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Klimàcek, B., Åkerström, T., Annebäck, M., Hellman, P., Norlén, O. & Stålberg, P. (2025). Evaluation of hand-assisted laparoscopic surgery of small intestinal neuroendocrine tumours as an alternative surgical treatment to open surgery. Langenbeck's archives of surgery (Print), 410(1), Article ID 90.
Open this publication in new window or tab >>Evaluation of hand-assisted laparoscopic surgery of small intestinal neuroendocrine tumours as an alternative surgical treatment to open surgery
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2025 (English)In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 410, no 1, article id 90Article in journal (Refereed) Published
Abstract [en]

Purpose Small intestinal neuroendocrine tumours (SI-NETs) are the most common malignancy of the small bowel. Curative treatment is surgical, with exploratory laparotomy considered the standard approach. This study aimed to assess the outcomes of minimally invasive surgery compared to open approach for SI-NETs at the Endocrine surgical unit at Uppsala University Hospital. Methods This retrospective cohort study included patients who underwent surgery for SI-NET between 2013 and 2023 at Uppsala University Hospital. Variables such as operative time, length of hospital stay, use of analgesia and radicality were compared between groups of patients operated on before and after 2019, when hand-port assisted laparoscopic surgery (HALS) for SI-NETs was introduced at our unit. Outcomes were further compared between open and hand-port assisted laparoscopic approaches. The primary outcome was the rate of radicality achieved for stage II-III patients. Secondary outcomes included operative time, the length of hospital stay and the use of epidural and patient-controlled analgesia. Results Of 97 patients, 58 (59.8%) underwent open surgery and 39 (40.2%) underwent hand-port assisted laparoscopic surgery. There was no significant difference in operative time (121 min [91.3-150.3] vs 108 min [83-141]), length of hospital stay, 6 days [4-7] vs 5 days [4-8]), and surgical radicality in patients with stage II-III, 85.2% vs 100%, (p = 0.079). 86.2% of patients with explorative laparotomy required epidural analgesia compared to only 23.1% with HALS (p < 0.001). Conclusion Hand-port assisted laparoscopic surgery of SI-NETs is a feasible approach that preserves radical resection while enhancing postoperative recovery, with a lower requirement of epidural analgesia.

Place, publisher, year, edition, pages
Springer Nature, 2025
Keywords
Hand-assisted laparoscopic surgery, Small intestinal neuroendocrine tumours, Open surgery, Radicality, Minimally invasive surgery
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-553121 (URN)10.1007/s00423-025-03658-z (DOI)001439675400001 ()40047926 (PubMedID)2-s2.0-86000287810 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2025-03-26 Created: 2025-03-26 Last updated: 2025-03-26Bibliographically approved
Flynn, A., Pattison, A. D., Balachander, S., Boehm, E., Bowen, B., Dwight, T., . . . Tothill, R. W. (2025). Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles. Nature Communications, 16(1), Article ID 2632.
Open this publication in new window or tab >>Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles
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2025 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 16, no 1, article id 2632Article in journal (Refereed) Published
Abstract [en]

Hereditary SDHB-mutant pheochromocytomas (PC) and paragangliomas (PG) are rare tumours with a high propensity to metastasize although their clinical behaviour is unpredictable. To characterize the genomic landscape of these tumours and identify metastasis biomarkers, we perform multi-omic analysis on 94 tumours from 79 patients using seven molecular methods. Sympathetic (chromaffin cell) and parasympathetic (non-chromaffin cell) PCPG have distinct molecular profiles reflecting their cell-of-origin and biochemical profile. TERT and ATRX-alterations are associated with metastatic PCPG and these tumours have an increased mutation load, and distinct transcriptional and telomeric features. Most PCPG have quiet genomes with some rare co-operative driver events, including EPAS1/HIF-2 alpha mutations. Two mechanisms of acquired resistance to DNA alkylating chemotherapies are identifiable; MGMT overexpression and mismatch repair-deficiency causing hypermutation. Our comprehensive multi-omic analysis of SDHB-mutant PCPG therefore identifies features of metastatic disease and treatment response, expanding our understanding of these rare neuroendocrine tumours.

