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Cancers Apr 2024Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It... (Review)
Review
BACKGROUND
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing, inadequately understood neoplasm with a 5-year progression-free survival rate of as low as 48%. It is characterized by varying degrees of malignancy and the production of mucinous and gelatinous structures. Typically, the development of pseudomyxoma peritonei is associated with the rupture of appendiceal mucinous tumors and other gastrointestinal or ovarian mucinous tumors. The goal of our literature review was to identify various aspects that characterize the ovarian causes of pseudomyxoma peritonei.
MATERIALS AND METHODS
The authors performed an extensive literature search between 1 February 2024 and 2 March 2024 on the following databases: Pubmed, Scopus, Oxford Journals, and Reaxys, and the findings were summarized into seven main clinical and paraclinical situations.
RESULTS
According to our research, the main instances in which pseudomyxoma peritonei can be triggered by an ovarian cause are the following: (1) mucinous cystadenoma; (2) mucinous ovarian cancer; (3) colon cancer with ovarian metastasis; (4) malignant transformation of an ovarian primary mature cystic teratoma; (5) appendiceal mucocele with peritoneal dissemination mimicking an ovarian tumor with peritoneal carcinomatosis; (6) mucinous borderline tumor developing inside an ovarian teratoma; and (7) the association between a mucinous bilateral ovarian cancer and a colonic tumor.
CONCLUSIONS
In our study, we aimed to provide a comprehensive overview of the ovarian causes of pseudomyxoma peritonei, including its epidemiology, imagery characteristics, symptoms, current treatment, and promising future therapies, in the hopes of finding feasible solutions, as a lack of understanding of this mucus-secreting malignant disease increases the risk of delayed diagnosis or uncontrolled deterioration.
PubMed: 38672528
DOI: 10.3390/cancers16081446 -
Cancer Medicine Dec 2023As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based...
AIM
As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment.
METHODS
A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed.
RESULTS
Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1-positive samples were more common in the chemoresistant group than in the platinum-sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis.
CONCLUSION
This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.
Topics: Female; Humans; Tryptophan; Tryptophan Oxygenase; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; L-Amino Acid Oxidase
PubMed: 38062922
DOI: 10.1002/cam4.6778 -
Cureus Feb 2023Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a...
Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a 34-year-old Japanese woman with a life-threatening hemoperitoneum in the first trimester coexisting with ovarian endometrioma and ovarian pregnancy. The patient was hospitalized in our department for acute hypogastric pain and massive hemoperitoneum during pregnancy. She had a history of miscarriage at eight weeks of gestation one year prior. Her serum beta-human chorionic gonadotropin (hCG) level was >2,000 mIU/mL. Also, a transvaginal ultrasound showed an empty uterus, an intact right ovary, an inhomogeneous left ovary, and a massive hemoperitoneum. An exploratory laparoscopy revealed a rupture of the left ovarian endometrioma, a left corpus luteal cyst, and intraperitoneal bleeding of approximately 1,200 mL. However, no ectopic lesions were observed. Microscopic examination revealed an endometriotic cyst with decidual changes in the stroma, a corpus luteal cyst, and chorionic villi with hemorrhage. Serum beta-hCG levels became negative on the 27th postoperative day. The postoperative course was uneventful. This case shows that, in addition to the differential diagnosis of ovarian pregnancy from ovarian endometrioma, clinicians should consider the coexistence of both conditions.
PubMed: 37007423
DOI: 10.7759/cureus.35608 -
Cells May 2022Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone...
Progesterone receptor (PGR) activity is obligatory for mammalian ovulation; however, there is no established direct functional pathway explaining how progesterone receptor completely and specifically regulates oocyte release. This study examined the overarching cell- and isoform-specific effects of the PGR within each cellular compartment of the ovary, using mice null for the PGR (PRKO), as well as isoform-specific null mice. The PGR was expressed in ovarian granulosa and stromal cells and although PRKO ovaries showed no visible histological changes in preovulatory ovarian morphology, follicle rupture did not occur. Reciprocal ovarian transplant experiments established the necessity of ovarian PGR expression for ovulation. Cumulus-oocyte complexes of PRKO mice exhibited normal morphology but showed some altered gene expression. The examination of mitochondrial activity showed subtle differences in PRKO oocytes but no differences in granulosa cell respiration, glycolysis or β-oxidation. Concurrently, RNA-seq identified novel functional pathways through which the PGR may regulate ovulation. PGR-A was the predominant transcriptionally active isoform in granulosa cells and 154 key PGR-dependent genes were identified, including a secondary network of transcription factors. In addition, the PGR regulated unique gene networks in the ovarian stroma. Collectively, we establish the effector pathways activated by the PGR across the ovarian cell types and conclude that PGR coordinates gene expression in the cumulus, granulosa and stromal cells at ovulation. Identifying these networks linking the PGR to ovulation provides novel targets for fertility therapeutics and nonhormonal contraceptive development.
