Inflammation of the rectal remnant endangers the outcome of ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: Inflammation of the rectal remnant may affect the postoperative outcome of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We aimed to determine the extent of inflammation in the anastomotic area during IPAA and to investigate the impact of proctitis on postoperative complications and long-term outcomes. METHODS: Three hundred thirty-four UC patients with primary IPAA were included in this retrospective case-control study. The histopathologic degree of inflammation in the anastomotic area was graded into three stages of no proctitis ("NOP"), mild to medium proctitis ("MIP"), and severe proctitis ("SEP"). Preoperative risk factors, 30-day morbidity, and follow-up data were assessed. Kaplan-Meier analysis was performed in the event of pouch failure. RESULTS: The prevalence of proctitis was high (MIP 40.4%, and SEP 42.8%). During follow-up, the incidence of complications was highest among SEP: resulting in re-intervention (n = 40; 28.2%, p = 0.017), pouchitis (n = 36; 25.2%, p < 0.01), and pouch failure (n = 32; 22.4%, p = 0.032). The time interval to pouch failure was 5.0 (4.0-6.9) years among NOP, and 1.2 (0.5-2.3) years in SEP (p = 0.036). ASA 3, pouchitis, and pouch fistula were independent risk factors for pouch failure. CONCLUSION: Proctitis at the time of IPAA is common. A high degree of inflammation is associated with poor long-term outcomes, an effect that declines over time. In addition, a higher degree of proctitis leads to earlier pouch failure.

Risk factors for failure of ileal pouch-anal anastomosis in patients with refractory ulcerative colitis.

BACKGROUND: Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. METHODS: In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. RESULTS: The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P < .001), and had extraintestinal manifestations more frequently (65.4% vs 26.3%, P < .001). Further risk factors for failed ileal pouch-anal anastomosis were hypertension and Cushing's syndrome. CONCLUSION: Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

Sources of Support and Information During Disease: An Exploratory Study, Comparing Migrant and Nonmigrant Colorectal Cancer Patients in Germany.

Introduction: The prevalence of cancer diseases among migrants is lower relative to nonmigrants, although this equalizes with increasing duration of residence. There are differences in the health behaviors and disease coping strategies between these two groups. The aim of this analysis is to compare migrant and nonmigrant colorectal cancer (CRC) patients in Germany regarding their sources of support and information during disease. Method: Data from 522 CRC patients, collected through a survey about satisfaction with care, were analyzed by descriptive and multivariate statistics. Results: Migrants and nonmigrants differed in two aspects: Migrants reported to receive the most relevant support during disease more often by nonmedical people, compared with nonmigrants, and they favored videos explaining the therapeutic steps of CRC more than nonmigrants. Discussion: Anticipating which types of support and information sources patients will access during their disease may help guide future diversity management across the field of cancer care.

T-cell Composition in Ileal and Colonic Creeping Fat - Separating Ileal from Colonic Crohn's Disease.

BACKGROUND AND AIMS: Creeping fat [CF] is a hyperplasia of adipose tissue adjacent to inflamed intestine in Crohn's disease [CD]. Data from genome-wide association studies [GWAS] distinguished Crohn's colitis from ileal CD and ulcerative colitis [UC]. This study analysed the T-cell compartments of ileal and colonic mesenteric fat and corresponding mucosa to provide cellular proof for the suggested GWAS classification. METHODS: Samples were obtained from 34 CD or UC patients. Cells were analysed by immunohistochemistry and flow cytometry, and tissue cytokine release was assessed by cytometric bead array. RESULTS: Only ileal CF revealed the distinct adipocyte hyperplasia combined with dense T-cell infiltration and fibrosis; colonic fat from CD and UC patients lacked these findings. T-cell subpopulations differed between mesenteric fat in ileal CD, colonic CD and UC: ileal CF had nearly 10 times more T-cells than colonic fat. The proportions of regulatory and central memory T-cells were significantly higher in ileal CF compared with colonic fat in CD and UC. In all groups, the mucosal T-cell compartment was distinct from the mesenteric fat. Remarkably, correlation between disease activity and proportion of pro- and anti-inflammatory T-cell subpopulations was inverse, comparing ileal and colonic fat in CD. CONCLUSIONS: This first in-depth analysis of the T-cell compartment in ileal and colonic mesenteric adipose tissue in CD and UC identifies a unique T-cell niche in the ileal mesenteric fat tissue in CD. From a clinical point of view, our findings underscore the novel concept of colonic and ileal CD as distinct IBD entities.

