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Publications (10 of 201) Show all publications
Wennerlund, J., Thalén, D., Östevind, A., Gunnarsson, U. & Strigård, K. (2026). Change in faecal incontinence pattern after gastric bypass surgery: related to change in anal sphincter thickness?. International Journal of Colorectal Disease, 41(1), Article ID 27.
Open this publication in new window or tab >>Change in faecal incontinence pattern after gastric bypass surgery: related to change in anal sphincter thickness?
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2026 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 41, no 1, article id 27Article in journal (Refereed) Published
Abstract [en]

Purpose: Faecal incontinence is common in persons with severe obesity. Little is known about how the thicknesses of the internal anal sphincter (IAS) and the external anal sphincter (EAS) change in relation to weight loss following metabolic bariatric surgery (MBS). This study aims to investigate any change in IAS and EAS thickness 6 months after Roux-en-Y gastric bypass surgery (RYGB) and to determine whether any such change correlates with a change in faecal incontinence pattern. Methods: Thirty-one patients underwent three-dimensional endoanal ultrasound to measure anal sphincter thickness before and 6 months after RYGB. Patients completed the validated Wexner and LARS (low anterior resection syndrome) questionnaires at the same time to evaluate any change in faecal incontinence and urgency symptoms following surgery. Results: No significant change in the thicknesses of the IAS and EAS was seen. The Wexner score decreased from 18 to 13 (less incontinence). Conversely, the number of patients with LARS increased from 10 to 15 six months after surgery (more urgency). Conclusion: RYGB had no effect on the thickness of the anal sphincter 6 months after surgery. However, the pattern of faecal incontinence changed, with a decrease in leakage and whole faecal incontinence and an increase in urgency.

Place, publisher, year, edition, pages
Springer Nature, 2026
Keywords
Anal sphincter, Endoanal ultrasonography, Faecal incontinence, Gastric bypass, Obesity
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-248872 (URN)10.1007/s00384-025-05071-w (DOI)2-s2.0-105027003649 (Scopus ID)
Available from: 2026-02-26 Created: 2026-02-26 Last updated: 2026-02-26Bibliographically approved
Thalén, D., Hellman, U., Wennerlund, J., Gunnarsson, U., Sundbom, M. & Strigård, K. (2026). Hyaluronan and associated biomarkers: a longitudinal cohort study in patients with obesity following gastric bypass surgery. Obesity Surgery, 36, 1696-1704
Open this publication in new window or tab >>Hyaluronan and associated biomarkers: a longitudinal cohort study in patients with obesity following gastric bypass surgery
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2026 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 36, p. 1696-1704Article in journal (Refereed) Published
Abstract [en]

Introduction: Roux-en-Y Gastric Bypass (RYGB) is a common treatment option for obesity. After RYGB, loss of both adipose tissue and lean body mass is seen. In this study, we have investigated the dynamic metabolic changes of hyaluronan (HA) and associated biomarkers reflecting the extracellular matrix after RYGB.

Materials and Methods: In this exploratory cohort study, a total of 306 serum samples were collected at 5 different times from 96 RYGB patients, preoperatively until 6 months after surgery, where 44/96 (46%) contributed samples at 6 months. HA and the cell-surface receptor CD44 were studied by enzyme-linked immunosorbent assay (ELISA), while Luminex Multiplex assays were used for MMP-2, MMP-9, TNF-α, IL-1β, IL-6 and IL-10.

Results: Preoperatively, an elevated HA-concentration (> 120 ng/ml) was seen in 39.6% of the study population. From baseline to day of surgery, we found a statistically significant decrease (p < 0.05) in HA (Δ-21.4ng/mL [-42.6, -0.27]), CD44 (Δ-26.7ng/mL [-46.4, -6.9]), MMP-2 (Δ-32.4 ng/mL [-41.4 -23.4]) and MMP-9 (Δ-138.2 ng/mL [-188.0, -88.4]), TNF-α(Δ-3.1 pg/mL [-5.4, -0.8]), IL-1β (Δ-14.4 pg/mL [-22.2, -6.6]) and IL-6 (Δ-2.0 pg/mL [-3.1, -0.9]). At one month postoperatively, a subsequent increase was seen. Although the mean concentration of HA was unchanged at 6 months, patients with baseline HA ≥ 120 ng/mL demonstrated a decrease, (Δ-37.1 [-55.8 to -14.7] p < 0.01; exploratory analysis)

Conclusion: Although mean HA levels returned to baseline at 6 months, a significant transient decrease was observed immediately postoperatively, and patients with elevated preoperative HA (> 120ng/ml) showed a sustained reduction. The postoperative increase of MMP-2 suggests a continuous remodeling of the extracellular matrix.

