Publications by authors named "Martin Biermann"

38 Publications

Gastroparesis Symptoms Associated with Intestinal Hypomotility: An Explorative Study Using Wireless Motility Capsule.

Clin Exp Gastroenterol 2021 28;14:133-144. Epub 2021 Apr 28.

Norwegian Competence Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.

Objective: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule.

Patients And Methods: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI).

Results: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric ( = -0.31, = 0.007), small bowel ( = -0.41, < 0.001) and colonic ( = -0.33, = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index ( = -0.81, < 0.001) and mean stomach pressure ( = -0.64, = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel ( = -0.77, < 0.001) and colon ( = -0.74, = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index ( = -0.34, = 0.012), and mean pressure of the colon correlated with upper abdominal pain ( = -0.37, = 0.007). We found no association between symptoms, gastric emptying nor any other transit times.

Conclusion: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.
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http://dx.doi.org/10.2147/CEG.S304854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088984PMC
April 2021

An Open Source Solution for "Hands-on" teaching of PET/CT to Medical Students under the COVID-19 Pandemic.

Nuklearmedizin 2021 Feb 26;60(1):10-15. Epub 2020 Oct 26.

Department of Education, University of Bergen Faculty of Humanities, Bergen, Norway.

Aims:  Since 2017, medical students at the University of Bergen were taught PET/CT "hands-on" by viewing PET/CT cases in native format on diagnostic workstations in the hospital. Due to the COVID-19 pandemic, students were barred access. This prompted us to launch and evaluate a new freeware PET/CT viewing system hosted in the university network.

Methods:  We asked our students to install the multiplatform Fiji viewer with Beth Israel PET/CT plugin (http://petctviewer.org) on their personal computers and connect to a central image database in the university network based on the public domain orthanc server (https://orthanc-server.com). At the end of course, we conducted an anonymous student survey.

Results:  The new system was online within eight days, including regulatory approval. All 76 students (100 %) in the fifth year completed their course work, reading five anonymized PET/CT cases as planned. 41 (53 %) students answered the survey. Fiji was challenging to install with a mean score of 1.8 on a 5-point Likert scale (5 = easy, 1 = difficult). Fiji was more difficult to use (score 3.0) than the previously used diagnostic workstations in the hospital (score 4.1; p < 0.001, paired t-test). Despite the technical challenge, 47 % of students reported having learnt much (scores 4 and 5); only 11 % were negative (scores 1 and 2). 51 % found the PET/CT tasks engaging (scores 4 and 5) while 20 % and 5 % returned scores 2 and 1, respectively.

Conclusion:  Despite the initial technical challenge, "hands-on" learning of PET/CT based on the freeware Fiji/orthanc PET/CT-viewer was associated with a high degree of student satisfaction. We plan to continue running the system to give students permanent access to PET/CT cases in native format regardless of time or location.
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http://dx.doi.org/10.1055/a-1267-9017DOI Listing
February 2021

Multimodal imaging of thyroid cancer.

Curr Opin Endocrinol Diabetes Obes 2020 10;27(5):335-344

Nuclear Medicine/PET-center, Department of Radiology, Haukeland University Hospital.

Purpose Of Review: Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls.

Recent Findings: Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer.

Summary: The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [F]FDOPA and [Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.
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http://dx.doi.org/10.1097/MED.0000000000000574DOI Listing
October 2020

Assessing Extraprostatic Extension with Multiparametric MRI of the Prostate: Mehralivand Extraprostatic Extension Grade or Extraprostatic Extension Likert Scale?

Radiol Imaging Cancer 2020 01 17;2(1):e190071. Epub 2020 Jan 17.

Departments of Radiology (L.A.R.R., A.L., J.M., M.B.), Pathology (O.J.H., K.G., L.A.A.), and Urology (C.B., A.H.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine (L.A.R.R., C.B., A.L., M.B.) and Centre for Cancer Biomarkers CCBIO (O.J.H., L.A.A.), University of Bergen, Jonas Liesvei 65, N-5021 Bergen, Norway.

Purpose: To validate the MRI grading system proposed by Mehralivand et al in 2019 (the "extraprostatic extension [EPE] grade") in an independent cohort and to compare the Mehralivand EPE grading system with EPE interpretation on the basis of a five-point Likert score ("EPE Likert").

Materials And Methods: A total of 310 consecutive patients underwent multiparametric MRI according to a standardized institutional protocol before radical prostatectomy was performed by using the same 1.5-T MRI unit at a single institution between 2010 and 2012. Two radiologists blinded to clinical information assessed EPE according to standardized criteria. On the basis of the readings performed until 2017, the diagnostic performance of EPE Likert and Mehralivand EPE score were compared using receiver operating characteristics (ROC) and decision curve methodology against histologic EPE as standard of reference. Prediction of biochemical recurrence-free survival (BRFS) was assessed by Kaplan-Meier analysis and log rank test.

Results: Of the 310 patients, 80 patients (26%) had EPE, including 33 with radial distance 1.1 mm or greater. Interrater reliability was fair (weighted κ 0.47 and 0.45) for both EPE grade and EPE Likert. Sensitivity for identifying EPE using EPE grade versus EPE Likert was 0.83 versus 0.86 and 0.86 versus 0.91 for radiologist 1 and 2, respectively. Specificity was 0.48 versus 0.58 and 0.39 versus 0.70 ( < .05 for radiologist 2). There were no significant differences in the ROC area under the curve or on decision curve analysis. Both EPE grade and EPE Likert were significant predictors of BRFS.

