Does total omentectomy prevent peritoneal seeding for advanced gastric cancer with serosal invasion?

BACKGROUND: Radical gastrectomy is composed of gastrectomy, lymph node dissection, and omentectomy. Total omentectomy (TO) is expected to reduce the incidence of peritoneal recurrence. We aimed to investigate the necessity of TO for advanced gastric cancer (AGC) with serosal invasion. METHODS: We retrospectively reviewed 310 patients who underwent radical gastrectomy with TO and 93 patients who underwent partial omentectomy (PO) for gastric cancer with serosal invasion between August, 2005 and December, 2017. Finally, 91 patients in the PO group and 91 in the TO group were enrolled based on a 1:1 propensity-score matching analysis. We evaluated surgical and oncological outcomes, including 5-year overall and recurrence-free survival rates. RESULTS: There was no statistically significant difference between the two groups in postoperative complications. Recurrence sites showed similar patterns in both groups, including peritoneal recurrence (PO vs. TO, 18.7% vs. 28.6%; p = 0.188). Five-year overall survival was better in the PO group (p = 0.018), while 5-year recurrence-free survival was similar in both groups (p = 0.066). CONCLUSION: TO might not be an essential part of preventing peritoneal recurrence for AGC with serosal invasion. PO could be considered a radical gastrectomy for T4a gastric cancer.

Eimeria granulosa causes spots visible through the serous membrane of small intestine in sheep.

Coccidiosis, also known as Eimeriosis, is a highly prevalent parasitic disease affecting sheep in nearly all sheep-rearing nations across the globe. Currently, there is a scarcity of literature documenting the specific lesions in sheep resulting from coccidia infection. This study aimed to investigate these characteristic lesions through necropsy, microscopic observation, and molecular biological techniques. As a result, Eimeria granulosa was identified as the causative agent, which induced distinct pathological alterations in the small intestine of lambs as observed during necropsy. Notably, E. granulosa manifested as small scattered petechiae and white spots, visible through the serous membrane of the small intestine, akin to the pathology observed in E. necatrix. Therefore, this study provides valuable insights for the accurate diagnosis of coccidiosis in sheep.

[A decade's review for membrane anatomy: the setting,events in it, order formed by primary fascia and serous membrane].

The successful report of total mesorectal excision (TME)/complete mesocolic excision (CME) has encouraged people to apply this concept beyond colorectal surgery. However, the negative results of the JCOG1001 trial denied the effect of complete resection of the "mesogastrium" including the greater omentum on the oncological survival of gastric cancer patients. People even believe that the mesentery is unique in the intestine, because they have a vague understanding of the structure of the mesentery. The discovery of proximal segment of the dorsal mesogastrium (PSDM) proved that the greater omentum is not the mesogastrium, and further revised the structure (definition) of the mesentery and revealed its container characteristics, i.e. the mesentery is an envelope-like structure, which is formed by the primary fascia (and serosa) that enclose the tissue/organ/system and its feeding structures, leading to and suspended on the posterior wall of the body. Breakdown of this structure leads to the simultaneous reduction of surgical and oncological effects of surgery. People quickly realized the universality of this structure and causality which cannot be matched by the existing theories of organ anatomy and vascular anatomy, so a new theory and surgical map- membrane anatomy began to form, which led to radical surgery upgraded from histological en bloc resection to anatomic en bloc resection.

Comparison of Surgical and Oncological Outcomes of Laparoscopic and Open Gastrectomy for Pathologically Serosa-Invasive (pT4a) Advanced Gastric Cancer-Retrospective Propensity Score-Matched Analysis.

Background: We aimed to clarify the operative feasibility and oncological efficacy of a laparoscopic gastrectomy (LG) for pT4a gastric cancer through comparison with open gastrectomy (OG). Materials and Methods: We compared surgical and oncological outcomes in 178 patients with pT4a gastric cancer who underwent LG or OG between 2002 and 2016; the background was adjusted using propensity score matching. Results: After score matching, 45 patients were included in each group. The LG group had a significantly longer operation time (277 minutes versus 175 minutes, P < .001) and lower estimated blood loss (50 mL versus 280 mL, P < .001). The total number of dissected lymph nodes did not differ between groups (46 versus 38, P = .119); however, the number of dissected suprapancreatic lymph nodes was significantly higher in the LG group (11 versus 7.5, P = .011). Postoperative morbidity rates did not differ between groups. Postoperative hospitalization was significantly shorter in the LG group (7 days versus 13 days, P < .01), whereas overall survival, disease-free survival, and cancer recurrence rates and patterns were similar between groups. Conclusions: LG for pT4a gastric cancer has feasible and acceptable outcomes compared with OG.

