Introduction

Although traditionally regarded as a vestigial organ, the appendix is increasingly recognized for its potential role in modulating gut immunity and contributing to the development of significant inflammatory or neoplastic intestinal diseases [1]. However, the underlying mechanisms linking the appendix to these immune and pathological processes remain poorly understood. This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.

Aims & Methods

This study aimed to investigate the relationship between the local immune microenvironment and the mutational landscape of rectal carcinomas in the context of prior or progressive appendectomy status.
Patients enrolled in the IMMUNOREACT 1 and 2 studies (NCT04915326 and NCT04917263, respectively) were stratified according to appendectomy status. Immunohistochemical analysis was performed to assess a range of immune markers, including CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, PMS2, and CD80. Additionally, flow cytometry was employed to evaluate the percentage of epithelial cells expressing CD80, CD86, CD40, HLA-ABC, or HLA-DR, as well as to quantify activated CD8+ T cells, CD4+ Th1 cells, and regulatory T cells (Tregs). Non-parametric tests were used.

Results

In this cohort, 41 patients out of 163 underwent appendectomy for other causes (e.g. appendicitis) before having been diagnosed with a rectal cancer. When the two groups were compared for microenvironmental features, in the normal mucosa of patients who had a previous appendectomy there was a higher rate of epithelial cells expressing HLA-abc (p=0,04) and a higher expression of CTLA4 on CD3+ T cells (p=0,03) when compared to appendectomy-naive patients. Within the rectal cancer tissue, a higher expression of CD86 on epithelial (cancer) cells expression was found in patients who already had an appendectomy (p=0,03). In therapy naïve patients, previous appendectomy was associated to a higher activation of CD4+ T helpers (expression of CD25), (p=0.04), and to tendency of higher rate of epithelial cells expressing HLA-abc (p=0,06) and of T cells expressing CTLA-4 (p=0.08). In patients who had neoadjuvant therapy, lower level of PD-L1 on the leukocyte surface were observed in patients who had a previous appendectomy (p=0.039).

Conclusion

Our findings suggest that prior appendectomy may be associated with distinct alterations in the local immune microenvironment of rectal carcinomas, including increased expression of antigen-presenting and immune-regulatory molecules such as HLA-BC, CTLA4, and CD86. In therapy naïve patients, appendectomy seem to increase the activation of T helper cells counterbalanced by an increase of the number of T cells expressing CTLA-4. These immune shifts in both tumour tissue and adjacent healthy mucosa support the hypothesis that the appendectomy may in somehow alter the interaction between epithelia cells and intraepithelial T cells. Further trancriptomic ​analysis will shed light on the effect of appendectomy on mucosal microevironment of ​rectal cancer patients.

References

1. Collard MK, Tourneur-Marsille J, Uzzan M, Albuquerque M, Roy M, Dumay A, Freund JN, Hugot JP, Guedj N, Treton X, Panis Y, Ogier-Denis E. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer. Cell Mol Gastroenterol Hepatol. 2023;15(3):665-687.

Introduction

Superior Mesenteric Artery Syndrome (SMAS), also known as Wilkie’s syndrome, is a rare gastrointestinal condition characterized by compression of the distal duodenum between the abdominal aorta (AA) and the superior mesenteric artery (SMA). Evidence on Wilkie’s syndrome is limited, reviews are based on small cohorts and case studies^1-3. Patients with SMAS typically present with postprandial epigastric discomfort, nausea, vomiting, stomach distention, and reflux, leading to malnutrition and weight loss. As mesenteric fat decreases due to the weight loss, the duodenal obstruction worsens, increasing SMAS symptoms. SMAS mostly affects young females aged 20-30 years and is challenging to diagnose due its overlap with dyspepsia, anorexia nervosa and median arcuate ligament syndrome^1-3. SMAS can present acutely, after weight loss from bariatric surgery, malnutrition or (hyper)metabolic disorders. It also presents chronically, due to an anatomically high duodenal position or a low aortic SMA origin^1-3. Diagnostic imaging, including computed tomography (CT) typically reveals a reduced SMA-AA angle <25° and a characteristic vertical, abrupt duodenal obstruction on barium X-ray series^1,2. Conservative treatment focuses on improving gastrointestinal motility and increasing the SMA-AA angle by weight gain to regain mesenteric fat¹. If conservative treatment fails, surgical intervention is considered, with duodenojejunostomy being most commonly performed. Yet, this carries potential severe complications such as anastomotic leakage and non-physiological gastro-duodenal changes. Recent evidence suggests laparoscopic Treitz ligament release may offer a viable and low-risk alternative^3,4.

