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Biochimie Jun 2022Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding... (Review)
Review
Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens, Anaerococcus tetradius, and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies.
Topics: Biomarkers; Dysbiosis; Female; Genital Neoplasms, Female; Humans; Lactobacillus; Microbiota
PubMed: 35176353
DOI: 10.1016/j.biochi.2022.02.005 -
Pathology, Research and Practice Jun 2016Müllerianosis is the term used to designate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic location. In this...
Müllerianosis is the term used to designate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic location. In this report, we describe a case of incidental vaginal müllerianosis in a 59-year-old woman who underwent rectosigmoidectomy for rectal adenocarcinoma. In the vaginal cuff removed for neoplastic invasion, a separate multilocular mass measuring 1.5cm was found. The microscopic examination of the vaginal wall revealed endosalpingeal, endocervical and endometrial dilated or cystic glands with predominance of the endosalpingeal epithelium. Müllerian epithelium showed positivity for cytokeratins 7 and 8/18, high molecular weight cytokeratin, estrogen receptor alpha, and androgen receptor. The periglandular stroma was condensed and reactive for smooth-muscle actin, h-caldesmon, and CD10. To the best of our knowledge, a case of vaginal müllerianosis has not been previously reported. This lesion should be differentiated form vaginal adenosis and primary well-differentiated vaginal adenocarcinoma. The vagina should be added to the list of locations in which müllerianosis can be observed.
Topics: Adenocarcinoma; Cervix Uteri; Choristoma; Endometrium; Fallopian Tubes; Female; Humans; Incidental Findings; Keratins; Middle Aged; Rectal Neoplasms; Vaginal Diseases
PubMed: 26970930
DOI: 10.1016/j.prp.2016.02.023 -
International Journal of Applied &... 2016Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a... (Review)
Review
Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a proven association of HPV with these cancers, questions regarding HPV testing, vaccination, and treatment of HPV-related cancers continue to remain unanswered. The present article provides an overview of the HPV-associated cancers.
PubMed: 27127735
DOI: 10.4103/2229-516X.179027 -
International Journal of Gynecological... Mar 2021Uterine transposition has emerged as an alternative for fertility preservation in women with pelvic malignancies that require radiotherapy. The goal of this study was to...
OBJECTIVE
Uterine transposition has emerged as an alternative for fertility preservation in women with pelvic malignancies that require radiotherapy. The goal of this study was to evaluate the short-term outcomes of patients undergoing uterine transposition after trachelectomy for cervical cancer or before chemoradiation for vaginal cancer.
METHODS
We retrospectively evaluated patients with early stage cervical cancer after radical trachelectomy or with vaginal cancer with indication for pelvic radiation who had uterine transposition performed as fertility sparing strategy.
RESULTS
Four patients with cervical cancer and one patient with vaginal cancer were included. Median age was 32 years (range 28-38). All patients had squamous cell carcinomas. All patients with cervical cancer had radical trachelectomies with sentinel lymph node dissection (SLN). Two of these patients also had pelvic lymphadenectomies. Indications for adjuvant radiotherapy was due to Sedlis criteria in two patients and to lymph node metastasis in the other two patients. The patient with stage IIB vaginal cancer was recommended primary chemoradiation. All patients underwent uterine transposition before radiotherapy. The median uterine transposition surgical time was 90 min (range 80-205) and no early complications (30 days) occurred. Average time from uterine transposition to start of radiotherapy was 16 days (10-28). After radiation, the uterus along with the ovaries and tubes were repositioned and the residual cervix sutured to the vagina. One patient declined uterine reimplantation after radiation and underwent a hysterectomy. After a median follow-up of 25 months (range 1-30), all patients were without evidence of disease. All patients with preserved uterus have normal menses after treatment. One patient has attempted to conceive with IVF techniques without success.
CONCLUSIONS
Uterine transposition may be an option in selected patients with cervical and vaginal cancers who want to preserve fertility. However, further studies that address its oncological safety and obstetrical outcomes are encouraged.
