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Hennings, Joakim
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Publications (9 of 9) Show all publications
Hennings, J., Sundin, A., Hägg, A. & Hellman, P. (2010). 11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism. Langenbeck's archives of surgery (Print), 395(7), 963-967
Open this publication in new window or tab >>11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism
2010 (English)In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, no 7, p. 963-967Article in journal (Refereed) Published
Abstract [en]

Purpose: To evaluate whether dexamethasone suppression treatment can improve 11 C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA).

Materials and Methods: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small “hot-spot” regions of interest (ROIs) comprising 4-pixels (SUVhs) and 1-pixel  (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded.

Results: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to non-functional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p<0.05) but tumour SUV was not significantly decreased after suppression in either PA or non-functional tumours (p>0.05).  However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p>0.05).

Conclusion: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series dexamethasone-suppressed MTO-PET was ubable to increase the tumour-to-normal-adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.

Keywords
Metomidate, PET, Primary aldosteronism, Dexamethasone, Adrenal, Suppression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-108798 (URN)10.1007/s00423-010-0681-7 (DOI)000283474100020 ()20644954 (PubMedID)
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2017-12-13Bibliographically approved
Hennings, J., Andreasson, S., Botling, J., Hägg, A., Sundin, A. & Hellman, P. (2010). Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism. Langenbeck's archives of surgery (Print), 395(2), 133-137
Open this publication in new window or tab >>Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism
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2010 (English)In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, no 2, p. 133-137Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.

Keywords
Primary aldosteronism, Long-time follow-up, Surgery, Nodular hyperplasia
National Category
Medical and Health Sciences
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-104657 (URN)10.1007/s00423-009-0498-4 (DOI)000274652000006 ()19418066 (PubMedID)
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2017-12-13Bibliographically approved
Hellman, P., Hessman, O., Åkerström, G., Stålberg, P., Hennings, J., Björck, M. & Eriksson, L.-G. (2010). Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses. World Journal of Surgery, 34(6), 1373-1379
Open this publication in new window or tab >>Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses
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2010 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 34, no 6, p. 1373-1379Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-126923 (URN)10.1007/s00268-009-0361-3 (DOI)000277714300033 ()20066417 (PubMedID)
Available from: 2010-06-30 Created: 2010-06-30 Last updated: 2017-12-12Bibliographically approved
Hennings, J. (2009). Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adrenal tumours, discovered en passant in patients undergoing radiological examinations for non-adrenal disease, so-called adrenal incidentalomas, have increased dramatically in the recent era of more sophisticated diagnostic modalities such as high resolution multidetector computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, primary aldosteronism (PA) has been documented in several screening studies as being far more common than previously believed among hypertensive patients.

In this thesis, a long-term follow-up cohort of patients who had undergone surgery for PA revealed that there was an excellent effect on blood-pressure, reduction of anti-hypertensive medication and hypokalaemia after surgery, even though the majority of these patients still required some anti-hypertensive medication. This was also true, in the higher than expected number of dominant nodular hyperplasia (nIHA) found in the study, but was slightly less pronounced than in aldosterone producing adenomas (APA).  Surgery was thus effective in lateralized PA.

Metomidate positron emission tomography (MTO-PET) was explored in relation to histopathology in post-operative patients and found to be highly specific and sensitive in categorizing adrenocortical disease. Also, a higher standardized uptake value (SUV) ratio between tumours and normal adrenal cortex was found in hormonally hypersecreting adenomas as well as in adrenocortical cancer (ACC). The resolution limited the diagnosis of small tumours (<1-1.5 cm).

MTO-PET was compared to standard radiological modalities (CT and MRI) in the diagnostic work-up of adrenal incidentalomas. All three modalities categorized and characterized the lesions well, with MTO-PET showing the highest sensitivity and specificity.  However this method is currently recommended to be used as complementary to the others in unclear cases, due to high costs and less availability.

The resolution of MTO-PET was improved with respect to less noise and better delineation of small tumours when applying masked volume-wise principal component analysis (MVW-PCA), which will possibly enable future detection of small tumours in PA patients.

Dexamethasone suppression treatment prior to MTO-PET examinations in PA patients decreased SUV in normal adrenal cortex but could not be shown to increase the SUV ratio between adenoma and normal cortex enabling better detection of small tumours, even though all the tumours were readily categorized in the study. Heterogenic SUV reactions to dexamethasone treatment indicate a need for further studies and refinement of the suppression method.