Topics: Animals; Female; Granulosa Cells; Mammals; Mice; Mice, Knockout; Ovulation; Progesterone; Protein Isoforms; Receptors, Progesterone
PubMed: 35563869
DOI: 10.3390/cells11091563 -
Frontiers in Cell and Developmental... 2020Ovulation is a unique physiological phenomenon that is essential for sexual reproduction. It refers to the entire process of ovarian follicle responses to hormonal... (Review)
Review
Ovulation is a unique physiological phenomenon that is essential for sexual reproduction. It refers to the entire process of ovarian follicle responses to hormonal stimulation resulting in the release of mature fertilization-competent oocytes from the follicles and ovaries. Remarkably, ovulation in different species can be reproduced out-of-body with high fidelity. Moreover, most of the molecular mechanisms and signaling pathways engaged in this process have been delineated using ovulation models. Here, we provide an overview of the major molecular and cytological events of ovulation observed in frogs, primarily in the African clawed frog , using mainly approaches, with the focus on meiotic oocyte maturation and follicle rupture. For the purpose of comparison and generalization, we also refer extensively to ovulation in other biological species, most notoriously, in mammals.
PubMed: 33363163
DOI: 10.3389/fcell.2020.605379 -
Molecular Cell Mar 2024The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and...
The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities. Mechanistically, we unveil unique dynamics of the centromeric replisome distinct from the rest of the genome. Locus-specific proteomics identifies specialized DNA replication and repair proteins at centromeres, highlighting them as difficult-to-replicate regions. The translesion synthesis pathway, along with other factors, acts to sustain centromere replication and integrity. Prolonged stress causes centromeric alterations like ruptures and translocations, as observed in ovarian cancer models experiencing replication stress. This study provides unprecedented insights into centromere replication and integrity, proposing mechanistic insights into the origins of centromere alterations leading to abnormal cancerous karyotypes.
Topics: Humans; Centromere; Repetitive Sequences, Nucleic Acid; Mitosis; Genomic Instability
PubMed: 38359824
DOI: 10.1016/j.molcel.2024.01.018 -
Journal of Minimally Invasive Gynecology Sep 2022In this video, we describe a 5-step surgical technique that allows us to safely incise and aspirate the content of large ovarian cysts through a single-port laparoscopic...
STUDY OBJECTIVE
In this video, we describe a 5-step surgical technique that allows us to safely incise and aspirate the content of large ovarian cysts through a single-port laparoscopic incision. This allows performing laparoscopic oophorectomies instead of large xipho-pubic laparotomies.
DESIGN
A stepwise demonstration of the technique with narrated video footage.
SETTING
Ovarian masses, especially cysts, are common gynecologic conditions [1]. However, depending on their size, large adnexal cysts are usually managed with transverse or midline laparotomies [2]. This is to prevent cyst ruptures and abdominal contamination and ensure oncological safety of the procedure [3-5]. Different leak-proof aspiration techniques have been described in the literature allowing for safe large cyst aspiration and adnexectomy through a mini-laparotomy incision or via laparoscopy [2,3,6-10]. We describe a 5-step surgical technique allowing for closed aspiration of ovarian intracystic fluid and adnexectomy while respecting oncological safety.
INTERVENTIONS
Step 1: Perform diagnostic laparoscopy to rule out peritoneal carcinomatosis contraindicating this procedure and then after cyst exposition, thoroughly dry the cyst wall. Step 1 Bis: Cut the cuff of a sterile glove to prepare a square piece of membrane. Step 2: Place a protective gauze and then apply the surgical glue to the ovarian cyst wall followed by the glove/membrane application. Perform a purse suture through the glove/membrane and the ovarian wall superficially to ensure further adhesion and prevent ovarian fluid spillage. Step 3: Incise the ovarian wall, introduce the aspiration cannula and tighten the purse suture to aspirate the cystic fluid. Step 4: After aspiration is complete, tighten the suture and close the glove to guarantee a closed space and prevent abdominal contamination. Step 5: Perform laparoscopic oophorectomy or cystectomy. Safely remove the specimen in an endoscopic retrieval bag through the trocar incision.