Place, publisher, year, edition, pages
Springer Nature, 2025
National Category
Cancer and Oncology Medical Genetics and Genomics Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-554525 (URN)10.1038/s41467-025-57595-y (DOI)001446704900002 ()40097403 (PubMedID)2-s2.0-105000409486 (Scopus ID)
Available from: 2025-04-14 Created: 2025-04-14 Last updated: 2025-04-14Bibliographically approved
Annebäck, M., Wachtmeister, S., Hedberg, J., Stålberg, P. & Norlén, O. (2025). Quality of life in patients with permanent hypoparathyroidism after thyroidectomy for benign thyroid disease: population-based study with long-term follow-up. BJS Open, 9(3), Article ID zraf032.
Open this publication in new window or tab >>Quality of life in patients with permanent hypoparathyroidism after thyroidectomy for benign thyroid disease: population-based study with long-term follow-up
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2025 (English)In: BJS Open, E-ISSN 2474-9842, Vol. 9, no 3, article id zraf032Article in journal (Refereed) Published
Abstract [en]

Background: In recent years, several studies have shown that permanent hypoparathyroidism has a negative impact on health-related quality of life. However, these results could have been affected by short-term follow-up, selection bias and confounding factors. The aim of this study was to investigate health-related quality of life in patients with and without permanent hypoparathyroidism after total thyroidectomy for benign thyroid disease, using a strict definition of permanent hypoparathyroidism and long-term follow-up data.

Methods: All patients who underwent total thyroidectomy for benign thyroid disease in a region of Sweden between 1 January 2005 and 31 December 2015 were assessed for eligibility. Eligible patients were invited to participate in the study through a letter on 26 August 2021. The 36-item Short Form Health Survey version 2 was used to compare health-related quality of life in patients with and without permanent hypoparathyroidism.

Results: Of 1636 patients, 1483 patients were invited to participate in the study. In total, 716 (48.3%) patients answered the Short Form Health Survey questionnaire and were included in the study cohort. Mean(s.d.) follow-up was 10.9(3.2) years. Patients with and without permanent hypoparathyroidism did not differ in baseline characteristics, with the exception that patients with permanent hypoparathyroidism were younger. There were no evident differences in health-related quality of life between the two groups, encompassing all health domains and summary component scores (P > 0.05).

Conclusion: No difference in health-related quality of life was found between patients with and without permanent hypoparathyroidism after total thyroidectomy on long-term follow-up. These results challenge previous findings and highlight the need for comprehensive, long-term studies to better understand the impact of this condition on health-related quality of life.

Place, publisher, year, edition, pages
Oxford University Press, 2025
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-556601 (URN)10.1093/bjsopen/zraf032 (DOI)001482813300001 ()40331892 (PubMedID)
Available from: 2025-05-21 Created: 2025-05-21 Last updated: 2025-05-21Bibliographically approved
Makhnov, N., Axling, F., Barazeghi, E., Stålberg, P., Åkerström, T. & Hellman, P. (2025). Serum microRNAs as peripheral markers of primary aldosteronism. Frontiers in Endocrinology
Open this publication in new window or tab >>Serum microRNAs as peripheral markers of primary aldosteronism
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2025 (English)In: Frontiers in Endocrinology, E-ISSN 1664-2392Article in journal (Refereed) Published
Abstract [en]

Background: Primary aldosteronism (PA) is the principal cause of secondaryhypertension; it leads to significantly elevated cardiovascular morbidity andmortality, but only a fraction of its cases ever get detected, partially due todiagnostic procedures that are difficult to perform and to interpret. Morestraightforward diagnostic methods are needed. Lateralized, or unilateral PA(uPA), is best treated by surgery. Bilateral PA (bPA) is treated medically.Aim: The aim of our study was to explore microRNA (miRNA) in peripheral bloodas markers of PA, uPA and bPA.