Timing of surgery in ulcerative colitis in the biologic therapy era-the patient's perspective.

BACKGROUND: There is no general consensus regarding the ideal timing of surgery in patients with refractory ulcerative colitis (UC). Decision-making and timing of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is influenced by treating physicians and patients themselves. The aim of this study was to determine whether or not patients would have preferred the operation to be performed earlier, at the same time, or at a later point of time and to determine the reasons for their preference. METHODS: Clinical data of 193 patients with UC who have undergone IPAA were documented in a prospective database at our institution between 2004 and 2015. From this database, 190 patients were identified and a standardized custom-made questionnaire was mailed for follow-up survey. Patients who did not respond were called by telephone and encouraged to complete the questionnaire. RESULTS: One hundred nine questionnaires were eligible for analysis (57.4%). Average time between diagnosis and surgery was 11.2 ± 10.8 years (mean ± SD). Indications for surgery were refractory disease (70.6%), colitis-associated colorectal cancer (11.0%), high-grade dysplasia or stenosis (11.9%), and septic complications of UC (6.4%); 39 of 77 patients (50.6%) with refractory UC reported to have preferred their operation to be carried out earlier as it was actually performed (16.8 ± 11.9 months). Refractory course of the disease was identified as a predictor for a retrospectively desired earlier surgical approach (p = 0.014). CONCLUSION: A substantial proportion of patients felt that they should have undergone surgery earlier than actually performed. It appears that timing of the decision to undergo surgery is suboptimal. This situation may be improved by earlier surgical consultation in the course of the disease.

Accuracy of Various Lymph Node Staging Criteria in Rectal Cancer with Magnetic Resonance Imaging.

INTRODUCTION: The accuracy of pretherapeutic staging of lymph nodes (LN) in rectal cancer by MR imaging (MRI) is still limited. The aim of the study was to determine the sensitivity and specificity of different morphological criteria in nodal staging. MATERIAL AND METHODS: LN were analyzed by MRI in 60 patients with rectal cancer and primary surgery. Signs of LN metastasis (cN+) were spiculated/indistinct border contour, inhomogeneous signal intensity, or LN size. The accuracy of these signs for clinical LN staging was analyzed with conclusive postoperative histological lymph node examination. RESULTS: 68.3% of patients with nodal metastasis (pN+) were correctly identified by size with a cutoff value of 7.2 mm. This, however, was not inferior to the 76.7% identified using the inhomogeneous morphological signal intensity and spiculated/indistinct border contour criteria (p = 0.096). 3.3 versus 5% were overstaged, and 28.3 versus 18.3% understaged by these criteria. Sensitivities/specificities for (a) size, (b) spiculated/indistinct border contour, and (c) inhomogeneous signal intensity and spiculated/indistinct border contour were (a) 32%/94%, (b) 56%/86%, and (c) 56%/91%, respectively. CONCLUSIONS: The accuracy of LN staging in rectal cancer was not improved by morphological criteria. These limitations suggest being reticent when recommending neoadjuvant chemoradiation merely based on preoperative positive LN staging.

Surgical Management of Iatrogenic Perforation of the Gastrointestinal Tract: 15 Years of Experience in a Single Center.

BACKGROUND: Gastrointestinal (GI) tract perforation during endoscopy is a rare but severe complication. The aim of this study was to determine predictors of morbidity and mortality after iatrogenic endoscopic perforation. MATERIALS AND METHODS: All cases with iatrogenic endoscopic perforation receiving surgery at a tertiary referral center in a 15-year period (2000-2015) were retrospectively analyzed. Demographics, type of endoscopy, site of perforation, operative procedure, morbidity and mortality were analyzed. Multiple logistic regression was used to identify parameters predicting survival. RESULTS: A total of 106.492 endoscopies were performed, and 82 (0.08%) patients were diagnosed with GI perforation. Most perforations (63.4%) occurred in the lower GI tract, compared to 36.6% in the upper GI tract. In 21 cases (25%), perforation was noticed during endoscopy, whereas 61 perforations (75%) were diagnosed during the further clinical course. Operative care was applied within 24 h in 61%. Surgery of perforations was almost completely performed maintaining the intestinal continuity (68%), whereas diversion was performed in 32%. Mortality was associated with age above 70 (OR 4.89, p = 0.027), ASA class > 3 (OR 4.08, p = 0.018), delayed surgery later than 24 h after perforation (OR 5.9, p = 0.015), peritonitis/mediastinitis intraoperatively (OR 4.68, p = 0.031) and severe postoperative complications with a Clavien-Dindo grade ≥III (OR 5.12, p = 0.023). CONCLUSION: The prevalence of iatrogenic endoscopic perforation is low, although it is associated with a serious impact on morbidity and mortality. Delayed management worsens prognosis. To achieve successful management of endoscopic perforations, early diagnosis is essential in cases of deviation from the normal post-interventional course, especially in elderly.

