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1.
  • Loftås, Per, 1964- (författare)
  • Response to neoadjuvant treatment in rectal cancer surgery
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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2.
  • Näsvall, Pia, 1967- (författare)
  • Parastomal hernia : investigation and treatment
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundParastomal hernia is a common stoma complication causing the patient considerable inconvenience. The patient becomes aware of a bulge around the stoma, but a bulge is not always a parastomal hernia and diagnostics must be performed to enable differential treatment. It is difficult to distinguish between a bulge and a hernia. Results based on clinical examination and computerised tomography (CT) in the supine position, have not been convincing. Three-dimensional intrastomal ultrasonography (3D US) is a novel technique shown to be promising in the assessment of stoma complaints. Two studies were performed to determine inter- and intra-observer reliability as well as the validity of 3D US as an alternative to CT when assessing stoma complaints.There are numerous options for the treatment of parastomal hernia, but none has been shown superior. In the recent decades the use of mesh in the repair of incisional and inguinal hernia has become routine. New materials must be evaluated as there are potential morbidity and even mortality risks with mesh repair. As recurrence of a parastomal hernia is an even greater challenge, the method of choice should have a low risk for recurrence. A prospective multicenter study was performed to evaluate safety and recurrence rate when using Parastomal Hernia Patch BARDTM (PHP), a mesh specially designed for parastomal hernia repair.A stoma has a profound impact on the patient´s daily life, both physical and psychological. A parastomal hernia with its associated risk for leakage and incarceration worsens the situation. Patient driven assessment of healthcare outcome is important if we are to improve medical care. A quality of life (QoL) survey was performed to assess the impact of parastomal bulging and hernia on the patient´s daily life.MethodsForty patients were investigated and the 3D US images were twice evaluated by two or three physicians to assess inter- and intra-observer reliability. Totally 20 patients with stoma complaints requiring surgery were examined with CT and 3D US prior to surgery. The findings were compared with the intraoperative findings – regarded as the true outcome.Fifty patients with parastomal hernia requiring surgery were enrolled from three hospitals. Patients were followed up one month and one year after repair using PHP.Patients still alive in 2008 who had been operated between1996 and 2004 for rectal cancer in Uppsala/Örebro-, Stockholm/Gotland-, and Northern Regions (986 patients) and registered in the Swedish Rectal Cancer Registry (SRCR) were invited to fill in four QoL questionnaires.ResultsInter-observer agreement using 3D US reached 80% for the last 10 patients examined, with a kappa value of 0.70. Intra-observer agreement for two examiners was 80% and 95%. The learning curve levelled out at 30 patients. Both CT and 3D US showed high sensitivity and specificity when compared with intraoperative findings.After surgery for parastomal hernia with a PHP, the complication rate at one month was 30% and recurrence rate at one year was 22%. Twelve patients were reoperated within one year.In the QoL study, 31.5% of the patients with a stoma reported a bulging or a hernia. 11.7% had been operated for parastomal hernia. A hernia or a bulge gave rise to significantly more pain and impaired stoma function. Overall QoL was inferior in patients with a permanent stoma compared to a group without a stoma.
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