Place, publisher, year, edition, pages
Springer, 2026
Keywords
Bariatric surgery, Gastric Bypass, Hyaluronan, Metabolic effects, Obesity
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-251086 (URN)10.1007/s11695-026-08564-x (DOI)001705640300001 ()41774373 (PubMedID)2-s2.0-105032133327 (Scopus ID)
Available from: 2026-03-27 Created: 2026-03-27 Last updated: 2026-05-21Bibliographically approved
Westin, L., Sandblom, G., Gunnarsson, U. & Dahlstrand, U. (2026). The impact of nerve management on the risk for persistent postoperative pain one year after open anterior mesh inguinal hernia repair. Hernia, 30(1), Article ID 74.
Open this publication in new window or tab >>The impact of nerve management on the risk for persistent postoperative pain one year after open anterior mesh inguinal hernia repair
2026 (English)In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 30, no 1, article id 74Article in journal (Refereed) Published
Abstract [en]

Purpose: Persistent postoperative pain is a major challenge in inguinal hernia surgery. However, the impact of intraoperative nerve management on postoperative pain is poorly understood. The aim was to evaluate how management of the three inguinal nerves during anterior mesh repair of inguinal hernia affects the risk for persistent postoperative pain.

Methods: Cohort study based on data from the Swedish Hernia Register (SHR) concerning management of the three inguinal nerves. Adult patients with an open anterior mesh repair between 2012 and 2017 and who had responded to a patient-reported outcome measure (PROM) questionnaire one year after surgery were included in the study.

Results: Out of eligible patients, 34,115 (69%) responded to the PROM questionnaire. Of these, 25.9% reported pain that could not be ignored and 15.7% reported pain interfering with daily activities one year after surgery. Identifying and/or preserving any of the three groin nerves was not seen to have a significant impact on the risk for persistent groin pain in multivariable ordinal regression analysis adjusted for type of anaesthesia, gender, age and emergency surgery.

Conclusion: In a setting where the nerves are handled according to the surgeon’s intraoperative judgement focusing on identifying and/or preserving the nerves, there was no association between intraoperative management of the three inguinal nerves and the risk for persistent postoperative pain one year after surgery. While careful tissue handling is crucial to the avoidance of postoperative pain, pragmatic nerve resection did not increase the risk for persistent pain one year after surgery.

Place, publisher, year, edition, pages
Springer Nature, 2026
Keywords
Pain, Nerves, Open repair, Register
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-249164 (URN)10.1007/s10029-025-03510-9 (DOI)001665622900002 ()41557045 (PubMedID)2-s2.0-105027946711 (Scopus ID)
Funder
Karolinska InstituteSjukvårdsregionala forskningsrådet Mellansverige, RFR-981376
Available from: 2026-02-03 Created: 2026-02-03 Last updated: 2026-02-03Bibliographically approved
Kaprio, T., Hagström, J., Kasurinen, J., Gkekas, I., Edin, S., Beilmann-Lehtonen, I., . . . Haglund, C. (2025). An immunohistochemistry-based classification of colorectal cancer resembling the consensus molecular subtypes using convolutional neural networks. Scientific Reports, 15(1), Article ID 19105.
Open this publication in new window or tab >>An immunohistochemistry-based classification of colorectal cancer resembling the consensus molecular subtypes using convolutional neural networks
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2025 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 15, no 1, article id 19105Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) represents a major global disease burden with nearly 1 million cancer-related deaths annually. TNM staging has served as the foundation for predicting patient prognosis, despite variation across staging groups. The consensus molecular subtype (CMS) is a transcriptome-based system classifying CRC tumors into four subtypes with different characteristics: CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Transcriptomics is too complex and expensive for clinical implementation; therefore, an immunohistochemical method is needed. The prognostic impact of the immunohistochemistry-based four CMS-like subtypes remains unclear. Due to the complexity and costs associated with transcriptomics, we developed an immunohistochemistry (IHC)-based method supported by convolutional neural networks (CNNs) to define subgroups that resemble CMS biological characteristics. Building on previous IHC-classifiers and incorporating β-catenin to refine differentiation between CMS2- and CMS3-like profiles, we categorized CRC tumors in a cohort of 538 patients. Classification was successful in 89.4% and 15.9% of tumors were classified as CMS1-like, 35.1% as CMS2-like, 38.7% as CMS3-like, and 11.7% as CMS4-like. CMS2-like patients exhibited the best overall survival (p = 0.018), including when local and metastasized disease were analyzed separately. Our method offers an accessible and clinically feasible CMS-inspired classification, although it does not serve as a replacement for transcriptomic CMS classification.