Methods: In groups of subjects with primary hypertension (HT, n = 11), bPA (n =12), and uPA (n = 16), peripheral serum was used for isolation of total RNA, librarypreparation, and NGS sequencing to achieve a comparative analysis of miRNAexpression. Five-fold cross-validation support vector machine learning (ML)models were employed to search for miRNA that could be used as markers ofPA and its forms.

Results: In our cohort of patients, the discovered combinations of miRNAs could,with a high level of accuracy, sensitivity, and specificity, characterize thedifference between HT and PA, as well as between a combined group of HT +bPA vs. uPA. The differentiating parameters were moderately good forcomparison of bPA vs. uPA.

Conclusion: Within our patient cohort, and using ML, the study identifieddistinctly different miRNA profiles between HT and PA, as well as between bPAand uPA. Further validation studies may lead to the emergence of a new tool forclinical diagnostics of PA.

Place, publisher, year, edition, pages
Lausanne: Frontiers Media S.A., 2025
National Category
Surgery
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-553580 (URN)10.3389/fendo.2025.1511096 (DOI)001457813300001 ()40182638 (PubMedID)2-s2.0-105001691132 (Scopus ID)
Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-04-24Bibliographically approved
Van Den Heede, K., van Beek, D.-J., Van Slycke, S., Borel Rinkes, I., Norlén, O., Stålberg, P. & Nordenstrom, E. (2024). Surgery for advanced neuroendocrine tumours of the small bowel: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES). British Journal of Surgery, 111(4), Article ID znae082.
Open this publication in new window or tab >>Surgery for advanced neuroendocrine tumours of the small bowel: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES)
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2024 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 111, no 4, article id znae082Article, review/survey (Refereed) Published
Abstract [en]

Background Small bowel neuroendocrine tumours often present with locally advanced or metastatic disease. The aim of this paper is to provide evidence-based recommendations regarding (controversial) topics in the surgical management of advanced small bowel neuroendocrine tumours.Methods A working group of experts was formed by the European Society of Endocrine Surgeons. The group addressed 11 clinically relevant questions regarding surgery for advanced disease, including the benefit of primary tumour resection, the role of cytoreduction, the extent of lymph node clearance, and the management of an unknown primary tumour. A systematic literature search was performed in MEDLINE to identify papers addressing the research questions. Final recommendations were presented and voted upon by European Society of Endocrine Surgeons members at the European Society of Endocrine Surgeons Conference in Mainz in 2023.Results The literature review yielded 1223 papers, of which 84 were included. There were no randomized controlled trials to address any of the research questions and therefore conclusions were based on the available case series, cohort studies, and systematic reviews/meta-analyses of the available non-randomized studies. The proposed recommendations were scored by 38-51 members and rated 'strongly agree' or 'agree' by 64-96% of participants.Conclusion This paper provides recommendations based on the best available evidence and expert opinion on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours. This paper provides evidence-based recommendations on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours, primary tumour resections in the setting of metastatic disease, and surgical indications for grade 3 small bowel neuroendocrine tumours and small bowel neuroendocrine carcinomas. The recommendations are the result of a working group of experts, created by the European Society of Endocrine Surgeons. The group addressed 11 relevant clinical questions regarding surgery for advanced disease, emphasizing and confirming the key role of the surgeon for advanced small bowel neuroendocrine tumours.

