoscopy, however non-invasive methods (stool for HP antigen) are not reliable up to the mark also need to wait for two weeks without symptomatic treatment. It is important to have a reliable, cost effective and easily accessible non-invasive marker to diagnose patients with H. pylori infection. Several non-invasive laboratory have been predicted in having the role in diagnosis of H.pylori infection. Therefore, the aim of our study was to determine the diagnostic accuracy of platelet to lymphocyte ratio in predicting H.Pylori infection in patients with dyspepsia.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
•
Fibrous
•
Fibro glandular
•
Adipose (Fatty)
What is Tomosynthesis?
•
Is a 3 dimensional projection
•
Reduces overlapping tissue seen with 2D only
•
15 projections are taken with each combo exposure (7.5) (-7.5)
•
With an average breast (18*24) 3D dose is 1.34, combo is 2.56 Milligrey. (3 Milligrey FDA) (2D is 1.2
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaJohnJulie1
Gut microbiota has been implicated as a critical role in the development of colorectal cancer (CRC) and colorectal adenoma (CRA). However, few basic research has revealed the association between gut microbiota and the development of CRA and CRC. We aim to compare the diversity and composition of intestinal flora in CRA and CRC patients, to reveal the changes of intestinal microorganism in the evolution of normal intestinal mucosa-CRA-CRC axis, and to explore potential biomarkers.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...JohnJulie1
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...JohnJulie1
To report the lessons we have learned in the management of uretero-enteric anastomosis stricture (UEAS) in a tertiary urology center over a decade of experience.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Combined Analysis of Micro RNA and Proteomic Profiles and Interactions in Pat...JohnJulie1
Liquid Chromatography Tandem Mass Spectrometry
The Liquid Mass System(LMS) includes an Easy nLC1000 (Thermo Fisher) coupled ultra-high resolution mass spectrometer Orbitrap Fusion Lumos (Thermo Fisher) with a Thermo Fisher electrospray source. Each injection is sent to a preset column (Acclaim PepMap C18, 100 μm x 2 cm, Thermo Scientific) for adsorption at a flow rate of 3 L/min. The sample is then sent to the analyzer column (Acclaim PepMap C18, 75 μm x 15 cm, Thermo Scientific) for separation.
Skeletal muscle channelopathy are rare heterogeneous episodic disorders with marked genotypic and phenotypic variability resulting in periodic paralysis, and falls in young people which often misdiagnosed or undiagnosed due to its rarity, often the symptoms are miscommunicated to the treating phycision due to its episodic nature and not uncommonly physical examination by the time patient attend the clinic or hospital will be unremarkable apart from periodic muscle paralysis where patient will presented to ED with flaccid weakness,
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...JohnJulie1
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Follow-Up Strategies in Focal Liver Lesions And Treatment MethodsJohnJulie1
Today, advances in cross-sectional imaging have led to the detection and early recognition of incidental/focal liver lesions (FCL). In approximately 17,000 cases of chest CT, incidental liver lesions were found in 6% [1]. In general, FCL consists of hepatocytes, biliary epithelium, mesenchymal tissue, connective tissue, or metastasized cells from distant sites. Most incidental lesions are benign, some may require careful management and treatment.
Contextual Factors Associated with Health-Related Quality of Life in Older Ad...JohnJulie1
The purpose of this study was to examine contextual factors associated with physical and mental health-related quality of life (HRQOL) in older adult cancer survivors.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...JohnJulie1
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...JohnJulie1
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesions.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Anemia is a common condition of cancer patients. This is because cancers cause inflammation that decrease red blood cell production. In addition, many chemotherapies are myelosuppressive, meaning they slow down the production of new blood cells by the bone marrow.
Drug Repurposing: Recent Advancements, Challenges, and Future Therapeutics fo...JohnJulie1
Cancer is a prime public health burden that accounts for approximately 9.9 million deaths worldwide. Despite recent advances in treatment regimen and huge capital investment in the pharmaceutical sector, there has been little success in improving the chances of survival of cancer patients.
Abnormal Sodium and Chlorine Level Is Associated With Prognosis of Lung Cance...JohnJulie1
The imbalance of sodium and chloride ions occurs frequently in patients with lung cancer. However, the correlation between ion concentration change and patients prognosis have not been studied thoroughly. Our research will fill the gap, especially for high ion concentration.
