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- Baban, Bayar, 1973-, et al.
(författare)
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Altered insulin sensitivity and immune function in patients with colorectal cancer
- 2023
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier. - 2405-4577. ; 58, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls.Methods: Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups.Results: Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1b(patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1b production, within circulating immune cells.Conclusion: Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1b and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.
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| 2. |
- Baban, Bayar, 1973-
(författare)
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Colorectal cancer and surgery : Insights into insulin resistance and inflammatory markers
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The art of surgery has progressively extended from the realm of anatomy to encompass physiology and beyond, in search of further refinement and optimal recovery. Integral to this is a deeper understanding of the body’s essential metabolic and inflammatory responses to surgical trauma.This thesis aims to provide insights into the intricate interplay between insulin resistance, inflammation and surgical interventions in colorectal cancer patients, as each has an influence on postoperative recovery. Particular emphasis is placed on the role of inflammasomes – central mediators of the innate immune response, adept at detecting and responding to a diverse range of triggers, yet insufficiently explored in these specific contexts.Study I is a comparative analysis of the hyperinsulinemic–euglycaemic clamp and homeostatic model assessment (HOMA) in determining postoperative insulin resistance in 113 patients undergoing various elective surgeries. The findings establish the clamp as the accurate method, detecting key physiological distinctions missed by HOMA.Study II, an exploratory case–control study, assesses insulin sensitivity and inflammatory markers in 20 colorectal cancer patients compared to 10 matched healthy controls. Results indicate insulin resistance, reduced inflammasome activity in circulating immune cells and elevated systemic IL-1β and IL-6 levels in patients.Study III, a pilot exploratory study of 17 patients from Study II, assesses the impact of surgical technique, open versus minimally invasive surgery, on postoperative insulin resistance and inflammation in colorectal cancer resections. It indicates a differential inflammatory response with higher levels in open surgeries, yet a consistent degree of insulin resistance across both surgical techniques.Study IV explores the perioperative temporal sequencing of inflammation and inflammasome action in 18 patients from Study II undergoing elective colorectal cancer resections. It points to a more immediate and pronounced inflammatory response in open surgery compared to minimally invasive surgery, though both techniques show reduced intraoperative caspase-1 activity.In conclusion, the hyperinsulinemic euglycaemic clamp is the accurate method in determinations of postoperative insulin resistance. Patients with colorectal cancer, in comparison to matched healthy controls, exhibit insulin resistance and higher levels of inflammation, but decreased inflammasome (caspase-1) activity in circulating immune cells. Finally, colorectal cancer resections induce both insulin resistance and inflammation; however, the surgical technique utilized only significantly affects the latter, with generally higher inflammatory / inflammasome responses in open surgery.
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| 3. |
- Baban, Bayar, 1973-, et al.
(författare)
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Determination of insulin resistance in surgery : the choice of method is crucial
- 2015
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 34:1, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: In elective surgery, postoperative hyperglycaemia and insulin resistance are independent risk factors for complications. Since the simpler HOMA method has been used as an alternative to the hyperinsulinemic normoglycemic clamp in studies of surgery induced insulin resistance, we compared the two methods in patients undergoing elective surgery.METHODS: Data from 113 non-diabetic patients undergoing elective surgery were used. Insulin sensitivity, both before and after surgery, was quantified by the clamp and HOMA. Pre- and postoperatively, the results of the clamp were compared to HOMA using regression- and correlation analysis. Degree of agreement between the methods was studied using weighted linear kappa and the Bland-Altman test.RESULTS: Both the clamp and HOMA recorded a mean relative reduction in insulin sensitivity of 39 ± 24% and 39 ± 61% respectively after surgery; with significant correlations (p < 0.01) for pre- and post-operative measures as well as for relative changes. However r(2) values were low: 0.04, 0.07 and 0.03 respectively. The degree of agreement for the relative change in insulin sensitivity using the Bland-Altman test gave a mean of difference 0% but "limits of agreement" (±2SD) was ±125%. This poor inter-method agreement was consolidated by a weighted linear kappa value of 0.18.CONCLUSION: While the hyperinsulinemic euglycemic clamp measures the postoperative changes in insulin sensitivity, HOMA measures something different. Data using the HOMA method must therefore be interpreted cautiously and is not interchangeable with data obtained from the clamp.
