Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.

Epithelial ovarian cancer (EOC) is often diagnosed in advanced stage with peritoneal dissemination. Recent studies indicate that aberrant accumulation of collagen fibers in tumor stroma has a variety of effects on tumor progression. We refer to remodeled fibrous stroma with altered expression of collagen molecules, increased stiffness, and highly oriented collagen fibers as tumor-associated fibrosis (TAF). TAF contributes to EOC cell invasion and metastasis in the intraperitoneal cavity. However, an understanding of molecular events involved is only just beginning to emerge. Further development in this field will lead to new strategies to treat EOC. In this review, we focus on the recent findings on how the TAF contributes to EOC malignancy. Furthermore, we will review the recent initiatives and future therapeutic strategies for targeting TAF in EOC.

Chondroitin Sulfate Proteoglycan 4 Provides New Treatment Approach to Preventing Peritoneal Dissemination in Ovarian Cancer.

Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell-cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.

The prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis.

OBJECTIVE: Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. METHODS: We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. RESULTS: In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. CONCLUSIONS: The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer.

OBJECTIVE: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. METHODS: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. RESULTS: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. CONCLUSIONS: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

Ovarian cancer: Novel mechanisms and therapeutic targets regarding the microenvironment in the abdominal cavity.

Ovarian cancer is an intractable disease that is mostly diagnosed at an advanced stage and has a high recurrence rate. The early development of characteristic peritoneal dissemination via ascites contributes to a poor prognosis. Based on the "seed and soil" theory, ovarian cancer is considered to form a disseminated tumor that interacts with the peritoneum; superficial mesothelial cells are structurally important. Thus far, we have reported that peritoneal mesothelial cells, which originally are ecological defenses, transform into ovarian cancer-associated mesothelial cells, which are allies of cancer. They are found to be actively involved in the formation of a friendly "soil" that promotes the survival of "seeds" of ovarian cancer cells. We also demonstrated that the progression of ovarian cancer and the induction of its refractory nature are partially mediated through competition and cooperation between ovarian cancer and mesothelial cells. We believe that it is necessary to shift the aim of treatment strategies from solely targeting cancer cells to focusing on the crosstalk between the surrounding environment and ovarian cancer, an approach that ultimately aims to achieve "coexistence" with cancer through disease control.

Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study.

BACKGROUND: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. METHODS: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. RESULTS: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. CONCLUSION: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-ß can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.

Recent Insights into Human Endometrial Peptidases in Blastocyst Implantation via Shedding of Microvesicles.

Blastocyst implantation involves multiple interactions with numerous molecules expressed in endometrial epithelial cells (EECs) during the implantation window; however, there is limited information regarding the molecular mechanism underlying the crosstalk. In blastocysts, fibronectin plays a major role in the adhesion of various types of cells by binding to extracellular matrix proteins via the Arg-Gly-Asp (RGD) motif. In EECs, RGD-recognizing integrins are important bridging receptors for fibronectin, whereas the non-RGD binding of fibronectin includes interactions with dipeptidyl peptidase IV (DPPIV)/cluster of differentiation (CD) 26. Fibronectin may also bind to aminopeptidase N (APN)/CD13, and in the endometrium, these peptidases are present in plasma membranes and lysosomal membranes. Blastocyst implantation is accompanied by lysosome exocytosis, which transports various peptidases and nutrients into the endometrial cavity to facilitate blastocyst implantation. Both DPPIV and APN are released into the uterine cavity via shedding of microvesicles (MVs) from EECs. Recently, extracellular vesicles derived from endometrial cells have been proposed to act on trophectoderm cells to promote implantation. MVs are also secreted from embryonal stem cells and may play an active role in implantation. Thus, crosstalk between the blastocyst and endometrium via extracellular vesicles is a new insight into the fundamental molecular basis of blastocyst implantation.

Detection of Rhizopus-specific antigen in human and murine serum and bronchoalveolar lavage.

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.

Three-Dimensional Measurement of the Lateral Lip Element Sacrificed in Primary Repair of a Unilateral Cleft Lip.