Conclusion: Mehralivand EPE grade and EPE Likert have equivalent diagnostic performance for predicting EPE and BRFS with a similar degree of observer dependence.© RSNA, 2020 MR-Imaging, Neoplasms-Primary, Observer Performance, Outcomes Analysis, Prostate, StagingSee also the commentary by Choyke in this issue.
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http://dx.doi.org/10.1148/rycan.2019190071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983691PMC
January 2020

Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis.

Neurogastroenterol Motil 2020 04 30;32(4):e13771. Epub 2019 Dec 30.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Background: Gastroparesis is a potentially severe late complication of diabetes mellitus. Today, delayed gastric emptying (GE) is mandatory for establishing the diagnosis. In this study, we compared wireless motility capsule (WMC) with gastric emptying scintigraphy (GES).

Methods: Seventy-two patients (49 women) with diabetes mellitus (59 type 1) and symptoms compatible with gastroparesis were prospectively included between 2014 and 2018. Patients were simultaneously examined with GES and WMC. Symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) questionnaire. All patients were on intravenous glucose-insulin infusion during testing.

Key Results: WMC and GES correlated r = .74, P < .001. Compared to GES, WMC at ordinary cutoff for delayed GE (300 minutes) had a sensitivity of 0.92, specificity 0.73, accuracy 0.80, and Cohen's kappa κ = 0.61 (P < .001). By receiver operating characteristics (ROC), the area under the curve was 0.95 (P < .001). A cutoff value for delayed GE of 385 minutes produced sensitivity 0.92, specificity 0.83, accuracy 0.86, and Cohen's kappa κ = 0.72 (P < .001). Inter-rater reliability for GE time with WMC was r = .996, κ = 0.97, both P < .001. There was no difference in symptom severity between patients with normal and delayed GE.

Conclusions & Inferences: Our findings demonstrate the applicability of WMC as a reliable test to assess gastric emptying in diabetic gastroparesis showing very high inter-observer correlation. By elevating the cutoff value for delayed emptying from 300 to 385 minutes, we found higher specificity without reducing sensitivity.
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http://dx.doi.org/10.1111/nmo.13771DOI Listing
April 2020

Evaluation of a new e-learning framework for teaching nuclear medicine and radiology to undergraduate medical students.

Acta Radiol Open 2019 Jul 18;8(7):2058460119860231. Epub 2019 Jul 18.

Nuclear Medicine/PET Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.

Background: Radiology and nuclear medicine have traditionally been taught in a series of lectures and seminars concluded by an examination testing knowledge rather than skills.

Purpose: To emphasize skills in the students' learning process, we developed and evaluated a new e-learning framework for teaching medical imaging.

Material And Methods: The framework consists of electronic lectures, a learning management system (LMS), and a diagnostic viewing system. Students were to review positron emission tomography/computed tomography (PET/CT) examinations of five cases of lung cancer. The framework was evaluated in an objective structured clinical examination (OSCE) taken by 139 undergraduate students at the end of their third year, and in a comparative survey of two groups of 85 and 84 students in the fifth and sixth year who were taught the same oncology course with and without mandatory PET/CT exercises, respectively.

Results: Of the 139 third-year students, 134 (96%) passed the OSCE PET/CT station according to the predefined criteria. While 85/85 (100%) of the fifth-year students had taken exercises when they were mandatory, only 2/84 (2%) of the sixth-year students had reviewed the cases on a voluntary basis ( < 0.001). Of the 25 survey responders in the fifth year, 24 (96%) agreed that the mandatory PET/CT exercises had promoted their learning while the sixth-year students, whose course concluded with a multiple-choice examination, emphasized the utility of online lectures.

Conclusion: The new e-learning framework teaches students basic competency in PET/CT navigation and interpretation and is associated with a high degree of student satisfaction.
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http://dx.doi.org/10.1177/2058460119860231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640061PMC
July 2019

Adrenal Venous Sampling for Assessment of Autonomous Cortisol Secretion.

J Clin Endocrinol Metab 2018 12;103(12):4553-4560

Department of Clinical Science, University of Bergen, Bergen, Norway.

Context: Autonomous cortisol secretion (ACS) can be unilateral or bilateral irrespective of the presence of an adrenal tumor. A reliable method to distinguish between unilateral and bilateral ACS is lacking.

Objective: Evaluate the use of adrenal venous sampling (AVS) to distinguish between unilateral and bilateral ACS.

Design And Methods: This was a prospective study of AVS in patients with adrenal tumors who received a diagnosis of ACS or adrenal Cushing syndrome (CS). Unilateral secretion was defined as >2.3-fold difference in cortisol levels between the two adrenal veins. Metanephrine levels were used to ascertain correct catheter position. Results were correlated with findings on CT and iodine-131-cholesterol scintigraphy.