Topics: Adult; Carcinoma, Squamous Cell; Female; Fertility Preservation; Humans; Operative Time; Retrospective Studies; Uterine Cervical Neoplasms; Uterus; Vaginal Neoplasms
PubMed: 33649011
DOI: 10.1136/ijgc-2020-001780 -
Advances in Experimental Medicine and... 2021Ovarian Cancer is one of the most lethal and widespread gynecological malignancies. It is the seventh leading cause of all cancer deaths worldwide. High-Grade Serous... (Review)
Review
Ovarian Cancer is one of the most lethal and widespread gynecological malignancies. It is the seventh leading cause of all cancer deaths worldwide. High-Grade Serous Cancer (HGSC), the most commonly occurring subtype, alone contributes to 70% of all ovarian cancer deaths. This is mainly attributed to the complete lack of symptoms during the early stages of the disease and absence of an early diagnostic marker.PAX8 is emerging as an important histological marker for most of the epithelial ovarian cancers, as it is expressed in about 90% of malignant ovarian cancers, specifically in HGSC. PAX8 is a member of the Paired-Box gene family (PAX1-9) of transcription factors whose expression is tightly controlled temporally and spatially. The PAX genes are well known for their role in embryonic development and their expression continues to persist in some adult tissues. PAX8 is required for the normal development of Müllerian duct that includes Fallopian tube, uterus, cervix, and upper part of vagina. In adults, it is expressed in the Fallopian tube and uterine epithelium and not in the ovarian epithelium. Considering the recent studies that predict the events preceding the tumorigenesis of HGSC from the Fallopian tube, PAX8 appears to have an important role in the development of ovarian cancer.In this chapter, we review some of the published findings to highlight the significance of PAX8 as an important marker and an emerging player in the pathogenesis of ovarian cancer. We also discuss regarding the future perspectives of PAX8 wherein it could contribute to the betterment of ovarian cancer diagnosis and treatment.
Topics: Adult; Carcinoma, Ovarian Epithelial; Fallopian Tubes; Female; Humans; Neoplasm Grading; Ovarian Neoplasms; PAX8 Transcription Factor
PubMed: 34339032
DOI: 10.1007/978-3-030-73359-9_6 -
The New England Journal of Medicine Jan 2021Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally...
Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).
Topics: Adenocarcinoma, Mucinous; Adult; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Child; Fatal Outcome; Female; High-Throughput Nucleotide Sequencing; Humans; Infant; Lung; Lung Neoplasms; Male; Mothers; Pregnancy; Pregnancy Complications, Neoplastic; Uterine Cervical Neoplasms; Vagina; Exome Sequencing
PubMed: 33406329
DOI: 10.1056/NEJMoa2030391 -
Maturitas Sep 2023Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the...
UNLABELLED
Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus.
METHODS
A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio.
RESULTS
Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer.
CONCLUSIONS
Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.
Topics: Humans; Female; Vulvar Lichen Sclerosus; Lichen Sclerosus et Atrophicus; Vulvar Neoplasms; Retrospective Studies; Carcinoma, Squamous Cell; Vulva; Oropharyngeal Neoplasms
PubMed: 37302181
DOI: 10.1016/j.maturitas.2023.04.010 -
Journal of Lower Genital Tract Disease Jan 2023Small cell carcinoma of the vagina (SmCCV) is an extremely rare disease. Evidence-based data and specific guidelines are lacking. We conducted the first systematic...
OBJECTIVES
Small cell carcinoma of the vagina (SmCCV) is an extremely rare disease. Evidence-based data and specific guidelines are lacking. We conducted the first systematic review of case reports to provide the most overall picture of SmCCV.
MATERIALS AND METHODS
Literature search in PubMed and Scopus was performed using the terms "small cell carcinoma" and "vagina." English-language case reports of primary SmCCV up to January 2022 were included.
RESULTS
Twenty-nine articles describing 44 cases met our inclusion criteria. We report a new case of our hospital. The global median overall survival (mOS) was 12.00 months (95% CI = 9.31-14.69). The mOS was not reached for stage I, and it was 12.00, 12.00, 9.00, and 8.00 months for stages II, III, IVA, and IVB, respectively (statistically significant differences between stage I and stages II, III, or IVA [log rank p = .003-.017]). Thirty-five cases received local treatments (77.8%). The mOS of patients treated with surgery ± complementary chemotherapy, radiotherapy ± complementary chemotherapy, chemoradiation ± complementary chemotherapy, and surgery + radiotherapy ± complementary chemotherapy were 11.00, 12.00, 17.00, and 29.00 months, respectively. The use of adjuvant or neoadjuvant chemotherapy (64.5%, mostly platinum + etoposide) showed longer mOS (77.00 vs 15.00 months). Four of 5 tested cases presented human papillomavirus infection, 3 of them presenting type 18.