BACKGROUND: In most children with a unilateral cleft lip (UCL), because lateral lip tissue on the cleft side is congenitally short, the lateral lip element should be appropriately excised during primary cheiloplasty so that symmetric nasolabial features are obtained after surgery. The purpose of this study was to measure how much of the lateral lip element is removed during primary cheiloplasty and compare the amount of sacrifice between different incision designs. METHODS: Preoperative 3-dimensional images of 50 infants with UCL were randomly selected. The incision designs of 3 representative techniques (Millard, Onizuka, and Fisher) were drawn on the images that were obtained before the primary repair. The lateral lip tissue excised by each technique was estimated as a percentage of the surface area of the sacrificed lateral lip to the entire lateral lip of the cleft side. RESULTS: In the case of incomplete UCL, the median values (range) were 3.2% (1.1%-5.9%), 11.6% (8.3%-20.1%), and 27.2% (15.1%-42.3%) for the Millard, Onizuka, and Fisher repairs, respectively. In cases of complete UCL, no sacrifice was needed for the Millard repair, whereas the median values (range) were 10.6% (5.2%-28.9%) and 22.5% (11.5%-48.6%) for the Onizuka and Fisher repairs, respectively. In Millard repair, the median values (range) of the lateral lip element that was resected before skin closure according to the "cut-as-you-go" policy were 5.8% (2.2%-11.8%) in cases with an incomplete UCL and 4.9% (2.7%-9.1%) in cases with a complete UCL. CONCLUSIONS: Our study demonstrated that sacrifice of the lateral lip element was minimal in the Millard repair, whereas it could exceed 20% in the Fisher repair. However, additional sacrifice of the advancement flap was needed in the Millard-type repair. The ratio of the lateral lip sacrifice varied between patients. Although UCL repair techniques should not be evaluated with the sacrifice ratio, excessive sacrifice of the lateral lip tissue can complicate the secondary lip correction. We recommend that surgeons estimate preoperatively how much lateral lip element will be sacrificed with each incision design using a 3-dimensional image for each child with a UCL.

Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer.

Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.

Successful treatment of invasive pulmonary aspergillosis caused by Aspergillus felis, a cryptic species within the Aspergillus section Fumigati: A case report.

Aspergillus species are a major cause of life-threatening infections in immunocompromised hosts, and the most common pathogen of invasive aspergillosis is Aspergillus fumigatus. Recently, the development of molecular identification has revealed cryptic Aspergillus species, and A. felis is one such species within the Aspergillus section Fumigati reported in 2013. We describe a case of invasive pulmonary aspergillosis caused by A. felis in a 41-year-old Japanese woman diagnosed with myelodysplastic syndrome. She presented with fever 19 days after undergoing autologous peripheral blood stem cell transplantation and was clinically diagnosed with invasive pulmonary aspergillosis. Bronchoscopy and bronchoalveolar lavage were performed for definitive diagnosis. The ß-tubulin genes of the mold isolated from the bronchoalveolar lavage fluid, and sequenced directly from the PCR products using a primer pair were found to have 100% homology with A. felis. We successfully treated the patient with echinocandin following careful susceptibility testing. To the best of our knowledge, this is the first published case reporting the clinical course for diagnosis and successful treatment of invasive aspergillosis by A. felis.

The intervention by an antimicrobial stewardship team can improve clinical and microbiological outcomes of resistant gram-negative bacteria.

Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes. This retrospective study enrolled patients with bloodstream infections (BSI) and long-term use of broad-spectrum antibiotics (more than 7 days). The main outcomes were 30-day and in-hospital mortality of patients with BSI. The secondary outcomes were the day of therapy (DOT) and susceptibility of antipseudomonal agents. Cases were classified into two groups: the pre-ASP group comprised cases between 2011 and 2013 and the post-ASP group, between 2014 and 2016. The outcomes were then compared between the two groups. Among the patients with all BSI (n = 1187), no significant differences in 30-day mortality were observed between those in the pre-ASP and post-ASP groups. However, in-hospital mortality was significantly lower in the post-ASP group than that in the pre-ASP group (24.8% vs. 18.0%; P = 0.004). Furthermore, the 30-day and in-hospital mortality of resistant gram-negative bacteraemia was significantly lower (20.4% vs.10.5%; P = 0.04 and 28.0% vs.16.1%; P = 0.03). The DOT of broad-spectrum antibiotics decreased except that of tazobactam/piperacillin. The susceptibilities of tazobactam/piperacillin, ceftazidime, cefepime, sulbactam/cefoperazone, gentamicin, ciprofloxacin levofloxacin, imipenem and meropenem were significantly better. Interventions by the AST can improve the clinical and microbiological outcomes, especially resistant gram-negative bacteria. Furthermore, this effect of our ASP can continue for a long term.

