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  • 1.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Barmparas, Galinos
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Riddez, Louis
    Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Ley, Eric J.
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden; Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Does beta-blockade reduce the risk of depression in patients with isolated severe extracranial injuries?2017In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 41, no 7, p. 1801-1806Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury.

    METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011. Severe extracranial injuries were defined as extracranial injuries with Abbreviated Injury Scale score ≥3, intracranial Abbreviated Injury Scale score <3 and an Injury Severity Score ≥16. In-hospital deaths and patients prescribed antidepressant therapy ≤1 year prior to admission were excluded. Patients were stratified into groups based on pre-admission beta-blocker status. The primary outcome was post-traumatic depression, defined as receiving antidepressants ≤1 year following trauma.

    RESULTS: Five hundred and ninety-six patients met the inclusion criteria with 11.4% prescribed pre-admission beta-blockade. Patients receiving beta-blockers were significantly older (57 ± 18 vs. 42 ± 17 years, p < 0.001) with lower Glasgow Coma Scale score (12 ± 3 vs. 14 ± 2, p < 0.001). The beta-blocked cohort spent significantly longer in hospital (21 ± 20 vs. 15 ± 17 days, p < 0.01) and intensive care (4 ± 7 vs. 3 ± 5 days, p = 0.01). A forward logistic regression model was applied and predicted lack of beta-blockade to be associated with increased risk of depression (OR 2.7, 95% CI 1.1-7.2, p = 0.04). After adjusting for group differences, patients lacking beta-blockers demonstrated an increased risk of depression (AOR 3.3, 95% CI 1.2-8.6, p = 0.02).

    CONCLUSIONS: Pre-admission beta-blockade is associated with a significantly reduced risk of depression following severe traumatic injury. Further investigation is needed to determine the beneficial effects of beta-blockade in these instances.

  • 2.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Matthiessen, Peter
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Effects of beta-blocker therapy on mortality after elective colon cancer surgery: a Swedish nationwide cohort study2020In: BMJ Open, E-ISSN 2044-6055, Vol. 10, no 7, article id e036164Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.

    DESIGN: Retrospective cohort study.

    SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.

    PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.

    RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001).

    CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.

  • 3.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Matthiessen, Peter
    School of Medical Science, Örebro University, Örebro, sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    The Effects of Beta-Blocker Therapy on Mortality After Elective Colon Cancer SurgeryManuscript (preprint) (Other academic)
  • 4.
    Aktypis, Charalampos
    et al.
    Department of Gastroenterology, Laiko General Hospital, Medical School of National & Kapodistrian University, Athens, Greece.
    Spei, Maria-Eleni
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Yavropoulou, Maria
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Koumarianou, Anna
    Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greec.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Kassi, Eva
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.2021In: Cancers, ISSN 2072-6694, Vol. 13, no 9, article id 2159Article, review/survey (Refereed)
    Abstract [en]

    A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87-3.12 and OR: 3.41, 95% CI: 1.46-7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47-1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35-1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66-6.48) followed by TKIs (OR:1.51, 95% CI: 0.59-3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64-4.64) and TKIs (OR:1.64, 95% CI: 0.35-7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87-5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

  • 5.
    Alevroudis, Emmanouil
    et al.
    2nd Department of Radiology, Nuclear Medicine Unit, National and Kapodistrian University of Athens, General University Hospital Attikon, Athens, Greece.
    Spei, Maria-Eleni
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Chatziioannou, Sofia N.
    2nd Department of Radiology, Nuclear Medicine Unit, National and Kapodistrian University of Athens, General University Hospital Attikon, Athens, Greece; Nuclear Medicine Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Efesiou St., Athens, Greece.
    Tsoli, Marina
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Clinical utility of 18f-fdg pet in neuroendocrine tumors prior to peptide receptor radionuclide therapy: A Systematic Review and Meta-Analysis2021In: Cancers, ISSN 2072-6694, Vol. 13, no 8, article id 1813Article, review/survey (Refereed)
    Abstract [en]

    The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

  • 6.
    Ali, Fathalla
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Sandblom, G.
    Department of Surgery, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Södersjukhuset, Stockholm, Sweden.
    Wikner, A.
    Department of Surgery, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Laparoscopic ventral and incisional hernia repair using intraperitoneal onlay mesh with peritoneal bridging2022In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 26, no 2, p. 635-646Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to assess the feasibility and safety of a novel IPOM procedure with peritoneal bridging (IPOM-pb) for laparoscopic ventral hernia repair, and to compare the outcomes of this procedure with IPOM with- (IPOM-plus) and IPOM without (sIPOM) defect closure.

    Method: A single-centre retrospective study comparing a novel IPOM technique with peritoneal bridging (IPOM-pb) with the two commonly used IPOM techniques, IPOM with defect closure (IPOM-plus) and without defect closure (sIPOM). The intraoperative and postoperative data of patients who underwent laparoscopic IPOM ventral hernia repair were reviewed. Preoperative data, recurrence, and postoperative seroma, surgical site infection, and pain, were compared.

    Results: From January 2017 to June 2020, a total of 213 patients underwent laparoscopic ventral and incisional hernia repair with IPOM technique. The mean length and width of the ventral hernia was 4.4 +/- 1.8 cm and 3.6 +/- 1.4 cm, respectively, and the mean BMI was 30.1 +/- 5.2 kg/m(2). The mean operating time was 67 +/- 28 min and was longer for IPOM-pb (71 +/- 27 min), less for IPOM-plus (63 +/- 28 min), and least for sIPOM (61 +/- 26 min). The incidence of early postoperative seroma was least in IPOM-pb (1/98, 1%), and similar in the IPOM-plus (4/94, 4%) and sIPOM (1/21, 5%) group. Late postoperative seroma was found only in IPOM-plus (2, 2%). The incidence of early and late postoperative pain was relatively higher in sIPOM (3, 14%; 1, 5%, respectively) compared to IPOM-pb and IPOM-plus in the early (5, 5% and 6, 6%) and late (2, 2% and 1, 1%) postoperative period, respectively. Surgical site infection was higher in sIPOM group (3, 14%), compared to IPOM-pb (1, 1%), and IPOM-plus (3, 3%). Recurrence rates were similar in IPOM-pb group (3/98, 3%) and IPOM-plus (3/94, 3%), and none in sIPOM (0/21).

    Conclusion: IPOM with peritoneal bridging is as feasible and safe as conventional IPOM with defect closure and simple non-defect closure. However, a large randomised controlled trial is required to confirm this finding.

  • 7.
    Ali, Fathalla
    et al.
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Department of Surgery, Örebro University, Örebro, Sweden; Department of Surgery, Karlskoga Hospital, 69144, Karlskoga, Sweden.
    Sandblom, Gabriel
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden.
    Fathalla, Blend
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden; Emergency Department, Södersjukhuset, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Effect of the SARS-CoV-2 pandemic on planned and emergency hernia repair in Sweden: a register-based study2023In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 27, no 5, p. 1103-1108Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The COVID-19 has had a profound impact on the health care delivery in Sweden, including deprioritization of benign surgeries during the COVID-19 pandemic. The aim of this study was to assess the effect of COVID-19 pandemic on emergency and planned hernia repair in Sweden.

    METHODS: Data on hernia repairs from January 2016 to December 2021 were retrieved from the Swedish Patient Register using procedural codes. Two groups were formed: COVID-19 group (January 2020-December 2021) and control group (January 2016-December 2019). Demographic data on mean age, gender, and type of hernia were collected.

    RESULTS: This study showed a weak negative correlation between the number of elective hernia repairs performed each month during the pandemic and the number of emergency repairs carried out during the following 3 months for inguinal hernia repair (p = 0.114) and incisional hernia repair (p = 0.193), whereas there was no correlation for femoral or umbilical hernia repairs.

    CONCLUSION: The COVID-19 pandemic had a great impact on planned hernia surgeries in Sweden, but our hypothesis that postponing planned repairs would increase the risk of emergency events was not supported.