Place, publisher, year, edition, pages
Nature Publishing Group, 2025
Keywords
Colorectal cancer, Consensus molecular subtypes, Convoluted neural network, Immunohistochemistry, Prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-240984 (URN)10.1038/s41598-025-03618-z (DOI)001499627100001 ()40447758 (PubMedID)2-s2.0-105006917189 (Scopus ID)
Available from: 2025-06-24 Created: 2025-06-24 Last updated: 2025-06-24Bibliographically approved
Lindmark, M., Tall, J., Darkahi, B., Österberg, J., Strigård, K., Thorell, A. & Gunnarsson, U. (2025). Recurrence rate and mesh bulging are reduced with primary fascial closure in ventral hernia repair: the PROSECO randomized clinical trial. British Journal of Surgery, 112(9), Article ID znaf169.
Open this publication in new window or tab >>Recurrence rate and mesh bulging are reduced with primary fascial closure in ventral hernia repair: the PROSECO randomized clinical trial
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2025 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 112, no 9, article id znaf169Article in journal (Refereed) Published
Abstract [en]

Background: Laparoscopic intraperitoneal onlay mesh repair using a bridging technique has shown high rates of hernia site complications. Primary fascial closure before mesh placement has been utilized to address this. This randomized, parallel, double-blind, multicentre controlled trial investigated whether primary fascial closure reduces hernia site complications.

Methods: Adults undergoing laparoscopic intraperitoneal onlay mesh repair for a midline hernia were randomized to primary fascial closure or bridging. Clinical assessment and the Ventral Hernia Pain Questionnaire were completed preoperatively and at 3 and 12 months post-surgery. CT scans were performed pre- and 12 months post-surgery. It was hypothesized that non-resorbable suture closure would reduce complication rates from 30% to 13% at 12 months, requiring 180 patients for 80% power and 95% significance.

Results: One hundred and ninety-two patients were randomized (97 closure, 95 bridging), with 173 (90%) completing 1-year follow-up. At 12 months, overall hernia site complication rates showed no significant difference clinically (18% versus 20%, P = 0.85) or on CT (25% versus 28%, P = 0.50). However, recurrence and mesh bulging were significantly lower with fascial closure (4% versus 20%, P = 0.006). This group also reported significantly less pain at 12 months.

Conclusion:: Although there was no difference in the primary endpoint, fascial closure resulted in significantly lower rates of recurrence and mesh bulging, along with reduced postoperative pain. These findings suggest that primary fascial closure should be recommended alongside intraperitoneal onlay mesh repair in midline hernias.