CONCLUSION
This technique allows safe laparoscopic large ovarian cysts resections while respecting oncologic safety and preventing intra-abdominal spillage and contamination.
Topics: Cysts; Female; Humans; Laparoscopy; Laparotomy; Ovarian Cysts; Ovariectomy
PubMed: 35753617
DOI: 10.1016/j.jmig.2022.06.018 -
Cureus Mar 2022Immature teratomas are rare malignant tumors of the ovary. They are made of immature components of germ cell origin. The incidence of immature teratomas is highest in...
Immature teratomas are rare malignant tumors of the ovary. They are made of immature components of germ cell origin. The incidence of immature teratomas is highest in young adults aged 18 to 39. The prognosis heavily depends on the International Federation of Gynecology and Obstetrics (FIGO)staging system and is influenced by factors such as cell type, tumor grade, capsular rupture, and metastatic risk factors. Initial treatment is complete surgical resection. When indicated, platinum-based adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP) is the treatment of choice. Next-generation sequencing of the tumor can influence treatment in the recurrent setting. Temozolomide is an alkylating agent used to target high-grade gliomas. Bevacizumab is a targeted therapy that interferes with the process of angiogenesis by inhibiting vascular endothelial growth factor (VEGF). We report a 36-year-old female who presented with a 17.6cm x 10.5cm x 24.2cm intraabdominal mass and ascites. Upon tumor resection, she was found to have a stage IIIa, grade 2 immature teratoma of the left ovary, with glial tissue being the metastatic cell type. Disease progression continued despite treatment with BEP. She was then treated experimentally with six months of bevacizumab and temozolomide, given its rarity and targeted therapy for glial tissue. Despite monoclonal antibody therapy, the tumor progressed again and was treated with docetaxel and gemcitabine. A repeat CT of the chest, abdomen, and pelvis demonstrated scattered peritoneal implants that were increasing in size. Chromosome analysis was performed and revealed somatic mutations of MLH1, MSH2, MSH6, and PD-L1. The patient has requested a break from chemotherapy but will be treated with direct immunotherapy when she restarts. This case's importance lies in its rarity because fewer than 10 cases of immature teratomas with metastatic glial tissue are noted in the world's literature. Furthermore, this is the first reported case of this cell type being treated with immunotherapy in the world literature.
PubMed: 35371894
DOI: 10.7759/cureus.22748 -
Gynecology and Minimally Invasive... 2022To evaluate the feasibility and safety of laparoscopic surgery for large ovarian masses with benign features.
OBJECTIVES
To evaluate the feasibility and safety of laparoscopic surgery for large ovarian masses with benign features.
MATERIALS AND METHODS
Women who underwent laparoscopic surgery for an ovarian mass with benign features between 2017 and 2019 at a tertiary referral center were included in the retrospective study. Based on the size of the ovarian mass, the women were divided into the case and control groups of ≥10 cm and <10 cm, respectively. Clinical characteristics, operative findings, histopathological results, and complication rates of the groups were compared.
RESULTS
A total of 260 women, 64 women with large masses and 196 with small masses were included in the study. The operation time, intraoperative cyst rupture rate, complication rate, and hospital stay were similar in the case and control groups ( > 0.05). The cyst aspiration rate (29.7% vs. 5.1%, < 0.001) and the unexpected malignancy rate (7.8% vs. 0.0% = 0.001) were significantly higher in the case group than in the control group.
CONCLUSION
Laparoscopic surgery was found feasible for the treatment of women with large ovarian masses. However, a higher unexpected malignancy rate requires the careful patient selection and appropriate counseling preoperatively in these cases.
PubMed: 36660330
DOI: 10.4103/gmit.gmit_122_21 -
International Journal of Gynecological... May 2023Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical...
OBJECTIVE
Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival.
METHODS
We conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined.
RESULTS
Of 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6-8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5-3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3-2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5-3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival.
CONCLUSIONS
In clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Retrospective Studies; Lymph Node Excision; Prognosis; Rupture; Adenocarcinoma, Mucinous; Neoplasm Staging
PubMed: 36914170
DOI: 10.1136/ijgc-2023-004327