Ingfrid Haldorsen - Academia.edu (original) (raw)
Papers by Ingfrid Haldorsen
PLOS ONE, 2015
Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metas... more Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.
PURPOSE Our objective was to assess exocrine pancreatic function in healthy controls by secretin ... more PURPOSE Our objective was to assess exocrine pancreatic function in healthy controls by secretin stimulated magnetic resonance cholangiopancreaticography (s-MRCP) and diffusion weighted imaging (DWI), and compare these findings to morphological features i.e. pancreatic volume and fat content. We also aimed to compare pancreatic imaging features with peak bicarbonate concentration. METHOD AND MATERIALS We imaged 20 healthy volunteers of which 10 also underwent secretin stimulated, endoscopic collection of duodenal juice with determination of peak bicarbonate concentration. The MRI (1.5 T) protocol included DWI and coronal T2-weighted images before and 1, 5, 9 and 13 min after secretin, in addition to pre secretin T1- and T2-weighted- and two-point Dixon images. On T2-weighed series we estimated the hyperintense bowel content (regarded as fluid) and multiplied it by its mean signal intensity divided by maximum intensity of pure water (placed adjacent the subjects’ chest). These fluid ...
Research article AIDS-related primary central nervous system lymphoma: a
PURPOSE To evaluate agreement between radiologists on pelvic MR imaging findings of deep myometri... more PURPOSE To evaluate agreement between radiologists on pelvic MR imaging findings of deep myometrial invasion, cervical stroma invasion, and lymph node metastases in endometrial carcinomas, and to compare these imaging findings with final histopathological results. METHOD AND MATERIALS We included 57 histologically confirmed endometrial carcinoma patients in a study of preoperative pelvic 1.5T MR imaging after informed consent and IRB approval. The protocol included axial oblique T1-weighted sequences before and after i.v. contrast injection (2 min delay) and sagittal and axial oblique T2-weighted images. Four radiologists (three consultants with experience in pelvic imaging and one resident), blinded to clinical and histopathological data, independently reviewed the images for presence of deep myometrial invasion, cervical stroma invasion, and lymph node metastases. We calculated kappa-coefficients [with 95% confidence intervals] for interobserver agreement, and sensitivity and spec...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 4, 2015
Prospectively explore the diagnostic value of 2-deoxy-2-[(18)F]fluoroglucose positron emission to... more Prospectively explore the diagnostic value of 2-deoxy-2-[(18)F]fluoroglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) for preoperative staging in endometrial carcinomas. Investigate if (18)F-FDG-PET specific quantitative tumor parameters reflect clinical and histological characteristics. Preoperative (18)F-FDG-PET/CT was prospectively performed in 129 consecutive endometrial carcinoma patients. Two physicians, blinded for clinical findings and staging results, independently reviewed the images assessing primary tumor, cervical stroma involvement and metastatic spread, and measured tumor standardized uptake value (SUV)max, SUVmean and metabolic tumor volume (MTV) with calculation of total lesion glycolysis (TLG). All parameters were analysed in relation to histomorphological and clinical tumor characteristics. Receiver operating characteristics (ROC) curves for identification of deep myometrial invasion and lymph node metastases were generated and MTV cut-o...
Oncotarget, Jan 10, 2015
Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel pr... more Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel proliferation is associated with gene expression profiles or copy number alterations in endometrial cancer. A prospective series of endometrial carcinomas was studied for angiogenesis markers, gene expression profiles, and gene copy number data. For validation, an independent series of endometrial carcinomas as well as an external cohort of endometrial cancer patients were examined by gene expression microarrays. Increased microvessel proliferation (MVP) was associated with aggressive tumor features and reduced survival, and a 32-gene expression signature was found to separate tumors with high versus low MVP. An increased 32-gene signature score was confirmed to associate with high-grade tumor features and reduced survival by independent cohorts. Copy number studies revealed that amplification of the 6p21 region was significantly associated with MVP, a high 32-gene score, as well as reduce...