Results: Thirty-nine patients underwent AVS; there were no complications. The procedure was inconclusive in six patients and repeated with success in one, giving a success rate of 85%, and leaving 34 procedures for evaluation (adrenal CS, n = 2; ACS, n = 32). Of 14 patients with bilateral tumors, 10 had bilateral and 4 had unilateral overproduction. Of 20 patients with unilateral tumors, 11 had lateralization to the side of the tumor and the remaining had bilateral secretion. Cholesterol scintigraphy findings were concordant with those of AVS in 13 of 18 cases (72%) and discordant in 5 (28%).

Conclusion: Laterality of ACS does not always correspond to findings on CT images. AVS is a safe and valuable tool for differentiation between unilateral and bilateral cortisol secretion and should be considered when operative treatment of ACS is a possibility.
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http://dx.doi.org/10.1210/jc.2018-01198DOI Listing
December 2018

Optimising preoperative risk stratification tools for prostate cancer using mpMRI.

Eur Radiol 2018 Mar 6;28(3):1016-1026. Epub 2017 Oct 6.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Purpose: To improve preoperative risk stratification for prostate cancer (PCa) by incorporating multiparametric MRI (mpMRI) features into risk stratification tools for PCa, CAPRA and D'Amico.

Methods: 807 consecutive patients operated on by robot-assisted radical prostatectomy at our institution during the period 2010-2015 were followed to identify biochemical recurrence (BCR). 591 patients were eligible for final analysis. We employed stepwise backward likelihood methodology and penalised Cox cross-validation to identify the most significant predictors of BCR including mpMRI features. mpMRI features were then integrated into image-adjusted (IA) risk prediction models and the two risk prediction tools were then evaluated both with and without image adjustment using receiver operating characteristics, survival and decision curve analyses.

Results: 37 patients suffered BCR. Apparent diffusion coefficient (ADC) and radiological extraprostatic extension (rEPE) from mpMRI were both significant predictors of BCR. Both IA prediction models reallocated more than 20% of intermediate-risk patients to the low-risk group, reducing their estimated cumulative BCR risk from approximately 5% to 1.1%. Both IA models showed improved prognostic performance with a better separation of the survival curves.

Conclusion: Integrating ADC and rEPE from mpMRI of the prostate into risk stratification tools improves preoperative risk estimation for BCR.

Key Points: • MRI-derived features, ADC and EPE, improve risk stratification of biochemical recurrence. • Using mpMRI to stratify prostate cancer patients improves the differentiation between risk groups. • Using preoperative mpMRI will help urologists in selecting the most appropriate treatment.
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http://dx.doi.org/10.1007/s00330-017-5031-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811593PMC
March 2018

Injury mechanisms and electromyographic changes after injury of the recurrent laryngeal nerve: Experiments in a porcine model.

Head Neck 2018 02 30;40(2):274-282. Epub 2017 Sep 30.

Department of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.

Background: Recurrent laryngeal nerve (RLN) injury during surgery may reveal differences in electromyographic (EMG) changes after sustained compression or traction.

Methods: In 20 pigs with the NIM-FLEX EMG-endotracheal tube, EMG was recorded at baseline, during sustained RLN compression, or traction until 70% amplitude decrease and during 30 minutes of recovery.

Results: Seventy percent amplitude decrease from baseline was reached after 110 ± 98 seconds (compression group) and 2034 ± 2108 seconds (traction group). Traction induced a pronounced latency increase, peaking at 122 ± 8% in contrast to compression with 106 ± 5% (P < .001). The EMG amplitude recovery to ≥50% of baseline failed in 7 nerves after compression and 8 nerves after traction.

Conclusion: Compression caused a fast decrease of EMG amplitude with minor effects on latency. In contrast, RLN traction showed early and significant latency increase preceding a delayed amplitude decrease. Recovery rate of the EMG signals were similar in both groups.
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http://dx.doi.org/10.1002/hed.24940DOI Listing
February 2018

E-learning for medical imaging specialists: introducing blended learning in a nuclear medicine specialist course.

Acta Radiol Open 2017 Jul 25;6(7):2058460117720858. Epub 2017 Jul 25.

Nuclear Medicine and PET Center, Department of Radiology, Haukeland University Hospital, Bergen, Norway.

Background: While e-learning has become an important tool in teaching medical students, the training of specialists in medical imaging is still dominated by lecture-based courses.

Purpose: To assess the potential of e-learning in specialist education in medical imaging.

Material And Methods: An existing lecture-based five-day course in Clinical Nuclear Medicine (NM) was enhanced by e-learning resources and activities, including practical exercises. An anonymized survey was conducted after participants had completed and passed the multiple choice electronic course examination.

Results: Twelve out of 15 course participants (80%) responded. Overall satisfaction with the new course format was high, but 25% of the respondents wanted more interactive elements such as discussions and practical exercises. The importance of lecture handouts and supplementary online material such as selected original articles and professional guidelines was affirmed by all the respondents (92% fully, 8% partially), while 75% fully and 25% partially agreed that the lectures had been interesting and relevant.

Conclusion: E-learning represents a hitherto unrealized potential in the education of medical specialists. It may expedite training of medical specialists while at the same time containing costs.
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http://dx.doi.org/10.1177/2058460117720858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533268PMC
July 2017

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

Pediatr Radiol 2017 Jan 4;47(1):82-88. Epub 2016 Nov 4.