In conclusion, long-term results of surgery for lateralized PA are good. MTO-PET is a highly sensitive and specific method for categorizing adrenocortical disease. Modulation of the method, e.g. by using MVW-PCA and refined dexamethasone suppression treatment, may improve the resolution of the method in delineating small tumours in PA, thus making MTO-PET a non-invasive and non-operator dependent future alternative to the currently recommended adrenal venous sampling (AVS) for lateralization diagnosis prior to surgery for PA.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. p. 33
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 486
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-108797 (URN)978-91-554-7618-2 (ISBN)
Public defence
2009-11-14, Auditorium Minus, Museum Gustavianum, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2009-10-23 Created: 2009-09-29 Last updated: 2009-10-23Bibliographically approved
Hennings, J., Hellman, P., Ahlström, H. & Sundin, A. (2009). Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas. European Journal of Radiology, 69(2), 314-23
Open this publication in new window or tab >>Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas
2009 (English)In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 69, no 2, p. 314-23Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Given the higher sensitivity of modern computed tomography (CT) scanners, adrenal incidentalomas are being discovered increasingly often. This implies a growing quantitative diagnostic and clinical problem. CT and/or magnetic resonance imaging (MRI) and usually thorough hormonal testing are routinely used to determine the origin of these lesions. Recently, positron emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been established as an alternative diagnostic method with high sensitivity for identifying adrenocortical lesions. The aim of this study was to evaluate the clinical use and value of MTO-PET compared to CT and MRI in the characterisation and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO-PET and from whom we had either histopathological diagnosis or clinical follow-up data. After this analysis we conducted a prospective study in order to compare the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT, MRI and MTO-PET and the results were correlated to those from histopathology (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the retrospective analysis, MRI and especially MTO-PET, correlated well to histopathology and clinical diagnosis after follow-up, whereas specificity with CT was low. This was possibly due to the presence of several haematomas/fibrosis which were misdiagnosed as adrenocortical adenomas. In the prospective cohort, sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The diagnosis of an adrenocortical adenoma may be established by CT in most patients and by MRI in an additional number. For the few remaining patients needing further characterisation, MTO-PET is advantageous as an additional imaging modality.

Keywords
adrenal, incidentalomas, metomidate, PET, MRI, CT
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Diagnostic Radiology
Identifiers
urn:nbn:se:uu:diva-104627 (URN)10.1016/j.ejrad.2007.10.024 (DOI)000264220600017 ()18082990 (PubMedID)
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2017-12-13Bibliographically approved
Enberg, U., Hennings, J., Volpe, C., Hellman, P., Höög, A., Hamberger, B. & Thorén, M. (2009). Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors. Journal of Endocrinological Investigation, 32(10), 810-815
Open this publication in new window or tab >>Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors
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2009 (English)In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 32, no 10, p. 810-815Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.

Keywords
Adrenocortical tumor, autonomous cortisol production, Cushing's syndrome, CYP1161, CYP17
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-113076 (URN)10.3275/6383 (DOI)000274444900004 ()19564722 (PubMedID)
Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2017-12-12Bibliographically approved
Hellman, P., Linder, F., Hennings, J., Hessman, O., Eriksson, B., Örlefors, H. & Åkerström, G. (2006). Bilateral adrenalectomy for ectopic Cushing syndrome -: discussions on technique and indication. World J Surg, 30(5), 909-916
Open this publication in new window or tab >>Bilateral adrenalectomy for ectopic Cushing syndrome -: discussions on technique and indication
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2006 (English)In: World J Surg, Vol. 30, no 5, p. 909-916Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-74397 (URN)16467980 (PubMedID)
Available from: 2006-06-08 Created: 2006-06-08 Last updated: 2011-01-11
Hellman, P., Hennings, J., Åkerström, G. & Skogseid, B. (2005). Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1.. Br J Surg, 92(12), 1508-12
Open this publication in new window or tab >>Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1.
2005 (English)In: Br J Surg, ISSN 0007-1323, Vol. 92, no 12, p. 1508-12Article in journal (Refereed) Published
Keywords
Adolescent, Adult, Aged, Endosonography/*instrumentation/methods, Equipment Design, Female, Humans, Male, Middle Aged, Multiple Endocrine Neoplasia Type 1/*ultrasonography, Pancreatic Neoplasms/surgery/*ultrasonography, Preoperative Care/methods
Identifiers
urn:nbn:se:uu:diva-75208 (URN)16231278 (PubMedID)
Available from: 2006-01-26 Created: 2006-01-26 Last updated: 2017-01-25
Hennings, J., Garske, U., Botling, J. & Hellman, P. (2005). Malignant insulinoma in ectopic pancreatic tissue.. Dig Surg, 22(5), 377-9
Open this publication in new window or tab >>Malignant insulinoma in ectopic pancreatic tissue.
2005 (English)In: Dig Surg, ISSN 0253-4886, Vol. 22, no 5, p. 377-9Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-80609 (URN)16432300 (PubMedID)
Available from: 2006-06-26 Created: 2006-06-26 Last updated: 2011-01-11
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