  • 8.
    Ali, Fathalla
    et al.
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Department of Surgery, Örebro University, Örebro, Sweden; Department of Surgery, Karlskoga Hospital, Karlskoga, Sweden .
    Sandblom, Gabriel
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Southern Hospital (Södersjukhuset), Stockholm, Sweden.
    Forgo, Bianka
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Radiology.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Peritoneal Bridging Versus Nonclosure in Laparoscopic Ventral Hernia Repair2023In: Annals of Surgery Open, E-ISSN 2691-3593, Vol. 4, no 1, article id e257Article in journal (Refereed)
    Abstract [en]

    Introduction: Postoperative seroma and pain are common problems following laparoscopic intraperitoneal onlay mesh (IPOM) repair of ventral hernias. These advers outcomes may be avoided by dissecting and using the peritoneum in the hernial sac to bridge the hernia defect.

    Methods: This was a patient- an and outcome assesor-blinded, parallel-design, randomized controlled trial compairing nonclosure and peritoeal bridging approaches in patients schedueled for elective midline ventral hernia repair. The primary end point was seroma volume on ultrasonography. The secondary end points were postoperative pain, recurrence, and complications.

    Results: Between November 2018 and December 2020, 112 patients were randomized of whom 60 were in the nonclosure group and 52 were in the peritoneal bridging group. The seroma volume in the nonclosure and peritoneal bridging groups were 17cm3(6-53cm3) versus 0cm3(0-26cm3) at 1-moth follow-up (P=0.013). The median volume was zero at 3-, 6-, and 12-month follow-ups in both groups. No significant differences were observed in early postoperative pain (P=0.447) and in recurrencerate (P=0.684). There were 4(7%) and 1(2%) perioperative complictions that lead to reoperations in simple IPOM(sIPOM) and IPOM with peritoneal bridging (IPOM-pb), respectively.

    Conclusion: Seroma was less prevalent after IPOM-pb at 1-month follow-up compaired with sIPOM, with simillar posoperative pain 1 week after index of surgery in both groups. At subsequent follow-ups, the differences in seroma were not statiscally significant. Further studies are required to confirm these results. Trial registration (NCT04229940)

    Keywords: epigastric hernia, incisional hernia, IPOM with fascia closure, IPOM with peritoneal bridging, laparoscopic hernia repair, simple IPOM, umblical hernia, ventral hernia

  • 9.
    Ali, Fathalla
    et al.
    Örebro University, School of Medical Sciences. Departments of Surgery, Örebro University Hospital, Örebro, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. epartments of Surgery, Örebro University Hospital, Örebro, Sweden.
    Fathalla, B.
    Emergency Department, Södersjukhuset, Stockholm, Sweden.
    Sandblom, G.
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Södersjukhuset, Stockholm, Sweden.
    Peritoneal bridging versus fascial closure in laparoscopic intraperitoneal onlay ventral hernia mesh repair: a randomized clinical trial2020In: BJS Open, E-ISSN 2474-9842, Vol. 4, no 4, p. 587-592Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many patients develop seroma after laparoscopic ventral hernia repair. It was hypothesized that leaving the hernial sac in situ may cause this complication.

    METHODS: In this patient- and outcome assessor-blinded, parallel-design single-centre trial, patients undergoing laparoscopic intraperitoneal onlay mesh ventral hernia repair were randomized (1 : 1) to either conventional fascial closure or peritoneal bridging. The primary endpoint was the incidence of seroma 12 months after index surgery detected by CT, evaluated in an intention-to-treat analysis.

    RESULTS: Between September 2017 and May 2018, 62 patients were assessed for eligibility, of whom 25 were randomized to conventional closure and 25 to peritoneal bridging. At 3 months, one patient was lost to follow-up in the conventional and peritoneal bridging groups respectively. No seroma was detected at 6 or 12 months in either group. The prevalence of clinical seroma was four of 25 (16 (95 per cent c.i. 2 to 30) per cent) versus none of 25 patients in the conventional fascial closure and peritoneal bridging groups respectively at 1 month after surgery (P = 0·110), and two of 24 (8 (0 to 19) per cent) versus none of 25 at 3 months (P = 0·235). There were no significant differences between the groups in other postoperative complications (one of 25 versus 0 of 25), rate of recurrent hernia within 1 year (none in either group) or postoperative pain.

    CONCLUSION: Conventional fascial closure and peritoneal bridging did not differ with regard to seroma formation after laparoscopic ventral hernia repair.

    TRIAL REGISTRATION: ClinicalTrials.gov (NCT03344575).

  • 10.
    Daskalakis, Kosmas
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Tsoli, M.
    National and Kapodistrian University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Kogut, A.
    Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Medical University of Silesia, Katowice, Poland.
    Srirajaskanthan, R.
    ENETS Centre of Excellence, Neuroendocrine Tumour Unit, King’s College Hospital, London, United Kingdom.
    Giovos, G.
    The ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence (CoE), University Hospitals Coventry and Warwickshire NHS Trust, London, United Kingdom.
    Weickert, M. O.
    The ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence (CoE), University Hospitals Coventry and Warwickshire NHS Trust, London, United Kingdom.
    Kos-Kudla, B.
    ENETS Centre of Excellence, Neuroendocrine Tumour Unit, King’s College Hospital, London, United Kingdom.
    Kaltsas, G.
    National and Kapodistrian University of Athens, Athens, Greece.
    MODIFIED HISTOPATHOLOGICAL GRADING OPTIMIZES PREDICTION OF SURVIVAL OUTCOMES IN SMALL INTESTINAL NEUROENDOCRINE TUMOURS2024In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 111, no Suppl. 4, article id znae104002Article in journal (Other academic)
    Abstract [en]

    Background: We aimed to identify optimal grading Ki-67 cut-offs to delineate differences in prognosis of patients with small intestinal neuroendocrine tumours (SI-NETs) in terms of overall- and event-free survival rates.

    Methods: We included 551 patients with SI-NETs diagnosed from June 15th, 1993, through March 8th, 2021, identified using the SI-NET databases from five European referral centers.

    Results: Median age at baseline was 62.3(17-90) years; 252 patients were women (45.7%). All tumours were well-differentiated; 326 were G1 tumours (59.2%), 169 G2(30.7%), only 8 G3(1.5%), while 48 tumourswere of unspecified grade (8.7%). The median Ki67 was 2%(1-70%). 247 patients(44.8%) had distant metastases at baseline (stage IV), 217locoregional disease (41.1%; stage III), whereas 29(7.1%) and 25(4.5%) presented at stages II and I, respectively. Within a mean(SD) follow-up of 51.5(52.9) months, 94 patients(17.1%) died, whereas overall 188 experienced disease recurrence, progression and/or death(34.1%). The median OS was 214.7(95%CI: 152.7-276.6) months and the median EFS was 79.8(95%CI: 68.2-91.5) months, respectively. In multivariable Cox-regression OS analysis, age (HR=1.07, 95%CI: 1.04-1.09; p<0.001), Charlson Comorbidity Index(HR=1.1, 95%CI: 1.03-1.17; p=0.006) and the proposed modified histopathological Ki67 grading system(K67:5-10% group: HR=2.4, 95%CI: 1.3-4.5; p=0.007 and K67≥10% group: HR=5.1, 95%CI: 2.9-9.2; p<0.001) were independent predictors for death. Pertinent EFS analysis, confirmed age(HR=1.04, 95%CI: 1.02-1.05;p<0.001) and the proposed modified histopathological Ki67 grading system(K67≥10% group: HR=4; 95%CI:2.5-6.2;p<0.001) as independent predictors for recurrence, progression and/or death.

