The omental bursa (OB) is a complex upper abdominal structure in adults. Its morphological complexity stems from embryonic development. Approximately 200 years ago, the first theory regarding OB ...development was reported, describing that the OB developed from changes in the position of the stomach and its dorsal mesentery. Thereafter, the second theory reported that the OB originated from three recesses: the right pneumato‐enteric recess (rPER), hepato‐enteric recess (HER), and pancreatico‐enteric recess (PaER). However, the first theory, focusing on the rotation of the stomach, is still described in certain modern embryology textbooks. These two coexisting embryological theories deter the understanding of the anatomical complexity of the OB. This study aimed to unify these two theories into realistic illustrations. Approximately 10 samples per stage among Carnegie stage (CS) 13 and CS21 were microscopically observed and histological serial sections of the representative samples were aligned using the new automatic alignment method. The aligned images were segmented computationally and reconstructed into 3D models. The rPER and the HER encompassed the right half circumference of the esophagus and the stomach at CS13 and CS14, the PaER spread dorsal to the stomach and formed a discoid shape at CS15 and CS16, the infracardiac bursa (ICB) was separated by the diaphragm at CS17 and CS18, and the fourth recess, which we called the greater omental recess (GOR), extended caudally from the PaER among CS19 and CS21. The present results indicate that the fourth recess is also the origin of the OB. These two theories over 200 years can be generally unified into one embryological description indicating a new recess as the origin of the OB.
We visualized the 3D morphogenesis of the OB from four recesses in staged human embryos through automatic alignment of serial sections. Our results potentially unify the previous theories into one modern embryological description considering the new recess.
Milky spots of the omentum enable lymphocyte access to the peritoneal cavity. In this issue of JEM, Yoshihara and Okabe (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221813) demonstrate how ...secretion of retinoic acid by fibroblastic reticular cells allows lymphocyte entry into milky spots and the peritoneal cavity.
Bursectomy, the total resection of the bursa omentalis, is a standard procedure in gastrectomy for resectable gastric cancer. A phase III trial (JCOG1001) comparing bursectomy and omentectomy alone ...was terminated early at the interim analysis. The final results of the updated analysis after a minimum follow-up of 5 years are reported here.
Patients with histologically proven adenocarcinoma of the stomach (cT3-T4a) were randomized (1 : 1) during surgery to bursectomy or omentectomy-alone groups and then underwent D2 gastrectomy. The primary endpoint was overall survival, analysed on an intention-to-treat basis.
A total of 1204 patients (602 bursectomy and 602 omentectomy alone) were enrolled between June 2010 and March 2015. The bursectomy group had a significantly higher incidence of Clavien-Dindo grade III-IV intra-abdominal abscess than the omentectomy-alone group (5.5 versus 2.5 per cent respectively; P = 0.008). The updated 5-year overall survival rates were 74.9 (95 per cent c.i. 71.2 to 78.2) per cent in the bursectomy group and 76.5 (72.8 to 79.7) per cent in the omentectomy-alone group; the adjusted HR for death in the bursectomy group was 1.03 (95 per cent c.i. 0.83 to 1.27) (1-sided P = 0.598). Bursectomy did not decrease peritoneal recurrence (12.1 versus 12.3 per cent respectively; P = 1.000). In a multivariable analysis, old age (above 65 years), tumour located in the lower third or posterior wall of the stomach, macroscopic type 3/5, total gastrectomy, and cT4a were independent predictors of poor overall survival, but omentectomy alone was not.
In D2 gastrectomy, bursectomy is not recommended as a standard procedure for cT3-T4a gastric cancer. Registration number: UMIN000003688 (https://www.umin.ac.jp/ctr/).
Although internal hernias are uncommon, they must be beared in mind in the differential diagnosis in cases of intestinal obstruction, especially in patients with no history of previous surgery or ...trauma. Because of the high possibility of strangulation and ischemia of the affected loops, internal hernias represent a potentially life-threatening condition and surgical emergency that needs to be quickly recognized and managed promptly. Imaging plays a leading role in the diagnosis and in particular multidetector computed tomography (MDCT), with its thin-section and high-resolution multiplanar reformatted (MPR) images, represents the first line image technique in these patients. The purpose of the present paper is to illustrate the characteristic anatomic location, the clinical findings and the CT appearance associated with main types of internal hernia, including paraduodenal, foramen of Winslow, pericecal, sigmoid-mesocolon- and trans-mesenteric-related, transomental, supravesical and pelvic hernias. (
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Alpha-synuclein (αS) is causally involved in the development of Parkinson disease (PD); however, its role in normal vertebrate physiology has remained unknown. Recent studies demonstrate that αS is ...induced by noroviral infection in the enteric nervous system of children and protects mice against lethal neurotropic viral infection. Additionally, αS is a potent chemotactic activator of phagocytes. In this report, using both wild-type and αS knockout mice, we show that αS is a critical mediator of inflammatory and immune responses. αS is required for the development of a normal inflammatory response to bacterial peptidoglycan introduced into the peritoneal cavity as well as antigen-specific and T cell responses following intraperitoneal immunization. Furthermore, we show that neural cells are the sources of αS required for immune competence. Our report supports the hypothesis that αS accumulates within the nervous system of PD individuals because of an inflammatory/immune response.
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•Peritoneal inflammation triggers αS production by neurons that innervate peritoneum•αS activates APCs by triggering TLR4 and promotes innate and adaptive immune responses•Neuronal αS is required for the induction of peritonitis and immune responses•αS-triggered immune responses may contribute to PD development and/or progression
Alam et al. show that αS produced by the neurons of the gastrointestinal system is critical for the manifestation of peritoneal inflammation and systemic antigen-specific immune responses, which may in turn, promote neuronal αS accumulation and contribute to the development and/or progression of Parkinson disease.
Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing ...debulking surgery.
We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022.
Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9).
Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.
The relationship between macrophages of the peritoneal cavity and the adjacent omentum remains poorly understood. Here, we describe two populations of omental macrophages distinguished by CD102 ...expression and use an adoptive cell transfer approach to investigate whether these arise from peritoneal macrophages, and whether this depends upon inflammatory status, the origin of peritoneal macrophages and availability of the omental niches. We show that whereas established resident peritoneal macrophages largely fail to migrate to the omentum, monocyte‐derived resident cells readily migrate and form a substantial component of omental CD102+ macrophages in the months following resolution of peritoneal inflammation. In contrast, both populations had the capacity to migrate to the omentum in the absence of endogenous peritoneal and omental macrophages. However, inflammatory macrophages expanded more effectively and more efficiently repopulated both CD102+ and CD102− omental populations, whereas established resident macrophages partially reconstituted the omental niche via recruitment of monocytes. Hence, cell origin determines the migration of peritoneal macrophages to the omentum and predisposes established resident macrophages to drive infiltration of monocyte‐derived cells.
Peritoneal inflammation results in recruitment of long‐lived monocyte‐derived macrophages that, unlike established resident cavity macrophages, readily migrate to and outpopulate omental FALC. These data reveal the complex relationship between peritoneal and omental macrophages, the importance of origin in peritoneal macrophage function, and long‐term effects of inflammation on cavity immune homeostasis
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to ...atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1 / -deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 ...(PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.
Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1-overexpression cell line and PD-L1-depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.
Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1-overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.
PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1-targeted therapy is a promising strategy for preventing and treating peritoneal dissemination.
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