Tumor free distance from serosa and survival rates of endometrial cancer patients: A meta-analysis.

Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease.

Serosal Adhesion Ex Vivo of Hydrogels Prepared from Apple Pectin Cross-Linked with Fe3+ Ions.

The study aims to investigate the adhesion of a hydrogel made of cross-linked low-methyl esterified pectin to rat intestinal serosa ex vivo. The adhesivity of the FeP hydrogel, which was cross-linked by Fe3+ cations, exceeded that of hydrogels cross-linked by Ca2+, Zn2+, and Al3+ cations. The concentration of the cross-linking cation failed to influence the adhesion of the pectin hydrogel to the serosa. The mechanical properties and surface microrelief of the pectin hydrogel were influenced by the type and concentration of the cross-linking cations. Fe3+ cations form a harder and more elastic gel than Ca2+ cations. Scanning electron microscopy analysis revealed the characteristic surface pattern of FeP hydrogel and its denser internal structure compared to Ca2+ cross-linked hydrogel. The effect of the salt composition of the adhesion medium was shown since the FeP hydrogel's adhesion to the serosa was lower in physiological solutions than in water, and adhesion in Hanks' solution was higher than in phosphate buffered saline. Serum proteins and peritoneal leukocytes did not interfere with the serosal adhesion of the FeP hydrogel. Pre-incubation in Hanks' solution for 24 h significantly reduced the adhesion of the FeP hydrogel to the serosa, regardless of the pH of the incubation. Thus, serosal adhesion combined with excellent stability and mechanical properties in physiological environments appeared to be advantages of the FeP hydrogel, demonstrating it to be a promising bioadhesive for tissue engineering.

Stomach Geometry Reconstruction Using Serosal Transmitting Coils and Magnetic Source Localization.

OBJECTIVE: Bioelectric slow waves (SWs) are a key regulator of gastrointestinal motility, and disordered SW activity has been linked to motility disorders. There is currently a lack of practical options for the acquisition of the 3D stomach geometry during research studies when medical imaging is challenging. Accurately recording the geometry of the stomach and co-registering electrode and sensor positions would provide context for in-vivo studies and aid the development of non-invasive methods of gastric SW assessment. METHODS: A stomach geometry reconstruction method based on the localization of transmitting coils placed on the gastric serosa was developed. The positions and orientations of the coils, which represented boundary points and surface-normal vectors, were estimated using a magnetic source localization algorithm. Coil localization results were then used to generate surface models. The reconstruction method was evaluated against four 3D-printed anatomically realistic human stomach models and applied in a proof of concept in-vivo pig study. RESULTS: Over ten repeated reconstructions, average Hausdorff distance and average surface-normal vector error values were 4.7 ±0.2 mm and 18.7 ±0.7° for the whole stomach, and 3.6 ±0.2 mm and 14.6 ±0.6° for the corpus. Furthermore, mean intra-array localization error was 1.4 ±1.1 mm for the benchtop experiment and 1.7 ±1.6 mm in-vivo. CONCLUSION AND SIGNIFICANCE: Results demonstrated that the proposed reconstruction method is accurate and feasible. The stomach models generated by this method, when co-registered with electrode and sensor positions, could enable the investigation and validation of novel inverse analysis techniques.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Immune function of the serosa in hemimetabolous insect eggs.

Insects comprise more than a million species and many authors have attempted to explain this success by evolutionary innovations. A much overlooked evolutionary novelty of insects is the serosa, an extraembryonic epithelium around the yolk and embryo. We have shown previously that this epithelium provides innate immune protection to eggs of the beetle Tribolium castaneum. It remained elusive, however, whether this immune competence evolved in the Tribolium lineage or is ancestral to all insects. Here, we expand our studies to two hemimetabolous insects, the bug Oncopeltus fasciatus and the swarming grasshopper Locusta migratoria. For Oncopeltus, RNA sequencing reveals an extensive response upon infection, including the massive upregulation of antimicrobial peptides (AMPs). We demonstrate antimicrobial activity of these peptides using in vitro bacterial growth assays and describe two novel AMP families called Serosins and Ovicins. For both insects, quantitative polymerase chain reaction shows immune competence of the eggs when the serosa is present, and in situ hybridizations demonstrate that immune gene expression is localized in the serosa. This first evidence from hemimetabolous insect eggs suggests that immune competence is an ancestral property of the serosa. The evolutionary origin of the serosa with its immune function might have facilitated the spectacular radiation of the insects. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.

