| 1. |
- Angenete, Eva, 1972, et al.
(författare)
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Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.
- 2009
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Ingår i: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:8, s. 1144-1151
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Tidskriftsartikel (refereegranskat)abstract
- Background. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. Materials and methods. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. Results. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. Conclusions. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.
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| 2. |
- Angenete, Eva, 1972, et al.
(författare)
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Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients
- 2007
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Ingår i: Int J Colorectal Dis. - 0179-1958. ; 11, s. 1331-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-beta1 (TGF-beta1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-beta1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome. MATERIALS AND METHODS: One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 x 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-beta1 and active TGF-beta1. Patients were then followed for 3 years. RESULTS: Total and active TGF-beta1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-beta1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-beta1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-beta1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-beta1 in the rectal mucosa (p = 0.038). CONCLUSIONS: Higher levels of total TGF-beta1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-beta1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-beta1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-beta1 in rectal cancer patients may be of clinical use in the future.
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| 3. |
- Angenete, Eva, 1972, et al.
(författare)
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uPA and PAI-1 in rectal cancer--relationship to radiotherapy and clinical outcome.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 153:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is well known that the fibrinolytic system is of importance in inflammation, wound healing, and fibrosis development. However, it is also important in the process of tumor invasion and metastasis. We have investigated protein levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rectal cancer and effects of radiotherapy, links to clinical outcome, and potential use as prognostic factors. MATERIALS AND METHODS: Ninety-one patients with rectal cancer were studied. Blood samples and biopsies were taken during surgery and assayed with enzyme-linked immunosorbent assay for uPA and PAI-1, and patients were followed prospectively (0-96 mo). RESULTS: Higher levels of uPA (P < 0.0001) and PAI-1 (P < 0.0001) were found in tumor compared with mucosa. Mucosa exposed to radiotherapy had higher levels of uPA (P < 0.0001) and of PAI-1 (P < 0.0001). Irradiated tumor tissue had higher levels of PAI-1 (P < 0.001). PAI-1 in tumor was correlated with T stage (P < 0.001) and N stage (P < 0.01). PAI-1 in plasma was higher in patients with synchronous distant metastases (P < 0.001). Cox regression was used to identify high levels of PAI-1 in tumor as an independent factor related to short disease-free survival (P < 0.01) and the ratio of uPA/PAI-1 to development of metastases (P < 0.01). CONCLUSIONS: There is a relationship between PAI-1 in plasma and rectal cancer metastases. PAI-1 in tumor tissue is correlated to histopathological data and to outcome of rectal cancer. If these findings can be confirmed in larger trials, there will be a possibility to use PAI-1 as a prognostic factor.
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| 4. |
- Azhar, Najia, et al.
(författare)
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Laparoscopic lavage for Hinchey III perforated diverticulitis : factors for treatment failure in two randomized clinical trials
- 2023
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Ingår i: The British journal of surgery. - 1365-2168. ; 110:7, s. 846-851
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis.METHODS: This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable.RESULTS: The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010).CONCLUSION: Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis.
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| 5. |
- Azhar, Najia, et al.