Diagnostic Accuracy of Raised Platelet to Lymphocyte Ratio in Predicting Heli...JohnJulie1
Helicobacter Pylori (HP) infection is prevalent among patients with dyspepsia in developing countries with low socioeconomic status. The gold standard investigation is invasive method gastric biopsy through upper GI endoscopy, however non-invasive methods (stool for HP antigen) are not reliable up to the mark also need to wait for two weeks without symptomatic treatment. It is important to have a reliable, cost effective and easily accessible non-invasive marker to diagnose patients with H. pylori infection. Several non-invasive laboratory have been predicted in having the role in diagnosis of H.pylori infection. Therefore, the aim of our study was to determine the diagnostic accuracy of platelet to lymphocyte ratio in predicting H.Pylori infection in patients with dyspepsia.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
•
Fibrous
•
Fibro glandular
•
Adipose (Fatty)
What is Tomosynthesis?
•
Is a 3 dimensional projection
•
Reduces overlapping tissue seen with 2D only
•
15 projections are taken with each combo exposure (7.5) (-7.5)
•
With an average breast (18*24) 3D dose is 1.34, combo is 2.56 Milligrey. (3 Milligrey FDA) (2D is 1.2
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaJohnJulie1
Gut microbiota has been implicated as a critical role in the development of colorectal cancer (CRC) and colorectal adenoma (CRA). However, few basic research has revealed the association between gut microbiota and the development of CRA and CRC. We aim to compare the diversity and composition of intestinal flora in CRA and CRC patients, to reveal the changes of intestinal microorganism in the evolution of normal intestinal mucosa-CRA-CRC axis, and to explore potential biomarkers.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...JohnJulie1
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...JohnJulie1
To report the lessons we have learned in the management of uretero-enteric anastomosis stricture (UEAS) in a tertiary urology center over a decade of experience.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Combined Analysis of Micro RNA and Proteomic Profiles and Interactions in Pat...JohnJulie1
Liquid Chromatography Tandem Mass Spectrometry
The Liquid Mass System(LMS) includes an Easy nLC1000 (Thermo Fisher) coupled ultra-high resolution mass spectrometer Orbitrap Fusion Lumos (Thermo Fisher) with a Thermo Fisher electrospray source. Each injection is sent to a preset column (Acclaim PepMap C18, 100 μm x 2 cm, Thermo Scientific) for adsorption at a flow rate of 3 L/min. The sample is then sent to the analyzer column (Acclaim PepMap C18, 75 μm x 15 cm, Thermo Scientific) for separation.
Skeletal muscle channelopathy are rare heterogeneous episodic disorders with marked genotypic and phenotypic variability resulting in periodic paralysis, and falls in young people which often misdiagnosed or undiagnosed due to its rarity, often the symptoms are miscommunicated to the treating phycision due to its episodic nature and not uncommonly physical examination by the time patient attend the clinic or hospital will be unremarkable apart from periodic muscle paralysis where patient will presented to ED with flaccid weakness,
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...JohnJulie1
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Follow-Up Strategies in Focal Liver Lesions And Treatment MethodsJohnJulie1
Today, advances in cross-sectional imaging have led to the detection and early recognition of incidental/focal liver lesions (FCL). In approximately 17,000 cases of chest CT, incidental liver lesions were found in 6% [1]. In general, FCL consists of hepatocytes, biliary epithelium, mesenchymal tissue, connective tissue, or metastasized cells from distant sites. Most incidental lesions are benign, some may require careful management and treatment.
Contextual Factors Associated with Health-Related Quality of Life in Older Ad...JohnJulie1
The purpose of this study was to examine contextual factors associated with physical and mental health-related quality of life (HRQOL) in older adult cancer survivors.
Pancreatic Adenocarcinoma with Isolated Venous Involvement: Is Neoadjuvant Tr...JohnJulie1
Neoadjuvant Treatment (NAT) is indicated in locally advanced tumors and improves the results of subsequent surgery. In borderline tumors, the place of this preoperative treatment is more controversial, probably because borderline tumors are a heterogeneous group. We focused on the tumors with venous involvement without any arterial involvement and studied the results of neoadjuvant treatment in this particular group.