Department of Radiology, Paediatric Section, Haukeland University Hospital, Bergen, Norway.

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

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

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

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

Conclusion: There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT.
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http://dx.doi.org/10.1007/s00247-016-3720-xDOI Listing
January 2017

A human clinical trial using ultrasound and microbubbles to enhance gemcitabine treatment of inoperable pancreatic cancer.

J Control Release 2016 12 12;243:172-181. Epub 2016 Oct 12.

National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Background: The primary aim of our study was to evaluate the safety and potential toxicity of gemcitabine combined with microbubbles under sonication in inoperable pancreatic cancer patients. The secondary aim was to evaluate a novel image-guided microbubble-based therapy, based on commercially available technology, towards improving chemotherapeutic efficacy, preserving patient performance status, and prolonging survival.

Methods: Ten patients were enrolled and treated in this Phase I clinical trial. Gemcitabine was infused intravenously over 30min. Subsequently, patients were treated using a commercial clinical ultrasound scanner for 31.5min. SonoVue® was injected intravenously (0.5ml followed by 5ml saline every 3.5min) during the ultrasound treatment with the aim of inducing sonoporation, thus enhancing therapeutic efficacy.

Results: The combined therapeutic regimen did not induce any additional toxicity or increased frequency of side effects when compared to gemcitabine chemotherapy alone (historical controls). Combination treated patients (n=10) tolerated an increased number of gemcitabine cycles compared with historical controls (n=63 patients; average of 8.3±6.0cycles, versus 13.8±5.6cycles, p=0.008, unpaired t-test). In five patients, the maximum tumour diameter was decreased from the first to last treatment. The median survival in our patients (n=10) was also increased from 8.9months to 17.6months (p=0.011).

Conclusions: It is possible to combine ultrasound, microbubbles, and chemotherapy in a clinical setting using commercially available equipment with no additional toxicities. This combined treatment may improve the clinical efficacy of gemcitabine, prolong the quality of life, and extend survival in patients with pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1016/j.jconrel.2016.10.007DOI Listing
December 2016

F-18-FDG PET-CT in children and young adults with Ewing sarcoma diagnosed in Norway during 2005-2012: a national population-based study.

Clin Physiol Funct Imaging 2016 Nov 3;36(6):441-446. Epub 2015 Jun 3.

Pediatric Section, Department of Radiology, Haukeland University Hospital, Bergen, Norway.

Background: To examine national imaging strategies regarding the use of F-18-FDG PET-CT in patients with Ewing sarcoma and study factors that might influence the use of PET-CT, such as tumour biology (Picci grade of operation specimen), clinical disease stage and age.

Methods: We examined the medical records including pathology and imaging of all patients below 30 years diagnosed with Ewing sarcoma in Norway in 2005-2012.

Results: Of 61 patients treated at one of the two national sarcoma treatment service centres (Oslo: 35, Bergen: 26), 29 patients had localized disease, 8 had tumour extending to organs nearby and 24 had metastases. Among 35 operated patients with neoadjuvant chemotherapy, 15 had Picci grades II and III (good responders) and 20 grade I (poor responders). We found a significant difference in the use of PET-CT (Oslo/Bergen 0·9 versus 2·0 scans per patient, P = 0·010) and in the use of MRI (Oslo/Bergen: eight versus 13, P = 0·006). No differences were proven for ultrasound, radiography, CT or skeletal scintigraphy. The number of PET-CTs was associated with clinical disease stage at diagnosis (P = 0·041) but not with Picci grade or age. The number of PET studies was not correlated to the number of MR studies.

Conclusions: The use of PET-CT in children and young adults diagnosed with Ewing sarcoma in Norway during 2005-2012 at the two national sarcoma treatment service centres differed significantly. The use of PET-CT imaging was related to the clinical disease stage at diagnosis but unrelated to patient age and tumour biology (Picci grade).
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http://dx.doi.org/10.1111/cpf.12247DOI Listing
November 2016

[Gastroparesis - causes, diagnosis and treatment].

Tidsskr Nor Laegeforen 2016 May 24;136(9):822-6. Epub 2016 May 24.

Gastroenterologisk seksjon Medisinsk avdeling Haukeland universitetssykehus og Klinisk institutt 1 Universitetet i Bergen.

BACKGROUND Gastroparesis is a motility disorder of the stomach. The symptoms are non-specific: nausea and vomiting are most common. Stomach pains, early satiety, postprandial fullness and bloating are also frequent symptoms. Current diagnostic criteria require delayed gastric emptying in the absence of any detectable mechanical obstruction. In this review article we elucidate the causes, assessment and treatment options.MATERIAL AND METHOD Structured article search in Embase and PubMed.RESULTS A number of conditions can lead to gastroparesis. The most frequent somatic cause is diabetes mellitus. Gastroparesis may also be iatrogenically inflicted by means of surgery or drugs. It may be difficult to discriminate between functional dyspepsia and idiopathic gastroparesis. Examination is based on patient history, gastroscopy and measurement of the rate of gastric emptying. Biochemical tests are also relevant for differential diagnosis. The treatment is primarily symptomatic, and consists of dietary measures, fluid therapy, drugs, gastric electrical stimulation, or endoscopic or surgical intervention in the form of insertion of a feeding tube for nutrition and abdominal relief, pyloroplasty or gastrectomy.INTERPRETATION Gastroparesis is a serious motility disorder. The condition may have significant consequences for patients, entailing reduced quality of life, reduced workforce participation and a considerable need for health assistance.
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http://dx.doi.org/10.4045/tidsskr.15.0503DOI Listing
May 2016

EMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine model.