Longitudinal Follow-up of Individuals With Cleft Lip Using Three-Dimensional Stereophotogrammetry.

The usefulness of three-dimensional (3D) stereophotogrammetry for treating cleft lip (CL) has been well documented. However, there are only a few reliable anthropometric analyses in infants with CL because at this age they cannot assume a resting facial position. Since 2014, we have used a handheld 3D imaging system in the operating room to obtain optimal images of infants with CL and palate under general anesthesia. Currently, 168 infants with a unilateral cleft, 50 infants with bilateral clefts, and 47 infants with an isolated cleft palate are being followed up in this way for a maximum of 30 months. Most patients ≥3 years of age are cooperative and allow staff to obtain 3D images without sedation. We plan to follow them until adulthood, obtaining 3D images at every intervention. Each year, >150 infants can be added to this ongoing longitudinal study. Using an archive of these digital images, various retrospective studies can be attempted in the future, which include comparisons of the long-term outcomes of various surgical techniques and interventions at different time intervals. This is the first 2-year preliminary report of a 20-year longitudinal study.

Clinical Characteristics and Low Susceptibility to Daptomycin in Enterococcus faecium Bacteremia.

Enterococcus faecium has high levels of resistance to multiple antibiotics, and the mortality due to E. faecium bacteremia is high. Accordingly, E. faecium strains with low susceptibility to daptomycin are a concern in clinical practice. This study assessed the predictive factors and prognosis of patients with bacteremia due to E. faecium as well as the antimicrobial susceptibility, particularly to daptomycin, among E. faecium isolates. The medical records of patients admitted to Osaka City University Hospital with E. faecalis (n = 60) and E. faecium (n = 48) bacteremia between January 2011 and March 2016 were retrospectively reviewed. The E. faecalis group (mean age: 62.0 years) included 22 women, and the E. faecium group (mean age: 59.1 years) included 19 women. Predictive factors for infection, prognosis, and isolate antimicrobial susceptibilities were evaluated. The mean Sequential Organ Failure Assessment score and mortality rate did not differ between the two groups. The independent predictors of E. faecium bacteremia in multivariate analysis included quinolone use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p = 0.016). Cardiovascular disease was associated with a reduced risk of E. faecium bacteremia (p = 0.015). Notably, the percentage of E. faecium isolates with low daptomycin susceptibility was higher than that of E. faecalis (8.5% vs. 0%, p = 0.036). Thus, E. faecium should be considered when administering antibiotic therapy to patients with a history of these predictors. Furthermore, the use of daptomycin should be avoided in case of E. faecium with low susceptibility to daptomycin.

Two unusual cases of successful treatment of hypermucoviscous Klebsiella pneumoniae invasive syndrome.

