| 1. |
- Daskalakis, Kosmas, 1979-, et al.
(author)
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Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumours
- 2024
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In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197.
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Journal article (peer-reviewed)abstract
- CONTEXT: One of the major prognostic indices in neuroendocrine tumours (NETs) is Ki67 proliferation index.OBJECTIVE: To identify optimal grading Ki-67 cut-offs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs).DESIGN, SETTING, PARTICIPANTS: Multicentre retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at five European referral centres with a mean(±SD) follow-up time of 51.5(±52.9) months.MAIN OUTCOME MEASURES: Overall- and event-free survival (OS and EFS) rates.RESULTS: Median age at baseline was 62.3(range:17-90) years; 252(45.7%) patients were female. All SI-NETs were well-differentiated with 326 being grade 1(G1; 59.2%), 169G2(30.7%), and only 8G3(1.5), while 48 tumours were of unspecified grade (8.7%). The median Ki67 was 2%(range:1-70%). Two-hundred forty-seven patients (44.8%) had distant metastases at baseline (stage IV), 217 locoregional disease (41.1%; stage III), whereas 29(7.1%) and 25(4.5%) presented at stages II and I, respectively. 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, the proposed modified histopathological Ki67 grading system (K67:5-10% group: HR=2.2, 95%CI:1.15-4.31; p=0.018 and K67≥10% group: HR=5.11, 95%CI:2.87-9.09; p<0.001), age (HR=1.07, 95%CI:1.04-1.09; p<0.001), Charlson Comorbidity Index (HR=1.08, 95%CI:1-1.16; p=0.028) and TNM stage (HR=1.79, 95%CI:1.05-3.06; p=0.034) were independent predictors for death. Pertinent EFS analysis, confirmed the proposed modified histopathological Ki67 grading system (K67≥10% group: HR=4.01, 95%CI:2.6-6.37; p<0.001) and age (HR=1.04, 95%CI:1.02-1.05; p<0.001) as independent predictors for recurrence, progression and/or death.CONCLUSIONS: Ki-67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki-67 cut-offs of 5 and 10% could be superior to predict differences in SI-NET patient survival outcomes.
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| 2. |
- Lind, Patrik, 1985-, et al.
(author)
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Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer
- 2024
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In: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 409:1
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Wedin, Maria, 1977-, et al.
(author)
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Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis : Biologic Patterns of a Series with Virchow's Node Involvement
- 2022
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In: Cancers. - : MDPI. - 2072-6694. ; 14:4
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Wedin, Maria, 1977-, et al.
(author)
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Prognostic and diagnostic value of serum 5-HIAA in well-differentiated neuroendocrine neoplasms
- 2021
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In: Journal of neuroendocrinology (Print). - : European Neuroendocrine Association. - 0953-8194 .- 1365-2826. ; 33:S1, s. 117-117
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Journal article (other academic/artistic)abstract
- 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.
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| 5. |
- Wedin, Maria, 1977-, et al.
(author)
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Rare metastases diagnosed on 68Ga-DOTATOC-PET/CT in small intestinal and pancreatic NETs
- 2023
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In: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 35:Suppl. 1, s. 116-116
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Journal article (other academic/artistic)abstract
- 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.
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| 6. |
- Wedin, Maria, et al.
(author)
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The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms
- 2021
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In: Biology. - : MDPI. - 2079-7737. ; 10:2
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Journal article (peer-reviewed)abstract
- 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.
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