Place, publisher, year, edition, pages
Oxford University Press, 2024
National Category
Surgery Gastroenterology and Hepatology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-527719 (URN)10.1093/bjs/znae082 (DOI)001203782000001 ()38626261 (PubMedID)
Available from: 2024-05-07 Created: 2024-05-07 Last updated: 2025-02-11Bibliographically approved
Van Beek, D.-J., Van Den Heede, K., Rinkes, I. B., Norlén, O., Van Slycke, S., Stålberg, P. & Nordenström, E. (2024). Surgery for advanced pancreatic neuroendocrine neoplasms: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES). British Journal of Surgery, 111(2), Article ID znae017.
Open this publication in new window or tab >>Surgery for advanced pancreatic neuroendocrine neoplasms: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES)
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2024 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 111, no 2, article id znae017Article in journal (Refereed) Published
Abstract [en]

This European Society of Endocrine Surgeons (ESES) guideline provides evidence-based recommendations based on the surgical management for locally advanced pancreatic neuroendocrine neoplasms, indications for neoadjuvant therapy, primary tumor resections in the setting of metastatic disease and surgical indications for Grade 3 pancreatic neuroendocrine tumours and pancreatic neuroendocrine carcinoma.

Place, publisher, year, edition, pages
Oxford University Press, 2024
National Category
Surgery Cancer and Oncology Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-529850 (URN)10.1093/bjs/znae017 (DOI)001163690700002 ()38364061 (PubMedID)
Available from: 2024-06-04 Created: 2024-06-04 Last updated: 2025-02-11Bibliographically approved
Backman, S., Botling, J., Nord, H., Ghosal, S., Stålberg, P., Juhlin, C. C., . . . Crona, J. (2024). The evolutionary history of metastatic pancreatic neuroendocrine tumours reveals a therapy driven route to high-grade transformation. Journal of Pathology, 264(4), 357-370
Open this publication in new window or tab >>The evolutionary history of metastatic pancreatic neuroendocrine tumours reveals a therapy driven route to high-grade transformation
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2024 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 264, no 4, p. 357-370Article in journal (Refereed) Published
Abstract [en]

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular may progress from a low/intermediate to a high-grade disease. The aim of this work was to understand the molecular mechanisms underlying metastatic progression as well as PanNET transformation from a low/intermediate to a high-grade disease. We performed multi-omics analysis (genome/exome sequencing, total RNA-sequencing and methylation array) of 32 longitudinal samples from six patients with metastatic low/intermediate grade PanNET. The clonal composition of tumour lesions and underlying phylogeny of each patient were determined with bioinformatics analyses. Findings were validated in post-alkylating chemotherapy samples from 24 patients with PanNET using targeted next generation sequencing. We validate the current PanNET evolutionary model with MEN1 inactivation that occurs very early in tumourigenesis. This was followed by pronounced genetic diversity on both spatial and temporal levels, with parallel and convergent tumour evolution involving the ATRX/DAXX and mechanistic target of the rapamycin (mTOR) pathways. Following alkylating chemotherapy treatment, some PanNETs developed mismatch repair deficiency and acquired a hypermutational phenotype. This was validated among 16 patients with PanNET who had high-grade progression after alkylating chemotherapy, of whom eight had a tumour mutational burden >50 (50%). In comparison, among the eight patients who did not show high-grade progression, 0 had a tumour mutational burden >50 (0%; odds ratio ‘infinite’, 95% confidence interval 1.8 to ‘infinite’, p = 0.02). Our findings contribute to broaden the understanding of metastatic/high-grade PanNETs and suggests that therapy driven disease evolution is an important hallmark of this disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
neuroendocrine tumours, tumour evolution, heterogeneity, multi-omics, pancreas, metastasis, mismatch repair, alkylating chemotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-523490 (URN)10.1002/path.6348 (DOI)001327034800001 ()38313278 (PubMedID)2-s2.0-85205548822 (Scopus ID)
Funder
Swedish Research Council, 2022-06725Swedish Cancer SocietyInsamlingsstiftelsen Lions Cancerforskningsfond Mellansverige Uppsala-ÖrebroÅke Wiberg Foundation
Available from: 2024-02-19 Created: 2024-02-19 Last updated: 2025-01-30Bibliographically approved
Kjaer, J., Norlén, O., Hellman, P. & Stålberg, P. (2023). Author's Reply: Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation [Letter to the editor]. World Journal of Surgery, 47(4), 1084-1085
Open this publication in new window or tab >>Author's Reply: Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation
2023 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 47, no 4, p. 1084-1085Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-502358 (URN)10.1007/s00268-023-06916-7 (DOI)000923116400001 ()36705741 (PubMedID)
Note

