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.

Association between the microbiota and women's cancers - Cause or consequences?

Breast, ovarian and uterine cancers are the most common neoplasms among women. Several mechanisms may be involved in oncogenesis and these include environmental and genetic factors. Bacteria may affect the development of some cancers, with bacterial components, their products and metabolites interacting with susceptible tissues. Commensalism and dysbiosis are important potential mechanisms involved in oncogenesis, and an effective strategy for diagnosis and treatment is required. The purpose of this review was to analyze the complex associations between these cancers in women, and the microbiota, specifically bacterial microbes. However, several cancers have an increased prevalence among individuals with HIV and HPV so the relationship between viral infections and malignancies in women is also referred to. We described how different phylum of bacteria, particularly in the gut, mammary tissue and vaginal microbiome may be involved in carcinogenesis; and we discuss the potential pathways involved: (I), that lead to cell proliferation, (II), immune system perturbation, (III), cell metabolic changes (e.g., hormonal factors), and (IV), DNA damage. Studies investigating the differences between the composition of the bacterial microbiota of healthy women compared to that present in various conditions, and the clinical trials are summarized for the few studies that have addressed the microbiota and related conditions, are also reviewed.

[Life-threatening intrauterine infection with Clostridium perfringens].

In this case report, a 40-year-old woman with a history of a uterine leiomyoma presented with abdominal pain and fever. Initially, her symptoms were associated with a bleeding from an ovarian cyst seen on a CT scan of the abdomen showing free intraperitoneal fluid surrounding the internal genitals. Meanwhile, her blood cultures came out positive for Clostridium perfringens, and her condition deteriorated despite intravenous antibiotics. A new CT scan revealed intrauterine gas development. A laparotomy was performed with removal of the internal genitals, and the patient improved on continuous antibiotics.

Chlamydia trachomatis Seroprevalence and Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young African-American Women.

Reproductive tract infections have long been hypothesized to increase the risk of uterine fibroids. Few studies have been conducted, even for the common infection genital Chlamydia trachomatis (gCT), and only with self-reported gCT data. Our investigation used micro-immunofluorescence serology for gCT to characterize past exposure. We used cross-sectional enrollment data from a prospective fibroid study carried out in the Detroit, Michigan, area; ultrasound examinations systematically screened for fibroids. Participants were African-American women aged 23-34 years (recruited in 2010-2012). Age- and multivariable-adjusted logistic regression models were used to estimate odds ratios. A total of 1,587 women (94% of participants) had unequivocal gCT serology results; 22% had fibroids. Those who were seropositive for gCT were less likely to have fibroids (age-adjusted odds ratio = 0.68, 95% confidence interval: 0.54, 0.87; multivariable-adjusted odds ratio = 0.80, 95% confidence interval: 0.62, 1.03). Inverse associations were similar across categories of fibroid size, number, and total volume. Participant groups likely to have had multiple or severe infections (multiple serovar groups, more sex partners, clinically diagnosed chlamydia) all showed statistically significantly reduced odds of fibroids. A protective association of gCT with fibroids was unexpected but plausible. gCT infection might increase immune surveillance and eliminate early lesions. Further investigation on the relationship between fibroid development and reproductive tract infections is needed.

[EFFECT OF LONGIDAZE ON MICROBIAL LANDSCAPE OF CERVICAL CANAL AND UTERINE CAVITY DURING THERAPY OF WOMEN WITH CHRONIC NONSPECIFIC ENDOMETRITIS AND UTERUS MYOMA].

AIM: Evaluation of microbiological effectiveness of longidaze preparation use during therapy of active non-specific endometritis in women with uterus myoma. MATERIALS AND METHODS: 2 groups of women were formed by a method of random selection. The first was composed of patients with active chronic endometritis, that had received standard etiotropic antibacterial therapy. The second included patients, that had received longidaze in addition to the standard therapy. Therapy effectiveness evaluation was carried out based on the analysis of microbial landscape of cervical canal and uterine cavity 2 months after the therapy during phase I of the menstrual cycle. RESULTS: Non-plasma-coagulating staphylococci, enterococci and anaerobes were established to be present predominately in the examined women of both the first and the second group. CONCLUSION: The application of longidaze in combination with antibacterial therapy results in the most significant improvement of microbial landscape of cervical canal and uterine cavity.

Fibroid infected with Escherichia coli requiring surgical removal following uterine artery embolization.

BACKGROUND: Uterine fibroid necrosis and infection is a rare but potentially serious event following uterine artery embolization (UAE). We describe a case of surgical removal of an infected necrotic uterine fibroid. CASE: A 31-year-old Jehovah's Witness with severe anemia presented with sepsis following UAE. The uterus was preserved by performing transvaginal surgical removal. Final pathology demonstrated Escherichia Coli infection of the necrotic fibroid. The patient improved postoperatively. CONCLUSION: Surgical removal of an infected necrotic fibroid may be a preferred option for women wishing to avoid hysterectomy following UAE. Appropriate case selection and optimization of hemoglobin concentration before UAE is important to minimize complications.