How two extraembryonic epithelia became one: serosa and amnion features and functions of Drosophila's amnioserosa.

The conservation of gene networks that specify and differentiate distinct tissues has long been a subject of great interest to evolutionary developmental biologists, but the question of how pre-existing tissue-specific developmental trajectories merge is rarely asked. During the radiation of flies, two extraembryonic epithelia, known as serosa and amnion, evolved into one, called amnioserosa. This unique extraembryonic epithelium is found in fly species of the group Schizophora, including the genetic model organism Drosophila melanogaster, and has been studied in depth. Close relatives of this group develop a serosa and a rudimentary amnion. The scuttle fly Megaselia abdita has emerged as an excellent model organism to study this extraembryonic tissue organization. In this review, development and functions of the extraembryonic tissue complements of Drosophila and Megaselia are compared. It is concluded that the amnioserosa combines cells, genetic pathway components and functions that were previously associated either with serosa development or amnion development. The composite developmental trajectory of the amnioserosa raises the question of whether merging tissue-specific gene networks is a common evolutionary process. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.

The extended analogy of extraembryonic development in insects and amniotes.

It is fascinating that the amnion and serosa/chorion, two extraembryonic (EE) tissues that are characteristic of the amniote vertebrates (mammals, birds and reptiles), have also independently evolved in insects. In this review, we offer the first detailed, macroevolutionary comparison of EE development and tissue biology across these animal groups. Some commonalities represent independent solutions to shared challenges for protecting the embryo (environmental assaults, risk of pathogens) and supporting its development, including clear links between cellular properties (e.g. polyploidy) and physiological function. Further parallels encompass developmental features such as the early segregation of the serosa/chorion compared to later, progressive differentiation of the amnion and formation of the amniotic cavity from serosal-amniotic folds as a widespread morphogenetic mode across species. We also discuss common developmental roles for orthologous transcription factors and BMP signalling in EE tissues of amniotes and insects, and between EE and cardiac tissues, supported by our exploration of new resources for global and tissue-specific gene expression. This highlights the degree to which general developmental principles and protective tissue features can be deduced from each of these animal groups, emphasizing the value of broad comparative studies to reveal subtle developmental strategies and answer questions that are common across species. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

Impact of Subclassification of Serosal Invasion on the Survival of Patients With T4a Gastric Cancer.

BACKGROUND/AIM: In the Japanese Classification of Gastric Carcinoma, T4a gastric cancer is defined as tumor invasion contiguous to the serosa or penetrating the serosa with exposure to the peritoneal cavity. The aim of this study was to assess the impact of T4a subclassification of gastric cancer on survival. PATIENTS AND METHODS: A total of 326 patients with T4a cancer who had undergone gastrectomy were enrolled. The T4a tumors were classified into two groups: serosa-contiguous or serosa-exposed. RESULTS: The serosa-exposed group had a significantly worse prognosis, and multivariate analysis identified the T4a subclass as an independent prognostic factor. Analysis of the risk factors for recurrence identified the T4a subclass as a significant risk factor for peritoneal recurrence in patients undergoing curative gastrectomy. CONCLUSION: The serosa-contiguous and serosa-exposed subgroups of T4a gastric cancer showed different biological behaviors. These groups may need to be treated as separate.

Targeted ablation of gastric pacemaker sites to modulate patterns of bioelectrical slow wave activation and propagation in an anesthetized pig model.

Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in gastrointestinal (GI) motility disorders, but there are no validated methods for eliminating dysrhythmias. We hypothesized that targeted ablation could eliminate pacemaker sites in the stomach, including dysrhythmic ectopic pacemaker sites. In vivo high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to localize normal and ectopic gastric pacemaker sites in 13 anesthetized pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Postablation high-resolution mapping revealed that ablation successfully induced localized conduction blocks after 18 min (SD 5). Normal gastric pacemaker sites were eliminated by ablation (n = 6), resulting in the emergence of a new pacemaker site immediately distal to the original site in all cases. Ectopic pacemaker sites were similarly eliminated by ablation in all cases (n = 7), and the surrounding mapped area was then entrained by normal antegrade activity in five of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localized interruption of the interstitial cell of Cajal (ICC) network through the ablation lesions. This study demonstrates that targeted gastric ablation can effectively modulate gastric electrical activation, including eliminating ectopic sites of slow wave activation underlying gastric dysrhythmias, without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.NEW & NOTEWORTHY This study presents gastric ablation as a novel tool for modulating gastric bioelectrical activation, including eliminating the normal gastric pacemaker site as well as abnormal ectopic pacemaker sites underlying gastric dysrhythmias. Targeted application of radiofrequency ablation was able to eliminate these pacemaker sites without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.