(författare)
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Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: Long-term Outcomes From the Scandinavian Diverticulitis (SCANDIV) Randomized Clinical Trial
- 2021
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Ingår i: JAMA Surgery. - Chicago, IL, United States : American Medical Association. - 2168-6254 .- 2168-6262. ; 156:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that laparoscopic lavage is a feasible alternative to resection. However, it appears that no long-term results are available.OBJECTIVE To compare long-term (5-year) outcomes of laparoscopic peritoneal lavage and primary resection as treatments of perforated purulent diverticulitis.DESIGN, SETTING, AND PARTICIPANTS This international multicenter randomized clinical trial was conducted in 21 hospitals in Sweden and Norway, which enrolled patients between February 2010 and June 2014. Long-term follow-upwas conducted between March 2018 and November 2019. Patients with symptoms of left-sided acute perforated diverticulitis, indicating urgent surgical need and computed tomography-verified free air, were eligible. Those available for trial intervention (Hinchey stagesINTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage or colon resection based on computer-generated, center-stratified block randomization.MAIN OUTCOMES AND MEASURES The primary outcome was severe complications within 5 years. Secondary outcomes included mortality, secondary operations, recurrences, stomas, functional outcomes, and quality of life.RESULTS Of 199 randomized patients, 101were assigned to undergo laparoscopic peritoneal lavage and 98were assigned to colon resection. At the time of surgery, perforated purulent diverticulitiswas confirmed in 145 patients randomized to lavage (n = 74) and resection (n = 71). The median follow-upwas 59 (interquartile range, 51-78; full range, 0-110) months, and 3 patientswere lost to follow-up, leaving a final analysis of 73 patients who had had laparoscopic lavage (mean [SD] age, 66.4 [13] years; 39 men [53%]) and 69 who had received a resection (mean [SD] age, 63.5 [14] years; 36 men [52%]). Severe complications occurred in 36%(n = 26) in the laparoscopic lavage group and 35%(n = 24) in the resection group (P = .92). Overall mortalitywas 32%(n = 23) in the laparoscopic lavage group and 25%(n = 17) in the resection group (P = .36). The stoma prevalencewas 8%(n = 4) in the laparoscopic lavage group vs 33% (n = 17; P =.002) in the resection group among patients who remained alive, and secondary operations, including stoma reversal, were performed in 36%(n = 26) vs 35%(n = 24; P = .92), respectively. Recurrence of diverticulitiswas higher following laparoscopic lavage (21% [n = 15] vs 4%[n = 3]; P = .004). In the laparoscopic lavage group, 30%(n = 21) underwent a sigmoid resection. Therewere no significant differences in the EuroQoL-5Dquestionnaire or Cleveland Global Quality of Life scores between the groups.CONCLUSIONS AND RELEVANCE Long-term follow-up showed no differences in severe complications. Recurrence of diverticulitis after laparoscopic lavage was more common, often leading to sigmoid resection. This must be weighed against the lower stoma prevalence in this group. Shared decision-making considering both short-term and long-term consequences is encouraged.
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| 6. |
- Bengtsson, Jonas, 1961, et al.
(författare)
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Can a failed ileal pouch anal anastomosis be left in situ?
- 2007
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Ingår i: Colorectal disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 9:6, s. 503-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.
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| 7. |
- Bengtsson, Jonas, 1961, et al.
(författare)
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Long-term function and manovolumetric characteristics after ileal pouch-anal anastomosis for ulcerative colitis
- 2007
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 94:3, s. 327-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Long-term pouch function and physiological characteristics after ileal pouch-anal anastomosis (IPAA) are poorly described. The aim of this study was to undertake a prospective investigation of long-term pouch function and manovolumetric characteristics. METHODS: Forty-two patients with a median follow-up of 16 years after IPAA were included. Function was assessed using a questionnaire and a score was calculated ranging from 0 to 15 (15 being the worst). Manovolumetry was performed and pouchitis recorded. A paired analysis was conducted, as the results were compared with previous data for each patient. RESULTS: The median functional score was 3.5 (range 0-10) at 2 years and 5 (range 1-11) at 16 years (P = 0.013). Resting anal canal pressures were higher (P < 0.001) and squeeze pressures lower (P = 0.008) at long-term follow-up. Ileal pouch volumes at distension pressures of 10, 20 and 40 cm H(2)O were diminished at 16 years (P < 0.001, P = 0.005 and P = 0.058 respectively). The volume and pressure for first sensation and urge to defaecate were reduced. Increased age correlated positively with a poor functional score. A history of pouchitis did not affect functional or physiological characteristics. CONCLUSION: Ileal pouch function declines in the long term. The reasons are unclear, but the ageing process may have an impact.
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| 8. |
- Berndtsson, Ina, 1953, et al.
(författare)
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Health-related quality of life and pouch function in continent ileostomy patients: a 30-year perspective.
