A randomized trial evaluated whether resection of lymph nodes that appeared macroscopically normal during surgery for ovarian cancer would lead to improved outcomes. Progression-free and overall ...survival were unaffected, and resection was associated with longer operations and more complications.
The Commentary reports on our experience in Centro di Riferimento Oncologico IRCCS Aviano about the integrated and combined treatment with percutaneous endoscopic gastrostomy and lanreotide in ...patients with bowel obstructions by ovarian cancer and peritoneal carcinomatosis. We treated patients with gynecological cancers and bowel obstruction with percutaneous endoscopic gastrostomy and, when patients were partially responsive, with lanreotide. We registered a constant overall benefit for the quality of life and for the control of symptoms, which is very important especially during the home care follow-up of terminal patients.
Epithelial ovarian cancer (EOC) is an infrequent but highly lethal disease, almost invariably treated with platinum‐based therapies. Improving the response to platinum represents a great challenge, ...since it could significantly impact on patient survival. Here, we report that silencing or pharmacological inhibition of CDK6 increases EOC cell sensitivity to platinum. We observed that, upon platinum treatment, CDK6 phosphorylated and stabilized the transcription factor FOXO3, eventually inducing ATR transcription. Blockage of this pathway resulted in EOC cell death, due to altered DNA damage response accompanied by increased apoptosis. These observations were recapitulated in EOC cell lines in vitro, in xenografts in vivo, and in primary tumor cells derived from platinum‐treated patients. Consistently, high CDK6 and FOXO3 expression levels in primary EOC predict poor patient survival. Our data suggest that CDK6 represents an actionable target that can be exploited to improve platinum efficacy in EOC patients. As CDK4/6 inhibitors are successfully used in cancer patients, our findings can be immediately transferred to the clinic to improve the outcome of EOC patients.
Synopsis
In epithelial ovarian cancer cells, platinum favours binding and phosphorylation of FOXO3 by the CDK6/cyclin D3 complex. FOXO3 is thus stabilized and binds the ATR promoter thereby inducing its transcription and preventing platinum‐induced cell death.
CDK6 in complex with cyclin D3 participates in the control of DNA damage response.
CDK6 binds and phosphorylates FOXO3 on serine 325 to control ATR expression.
High CDK6 expression predicts poor survival of EOC patients.
A combination of platinum‐based chemotherapy with pharmacological CDK6 inhibition might be a new therapeutic option for EOC patients.
In epithelial ovarian cancer cells, platinum favours binding and phosphorylation of FOXO3 by the CDK6/cyclin D3 complex. FOXO3 is thus stabilized and binds the ATR promoter thereby inducing its transcription and preventing platinum‐induced cell death.
Neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory index (SII) are prognostic factors in epithelial ovarian cancer (EOC). Their predictive value for platinum-sensitivity and their role in ...recurrent EOC are unknown. A total of 375 EOC patients were retrospectively analyzed. The correlation between baseline NLR and SII, and platinum-free interval (PFI) according to first line bevacizumab treatment were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Subsequently NLR and SII calculated before second line treatment initiation were evaluated to identify a potential correlation with progression-free survival (PFS) and overall survival (OS) in platinum-sensitive and in platinum-resistant population. In multivariate analysis, NLR ≥ 3 is an independent predictive factor for PFI at 6 months in the chemotherapy group (OR = 2.77, 95% CI 1.38-5.56, p = 0.004), not in bevacizumab treated patients. After having adjusted for ECOG performance status, histology, ascites, bevacizumab treatment at second line and BRCA status, NLR ≥ 3 and SII ≥ 730 are significantly associated with worse OS in platinum-sensitive (HR = 2.69, 95% CI 1.60-4.53, p = 0.002; HR = 2.11, 95% CI 1.29-3.43, p = 0.003, respectively), not in platinum-resistant EOC patients. Low NLR is an independent predictive factor for platinum-sensitivity in patients treated without bevacizumab. NLR and SII are prognostic factors in recurrent platinum-sensitive EOC patients.
Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free ...survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering
genes status.
We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to
genes status as follows: all comers (AC) population,
1/2 mutated (BRCAm), and
wild type patients (BRCAwt).
In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the
mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36-0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63-1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively).
PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.
Cotyledonoid leiomyoma is an unusual uterine myoma due to some ultrasound features that mimic a malignant lesion facilitating the choice of radical surgery. This study aims to summarize the ...ultrasound and the magnetic resonance imaging aspects of this atypical lesion, and also discuss surgical treatment and pathological exam. It included all English case reports or case series until August 2021 found through PubMed, Google Scholar, and Scopus. A total of 94 cotyledonoid leiomyomas were reported, with a median tumor size of 12 cm. The typical ultrasound image is characterized by a large solid heterogeneous mass, with high vascularity, no shadowing, and indistinct margins within the myometrium. Magnetic resonance imaging shows the presence of merging isointense nodules to the myometrium in T1-weighted images, hyperintense in T2-weighted images, and contrast agent enhancement. Surgical treatment consists of hysterectomy (75 cases, 80%) or myomectomy (19 cases, 20%), without evidence of recurrence if complete. The placenta-like appearance observed during surgery supports this rare fibroid hypothesis. The intraoperative frozen section can be considered. Microscopically, no atypical cells, signs of mitotic activity or cell necrosis are found. To conclude, some preoperative and intraoperative aspects of this lesion are distinctive and may lead surgeons to opt for conservative surgery.
