| 1. |
- Lindmark, Gudrun, et al.
(författare)
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qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes : An improved method for assessment of tumor stage and prognosis
- 2024
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 154:3, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, −1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, −1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P =.01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.
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| 2. |
- Sakari, Thorbjörn B.
(författare)
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Adhesive small bowel obstruction: aspects on epidemiology, treatment, costs and prevention
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small bowel obstruction (SBO) is a common and sometimes life-threatening clinical condition, usually caused by post-operative adhesions. The aims of this thesis were to investigate the outcome after SBO surgery (Paper I), cost of SBO surgery including follow-up (Paper II), incidence of SBO after colorectal cancer (CRC) surgery (Paper III), and to assess the safety of using the adhesion preventing substance icodextrin in CRC surgery (Paper IV).Paper I, a population-based retrospective study on all patients operated for adhesive SBO (n=402) in the Uppsala and Gävleborg counties between 2007 and 2012. The SBO mechanism was a fibrous band in 56%. Complications and reoperations were recorded in 48% and 10% of patients, respectively. Complications, ICU care and early mortality were associated with age and ASA class. Seventy two patients had a recurrence of SBO, 26 of whom were re-operated. Previous laparotomies, diffuse adhesions, and complicated surgery (bowel injury, longer operation times and bleeding) were predictors of recurrent SBO. Paper II used the same cohort as in Paper I with an extended follow-up (8 years in median). Mean total cost estimates per patients were €40,467 during the study period. Diffuse adhesions and complications were associated with increased costs for SBO in a multivariable analysis (p<0.001).Paper III is a population-based register study based on all CRC cancer patients in Sweden 2007–2017. Among 33,632 CRC patients operated for stage I–III disease, the 5-year cumulative incidence was 7.6% for SBO and 2.2% for SBO surgery. In 198,649 matched CRC-free comparators the corresponding incidences were 0.6% and 0.2%, respectively. Open surgery and radiotherapy were associated with an increased incidence of SBO and SBO surgery. Paper IV is an interim analysis regarding morbidity and mortality, of a randomized controlled multicenter study assessing whether the adhesion preventing substance icodextrin can reduce the risk of postoperative SBO in stage I–III CRC patients. Randomization, to standard treatment with or without icodextrin, was blinded to the authors. Demographic data and overall complications were similar in the groups. Mortality, ICU care, anastomotic leaks and reoperations did not differ.
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| 3. |
- Sakari, Thorbjörn B., et al.
(författare)
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Mechanisms of adhesive small bowel obstruction and outcome of surgery : a population-based study
- 2020
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Ingår i: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThis study aims to describe the mechanisms of adhesive small bowel obstruction (SBO) and its morbidity, mortality and recurrence after surgery for SBO in a defined population.MethodRetrospective study of 402 patients (240 women, median age 70 years, range 18–97) who underwent surgery for SBO in the Uppsala and Gävleborg regions in 2007–2012. Patients were followed to last note in medical records or death.ResultThe cause of obstruction was a fibrous band in 56% and diffuse adhesions in 44%. Early overall postoperative morbidity was 48 and 10% required a re-operation. Complications, intensive care and early mortality (n = 21, 5.2%) were related to age (p < 0.05) and American Society of Anesthesiologist’s class (p < 0.01). At a median follow-up of 66 months (0–122), 72 patients (18%) had been re-admitted because of SBO; 26 of them underwent a re-operation. Previous laparotomies (p = 0.013), diffuse adhesions (p = 0.050), and difficult surgery (bowel injury, operation time and bleeding, p = 0.034–0.003) related to recurrent SBO. The cohort spent 6735 days in hospital due to SBO; 772 of these days were due to recurrent SBO. In all, 61% of the cohort was alive at last follow-up. Late mortality was related to malignancies, cardiovascular disease, and other chronic diseases.ConclusionsAbout half of patients with SBO are elderly with co-morbidities which predispose to postoperative complications and mortality. Diffuse adhesions, which make surgery difficult, were common and related to future SBO. Overall, nearly one-fifth of patients needed re-admission for recurrent SBO. Continued research for preventing SBO is desirable.
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| 4. |
- Sakari, Thorbjörn B., et al.