Suspension culture promotes serosal mesothelial development in human intestinal organoids.

Pluripotent-stem-cell-derived human intestinal organoids (HIOs) model some aspects of intestinal development and disease, but current culture methods do not fully recapitulate the diverse cell types and complex organization of the human intestine and are reliant on 3D extracellular matrix or hydrogel systems, which limit experimental control and translational potential for regenerative medicine. We describe suspension culture as a simple, low-maintenance method for culturing HIOs and for promoting in vitro differentiation of an organized serosal mesothelial layer that is similar to primary human intestinal serosal mesothelium based on single-cell RNA sequencing and histological analysis. Functionally, HIO serosal mesothelium has the capacity to differentiate into smooth-muscle-like cells and exhibits fibrinolytic activity. An inhibitor screen identifies Hedgehog and WNT signaling as regulators of human serosal mesothelial differentiation. Collectively, suspension HIOs represent a three-dimensional model to study the human serosal mesothelium.

Prediction of the peritoneal recurrence via the macroscopic diagnosis of the serosal invasion in patients with gastric cancer: Supplementary analysis of JCOG0110.

BACKGROUND: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence. METHODS: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates. FINDINGS: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively. CONCLUSION: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended.

Surgical and survival outcomes after laparoscopic and open gastrectomy for serosa-invasive Siewert type II/III esophagogastric junction carcinoma: a propensity score matching analysis.

BACKGROUND: The potential advantage of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for serosa-invasive (pT4a) Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Thus, the purpose of this study was to investigate the short- and long-term outcomes of LG compared to OG for pT4a Siewert type II/III AEG cancers. METHODS: We retrospectively evaluated 283 patients with pathological confirmed T4a Siewert type II and type III AEG who underwent LG or OG in our center between January 2004 and September 2015. The short- and long-term outcomes were compared between the groups using a 1:1 matched propensity score matching method (PSM). RESULTS: The LG group had a longer operation time, less estimated blood loss, less time to first flatus, less time to start liquid diet, less time to first ambulation, and shorter length of incision than the OG group. The conversion rates were 5.4% in the LG groups. There was no significant difference in the overall complication rate between the LG and OG groups. The 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were comparable between the LG and OG groups (35.4% vs 32.1%, p = 0.541; 34.1% vs 31.0%, p = 0.523, respectively). There was no significant difference in the recurrence rate and pattern between the LG and OG groups. CONCLUSIONS: Laparoscopic gastrectomy is associated with better short-term outcomes and similar long-term outcomes for pT4a Siewert type II/III AEG. This study reveals that LG could be a safe and feasible option for pT4a Siewert type II/III AEG compared to OG.

Characterization of the endometrial, cervicovaginal and anorectal microbiota in post-menopausal women with endometrioid and serous endometrial cancers.

OBJECTIVE: To characterize the microbiota of postmenopausal women undergoing hysterectomy for endometrioid (EAC) or uterine serous cancers (USC) compared to controls with non-malignant conditions. METHODS: Endometrial, cervicovaginal and anorectal microbial swabs were obtained from 35 postmenopausal women (10 controls, 14 EAC and 11 USC) undergoing hysterectomy. Extracted DNA was PCR amplified using barcoded 16S rRNA gene V4 primers. Sequenced libraries were processed using QIIME2. Phyloseq was used to calculate α- and ß- diversity measures. Biomarkers associated with case status were identified using ANCOM after adjustment for patient age, race and BMI. PICRUSt was used to identify microbial pathways associated with case status. RESULTS: Beta-diversity of microbial communities across each niche was significantly different (R2 = 0.25, p < 0.001). Alpha-diversity of the uterine microbiome was reduced in USC (Chao1, p = 0.004 and Fisher, p = 0.007) compared to EAC. Biomarkers from the three anatomical sites allowed samples to be clustered into two distinct clades that distinguished controls from USC cases (p = 0.042). The USC group was defined by 13 bacterial taxa across the three sites (W-stat>10, FDR<0.05) including depletion of cervicovaginal Lactobacillus and elevation of uterine Pseudomonas. PICRUSTt analysis revealed highly significant differences between the USC-associated clades within the cervicovaginal and uterine microbiota. CONCLUSIONS: The microbial diversity of anatomic niches in postmenopausal women with EAC and USC is different compared to controls. Multiple bacteria are associated with USC case status including elevated levels of cervicovaginal Lactobacillus, depletion of uterine Pseudomonas, and substantially different functional potentials identified within cervicovaginal and uterine niches.