Langenbecks Arch Surg 2017 Jun 16;402(4):675-681. Epub 2016 Apr 16.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Purpose: Traction is the most common cause of injury to the recurrent laryngeal nerve (RLN) in endocrine neck surgery. The purpose of this study was to evaluate specific alterations to the electromyogram (EMG) and verify safe alarm limits in a porcine model of sustained traction of the RLN using continuous intraoperative neuromonitoring (C-IONM).

Methods: Sixteen Norwegian Landrace pigs were anesthetized and intubated with a tracheal tube with a stick-on laryngeal electrode. EMG was recorded at baseline (BL) and during sustained traction applied to each RLN until 70 % amplitude decrease from BL, and during 30-min recovery.

Results: In 29 nerves at risk (NAR), BL amplitude and latency values were 1098 ± 418 (586-2255) μV (mean ± SD (range)) (right vagus) and 845 ± 289 (522-1634) μV (left vagus), and 4.7 ± 0.5 (4.1-5.9) ms and 7.9 ± 0.8 (6.7-9.6) ms, respectively. At 50 % amplitude decrease, latency increased by 14.0 ± 5.7 % (right side) and 14.5 ± 9.1 % (left side) compared with BL. Corresponding values for 70 % amplitude depression were 17.9 ± 6.1 % and 17.3 ± 12.8 %. Traction time to 50 and 70 % amplitude decrease ranged from 3 to 133 min and 3.9-141 min, respectively. In 16 NAR (55 %), time from 50 to 70 % reduction in amplitude was ≤5 min, but in six NAR (21 %) ≤1 min. In only 11 (38 %) of 29 nerves, the amplitude recovered to more than 50 % of BL.

Conclusions: Latency increase may be the first warning of RLN stretch injury. Given the short interval between 50 and 70 % amplitude reduction of the EMG, amplitude reduction by 50 % can be taken as an appropriate alert limit.
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http://dx.doi.org/10.1007/s00423-016-1419-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437198PMC
June 2017

Mitochondrial DNA homeostasis is essential for nigrostriatal integrity.

Mitochondrion 2016 05 12;28:33-7. Epub 2016 Mar 12.

Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Norway.

Mitochondrial involvement in the pathogenesis of Parkinson's disease has been suggested by multiple studies, but the mechanisms involved remain unresolved. Here, we sought to identify which mitochondrial defects are associated with degeneration of the nigrostriatal system. Nigrostriatal integrity was assessed in vivo by dopamine transporter (DAT) imaging in twenty-one patients with mitochondrial disorders of different molecular aetiology including: maternally inherited mitochondrial DNA (mtDNA) point mutations, primary single mtDNA deletions, nuclear-encoded disorders of mtDNA replication and maintenance due to mutations in POLG or C10orf2 (Twinkle), and mutations in other nuclear mitochondrial genes including the mitochondrial aspartyl-tRNA synthetase (DARS2) and ADCK3 genes. Patients with mitochondrial disease were compared with twenty patients with Parkinson's disease and eighteen controls. Nigrostriatal degeneration occurred exclusively in patients with defective mtDNA replication and maintenance. In these patients, nigrostriatal degeneration was progressive and at least as severe as in patients with advanced Parkinson's disease. None of the patients with other mitochondrial defects showed evidence of nigral involvement. Our findings demonstrate that dopaminergic neurons of the substantia nigra are specifically vulnerable to defective mtDNA replication/repair or quality control and not to primary point mutations of mtDNA. These results support the hypothesis that accumulating somatic mtDNA damage plays an important role in neurodegeneration.
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http://dx.doi.org/10.1016/j.mito.2016.03.003DOI Listing
May 2016

Impact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgery.

World J Surg 2016 Mar;40(3):672-80

Department of Surgery, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.

Background: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high-risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence.

Methods: Fifty-five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high-risk endocrine neck surgery. CIONM was performed using the commercially available NIM-Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded.

Results: APS malfunction occurred on three sides (3%). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34%) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66%) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42%) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients.

Conclusions: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high-risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time.
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http://dx.doi.org/10.1007/s00268-015-3368-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746223PMC
March 2016

Introduction of positron emission tomography into the Western Norwegian Health Region: Regional balance in resource utilization from 2009 to 2014.

Clin Physiol Funct Imaging 2017 Sep 17;37(5):512-517. Epub 2015 Dec 17.

Nuclear Medicine/PET-centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.

Background: The aim was to compare resource utilization across the four health trusts within the Western Norway Regional Health Authority since the establishment of positron emission tomography (PET) at Haukeland University Hospital in Bergen in 2009.

Methods: Metadata from all PET examinations from 2009 to 2014 were automatically imported from the PET centre's central production database into a custom-developed database system, MDCake. A PET examination was defined as a procedure based on a single injection of radioactive tracer. The patients' place of residence and tentative diagnosis were coded based on the available clinical information.