(författare)
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Role of icodextrin in the prevention of small bowel obstruction. Safety randomized patients control of the first 300 in the ADEPT trial
- 2016
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 18:3, s. 295-300
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Tidskriftsartikel (refereegranskat)abstract
- AimAdhesions are the most common cause of small bowel obstruction (SBO). The costs of hospitalization and surgery for SBO are substantial for the health-care system. The adhesion-limiting potential of icodextrin has been shown in patients undergoing surgery for gynaecological diseases. A randomized, multicentre trial in colorectal cancer surgery started in 2009 with the aim of evaluating whether icodextrin could reduce the long-term risk of surgery for SBO. Because of some concerns about complications (especially anastomotic leakage) after icodextrin use, a preplanned interim analysis of morbidity and mortality was conducted. MethodPatients with colorectal cancer without metastasis were randomized 1:1 to receive standard surgery, with or without instillation of icodextrin in the abdominal cavity. For the first 300 patients, the 30-day follow-up data were collected from the Swedish ColoRectal Cancer Registry (SCRCR). Pre-, per- and postoperative data, morbidity and mortality were analysed. ResultsOf the 300 randomized patients, 288 had a data file in the SCRCR. Twelve patients did not have cancer and another five did not have a resection, leaving 283 for analysis. The authors were blinded to the randomization groups. Demographic data were similar in both groups. The overall complication rate was 24% in Group 1 and 23% in Group 2 (P=0.89). Four cases of anastomotic leakage were reported in Group 1 and five were reported in Group 2 (P=1.0). Mortality, intensive care unit (ICU) stay and re-operations did not differ between the groups. ConclusionThe pre-planned safety analysis of the first 300 patients enrolled in this randomized trial did not show any differences in adverse effects related to the use of icodextrin. All data were gathered from the SCRCR, giving us a strong message that we can continue to include patients in the trial.
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| 5. |
- Sakari, Thorbjörn, et al.
(författare)
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Economic Consequences of Surgery for Adhesive Small Bowel Obstruction : A Population-Based Study
- 2023
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Ingår i: Gastroenterology Research and Practice. - : Hindawi Publishing Corporation. - 1687-6121 .- 1687-630X. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims. Most patients develop adhesions after abdominal surgery, some will be hospitalized with small bowel obstruction (SBO), and some also require surgery. The operations and follow-up are expensive, but recent data of costs are scarce. The aim of this study was to describe the direct costs of SBO-surgery and follow-up, in a population-based setting. The association between cost of SBO and peri- and postoperative data was also studied.Methods. In a retrospective cohort study, all patients (n = 402) operated for adhesive SBO in Gävleborg and Uppsala counties (2007–2012) were studied. The median follow-up was 8 years. Costs were calculated according to the pricelist of Uppsala University Hospital, Uppsala, Sweden.Results. Overall total costs were €16.267 million, corresponding to a mean total cost per patient of €40,467 during the studied period. Diffuse adhesions and postoperative complications were associated with increased costs for SBO in a multivariable analysis (P < 0.001). Most costs, about €14 million (85%), arouse in conjunction with the SBO-index surgery period. In-hospital stay was the dominating cost, accounting for 70% of the total costs.Conclusion. Surgery for SBO generates substantial economic burden for healthcare systems. Measures that reduce the incidence of SBO, the frequency of postoperative complication, or the length of stay have the potential to reduce this economic burden. The cost estimates from this study may be valuable for future cost–benefit analyses in intervention studies.
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| 6. |
- Sakari, Thorbjörn, et al.
(författare)
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Incidence of adhesive small bowel obstruction after surgery for colorectal cancer in Sweden 2007-2016
- 2024
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Ingår i: Colorectal Disease. - : John Wiley & Sons. - 1462-8910 .- 1463-1318. ; 26:2, s. 300-308
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Tidskriftsartikel (refereegranskat)abstract
- AimPopulation-based data on incidence and risk factors of adhesive small bowel obstruction (SBO) are limited. The aims of this study were to assess the risk of SBO and SBO surgery after bowel resection for colorectal cancer (CRC) and to assess whether this risk is modified by minimally invasive surgery (MIS) and radiotherapy in a retrospective national study.MethodsCRCBaSe, a nationwide register linkage originating from the Swedish Colorectal Cancer Register, was used to identify Stage I–III CRC patients who underwent resection in 2007–2016, with follow-up throughout 2017. Matched CRC-free comparators (1:6) were included as a reference of SBO and SBO surgery incidence. The association between MIS and preoperative radiotherapy and the incidence rate of SBO was evaluated in adjusted multivariable Cox regression models.ResultsAmong 33 632 CRC patients and 198 649 comparators, the 5-year cumulative incidence of SBO and SBO surgery was 7.6% and 2.2% among patients and 0.6% and 0.2% among comparators, with death as a competing risk. In all patients, MIS was associated with a reduced incidence of SBO (hazard ratio [HR] 0.7, 95% CI 0.6–0.8) and SBO surgery (HR 0.5, 95% CI 0.3–0.7). In rectal cancer patients, radiotherapy was associated with an increased incidence of SBO (HR 1.6, 95% CI 1.4–1.8) and SBO surgery (HR 1.7, 95% CI 1.3–2.3).DiscussionColorectal cancer surgery is associated with a marked increase in risk of SBO, compared with the general population. The incidence is further increased if open surgery or radiotherapy is performed.
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