CT-based measurement of the inner pelvic volume.

Background Surgery in the lesser pelvis is associated with a high complication rate as surgeons are spatially limited by solid anatomic structures and soft tissue borders. So far, only two-dimensional (2D) parameters have been used for risk stratification. Purpose To precisely measure the inner pelvic volume a computed tomography (CT)-based three-dimensional (3D) approach was established and compared to approximations by 2D parameter combinations. Material and Methods Thin-layered multi-slice CT datasets were used retrospectively for slice by slice depiction of the inner pelvic surface. The inner pelvic volume was then automatically compounded. Combinations of two to four 2D dimensions determined in 3D volume rendered reconstructions were correlated with the inner pelvic volume. Pearson's correlation coefficient and Chi square test were used for statistical calculations. Significance level was set at P < 0.05. Results In total 142 patients (91 men, 51 women) aged 64.8 ± 10.6 years at surgery were included in the study. Mean calculated pelvic volume was 1031.13 ± 180.06 cm3 (men, 996.57 ± 172.43 cm3; women, 1093.34 ± 178.39 cm3). Best approximations were obtained by combination of the 2D measurements transverse inlet and pelvic height for men (r = 0.799, P < 0.05) as well as transverse inlet, obstetric conjugate, interspinous distance and pelvic depth for women (r = 0.855, P < 0.05). Conclusion We describe a precise and reproducible CT-based method for pelvic volumetry. A less time consuming but still reliable approximation can be achieved by combination of two to four 2D dimensions.

Impact of staged surgery on quality of life in refractory ulcerative colitis.

INTRODUCTION: Coloproctomucosectomy (CPM) with ileopouchanal anastomosis (IPAA), as the procedure of choice for surgical management of ulcerative colitis (UC), is commonly performed either as a 2- or 3-staged procedure. For patients with considerable immunosuppression, reduced nutritional or general health status, and as part of emergency treatment, a 3-staged (3S) procedure is recommended by guidelines to minimize perioperative complication rates compared to 2-staged (2S) procedure. However, the necessity of additional hospitalization and surgery is suspect to affect quality of life (QoL). In this prospective, observational study, we evaluate the long-term QoL after 2- and 3-staged interventions of CPM with IPAA for patients with UC. PATIENTS AND METHODS: Between 1997 and 2011, a total of 233 patients underwent CPM and had a 2- or 3-staged procedure. In 108 patients, surgical procedure was completed, and evaluation of QoL was performed by specific questionnaires (IBDQ, FIQoL, SF-12, CCS) up to 20 years after ileostomy closure. Data were collected within the framework of a prospective study. RESULTS: Observing a total of 84 patients (2S: n = 59; 3S: n = 25), QoL measured by IBDQ was higher after CPM, compared to preoperative (2S: 15 â†’ 31; 3S: 17 â†’ 28; p < 0.01), with no differences between 2S or 3S procedures (p > 0.05). Specific QoL assessment concerning incontinence and stool frequency (CCS, FIQoL) did not differ either (CCS: 2S:3S = 12:15; p > 0.05). General health-related QoL, determined by SF-12 score, did not differ between 2S or 3S procedures. CONCLUSION: The indication for a 2-staged or 3-staged procedure should be adjusted to the severity of the underlying disease, nutritional status of the patient, and the extent of immunosuppression at the time of surgery. It should not be affected by the fear of complications or a reduced quality of life by additional surgery in 3-staged versus 2-staged procedures.

Tissue-infiltrating plasma cells are an important source of carboxylesterase 2 contributing to the therapeutic efficacy of prodrugs.