Results: The total number of PET examinations increased from 293 in 2009 to 1616 in 2014. The number of PET examinations per year increased across all diagnostic groups, but plateaued for lung cancer, gastrointestinal cancer and malignant melanoma since 2013. The number of examinations per capita was evenly distributed between the three northern health trusts with an average of 1260 PET studies per million inhabitants in 2014. However, patients residing in the most southerly health trust received between 44% (2010) and 27% (2014; P<0·001, repeated measures ANOVA) fewer examinations per capita per year.

Conclusion: Centralized PET in the Western Norwegian health region meets the current clinical demand for patients residing in the three northern health trusts while patients from the most southern health trust receive approximately 30% fewer PET examinations. Access to specialized health care should be monitored routinely in order to identify inequalities in referral patterns and resource utilization.
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http://dx.doi.org/10.1111/cpf.12335DOI Listing
September 2017

F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis.

Acta Radiol 2016 Oct 9;57(10):1193-200. Epub 2015 Jul 9.

Nuclear Medicine/PET-Center, Department of Radiology, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, University of Bergen, Bergen/Norway

Background: Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC).

Purpose: To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy.

Material And Methods: A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma's bivariate model.

Results: Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9-84.1) and 79.4% (95% CI, 71.2-85.4), respectively, with an area under the curve of 0.858.

Conclusion: F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy.
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http://dx.doi.org/10.1177/0284185115594645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015757PMC
October 2016

Metabolic Tumor Volume on 18F-FDG PET/CT Improves Preoperative Identification of High-Risk Endometrial Carcinoma Patients.

J Nucl Med 2015 Aug 4;56(8):1191-8. Epub 2015 Jun 4.

Center for PET/NM and Department of Radiology, Haukeland University Hospital, Bergen, Norway Section for Radiology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Unlabelled: Our objective was to prospectively explore the diagnostic value of (18)F-FDG PET/CT for preoperative staging in endometrial carcinomas and to investigate whether (18)F-FDG PET-specific quantitative tumor parameters reflect clinical and histologic characteristics.

Methods: Preoperative (18)F-FDG PET/CT was prospectively performed on 129 consecutive endometrial carcinoma patients. Two physicians who did not know the clinical findings or staging results independently reviewed the images, assessing primary tumor, cervical stroma involvement and metastatic spread, and determining maximum and mean standardized uptake value (SUVmax and SUVmean, respectively) for tumor, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). All parameters were analyzed in relation to histomorphologic and clinical tumor characteristics. Receiver-operating-characteristic curves for identification of deep myometrial invasion and lymph node metastases were generated, and MTV cutoffs for predicting deep myometrial invasion and lymph node metastases were calculated.

Results: The sensitivity, specificity, and accuracy of (18)F-FDG PET/CT for the detection of lymph node metastases were 77%-85%, 91%-96%, and 89%-93%, respectively. SUVmax, SUVmean, MTV, and TLG were significantly related to deep myometrial invasion, presence of lymph node metastases, and high histologic grade (P < 0.015 for all) and independently predicted deep myometrial invasion (P < 0.015) and lymph node metastases (P < 0.025) after adjustment for preoperative histologic risk (based on subtype and grade) in endometrial biopsies. Optimal cutoffs for MTV in predicting deep myometrial invasion (20 mL) and the presence of lymph node metastases (30 mL) yielded odds ratios of 7.8 (P < 0.001) and 16.5 (P = 0.001), respectively.

Conclusion: (18)F-FDG PET/CT represents a clinically valuable tool for preoperatively evaluating the presence of lymph node metastases in endometrial carcinoma patients. Applying MTV cutoffs for the prediction of deep myometrial invasion and lymph node metastases may increase diagnostic accuracy and aid preoperative identification of high-risk patients, enabling restriction of lymphadenectomy for patients with a low risk of aggressive disease.
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http://dx.doi.org/10.2967/jnumed.115.159913DOI Listing
August 2015

Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report.

BMC Res Notes 2015 Apr 30;8:171. Epub 2015 Apr 30.

Department of Pathology, Haukeland University Hospital, Bergen, Norway.

Background: Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment.

Case Presentation: In this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720 mg daily) for a period of three months resulted in significant tumor shrinkage by >60% and regression of contrast enhancement and fluorodeoxyglucose uptake on positron-emission tomography. The patient's spastic paraparesis and gait function improved dramatically. She currently walks unaided and reports a substantially improved quality of life.

Conclusion: Our findings show that vemurafenib therapy, even at low doses, can be effective for the treatment of intra-axial central nervous system involvement in BRAF-positive Erdheim-Chester disease.
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http://dx.doi.org/10.1186/s13104-015-1135-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450489PMC
April 2015

Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity.

Acta Radiol 2015 Nov 13;56(11):1350-60. Epub 2015 Mar 13.

Section for Endocrine Surgery, Haukeland University Hospital, Bergen/Norway Department of Clinical Science, University of Bergen, Bergen/Norway.

Background: Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).

Purpose: To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT.

Material And Methods: Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard.

Results: Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%).

Conclusion: In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed.
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http://dx.doi.org/10.1177/0284185115574298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768638PMC
November 2015

Default-mode network functional connectivity is closely related to metabolic activity.