Predictive Value of Biomarkers Fibrinogen Like Protein-2 and A-Fetoprotein fo...JohnJulie1
Data concerning the utility of biomarkers for accurate early HCC detection in cirrhotic patients are lacking. 1.2. Methods: We evaluated 112 consecutive Caucasian cirrhotic patients with (n=28) or without (n=84) concomitant HCC at baseline for serum AFP and plasma fibrinogen like protein-2 (FGL-2) levels. Patients without confirmed HCC at baseline were further followed up every six months with ultrasound and serum AFP levels, according to HCC surveillance program. Imaging as well as histological confirmation of HCC was established in patients with new lesions.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Volumetric-Based Analysis of In-Vivo and Ex-Vivo Quantita-tive MR Diffusion Parameters in Pancreatic Adenocarcinoma: Correlation with Pathologic Findings
2. Citation: Meten T, Volumetric-Based Analysis of In-Vivo and Ex-Vivo Quantitative MR Diffusion Parameters in Pancreatic
Adenocarcinoma: Correlation with Pathologic Findings. Japanese Journal of Gastroenterology and Hepatology. 2019; 1(4):1-8. 2
Take home message: A statistically significant positive
correlation between ADC and D and degree of fibrosis was
found in pancreatic adenocarcinoma, indicating the presence of
a relatively larger extracellular space when fibrosis increases.
3. Introduction
Pancreatic adenocarcinoma (PA) is the fourth cause of cancer-
related death in western countries with an overall 5-year survival
rate below 8% [1, 2]. PA is characterized by an extensive stroma
reaction along with poor vascularization that promote the
creation of a hypoxic environment which may act as a mechanical
barrier for drug delivery contributing to treatment failure [3].
Surgery is the only curative treatment. Currently, less than 20%
of the patients are eligible for potentially curative resection [1]
and chemotherapy or chemoradiation therapy are indicated for
unresectable locally advanced and metastatic PA [2]. Studies
evaluating the association of stroma-targeted drugs with
conventional cytotoxic chemotherapy have reported encouraging
results, with significant reduction of the stroma, decreased intra-
tumoural pressure, increased perfusion and drug delivery [4].
RECIST, the currently used imaging criteria to monitor tumour
response to conventional anticancer cytotoxic drugs is based on
morphological assessment, i.e. size modification using a one-
dimensional measurement of the tumour (longest diameter) [5].
However these criteria may not be appropriate when anti-cancer
agents with a novel model of action are administered.
Thus, there is an unmet need of new imaging biomarkers in order
to follow up modification of different PA tumour components
induced by stroma-targeted therapies. These therapies aim at
counteracting tumour growth and invasion promoted by PA
stromal cells. Diffusion-Weighted magnetic resonance Imaging
(DWI) may reveal as a potential imaging tool in this setting. DWI
is sensitive to microscopic movements of water molecules within
biological tissue, which reflect tissue cellularity, tortuosity of the
extracellular space, integrity of cell membranes and viscosity of
fluids. The image contrast on DWI derives from differences in
mobility of water molecules within tissues [6]. Several quantitative
parameters are derived: the apparent diffusion coefficient, ADC,
calculated using a mono-exponential fitting, which is a combined
measure of the movement of water molecules within the intra
and extracellular spaces (true diffusion) and the intravascular
space (flow-related pseudo-perfusion). Alternatively, applying
a biexponential model (Intra-Voxel Incoherent Motion, IVIM)
allows the separation between the true diffusion and the pseudo-
perfusion [7].
Results from previous studies which have assessed the correlation
between PA histopathological characteristics and ADC are
conflicting: some described a negative association [8-10], while
others did not demonstrate any association [11, 12] or suggested
a positive association between ADC and tumoral fibrosis [13].
In view of these contradictory results, further studies are definitely
needed. Hence the aim of the present study is to investigate
possible correlations between IVIM diffusion parameters
obtained in vivo and ex vivo using a volumetric approach and
pathologic findings including fibrosis, vascular and total nuclear
densities in patients with PA.
4. Material and Methods
This prospective study was approved by the institutional review
board and informed consent was obtained from all participants.
14 consecutive patients, 7 men (mean age: 66 years; range: 36–82
years) and 7 women (mean
age: 69 years; range: 55–82 years), were enrolled. The inclusion
criteria consisted of the presence of a resectable pancreatic
solid tumour with histopathology confirmation of PA. Previous
chemotherapy and chemoradiation therapy represented exclusion
criteria together with common contraindications to MR
examination.
4.1. MR Acquisitions
In vivo MR investigations were carried out on all patients within
4 days before surgery and were performed on a1.5-Tesla magnet
(Achieva; Philips Healthcare, Best, The Netherlands) equipped
with a 16-channel phased-array coil. All patients were placed in
the magnet in the supine position.
Morphologic images were acquired with transverse and coronal
respiratory-triggered T2weighted single-shot turbo spin-echo (SS-
TSE), covering the upper abdomen (TE=80ms, echo train length
72, 40 slices, no gap, field-of-view 400x400mm2
, acquisition voxel
1.8x1x5mm³, Sense-acceleration=2).