BACKGROUND: A few Japanese cases of hypermucoviscous Klebsiella pneumoniae (K. pneumoniae) invasive syndrome have recently been reported. Although extrahepatic complications from bacteremic dissemination have been observed, infected aneurysms are rare. Furthermore, the primary source of infection is generally a liver abscess, and is rarely the prostate. Therefore, we report two atypical cases of hypermucoviscous K. pneumoniae invasive syndrome. CASE PRESENTATION: The first case was an 81-year-old Japanese man with no significant medical history, who was referred to our hospital for vision loss in his right eye. Contrast-enhanced whole-body computed tomography revealed abscesses in the liver and the prostate, and an infected left internal iliac artery aneurysm. Contrast-enhanced head magnetic resonance imaging revealed brain abscesses. Cultures of the liver abscess specimen and aqueous humor revealed K. pneumoniae with the hypermucoviscosity phenotype, which carried the magA gene (mucoviscosity-associated gene A) and the rmpA gene (regulator of mucoid phenotype A). We performed enucleation of the right eyeball, percutaneous transhepatic drainage, coil embolization of the aneurysm, and administered a 6-week course of antibiotic treatment. The second case was a 69-year-old Japanese man with diabetes mellitus, who was referred to our hospital with fever, pollakiuria, and pain on urination. Contrast-enhanced whole-body computed tomography revealed lung and prostate abscesses, but no liver abscesses. Contrast-enhanced head magnetic resonance imaging revealed brain abscesses. The sputum, urine, prostate abscess specimen, and aqueous humor cultures revealed K. pneumoniae with the hypermucoviscosity phenotype, which carried magA and rmpA. We performed enucleation of the left eyeball, percutaneous drainage of the prostate abscess, and administered a 5-week course of antibiotic treatment. CONCLUSIONS: Hypermucoviscous K. pneumoniae can cause infected aneurysms, and the prostate can be the primary site of infection. We suggest that a diagnosis of hvKP invasive syndrome should be considered in all patients who present with K. pneumoniae infection and multiple organ abscesses.

Effectiveness of weekly polymerase chain reaction-based open reading frame typing analysis of all newly isolated methicillin-resistant Staphylococcus aureus strains for controlling nosocomial infections.

Polymerase chain reaction (PCR)-based open reading frame typing (POT) helps differentiate between bacterial strains based on the open reading frames (ORFs) of the prophage-encoding genes; multiplex PCR screening is performed to identify strains based on keeping patterns. At our hospital, surveillance of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) transmission is undertaken using POT to conduct molecular epidemiological analysis for all newly detected MRSA strains. In 2014, we performed POT only once a month; however, in 2015, we increased the frequency of POT to once a week, which helped us detect nosocomial transmission that would normally be difficult to detect, and thus achieve 40% reduction in nosocomial transmission, compared to that in 2014. This suggests that weekly POT screening for all MRSA strains is one of the effective methods available for minimizing nosocomial transmission of MRSA.

Factors affecting the long-term prognosis of patients in the AYA generation with epithelial ovarian cancer: A multicenter propensity score matching analysis.

OBJECTIVE: Ovarian carcinoma (OvCa) is more common in the elderly, but also affects the adolescent and young adult (AYA) generation, which refers to those aged 15-39 years. Although the characteristics of OvCa may differ between AYAs and non-AYAs, limited information is currently available on differences in prognostic factors. Therefore, we herein investigated prognostic factors for and the prognosis of OvCa in AYAs. We also examined the prognostic impact of fertility-sparing surgery in a subgroup analysis. METHODS: We retrospectively collected data on 4897 patients with OvCa from the databases of multiple institutions and ultimately included 1161 patients with epithelial ovarian cancer (EOC). We performed a survival analysis to compare AYAs and non-AYAs with backgrounds that conformed to those of AYAs using the propensity score (PS) matching method. A Cox regression analysis was also conducted to evaluate each predictor of recurrence-free survival (RFS) and overall survival (OS) in the original population. As a subgroup analysis, a multivariate analysis stratified by the AYA and non-AYA generations was performed. RESULTS: In total, 119 AYA patients were included in this study. After PS adjustments, no significant differences were observed in RFS or OS between AYAs and non-AYAs. Prognostic factors differed between AYAs and non-AYAs, particularly in histology and cytology. A multivariate analysis stratified by the AYA and non-AYA generations described that uterine-preserving surgery (UPS) did not have a significant impact on the prognosis of AYAs or non-AYAs. In cases with recurrence, no significant differences were observed in RFS and recurrent sites in the two groups. CONCLUSION: Characteristic prognostic factors for EOC in AYAs were identified. The present results indicate the limited prognostic impact of UPS for EOC in AYAs.

Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study.

Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.