Place, publisher, year, edition, pages
Oxford University Press, 2025
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-244157 (URN)10.1093/bjs/znaf169 (DOI)001561857200001 ()40893041 (PubMedID)2-s2.0-105015120071 (Scopus ID)
Funder
Region Västerbotten, RV-979794Region Västerbotten, RV-978927Region Västerbotten, RV-965797Visare Norr, 929704Familjen Erling-Perssons Stiftelse
Available from: 2025-09-29 Created: 2025-09-29 Last updated: 2025-09-29Bibliographically approved
Tjust, A. E., Hellman, U., Giannopoulos, A., Winsnes, A., Strigård, K. & Gunnarsson, U. (2024). Evaluation of extracellular matrix remodeling in full-thickness skin grafts in mice. Journal of Histochemistry and Cytochemistry, 72(2), 79-94
Open this publication in new window or tab >>Evaluation of extracellular matrix remodeling in full-thickness skin grafts in mice
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2024 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 72, no 2, p. 79-94Article in journal (Refereed) Published
Abstract [en]

Abdominal hernia is a protruding weakness in the abdominal wall. It affects abdominal strength and life quality and can lead to complications due to intestinal entrapment. Autologous full-thickness skin graft (FTSG) has recently become an alternative material for reinforcement in the surgical repair of large abdominal hernias instead of synthetic mesh. FTSG eventually integrates with the abdominal wall, but the long-term fate of the graft itself is not fully understood. This has implications as to how these grafts should be optimally used and handled intraoperatively. This study investigates the remodeling of FTSG in either the onlay or the intraperitoneal position 8 weeks after FTSG transplantation in an experimental mouse model. There was a significant presence of fibroblasts, indicated by vimentin and S100A4 staining, but there were significant variations among animals as to how much of the graft had been remodeled into dense connective tissue. This correlated significantly with the proportion of vimentin-positive cells in the dense connective tissue. We also found that collagen hybridizing peptide staining intensity, a marker of active remodeling, was significantly associated with the proportion of S100A4-positive cells in the dense connective tissue of the FTSG.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
collagen, extracellular matrix, fibroblasts, hernia, hyaluronan, mouse model, S100A4, vimentin
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-221051 (URN)10.1369/00221554231225995 (DOI)001147995400001 ()38264898 (PubMedID)2-s2.0-85184511984 (Scopus ID)
Funder
Swedish Research Council, 2021-00972Region Västerbotten, RV-927121Region Västerbotten, RV-965797
Available from: 2024-02-21 Created: 2024-02-21 Last updated: 2025-04-02Bibliographically approved
Odensten, C., Gunnarsson, U., Johansson, J. & Näsvall, P. (2024). Impact of parastomal hernia on colostomy costs at 1 year: secondary analysis of a randomized clinical trial (STOMAMESH). Scandinavian Journal of Surgery, 113(1), 33-39
Open this publication in new window or tab >>Impact of parastomal hernia on colostomy costs at 1 year: secondary analysis of a randomized clinical trial (STOMAMESH)
2024 (English)In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 113, no 1, p. 33-39Article in journal (Refereed) Published
Abstract [en]

Background and aims: Parastomal hernia (PSH) is a common complication after the creation of a colostomy, with a prevalence of approximately 50%. Despite the high frequency, little is known how PSH affects the cost of colostomy care. The hypothesis in this study was that PSH increases the cost of colostomy care compared with not having a PSH.

Methods: Two groups with (N = 61) and without (n = 147) PSH were compared regarding costs of stoma appliances and visits. The population from a large randomized trial comparing construction of colostomy with or without prophylactic mesh (STOMAMESH) was used and cross-matched with health economic data from the National Pharmaceutical Register, 1 year after initial surgery.

Results: Patients with and without a PSH were similar in basic demographic data. No difference in cost of stoma appliances (with PSH 2668.3 EUR versus no PSH 2724.5 EUR, p = 0.938) or number of visits to a stoma therapist (p = 0.987) was seen, regardless of the presence or not of a PSH.

Conclusions: PSH appears not to affect costs due to colostomy appliances or the need to visit a stoma therapist, in the first year. The lesson to be learnt is that PSHs are not a driver for costs. Other factors may be determinants of the cost of a colostomy, including manufacturers' price and persuasion, means of procurement, and presence of guidelines.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
Colostomy, health economy, parastomal hernia
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-213413 (URN)10.1177/14574969231188021 (DOI)001046532600001 ()37563916 (PubMedID)2-s2.0-85167775479 (Scopus ID)
Funder
Swedish Research Council, 214-7196Norrbotten County CouncilRegion Västerbotten, RV-927121
Available from: 2023-08-25 Created: 2023-08-25 Last updated: 2024-05-02Bibliographically approved
Silfvenius, A. U. .., Lindmark, M., Tall, J. V., Österberg, J. K., Strigård, K. K., Thorell, A. & Gunnarsson, U. (2024). Laparoscopic ventral hernia repair: early follow-up of a randomized controlled study of primary fascial closure before mesh placement. British Journal of Surgery, 111(1), Article ID znad434.
Open this publication in new window or tab >>Laparoscopic ventral hernia repair: early follow-up of a randomized controlled study of primary fascial closure before mesh placement
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2024 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 111, no 1, article id znad434Article in journal (Refereed) Published
Abstract [en]