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| 4. |
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| 5. |
- Baban, Bayar, 1973-, et al.
(författare)
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Inflammasome activation, colonic cancer and glucose metabolism
- 2016
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier. - 2405-4577. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study the association between inflammasome activation (a potent initiator of inflammation acting via caspase-1 and maturation of interleukin-1β), colonic cancer and glucose metabolism.Methods: Five patients with colon cancer and ten matched controls without cancer were measured for insulin sensitivity using the hyperinsulinemic euglycemic clamp. For detection of inflammasome activation the caspase-1 activity, determined by detecting FLICA using flow cytometry, was measured in both monocytes and granulocytes at the start of, and at 120 minutes into the clamp. Descriptive and analytical statistics were performed using nonparametric methods by SPSS.Results: There was no difference in levels of insulin sensitivity between the two groups (p=0.09). The cancer patients had significantly lower levels of caspase-1 both in monocytes (p<0.05) and granulocytes (p<0.05) compared with the controls. However both patients and controls had significantly higher levels of both mono- and granulocyte caspase-1 activity at 120 minutes into the clamp as compared to at start (p<0.05). Patients showed an overall higher relative increase in caspase-1 during the clamp, however this finding did not reach statistical significance (monocytes; p=0.27, granulocytes; p=0.22).
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| 7. |
- Popiolek, M., et al.
(författare)
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Total Mesorectal Excision for Mid-Rectal Cancer Without Anastomosis : Low Hartmann's Operation or Intersphincteric Abdomino-Perineal Excision?
- 2019
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 108:3, s. 233-240
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: In mid-rectal cancer, the low colorectal anastomosis is, although feasible, sometimes avoided. The aim was to compare low Hartmann's procedure with intersphincteric abdomino-perineal excision of the rectum, in patients operated with total mesorectal excision for mid-rectal cancer in whom the low anastomosis was technically feasible but for patient-related reasons undesired.MATERIAL AND METHODS: A total of 64 consecutive patients with mid-rectal cancer who underwent low Hartmann's procedure (n = 34) or intersphincteric abdomino-perineal excision (n = 30) at one colorectal unit were compared regarding patient demography, short-term oncology, surgical outcome at 3 and 24 months, and long-term overall survival.RESULTS: There were no significant differences between intersphincteric abdomino-perineal excision and Hartmann's procedure regarding age, gender distribution, body mass index, preoperative radiotherapy, tumor level, or cancer stages. Operation time was shorter in Hartmann's procedure as compared with intersphincteric abdomino-perineal excision, median 174 and 256 min, (P < 0.001), and intraoperative blood loss was increased, 600 and 500 mL, respectively (P = 0.045). Number of lymph nodes and circumferential resection margin were comparable. In Hartmann's procedure compared with intersphincteric abdomino-perineal excision, the need for reoperation was 24% and 3%, (P = 0.020), complications classified as Clavien-Dindo 3-4 occurred in 32% and 10%, (P = 0.031), pelvic abscess in 21% and 10%, (P = 0.313), and mortality within 90 days was 3% and 0%, respectively, (P = 0.938). In intersphincteric abdomino-perineal excision, the perineal wound was not healed at 3 months in 13%, and in Hartmann's procedure 15% had chronic secretion from the anorectal remnant at 2 years postoperatively.CONCLUSION: The results from this study suggest that intersphincteric abdomino-perineal excision might be an alternative to Hartmann's procedure in patients with mid-rectal cancer, in whom a low colorectal anastomosis is undesired.
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