Hum Brain Mapp 2015 Jun 3;36(6):2027-38. Epub 2015 Feb 3.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; NORMENT Center of Excellence, University of Oslo, Norway.

Over the last decade, the brain's default-mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood-oxygen level-dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2-deoxy-2-[(18) F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy ((1) H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG-uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal.
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http://dx.doi.org/10.1002/hbm.22753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006878PMC
June 2015

Latencies longer than 3.5 ms after vagus nerve stimulation does not exclude a nonrecurrent inferior laryngeal nerve.

BMC Surg 2014 Aug 28;14:61. Epub 2014 Aug 28.

Department of Surgery, Haukeland University Hospital, Bergen, Norway.

Background: It has recently been reported that a signal latency shorter than 3.5 ms after electrical stimulation of the vagus nerve signify a nonrecurrent course of the inferior laryngeal nerve. We present a patient with an ascending nonrecurrent inferior laryngeal nerve. In this patient, the stimulation latency was longer than 3.5 ms.

Case Presentation: A 74-years old female underwent redo surgery due to a right-sided recurrent nodular goitre. The signal latency on electrical stimulation of the vagus nerve at the level of the carotid artery bifurcation was 3.75 ms. Further dissection revealed a nonrecurrent but ascending course of the inferior laryngeal nerve. Caused by the recurrent goitre, the nerve was elongated to about 10 cm resulting in this long latency.

Conclusion: This case demonstrates that the formerly proposed "3.5 ms rule" for identifying a nonrecurrent course of the inferior laryngeal nerve has exceptions. A longer latency does not necessarily exclude a nonrecurrent laryngeal nerve.
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http://dx.doi.org/10.1186/1471-2482-14-61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149872PMC
August 2014

1.5-T multiparametric MRI using PI-RADS: a region by region analysis to localize the index-tumor of prostate cancer in patients undergoing prostatectomy.

Acta Radiol 2015 Apr 12;56(4):500-11. Epub 2014 May 12.

Department of Radiology, Haukeland University Hospital, Bergen Norway Department of Clinical Medicine, University of Bergen, Norway.

Background: The use of multiparametric magnetic resonance imaging (mpMRI) to detect and localize prostate cancer has increased in recent years. In 2010, the European Society of Urogenital Radiology (ESUR) published guidelines for mpMRI and introduced the Prostate Imaging Reporting and Data System (PI-RADS) for scoring the different parameters.

Purpose: To evaluate the reliability and diagnostic performance of endorectal 1.5-T mpMRI using the PI-RADS to localize the index tumor of prostate cancer in patients undergoing prostatectomy.

Material And Methods: This institutional review board IRB-approved, retrospective study included 63 patients (mean age, 60.7 years, median PSA, 8.0). Three observers read mpMRI parameters (T2W, DWI, and DCE) using the PI-RADS, which were compared with the results from whole-mount histopathology that analyzed 27 regions of interest. Inter-observer agreement was calculated as well as sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV) by dichotomizing the PI-RADS criteria scores ≥3. A receiver-operating curve (ROC) analysis was performed for the different MR parameters and overall score.

Results: Inter-observer agreement on the overall score was 0.41. The overall score in the peripheral zone achieved sensitivities of 0.41, 0.60, and 0.55 with an NPV of 0.80, 0.84, and 0.83, and in the transitional zone, sensitivities of 0.26, 0.15, and 0.19 with an NPV of 0.92, 0.91, and 0.92 for Observers 1, 2, and 3, respectively. The ROC analysis showed a significantly increased area under the curve (AUC) for the overall score when compared to T2W alone for two of the three observers.

Conclusion: 1.5 T mpMRI using the PI-RADS to localize the index tumor achieved moderate reliability and diagnostic performance.
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http://dx.doi.org/10.1177/0284185114531754DOI Listing
April 2015

High cardiac background activity limits 99mTc-MIBI radioguided surgery in aortopulmonary window parathyroid adenomas.

BMC Surg 2014 Apr 23;14:22. Epub 2014 Apr 23.

Department of Radiology, Centre for Nuclear Medicine/PET, Haukeland University Hospital, Jonas Liesvei 65, Bergen 5021, Norway.

Background: Radioguided surgery using 99m-Technetium-methoxyisobutylisonitrile (99mTc-MIBI) has been recommended for the surgical treatment of mediastinal parathyroid adenomas. However, high myocardial 99mTc-MIBI uptake may limit the feasibility of radioguided surgery in aortopulmonary window parathyroid adenoma.

Case Presentation: Two female patients aged 72 (#1) and 79 years (#2) with primary hyperparathyroidism caused by parathyroid adenomas in the aortopulmonary window were operated by transsternal radioguided surgery. After intravenous injection of 370 MBq 99mTc-MIBI at start of surgery, the maximum radioactive intensity (as counts per second) was measured over several body regions using a gamma probe before and after removal of the parathyroid adenoma. Relative radioactivity was calculated in relation to the measured ex vivo radioactivity of the adenoma, which was set to 1.0. Both patients were cured by uneventful removal of aortopulmonary window parathyroid adenomas of 4400 (#1) and 985 mg (#2). Biochemical cure was documented by intraoperative measurement of parathyroid hormone as well as follow-up examination. Ex vivo radioactivity over the parathyroid adenomas was 196 (#1) and 855 counts per second (#2). Before parathyroidectomy, relative radioactivity over the aortopulmonary window versus the heart was found at 1.3 versus 2.6 (#1) and 1.8 versus 4.8 (#2). After removal of the adenomas, radioactivity within the aortopulmonary window was only slightly reduced.