    Conclusions: Ki-67 proliferation index is an independent predictor of EFS and OS. A modified site-specific histopathological grading system applying Ki-67 cut-offs of 5% and 10% seems more optimal to predict differences in SI-NET patient prognosis

  • 11.
    Dehlaghi Jadid, Kaveh
    et al.
    Örebro University, School of Medical Sciences.
    Gadan, Soran
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Matthiessen, Peter
    Örebro University, School of Medical Sciences.
    Postoperative inflammatory response in patients undergoinglaparoscopic and robotic rectal cancer resectionManuscript (preprint) (Other academic)
  • 12.
    Dehlaghi Jadid, Kaveh
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Gadan, Soran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Nordenwall, Caroline
    Department of Pelvic Cancer, GI Oncology and Colorectal Surgery Unit, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden .
    Boman, Sol Erika
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Hed Myrberg, Ida
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Matthiessen, Peter
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Does socio-economic status influence the choice of surgical techniquein abdominal rectal cancer surgery?Manuscript (preprint) (Other academic)
  • 13.
    Falhammar, Henrik
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Deptartment of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Calissendorff, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Acute suppurative thyroiditis with thyroid abscess in adults: clinical presentation, treatment and outcomes2019In: BMC Endocrine Disorders, E-ISSN 1472-6823, Vol. 19, no 1, article id 130Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Abscess in the thyroid gland is a rare but severe infectious disease. The condition can have anatomic or iatrogenic underlying causes. If untreated it could be fatal. Pathogens vary considerably. Treatment is intravenous antibiotics, drainage, and sometimes surgery.

    METHODS: The electronic medical records of all adult patients with acute thyroiditis 2003-2017 treated at the Karolinska University Hospital (catchment area 2 million) in Sweden were systematically reviewed.

    RESULTS: Five patients were found in the catchment area. One patient from another region but known to us was also included. Thus, six patients (aged 28-73 years) were included in the study. Median length of hospital stay was 7.5 days (4-79 days). All were treated with antibiotics (intravenous n = 5, oral n = 1). Total antibiotic treatment duration was 13.5 days (10-41 days). Blood cultures were positive in three (streptococcus pneumonia, streptococci sanguineous, pepto streptococci), deep tissue culture in three (Escherichia coli, Candida, Hemophilic influenza) and no positive culture at all in two. Drainage was used in three patients. All patients recovered without recurrences. Surgery was performed twice in the acute phase in one. There was no recurrence during 7 years (3-12) of follow-up, but one patient died after three years (severe heart failure and pneumonia).

    CONCLUSION: Thyroid abscess in adults is extremely rare nowadays in the developed world. With prompt antibiotic therapy, drainage and in some cases thyroidectomy the prognosis seems favourable.

  • 14.
    Giesecke, Peter
    et al.
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Frykman, Viveka
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Wallin, Göran K.
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lönn, Stefan
    Department of Research and Development, Region Halland, Halmstad, Sweden.
    Discacciati, Andrea
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Törring, Ove
    Department of Clinical Research and Education, Karolinska Institute, Stockholm, Sweden.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    All-cause and cardiovascular mortality risk after surgery versus radioiodine treatment for hyperthyroidism2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 3, p. 279-286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women.

    METHODS: Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery between 1976 and 2000. Comparisons between treatments were made to assess all-cause and cause-specific deaths to 2013. Three different statistical methods were applied: Cox regression, propensity score matching and inverse probability weighting.

    RESULTS: Of the 10 992 patients included, 10 250 had been treated with radioiodine (mean age 65·1 years; 8668 women, 84·6 per cent) and 742 had been treated surgically (mean age 44·1 years; 633 women, 85·3 per cent). Mean duration of follow-up varied between 16·3 and 22·3 years, depending on the statistical method used. All-cause mortality was significantly lower among surgically treated patients, with a hazard ratio of 0·82 in the regression analysis, 0·80 in propensity score matching and 0·85 in inverse probability weighting. This was due mainly to lower cardiovascular mortality in the surgical group. Men in particular seemed to benefit from surgery compared with radioiodine treatment.

    CONCLUSION: Compared with treatment with radioiodine, surgery for hyperthyroidism is associated with a lower risk of all-cause and cardiovascular mortality in the long term. This finding was more evident among men.

  • 15.
    Giesecke, Peter
    et al.
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Frykman, Viveka
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Friberg, Leif
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Höijer, Jonas
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lönn, Stefan
    Research and Development, Region Halland, Halmstad, Sweden.
    Törring, Ove
    Department of Clinical Research and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter2017In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 27, no 7, p. 878-885Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.

    METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.

    RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.

    CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

  • 16.
    Holmberg, M.
    et al.
    University of Gothenburg, Institute of Medicine, Sahlgrenska Academy, Stockholm, Sweden; Karolinska University Hospital, ANOVA, Stockholm, Sweden.
    Sjölin, Gabriel
    Örebro University Hospital, Faculty of Medicine and Health, Örebro, Sweden.
    Byström, Kristina
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Khamisi, S.
    Deparment of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Medicine, Uppsala University Hospital, Uppsala, Sweden.
    de Laval, D.
    Department of Medicine, Blekinge Hospital, Karlskrona, Sweden.
    Abraham-Nordling, M.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Calissendorff, J.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Lantz, M.
    Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.
    Hallengren, B.
    Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.
    Filipsson Nyström, H.
    University of Gothenburg, Institute of Medicine, Sahlgrenska Academy, Stockholm, Sweden; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Törring, O.
    Institution for Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Internal Medicine, Södersjukhuset, Stockholm, Sweden.
    Wallin, Göran
    Örebro University Hospital, Faculty of Medicine and Health, Örebro, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Treatment outcome 6-10 years after diagnosis of hyperthyroidism in 2916 patients: a longitudinal evaluation of a swedish incidence cohort2018In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, no S1, article id 219Article in journal (Other academic)
    Abstract [en]

    Treatment of Graves’ disease (GD) and toxic nodular goiter (TNG) has the objectives to cure hyperthyroidism, prevent recurrent disease and preserve thyroid function. Treatment efficacies and long-termout comes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery varies in the literature. We report outcome of treatment, cure rate and risk factors for relapse for GD and TNG in an unselected cohort. A prospective incidence-cohort of de novo diagnosed GD and TNG patients (n = 2916) from 2003-05, were invited to a follow-up 6 - 10 years after diagnosis. Questionnaires were sent to 2430 patients regarding treatments, cure rate, recurrence, quality of life, demographic data, comorbidities and life-style factors. Patients were treated according to clinical routine with ATD, RAI or surgery. Of those included, 1186 (83.3%) had GD and 237 (16.7%) had TNG. In GD patients, 351 (45.3%), 264 (81.5%), and 52 (96.3%) were cured by ATD, RAI or surgery respectively as first line treatment. Of those, 77.0%, 15.4% and 3.8% respectively were without levothyr-oxine supplementation at follow-up at 8 – 0.9 years. Including all treatment modalities, 851 (71.8%) of GD patients were cured within one treatment period. At follow-up, 278 (23%) of GD patients had been operated. In TNG patients, RAI cured 88.6% and surgery 92.9%, whereof 52/154 (33.8%) and 3/15 (20%) had no levothyroxine supplementation post RAI and surgery, respectively.The proportion that did not feel fully recovered at follow-up was 25.3% of GD and 18.1% of the TNG patients. Overall, treatment of hyperthyroidism results in preserved thyroid function only in 35.3% and 44.7% of GD and TNG cases, respectively. As many as 23.4% of the GD patients end up with surgery although only 4.6% choose it from the beginning. Our treatment tradition cures 71.8% of GD patients and 78.1% of TNG patients within one treatment period. The high number of patients who do not feel recovered 6 -10 years after hyperthyroidism in GD and TNG is are minder of the chronic nature of hyperthyroidism.

