| 1. |
- Druvefors, Emma, 1985-
(författare)
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Fertility in Inflammatory Bowel Disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory bowel diseases (IBD) often present in adolescence or early adulthood and is thus frequently diagnosed in men and women in their reproductive age. Previous population-based studies of fertility in patients with IBD are scarce.From the Swedish National Patient Register (NPR) all patients diagnosed with IBD of fertile age between 1964–2014 were identified. Statistics Sweden identified a matched reference cohort (ratio 1:5) from the general population matched for sex, age and place of birth. Children born were identified through the Medical Birth Register and the Swedish Multigeneration Register. For subgroup analyses information about medication was collected through Medical Drug Register and information about socioeconomic status from Longitudinal Integrated Database for Health Insurance and Labour Market Studies. From the SWedish Inflammatory Bowel disease quality REGister (SWIBREG) a cohort of women with UC who underwent colectomy 2000–2020 was identified. Demographic data from SWIBREG and information from a study specific questionnaire regarding reproductive history and voluntary childlessness were analysed.From the NPR 27,331 women and 29,104 men with IBD were identified, corresponding to 272,793 matched individuals.The fertility rate in women with IBD was 1.52 (standard deviation [SD] 1.22) births per 1000 person-years, compared with 1.62 (SD 1.28) (p <0.001) in the matched reference cohort. Fertility was negatively affected mainly in women with Crohn's disease (CD) and IBD-unclassified (IBD-U) and to a lesser extent in ulcerative colitis (UC). Disease activity, bowel resections and, in the case of CD, also perianal disease further adversely affected fertility. For women with UC and IBD-U, but not for women with CD, fertility improved throughout the study period. Contraceptive use was higher in female IBD patients, both before and after the diagnosis.In total 2,989 women underwent colectomy during the study period. Reconstruction with ileal pouch anal anastomosis (IPAA) and ileorectal anastomosis (IRA) was used to about the same extent in UC and IBD-U, although this was rare in CD. Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (HR 0.65, CI 0.61–0.69), with least impact for operations that left the rectum intact (HR 0.79, CI 0.70–0.90). When the comparison was made within the group of patients undergoing colectomy, fertility in female patients remained nearly unaffected after IRA in all subtypes of IBD, but was impaired after IPAA, especially in UC (HR 0.67 CI 0.50–0.88), and after completion proctectomy in all subtypes of IBD (CD 0.61 CI 0.38–0.96), UC HR 0.65, CI 0.49–0.85 and IBD-U0.68, 0.55–0.85).The survey regarding reproductive behavior after colectomy was completed by 214 (73%) out of 294 eligible women identified in SWIBREG. The desire to have children was negatively affected by disease onset in 59% of the women, colectomy in 44% and by reconstruction in 37%. Altogether, 39% women with UC estimated that they chose to have fewer children in the end because of the disease, but only 10% expressed that the disease made them completely restrain from having children. On the contrary 37% of the women reported that they had experienced difficulties to conceive and 19% expressed that they could not conceive at all. Of the women undergoing reconstruction post colectomy, 37% reported that the choice of reconstruction method was influenced by their desire to have children. Difficulty conceiving was more commonly reported after reconstruction with IPAA (odds ratio [OR] 5.54) than IRA (OR 2.57).Men with IBD also had lower fertility rate compared with the matched reference population, although the impact on parity was limited; 1.28 (SD 1.27) versus 1.35 (SD 1.31) (p < 0.001). Fertility in men was nevertheless impaired in all IBD subtypes. The disease severity measured as order of hospital admissions (UC and IBD-U), intensity of medical treatment (CD), and bowel surgery (IBD-U) were further associated with impaired fertility in men. In the 3,771 men undergoing colectomy during the study period, fertility was only marginally (HR 0.89, CI 0.85–0.94) impaired, regardless of reconstruction.In conclusion, women with IBD have only slightly reduced fertility rates compared with the matched reference population with some exceptions. In non-surgically treated patients, the impact was most pronounced in female patients with CD. Women post colectomy have a particularly marked impact on fertility independent of IBD subtype. Bowel reconstruction with IPAA and proctectomy had a pronounced negative impact on fertility, while fertility was not further affected after IRA. More than half of the women with UC post colectomy reported that developing UC has affected their desire to have children, but difficulty to conceiving is also commonly reported. The impact of IBD in men was only minor.