Peter Stålberg is noted as Peter Stalberg in the publication list of authors

Correction in: World Journal of Surgery, vol. 47, page 1086, DOI: 10.1007/s00268-023-06938-1

Available from: 2023-05-31 Created: 2023-05-31 Last updated: 2023-05-31Bibliographically approved
Karakatsanis, A., Eriksson, S., Pistiolis, L., Olofsson Bagge, R., Nagy, G., Man, V., . . . Wärnberg, F. (2023). Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study. Annals of Surgical Oncology, 30(7), 4064-4072
Open this publication in new window or tab >>Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study
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2023 (English)In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 30, no 7, p. 4064-4072Article in journal (Refereed) Published
Abstract [en]

Background

Difficulty in preoperatively assessing the risk for occult invasion or surgery that precludes future accurate axillary mapping in patients with ductal cancer in situ (DCIS) account for overutilization of SLND.

Methods

Prospective, multicenter, cohort study, including women with any DCIS planned for mastectomy or DCIS grade 2 and > 20 mm, any DCIS grade 3, any mass-forming DCIS and any planned surgery. Patients received an interstitial SPIO injection during breast surgery, but no upfront SLND was performed. If invasion was identified on final pathology, delayed SLND (d-SLND) was performed separately with the coadministration of isotope ± blue dye (BD). Study outcomes were proportion of upfront SLNDs that were avoided, detection rates during d-SLND, and impact on healthcare costs.

Results

In total, 78.7% of study participants (N = 254, mean age 60 years, mean DCIS size 37.8 mm) avoided upfront SLND. On d-SLND (median 28 days, range 9–46), SPIO outperformed Tc99 with (98.2% vs. 63.6%, p < 0.001) or without BD (92.7% vs. 50.9%, p < 0.001) and had higher nodal detection rate (86.9% vs. 32.3%, p < 0.001) and with BD (93.9% vs. 41.4%, p < 0.001). Only 27.9% of all SLNs retrieved were concordant for Tc99 and SPIO. Type of breast procedure (WLE vs. oncoplastic BCT vs. mastectomy) affected these outcomes and accounted for the low performance of Tc99 (p < 0.001). d-SLND resulted in a 28.1% total cost containment for women with pure DCIS on final pathology (4190 vs. 5828 USD, p < 0.001).

Conclusions

Marking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.

Place, publisher, year, edition, pages
Springer, 2023
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-556744 (URN)10.1245/s10434-022-13064-0 (DOI)000924165400001 ()36719570 (PubMedID)2-s2.0-85147299527 (Scopus ID)
Funder
Uppsala UniversityRegion UppsalaBröstcancerförbundet
Note

De två första författarna delar förstaförfattarskapet

Abdi Fatah Hersi, Allan Jazrawi och Peter Stålberg ingår i gruppen SentiNot Trialists Group

Available from: 2025-05-19 Created: 2025-05-19 Last updated: 2025-05-19Bibliographically approved
Stålberg, P. (2023). Metastatic small-bowel neuroendocrine tumours: medical management of the primary. British Journal of Surgery, 110(10), 1296-1297
Open this publication in new window or tab >>Metastatic small-bowel neuroendocrine tumours: medical management of the primary
2023 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 110, no 10, p. 1296-1297Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-533667 (URN)10.1093/bjs/znad248 (DOI)001049866700001 ()37527436 (PubMedID)
Funder
Swedish Cancer SocietyInsamlingsstiftelsen Lions Cancerforskningsfond Mellansverige Uppsala-Örebro
Available from: 2024-07-03 Created: 2024-07-03 Last updated: 2025-02-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9625-1394

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