Background: Suturing of the hernia aperture in laparoscopic ventral hernia repair has increased during the past decade. The primary aim of this is to restore the anatomy of the abdominal wall. Closure of the aperture, however, may cause additional tension in the abdominal wall which could increase postoperative pain. The aim of this study was to investigate whether suturing of the hernia aperture affects postoperative pain and hernia-site complications, including seroma, infection, pseudohernia, and mesh migration, 3 months after repair.

Methods: Some 192 patients with a midline hernia between 2 and 8 cm in transverse diameter were included in a randomized controlled double-blinded multicentre study. Patients were randomized to mesh repair with (intervention) or without (control) suturing of the hernia aperture before mesh placement. Patients completed the Ventral Hernia Pain Questionnaire before and 3 months after surgery. Abdominal wall pain and hernia-site complications were assessed 3 months after surgery.

Results: Ninety-seven patients were randomized to the intervention group and 95 to the control group. Among all patients, median age and BMI was 56 years and 31 kg/m2 respectively. Overall pain experienced decreased by 3 months after operation (P < 0.001). There was no difference between groups regarding hernia-site complications or pain experienced during the past week (13 versus 23 patients; P = 0.111). Seroma and pseudohernia occurred in 13 and 11 patients in the intervention and control groups respectively (P = 0.975 and P = 0.977).

Conclusion: Restoration of the abdominal wall anatomy by suturing the hernia aperture before mesh placement does not increase the risk of hernia-site complication or pain 3 months after surgery. This implies that fascial suturing of the aperture can be justified if there are potential long-term benefits such as lower recurrence and/or complication rates.

Registration number: ISRCTN51495042 (http://www.controlled-trials.com).

Place, publisher, year, edition, pages
Oxford University Press, 2024
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-219817 (URN)10.1093/bjs/znad434 (DOI)001134437500001 ()38159027 (PubMedID)2-s2.0-85181781906 (Scopus ID)
Funder
Umeå UniversityRegion Västerbotten, RV-979794Region Västerbotten, RV-978927Region Västerbotten, RV-965797Visare Norr, 929704Familjen Erling-Perssons Stiftelse, 20190200
Available from: 2024-01-22 Created: 2024-01-22 Last updated: 2025-03-26Bibliographically approved
Li, Y., Feng, X., Chen, D., He, Y., Fang, T., Tai, L., . . . Pan, W. (2024). Single-point ultrasound-guided iliohypogastric-ilioinguinal-genitofemoral nerve block for inguinal hernia surgery in older adult patients: a randomized controlled trial. Quantitative Imaging in Medicine and Surgery, 14(12), 8249-8259
Open this publication in new window or tab >>Single-point ultrasound-guided iliohypogastric-ilioinguinal-genitofemoral nerve block for inguinal hernia surgery in older adult patients: a randomized controlled trial
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2024 (English)In: Quantitative Imaging in Medicine and Surgery, ISSN 2223-4292, Vol. 14, no 12, p. 8249-8259Article in journal (Refereed) Published
Abstract [en]