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| 2. |
- Ahle, Margareta, 1966-
(författare)
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Necrotising Enterocolitis : epidemiology and imaging
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.
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| 3. |
- Isacson, Daniel
(författare)
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Treatment of Acute Uncomplicated Colonic Diverticulitis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to evaluate the clinical management of AUD with regard to the no-antibiotic policy and its long-term effect, treatment on an outpatient basis and the potential health-care cost savingsStudy I: a retrospective study at Västmanlands Hospital that evaluated and confirmed the adherence to the no-antibiotic policy in patients with AUD and its safety regarding complications and recurrences. A total of 246 patients with acute diverticulitis were identified, of which 195 had computed tomography (CT) confirmed AUD. In total, 91.3% of these patients did not receive any antibiotics and only two developed complications.Study II: a retrospective study with the aim to conduct a long-term follow-up of all Swedish patients who participated in the AVOD trial in terms of recurrences, complications, surgery and quality of life. The medical records of 96% of the patients were reviewed with a mean follow up of 11 years. Quality of life questionnaires were sent out to all patients. There were no differences regarding the rates of recurrence, complications or surgery for diverticulitis. There were no differences in the quality of life between groups according to the EQ-5D questionnaire.Study III: a prospective study where 155 patients with CT-verified AUD as were treated as outpatients without antibiotics. On day 3, patients reported an average pain score of 1.8 of 10 on the VAS scale and only 30% of patients were using analgesia. Four patients returned to hospital because of treatment failure.Study IV: a retrospective cohort study at Västmanland’s Hospital evaluated the impact on admissions, complication rates and health-care costs of the policy of outpatient treatment without using antibiotics. Medical records of all patients diagnosed with AUD in the year before (2011) and after (2014) the implementation of outpatient management without antibiotics were reviewed. Overall 494 episodes of AUD were identified: 254 in 2011 and 240 in 2014. Three patients developed complications in 2011 and four in 2014. The proportion of patients managed as outpatients was 20% in 2011 compared with 61% in 2014. The hospital admissions, total length of stay of and total health-care costs were almost halved.In conclusion, these studies confirm the low complication and recurrence rates of AUD and strengthens findings that antibiotics have no benefit in the treatment of this disease. The no-antibiotic policy had no impact on short- or long-term outcomes regarding the rates of recurrence, complications, surgery or quality of life. Outpatient management was found to be feasible and safe, and significantly reduced admissions, which led to large health-care cost savings.
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| 4. |
- Slind Olsen, Renate
(författare)
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Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis?
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.
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| 5. |
- Andersson, Manne
(författare)
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Structured management of patients with suspected acute appendicitis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Acute appendicitis (“appendicitis”) is one of the most common abdominal surgical emergencies worldwide. In spite of this, the diagnostic pathways are highly variable across countries, between centres and physicians. This has implications for the use of resources, exposure of patients to ionising radiation and patient outcome. The aim of this thesis is to construct and validate a diagnostic appendicitis score, to evaluate new inflammatory markers for inclusion in the score, and explore the effect of implementing a structured management algorithm for patients with suspected appendicitis. Also, we compare the outcome of management with routine diagnostic imaging versus observation and selective imaging in equivocal cases.Methods. In study I, the Appendicitis Inflammatory Response (AIR) score was constructed from eight variables with independent diagnostic value (right lower quadrant pain, rebound tenderness or muscular defence, WBC count, proportion of polymorphonuclear granulocytes, CRP, body temperature and vomiting). Its diagnostic properties were evaluated and compared with the Alvarado score. In study II, we performed an external validation and evaluation of novel inflammatory markers for inclusion in the score on patients with suspected appendicitis at two Swedish hospitals. In study III we externally validated and evaluated the impact of an AIR-scorebased algorithm assigning patients to a low or high risk of having appendicitis in an interventional multicentre study involving 25 Swedish hospitals and 3791 patients. In study IV, we compared the efficiency of routine diagnostic imaging with repeated clinical assessment followed by selective imaging in a randomised trial of 1028 patients with equivocal signs of appendicitis, as indicated by an intermediate AIR score, from study III.Main results. In study I we found that the AIR score could assign 63% of the patients to either a high- or low-risk group of appendicitis with an accuracy of 97%, which compared favourably with the Alvarado score. In study II, the diagnostic properties of the AIR score proved to be reproducible, but the inclusion of novel inflammatory markers did not improve the diagnostic accuracy. In study III, the AIR-score-based algorithm led to a reduction in negative explorations, operations for nonperforated appendicitis and hospital admissions in the low-risk group and reduced use of imaging in both low- and high-risk groups. In study IV, routine imaging led to more operations for nonperforated appendicitis but had no effect on negative explorations or perforated appendicitis.Conclusions. The AIR score was found to have promising diagnostic properties that were not improved further with the inclusion of novel inflammatory variables. Structured management of patients with suspected appendicitis according to an AIR-score-based algorithm may improve outcome while reducing hospital admissions and use of imaging. Patients with equivocal signs of appendicitis do not benefit from routine imaging which may lead to an increased detection of, and treatment for, uncomplicated cases of appendicitis that are otherwise allowed to resolve spontaneously.