  • 17.
    Inabnet, William B.
    et al.
    Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, USA.
    Palazzo, Fausto
    Hammersmith Hospital and Imperial College, London, UK.
    Sosa, Julie Ann
    University of California, San Francisco, CA, USA.
    Kriger, Joshua
    Columbia University Mailman School of Public Health, New York, NY, USA.
    Aspinall, Sebastian
    Aberdeen Royal Infirmary, Aberdeen, Scotland, UK.
    Barczynski, Marcin
    Department of Endocrine Surgery, Third Chair of General Surgery, Jagiellonian University Medical College, Krakow, Poland.
    Doherty, Gerard
    Brigham and Women's Hospital, Boston, MA, USA.
    Iacobone, Maurizio
    University of Padua, Padua, Italy.
    Nordenström, Erik
    Lund University, Lund, Sweden.
    Scott-Coombes, David
    University Hospital of Wales, Cardiff, UK.
    Wallin, Göran
    Örebro University, School of Medical Sciences.
    Williams, Lauren
    Columbia University Mailman School of Public Health, New York, NY, USA.
    Bray, Rachel
    Columbia University Mailman School of Public Health, New York, NY, USA.
    Bergenfelz, Anders
    Lund University, Lund, Sweden.
    Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents2020In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 44, no 2, p. 426-435Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category.

    METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed.

    RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males.

    CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

  • 18.
    Katawazai, A
    et al.
    Örebro University, School of Medical Sciences. Departments of Surgery, School of Medical Sciences, Örebro University Hospital, Örebro University, Stockholm, Sweden; Örebro University Hospital, Faculty of Medicine and Health, Örebro University, Stockholm, Sweden; Department of Surgery, Karlskoga Hospital, Karlskoga, Sweden.
    Wallin, G.
    Örebro University, School of Medical Sciences. Departments of Surgery, School of Medical Sciences, Örebro University Hospital, Örebro University, Stockholm, Sweden; Örebro University Hospital, Faculty of Medicine and Health, Örebro University, Stockholm, Sweden.
    Sandblom, G.
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden; Department of Surgery, Södersjukhuset, Stockholm, Sweden.
    Long-term reoperation rate following primary ventral hernia repair: a register-based study2022In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 26, no 6, p. 1551-1559Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to analyse the risk for reoperation following primary ventral hernia repair.

    Methods: The study was based on umbilical hernia and epigastric hernia repairs registered in the population-based Swedish National Patient Register (NPR) 2010-2019. Reoperation was defined as repeat repair after primary repair.

    Results: Altogether 29,360 umbilical hernia repairs and 6514 epigastric hernia repairs were identified. There were 624 reoperations registered following primary umbilical repair and 137 following primary epigastric repairs. In multivariable Cox proportional hazard analysis, the hazard ratio (HR) for reoperation was 0.292 (95% confidence interval (CI) 0.109-0.782) after open onlay mesh repair, 0.484 (CI 0.366-0.641) after open interstitial mesh repair, 0.382 (CI 0.238-0.613) after open sublay mesh repair, 0.453 (CI 0.169-1.212) after open intraperitoneal onlay mesh repair, 1.004 (CI 0.688-1.464) after laparoscopic repair, and 0.940 (CI 0.502-1.759) after other techniques, when compared to open suture repair as reference method. Following umbilical hernia repair, the risk for reoperation was also significantly higher for patients aged < 50 years (HR 1.669, CI 1.389-2.005), for women (HR 1.401, CI 1.186-1.655), and for patients with liver cirrhosis (HR 2.544, CI 1.049-6.170). For patients undergoing epigastric hernia repair, the only significant risk factor for reoperation was age < 50 years (HR 2.046, CI 1.337-3.130).

    Conclusions: All types of open mesh repair were associated with lower reoperation rates than open suture repair and laparoscopic repair. Female sex, young age and liver cirrhosis were risk factors for reoperation due to hernia recurrence, regardless of method.

  • 19.
    Katawazai, Asmatullah
    et al.
    Örebro University, School of Medical Sciences. Departments of Surgery.
    Sandblom, G.
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Departments of Surgery.
    BJS-02 LONG-TERM REOPERATION RATE FOLLOWING PRIMARY VENTRAL HERNIA REPAIR: A REGISTER-BASED STUDY2022In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 109, no Suppl. 7Article in journal (Other academic)
    Abstract [en]

    Aim: The aim of this study was to analyse the risk for reoperation following primary ventral hernia repair.

    Methods: The study was based on umbilical hernia and epigastric hernia repairs registered in the population-based Swedish National Patient Register (NPR) 2010–2019. Reoperation was defined as repeat repair after primary repair.

    Results: Altogether 30,253 umbilical hernia repairs and 7407 epigastric hernia repairs were identified. There were 624 reoperations registered following primary umbilical repair and 137 following primary epigastric repairs. In multivariable Cox proportional hazard analysis, the hazard ratio (HR) for reoperation was 0.284 (95% confidence interval (CI) 0.106–0.760) after open onlay mesh repair, 0.476 (CI 0.359–0.629) after open interstitial mesh repair, 0.368 (CI 0.230–0.590) afteropen sublay mesh repair, 0.446 (CI 0.167–1.194) after open intraperitoneal onlay mesh repair, 0.931 (CI 0.639–1.357) after laparoscopic repair, and 0.939 (CI 0.502–1.757) after other (unknown) techniques, when compared to open suture repair as reference method. Following umbilical hernia repair, the risk for reoperation was also significantly higher for patients aged ≤49 years (HR 1.669, CI 1.391–2.002), for women (HR 1.390, CI 1.178–1.641), and for patients with liver cirrhosis (HR 2.546, CI 1.050–6.174). For patients undergoing epigastric hernia repair, the only significant risk factor for reoperation was age ≤49 years (HR 2.079, CI 1.380–3.134).

    Conclusions: All types of open mesh repair were associated with lower reoperation rates than open suture repair and laparoscopic repair. Female sex, young age and liver cirrhosis were risk factors for reoperation due to hernia recurrence, regardless of method.

  • 20.
    Khamisi, Selwan
    et al.
    Uppsala University Department of Medical Sciences, 214437, Uppsala, Sweden; Uppsala University Hospital, 59561, Uppsala, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Calissendorff, Jan
    Karolinska Institute Department of Molecular Medicine and Surgery, 174449, Stockholm, Stockholm, Sweden.
    Filipsson Nyström, Helena
    Sahlgrenska Academy, 70712, Dept. of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden.
    Holmberg, Mats
    Sahlgrenska Academy, 70712, Goteborg, Sweden.
    Hallengren, Bengt
    Lund University Faculty of Medicine, 59568, Dept. of Endocrinology, Skånes University Hospital, Lund, Sweden.
    Lantz, Mikael
    Lund University, Department of Clinical Sciences, Diabetes & Endocrinology, Department of Endocrinology, Jan Waldenströmsgata 15, Skåne University Hospital, Malmö, Sweden.
    Planck, Tereza
    Department of Clinical Sciences, Diabetes & Endocrinology, CRC, Ing 72, hus 91, plan 12, Skåne University Hospital, Malmö, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Institutet, 27106, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Departgment of Surgery.
    Ljunggren, Östen
    Uppsala University Department of Medical Sciences, 214437, Uppsala, Sweden.
    Fracture incidence in Graves' disease: A population-based study2023In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 33, no 11, p. 1349-1357Article in journal (Refereed)
    Abstract [en]

    Background Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods A total of 2134 patients with incident GD and 21261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to ten age, sex- and county-matched controls per patient were selected from databases from The National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and 95% confidence intervals. Results There were no significant differences in fracture rates between GD and controls but after adjustment for co-morbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 (1.05-7.64). The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