Diffusion-weighted MR images were acquired with a transverse
respiratory-triggered spin echo echo-planar (SE-EPI)
sequence (TE=70ms, echo train length 61, 40 slices, no gap,
field-of-view 400x400mm², acquisition voxel 2.3x3x5mm3
,
Sense-acceleration=2). A spatial-selective inversion recovery
prepulse provided fat suppression (TI=180ms). Diffusion-
probing gradients with b values of 0, 10, 20, 30, 40, 50, 150, 300
and 1000s/mm2
were applied in three orthogonal directions. For
each b value the isotropic mean image was reconstructed. The
whole MR examination lasted approximately 30 minutes.
The respected pancreatic specimens were scanned within 3 hours
ensuing surgery and before histopathology procedures. Ex vivo
2019, V(4): 1-8
3. 3
MR investigations were carried out with the same magnet as
above using a 2-channel phased-array coil.
Morphologic images were acquired with SS-TSE sequences,
covering the whole surgical specimen in transverse (20 slices,
field-of-view 120x89mm2
) and coronal (12 slices, field-of-view
120x111mm2
) orientations (TE=100ms, echo train length 14, no
gap, acquisition voxel 0.6x0.9x4.0mm3
, Sense-acceleration=2).
Diffusion-weighted MR images were acquired with a transverse
SE-EPI sequence (TE=70ms, echo train length 17, 15 slices, no
gap, field-of-view 100x53mm², acquisition voxel 1.5x1.9x4.0mm3
,
Sense-acceleration=2, TI=180ms, same b values as in vivo).
Image analysis was performed independently by two readers
(both were 5th-year radiology
residents - MP, EG) with 1 year of experience in abdominal MR
imaging.
An image J-based software [14] was used with a specific
graphical user interface [15] to segment the whole tumour
volume and calculate diffusion parameters. DW-images acquired
with b=1000s/mm2
were used for segmentation. User-defined
boxes were manually fitted around the whole tumour which was
automatically segmented by thresholding all the inner voxels
holding a signal value over the mean +0.5 standard deviation. The
resulted volume was manually readjusted on the basis of b=0s/
mm2
DW images and T2-weighted images so that the whole
tumour was enclosed while avoiding contiguous lymph nodes,
non-tumoural tissue, biliary or pancreatic ducts and distortion
artefacts on ex vivo images (Figure 1).
Figure 1a. In vivo axial T2-weighted image showing a solid tumour in the
pancreatic tail..
Figure 1b. Corresponding DW images (b=150, 300 and 1000 s/mm²) and ADC
map with tumour segmentation (red contour: intersection between DW-volume
and image section).
Figure 1c. Ex vivo axial T2-weighted image of the corresponding resected
tumour.
Figure 1d: Corresponding ex vivo ADC map with tumour segmentation (red
contour: intersection between DW-volume and image section).
The software calculated the whole tumour volume (DW-volume),
from which diffusion parameters were generated.
A mono-exponential model S(b) = S0 exp(-b ADC) including all
b values was used to calculate the ADC, whilst a biexponential
model S(b)/ S0 = (1-f) exp(-bD) + f exp (-bD*
) was employed to
derive the pure diffusion coefficient D, the perfusion fraction f
and the pseudo-diffusion D*
(D*
was not used in further analysis);
S(b) being the signal at a given b value and S0 being the signal at
b=0s/mm2
.
The biexponential fit was performed using approximate values
of D and f as initial fit value: the initial D value was obtained
from a mono-exponential fit involving data from high b values
(b=150 to 1000s/mm2
), S(b) = Sint exp(-bD) where Sint is the
b=0s/mm2
intercept resulting from the fit, while the initial f
value was calculated from f = (S0-Sint)/ S0.
The mean values of ADC, D and f were considered for each
patient. The analysis was applied to both in vivo and ex vivo
images.
4.2. Histopathology Analysis
Histopathology analysis was performed on all 14 surgical
specimens by a pathologist with 6 years of experience who was
blinded to MR-analysis results.