British journal of cancer, Jan 7, 2014
We aimed to study the angiogenic profile based on histomorphological markers in endometrial carci... more We aimed to study the angiogenic profile based on histomorphological markers in endometrial carcinomas in relation to imaging parameters obtained from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) and to explore the potential value of these markers to identify patients with poor outcome. In fifty-four surgically staged endometrial carcinoma patients, immunohistochemical staining with factor VIII and Ki67 allowed assessment of microvessel density (MVD) and microvascular proliferation reflecting tumour angiogenesis. In the same patients, preoperative pelvic DCE-MRI and DWI allowed the calculation of parameters describing tumour microvasculature and microstructure in vivo. Microvascular proliferation was negatively correlated to tumour blood flow (Fb) (r=-0.36, P=0.008), capillary permeability surface area product (PS) (r=-0.39, P=0.004) and transfer from the blood to extravascular extracellular space (EES) (Ktrans) (r=...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 2000
In order to improve the quality of our activity at the Department of Radiology, Haukeland Univers... more In order to improve the quality of our activity at the Department of Radiology, Haukeland University Hospital, we investigated how the referring clinical departments registered the results from diagnostic imaging. We made a prospective registration of all hospitalized patients who received one or more diagnostic imaging or interventional procedures during a 24-hour period. Starting three months later, we performed a survey of how the radiological reports had been recorded by the referring departments. Results from 11 of a total of 177 examinations (6%) could not be found in the medical records. Altogether 67 examinations (38%) were not mentioned even as a note in the patient files, and 57 examinations (32%) were not mentioned in the final report at discharge. In our opinion this study demonstrates a considerable potential for improvement in making important information more available to doctors, in the hospital and in general practice.
| In neonatal diabetes mellitus resulting from mutations in EIF2AK3, PTF1A, HNF1B, PDX1 or RFX6, ... more | In neonatal diabetes mellitus resulting from mutations in EIF2AK3, PTF1A, HNF1B, PDX1 or RFX6, pancreatic aplasia or hypoplasia is typical. In maturity-onset diabetes mellitus of the young (MODY), mutations in HNF1B result in aplasia of pancreatic body and tail, and mutations in CEL lead to lipomatosis. The pancreas is not readily accessible for histopathological investigations and pancreatic imaging might, therefore, prove important for diagnosis, treatment, and research into these β-cell diseases. Advanced imaging techniques can identify the pancreatic features that are characteristic of these inherited diabetes subtypes, including alterations in organ size (diffuse atrophy and complete or partial pancreatic agenesis), lipomatosis and calcifications. Consequently, in patients with suspected monogenic diabetes mellitus, the results of pancreatic imaging could help guide the molecular and genetic investigation. Imaging findings also highlight the critical roles of specific genes in normal pancreatic development and differentiation and provide new insight into alterations in pancreatic structure that are relevant for β-cell disease.
Lymphoma and Leukemia of the Nervous System, 2010
ABSTRACT Primary central nervous system lymphoma (PCNSL) is commonly lethal, affects vulnerable i... more ABSTRACT Primary central nervous system lymphoma (PCNSL) is commonly lethal, affects vulnerable immunosuppressed populations, and continues to increase in incidence among immunocompetent individuals in several countries. During the last decades, epidemiological studies from different parts of the world have demonstrated varying incidence rates of PCNSL, as well as discrepant findings concerning whether the incidence of PCNSL is increasing or stable. These findings suggest that there may be some factor or factors other than immunodeficiency that either causes or increases the susceptibility of an individual to PCNSL.