  • 21.
    Kjellman, Magnus
    et al.
    Endocrine Surgery Unit, Karolinska Hospital, Stockholm, Sweden.
    Knigge, Ulrich
    Department of Endocrinology and Gastrointestinal Surgery, ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Welin, Staffan
    Department of Endocrine Oncology, ENETS Neuroendocrine Tumor Centre of Excellence, Uppsala University Hospital, Uppsala, Sweden.
    Thiis-Evensen, Espen
    Department of Gastroenterology, ENETS Neuroendocrine Tumor Centre of Excellence, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
    Gronbaek, Henning
    Department of Hepatology and Gastroenterology, ENETS Neuroendocrine Tumor Centre of Excellence, Aarhus University Hospital, Aarhus, Denmark.
    Schalin-Jäntti, Camilla
    Department of Endocrinology, Abdominal Center, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland.
    Sorbye, Halfdan
    Department of Oncology and Department of Clinical Science, Haukeland University Hospital, Bergen, Norway.
    Joergensen, Maiken Thyregod
    Department of Medical Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
    Johanson, Viktor
    Department of Surgery, Institute of Clinical Sciences at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Metso, Saara
    Unit of Endocrinology, Department of Internal Medicine, Tampere University Hospital, Teiskontie Tampere, Tampere, Finland.
    Waldum, Helge
    St. Olavs Hospital, Trondheim, Norway.
    Søreide, Jon Arne
    Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
    Ebeling, Tapani
    Faculty of Medicine, University of Oulu, Oulu, Finland; Division of Endocrinology, Oulu University Hospital, Oulu, Finland.
    Lindberg, Fredrik
    Department of Surgery, Norrland University Hospital, Umeå, Sweden.
    Landerholm, Kalle
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Surgery, Ryhov County Hospital, Jönköping, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences.
    Salem, Farhad
    Skånes University Hospital, Unit for Endocrine and Sarcoma Surgery, Lund, Sweden.
    Schneider, Maria del Pilar
    IPSEN Innovation SAS, Les Ulis, France.
    Belusa, Roger
    IPSEN, Kista Science Tower, Kista, Sweden.
    A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors2021In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 111, no 9, p. 840-849Article in journal (Refereed)
    Abstract [en]

    Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs.

    Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques.

    Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake.

    Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.

  • 22.
    Koumarianou, Anna
    et al.
    Hematology Oncology Unit, Fourth Department of Internal Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece..
    Alexandraki, Krystallenia I.
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review2020In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, no 6, article id E1777Article, review/survey (Refereed)
    Abstract [en]

    Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.

  • 23.
    Lind, Patrik
    et al.
    Örebro University, School of Medical Sciences. Anesthesiology Department, Skellefteå Hospital, Skellefteå, Sweden; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nordenström, Erik
    Department of Surgery, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
    Johansson, Lars
    Department of Public Health and Clinical Medicine, Skellefteå Research Unit, Umeå University, 901 81, Umeå, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery; Second Department of Surgery, "Korgialenio-Benakio," Red Cross General Hospital, Athens, Greece.
    Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer2024In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 409, no 1, article id 68Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting.

    METHODS: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports.

    RESULTS: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18-94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001).

    CONCLUSIONS: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

  • 24.
    Mauri, Giovanni
    et al.
    Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Division of Interventional Radiology, European Institute of Oncology, IRCCS, Milan, Italy.
    Hegedüs, Laszlo
    Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
    Bandula, Steven
    Interventional Oncology Service, University College Hospital, London, United Kingdom.
    Cazzato, Roberto Luigi
    Department of Interventional Radiology, University Hospital of Strasbourg, Strasbourg, France.
    Czarniecka, Agnieszka
    The Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland.
    Dudeck, Oliver
    Center for Microtherapy, Klinik Hirslanden, Zurich, Switzerland.
    Fugazzola, Laura
    Department of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
    Netea-Maier, Romana
    Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
    Russ, Gilles
    Thyroid and Endocrine Tumors Unit, La Pitie-Salpetriere Hospital, Sorbonne University, Paris, France.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Papini, Enrico
    Department of Endocrinology & Metabolism, Ospedale Regina Apostolorum, Albano, Italy.
    European Thyroid Association and Cardiovascular and Interventional Radiological Society of Europe 2021 Clinical Practice Guideline for the Use of Minimally Invasive Treatments in Malignant Thyroid Lesions2021In: European thyroid journal, ISSN 2235-0640, Vol. 10, no 3, p. 185-197Article in journal (Refereed)
    Abstract [en]

    The growing detection of papillary thyroid microcarcinomas (PTMCs) is paralleled by an increase in surgical procedures. Due to the frequent indolent nature, cost, and risk of surgery, active surveillance (AS) and ultrasound-guided minimally invasive treatments (MITs) are in suitable cases of incidental PTMC proposed as alternatives to thyroidectomy. Surgery and radioiodine are the established treatments for relapsing cervical differentiated thyroid carcinoma (DTC) metastases. But radioiodine refractoriness, risk of surgical complications, adverse influence on quality of life, or declining repeat surgery have led to AS and MIT being considered as alternatives for slow-growing DTC nodal metastases. Also, for distant radioiodine-refractory metastases not amenable to surgery, MIT is proposed as part of a multimodality therapeutic approach. The European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe commissioned these guidelines for the appropriate use of MIT. Based on a systematic PubMed search, an evidence-based approach was applied, and both knowledge and practical experience of the panelists were incorporated to develop the manuscript and the specific recommendations. We recommend that when weighing between surgery, radioiodine, AS, or MIT for DTC, a multidisciplinary team including members with expertise in interventional radiology assess the demographic, clinical, histological, and imaging characteristics for appropriate selection of patients eligible for MIT. Consider TA in low-risk PTMC patients who are at surgical risk, have short life expectancy, relevant comorbidities, or are unwilling to undergo surgery or AS. As laser ablation, radiofrequency ablation, and microwave ablation are similarly safe and effective thermal ablation (TA) techniques, the choice should be based on the specific competences and resources of the centers. Use of ethanol ablation and high-intensity focused ultrasound is not recommended for PTMC treatment. Consider MIT as an alternative to surgical neck dissection in patients with radioiodine refractory cervical recurrences who are at surgical risk or decline further surgery. Factors that favor MIT are previous neck dissection, presence of surgical complications, small size metastases, and <4 involved latero-cervical lymph nodes. Consider TA among treatment options in patients with unresectable oligometastatic or oligoprogressive distant metastases to achieve local tumor control or pain palliation. Consider TA, in combination with bone consolidation and external beam radiation therapy, as a treatment option for painful bone metastases not amenable to other established treatments.

  • 25.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Department of Geriatrics, Örebro University Hospital, Örebro, Sweden.
    Humble, Mats B.
    Örebro University, School of Medical Sciences. Psychiatric Research Centre, Örebro University Hospital, Örebro, Sweden.
    Yazarloo, Payam
    Department of Psychiatry, Ryhov Hospital, Jönköping, Sweden .
    Järhult, Johannes
    Department of Surgery, Ryhov Hospital, Jönköping, Sweden .
    Wallin, Göran
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Reply to comments From Dr Lozano, et al - Concerning the prevalence of lithium-associated hyperparathyroidism2016In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 36, no 2, p. 191-192Article in journal (Refereed)
  • 26.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Department of Geriatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Kardell, Mathias
    Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden.
    Landén, Mikael
    Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden: Sahlgrenska University Hospital, Gothenburg, Sweden.
    Järhult, Johannes
    Department of Surgery, Ryhov Hospital, Jönköping, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 415-424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.

    METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.

    RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.

    CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

  • 27.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Department of Geriatrics.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Järhult, Johannes
    Department of Surgery, Ryhov Hospital, Jönköping, Sweden.
    Characterization of Calcium Homeostasis in Lithium-Treated Patients Reveals Both Hypercalcaemia and Hypocalcaemia2020In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 44, no 2, p. 517-525Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Prevalence studies demonstrate that a significant proportion of lithium-treated patients develop hypercalcaemia (3-30%). Lithium-associated hyperparathyroidism (LHPT) is poorly defined, and calcium homeostasis may be affected in a more complicated fashion than purely by elevated PTH secretion. The current study aims to examine in detail calcium homeostasis principally with regard to lithium duration.

