Non-human primate (NHPs) species have many biological characteristics similar to those of humans and have a wide range of applications in taxonomy, ecology, anatomy, genetics, behavior, evolution, reproductive biology, and other fields of study (1, 2). Pancreatic diseases have always been difficult to diagnose and treat because of its deep location, many surrounding adjacent organs and complex structure. While diabetes-inducing non-human primates (NHPs) can serve as an ideal model for this pancreatic disease due to their high similarity to diabetic patients in terms of metabolic, hormonal and pathological abnormalities (3). Zhang et al. reported four modeling methods in rhesus monkeys, including total and partial pancreatectomy, the latter is more effective but needs a fully comprehension of pancreas anatomy (4). And anatomical studies on the pancreatic arteries of rhesus monkeys are scarce so far.

In recent years, with the introduction of the concept of “mesopancreas”, defining the perineural structures that includes neurovascular bundle and lymph nodes extending from the posterior surface of the pancreatic head to behind the mesenteric vessels, there has been a great evolution in the way of pancreatic resection (5, 6). Accordingly, the concept of “Total mesopancreas excision (TMpE)” has been proposed and applied, suggesting that TMpE can help raise the R0 resection rate and improve the prognosis (7–12). Although the concept of TMpE has been upheld in clinical practice for surgeries, the existence or non-existence as well as boundaries and contents of the mesopancreas are disputed (13). Agrawal et al. revealed loose areolar tissue, adipose tissue, peripheral nerve, nerve plexus, lymphatics and capillaries in retropancreatic tissue from 20 fresh cadavers; but these structures were not surrounded by fibrous sheaths or fascia, similar to the mesentery (14). Meanwhile, the blood supply of the pancreaticoduodenal region is one of the most complicated parts of the abdominal cavity in humans (15, 16). The extent of clinical surgical resection and structural preservation in TMpE are also controversial, especially with regard to the state of existence of the mesopancreas in the corresponding tissues of the posterior part of the pancreas. Hence, a clear understanding of the coverage of the peripancreatic fascia/peritoneum and the relationship between the fascia and surrounding structures enables clinical staff to resolve questions in clinical practice from a morphological aspect (17).

The aim of our study is to compare the pancreatic vessels and fascia of human and rhesus monkeys and to provide the basis for the utilization of rhesus monkeys from anatomical and embryological perspectives. A comprehensive understanding of the features of the peripancreatic peritoneum in terms of gross observation and embryology, and the elucidation of the relationship with surrounding organs, blood vessels and nerves are of great importance for the improvement of surgical standards for TMpE based on the theory of mesopancreas, improving the R0 resection rate of malignant tumors and ensuring surgical outcomes.

The comparative anatomy of humans and NHPs has a long history. Galen used monkeys to infer human anatomy. Tyson's 1699 work showing that chimps share many anatomical similarities with humans (18). NHPs are very suitable as animal models of embryonic development and anatomy.In this study, 20 rhesus monkey cadavers were dissected and their mesopancreas location relationships and arterial distribution were analyzed. The term “mesopancreas” (similar to mesorectum) has been controversial since its introduction by Gockel et al. (5, 14). The results of the study by Gockel et al. showed that the mesopancreas was a whitish-firm, fatty tissue-like layer locating dorsally to the pancreas and reaching beyond the mesenteric vessels (5). However, Sharma et al. deemed that due to not having a fascial envelope attaching the pancreas to the posterior wall of the abdomen and not containing “all” its blood vessels and “all” its primary draining lymphatics and lymph nodes, mesopancreas is a misnomer and cannot be called a “true” mesentery (19). We compared the location and developmental patterns of mesopancreas in macaques and humans. The results showed that the distribution of pancreatic arteries in rhesus monkeys was the same as that in humans, which is consistent with phylogenetic similarities. However, the development of the mesopancreas and greater omentum is anatomically different from that of humans and macaques, including (1) the greater omentum is not connected to the transverse colon in monkeys (2). The presence of the dorsal mesopancreas of the rhesus monkey suggests that it may be an intraperitoneal organ. Comparative anatomical studies of mesopancreas and arteries in macaques and humans showed characteristic patterns of mesopancreas development and similarities in pancreatic artery development in nonhuman primates, consistent with phylogenetic differentiation.The pancreas is traditionally viewed as an extraperitoneal organ, and yet the idea of mesopancreas is in conflict with traditional anatomy. However, we found that the dorsal mesopancreas in rhesus monkeys is intact and may be an animal model for studying the development of the mesopancreas. From an embryological perspective, the ventral pancreas and dorsal pancreas develop from the differentiation of the foregut during the 5th week of embryogenesis, and they are surrounded by primitive peritoneum like other organs. The ventral pancreas and dorsal pancreas gradually fuse with the peritoneum of the posterior abdominal wall as the stomach rotates and the pancreas grows and develops during the 6th week of embryonic life, which makes the pancreas an extraperitoneal organ (Figures 4A,B) (20). However, the greater omentum of the rhesus monkey is not connected to the transverse colon, a finding consistent with Zhang's study (4), and the dorsal mesopancreas is also present. We hypothesize that it is possible that the ventral greater omentum, the dorsal peritoneum of the omental sac, and the mesentery fused at the rotation of stomach. During subsequent development, the transverse mesocolon separated from the greater omentum and fused with the mesopancreas, detaching it from the development of the dorsal gastric mesentery and thus preserving the intact mesopancreas,we summarized this hypothesis in Figures 4C,D. This allowed the rhesus monkey pancreas to become an intraretroperitoneal organ. The importance of this unique development remains unclear. This study is the first to report this finding.

Despite controversy over the concept of the mesopancreas, the total mesopancreas excision (TMpE) based on this theory has facilitated the development of pancreatic cancer surgery in clinical practice (21–23). Yi et al. considered the mesopancreas is not a classical mesentery, such as the mesorectum, and it may be better termed the mesopancreatoduodenum than the mesopancreas (17). Sugiyama et al. designed a novel artery-first approach, in which the anterior mesopancreas was divided into the head and neck of the mesopancreas and the body and tail of the mesopancreas by using the abdominal aorta, superior mesenteric artery and midline of the celiac trunk as the dividing line. This operation ensures a good surgical field of view through a simplified anatomical approach and facilitates the rational removal of the mesopancreas during pancreaticoduodenectomy, improving the accuracy of the operation (24). However, current surgical criteria for TMpE are variable, study sample sizes are small and prospective randomized controlled studies with larger samples and long-term follow-up are lacking. More researches are still needed.

At present, the understanding of mesenteric development in the embryonic period is too little, and the precise morphological changes and mechanism of the evolution are still unknown (25). In addition, the researches on the pancreas of rhesus monkeys have focused on endocrine diseases, drug experiments and other fields, and less on its morphology and embryology (26, 27). With the rapid development of “membrane anatomy”, the understanding of mesenteric development will be improved, and rhesus macaques can be used as an accurate model system to study human Mesenteric development. In future work we will use techniques such as MRI or CT to analyze the detailed anatomical relationships around the pancreas of rhesus monkeys through 3D reconstruction.

In summary, we found differences in the mesopancreas between humans and rhesus monkeys. According to our results, the morphological features of the mesopancreas and greater omentum is anatomically different from that of humans and macaques and the differences between the two developmental processes are also compared, which indicates the phylogenetic uniqueness. We did not find differences between monkey pancreatic vasculature and human, which indicates the phylogenetic similarity between human and rhesus monkeys. Future studies with larger samples are needed to understand the growth and developmental processes of mesopancreas and greater omentum.