Surgical specimens were fixed in formalin and cut into contiguous
transverse5-mmthickslicesinthecranio-caudaldirectioncarefully
aligned to allow a proper comparison with the corresponding
transverse DW-images. Tissue blocks containing the tumour were
selected (an average of 9 blocks per patient was analyzed) and were
cut into serial transverse, 5-µm thick slices for staining to evaluate
fibrosis, vascular and nuclear densities. Stained slices from each
tumour (9 slices, 1 slice per tumour block) were digitalized at a
2019, V(4): 1-8
4. 4
magnification of 20x using a calibrated scanner (NanoZoomer,
Hamamatsu, Japan). Using image annotations, the pathologist
defined different Regions Of Interest (ROI), i.e. the central
tumour region (TC) and the peripheral tumour region (TP) as the
invading edge of the tumour. The whole tumour region (TW) was
defined as the union of TC and TP. Quantification of fibrosis,
vascular and nuclear densities was achieved at a magnification of
20x using Visiomorph software (Visiopharm, Denmark). Regions
with artefacts, excessive staining or tissue damage were excluded
for assessment. Goldner’s trichrome staining was performed on a
Tissue-Tek DRS 2000 slide stainer (Sakura Finetek Europe B.V.,
The Netherlands) to detect fibrosis area on each slice (Figure
2). Fibrosis density was defined as the ratio of the fibrosis-
stained area to the whole tissue area in the ROI. ERG immune-
histochemical staining was used to identify endothelial cell nuclei,
whereas the other (negative) cell nuclei were evidenced by means
of hematoxylin counterstaining (Figure 3). Briefly, the slides
were subjected to standard IHC (Ventana discovery XT, Roche
Diagnostics, Belgium) using the rabbit monoclonal anti-ERG
antibody (ready-to-use antibody, clone EPR3864 from Ventana)
and the biotin free DAB detection system. Vascular density was
defined as the ratio of the ERG-positive nucleus area to that of
all (positive or negative) nuclei.
The total nuclear density was defined as the ratio of the total
(ERG-positive or negative) nucleus area to the whole tissue area
in the ROI. With these definitions the quantification of either
fibrosis, vascular or nuclear densities was represented by a single
value in TC and in TP.
4.3 Statistical Analysis
Quantitative diffusion parameters, including DW-volume, ADC,
D and f calculated in vivo and ex vivo, and histopathology
parameters, including fibrosis, vascular and total nuclear densities,
were reported as mean and standard deviation.
Intraclass correlation coefficients (ICC) were calculated to assess
inter-reader agreement for diffusion parameters.
The non-parametric Wilcoxon’s signed rank test was performed
to compare paired data samples:
1. In vivo and ex vivo values of ADC, D and f
2. ADC and D values
3. Histopathology findings (fibrosis, vascular and total nuclear
densities) between TC and TP regions.
The Spearman’s rank correlation test was used to assess
correlations between:
1. In vivo and ex vivo diffusion parameters (ADC, D, f) and
histopathology findings (fibrosis, vascular and total nuclear
densities)
2. Histopathology findings among them.
The statistical analysis was performed using SPSS (version 23,
SPSS, Chicago, Ill) and MedCalc (version 13.1.2, MedCalc
Software, Ostend, Belgium).
A P value of 0.05 or less was considered significant.
4.4. Results
Among the 14 respected pancreatic tumours, the histopathology
analysis disclosed 12 cases of pancreatic ductal adenocarcinoma,
1 case of pancreatic acinar cell carcinoma and 1 case of
pancreatic ductal adenocarcinoma arising from an intra-ductal
papillary mucinous neoplasm. Pancreatic tumours were found in
the pancreatic head in 12/14 (86%) patients and in the body-tail
of the pancreas in 2/14 (14%) patients.
4.4.1. DW-Image Analysis
An excellent agreement was obtained between readers (in vivo
ICC=0.95 for ADC, 0.94 for D, 0.99 for f and 0.89 for DW-
volume; ex vivo ICC=0.91 for both ADC and D, 0.96 for f and
0.61 for DW-volume). Therefore, measurements from Reader 1
were used for further analysis.
(Table 1) reports mean and standard deviations for DW-volume,
ADC, D and f in vivo and ex vivo.
DW-volumes calculated in vivo and ex vivo were not statistically
significantly different (P=.074). On average, ex vivo volumes were
Figure 2: Histopathologic slice of the tumour shown in Figure 1. Assessment
of fibrosis density: the upper image is the original image (Goldner’s trichrome
staining, x20) and the lower one is the processed image, with visualisation of
fibrosis in green and the remaining tissue area in dark pink.
Figure 3: Histopathologic slice of the tumour shown in Figure 1. Assessment of
vascular density: the upper image is the original image (ERG immunohistochemical
staining with hematoxylin counterstaining, x20), the lower one is the processed
image, with negative nuclei coloured in blue and endothelial (positive) nuclei
coloured in dark brown. The rest of the tissue is shown in grey.