The Lancet Oncology, 2012
Most endometrial carcinomas are diagnosed at an early stage. Still, 15-20% of these carcinomas re... more Most endometrial carcinomas are diagnosed at an early stage. Still, 15-20% of these carcinomas recur with limited effect of systemic therapies in metastatic disease. Improved ability to target surgical and systemic therapies to well selected patient populations will increase the likelihood of benefits. Retrospective studies have identified several markers for lymph-node metastasis and poor prognosis. No new targeted treatments are available in the clinic, but recent comprehensive molecular characterisations of tumours have identified drugs targeting the PI3K/PTEN/AKT/mTOR pathway and fibroblast growth factor receptor (FGFR) 2 as promising for further studies, also reflected in current clinical trials investigating endometrial carcinoma. A more systematic approach to integration of biomarkers in surgical trials and clinical trials of therapeutics, earlier characterisation and standardisation of diagnostic imaging and biomarker assessment, and prospective implementation studies are needed for clinical implementation. We summarise the present knowledge regarding biomarkers in endometrial carcinoma, assessing how such markers could be applied to address key clinical challenges for the treatment of this disease.
The Journal of Clinical Endocrinology & Metabolism, 2008
Context: There are interplays between the endocrine and exocrine pancreas. We recently reported a... more Context: There are interplays between the endocrine and exocrine pancreas. We recently reported an increased frequency of exocrine dysfunction in HNF1A-maturity-onset diabetes of the young (MODY3) patients, compared with controls. Reduced pancreatic volume is seen in HNF1B-MODY (MODY5) and diabetes types 1 and 2.
Gynecologic Oncology, 2012
Preoperative identification of cervical stromal invasion in endometrial carcinoma is important to... more Preoperative identification of cervical stromal invasion in endometrial carcinoma is important to select patients for primary radical hysterectomy. The objective of this prospective implementation study was to assess if introduction of magnetic resonance imaging (MRI) in addition to the standardly applied endocervical curettage (ECC), improved the preoperative prediction of cervical stromal invasion. Over a six-year period, a total of 338 patients were surgically staged after preoperative assessment of the uterine cervix by ECC (years 1 through 3), and a combination of MRI and ECC (years 4 through 6). Suggested presence of cervical stromal invasion based on ECC (n=321) and MRI (n=146) were compared for diagnostic performance applying surgical FIGO stage 2009 as reference standard. For assessment of cervical stromal invasion sensitivity (specificity) [accuracy] values were 65% (79%) [77%] for ECC and 59% (91%) [84%] for MRI. Among patients diagnosed with both preoperative tests (n=129), MRI yielded significantly higher specificity (p=0.001) and accuracy (p=0.005) than ECC. MRI independently predicted cervical stromal invasion with an odds ratio (OR) of 11.2 (p<0.001) compared to OR of 2.7 (p=0.07) for ECC. The diagnostic performance of MRI compares favorably to that of ECC for preoperative assessment of cervical stromal invasion in endometrial carcinoma. Thus, the findings in this prospective implementation study support the value of preoperative MRI for assessment of cervical stromal invasion before radical hysterectomy.
European Radiology, 2012
To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of ... more To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases in endometrial carcinoma patients in relation to surgical staging. Fifty-seven patients with histologically confirmed endometrial carcinoma were prospectively included in a study of preoperative 1.5-T MRI. Four radiologists, blinded to patient data, independently reviewed the images for the presence of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Kappa coefficients for interobserver agreement and diagnostic performances for each observer were calculated using final surgical staging results (FIGO 09) as reference standard. Overall agreement among all observers was moderate for cervical stroma invasion (κ = 0.50 [95% CI 0.27-0.73]) and lymph node metastases (κ = 0.56 [0.09-0.80]) and fair for deep myometrial invasion (κ = 0.39 [0.26-0.55]). Sensitivity (specificity) values for the four observers were 72-92% (44-63%) for deep myometrial invasion, 38-63% (82-94%) for cervical stroma invasion and 25-38% (90-100%) for lymph node metastases. Conventional MRI showed only modest interobserver agreement and diagnostic accuracy for detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Improved methods are needed for preoperative imaging in the staging of endometrial carcinomas. MRI is an important tool for preoperative endometrial cancer staging. • Staging agreement based on pelvic MRI was modest among different observers. • Preoperative MRI alone was suboptimal in identifying high-risk patients. • Improved imaging and biomarkers may refine preoperative risk stratification in endometrial cancer.
