Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms

Abstract

Introduction: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). Methods: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. Results: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). Conclusion: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha‐smooth muscle actin‐positive fibrosis and COMP‐expressing stromal cells

“…[44][45][46] Another obstacle was the limited sample input, due to the lack of cells in fibrotic tissue. 5 Additionally, the unconventional lysis buffer needed in HTG's extraction-free chemistry complicated RNA extraction within our validation. Another technical aspect not to be underestimated is under the given circumstances the challenging primer designing process, taking all biological and technological challenges into consideration as we did not seek to validate the genes in general, but the specific gene segments used in the HTG EdgeSeq library.…”

“…MF was defined as a mesenteric soft tissue mass displaying typical characteristics of a local LNM from the SI-NET(s), which exerts a desmoplastic reaction leading to drawing in of the adjacent mesentery and small bowel loops, potentially encasing and occluding mesenteric vessels and thereby causing combined arterial and venous ischemia of the affected bowel loops as defined previously. 5 In our experience, MF typically presents as a one-of-a-kind concrete-like, white and stringy induration with shrinkage of the mesentery. According to Clement et al 16 and Makridis et al, 17 MF was defined as angulation of the bowel with shrinkage of the mesentery resulting in fixation of the mesenteric root to the retroperitoneum.…”

“…[1][2][3][4] Furthermore, SI-NETs have a high tendency to metastasize-about 80% of patients have lymph node metastases (LNM) in the mesentery at the time of diagnosis. 5,6 In addition, around 50% of SI-NET patients develop mesenteric fibrosis (MF), a unique form of desmoplastic reaction in the mesentery, mostly associated with extensive fibrotic reaction around local LNM. 5,6 MF compromises both mobility and blood flow to the small intestine (SI) causing obstruction and ischemia, often necessitating surgery and implying an unfavorable prognosis.…”

“…5,6 In addition, around 50% of SI-NET patients develop mesenteric fibrosis (MF), a unique form of desmoplastic reaction in the mesentery, mostly associated with extensive fibrotic reaction around local LNM. 5,6 MF compromises both mobility and blood flow to the small intestine (SI) causing obstruction and ischemia, often necessitating surgery and implying an unfavorable prognosis. [7][8][9] Despite the clinical significance of MF for the patients, its pathomechanism remains poorly understood, mostly since studies focus only on the mechanisms in the tumor, neglecting predisposing factors from the surrounding stroma and their crosstalk.…”

“…6,9 To date, there is no therapeutical approach against MF apart from a challenging surgery, where the success is highly variable and dependent on the extent of fibrosis. 5,9,14,15 This study aimed to uncover the molecular pathomechanisms involved in the formation of MF, in both LNM cells and stromal compartment, to enable the development of new therapeutic alternatives and ultimately to improve patient management. MF was defined as a mesenteric soft tissue mass displaying typical characteristics of a local LNM from the SI-NET(s), which exerts a desmoplastic reaction leading to drawing in of the adjacent mesentery and small bowel loops, potentially encasing and occluding mesenteric vessels and thereby causing combined arterial and venous ischemia of the affected bowel loops as defined previously.…”