2019, V(4): 1-8
5. 5
14% lower than in vivo. Diffusion parameters were significantly
lower ex vivo compared with in vivo (all P=.001). A statistically
significant difference between ADC and D was also observed
both in vivo and ex vivo (both P=.001); the mean difference
between ADC and D was 178µm²/s in vivo and 33µm²/s ex vivo
(respectively 14% and 4% relative to ADC values).
(N=14) In vivo Ex vivo P value
DW-volume (cm³) 15.7 ± 7 13 ± 7.7 0.074
ADC [µm²/s] 1262 ± 322 771 ± 166 .001*
D [µm²/s] 1084 ± 263 738 ± 162 .001*
f [%] 24 ± 8 4.25 ± 1.4 .001*
Table 1: DW-volumes and diffusion parameters calculated in vivo and ex vivo.
4.4.2. Histopathology Analysis
(Table 2) reports histopathology results obtained for fibrosis,
vascular and total nuclear densities calculated in TC, TP and
TW. A statistically significant difference between TC and TP was
observed only for vascular density (P=.030), with higher values
in TP. There were no significant differences of fibrosis and total
nuclear density between TC and TP.
(Table 3) reports correlations among the histopathology findings.
A negative statistically significant correlation was observed
between TW fibrosis and TC total nuclear density (P=0.049). A
similar trend was observed between TW fibrosis and TW total
nuclear density although the correlation did not reach statistical
significance (P=.051).
4.4.3. Correlation between quantitative diffusion parameters
and histopathology findings
(Table 4) reports correlations between quantitative diffusion
parameters calculated in vivo and ex vivo and fibrosis, vascular
density and total nuclear density assessed in TC, TP and TW.
Mean ± standard deviation values are reported with P-values for comparison
between in vivo and ex vivo. Wilcoxon’s signed rank test, *
statistically significant,
P≤.05.
(N=14) TC TP TW
Fibrosis (%) 52 ± 12 52 ± 13 52 ± 11
Vascular density (%) 0.70 ± 0.34 0.98 ± 0.53 0.82 ± 0.41
Total nuclear density (%) 13.5 ± 6 13.9 ± 5 13.5 ± 5
Table 2: Histopathology results.
Mean ± standard deviation are given for the central tumour region (TC), the
peripheral tumour region (TP) and the whole tumour (TW). The vascular density
was significantly higher in TP compared with TC (P=.030).
TC total
nuclear
density
(%)
TC
vascular
density
(%)
TP
total
nuclear
density
(%)
TP
vascular
density
(%)
TW total
nuclear
density
(%)
TW
vascular
density
(%)
TC
fibrosis
(%)
Correlation
Coefficient
-0.411 -0.037 -0.213 0.415 -0.38 0.103
P value 0.144 0.899 0.464 0.14 0.18 0.725
TP fibrosis
(%)
Correlation
Coefficient
-0.415 -0.226 -0.464 -0.011 -0.429 -0.178
P value 0.14 0.436 0.095 0.97 0.126 0.543
TW
fibrosis
(%)
Correlation
Coefficient
-0.534 -0.011 -0.446 0.244 -0.53 0.055
P value .049*
0.97 0.11 0.401 0.051 0.852
Table 3: Correlations between fibrosis, vascular density, and total nuclear density
calculated in TC, TP and TW.
in vivo
ADC
in vivo
D
in vivo f
ex vivo
ADC
ex vivo D ex vivo f
TC
fibrosis
(%)
Correlation
Coefficient
0.64 0.596 0.253 0.626 0.626 -0.099
P value .014*
.025*
0.383 .017*
.017*
0.737
TP
fibrosis
(%)
Correlation
Coefficient
0.705 0.635 0.266 0.604 0.604 -0.301
P value .005*
.015*
0.358 .022*
.022*
0.296
TW
fibrosis
(%)
Correlation
Coefficient
0.758 0.732 0.407 0.719 0.719 -0.138
P value .002*
.003*
0.149 .004*
.004*
0.637
TC
vascular
density
(%)
Correlation
Coefficient
0.007 0.13 -0.138 0.002 0.002 0.073
P value 0.982 0.659 0.637 0.994 0.994 0.805
TP
vascular
density
(%)
Correlation
Coefficient
0.279 0.257 0.024 0.204 0.204 0.002
P value 0.334 0.375 0.935 0.483 0.483 0.994
TW
vascular
density
(%)
Correlation
Coefficient
0.125 0.218 -0.218 0.143 0.143 0.068
P value 0.67 0.455 0.455 0.626 0.626 0.817
TC total
nuclear
density
(%)
Correlation
Coefficient
-0.437 -0.411 -0.231 -0.666 -0.666 -0.055
P value 0.118 0.144 0.427 .009*
.009*
0.852
TP total
nuclear
density
(%)
Correlation
Coefficient
-0.415 -0.415 -0.134 -0.596 -0.596 -0.086
P value 0.14 0.14 0.648 .025*
.025*
0.771
TW total
nuclear
density
(%)
Correlation
Coefficient
-0.486 -0.464 -0.244 -0.657 -0.657 -0.046
P value 0.078 0.095 0.401 .011*
.011*
0.876
Table 4: Correlations between quantitative diffusion parameters and fibrosis,
vascular density, total nuclear density calculated in TC, TP and TW.