Carboxylesterase 2 (CES-2) is instrumental for conversion of ester-containing prodrugs in cancer treatment. CES-2 expression was analyzed by immunohistochemistry in colorectal cancer (CRC) compared to colonic inflammation as well as in liver and peripheral blood. In CRC, tumor grades showed no correlation with levels of CES-2 expression, which was heterogeneous within these tumors. Cellular infiltrates in the immediate tumor vicinity expressed high levels of CES-2. Thus, tissue adjacent to the tumor was a substantial source of CES-2 with high expression in plasma cells. CES-2(high) plasma cells were abundantly found in the colon of patients with inflammatory bowel disease. CES-2 expression is strong in hepatocytes of normal livers, while CES-2 expression in peripheral blood mononuclear cells of healthy donors was overall low at protein and mRNA levels. In summary, the conversion of ester-containing prodrugs by CES-2 is mainly to occur in the periphery, during liver passage and in the colon after enterohepatic recirculation. We here demonstrated plasma cells as strong producers of CES-2. Further studies should elucidate the role of CES-2(+) plasma cells in intestinal inflammation and cancer.

Indications and Specific Surgical Techniques in Crohn's Disease.

BACKGROUND: Crohn's disease (CD) as one of the major entities of chronic inflammatory bowel diseases can affect all segments of the gastrointestinal tract but occurs most often in the small bowel, the terminal ileum, the colon, and the rectum. Typical symptoms include tiredness, lower abdominal pain, fever, and diarrhea, which are initially treated by conservative measures. Most patients will eventually develop complications such as fistulas, abscesses, or strictures. Surgery is often unavoidable in these cases. METHODS: This review considers studies on the treatment of CD, published from 1979 up to now. The literature regarding the course, complications, and surgical therapy of CD was reviewed. Searches were performed in PubMed, using the following key words: CD, surgery, immunosuppression, guidelines, malnutrition as well as appropriate sub-items. In most cases the literature is limited to detailed information on specific therapeutic or diagnostic topics. Moreover, many studies are designed retrospectively and with a small number of patients. Additionally, our long-standing experience with patients suffering from CD is taken into consideration in this review. RESULTS: There is a wide variety of indications for surgery in CD which includes complications like strictures, fistulas and abscess formation, neoplasia, or refractoriness to medical therapy. The risk of developing complications is about 33% after 5 years, and 50% after 20 years. Furthermore, one-third of CD patients need surgical therapy within the first 5 years of diagnosis. The treatment requires close cooperation between gastroenterologists and surgeons. When indicated, surgery should be performed in a 'conservative' fashion, i.e. as limited as possible, in order to achieve the required result and to avoid small bowel syndrome. CONCLUSION: This article provides a complete overview of indications and specific surgical treatment in patients with CD. Surgery is typically indicated when complications of CD occur. An interdisciplinary collaboration is necessary in order to ensure optimal indications and timing of surgery. This is of paramount importance to achieve the ultimate goal, i.e. a good quality of life of the patients.

Human RORγt(+)CD34(+) cells are lineage-specified progenitors of group 3 RORγt(+) innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) are defined by the expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34(+) hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt(+)CD34(+) HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt(-)CD34(+) HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt(+)CD34(+) cells are lineage-specified progenitors of IL-22(+) ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.

Antiproliferative and apoptotic effects of telmisartan in human colon cancer cells.

Telmisartan is an angiotensin I (AT1) receptor blocker used in the treatment of essential hypertension, with partial peroxisome proliferator-activated receptor γ (PPARγ) agonism. In prior studies, PPARγ activation led to apoptosis and cell cycle inhibition in various cancer cells. The aim of the present study was to investigate the potential antiproliferative and apoptotic effects of telmisartan by partially activating PPARγ. HT-29, SW-480 and SW-620 cells were incubated with telmisartan (0.2-5 µM) or the full agonist, pioglitazone (0.2-5.0 µM). The antiproliferative and apoptotic effects of telmisartan in the human colon cancer cells were significant at therapeutic serum concentrations, and telmisartan exhibited a potency at least equivalent to the full PPARγ agonist, pioglitazone. The antiproliferative and apoptotic effects of pioglitazone in the human colon cancer cells were not completely deregulated by PPARγ blockade with GW9662. In the telmisartan-treated cells, PPARγ blockade resulted in an increased antiproliferative and apoptotic effect. These effects are not entirely explained by PPARγ activation, however, possible hypotheses that require further experimental investigation are as follows: i) Ligand-independent PPARγ activation through the activation-function 1 domain; ii) a PPARγ-independent mechanism; or iii) independent antiproliferative and apoptotic effects through GW9662.