European Radiology, 2013
To study the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for as... more To study the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of tumour microvasculature in endometrial carcinoma patients, and to explore correlations with histological subtype, clinical course and microstructural characteristics based on apparent diffusion coefficient (ADC) values. Diffusion-weighted imaging (DWI) and three-dimensional DCE-MRI (1.5 T) with high temporal resolution (2.49 s) were acquired preoperatively in 55 patients. Quantitative modelling allowed the calculation of four independent parameters describing microvasculature: blood flow (Fb), extraction fraction (E), capillary transit time (Tc) and transfer constant from the extravascular extracellular space [EES] to blood (Kep); and four derived parameters: blood volume (Vb), volume of EES (Ve), capillary permeability surface area product (PS) and transfer from blood to EES (Ktrans). Endometrial carcinoma tissue exhibited reduced Fb, E, Vb, Ve, PS and Ktrans compared with normal myometrium. Non-endometrioid carcinomas (n = 12) had lower Fb, and E than endometrioid carcinomas (n = 43; P < 0.05). Tumour Ve positively correlated with tumour ADC value (r = 0.29, P = 0.03). Reduced survival was observed in patients with low tumour Fb and high tumour Tc (P < 0.05). We demonstrate the feasibility of DCE-MRI in reflecting histological subtype and clinical course in primary endometrial carcinomas. DCE-MRI may potentially provide future biomarkers for preoperative risk stratification in endometrial carcinomas. • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers new information about endometrial carcinoma. • Pelvic DCE-MRI with subsequent quantitative modelling seems feasible in endometrial carcinoma patients. • Low tumour perfusion is a feature of a more aggressive tumour subtype. • DCE-MRI provides potential biomarkers for preoperative risk stratification in endometrial carcinoma patients.
Diabetic Medicine, 2008
Aims Hepatocyte nuclear factor 1B ( HNF1B ) gene mutation carriers have a systemic disease charac... more Aims Hepatocyte nuclear factor 1B ( HNF1B ) gene mutation carriers have a systemic disease characterized by congenital malformations in the urogenital tract, diabetes mellitus of maturity-onset diabetes of the young type and dysfunction of the liver and exocrine pancreas. We aimed to investigate pancreatic structure and exocrine function in carriers of HNF1B mutations.
Diabetes, 2007
Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. Th... more Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. The underlying molecular and pathological mechanisms are, however, poorly known, and it has been speculated that both features are secondary to diabetes. We have recently described pancreatic atrophy and lipomatosis in diabetic subjects of two Norwegian families with a novel syndrome of diabetes and exocrine pancreatic dysfunction caused by heterozygous carboxyl-ester lipase (CEL) mutations. To explore the early pathological events in this syndrome, we performed radiological examinations of the pancreas in nondiabetic mutation carriers with signs of exocrine dysfunction. In a case series study at a tertiary hospital, we evaluated 11 nondiabetic and mutation-positive children with fecal elastase deficiency and 11 age-and sex-matched control subjects using ultrasound and magnetic resonance imaging (MRI) to estimate pancreatic fat content. The pancreata of nondiabetic mutation carriers exhibited increased reflectivity on ultrasound and had MRI findings indicative of lipomatosis. Apparently, carriers of heterozygous CEL mutations accumulate fat in their pancreas before the anticipated development of diabetes. Our findings suggest that lipomatosis of the pancreas reflects early events involved in the pathogenesis of diabetes and exocrine pancreatic dysfunction syndrome. . MRI, magnetic resonance imaging; VIBE, volume interpolated breath-hold examination.