- 2004
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Ingår i: Diseases of the colon and rectum. - : Ovid Technologies (Wolters Kluwer Health). - 0012-3706. ; 47:12, s. 2131-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The principal aim of this study was to assess long-term pouch durability and health-related quality of life in an original series of patients operated on with a continent ileostomy. PATIENTS: Data from 68 of 88 patients who had a continent ileostomy performed at Sahlgrenska University Hospital between 1967 and 1974 were analyzed. Median age at follow-up was 60 (range, 40-89) years and median follow-up was 31 (range, 29-36) years. METHODS: Patients were sent a questionnaire on pouch function along with the Short Form-36 Health Survey 2.0. A random age-matched and gender-matched sample was drawn from the Swedish national Short Form-36 Health Survey norm database to compare with the patient group. RESULTS: The majority of the patients reported good physical condition and satisfactory pouch function. Patients evacuated the pouch a median of four times every 24 hours. Twelve patients (18 percent) had leakages. Forty-four patients (65 percent) had had at least one postoperative revision to restore continence. Generally minor peristomal skin irritation occurred in seven patients (10 percent). Patients with concurrent complaints (mostly age related) reported poorer health-related quality of life. Nevertheless, 78 percent of the patients rated their overall health as good, very good, or excellent. The patients' Short Form-36 Health Survey scores were comparable to reference values. CONCLUSIONS: Although revisional operations may be needed to restore continence, continent ileostomy has a good durability. Pouch function was satisfactory and patients' satisfaction was high. Health-related quality of life levels were similar to those of the general population.
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| 9. |
- Berndtsson, Ina, 1953-, et al.
(författare)
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Long-term outcome after ileal pouch-anal anastomosis : function and health-related quality of life
- 2007
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Ingår i: Diseases of the Colon & Rectum. - : Lippincott Williams & Wilkins. - 0012-3706 .- 1530-0358. ; 50:10, s. 1545-52
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study was designed to investigate long-term pouch function and health-related quality of life in a single, large cohort of patients with ileal pouch-anal anastomosis for ulcerative colitis. METHODS: Data from 370 patients were included in the study. Thirty-nine patients (11 percent) did not have a functioning pouch (failures) but were included in the health-related quality of life analyses. Pouch function (Oresland score) and health-related quality of life (Short Form-36) were evaluated by postal questionnaires. A total of 88 percent of the patients with a functioning ileal pouch-anal anastomosis returned the questionnaires vs. 76 percent of the failures. Median follow-up time after ileal pouch-anal anastomosis was 15 years vs. 11 years after failure. An age-matched and gender-matched reference sample (n = 286) was randomly drawn from the Swedish Short Form-36 database. RESULTS: Median bowel frequency was six per 24 hours: 76 percent emptied the reservoir at night, 23 percent had urgency, 12 percent had evacuation difficulties, and 17 percent experienced soiling during the day. Fifty-two percent of the males and 32 percent of the females suffered from soiling at night. More than one-half of the patients had occasional perianal soreness, 6 percent considered the pouch to be a social handicap, and 94 percent were satisfied with their pouch. Patients with a functioning ileal pouch-anal anastomosis did not differ from the reference sample on any Short Form-36 domain, except for a reduced score in General Health (P = 0.02). Pouch function was positively correlated to health-related quality of life. Patients with pouch failure had reduced health-related quality of life in most domains. CONCLUSIONS: Patients' satisfaction is high and functional outcome is good after ileal pouch-anal anastomosis. Poor pouch function affects health-related quality of life negatively. Patients with failure after ileal pouch-anal anastomosis are substantially limited in a variety of health-related quality of life domains.
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| 10. |
- Block, Mattias, 1968, et al.
(författare)
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Pouch design and long-term functional outcome after ileal pouch-anal anastomosis.
- 2009
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 96:5, s. 527-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional outcome is of utmost importance after ileal pouch-anal anastomosis. Although pouch design and construction of the anastomosis are known technical determinants of function, there are few long-term results. This retrospective study evaluated functional outcome for two different pouch designs, and for handsewn versus stapled pouch-anal anastomoses. METHODS: The analysis included 412 patients who had either a J or K pouch (double-folded J pouch), of whom 123 had a J pouch (96 handsewn and 27 stapled) and 289 had a K pouch (95 handsewn and 194 stapled). Functional outcome was evaluated by a mailed questionnaire to achieve an Oresland score (0 to 15; 15 worst). RESULTS: Mean functional scores were 6.1 for J pouches and 4.9 for K pouches (P < 0.001). Regression analysis showed that reservoir design and age at surgery were predictors of functional outcome (P < 0.001). A higher proportion of patients with a J pouch and handsewn anastomosis than with a K pouch and stapled anastomosis had a score of 8 or more, a level previously demonstrated to impact negatively on quality of life (32 versus 16 per cent; P = 0.006). CONCLUSION: The K pouch was associated with a better long-term functional outcome than the J pouch in this patient population.
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