    METHODS: Medical records of 297 lithium-treated patients (193 women, 104 men; median age 58 years) were examined, and information on gender, age, lithium treatment duration and calcium homeostasis was obtained. The median treatment duration with lithium was 16 (1.5-45) years.

    RESULTS: A total of 8504 calcium values were retrieved. Before initiation of lithium treatment, serum calcium was on average 2.33 mmol/l (2.02-2.60). During the treatment period, 178 patients (60%) remained normocalcaemic, 102 (34%) developed hypercalcaemia or were strongly suspected of LHPT, 17 (6%) had 3 or more intermittent episodes of hypocalcaemia. Forty-one per cent of patients with suspected or confirmed LHPT had low (<4 mmol) 24-h urine calcium levels. The success rate after 33 parathyroidectomies was 35%, hyperplasia being diagnosed in 75% of extirpated glands.

    CONCLUSIONS: The prevalence of hypercalcaemia during lithium treatment is very high. In addition, hypocalcaemic episodes appear to occur frequently, possibly reflecting a more complicated parathyroid dysfunction than previously known. Long-term surgical results are unsatisfactory. LHPT biochemical profile is different from that of primary hyperparathyroidism and is in some ways similar to familial hypocalciuric hypercalcaemia.

  • 28.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences.
    Järhult, Johannes
    Obstacles and possibilities in the evaluation of surgical treatment for lithium-associated hyperparathyroidism through a randomized controlled trial2020In: SAGE Research Methods Cases: Medicine and Health, Sage Publications, 2020Chapter in book (Refereed)
  • 29.
    Meehan, Adrian
    et al.
    Örebro University, School of Medical Sciences.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Järhult, Johannes
    Ryhov Hospital, Jönköping, Sweden.
    Characterization of Calcium homeostasis in Lithium-treated Patients: Disturbances reveal both hypercalcemia and hypocalcemiaManuscript (preprint) (Other academic)
  • 30.
    Pirouzram, Artai
    et al.
    Department of Cardiothoracic and Vascular Surgery, Linköping University Hospital, Sweden.
    Hamam, Leonardo
    Department of Surgery, Höglandssjukhuset Eksjö, Region Jönköping County Council, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Larzon, Thomas
    Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and Health, Örebro University, Sweden.
    Nilsson, Kristofer F.
    Örebro University, School of Medical Sciences. Department of Cardiothoracic and Vascular Surgery.
    Novel Experimental Technique to Create Size-Controlled Retroperitoneal Bleeding in the Infrarenal Aorta of Anesthetized Pigs2021In: Innovations (Philadelphia): technology and techniques in cardiothoracic and vascular surgery, ISSN 1556-9845, E-ISSN 1559-0879, Vol. 16, no 4, p. 379-385Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Rupture of abdominal aortic aneurysm (rAAA) with a contained retroperitoneal hematoma is potentially fatal. Physiological studies are difficult to perform in patients suffering from life-threatening conditions such as rAAA. A translational model of the condition is therefore needed. The aim was to develop and validate an endovascular animal model for retroperitoneal bleeding of the abdominal aorta with contained hematoma.

    METHODS: = 6). Onset of bleeding was verified by angiography and macroscopically examined on completion of the experiments. Survival up to 180 min was the primary outcome. Hemodynamic and metabolic markers in arterial blood were secondary outcomes.

    RESULTS: = 0.002), but not when comparing the 6 mm and 8 mm groups. Systemic hypotension, arterial acidosis, and lactatemia were provoked in the 6 mm and 8 mm groups but not in the 4 mm group.

    CONCLUSIONS: A porcine model for a controlled contained left posterolateral retroperitoneal bleeding was created using endovascular methods and validated. This model makes it possible to study the pathophysiology of a retroperitoneal hematoma.

  • 31.
    Sjölin, Gabriel
    et al.
    Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Byström, Kristina
    Örebro University, School of Medical Sciences. Dept. of Medicine, University Hospital, Örebro, Sweden.
    Holmberg, Mats
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg; ANOVA, Karolinska University Hospital, Stockholm .
    Törring, Ove
    Institution for Clinical Science and Education, Karolinska Institutet, Stockholm.
    Khamisi, Selwan
    Dept. of Endocrinology, Uppsala University Hospital, Uppsala; Dept. of Medical Sciences, Uppsala University, Uppsala .
    Calissendorff, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm .
    Lantz, Mikael
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Hallengren, Bengt
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Filipsson Nyström, Helena
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg; Dept. of Endocrinology, Sahlgrenska University Hospital, Göteborg; Wallenberg Center for Molecular and Translational Medicine, Göteborg.
    Planck, Teresa
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Wallin, Göran
    Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm .
    Treatment of patients with Graves' disease in Sweden compared to international surveys of an “index patient”Manuscript (preprint) (Other academic)
  • 32.
    Sjölin, Gabriel
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Holmberg, Mats
    Karolinska Universitetssjukhuset, ANOVA, Stockholm, Sweden.
    Törring, Ove
    Karolinska Institute, Stockholm County, Stockholm, Sweden.
    Byström, Kristina
    Örebro University, School of Medical Sciences. Dept. of Medicine, Örebro University Hostpital, Örebro, Sweden.
    Khamisi, Selwan
    Akademiska sjukhuset, Dept. of Endocrinology and diabetes, Uppsala, Sweden.
    de Laval, Dorota
    Blekingesjukhuset i Karlskrona, Department of Medicine, Karlskrona, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Stockholm County, Sweden.
    Calissendorff, Jan
    Karolinska Universitetssjukhuset, Dept. of Endocrinology, Metabolism and Diabetes, Stockholm, Sweden.
    Lantz, Mikael
    Lund University, Lund, Sweden.
    Hallengren, Bengt
    Lund University, Lund, Sweden.
    Filipsson Nyström, Helena
    Sahlgrenska Academy, Dept. of Endocrinology, Göteborg, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
    The long-term outcome of treatment for Graves' hyperthyroidism2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 11, p. 1545-1557Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The treatment efficacy of antithyroid drug therapy (ATD), radioactive iodine (I131) or surgery for Graves' hyperthyroidism is well described. However, there are few reports on the long-term total outcome of each treatment modality as how many require levothyroxine supplementation, the need of thyroid ablation or the individual patient's estimation of their recovery.

    METHODS: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003-2005 (n=2430). The patients were invited to participate in a longitudinal study spanning 8±0.9years (mean±SD) after diagnosis. We were able to follow 1186 (60%) patients that had been treated with ATD, I131 or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities and lifestyle factors through questionnaires and review of the individual medical history records.

    RESULTS: At follow-up the remission rate after first line treatment choice with ATD was 45.3% (351/774), with I-131 therapy 81.5% (324/264) and with surgery 96.3% (52/54). Among those patients who had a second course of ATD 29.4% achieved remission. The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of which 23% (278/1186) had received surgery, 43% (505/1186) I-131 therapy including 2% (20/1186) who received both surgery and I-131. Patients who received ATD as first treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the I131treated and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%.

    CONCLUSION: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus has unexpected long-term consequences for many patients.

  • 33.
    Sjölin, Gabriel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept. of Surgery, University Hospital, Örebro, Sweden.
    Watt, Torquil
    Department of Medical Endocrinology Rigshospitalet, Copenhagen, Denmark; Internal Medicine Herlev Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
    Byström, Kristina
    Örebro University, School of Medical Sciences. Dept. of Medicine, University Hospital, Örebro, Sweden.
    Calissendorff, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Cramon, Per Karkov
    Department of Medical Endocrinology Rigshospitalet, Copenhagen, Denmark; Internal Medicine Herlev Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
    Nyström, Helena Filipsson
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Dept. of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden; Wallenberg Center for Molecular and Translational Medicine, Göteborg, Sweden.
    Hallengren, Bengt
    Dept. of Endocrinology, Skåne University Hospital, Malmö, Sweden; Dept. of Clinical Sciences, Lund University, Lund, Sweden.
    Holmberg, Mats
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; ANOVA, Karolinska University Hospital, Stockholm, Sweden .
    Khamisi, Selwan
    Dept. of Endocrinology, Uppsala University Hospital, Uppsala, Sweden; Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Lantz, Mikael
    Dept. of Endocrinology, Skåne University Hospital, Malmö, Sweden; Dept. of Clinical Sciences, Lund University, Lund, Sweden.
    Planck, Tereza
    Dept. of Endocrinology, Skåne University Hospital, Malmö, Sweden; Dept. of Clinical Sciences, Lund University, Lund, Sweden.
    Törring, Ove
    Institution for Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Dept. of Surgery, University Hospital, Örebro, Sweden.
    Long term outcome after toxic nodular goitre2022In: Thyroid Research, ISSN 1756-6614, Vol. 15, no 1, article id 20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort.