PLOS ONE, 2015
Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metas... more Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.
PURPOSE Our objective was to assess exocrine pancreatic function in healthy controls by secretin ... more PURPOSE Our objective was to assess exocrine pancreatic function in healthy controls by secretin stimulated magnetic resonance cholangiopancreaticography (s-MRCP) and diffusion weighted imaging (DWI), and compare these findings to morphological features i.e. pancreatic volume and fat content. We also aimed to compare pancreatic imaging features with peak bicarbonate concentration. METHOD AND MATERIALS We imaged 20 healthy volunteers of which 10 also underwent secretin stimulated, endoscopic collection of duodenal juice with determination of peak bicarbonate concentration. The MRI (1.5 T) protocol included DWI and coronal T2-weighted images before and 1, 5, 9 and 13 min after secretin, in addition to pre secretin T1- and T2-weighted- and two-point Dixon images. On T2-weighed series we estimated the hyperintense bowel content (regarded as fluid) and multiplied it by its mean signal intensity divided by maximum intensity of pure water (placed adjacent the subjects’ chest). These fluid ...
Research article AIDS-related primary central nervous system lymphoma: a
PURPOSE To evaluate agreement between radiologists on pelvic MR imaging findings of deep myometri... more PURPOSE To evaluate agreement between radiologists on pelvic MR imaging findings of deep myometrial invasion, cervical stroma invasion, and lymph node metastases in endometrial carcinomas, and to compare these imaging findings with final histopathological results. METHOD AND MATERIALS We included 57 histologically confirmed endometrial carcinoma patients in a study of preoperative pelvic 1.5T MR imaging after informed consent and IRB approval. The protocol included axial oblique T1-weighted sequences before and after i.v. contrast injection (2 min delay) and sagittal and axial oblique T2-weighted images. Four radiologists (three consultants with experience in pelvic imaging and one resident), blinded to clinical and histopathological data, independently reviewed the images for presence of deep myometrial invasion, cervical stroma invasion, and lymph node metastases. We calculated kappa-coefficients [with 95% confidence intervals] for interobserver agreement, and sensitivity and spec...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 4, 2015
Prospectively explore the diagnostic value of 2-deoxy-2-[(18)F]fluoroglucose positron emission to... more Prospectively explore the diagnostic value of 2-deoxy-2-[(18)F]fluoroglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) for preoperative staging in endometrial carcinomas. Investigate if (18)F-FDG-PET specific quantitative tumor parameters reflect clinical and histological characteristics. Preoperative (18)F-FDG-PET/CT was prospectively performed in 129 consecutive endometrial carcinoma patients. Two physicians, blinded for clinical findings and staging results, independently reviewed the images assessing primary tumor, cervical stroma involvement and metastatic spread, and measured tumor standardized uptake value (SUV)max, SUVmean and metabolic tumor volume (MTV) with calculation of total lesion glycolysis (TLG). All parameters were analysed in relation to histomorphological and clinical tumor characteristics. Receiver operating characteristics (ROC) curves for identification of deep myometrial invasion and lymph node metastases were generated and MTV cut-o...
Oncotarget, Jan 10, 2015
Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel pr... more Angiogenesis is a hallmark of cancer. The aim of this study was to explore whether microvessel proliferation is associated with gene expression profiles or copy number alterations in endometrial cancer. A prospective series of endometrial carcinomas was studied for angiogenesis markers, gene expression profiles, and gene copy number data. For validation, an independent series of endometrial carcinomas as well as an external cohort of endometrial cancer patients were examined by gene expression microarrays. Increased microvessel proliferation (MVP) was associated with aggressive tumor features and reduced survival, and a 32-gene expression signature was found to separate tumors with high versus low MVP. An increased 32-gene signature score was confirmed to associate with high-grade tumor features and reduced survival by independent cohorts. Copy number studies revealed that amplification of the 6p21 region was significantly associated with MVP, a high 32-gene score, as well as reduce...
