| 1. |
- Nesti, Cedric, et al.
(author)
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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
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In: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
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Journal article (peer-reviewed)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
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| 2. |
- Bjordal, K, et al.
(author)
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- 1999
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In: Journal of Clinical Oncology. - 1527-7755. ; 17:3, s. 1008-1019
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Journal article (peer-reviewed)abstract
- PURPOSE: The aim of this study was to define the scales and test the validity, reliability, and sensitivity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N35, a questionnaire designed to assess the quality of life of head and neck (H&N) cancer patients in conjunction with the general cancer-specific EORTC QLQ-C30. PATIENTS AND METHODS: Questionnaires were given to 500 H&N cancer patients from Norway, Sweden, and the Netherlands as part of two prospective studies. The patients completed the questionnaires before, during (Norway and Sweden only), and after treatment, yielding a total of 2070 completed questionnaires. RESULTS: The compliance rate was high, and the questionnaires were well accepted by the patients. Seven scales were constructed (pain, swallowing, senses, speech, social eating, social contact, sexuality). Scales and single items were sensitive to differences between patient subgroups with relation to site, stage, or performance status. Most scales and single items were sensitive to changes, with differences of various magnitudes according to the site in question. The internal consistency, as assessed by Cronbach's alpha coefficient, varied according to assessment point and within subsamples of patients. A low overall alpha value was found for the speech and the senses scales, but values were higher in assessments of patients with laryngeal cancer and in patients with nose, sinus, and salivary gland tumors. Scales and single items in the QLQ-H&N35 seem to be more sensitive to differences between groups and changes over time than do the scales and single items in the core questionnaire. CONCLUSION: The QLQ-H&N35, in conjunction with the QLQ-C30, provides a valuable tool for the assessment of health-related quality of life in clinical studies of H&N cancer patients before, during, and after treatment with radiotherapy, surgery, or chemotherapy.
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| 3. |
- Fridell, F, et al.
(author)
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Effect of hyperoxygenation on the susceptibility of Atlantic salmon (Salmo salar L.) to experimental challenge of IPN virus
- 2007
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In: Aquaculture. - : Elsevier BV. - 0044-8486. ; 270:1-4, s. 23-35
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Journal article (peer-reviewed)abstract
- Intensive salmon smolt production normally includes reduced water flow and hyperoxygenation (added oxygen) of remaining water. There is little information on how different water quality parameters influence the fish health and the susceptibility to infectious diseases. The current experiment was carried out to evaluate if the combination of hyperoxygenation and reduced water flow (hyperoxic) can act as a chronic stressor to salmon in freshwater (FW) in such a way that it increases the susceptibility to IPN virus (IPNV) following seawater transfer. In FW, after 22 days of hyperoxic exposure plasma ion, TBARS and cortisol were measured. The cortisol levels were significantly (p = 0.011) higher in the hyperoxic group compared to controls maintained under normal oxygen saturation and water flow (normoxic), indicating chronic stress. Hyperoxygenation in FW caused decreased plasma [Cl−] compared to the normoxic group (p = 0.037), while [K+] tended to be higher in the hyperoxic group (p = 0.088). No significant differences were observed in plasma [Na+], total osmolality, TBARS or hematocrit, but there was a tendency towards a lower hct in the hyperoxic compared to the normoxic group. In SW the mortality was higher in the hyperoxic group challenged with IPNV (34%) compared to the normoxic group challenged with IPNV (20%) (p = 0.02), and no mortality was observed in the PBS injected fish. The challenged fish showed an overall increase in plasma cortisol day 8, 10, 12 and 14 post-challenge (p = 0.015, p = 0.000, p = 0.046 and p = 0.022 respectively). After SW transfer and challenge, plasma [K+] was elevated in both challenged groups, but no consistent trends were found for plasma [Cl−], [Na+] or total osmolality during the SW phase. There were no significant differences in the gene expression level of IFN 1α, Mx and IL 1β prior to challenge, suggesting that the basic expression level of these genes were not affected by hyperoxygenation. IPNV was detected in kidney and pylorus, by immunohistochemistry, cell culture, and RT-PCR in head kidney. This experiment indicates that chronic stress induced by a combination of low water flow and hyperoxygenation increases the susceptibility to IPNV challenge.
