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American Journal of Obstetrics and... Jan 2024Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk...
BACKGROUND
Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined.
OBJECTIVE
This study aimed to investigate a possible association between clinically verified pelvic inflammatory disease and the risk of epithelial ovarian cancer.
STUDY DESIGN
In this national population-based case-control study, all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and 10 controls for each were identified, matched for age and residential district. Using several Swedish nationwide registers, data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecologic surgery) were retrieved. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. Histotype-specific analyses were performed for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Moreover, hormonal contraceptives and menopausal hormone therapy were adjusted in addition to the aforementioned confounders.
RESULTS
This study included 15,072 women with epithelial ovarian cancer and 141,322 controls. Most women (9102 [60.4%]) had serous carcinoma. In a subgroup of cases diagnosed between 2015 and 2020, high-grade serous carcinoma (2319 [60.0%]) was identified. A total of 168 cases (1.1%) and 1270 controls (0.9%) were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17-1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18-1.80) for the entire study population. For the subgroup of women diagnosed in 2015-2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01-2.04). The odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02-1.06), mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56-4.29), and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90-5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and the risk of epithelial ovarian cancer (P<.001).
CONCLUSION
A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyses show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma and potentially also with clear cell carcinoma, but there is no significant association with other histotypes. Infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.
Topics: Female; Humans; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Sweden; Pelvic Inflammatory Disease; Case-Control Studies; Risk Factors; Inflammation
PubMed: 37778677
DOI: 10.1016/j.ajog.2023.09.094 -
Medicina (Kaunas, Lithuania) Aug 2023Gynecological fistulae are a rare but severe complication of radiation therapy, pelvic surgery, prolonged labor, cesarean deliveries, or inflammatory bowel diseases. A... (Review)
Review
Gynecological fistulae are a rare but severe complication of radiation therapy, pelvic surgery, prolonged labor, cesarean deliveries, or inflammatory bowel diseases. A gynecological fistula is an abnormal pathway formed between the urinary and gynecological tract, most commonly located between the urinary bladder and vagina. Vesico-uterine and vesicovaginal fistulae are an important health issue, common in women of reproductive age in developing countries with limited access to obstetrical care. Various surgical techniques have been described for VVF repair, depending on the location, severity, and cause of the fistula and the surgeon's experience. The purpose of our review was to evaluate the present state of knowledge about the prevalence and treatment of gynecological fistulae. The PubMed scientific database was searched for original articles on the subject of gynecological fistulae that had been published between 2013 and 2023.
Topics: Pregnancy; Female; Humans; Fistula; Obstetrics; Urinary Bladder; Cesarean Section; Databases, Factual
PubMed: 37629745
DOI: 10.3390/medicina59081455 -
EBioMedicine Aug 2023Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel...
BACKGROUND
Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.
METHODS
We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.
FINDINGS
942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.
INTERPRETATION
Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.
FUNDING
This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
PubMed: 37480626
DOI: 10.1016/j.ebiom.2023.104691 -
Animal Reproduction 2023Pelvic inflammatory disease (PID) is an inflammation of the upper genital tract. PID is the leading cause of some severe sequelae in the absence of timely and accurate...
Pelvic inflammatory disease (PID) is an inflammation of the upper genital tract. PID is the leading cause of some severe sequelae in the absence of timely and accurate diagnosis and treatment. An appropriate animal model is needed to explore the underlying mechanism of PID sequelae. This study introduced an animal model of PID by vaginal injection of liquid combined with fatigue and hunger (UVF). This study was designed to test the feasibility of a rat model. A rat model was established using UVF irradiation. Levels of some inflammatory cytokines in the serum and the homogenates of the fallopian tubes were measured by ELISA, RT-PCR, and flow cytometry and compared with another rat model of liquids injected into the two uterus horns during laparotomy. Inflammatory alterations and adhesions were observed after hematoxylin and eosin (H&E) staining and detected using the Blauer scoring system. The results showed that the combined UVF and rat model caused apparent obstruction, edema, and adhesion in the fallopian tubes and connective tissues. The rat model showed upregulated CD4, CD8, and CD4/CD8 in peripheral blood mononuclear cells (PBMCs) and significantly increased levels of IL-4, IL-6, IL-10, and IL-17. UVF also enhanced the expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) β, and matrix metalloproteinase (MMP)-2 (<0.05). The UVF rat model can induce inflammatory alterations in the fallopian tubes and connective tissues, and can be used as a model of PID.
PubMed: 38025994
DOI: 10.1590/1984-3143-AR2022-0106 -
Nature Communications Feb 2024Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the...
Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRACD142 fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRACD142 fibroblasts foster monocyte transition to CCR2CD206 macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2CD206 cells from co-cultures have a phenotype similar to intestinal CCR2CD206 macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
Topics: Humans; Animals; Mice; Child; Monocytes; Granulocyte-Macrophage Colony-Stimulating Factor; Macrophages; Inflammation; Inflammatory Bowel Diseases; Cell Differentiation
PubMed: 38409190
DOI: 10.1038/s41467-024-46076-3 -
International Immunopharmacology May 2024Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished... (Review)
Review
Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.
Topics: Humans; Female; Endometriosis; Depression; Anxiety; Animals; Neuroglia; Inflammation; Stress, Psychological; Cytokines; Brain
PubMed: 38565045
DOI: 10.1016/j.intimp.2024.111942 -
International Journal of Molecular... Feb 2024In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied... (Review)
Review
In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies.