Aims & Methods

This study aims to introduce a standardized, low risk treatment protocol for SMAS. The protocol includes: 1) Jejunal tube feeding for six-eight weeks, 2) Laparoscopic release of the Treitz ligament, and 3) SMA reimplantation⁵. The protocol was implemented at three hospitals in the Netherlands, Medisch Spectrum Twente, Franciscus, and Erasmus MC.

Results

A total of 12 patients were treated according to this protocol from 2020 until 2024. The cohort consisted of 7 (58.3%) female patients, with a mean age of 29.2 years (SD 11.8). The average weight and body mass index were 60.33 kg (SD 6.5) and 20.01 (SD 3.4). The mean SMA-AA angle measured on CT scans was 22.55° (SD 13.1). All patients started treatment with jejunal feeding. Nine patients underwent laparoscopic Treitz ligament release, with 7 experiencing complete resolution of symptoms. One patient with co-existing Nutcracker syndrome received primary SMA infra-renal reimplantation, with complete symptom release after the surgery. In two patients, symptoms persisted following Treitz ligament release, resembling gastroparesis and irritable bowel syndrome. The 2 remaining patients are planned for laparoscopic Treitz ligament release.

Conclusion

The combination of jejunal feeding followed by laparoscopic Treitz ligament release, represents a safe and effective treatment approach for SMAS; 7/9 patients who underwent the Treitz ligament release experienced resolution of all symptoms, demonstrating the efficacy of protocol. This approach offers an alternative to traditional surgical procedures, such as duodenojejunostomy, and reduces the risks of substantial short- and long-term complications. Further research with larger sample sizes is required to confirm the long-term outcomes and advantages of this protocol compared to other treatment strategies for SMAS.

References

1. Oka A, Awoniyi M, Hasegawa N, Yoshida Y, Tobita H, Ishimura N, Ishihara S. Superior mesenteric artery syndrome: Diagnosis and management. World J Clin Cases. 2023 May 26;11(15):3369-3384. doi: 10.12998/wjcc.v11.i15.3369. PMID: 37383896;
2. Navandhar PS, Shinde RK, Gharde P, Nagtode T, Badwaik N. Understanding Superior Mesenteric Artery Syndrome: Etiology, Symptoms, Diagnosis, and Management. Cureus. 2024 Jun 2;16(6):e61532. doi: 10.7759/cureus.61532. PMID: 38957238; PMCID: PMC11218894
3. Beita AKV, Whayne TF. The Superior Mesenteric Artery: From Syndrome in the Young to Vascular Atherosclerosis in the Old. Cardiovasc Hematol Agents Med Chem. 2019;17(2):74-81. doi: 10.2174/1871525717666190920100518. PMID: 31538906.
4. Fang JF, Wei B, Zheng ZH, Lei PR, Chen TF, Wei HB. Laparoscopic lysis of the ligament of treitz for superior mesenteric artery syndrome. Dig Surg. 2014;31(4-5):291-6. doi: 10.1159/000367670. Epub 2014 Oct 17. PMID: 25342434.
5. Ali T, Tomka J, Bakirli I, Bakirov I. Surgical Treatment of Wilkie's Syndrome by Vascular Transposition. Cureus. 2022 Apr 18;14(4):e24251. doi: 10.7759/cureus.24251. PMID: 35475250; PMCID: PMC9018456.
6. Pourhassan S, Grotemeyer D, Fürst G, Rudolph J, Sandmann W. Infrarenal transposition of the superior mesenteric artery: a new approach in the surgical therapy for Wilkie syndrome. J Vasc Surg. 2008 Jan;47(1):201-4. doi: 10.1016/j.jvs.2007.07.037. Epub 2007 Oct 18. PMID: 17949939