    METHODS: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines.

    RESULTS: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population.

    CONCLUSION: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.

  • 34.
    Sjölin, Gabriel
    et al.
    Örebro University, School of Medical Sciences.
    Watt, Torquil
    Department of Medical Endocrinology Rigshospitalet, Copenhagen, Denmark; Internal Medicine Herlev Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
    Byström, Kristina
    Örebro University, School of Medical Sciences.
    Calissendorff, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm .
    Karkov Cramon, Per
    Department of Medical Endocrinology Rigshospitalet, Copenhagen, Denmark; Internal Medicine Herlev Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
    Filipsson Nyström, Helena
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg; Dept. of Endocrinology, Sahlgrenska University Hospital, Göteborg; Wallenberg Center for Molecular and Translational Medicine, Göteborg.
    Hallengren, Bengt
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Holmberg, Mats
    Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg; ANOVA, Karolinska University Hospital, Stockholm .
    Khamisi, Selwan
    Dept. of Endocrinology, Uppsala University Hospital, Uppsala; Dept. of Medical Sciences, Uppsala University, Uppsala .
    Lantz, Mikael
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Planck, Tereza
    Dept. of Endocrinology, Skåne University Hospital, Malmö; Dept. of Clinical Sciences, Lund University, Lund.
    Törring, Ove
    Institution for Clinical Science and Education, Karolinska Institutet, Stockholm.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm .
    Thyroid-related quality of life impairment persists 6-10 years after diagnosis of toxic nodular goitreManuscript (preprint) (Other academic)
  • 35.
    Tsoli, Marina
    et al.
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Spei, Maria-Eleni
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 1st Department of Propaedeutic Internal Medicine, Endocrine Unit, National and Kapodistrian, University of Athens, Athens, Greece; Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden..
    Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis2020In: Cancers, ISSN 2072-6694, Vol. 12, no 8, article id E2246Article, review/survey (Refereed)
    Abstract [en]

    The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53-1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24-3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.

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    Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis
  • 36.
    Törring, Ove
    et al.
    Karolinska Institutet, Institution for Clinical Science and Education, Stockholm, Sweden .
    Watt, Torquil
    Copenhagen University Hospital Rigshospitalet, Department of Medical Endocrinology, Copenhagen, Danmark, Denmark .
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery.
    Byström, Kristina
    Örebro University, School of Medical Sciences. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Institute, Institute of molecular medicine and surgery, Colorectal surgery, Karolinska University Hospital, Stockholm, Sweden .
    Calissendorff, Jan
    Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Cramon, Per
    Copenhagen University Hospital Rigshospitalet, Department of Endocrinology, Copenhagen, Denmark .
    Filipsson Nyström, Helena
    Dept. of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden .
    Hallengren, Bengt
    Dept. of Endocrinology, Skånes University Hospital, Malmö, Sweden.
    Holmberg, Mats
    ANOVA, Karolinska University Hospital, Stockholm, Sweden.
    Khamisi, Selwan
    Dept. of Endocrinology, Uppsala University Hospital, Uppsala, Sweden .
    Lantz, Mikael
    Lund University, Department of Clinical Sciences, Diabetes & Endocrinology, Department of Endocrinology, Skåne University Hospital, Malmö, Sweden .
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
    Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves’ Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 3, p. 322-331Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hyperthyroidism is known to have a significant impact on the quality of life (QoL) at least in the short term. The purpose of the present study was to assess QoL in patients at 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both a thyroid-specific (ThyPRO) and general (SF-36) QoL surveys.

    METHODS: We evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 which had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n=975) and/or the SF-36 questionnaire (n=964) and informed consent at follow-up. Scores from ThyPRO were compared with scores from a general population sample (n=712), using multiple linear regression adjusting for age and gender as well as multiple testing. Treatment related QoL outcome for ATD, RAI and surgery were compared including adjustment for the number of treatments received, sex, age and co-morbidity.

    RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared with the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL-scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.

    CONCLUSIONS: Graves' disease is associated with a lower QoL many years after treatment compared to the general population. In a previous, small RCT we did not show any difference in patient satisfaction years after ATD, RAI or surgery. We now report that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and SF-36. These findings in a Swedish population are limited by comparison to normative data from Denmark, by older age and possibly a more prolonged course in those patients who received radioiodine, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown but since the results may be important for future considerations regarding treatment options for GD they need to be substantiated in further studies.

  • 37.
    Wedin, M.
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Tsoli, M.
    1st Department of Propaedeutic and Internal Medicine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Wallin, G.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Janson, E. T.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Koumarianou, A.
    Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Kaltsas, G.
    1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, Athens, Greece.
    Daskalakis, K.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Virchow's node metastasis from small intestinal neuroendocrine neoplasms: A bi-center cohort study2022In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no Suppl. 1, p. 88-88Article in journal (Other academic)
    Abstract [en]

    Introduction: Small Intestinal Neuroendocrine Neoplasms (SI-NENs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM).

    Aim(s): Data on prevalence, prognostic significance and clinical course of disease for SI-NEN patients with VM is limited.

    Materials and methods: In this retrospective analysis of 231 SI-NEN patients treated at two tertiary referal centers we found nine patients with VM. We used a control group of 18 age-and sex-matched SI-NEN patients from the same cohort with stage IV disease, but no extrahepatic metastases.

    Results: VM prevalence was 3.9% (9/231; 5 females, median age at VM diagnosis 65 years). Two patients had G1, 5 G2 tumours and 2 of unspecified grade. Four patients presented with synchronous VM, whereas 3 developed metachronous VM after a median of 24 months (range: 4.8–117.6 months). Hepatic metastases were present in 7 patients, extrahepatic metastases (EM) in 8 (6 para-aortic distant lymph node metastases, 1 lung and 1 pancreatic metastasis) and peritoneal carcinomatosis in 2 patients. There was no difference in best-recorded responses to 1st line treatment according to RECIST 1.1 as well as progression-free (PFS) and overall survival rates (PFS) between patients with VM and those in the control group (Chi-square p=0.516; PFS: 71.7 vs. 106.9 months [95%CI 38.1-175.8]; log-rank p=0.855; OS: 138.6 [95%CI 17.2–260] vs. 109.9 [95%CI 91.7–128] months; log-rank p=0.533).

    Conclusion: VM is relatively rare in patients with SI-NENs. It is more often encountered in patients withG2 tumors and EM, mainly to distant para-aortic lymph nodes. Its presence does not seem to impact patients’ survival outcomes and treatment responses, when compared to age-and sex-matched patients with stage IV disease. 

  • 38.
    Wedin, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Sundin, A.
    Faculty of Medicine and Health, Uppsala University, Uppsala, Sweden .
    Janson, Tiensuu E.
    Faculty of Medicine and Health, Uppsala University, Uppsala, Sweden .
    Rare metastases diagnosed on 68Ga-DOTATOC-PET/CT in small intestinal and pancreatic NETs2023In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 35, no Suppl. 1, p. 116-116, article id D58Article in journal (Other academic)
    Abstract [en]

    Introduction: Neuroendocrine metastases to the orbita, heart, breast, bone, Virchow's lymph node, and pancreas are rarely encountered in small intestinal (SI-NETs) and pancreatic NETs (P-NETs).