Repeatability of anorectal manometry in healthy volunteers and patients.

BACKGROUND: Anorectal manometry is used extensively in the assessment of patients with disorders of the pelvic floor. The present study investigated the repeatability of anorectal manometry in healthy volunteers and patients. PATIENTS AND METHODS: A total of 30 healthy volunteers (15 men and 15 women) and 10 patients with fecal incontinence (4 men and 6 women) underwent perfusion manometry and volumetry. Intraindividual variability was evaluated using the intraindividual correlation coefficient (ICC). Interindividual variability was expressed as the standard deviation from the calculated mean values. RESULTS: We found a high intraindividual correlation for the squeezing pressure (ICC 0.75-0.95), vector volume (ICC 0.88-0.97), and rectal perception (ICC 0.82-0.98). The anal resting pressure showed moderate repeatability (ICC 0.60-0.72). However, with regard to sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex, a wide range of variability was found. In the female volunteers, the squeezing pressure and vector volume were lower than in those in the male volunteers. The anal pressure, vector volume, thresholds for urgency, and the maximum tolerable volume were lower in the incontinent patients than in the healthy volunteers. CONCLUSIONS: The squeezing pressure, vector volume, and rectal perception allow a reliable analysis of anal sphincter function. Sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex were of limited diagnostic value.

RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.

RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

Dendritic cells from human mesenteric lymph nodes in inflammatory and non-inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDC) in mesenteric lymph nodes (MLN) may be important regulators of both inflammatory and non-inflammatory mucosal immune responses but human studies are rare. Here we compare pDC from human MLN and peripheral blood (PB) by phenotype and function. MLN from patients with or without inflammatory bowel disease (IBD) undergoing colon surgery and PB from patients with IBD and from controls were used to isolate mononuclear cells. The pDC were analysed by flow cytometry for the expression of CD40, CD80, CD83, CD86, CCR6, CCR7, CX3CR1, CD103 and HLA-DR. Purified pDC from MLN and PB were stimulated with staphylococcus enterotoxin B (SEB), CpG-A, interleukin-3 (IL-3), SEB + IL-3, CpG-A + IL-3 or left unstimulated, and cultured alone or with purified allogeneic CD4(+) CD45RA(+) HLA-DR- T cells. Subsequently, concentrations of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, interferon-α (IFN-α), IFN-γ and tumour necrosis factor-α (TNF-α) in culture supernatants were determined by multiplex bead array. The PB pDC from IBD patients exhibited an activated and matured phenotype whereas MLN pDC and control PB pDC were less activated. CpG-A and CpG-A + IL-3-stimulated MLN pDC secreted less IL-6 and TNF-α compared with PB pDC from controls. Compared with co-cultures of naive CD4 T cells with PB pDC, co-cultures with MLN pDC contained more IL-2, IL-10 and IFN-γ when stimulated with SEB and SEB + IL-3, and less IFN-α when stimulated with CpG-A. MLN pDC differ phenotypically from PB pDC and their pattern of cytokine secretion and may contribute to specific outcomes of mucosal immune reactions.

Endo-ß-N-acetylglucosaminidase H de-N-glycosylation in a domestic microwave oven: application to biomarker discovery.

Sample preparation is the rate-limiting step in glycan analysis workflows. Among all of the steps, enzymatic digestions, which are usually performed overnight, are the most time-consuming. In the current study, we report an economical and fast preparation of N-glycans from serum, including microwave-assisted enzymatic digestion in the absence of denaturing chemicals and solvents during the release. To this end, we used a household microwave oven to accelerate both pronase and endo-ß-N-acetylglucosaminidase H (Endo H) digestions. Purification was then performed using self-made SP20SS and carbon tips. We were able to prepare samples in 55 min instead of 21 h. Finally, the method was applied in the context of oncological biomarker discovery exemplarily to ovarian and colon cancer. We observed a significant downregulation of sialylated hybrid structures in ovarian cancer samples using capillary electrophoresis-laser-induced fluorescence (CE-LIF). Furthermore, sepsis, a systemic inflammatory response syndrome, was also included in the study to understand whether the changes observed in ovarian cancer patients were due to the cancer itself or to the inflammation that usually accompanies its development. Because sialylated hybrid structures were upregulated in sepsis samples, the downregulation of these structures in ovarian cancer is specific to the cancer itself and, therefore, could be used as a biomarker.