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| 6. |
- L. Du Rietz, Anita, 1947-
(författare)
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Dynamics of the internet
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Landerholm, Kalle, 1976-
(författare)
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Clinical and immunohistochemical studies of small bowel carcinoid tumours
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small bowel carcinoid tumours arising from enterochromaffin cells in the jejunum and ileum are neuroendocrine tumours (NETs) characterized by secretion of serotonin, tachykinins and other bioactive substances. These substances may lead to the typical carcinoid syndrome as well as pronounced fibrosis locally and in the heart. Although the most frequent histological subtype of malignancy in the small bowel, small bowel carcinoids are rare and therefore difficult to study. We found that previous studies either described selected patients at referral centres, or were based on limited data from large registries. The main objective of this thesis was to investigate small bowel carcinoid patients from a geographically defined cohort with no selection bias.PAPERS I AND IIThe aims of papers I and II were to investigate the incidence, histopathological characteristics, stage atdiagnosis, symptomatology, surgical treatment, prognostic factors and survival of small bowel carcinoid.All patients resident in Jönköping County when diagnosed with small bowel carcinoid between 1960 and2005 were eligible for inclusion. After thorough review of medical records and reexamination of availabletumour specimens, 145 patients were included.A higher incidence of small bowel carcinoid than previously described was found: 1.12 per 100,000 persons and year. The incidence increased during the study period. Symptoms were most often uncharacteristic: the carcinoid syndrome was seen in only 13% of symptomatic patients. Many small bowel carcinoid tumours presented as surgical emergencies without preceding symptoms, often as intestinal obstruction (35%) caused by mesenteric fibrosis. The majority of small bowel carcinoid tumours had metastasized to the mesentery or the liver at diagnosis. Disease-specific survival after 5 years was 75.0% and after 10 years 63.5%. Independent prognostic factors for worse disease-specific survival were higher age at diagnosis, more advanced disease stage at diagnosis and incomplete tumour resection. Completeness of resection was of particular importance in patients with regional metastases.PAPER IIIThere are previous case reports describing small bowel carcinoid in two first-degree relatives, but it is unknown whether this represents hereditary disease forms or chance. Paper III was the first article to describe metastasizing ileal carcinoid tumours in three consecutive generations − strongly suggestive of a hereditary disease form.PAPER IVWe recently demonstrated expression of cocaine- and amphetamine-regulated transcript (CART) in several types of NETs, including small bowel carcinoid. The aim of paper IV was to investigate whether content of CART in small bowel carcinoid tumours is associated with tumour characteristics, symptoms and survival. CART expression was examined in all available tumour specimens from the patients in Papers I and II − 97 patients were included.Presence of CART IR tumour cells was associated with histological grade, but not with stage or age. CART expression in small bowel carcinoid tumours was not associated with clinical symptoms. Increasing levels of CART IR in small bowel carcinoid tumour cells was associated with worse disease-specific survival. CART was also found to increase cell viability in an enteroendocrine cell line in vitro. The results suggest that CART could be used as a prognostic biomarker and that CART is a potential anti-tumour treatment target.