British journal of cancer, Jan 7, 2014
We aimed to study the angiogenic profile based on histomorphological markers in endometrial carci... more We aimed to study the angiogenic profile based on histomorphological markers in endometrial carcinomas in relation to imaging parameters obtained from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) and to explore the potential value of these markers to identify patients with poor outcome. In fifty-four surgically staged endometrial carcinoma patients, immunohistochemical staining with factor VIII and Ki67 allowed assessment of microvessel density (MVD) and microvascular proliferation reflecting tumour angiogenesis. In the same patients, preoperative pelvic DCE-MRI and DWI allowed the calculation of parameters describing tumour microvasculature and microstructure in vivo. Microvascular proliferation was negatively correlated to tumour blood flow (Fb) (r=-0.36, P=0.008), capillary permeability surface area product (PS) (r=-0.39, P=0.004) and transfer from the blood to extravascular extracellular space (EES) (Ktrans) (r=...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 2000
In order to improve the quality of our activity at the Department of Radiology, Haukeland Univers... more In order to improve the quality of our activity at the Department of Radiology, Haukeland University Hospital, we investigated how the referring clinical departments registered the results from diagnostic imaging. We made a prospective registration of all hospitalized patients who received one or more diagnostic imaging or interventional procedures during a 24-hour period. Starting three months later, we performed a survey of how the radiological reports had been recorded by the referring departments. Results from 11 of a total of 177 examinations (6%) could not be found in the medical records. Altogether 67 examinations (38%) were not mentioned even as a note in the patient files, and 57 examinations (32%) were not mentioned in the final report at discharge. In our opinion this study demonstrates a considerable potential for improvement in making important information more available to doctors, in the hospital and in general practice.
| In neonatal diabetes mellitus resulting from mutations in EIF2AK3, PTF1A, HNF1B, PDX1 or RFX6, ... more | In neonatal diabetes mellitus resulting from mutations in EIF2AK3, PTF1A, HNF1B, PDX1 or RFX6, pancreatic aplasia or hypoplasia is typical. In maturity-onset diabetes mellitus of the young (MODY), mutations in HNF1B result in aplasia of pancreatic body and tail, and mutations in CEL lead to lipomatosis. The pancreas is not readily accessible for histopathological investigations and pancreatic imaging might, therefore, prove important for diagnosis, treatment, and research into these β-cell diseases. Advanced imaging techniques can identify the pancreatic features that are characteristic of these inherited diabetes subtypes, including alterations in organ size (diffuse atrophy and complete or partial pancreatic agenesis), lipomatosis and calcifications. Consequently, in patients with suspected monogenic diabetes mellitus, the results of pancreatic imaging could help guide the molecular and genetic investigation. Imaging findings also highlight the critical roles of specific genes in normal pancreatic development and differentiation and provide new insight into alterations in pancreatic structure that are relevant for β-cell disease.
Lymphoma and Leukemia of the Nervous System, 2010
ABSTRACT Primary central nervous system lymphoma (PCNSL) is commonly lethal, affects vulnerable i... more ABSTRACT Primary central nervous system lymphoma (PCNSL) is commonly lethal, affects vulnerable immunosuppressed populations, and continues to increase in incidence among immunocompetent individuals in several countries. During the last decades, epidemiological studies from different parts of the world have demonstrated varying incidence rates of PCNSL, as well as discrepant findings concerning whether the incidence of PCNSL is increasing or stable. These findings suggest that there may be some factor or factors other than immunodeficiency that either causes or increases the susceptibility of an individual to PCNSL.