CONCLUSIONS
Small cell carcinoma of the vagina shows dismal prognosis. Multimodal local management plus complementary chemotherapy seems to achieve better outcomes. Human papillomavirus could be related to the development of SmCCV. A diagnostic-therapeutic algorithm is proposed.
Topics: Female; Humans; Algorithms; Carcinoma; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Vagina
PubMed: 36282979
DOI: 10.1097/LGT.0000000000000712 -
Diseases of the Colon and Rectum Mar 2023A 68-year-old woman presented with rectal bleeding, urgency, and tenesmus. A digital rectal examination confirmed a craggy mass infiltrating into the sphincter complex....
A 68-year-old woman presented with rectal bleeding, urgency, and tenesmus. A digital rectal examination confirmed a craggy mass infiltrating into the sphincter complex. Follow-up colonoscopy noted a low-rectal tumor (3 cm from the dentate), and histopathology confirmed a moderately differentiated adenocarcinoma. Subsequent staging with MRI confirmed a 5-cm circumferential low-rectal neoplasm with extramural vascular invasion and threatened circumferential resection margin. The neoplasm abutted the posterior vaginal wall and was invading the internal sphincter complex. Four enlarged mesorectal nodes (>7 mm) and several enlarged right pelvic sidewall nodes (largest at 17 mm) were also observed. There was no evidence of distant disease. The patient underwent long-course neoadjuvant chemoradiotherapy. Restaging showed a good treatment response with some regression and no involvement/encroachment of the vagina. All the mesorectal nodes had reduced in size (~4 mm), and all but one of the right pelvic sidewall nodes had also decreased in size. However, 1 pelvic sidewall node (obturator fossa) still remained at 10 mm. After the tumor board discussion, a decision to proceed to abdominoperineal resection with right sidewall clearance was made. Final histopathology confirmed a moderately differentiated adenocarcinoma with no mesorectal nodal involvement (19 nodes sampled), and 1 of 7 sidewall nodes had evidence of metastatic adenocarcinoma.
Topics: Female; Humans; Aged; Lymph Nodes; Rectal Neoplasms; Rectum; Pelvis; Adenocarcinoma; Neoplasm Staging; Neoadjuvant Therapy
PubMed: 36728599
DOI: 10.1097/DCR.0000000000002706 -
Medicina (Kaunas, Lithuania) Dec 2021Neuroendocrine neoplasms (NENs) are particularly rare in all sites of the gynecological tract and include a variety of neoplasms with variable prognosis, dependent on... (Review)
Review
Neuroendocrine neoplasms (NENs) are particularly rare in all sites of the gynecological tract and include a variety of neoplasms with variable prognosis, dependent on histologic subtype and site of origin. Following the expert consensus proposal of the International Agency for Research on Cancer (IARC), the approach in the latest World Health Organization (WHO) Classification System of the Female Genital Tumours is to use the same terminology for NENs at all body sites. The main concept of this novel classification framework is to align it to all other body sites and make a clear distinction between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The previous WHO Classification System of the Female Genital Tumours featured more or less the same principle, but used the terms 'low-grade neuroendocrine tumor' and 'high-grade neuroendocrine carcinoma'. Regardless of the terminology used, each of these two main categories include two distinct morphological subtypes: NETs are represented by typical and atypical carcinoid and NEC are represented by small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). High-grade NECs, especially small cell neuroendocrine carcinoma tends to be more frequent in the uterine cervix, followed by the endometrium, while low-grade NETs usually occur in the ovary. NENs of the vulva, vagina and fallopian tube are exceptionally rare, with scattered case reports in the scientific literature.
Topics: Carcinoma, Neuroendocrine; Female; Genital Neoplasms, Female; Humans; Neuroendocrine Tumors; Prognosis; World Health Organization
PubMed: 34946283
DOI: 10.3390/medicina57121338