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| 8. |
- Locmelis, Roland, 1984-
(författare)
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Structural biology studies of thylakoid lumen proteins required for photosystem II assembly and function
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Little is known about the structures and functions of thylakoid lumen proteins. However, some of these proteins have an essential role in photosynthesis. Photosystem II (PSII) complexes are embedded in the thylakoid membrane of oxygenic photosynthetic organisms and one of the central subunits, the D1 protein, is damaged by light during the light driven water – splitting reaction and must be replaced frequently. One of the thylakoid lumen proteins that is essential for assembly and renewal of PSII complexes is the High Chlorophyll Fluorescence 136 (HCF136) protein. Another important protein for the PSII complex assembly is the Low PSII Accumulation Protein 19 (LPA19). Both proteins, HCF136 and LPA19, were shown to bind to the core subunits of the PSII complex from the lumenal side and LPA19 has been shown to explicitly interact with the soluble C-terminus of the D1 protein, one of the core PSII complex proteins. Prior to the replacement of the damaged D1 protein, the PSII complex needs to be disassembled, which is done with the help of the Maintenance of Photosystem II under High light 2 (MPH2) protein. MPH2, also called TL16, is required during the repair cycle of the PSII complex particularly under increased and fluctuating light conditions.In this work I have determined the three-dimensional X-ray structures of the HCF136 protein at 1.6 Å resolution and the LPA19 protein at 1.2 Å resolution and have also biochemically analyzed possible interactions of HCF136 with the C-termini of D1 protein. In addition, we have determined the NMR structure of the MPH2 protein.The protein structures of HCF136, LPA19, and MPH2 determined from A. thaliana provide us with a starting point for further studies to improve our understanding of their functional roles in the assembly, maintenance, disassembly and renewal of the PSII complex. The structures are revealing the molecular details that are particularly important during the design of mutations to study protein-protein interactions and the binding of co-factors.Furthermore, I have contributed to the characterization of AnPrx6, the 1-Cyx peroxiredoxin from Anabaena sp. 7120. Peroxiredoxins are important caretakers of reactive oxygen species and a homolog PrxQ in A.thaliana is found in the thylakoid lumen. The dimeric AnPrx6 protein revealed different active site residues conformations in each of the dimers, which is probably coupled to its enzymatic activity. Unexpectedly, the protein acted also as a chaperone and showed chaperone activity in its dimeric state, which is a novelty for Prx proteins.
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| 9. |
- Sandzén, Birger, 1944-
(författare)
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Complicated gallstone disease in Sweden 1988-2006 : a register study
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background The gallstone prevalence in the western world is 10-20%. Most gallstones are silent, but symptoms and complications appear in 20-40%. The incidence of symptom development in patients with silent gallstones is 2-4% per year. The indication for surgical (including endoscopic) treatment of gallstones is symptoms of certain magnitude, and no contraindications. During the past three decades an intense technical development in imaging (ultrasound, computerised tomography and magnetic resonance imaging), endoscopic therapy, and surgery has taken place. The aim of this thesis is to scrutinize changes in management of complicated gallstone disease on a population-based level, using national register data. Have the new methods improved the treatment of acute pancreatitis, common bile duct stones and acute gallbladder disease?Methods Data is collected from National Patient Register (NPR) run by The Swedish National Board of Health and Welfare. NPR collects discharge data from every admission from every Swedish hospital. Mortality is calculated as standardised mortality ratio (SMR) using age-, gender-, and calendar year specific survival estimates. We have studied both general trends in admissions and treatment alternatives and outcomes in defined patient cohorts. Length of hospital stay, readmission, and mortality has been used as proxy indicators of the effectiveness of treatment strategies used.Results During the study period mortality in acute pancreatitis (SMR within 90 days of admission) improved and hospital stay for all patients with acute pancreatitis decreased. Cholecystectomy rate at or shortly after index stay for mild acute biliary pancreatitis increased from 14.5 % to 22.7 %. Of all patients with acute pancreatitis 68.4 % of the patients had no aetiological diagnosis in the register. The incidence of bile duct interventions increased 27.8% from 1988 through 2006. The favoured treatment of bile duct stones changed from open choledocholithectomy to endoscopic sphincterotomy with stone extraction during the same period. However, in 2006, still 19.6% of bile duct interventions for stones were performed as choledochotomy and in the great majority of these cases as open surgery. This indicates a continuing need of education in open bile duct surgery. Mean hospital stay for treatment of common bile duct stones decreased significantly (4.5 days) during the period studied. The mortality (SMR) diminished although without statistical significance during the time period, and there was no significant difference in SMR between choledochotomy and endoscopic sphincterotomy. For acute gallbladder disease a moderate increase of admissions occurred from 1988 through 2006. The relation between acute cholecystectomies versus all cholecystectomies did not change during this period. Of all patients admitted with acute gallbladder disease 32.3 % were cholecystectomised during their first hospital stay, whereas 20.3 % underwent elective cholecystectomy and 6.1 % emergency cholecystectomy within two years of first admission. 41.4 % of patients were not operated on for gallbladder disease within two years of first admission with this diagnosis. Mortality from first admission and 90 days onwards was elevated three-fold during the entire period without time trend, without statistical difference between age groups, and between patients who had cholecystectomy at first admission or later.Conclusion During the audit period treatment of acute pancreatitis improved. However, etiological classification and timing of cholecystectomy in mild acute biliary pancreatitis fell below accepted guidelines. Interventions on the common bile duct for gallstone disease increased significantly. Common bile duct clearance has been separated from cholecystectomy, and cholecystectomy often not done. Only one third of all patients with acute gallbladder disease underwent cholecystectomy at first admission. There is room for improvement in treatment of complicatedgallstone disease, and, gallstone surgeons still need good knowledge in open biliary surgery.