Conclusion: High myocardial uptake of 99mTc-MIBI limits the feasibility of radioguided surgery in aortopulmonary parathyroid adenoma.
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http://dx.doi.org/10.1186/1471-2482-14-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003509PMC
April 2014

A simple versatile solution for collecting multidimensional clinical data based on the CakePHP web application framework.

Authors:
Martin Biermann

Comput Methods Programs Biomed 2014 Apr 17;114(1):70-9. Epub 2014 Jan 17.

Nuclear Medicine and PET Centre, Department of Radiology, Haukeland University Hospital, N-5021 Bergen, Norway; Section for Radiology, Clinical Institute I, University of Bergen, Bergen, Norway. Electronic address:

Clinical trials aiming for regulatory approval of a therapeutic agent must be conducted according to Good Clinical Practice (GCP). Clinical Data Management Systems (CDMS) are specialized software solutions geared toward GCP-trials. They are however less suited for data management in small non-GCP research projects. For use in researcher-initiated non-GCP studies, we developed a client-server database application based on the public domain CakePHP framework. The underlying MySQL database uses a simple data model based on only five data tables. The graphical user interface can be run in any web browser inside the hospital network. Data are validated upon entry. Data contained in external database systems can be imported interactively. Data are automatically anonymized on import, and the key lists identifying the subjects being logged to a restricted part of the database. Data analysis is performed by separate statistics and analysis software connecting to the database via a generic Open Database Connectivity (ODBC) interface. Since its first pilot implementation in 2011, the solution has been applied to seven different clinical research projects covering different clinical problems in different organ systems such as cancer of the thyroid and the prostate glands. This paper shows how the adoption of a generic web application framework is a feasible, flexible, low-cost, and user-friendly way of managing multidimensional research data in researcher-initiated non-GCP clinical projects.
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http://dx.doi.org/10.1016/j.cmpb.2014.01.007DOI Listing
April 2014

Progressive striatal necrosis associated with anti-NMDA receptor antibodies.

BMC Neurol 2013 May 31;13:55. Epub 2013 May 31.

Department of Neurology, Haukeland University Hospital, Bergen 5021, Norway.

Background: We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity.

Case Presentation: An eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia. Clinical examination revealed a pure generalized dystonia with no cognitive or other neurological findings. Magnetic resonance imaging showed bilateral high T2 signal striatal lesions, which were slowly progressive over a period of nine years. New parts of the lesion showed restricted water diffusion suggesting cytotoxic oedema. Positron emission tomography of the brain showed frontal hypermetabolism and cerebellar hypometabolism. Antibodies against the NR1 subunit of the NMDA receptor were detected in the patient's serum and cerebrospinal fluid. There was no neoplasia or preceding infection or vaccination.

Conclusion: This is the first report of chronic progressive bilateral striatal necrosis associated with anti-NMDAR antibodies. Our findings expand the clinical spectrum of disease associated with anti-NMDAR antibodies and suggest that these should be included in the work-up of dystonia with striatal necrosis.
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http://dx.doi.org/10.1186/1471-2377-13-55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673874PMC
May 2013

Severe nigrostriatal degeneration without clinical parkinsonism in patients with polymerase gamma mutations.

Brain 2013 Aug 26;136(Pt 8):2393-404. Epub 2013 Apr 26.

Department of Neurology, Haukeland University Hospital, Bergen, Norway.

The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It is known that defects in proteins involved in mitochondrial quality control can cause Parkinson's disease, and there is increasing evidence linking mitochondrial dysfunction, and particularly mitochondrial DNA abnormalities, to neuronal loss in the substantia nigra. Mutations in the catalytic subunit of polymerase gamma are among the most common causes of mitochondrial disease and owing to its role in mitochondrial DNA homeostasis, polymerase gamma defects are often considered a paradigm for mitochondrial diseases generally. Yet, despite this, parkinsonism is uncommon with polymerase gamma defects. In this study, we investigated structural and functional changes in the substantia nigra of 11 patients with polymerase gamma encephalopathy. We characterized the mitochondrial DNA abnormalities and examined the respiratory chain in neurons of the substantia nigra. We also investigated nigrostriatal integrity and function using a combination of post-mortem and in vivo functional studies with dopamine transporter imaging and positron emission tomography. At the cellular level, dopaminergic nigral neurons of patients with polymerase gamma encephalopathy contained a significantly lower copy number of mitochondrial DNA (depletion) and higher levels of deletions than normal control subjects. A selective and progressive complex I deficiency was seen and this was associated with a severe and progressive loss of the dopaminergic neurons of the pars compacta. Dopamine transporter imaging and positron emission tomography showed that the degree of nigral neuronal loss and nigrostriatal depletion were severe and appeared greater even than that seen in idiopathic Parkinson's disease. Despite this, however, none of our patients showed any signs of parkinsonism. The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism.
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http://dx.doi.org/10.1093/brain/awt103DOI Listing
August 2013