Background: Ultrasound-guided nerve block can be used for perioperative analgesia and can potentially improve the course of recovery. Although iliohypogastric-ilioinguinal nerve block has been successfully used for inguinal hernia surgery, the poor blocking effect of intraoperative traction reflex remains a major drawback of this technique. The main objective of this study was to investigate the feasibility of single-point ultrasound-guided iliohypogastric-ilioinguinal-genitofemoral nerve (GFN) blockage for open anterior inguinal hernia repair in older adults. Methods: A total of 40 older adult patients [categorized as American Society of Anesthesiologists (ASA) I–III, body mass index (BMI) ≤28 kg/m2, age ≥60 years] undergoing open anterior inguinal hernia repair (the Lichtenstein technique) from June 2018 to December 2019 were recruited and randomly separated into an iliohypogastric-ilioinguinal nerve block group (group A; n=20) and an iliohypogastric-ilioinguinal-GFN block group (group B; n=20). The numerical rating scale (NRS) score in the post-anesthesia care unit (PACU) was the primary endpoint. Moreover, the following secondary indicators were recorded: the NRS score at 4 and 12 h after surgery and the duration of the nerve block; the total consumption of anesthetics; the occurrence of perioperative complications; and the mean arterial pressure (MAP), heart rate (HR), and respiration rate (RR), and oxygen saturation (SpO2) at baseline (T0), before skin incision (T1), 1 min after skin incision (T2), after dissection of the hernial sac (T3), at mesh placement (T4), and at the end of surgery (T5). Results: Patients in Group B had lower NRS scores in the PACU (0.9±0.7 vs. 2.1±0.9), at 4 hours post-operation (1.9±1 vs. 2.7±0.7), lower intraoperative traction response scores (0.6±0.8 vs. 1.7±1.2), and fewer postoperative complication scores (0.1±0.3 vs. 0.8±0.9) compared to group A (P<0.05). In addition, the MAP in group A was significantly higher than that in group B (P<0.01) at T2 (89.3±6.7 vs. 83.8±4.9), T3 (92.4±6.9 vs. 86.6±4.8), and T4 (87.8±5.2 vs. 83.1±4.6). The HR in group A was also higher than that in group B (P<0.05) at T2 (73.3±8.4 vs. 68.4±5.4) and T3 (77.0±14.7 vs. 68.7±6.9). Finally, compared to group B, group A showed a higher consumption of sufentanil (5.5±3.9 vs. 2.4±2.8) and lidocaine (3.4±2.3 vs. 1.0±2.0) (P<0.05). Conclusions: Performing an ultrasound-guided iliohypogastric-ilioinguinal-GFN block through a single puncture point is a feasible clinical approach. This strategy provides appropriate intraoperative and postoperative analgesia in older adult patients undergoing open anterior inguinal hernia repair and significantly reduces postoperative complications and thus has the potential to emerge as a novel analgesic option for inguinal hernia surgery.

Place, publisher, year, edition, pages
AME Publishing Company, 2024
Keywords
genitofemoral, Iliohypogastric, ilioinguinal, inguinal hernia, ultrasound-guided
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-233311 (URN)10.21037/qims-24-787 (DOI)001389784900001 ()2-s2.0-85211212822 (Scopus ID)
Available from: 2025-01-03 Created: 2025-01-03 Last updated: 2025-04-24Bibliographically approved
Gkekas, I., Novotny, J., Kaprio, T., Beilmann-Lehtonen, I., Fabian, P., Tavelin, B., . . . Gunnarsson, U. (2024). Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: a European multicenter cohort study. Journal of Surgical Oncology, 129(7), 1295-1304
Open this publication in new window or tab >>Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: a European multicenter cohort study
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2024 (English)In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 129, no 7, p. 1295-1304Article in journal (Refereed) Published
Abstract [en]

Background and Objectives: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status.

Methods: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex.

Results: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60–75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89–3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67–3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28–2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72–3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05–2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63–3.42, p = 0.005), respectively.

Conclusion: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
colorectal cancer, non-colorectal malignancy, sporadic deficient mismatch repair
National Category
Cancer and Oncology Surgery
Identifiers
urn:nbn:se:umu:diva-223081 (URN)10.1002/jso.27619 (DOI)001182569800001 ()38470492 (PubMedID)2-s2.0-85187434806 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, LP16‐2131Visare Norr
Available from: 2024-04-15 Created: 2024-04-15 Last updated: 2025-03-21Bibliographically approved
Projects
Stoma complaints ? a public health problem. Can this be solved by surgical intervention? [2014-07196_VR]; Umeå UniversityAbdominal Wall Defects ? surgical innovations based on understanding of biological interactions [2017-00824_VR]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3806-2114

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