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Sökning: WFRF:(Graf Wilhelm) > (2015-2019) > Doktorsavhandling

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1.
  • Danielson, Johan, 1975- (författare)
  • Anorectal Malformations : Long-term outcome and aspects of secondary treatment
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Faecal incontinence (FI) is defined as the inability to control bowel movements. The causes of FI are many and diverse. One of the more uncommon reasons for FI is Anorectal Malformations (ARMs). An ARM is a congenital anomaly that affects somewhere between 1/2500 and 1/5000 live born babies. Many ARM patients have persistent FI. Several different procedures have been utilised to address this issue. This thesis aims to evaluate (1) the long-term outcome in adulthood of ARMs in relation to the modern Krickenbeck classification, and (2) scope for treating FI with transanal injection with dextranomer in non-animal stabilised hyaluronic acid (NASHA/Dx), in patients both with and without ARMs.All patients treated for ARMs in Uppsala up to 1993 were invited to participate in a questionnaire study of quality of life and function. The study included 136 patients and compared them with 136 age- and sex-matched controls. The Krickenbeck classification was found to predict functional outcome, and ARM patients had more problems with incontinence and obstipation, as well as inferior Quality of Life (QoL), compared with controls. Thirty-six patients with FI, owing to causes other than ARMs, were treated with transanal submucous injection of NASHA/Dx. The patients were monitored for two years after treatment. Significant reductions in both their incontinence score and the number of their incontinence episodes were achieved.  A significant improvement in QoL was observed in patients who had at least a 75% reduction in incontinence episodes. No serious complications occurred.A prospective study of transanal injection of NASHA/Dx was conducted on seven patients with persistent FI after ARMs. After six months a significant reduction in the number of incontinence episodes was obtained. A significant improvement in QoL was also found. No serious complications occurred.In conclusion, adult patients with ARMs have inferior outcome of anorectal function and QoL compared with controls. NASHA/Dx is effective and appears to be safe in treating FI in general. This effect seems to be the same in selected patients with persistent FI after ARMs.
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2.
  • Enblad, Malin (författare)
  • Colorectal and appendiceal peritoneal metastases : From population studies to genetics
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Peritoneal dissemination of colorectal and appendiceal origin was previously considered the end-stage of malignant disease. Today, treatment with cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) has prolonged survival and cured some patients with peritoneal metastases (PM). Unfortunately, a majority of patients still have fatal outcomes. In this thesis, colorectal and appendiceal PM were studied from a wide population-based perspective down to the detailed perspectives of histopathology and genetics, with the aim of further contributing to prolonged survival.In Paper I, the heterogeneous histopathology of PM was investigated and a substantial proportion of patients undergoing CRS and HIPEC were found to have surgical specimens lacking neoplastic epithelium. These patients had a favourable prognosis and the results illustrate the importance of thorough analysing and reporting of histopathology for understanding differences in survival outcomes and for improving patient selection. In Paper II, the role of inflammation in colorectal and appendiceal carcinogenesis was investigated at a population-based level. Patients with non-surgical treatment of appendicitis had an increased incidence of cancer (especially of appendiceal and right-sided colon cancer) compared to the general population. This should be taken into consideration in the discussion of optimal management of patients with appendicitis. In Paper III, risk factors for PM were studied with the aim of aiding in the detection of PM at earlier stages. Appendiceal and right-sided colon cancer, advanced tumour and node stages, mucinous histopathology and vascular invasion were identified as high risk features for developing PM, and should increase awareness of potential PM. In Paper IV, genome-wide chromosomal copy number alterations of PM were explored and associated with prognosis after CRS and HIPEC. Colorectal PM exhibited a wide range of alterations of which copy number gain on parts of chromosome 1p and 15q were significantly associated with poor prognosis and have the potential to be used as prognostic molecular markers in the future.In conclusion, this thesis provides new insights into the field of colorectal and appendiceal cancer and PM to be used for improved patient selection, early detection and prevention, ultimately contributing to improved survival.
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3.
  • Isacson, Daniel (författare)
  • Treatment of Acute Uncomplicated Colonic Diverticulitis
  • 2018
  • 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.
  • Linder, Gustav, 1981- (författare)
  • Esophageal- and Gastroesophageal Junctional Cancer : Aspects on Staging, Treatment and Results
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Esophageal- and gastroesophageal junctional (GEJ) cancer is the sixth cause of cancer-related death worldwide. Some improvements in care are attributed to nationwide disease-specific registries, preoperative staging and increased understanding of mechanisms affecting patient selection. Surgery, however, is a cornerstone for treatment where minimally invasive surgery and increased understanding of perioperative physiology may be beneficial. The aims of this thesis were to validate the Swedish national registry for esophageal and gastric cancer (NREV) and to explore mechanisms in patient selection, perioperative physiology, treatment-related outcomes and staging.A validation study with re-abstracted data on 400 patients determined NREV comparable to other similar registries and to have a completeness of 95.5 %. Overall accuracy was 91.1 % throughout the registry and timeliness to reporting was adequate.In a cohort of 4112 patients from NREV, high education level was associated with an increased probability of being allocated to curative treatment, as was the presence of a multidisciplinary treatment conference. High education level was associated with improved survival.By measuring intramucosal pH (pHi) in 32 patients, to describe perfusion in the gastric conduit during esophagectomy, a reduction in perfusion was seen at all surgical steps altering vascular supply to the conduit but foremost after gastric tube construction by linear stapling. Patients with low pHi on the first postoperative day were more prone to anastomotic insufficiency.In 116 patients undergoing esophagectomy (65 open and 51 minimally invasive), a retrospective cohort study regarding surgical oncological results and postoperative complications was conducted. Lymph node yield was increased, peroperative blood loss and in-hospital stay were reduced with minimally invasive esophagectomy. Postoperative complications were unaffected by surgical approach. In a prospective study of nineteen patients, whole-body integrated PET/MRI was compared to PET/CT in preoperative staging. PET/MRI was safe and feasible. Accuracy and correlations between modalities were good regarding tumor characteristics and N- and M-staging. In T-staging there were discrepancies indicating differences between modalities.The thesis presents data on the quality of NREV for future research and elaborates on patient selection, staging, perioperative physiology and treatment-related outcomes for patients with esophageal- and GEJ cancer.
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