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| 10. |
- Abdalla, Maie
(författare)
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Cancer and reconstructive surgery in Inflammatory bowel disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. According to the literature, some thirty percent of UC patients may require a subtotal colectomy and ileostomy due to failure of medical treatment, acute toxic colitis or dysplasia/cancer diagnosis. Some patients choose to get continence restored with either an ileorectal anastomosis (IRA) or an ileal pouch-anal anastomosis (IPAA). Worldwide most surgeons prefer an IPAA to an IRA, despite reports of pouchitis, impaired fertility and fecundity. Fear of recurring proctitis and fear of rectal cancer in the remaining rectum is contributing to the choice of an IPAA. Little is known regarding the outcomes of IRA compared with IPAA in UC patients. We aimed to investigate the anorectal function, quality of life (QoL), risk of failure and rectal cancer in patients with UC restored with IRA and IPAA respectively. Methods: Data about all Inflammatory bowel disease (IBD) patients was obtained from the Swedish National Patient Register (NPR) between 1964-2014 and in one study from the Linköping University Hospital medical records 2006-2012. Patients who developed cancer were identified from the Swedish National Cancer Register. We investigated the risk of cancer and inflammation, functional outcome and failure as well as the quality of life for IRA and IPAA patients. Investigation of risk for cancer in IRA and IPAA compared with the background population was performed using survival analytic techniques: uni-and multivariate regression, Kaplan Meier curves and standardized incidence ratio. Results: Twelve percent (7,889 /63,795) of UC patients required colectomy according to the NPR. The relative risk for rectal cancer among patients with an IRA was increased (SIR 8.7). However, the absolute risk was 1.8% after a mean follow up of 8.6 years and the cumulative risk 10- and 20-years after IRA was 1.6% and 5.6%, respectively. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio 6.12), and severe dysplasia or cancer of the colon prior to subtotal colectomy in patients with a diverted rectum in place (hazard ratio 3.67). Regarding IPAA, the relative risk to develop rectal cancer was (SIR 0.4) compared with the background population and the absolute risk was only 0.06% after a mean of 12.2 years of follow up. Among patients operated at the Linköping University Hospital: IRA patients reported better overall continence according to the Öresland score with in median3 (IQR 2–5) for IRA (n=38) and 10 (IQR 5–15) for IPAA (n=39, p<0.001). There were no major differences regarding the QoL. According to the NPR, after a median follow up of 12.4 years failure occurred in 265(32%) out of 1112 patients, of which 76 were secondarily reconstructed with an IPAA. Failure of the IPAA occurred in 103 (6%) patients with primary and in 6 (8%) patients after secondary IPAA (log-rank p=0.38). Conclusion: IRA is a safe restorative procedure for selected UC patients. Patients should be aware of the annual postoperative endoscopic evaluation with biopsies as well as the need to the use of local anti-inflammatory preparations. However, IRA should not be offered for UC patients with an associated primary sclerosing cholangitis diagnosis due to the increased risk to develop rectal cancer in their rectal mucosa. In such case, IPAA is probably the treatment of choice.
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