| 51. |
- Franck-Larsson, Karin
(author)
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Gastrointestinal Manifestations and Pathophysiological Mechanisms in Systemic Sclerosis
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Systemic sclerosis (SSc) is a rare systemic, autoimmune disease characterized by vascular changes and fibrosis of the skin and internal organs. Patients with SSc more frequently than healthy controls reported upper gastrointestinal (GI) symptoms, which was more abundant in the diffuse cutaneous form (dcSSc) of the disease than in the limited (lcSSc). One-third of a population-based cohort of 79 SSc patients reported faecal incontinence, compared to 11% in 158 healthy matched controls (p<0.001), and this symptom negatively influenced general well-being and social life. Impaired rectal sensibility, rectal bleeding, irritable bowel syndrome-like symptoms, abdominal pain, the need for manual assistance at defecation, and the use of oral laxatives were more common in patients than in controls. SSc patients reported lower scores in both physical and mental scales of the SF-36 questionnaire than controls, indicating worse health-related quality of life. Gastric emptying was slower in patients than in controls, and a higher prevalence of delayed gastric emptying in patients with dcSSc indicated more severe GI tract involvement than in lcSSc. Electrogastrographic recordings did not correlate to gastric emptying results, indicating factors other than defective myoelectric signals contributed to disturbed gastric function. SSc patients with faecal incontinence had lower anal squeeze pressures than patients without this symptom. Only patients with faecal incontinence had ultrasonographic abnormalities in the internal and external anal sphincters, and absence of the rectoanal inhibitory reflex. Thus, faecal incontinence in SSc patients may depend on both neurogenic and structural mechanisms. A discrete increase in fibre density observed in a majority of SSc patients might have implications from a disease mechanistic perspective. Sera from 47% of 70 SSc patients had the capacity to induce interferon (IFN)-α, production which correlated to the presence of anti-RNP and anti-SSA autoantibodies. Increased serum levels of IFN-inducible protein were associated with vascular manifestations, and increased serum levels of IFN-α with digital ulcers. Increased serum levels of monocyte chemoattractant protein-1 or IFN-α were associated with lung fibrosis. An activated type I IFN system previously observed in several other systemic autoimmune diseases is also present in SSc and may contribute to vascular pathology and the pro-fibrotic process.
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| 52. |
- Franck-Larsson, Karin, et al.
(author)
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Lower gastrointestinal symptoms and quality of life in patients with systemic sclerosis : a population-based study
- 2009
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In: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 21:2, s. 176-182
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the frequency and nature of bowel symptoms in a population-based cohort of patients with systemic sclerosis (SSc), compared with healthy controls, and to relate these symptoms to health-related quality of life (HR-QOL). METHOD: Seventy-nine SSc patients and 158 matched controls answered a validated questionnaire on gastrointestinal (GI) symptoms and Medical Outcomes Study Short Form Health Survey (SF-36). Modified Miller Score, a composite score measuring faecal incontinence, was computed. RESULTS: Abnormal stool consistency, bloating, a feeling of incomplete evacuation, faecal incontinence and rectal bleeding were more frequently reported by SSc patients than controls. The ability for anorectal discrimination, and deferring defecation was diminished in SSc patients. Bowel function affected general well being in 30% of patients and social life in 20%. Patients had lower SF-36 scores, that is, worse HR-QOL than controls. Modified Miller Score did not correlate to the SF-36 scores in patients, but other lower GI symptoms, especially abdominal pain and bloating, were associated with diminished HR-QOL. CONCLUSION: Lower GI symptoms, including faecal incontinence, are more common in patients with SSc than in healthy controls and are of consequence to the individual patient's life. The lower prevalence of anorectal discrimination in the SSc patients suggests a neuronal defect in these patients. Increased awareness of these symptoms might stimulate a search for new diagnostic and therapeutic strategies.
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| 53. |
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| 54. |
- Franck-Larsson, Karin, et al.
(author)
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Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence
- 2014
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 49:9, s. 1073-1083
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Journal article (peer-reviewed)abstract
- ObjectiveFecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms.Materials and methodsTwenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound.ResultsEleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05).ConclusionLower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.
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| 55. |
- Frudinger, Andrea, et al.
(author)
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Skeletal muscle–derived cell implantation for the treatment of fecal incontinence : a randomized, placebo-controlled study
- 2023
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:2, s. 476-486.e8
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Journal article (peer-reviewed)abstract
- Background and Aims: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle–derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy.Methods: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months.Results: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. Conclusions: Injection of a high dose of autologous skeletal muscle–derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).
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| 56. |
- Frühling, Petter, et al.
(author)
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Clinical Significance of Circulating Tumor Cells in Epithelial Appendiceal Neoplasms with Peritoneal Metastases
- 2024
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In: Cancers. - : MDPI. - 2072-6694. ; 16:13
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Journal article (peer-reviewed)abstract
- Simple Summary This study aimed to assess the prognostic role of circulating tumor cells (CTCs) in patients with epithelial appendiceal neoplasms with peritoneal metastases. The presence of CTCs may be used for the early detection of invasive cancer in this rare diagnosis. Our study is the first study to assess the potential value of CTCs in this specific group of patients.Abstract Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.
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| 57. |
- Gerdin, Eva, et al.
(author)
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The role of maternal age and episiotomy in the risk of anal sphincter tears during childbirth
- 2007
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In: Australian and New Zealand journal of obstetrics and gynaecology. - 0004-8666 .- 1479-828X. ; 47:4, s. 286-290
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Journal article (peer-reviewed)abstract
- BACKGROUND: Many women who experience anal sphincter tear will suffer from anal incontinence. The most important tool to avoid this is to recognise the obstetric risk factors involved and thereby prevent injury. AIMS: The aim of this study was to analyse and evaluate the risk factors of anal sphincter tear during delivery. METHODS: Of a total of 57,943 vaginal deliveries, we identified 565 women with partial or total rupture of the anal sphincter and compared these women with 565 controls without sphincter tear with respect to possible risk factors. RESULTS: Several factors were significantly associated with sphincter tears, including nulliparity, birthweight, instrumental delivery, episiotomy, malpresentation, maternal age and epidural analgesia. The importance of these variables was further confirmed in a stepwise logistic regression analysis. Age was found to be a significant risk factor only when the birthweight was less than 4000 g. Episiotomy more than doubled the risk of sphincter tear when delivery was non-instrumental. CONCLUSION: There are several independent risk factors that should be considered when making decisions regarding delivery mode. Maternal age and episiotomy in non-instrumental delivery are two of these.
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| 58. |
- Ghanipour, Lana, et al.
(author)
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Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer : A phase I and III open label randomized controlled registry-based clinical trial protocol
- 2024
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:3
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Journal article (peer-reviewed)abstract
- Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.
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