Spearman’s rank correlation test; *
statistically significant, P≤.05
TC: center of the tumour, TP: peripheral tumour region, TW: whole tumour.
Statistically significant positive correlations were observed
between fibrosis and ADC or D both measured in vivo and ex
vivo (for P values see table). In contrast, no significant correlation
was observed between perfusion fraction f and fibrosis.
No statistically significant correlation was found between vascular
density and quantitative diffusion parameters calculated in vivo
and ex vivo.
Statistically significant negative correlations were observed
between ex vivo ADC or D and total nuclear density. In vivo,
negative correlations, although not statistically significant, were
also observed between ADC or D and total nuclear density. No
2019, V(4): 1-8
Spearman’s rank correlation test; * statistically significant, P≤.05 TC: central
tumour region, TP: peripheral tumour region, TW: whole tumour.
6. correlation was observed between perfusion fraction f and total
nuclear density.
5. Discussion
The main result of our study consisted of statistically significant,
moderate to high positive correlations between ADC or D and
fibrosis density within PA. This finding was obtained for diffusion
measurements performed both in vivo and ex vivo, using a
DW-image based volumetric approach with a careful alignment
between histopathologic sections and MR slices.
These results agree with the findings reported by Klauss et al
[13] who observed a significant increase in D from moderate to
severe degrees of fibrosis in PA.
They suggested that the presence of a more abundant tumoral
desmoplastic stroma which embeds the cancer and non-
cancer cells constitutes a non-tight, low diffusion restriction
microenvironment [13]. So on a comparative basis, a high content
of fibrosis will result in less diffusion restriction and in high ADC
and D values. Both ADC and D reflect diffusion water motion
within the intracellular and extracellular spaces, with the former
resulting in a more diffusion restricted environment because of
the various structural obstacles within the cell. According to these
considerations, we can hypothesize that, as fibrosis increases,
both ADC and D may reflect an increase of the extracellular over
the intracellular compartment ratio related to the high fibrosis
density which is a major histologic feature of PA. Consistently, in
our study, a statistically significant, moderate negative correlation
was found between TW fibrosis and TC total nuclear density.
These findings suggest the use of these quantitative imaging
biomarkers to assess treatment response in PA. Actually,
treatment-induced tumoral changes secondary to conventional
cytotoxic chemotherapy regimen as well as targeted-therapies
such as anti-stroma drugs could be monitored by ADC and D.
However, our findings appear to be in disagreement with other
previously published results which reported either a negative
correlation between ADC and fibrosis [8-10] or no evidence
of correlation [11,12]. Besides the differences in acquisition
parameters and post-processing methods between our study and
those cited, which could partially explain the difference in results,
we agree that ADC is influenced by many factors due to the
complex composition of PA microenvironment including cellular
density. Importantly, in [8] the degrees of fibrosis were compared
only inside a subgroup of moderately differentiated tumors with
relatively elevated ADC values. Therefore, correlations between
ADC and fibrosis might remain equivocal in absence of the
knowledge of these other parameters influencing ADC.
Our study also shows a statistically significant negative, moderate
correlation between ex vivo ADC or D and total nuclear density.
This relationship has been previously described in both oncologic
and non oncologic conditions [16].
The decrease of the ex vivo interstitial space (extracellular
compartment) due to the loss of fluids and the consequent
relative increase of the total nuclear density and thereby total cell
density, seems compatible with the higher diffusion restriction
and the decrease of respectively ADC and D, confirming
previous findings [16].
In vivo, a negative correlation was observed between those
same parameters, though not statistically significant: in vivo the
extracellular compartment of the tissue might contain more
water, as confirmed by the higher D value in vivo compared to ex
vivo, its relative volume occupancy might then be more elevated
in vivo and when the cell density increases, the corresponding
decrease in ADC and D might be relatively less important.