The Lancet Oncology, 2012
Most endometrial carcinomas are diagnosed at an early stage. Still, 15-20% of these carcinomas re... more Most endometrial carcinomas are diagnosed at an early stage. Still, 15-20% of these carcinomas recur with limited effect of systemic therapies in metastatic disease. Improved ability to target surgical and systemic therapies to well selected patient populations will increase the likelihood of benefits. Retrospective studies have identified several markers for lymph-node metastasis and poor prognosis. No new targeted treatments are available in the clinic, but recent comprehensive molecular characterisations of tumours have identified drugs targeting the PI3K/PTEN/AKT/mTOR pathway and fibroblast growth factor receptor (FGFR) 2 as promising for further studies, also reflected in current clinical trials investigating endometrial carcinoma. A more systematic approach to integration of biomarkers in surgical trials and clinical trials of therapeutics, earlier characterisation and standardisation of diagnostic imaging and biomarker assessment, and prospective implementation studies are needed for clinical implementation. We summarise the present knowledge regarding biomarkers in endometrial carcinoma, assessing how such markers could be applied to address key clinical challenges for the treatment of this disease.
The Journal of Clinical Endocrinology & Metabolism, 2008
Context: There are interplays between the endocrine and exocrine pancreas. We recently reported a... more Context: There are interplays between the endocrine and exocrine pancreas. We recently reported an increased frequency of exocrine dysfunction in HNF1A-maturity-onset diabetes of the young (MODY3) patients, compared with controls. Reduced pancreatic volume is seen in HNF1B-MODY (MODY5) and diabetes types 1 and 2.
Gynecologic Oncology, 2012
Preoperative identification of cervical stromal invasion in endometrial carcinoma is important to... more Preoperative identification of cervical stromal invasion in endometrial carcinoma is important to select patients for primary radical hysterectomy. The objective of this prospective implementation study was to assess if introduction of magnetic resonance imaging (MRI) in addition to the standardly applied endocervical curettage (ECC), improved the preoperative prediction of cervical stromal invasion. Over a six-year period, a total of 338 patients were surgically staged after preoperative assessment of the uterine cervix by ECC (years 1 through 3), and a combination of MRI and ECC (years 4 through 6). Suggested presence of cervical stromal invasion based on ECC (n=321) and MRI (n=146) were compared for diagnostic performance applying surgical FIGO stage 2009 as reference standard. For assessment of cervical stromal invasion sensitivity (specificity) [accuracy] values were 65% (79%) [77%] for ECC and 59% (91%) [84%] for MRI. Among patients diagnosed with both preoperative tests (n=129), MRI yielded significantly higher specificity (p=0.001) and accuracy (p=0.005) than ECC. MRI independently predicted cervical stromal invasion with an odds ratio (OR) of 11.2 (p<0.001) compared to OR of 2.7 (p=0.07) for ECC. The diagnostic performance of MRI compares favorably to that of ECC for preoperative assessment of cervical stromal invasion in endometrial carcinoma. Thus, the findings in this prospective implementation study support the value of preoperative MRI for assessment of cervical stromal invasion before radical hysterectomy.
European Radiology, 2012
To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of ... more To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases in endometrial carcinoma patients in relation to surgical staging. Fifty-seven patients with histologically confirmed endometrial carcinoma were prospectively included in a study of preoperative 1.5-T MRI. Four radiologists, blinded to patient data, independently reviewed the images for the presence of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Kappa coefficients for interobserver agreement and diagnostic performances for each observer were calculated using final surgical staging results (FIGO 09) as reference standard. Overall agreement among all observers was moderate for cervical stroma invasion (κ = 0.50 [95% CI 0.27-0.73]) and lymph node metastases (κ = 0.56 [0.09-0.80]) and fair for deep myometrial invasion (κ = 0.39 [0.26-0.55]). Sensitivity (specificity) values for the four observers were 72-92% (44-63%) for deep myometrial invasion, 38-63% (82-94%) for cervical stroma invasion and 25-38% (90-100%) for lymph node metastases. Conventional MRI showed only modest interobserver agreement and diagnostic accuracy for detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Improved methods are needed for preoperative imaging in the staging of endometrial carcinomas. MRI is an important tool for preoperative endometrial cancer staging. • Staging agreement based on pelvic MRI was modest among different observers. • Preoperative MRI alone was suboptimal in identifying high-risk patients. • Improved imaging and biomarkers may refine preoperative risk stratification in endometrial cancer.