Contexte : La nécrose et l'infection d'un fibromyome utérin constituent un événement rare, mais potentiellement grave, à la suite de l'embolisation de l'artère utérine (EAU). Nous décrivons un cas de retrait chirurgical d'un fibromyome utérin nécrosé et infecté. Cas : Une témoin de Jéhovah de 31 ans connaissant une anémie grave a présenté une sepsie à la suite d'une EAU. L'utérus a été préservé au moyen de l'exécution d'un retrait chirurgical transvaginal. L'examen pathologique final a démontré la présence d'une infection à Escherichia Coli dans le fibromyome nécrosé. L'état de la patiente s'est amélioré à la suite de l'opération. Conclusion : Le retrait chirurgical d'un fibromyome utérin nécrosé et infecté pourrait constituer l'option à privilégier pour les femmes qui souhaitent éviter l'hystérectomie à la suite d'une EAU. Avant la tenue d'une EAU, il s'avère important de bien sélectionner les patientes qui pourraient en tirer avantage et d'optimiser la concentration en hémoglobine, et ce, afin de minimiser les complications.

Pyomyoma after dilatation and curettage for missed abortion.

Infection of a leiomyoma is a very rare clinical entity called pyomyoma. Pathology may be encountered during the reproductive period, pregnancy, and even postmenopausal period. In this report, we present a case of pyomyoma which developed after dilatation and curettage managed by broad spectrum antibiotics and myomectomy to preserve the fertility in a 31-year-old patient.

Pyomyoma after uterine artery embolization.

BACKGROUND: Pyomyoma (suppurative leiomyoma of the uterus) is a rare condition resulting from infarction and infection of a leiomyoma. It can lead to sepsis and death unless treated with antibiotics and aggressive surgical intervention. CASE: A 47-year-old multigravid woman with symptomatic uterine leiomyomas presented with fever, pelvic pain, and leukocytosis after uncomplicated uterine artery embolization. Pyomyoma was suspected after computed tomography scan demonstrated an enlarged, heterogeneous uterus containing copious myometrial air. She underwent supracervical hysterectomy, lysis of adhesions, and right salpingo-oophorectomy. CONCLUSION: Surgical management of pyomyoma may be necessary early in the management of pyomyoma after uterine artery embolization.

Conservative laparoscopic approach to a perforated pyomyoma after uterine artery embolization.

We describe a conservative laparoscopic approach to treatment of a perforated pyomyoma after uterine artery embolization. A 36-year-old woman came to our emergency department 8 weeks after undergoing uterine artery embolization. She reported painful abdominal cramps. Physical examination revealed fever, tachycardia, hypotension, abdominal pain with rebound tenderness and pain during bimanual examination. Ultrasonography showed a fundal/subserosal leiomyoma and a moderate amount of fluid in the abdominal cavity. Because the patient desired preservation of the uterus, a laparoscopic approach was used for drainage and lavage of a perforated pyomyoma. The patient had an uneventful recovery and remained well at follow-up visits. Second-look diagnostic laparoscopy enabled treatment of the adhesions formed and revealed patent fallopian tubes. Surgery has been the primary approach to pyomyoma. However, hysterectomy leads to irreversible sterility and myomectomy can be difficult to perform. Therefore, there is need for a less invasive intervention in women who seek conservative treatment. Recently, computed tomography-guided drainage was successfully performed in two patients with pyomyoma. To our knowledge, this is the first report of a successful conservative laparoscopic approach to pyomyoma.

Urticaria associated with necrotic uterine leiomyomas infected with salmonella.

BACKGROUND: We describe a unique case of urticaria associated with a Salmonella infection of uterine leiomyomas. CASE: A 55-year-old woman with a known history of uterine leiomyomas and a chief complaint of recurrent small and coalescing urticarial lesions confined to the abdomen presented with an 18-year history of recurrent fever and flu-like symptoms associated with the urticaria. After confirming the presence of a leiomyoma containing necrotic tissue on the computed tomography scan, a hysterectomy was performed. A large, 11-cm intramural leiomyoma was removed, and a culture of the purulent content grew a previously untyped Salmonella. The urticaria resolved on removal of the necrotic tissue. Subsequent follow-up for more than 2 years shows no relapse of symptoms. CONCLUSION: Our patient harbored Salmonella bacteria in a necrotic uterine leiomyoma, where it was difficult to detect until the time of surgery. In patients presenting with localized urticaria of the abdomen, an infection in the pelvic and abdominal tissue should be considered in the differential diagnosis.

Pyomyoma in a premenopausal woman with fever of unknown origin.

