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- Ghanipour, Lana
(författare)
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Colorectal Cancer : Aspects of Heredity, Prognosis and Tumour Markers
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is one of the most common cancer types and leading causes of cancer death worldwide. Since CRC is a heterogenic disease, there is a demand for increased knowledge of the underlying genetic and epigenetic mechanisms. The aim of this thesis was to investigate heredity and potential tumour markers in relation to prognosis. In paper I, survival of patients with CRC and a positive family history of CRC in first-degree relatives was analysed. Patients with colon cancer and positive family history of CRC had improved survival compared to patients with negative family history. This improvement in survival could not be explained by known clinico-pathological factors. In paper II, we investigated the prognostic value of Tryptophanyl t-RNA synthetase (TrpRS) in tissues from patients operated for CRC. Low protein expression of TrpRS in primary tumour tissues correlated with increased risk of recurrence and poorer survival. In paper III, the prognostic value of microsatellite instability (MSI) and the correlation to heredity for CRC in first-degree relatives was investigated. Patients with proximal colon cancer and MSI had improved cancer specific survival. There were no correlation between MSI and heredity. In paper IV, we evaluated the potential use of proximity ligation assay (SP-PLA) in patients with CRC, by simultaneous analysis of 35 proteins in only 5 μl plasma. SP-PLA is a suitable method for protein detection and might give valuable guidance in pursuing new prognostic and predictive tumour markers. However, none of the markers selected for present SP-PLA analyses gave better prognostic information than CEA. In conclusion, heredity is related to better survival independent of MSI in patients with CRC and MSI is associated with better prognosis in proximal colon cancer. Detection and increased knowledge of molecular mechanism in CRC is important, however it needs to be further investigated and validated in clinical use.
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| 2. |
- Gerjy, Roger, 1969-
(författare)
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Outcome After Haemorrhoidopexy
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: This dissertation is composed of five individual studies of the stapled haemorrhoidopexy operation. The operation was launched to an international audience in 1998 by the Italian surgeon Antonio Longo. In conventional surgery the prolapsed piles are excised from the anodermal part of the prolapse up through the anal canal into the lower rectal mucosa where the pile is divided with diathermy or suture ligated and excised. It leaves open wounds throughout the anal canal. These wounds can be very painful, especially at defecation, and will take from three to six weeks to heal. In the stapled haemorrhoidopexy operation symptomatic haemorrhoids are seen as a disease of anodermal, haemorrhoidal and rectal mucosal prolapse of varying degree. The main component of the prolapse is the redundancy of rectal mucosa. By pushing back the prolapse into the anal canal followed by excision of the mucosal redundancy above the anal canal with a circular stapler devise a mucosal anastomosis is fashioned. This anastomosis is situated immediately above the haemorrhoids and will attach them to the rectal muscular wall to prevent further prolapse. The operation is associated with substantially less pain and a quicker recovery.Methods: For the five studies, a total of 334 patients were operated for haemorrhoidal prolapse. The first operations were performed in February 1998. All patients were assessed preoperatively and postoperatively with the same set of protocols as follows. The symptoms of haemorrhoids were scored with a questionnaire to patients to obtain their independent statements of the frequency of each of five cardinal symptoms: pain, bleeding, pruritus, soiling and prolapse in need of manual reduction. A diary was used by patients to report daily pain scores, use of pain medication and speed of recovery within the first 14 postoperative days. The surgeon rated the deranged anal anatomy before and after surgery. We also developed an algorithm based on the patients’ statement of digital reduction of prolapse (grade 3) and the surgeon’s assessment of lesser prolapse at proctoscopy (grade 2). Absence of prolapse was grade 1. The surgeon also provided statements about the conduct of the operation and rated the technical complexity. The information, for all patients, was entered into an electronic data base.Results: One registry based study and one prospective randomised controlled trial assessed the advantage of performing the operation under perianal local anaesthetic block. The postoperative pain and surgical outcome was independent of the type of anaesthesia. No operation under local block had to be converted to general anaesthesia. Anodermal prolapse is seen in 70 percent of the patients. In a registry-based study we found that excision of the anodermal folds did not increase the postoperative pain provided the excision stopped at the anal verge. In 270 patients with precise preoperative and postoperative classification we found that the symptomatic load was identical for grades 2 and 3. The symptoms were independent of the anodermal prolapse. The symptoms were greatly reduced when the operation turned out grade 1 prolapse. The long-term result was assessed in 153 patients operated 1 year to 6 years previously. The need for early re-intervention was 6.2 percent representing technical error to reduce the prolapse. At the final evaluation 12 patients (8.2 percent) complained of a mucoanal prolapse in need of digital reduction. The mean symptom burden had been reduced from 8.1 to 2.5 points but 17 percent had at least one cardinal symptom with a weekly frequency.Conclusions: Stapled haemorrhoidopexy should be performed as day surgery under local anaesthesia. Any remaining anodermal prolapse should be excised. The optimal long-term outcome is grade 1A or 1B with low symptom score. There was an 87 percent chance of cure of the prolapse with the first haemorrhoidopexy. About half the failures were insufficient primary surgery and half a relapse of the prolapse.
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| 3. |
- Kverneng Hultberg, Daniel, 1990-
(författare)
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Surgery for rectal cancer : the impact of perioperative factors
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is one of the most common and deadly cancer forms worldwide. A large proportion of rectal cancer patients are surgically treated with curative intention, with anterior resection being the most frequently used method today. During surgery, the inferior mesenteric artery is either ligated proximal (high tie) or distal to the left colic artery (low tie). It is not known whether the tie level affects the oncologic nor the functional outcome. Postoperatively, about one in ten patients develop an anastomotic leakage. It is unclear whether treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) affects the risk of leakage, or whether having a leakage influences the functional outcome. The general aims of this dissertation were to increase the knowledge of intra- and postoperative treatment for rectal cancer, with the goal of improving the oncologic and functional outcomes, as well as reducing postoperative complications. National registers, predominantly the Swedish Colorectal Cancer Registry, were used in all of the dissertation’s four retrospective cohort studies to identify and retrieve information regarding patients. Various statistical methods have been used in all studies with the aim of eliminating bias, including confounding.In Study I, high tie slightly increased the total number of harvested lymph nodes in the included 8287 patients, as compared with low tie, while the primary outcome cancer-specific survival, as well as secondary oncologic outcomes, were not affected. This indicates that the oncologic outcome does not have to be considered when the surgeon determines the level of tie.In Study II, investigating the effect of tie level on the functional outcome, the outcome was any defecatory or urogenital symptoms two years after anterior resection, assessed with a mailed questionnaire. With a response rate of 86%, 805 patients were included. High tie did not, except for increasing the need of defecation at night, influence the risk of major dysfunction. Again, this would facilitate the choice of tie level.Study III used the same outcome, and in part the same study population, as Study II, but instead with the exposure anastomotic leakage. With a response rate of 82%, 1180 patients were included. We found that anastomotic leakage increased the risk of reduced sexual activity and increased the use of aid products for fecal incontinence after anterior resection, while the risk of urinary incontinence was unexpectedly decreased. Other outcomes were not clearly affected. In Study IV, in addition to the register, information was gathered from patient records. In the included 1495 patients who had undergone anterior resection, postoperative NSAID treatment was not found to increase the risk of symptomatic anastomotic leakage. There were no differences between non-selective and COX-2 selective NSAIDs. This study does not support that NSAID treatment increases the risk of anastomotic leakage after such surgery.
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