Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Inge Fourneau, University of Leuven, Belgium
- Second opponent: Professor Morten Vetrhus, University of Bergen
- Third member and chair of the evaluation committee: Associate Professor Jarlis Wesche, University of Oslo
Chair of the Defence
Professor II Siri Rostoft, University of Oslo
Principal Supervisor
Professor II Jonny Hisdal, University of Oslo
Summary
Mesenteric ischemia is a disorder associated with diminished blood supply to the gastrointestinal tract due to internal or external narrowing of the mesenteric vessels. It may present as an acute or chronic process. The acute form, acute mesenteric ischemia is a serious clinical entity associated with ischemia of the gastrointestinal (GI) tract and gangrene of the bowels which in most cases causes death. The chronic form, chronic mesenteric ischemia (CMI), is a more insidious process proceeding over at least three months or years. However, CMI is an impairing state it is immediately not a life-threatening illness, although if left untreated more than half of the cases develop into the acute phase, which is associated with up to 70% mortality.
The most common cause of CMI is arteriosclerosis of the mesenteric vessels, characterized by the classical triad of postprandial abdominal pain, food aversion, and weight loss. A less frequent cause of CMI is external compression of the celiac artery and the celiac ganglion by the median arcuate ligament giving rise to the condition called median arcuate ligament syndrome (MALS). Although the classical triad is described only in 16 - 22% both atherosclerotic CMI and MALS have throughout history remained controversial because of their unspecific wide range of clinical symptoms, unclear findings on the physical examination, lack of specific biomarkers, imaging techniques for early diagnosis and that some have symptom relapse after treatment.
It was previously believed that at least two of the three major mesenteric arteries must be stenotic or occluded to receive treatment and that "single artery stenosis" does not cause problems. Consequently, there is great doubt in the existence of the disease MALS with "single artery stenosis", and disagreement about its etiology whether it is ischemic or neurological, and therefore excessive skeptics toward surgical treatment on the basis that not all develop symptom relief after surgery. Some studies have reported an average of three years from symptom debut to the diagnosis of CMI. Given the challenging nature of this disease, characterized by its low prevalence but high risk, guidelines have consistently emphasized the importance of accurate and timely diagnosis. Therefore, it is essential to explore diagnostic tools for early detection of CMI and MALS.
In Paper I, we investigated two different diagnostic tools for examining the mesenteric circulation in patients with atherosclerotic CMI and MALS. We used endoscopic duplex ultrasound, and transabdominal duplex ultrasound (E-DUS and TA-DUS) in detecting stenosis in the celiac artery and superior mesenteric artery. The results were then compared to computer tomography angiogram (CTA) findings, which is the standard diagnostic tool for CMI and MALS. Results showed that E-DUS has higher sensitivity and negative predictive value, but lower specificity than TA-DUS. The study concluded that E-DUS has great potential to be used as an initial screening test for patients suspected of CMI.
In Paper II and Paper III, we investigated the use of laser Doppler flowmetry (LDF) and visible light spectroscopy (VLS) for measuring microcirculation of the GI tract during minimally invasive esophagectomy in patients with esophageal cancer and laparoscopic decompression of coeliac artery in patients with MALS. The results gave significantly lower mixed arterial and venous saturation of hemoglobin levels measured with VLS in patients undergoing minimally invasive esophagectomy and in patients with MALS compared to healthy individuals. This indicates a decrease in tissue saturation. Thus, a significant effect of the combined use of LDF and VLS in detecting ischemic changes in the GI tract was demonstrated in both of our studies. This concludes that the combined use of LDF & VLS offers reliable and prompt feedback regarding the microcirculation of the GI tract. This valuable information assists surgeons in identifying the optimal anastomotic site for patients undergoing surgery for esophageal cancer. In addition, it serves as an early functional diagnostic test for individuals with MALS.
In papers III, IV, and V, we provided evidence that MALS is a medical condition primarily driven by an ischemic factor, and it can be effectively treated with laparoscopic decompression of the celiac artery. The motivation for conducting these studies emerged due to conflicting research, suggesting that MALS is not a vascular disease but rather a neurogenic one, thereby creating doubt on the efficacy of surgical treatment. Moreover, despite the relatively frequent occurrence of a 'J' configuration in CTA scans, signifying external compression of the celiac artery by the median arcuate ligament during expiration (10-24%), it leads to symptomatic manifestations in less than 1% of cases.
In Paper IV patients with MALS were treated with laparoscopic decompression of the CA and the results showed symptom relief for up to 90% of the patients with MALS. During the postoperative follow-up, it was observed that 67% of the patients achieved complete relief from symptoms, whereas 23% experienced partial relief within 3-6 months. The use of duplex ultrasound to evaluate the postoperative hemodynamics of CA demonstrated a significant improvement in peak systolic velocity values (p<0.001). Furthermore, the patients expressed overall satisfaction with the surgical procedure. The concluding statement in Paper IV emphasizes the significance of considering surgical intervention as a viable option for treating MALS. While the typical diagnostic approach involves excluding alternative causes and consulting a medical team to discuss diagnoses and treatment choices, it remains crucial to recognize the potential advantages associated with surgical treatment. In cases where individuals exhibit clinical symptoms of MALS and other potential diagnoses have been ruled out, and a CTA confirms mesenteric artery stenosis, it's advised to consider laparoscopic decompression of the celiac artery as the best course of treatment.
In Paper V, we identified intestinal ischemic biomarkers in patients with CMI and MALS. We analyzed four biomarkers namely, α-GST, I-FABP, citrulline, and ischemia-modified albumin in both healthy individuals and patients with MALS and CMI. Only α-GST showed statistical significance. The healthy individuals had plasma α-GST levels of 3.3 ng/mL. The plasma α-GST levels were elevated in patients with CMI to 7.8 ng/mL, and in patients with MALS to 8.4 ng/mL. However, after revascularization, the α-GST level returned to normal. The study used a cut-off value of 4 ng/mL for the normal median plasma α-GST level, which showed that the sensitivity and specificity for atherosclerotic CMI and MALS were 93% (95% CI 0.78 to 1.0) and 88% (95% CI 0.69 to 1.1), respectively. The Area Under the Curve was 0.96 (p<0.0001) for CMI and 0.85 (p<0.002) for MALS.
The observed postoperative clinical improvements, enhancement of hemodynamic values of the celiac artery in Paper III and Paper IV, and normalization of intestinal ischemic biomarkers after treatment in Paper V lend further support to the notion that MALS is an ischemic condition and should be considered for intervention.
Additional information
Contact the research support staff.