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| 4. |
- Hammerlid, Eva, 1957, et al.
(author)
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A prospective study of quality of life in head and neck cancer patients. Part I: At diagnosis
- 2001
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In: Laryngoscope. - : Wiley. - 0023-852X. ; 111:4 Pt 1, s. 669-680
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Journal article (peer-reviewed)abstract
- Purpose: A Swedish and Norwegian study was designed to examine health-related quality of life (HQL) in patients with head and neck cancer (head and neck) at diagnosis and during treatment and rehabilitation. The overall aim was to examine the impact on HQL at diagnosis depending on tumor location, stage, sex, and age (part I) and to describe HQL longitudinally and determine for which patients and during which period HQL deteriorated most (part II), This article presents the results at diagnosis. Method Patients with head and neck cancer at five hospitals in Sweden and Norway were consecutively requested to participate, They were asked to answer the EORTC QLQ-C30 and QLQ-H&N35 (the European Organization for Research and Treatment of Cancer, Core 30 questionnaire and head and neck cancer module) repeatedly during I year. A total of 357 patients (mean age, 63 y; 72% males) were included, Results: Patients with different tumor locations all had their special problems at diagnosis, for example, those with tumors in the larynx with communication, those with oral tumors with pain, and those with pharyngeal tumors with nutrition and pain. The patients with hypopharyngeal cancer reported the worst HQL. Stage appeared to have the strongest impact on HQL. Patients with a more advanced tumor stage reported significantly worse HQL scores for 24 of 32 variables reflecting functioning or problems. The females scored worse than the males for some areas, in particular, emotional functioning. The older patients scored significantly better for emotional and social functioning than patients <65 years but worse for physical functioning and various symptoms. The traditional way of grouping the tumor locations into oral, pharyngeal, laryngeal, and "other" tumors (salivary gland, sinus and nose, and unknown primary) was tested from a HQL point of view and found to be consistent. Conclusions: The chosen questionnaires differentiated between different sites of head and neck cancer at diagnosis. Tumor stage had the most powerful impact on HQL score.
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| 6. |
- Kjellman, M., et al.
(author)
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A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
- 2021
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:9, s. 840-849
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Sundh, Henrik, 1976, et al.
(author)
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The effect of hyperoxygenation and reduced flow in fresh water and subsequent infectious pancreatic necrosis virus challenge in sea water, on the intestinal barrier integrity in Atlantic salmon, Salmo salar L
- 2009
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In: Journal of Fish Diseases. - 1365-2761. ; 32:8, s. 687-98
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Journal article (peer-reviewed)abstract
- In high intensive fish production systems, hyperoxygenation and reduced flow are often used to save water and increase the holding capacity. This commonly used husbandry practice has been shown to be stressful to fish and increase mortality after infectious pancreatic necrosis virus (IPNV) challenge, but the cause and effect relationship is not known. Salmonids are particularly sensitive to stress during smoltification and the first weeks after seawater (SW) transfer. This work aimed at investigating the impact of hyperoxygenation combined with reduced flow in fresh water (FW), on the intestinal barrier in FW as well as during later life stages in SW. It further aims at investigating the role of the intestinal barrier during IPNV challenge and possible secondary infections. Hyperoxygenation in FW acted as a stressor as shown by significantly elevated plasma cortisol levels. This stressful husbandry condition tended to increase paracellular permeability (P(app)) as well as translocation of Aeromonas salmonicida in the posterior intestine of Atlantic salmon. After transfer to SW and subsequent IPNV challenge, intestinal permeability, as shown by P(app), and translocation rate of A. salmonicida increased in the anterior intestine, concomitant with further elevation in plasma cortisol levels. In the anterior intestine, four of five fish displayed alterations in intestinal appearance. In two of five fish, IPNV caused massive necrosis with significant loss of cell material and in a further two fish, IPNV caused increased infiltration of lymphocytes into the epithelium and granulocytes in the lamina propria. Hyperoxygenation and reduced flow in the FW stage may serve as stressors with impact mainly during later stages of development. Fish with an early history of hyperoxygenation showed a higher stress response concomitant with a disturbed intestinal barrier function, which may be a cause for the increased susceptibility to IPNV infection and increased susceptibility to secondary infections.
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