Platinum (PT)-resistant Epithelial Ovarian Cancer (EOC) grows as a metastatic disease, disseminating in the abdomen and pelvis. Very few options are available for PT-resistant EOC patients, and ...little is known about how the acquisition of PT-resistance mediates the increased spreading capabilities of EOC. Here, using isogenic PT-resistant cells, genetic and pharmacological approaches, and patient-derived models, we report that Integrin α6 (ITGA6) is overexpressed by PT-resistant cells and is necessary to sustain EOC metastatic ability and adhesion-dependent PT-resistance. Using in vitro approaches, we showed that PT induces a positive loop that, by stimulating ITGA6 transcription and secretion, contributes to the formation of a pre-metastatic niche enabling EOC cells to disseminate. At molecular level, ITGA6 engagement regulates the production and availability of insulin-like growth factors (IGFs), over-stimulating the IGF1R pathway and upregulating Snail expression. In vitro data were recapitulated using in vivo models in which the targeting of ITGA6 prevents PT-resistant EOC dissemination and improves PT-activity, supporting ITGA6 as a promising druggable target for EOC patients.
Synopsis
In EOC ITGA6 is overexpressed and secreted by PT-res cells favoring the formation of a pro-metastatic niche, adhesion and invasion of the mesothelium. ITGA6 inhibition prevents the activation of pro-invasive pathways, leading to decreased metastasis formation and increased response to PT.
PT treatment induces ITGA6 transcription and secretion, both in vitro and in vivo.
ITGA6 confers resistance to PT and higher adhesion and metastatic ability to EOC cells by upregulating Snail protein via IGFR1-Src activation.
Secreted ITGA6 favors EOC metastatic dissemination by modulating IGF1R signaling and Snail expression.
ITGA6 targeting in vivo is feasible, prevents dissemination and improves PT response.
In EOC ITGA6 is overexpressed and secreted by PT-res cells favoring the formation of a pro-metastatic niche, adhesion and invasion of the mesothelium. ITGA6 inhibition prevents the activation of pro-invasive pathways, leading to decreased metastasis formation and increased response to PT.
•Primary intestinal-type adenocarcinomas of the vulva (vPITA) are extremely rare.•To date, in the literature, only 23 cases of vPITA are described.•Radical surgery with inguinofemoral lymph nodes ...dissection should be performed in patients with clinical stage I/II disease.•Adjuvant therapy in high risk patients (nodal involvement) should be considered.
Primary non-squamous cell carcinomas of the vulva are rare entities including various tumor types. Among these, primary vulvar intestinal-type adenocarcinoma (vPITA) is extremely rare. Until 2021, less than twenty-five cases have been reported in the literature.
We report a case of vPITA in a 63 years old woman with a histopathological diagnosis of signet-ring cell intestinal type adenocarcinoma at vulvar biopsy. Accurate clinical and pathological work-up excluded secondary metastatic localization, and vPITA was diagnosed. The patient was treated with radical vulvectomy and bilateral inguinofemoral dissection. Adjuvant chemo-radiotherapy was performed because of a positive lymph node. At 20 months follow-up the patient was alive and free of disease.
The prognosis of this very rare disease is unclear and optimal treatment is not well established. About 40% of clinical early-stage diseases reported in literature had positive inguinal nodes, more than in vulvar squamous cell carcinomas. A proper histopathologic and clinical diagnosis is mandatory to exclude secondary disease and to recommend an adequate treatment.
Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. ...To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated.
A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed.
A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.55-2.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.40-0.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.83-2.25), though not significantly and with a moderate heterogeneity.
The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive ...adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed in women with available HPV testing before treatment. One hundred and forty-eight consecutive women were analyzed. The number of HPV-negative cases was 24 (16.2%). The survival rate was 100% in all participants. The recurrence rate was 7.4% (11 cases, including four invasive lesions (2.7%)). Cox proportional hazards regression showed no difference in recurrence rate between HPV-positive and HPV-negative cases (
= 0.148). HPV genotyping, available for 76 women and including 9/11 recurrences, showed a higher relapse rate for HPV-18 than HPV-45 and HPV-16 (28.5%, 16.6%, and 9.52%,
= 0.046). In addition, 60% and 75% of in situ and invasive recurrences, respectively, were HPV-18 related. The present study showed that most ACs were positive for high-risk HPV, and the recurrence rate was unaffected by HPV status. More extensive studies could help evaluate whether HPV genotyping may be considered for recurrence risk stratification in HPV-positive cases.
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