Topics: Female; Humans; Genital Neoplasms, Female; Genitalia, Female; Ovarian Neoplasms; Microbiota; Inflammation
PubMed: 38396914
DOI: 10.3390/ijms25042237 -
Diseases of the Colon and Rectum Sep 2023Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding.
BACKGROUND
Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding.
IMPACT OF INNOVATION
We report the utility of a transanal minimally invasive surgical approach to total pelvic exenteration.
TECHNOLOGY MATERIALS AND METHODS
A 2-team approach with a laparoscopic transabdominal approach and transanal minimally invasive surgery was adopted. During the transabdominal approach in the pelvis, dissection was performed to remove the pelvic organs and visceral branches of the internal iliac vessels. The dissection goal via the transabdominal approach is the levator ani. During the transperineal approach, dissection is performed along the levator ani, and the tendinous arch of the levator ani is penetrated at the lateral side to achieve rendezvous between the 2 approaches. The levator ani is then dissected circumferentially, with identification of the internal pudendal vessels passing through the levator ani at the 4 o'clock and 8 o'clock positions, known as Alcock's canal. The anterior wall of Alcock's canal is formed by the coccygeus muscle and sacrospinous ligament, which are dissected by the transperineal approach to open Alcock's canal, thus obtaining a clear view of the internal pudendal vessels. On the anterior side, the urethra is divided with a laparoscopic linear stapler via the transperineal approach.
PRELIMINARY RESULTS
Eight patients with rectal cancer underwent this procedure. The median (range) blood loss was 200 (120-1520) mL and operating time was 467 (321-833) minutes. Reoperation was performed in 1 internal hernia case; however, there were no mortalities, and there were no cases with severe complications or conversion to open surgery.
CONCLUSIONS AND FUTURE DIRECTIONS
When performing total pelvic exenteration, transanal minimally invasive surgery offers direct visualization behind the tumor from the anal side and shows the deep pelvic structures, including the retroperitoneal space of the pelvic sidewall.
Topics: Humans; Pelvic Exenteration; Neoplasm Recurrence, Local; Minimally Invasive Surgical Procedures; Pelvic Floor; Conversion to Open Surgery
PubMed: 37260267
DOI: 10.1097/DCR.0000000000002764 -
ACS Measurement Science Au Oct 2023Due to the increasing demand for clinical testing of infectious diseases at the point-of-care, the global market claims alternatives for rapid diagnosis tools such as...
Due to the increasing demand for clinical testing of infectious diseases at the point-of-care, the global market claims alternatives for rapid diagnosis tools such as disposable biosensors, avoiding the need for specialized laboratories and skilled personnel. Bacterial vaginosis (BV) is an infectious disease that commonly affects reproductive-age women and predisposes the infection of sexually transmitted diseases. Especially in asymptomatic cases, BV can lead to pelvic inflammatory conditions, postpartum endometritis, and preterm labor. Conventionally, BV diagnosis involves the microscopic analysis of vaginal swab samples; it thus requires highly trained personnel. In response, we report a novel microfluidic paper-based analytical device for BV diagnosis. Sialidase, a biomarker overexpressed in BV, was detected by exploiting an immunosensing mechanism previously discovered by our team. This technology employs a graphene oxide-coated surface as a quencher of fluorescence; the fluorescence of the immunoprobes that do not experiment immunoreactions (antibody-antigen) are deactivated by graphene oxide via non-radiative energy transfer, whereas those immunoprobes undergoing immunoreactions preserve their photoluminescence due to the distance and the low affinity between the immunocomplex and the graphene oxide-coated surface. Our paper-based test was typically carried out within 20 min, and the sample volume was 6 μL. Besides, it was tested with 14 vaginal swabs specimens to discriminate clinical samples of women with normal microbiota from those with BV. Our disposable device represents a new tool to prevent the consequences of BV.
PubMed: 37868361
DOI: 10.1021/acsmeasuresciau.3c00007 -
International Journal of Molecular... Sep 2023Seminal plasma (SP) accounts for more than 90% of semen volume. It induces inflammation, regulates immune tolerance, and facilitates embryonic development and... (Review)
Review
Seminal plasma (SP) accounts for more than 90% of semen volume. It induces inflammation, regulates immune tolerance, and facilitates embryonic development and implantation in the female reproductive tract. In the physiological state, SP promotes endometrial decidualization and causes changes in immune cells such as macrophages, natural killer cells, regulatory T cells, and dendritic cells. This leads to the secretion of cytokines and chemokines and also results in the alteration of miRNA profiles and the expression of genes related to endometrial tolerance and angiogenesis. Together, these changes modulate the endometrial immune microenvironment and contribute to implantation and pregnancy. However, in pathological situations, abnormal alterations in SP due to advanced age or poor diet in men can interfere with a woman's immune adaptation to pregnancy, negatively affecting embryo implantation and even the health of the offspring. Uterine pathologies such as endometriosis and endometritis can cause the endometrium to respond negatively to SP, which can further contribute to pathological progress and interfere with conception. The research on the mechanism of SP in the endometrium is conducive to the development of new targets for intervention to improve reproductive outcomes and may also provide new ideas for semen-assisted treatment of clinical infertility.
Topics: Pregnancy; Male; Humans; Female; Semen; Endometrium; Uterus; Embryo Implantation; Endometritis
PubMed: 37834087
DOI: 10.3390/ijms241914639