    Aim(s): We aimed to assessthe prevalence of rare metastatic locations in patients with well-differentiated SI-NETs and P-NETs, who had undergone 68Ga-DOTATOC-PET/CT at diagnosis and/or follow-up.

    Materials and methods: In this retrospective analysis of 753 SI-NET patients and 418 P-NET patients treated at two tertiary referral centers, rare metastases were evident in 26.5% (310/1171) of the patient cohort.

    Results: Among patients with rare metastases (n=310), 45 % were women and median age at metastases diagnosis was 70 years (43-90). Median Ki-67 was 7% (1-70); 106 were G1 tumors, 142 G2, 11 G3 and 51 of unknown grade. Rare metastatic sites were present in bone 18 % (215/1171), Virchow's lymph node 6 % (75/1171) and 4 % (42/1171) in the lung/pleura. Metastases to the pancreas, breast, heart and orbita were only encountered in SI-NET primaries with a frequency of 5 % (41/753), 2 % (17/753), 2 % (14/753) and 2 % (12/753) respectively. Concomitant liver metastases were present in 86 %. Uncommon metastases were more frequent in SI-NET as compared with P-NET primaries, 255/753 [34%] vs. 55/418 [13%], p ˂0.00001. Bone metastases were present in 23 % (175/753) of SI-NET and 10 % (40/418) of p-NET primaries.

    Conclusion: In conclusion, rare metastases are more frequent in SI-NET than p-NETs. The variety and pattern of rare metastases seems different between SI-NETs and P-NET primaries, as orbita, heart, breast and Virchow's lymph node deposits were only encountered in SI-NETs patients; and bone metastases were approximately twice more often inthis group. 

  • 39.
    Wedin, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Janson, Eva Tiensuu
    Department of Medical Sciences, Endocrine Oncology unit, Uppsala University, Uppsala, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Sundin, Anders
    Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2nd Department of Surgery, 'Korgialenio-Benakio', Red Cross General Hospital, Athens, Greece.
    Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours2024In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 36, no 5, article id e13391Article, review/survey (Refereed)
    Abstract [en]

    Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

  • 40.
    Wedin, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Mehta, S.
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Angerås-Kraftling, J.
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Prognostic and diagnostic value of serum 5-HIAA in well-differentiated neuroendocrine neoplasms2021In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 33, no S1, p. 117-117Article in journal (Other academic)
    Abstract [en]

    Introduction: There are only few studies on the diagnostic value of serum 5HIAA as compared to the 24-hours urinary sampling method and a lack of evidence on the prognostic significance of its serum levels, as well as the markers' ability to predict changes in disease status.

    Aim(s): Our aim was to investigate the clinical utility of serum 5HIAA for diagnostic purposes and disease surveillance in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs).

    Materials and methods: Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing as well as CT/MRI imaging were included.

    Results: A positive correlation between disease stage and serum 5HIAA positivity (Pearson Chi-square p=0.017), and between liver tumor burden and serum 5HIAA levels (Spearman’s rank correlation coefficient: 0.46; p=0.013) was confirmed. Further analysis did not reveal any correlation between RECIST 1.1 responses and >25% changes in serum 5HIAA levels (Fisher ́s exact test p=0.735). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients without any impairment of the renal function, the concordance between the two tests was as high as 89% and a sensitivity and specificity of 80% and 88.9%, respectively was evident (Cohen’s kappa coefficient=0.685).

    Conclusion: Serum 5HIAA performs well compared to urinary testing for diagnostic purposes and corresponds well to tumor stage and liver tumor burden. However, it is not adequate to predict tumor progression. 

  • 41.
    Wedin, Maria
    et al.
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mehta, Sagar
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Angerås-Kraftling, Jenny
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms2021In: Biology, E-ISSN 2079-7737, Vol. 10, no 2, article id 76Article in journal (Refereed)
    Abstract [en]

    Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, were included. Analysis of matching-pairs did not reveal any association between RECIST 1.1 responses and changes in serum 5HIAA levels (p = 0.673). In addition, no correlation was evident between RECIST 1.1 responses and >10%, >25% or >50% changes in serum 5HIAA levels (Fisher's exact test p = 0.380, p > 0.999, and p > 0.999, respectively). The presence of liver metastases and extensive liver tumor involvement were associated with higher serum 5HIAA levels (p = 0.045 and p = 0.041, respectively). We also confirmed a strong linear correlation between the measurements of serum and urine 5HIAA (n = 24, r = 0.791, p < 0.0001). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients with normal renal function tests, the concordance between the two methods was as high as 89%, and a sensitivity and specificity of 80% and 88.9%, respectively, was evident (Cohen's kappa coefficient = 0.685). In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes, mainly in advanced disease stages, and corresponds well to liver tumor burden. However, it is not adequate to predict tumor progression. 

  • 42.
    Wedin, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery.
    Tsoli, Marina
    1st Department of Propaedeutic Internal Medicine, National and Kapodistrian, University of Athens, Athens, Greece.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery.
    Janson, Eva Tiensuu
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Koumarianou, Anna
    Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Kaltsas, Gregory
    1st Department of Propaedeutic Internal Medicine, National and Kapodistrian, University of Athens, Athens, Greece.
    Daskalakis, Kosmas
    Örebro University, School of Medical Sciences. Örebro University Hospital. 2nd Department of Surgery, "Korgialenio-Benakio", Red Cross General Hospital, Athens, Greece.
    Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow's Node Involvement2022In: Cancers, ISSN 2072-6694, Vol. 14, no 4, article id 913Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow's node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2-15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8-117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1-175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2-260] vs. 109.9 [95% CI 91.7-128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients' survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.

  • 43.
    Woisetschlager, M.
    et al.
    Department of Radiology and Department of Medical and Health Sciences, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Gimm, O.
    Department of Surgery in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Johansson, K.
    Department of Surgery, Västervik, Sweden; Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences.
    Albert-Garcia, I
    Department of Radiology and Department of Medical and Health Sciences, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
    Spångeus, A.
    Department of Acute Internal Medicine and Geriatrics in Linköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Dual energy 4D-CT of parathyroid adenomas not clearly localized by sestamibi scintigraphy and ultrasonography - a retrospective study2020In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 124, article id 108821Article in journal (Refereed)
    Abstract [en]

    Purpose: At present, the gold standard for diagnosing PAs includes ultrasonography of the neck and sestamibi scans of the parathyroid. The objective of this study was to evaluate scans performed in 4D-DECT (4D-dualenergy mode) at three different time points, in order to analyze spectral information from PAs, lymph nodes (LNs), and thyroid gland (Thy).

    Method: Fifteen patients (mean age: 57 +/- 18.9 years) with primary hyperparathyroidism, in which previous ultrasound and sestamibi scanning proved to be negative or equivocal, underwent 4D-DECT in three different phases. Hounsfield units (HU), dual-energy information (electron density [Rho], atomic number [Z], dual-energy index [DEW, and spectral information (keV) were determined.

    Results: For all energies, PAs exhibited significantly lower HU-values than the Thy in non-contrast images, and higher HU-values than LNs in the arterial phase (p < 0.05). All three tissues differed significantly in HU in the venous phase at 90 kV, 150 kV, and mixed 0.8 images; the Thy showed significantly higher HU-values than PAs or LNs in non-contrast images at 90 kV, 150 kV, mixed 0.8 images, and [Rho] (p < 0.05). LNs exhibited significantly lower HU-values than PAs and Thy in the arterial phase at 90 kV, 150 kV, mixed 0.8, Rho, Z, and DEI (p < 0.05). With regards to spectral information, lower energies showed greater HU differences between the three tissues. During the venous phase, there were significant differences between all three tissues up to 100 keV (p < 0.05).

    Conclusions: We identified significant differences in HU-values and spectral information between PAs, LNs, and Thy at different energies and contrast phases.

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