BACKGROUND: Pyomyoma (suppurative leiomyoma) is a rare disease that is a serious complication. Most cases have occurred in pregnant or postmenopausal women. CASE: A perimenopausal woman presented with fever and shoulder pain. She had no predisposing factors or history of leiomyoma. Ultrasonographic as well as abdominal and pelvic computed tomography scans showed an enlarged uterus with two large masses. Internal heterogeneous echogenicity was noted in the lower segment and body of the uterus. The elevated temperature continued despite a 3-day antibiotic course of clindamycin, ceftriaxone, and gentamicin. With a clinical impression of infected leiomyoma, she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathological findings showed a leiomyoma with abscess formation. The patient responded well to surgery. CONCLUSION: Pyomyoma may be difficult to diagnose, especially in women with a nonspecific clinical presentation. Delayed diagnosis may result in serious complications, and surgery and broad spectrum antibiotics are indicated.

Sonographic appearance of a postpartum pyomyoma with gas production.

Pyomyoma or suppurative leiomyoma is a potentially fatal complication of uterine leiomyomas. It is a rare condition with only a small number of reported cases since the era of antibiotics, and the descriptions of its sonographic appearance has been limited. We present a case of a pyomyoma associated with gas production, including a brief review of the reported sonographic features.

Overexpression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in uterine carcinosarcomas.

PURPOSE: To evaluate the expression levels of claudin-3 and claudin-4, the low- and high-affinity receptors, respectively, for the cytotoxic Clostridium perfringens enterotoxin (CPE) in uterine carcinosarcomas and explore the potential for targeting these receptors in the treatment of this aggressive uterine tumor. EXPERIMENTAL DESIGN: We analyzed claudin-3 and claudin-4 receptor expression at mRNA and protein levels in flash frozen and formalin-fixed, paraffin-embedded carcinosarcoma specimens. Recombinant CPE was used as a novel therapy against chemotherapy-resistant carcinosarcoma cell lines in vitro. The therapeutic effect of sublethal doses of CPE was studied in severe combined immunodeficient mouse xenografts harboring large s.c. carcinosarcomas. RESULTS: All flash-frozen carcinosarcoma biopsies (12 of 12) and short-term carcinosarcoma cell lines evaluated overexpressed claudin-3 and claudin-4 by quantitative reverse transcription-PCR. Membranous immunoreactivity for claudin-4 protein expression was documented in 80% (20 of 25) of primary tumors and 100% (6 of 6) of the metastatic carcinosarcomas, whereas negligible staining was found in normal endometrial cells. Regardless of their resistance to chemotherapeutic agents, all short-term carcinosarcoma cell lines tested died within 1 h of exposure to 3.3 microg/mL of CPE in vitro. Intratumoral injections of well-tolerated doses of CPE in large s.c. carcinosarcoma xenografts led to large areas of tumor cell necrosis and tumor disappearance in all treated animals. CONCLUSIONS: Claudin-3 and claudin-4 receptors are highly overexpressed in carcinosarcoma. These proteins may offer promising targets for the use of CPE as a novel type-specific therapy against this biologically aggressive variant of endometrial cancer.

[Effect of mycoplasma contamination of the human uterine leiomyosarcoma cell line SK-UT-1B on karyotype structure]. / Vliianie mikoplazmennoi kontaminatsii kletochnoi linii leiomiosarkomy cheloveka SK-UT-1B na kariotipicheskuiu struktury.

The karyotypic variability has been investigated for human uterine leiomyosarcoma cell line SK-UT-1B, cultivated for 30-90 days after contamination with Acholeplasma laidlawii, strain PG-8. The character of cell distribution for chromosome number gradually changes in contaminated cells, comparatively to the control, with the lengthening of the term of contamination. So, in 30 days the analysed distributions do not differ in the experimental and in the control variants, the modal number of chromosomes being equal to 46. In 60 days the frequency of cells with modal number of chromosomes have a tendency to decrease, and the range of variability in the number of chromosomes tend to increase. In 90 days, the frequency of cells with modal number of chromosomes decreases significantly, and the range of variability on the number of chromosomes increases significantly. The number of chromosomal aberrations gradually increases in contaminated cells, as compared to the control, with the lengthening of the term of contamination. So, in 30 days the number of chromosomal aberrations does not increase, only the number of dicentrics (telomeric associations) has the tendency to increase. In 60 days, the number of chromosomal aberrations, mainly dicentrics, increases significantly. In 90 days, the number of chromosomal aberrations increases significantly, including both dicentrics and chromatid breaks. The possible reasons of the observed character of karyotypic variability is discussed. Our previous results make it possible to suppose that the increase in the number of dicentrics in "markerless" line SK-UT-1B with long term contamination may be an additional evidence on the role of dicentrics in cell adaptation to in vitro conditions in such lines.