European Radiology, 2013
To study the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for as... more To study the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for assessment of tumour microvasculature in endometrial carcinoma patients, and to explore correlations with histological subtype, clinical course and microstructural characteristics based on apparent diffusion coefficient (ADC) values. Diffusion-weighted imaging (DWI) and three-dimensional DCE-MRI (1.5 T) with high temporal resolution (2.49 s) were acquired preoperatively in 55 patients. Quantitative modelling allowed the calculation of four independent parameters describing microvasculature: blood flow (Fb), extraction fraction (E), capillary transit time (Tc) and transfer constant from the extravascular extracellular space [EES] to blood (Kep); and four derived parameters: blood volume (Vb), volume of EES (Ve), capillary permeability surface area product (PS) and transfer from blood to EES (Ktrans). Endometrial carcinoma tissue exhibited reduced Fb, E, Vb, Ve, PS and Ktrans compared with normal myometrium. Non-endometrioid carcinomas (n = 12) had lower Fb, and E than endometrioid carcinomas (n = 43; P < 0.05). Tumour Ve positively correlated with tumour ADC value (r = 0.29, P = 0.03). Reduced survival was observed in patients with low tumour Fb and high tumour Tc (P < 0.05). We demonstrate the feasibility of DCE-MRI in reflecting histological subtype and clinical course in primary endometrial carcinomas. DCE-MRI may potentially provide future biomarkers for preoperative risk stratification in endometrial carcinomas. • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers new information about endometrial carcinoma. • Pelvic DCE-MRI with subsequent quantitative modelling seems feasible in endometrial carcinoma patients. • Low tumour perfusion is a feature of a more aggressive tumour subtype. • DCE-MRI provides potential biomarkers for preoperative risk stratification in endometrial carcinoma patients.
Diabetic Medicine, 2008
Aims Hepatocyte nuclear factor 1B ( HNF1B ) gene mutation carriers have a systemic disease charac... more Aims Hepatocyte nuclear factor 1B ( HNF1B ) gene mutation carriers have a systemic disease characterized by congenital malformations in the urogenital tract, diabetes mellitus of maturity-onset diabetes of the young type and dysfunction of the liver and exocrine pancreas. We aimed to investigate pancreatic structure and exocrine function in carriers of HNF1B mutations.
Diabetes, 2007
Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. Th... more Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. The underlying molecular and pathological mechanisms are, however, poorly known, and it has been speculated that both features are secondary to diabetes. We have recently described pancreatic atrophy and lipomatosis in diabetic subjects of two Norwegian families with a novel syndrome of diabetes and exocrine pancreatic dysfunction caused by heterozygous carboxyl-ester lipase (CEL) mutations. To explore the early pathological events in this syndrome, we performed radiological examinations of the pancreas in nondiabetic mutation carriers with signs of exocrine dysfunction. In a case series study at a tertiary hospital, we evaluated 11 nondiabetic and mutation-positive children with fecal elastase deficiency and 11 age-and sex-matched control subjects using ultrasound and magnetic resonance imaging (MRI) to estimate pancreatic fat content. The pancreata of nondiabetic mutation carriers exhibited increased reflectivity on ultrasound and had MRI findings indicative of lipomatosis. Apparently, carriers of heterozygous CEL mutations accumulate fat in their pancreas before the anticipated development of diabetes. Our findings suggest that lipomatosis of the pancreas reflects early events involved in the pathogenesis of diabetes and exocrine pancreatic dysfunction syndrome. . MRI, magnetic resonance imaging; VIBE, volume interpolated breath-hold examination.