While we would expect a correlation between ADC and vascular
density and between f and vascular density, both ADC and f
being positively influenced by perfusion, no such correlation
was found. A possible explanation could be the presence of
altered and poorly functional vessels associated with tumor
neoangiogenesis, implying that an increase in vascular density
does not necessarily yield an increase in perfusion [17].
Statistically significant differences in PA between the DW-derived
quantitative parameters calculated respectively in vivo and in ex
vivo were observed, with the exception for the DW-volume that
as expected did not show any substantial change.
Our study evidenced a statistically significant decrease in
ADC, D and f values from in vivo to ex vivo. Change in tissue
microstructure, such as cell swelling due to osmotically driven
water flow into cells following ionic imbalance caused by disabled
ion pumps may explain the fall of ADC and D values from in
vivo to ex vivo [18]. This leads to a decrease in the extracellular
space, while the absence of perfusion in ex vivo explains the
decrease in perfusion fraction f.
Differences between ADC and D are statistically significant both
in vivo and ex vivo, but more pronounced in vivo and the decrease
in ADC from in vivo to ex vivo is more drastic than that in D.
There is a two-fold explanation: in vivo there is a contribution of
the intravascular pseudo-diffusivity to ADC and not to D, and
this perfusion-related phenomenon is absent ex vivo. Moreover,
the statistically significant difference between ADC and D which
recurs ex vivo may also be due to the fact that D was derived
from a biexponential model that is more sensitive to fit error and
is probably not appropriated ex vivo.
To be as much as possible representative of the whole tumor,
from each surgical specimen up to nine blocks containing
tumoral tissue have been analyzed at histopathology. All tumors
6
2019, V(4): 1-8
7. were subdivided into peripheral and central zones. A statistically
significant regional difference was seen only for vascular density
that was more pronounced in the peripheral region. As a matter
of fact, PA are classically known to be hypovascular tumors
and neovascularisation will tend to occur where the tumor is
in contact with surrounding non-tumoral tissue, which is more
richly supplied with blood [19]. Another explanation could be a
high interstitial fluid pressure present within PA due to abnormal
angiogenesis, which pushes interstitial fluid from center towards
periphery, carrying along proangiogenic factors to the tumor
surface where they promote neoangiogenesis [20].
Furthermore, no statistical difference was seen between tumor
regions for fibrosis and total nuclear density. To the best of
our knowledge, this finding has not been described before.
This interesting point, together with the absence of correlation
between ADC or D and vascular density, suggests that ADC
and D calculated on the whole segmented tumor appear to be
representative imaging biomarkers for tumor fibrotic content and
cellular density.
Our study has several limitations. The patient cohort is relatively
small and this may explain the lack of statistically significant
correlations between certain quantitative diffusion parameters
and the histopathology features. However, pancreatic cancer is a
relatively rare tumor (3.2%/year) with less than 20% of patients
candidate for surgery. Moreover, the new oncologic approach
to treat borderline patients with neoadjuvant chemotherapy or
chemo/radiotherapy has further contributed to the difficulty
to recruit treatment-naive subjects. Also, we did not take into
account tumor grade, which according to previous reports seems
to have an impact on quantitative diffusion parameters in PA
[8,11,12].
In addition, the smaller tumor volume obtained ex vivo could be
also related to distortion artefacts on diffusion images probably
leading to less accurate measurements.
Another limitation is the segmentation method used in our study.
It is based on tumor-to-tissue contrast on b=1000s/mm2 images,
aiming at the segmentation of the tumor volume where the
diffusivity is lower in the tumor than in the surrounding tissue,
which is the case in poorly differentiated PA. This approach may
not be accurate when the diffusivity of the tumor is not markedly
lower than in the surrounding tissue, as it might be the case in
some well differentiated PA. In our study, both b=0s/mm2 DW-
images and T2-weighted images were used to manually readjust
the volume segmentation.
Finally, the absence of cardiac triggering during in vivo MR
acquisition may have an impact on the repeatability and accuracy
of perfusion-related measurements.
In conclusion, a statistically significant positive correlation
between ADC or D and degree of fibrosis was found in PA,
indicating the presence of a relatively larger extracellular space
when fibrosis increases. Further studies involving a larger
number of patients and investigating the behavior of ADC and
D in treatment follow-up are required.
6. Acknowledgments
The CMMI is supported by the European Regional Development
Fund and the Walloon Region (« FEDER Wallonie-2020.EU
»program, « Wallonia Biomed » portfolio).
C. Decaestecker is a senior research associate with the National
(Belgian) Fund for Scientific Research (F.R.S.-FNRS).
The authors would like to thank Dr E Coppens for many
discussion related to the study.
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