Malignant ascites (MA) is a sign of advanced cancer and poor prognosis. MA can result in impairment in quality of life (QOL) and significant symptoms. As a supportive treatment, ascites can be drained by paracentesis (PC), percutaneously implanted catheters (tunneled, untunneled, central venous catheters), or peritoneal ports, or peritoneovenous shunts. The aim of this study was to evaluate the effectiveness, safety, and patient-reported outcomes (PRO) of different drainage methods for the management of MA. A systematic review of the literature was performed, and 32 original articles met the inclusion criteria. Patients selected for permanent drain insertion demonstrated symptoms related to MA and had undergone repeated PC. The primary focus of the reviewed articles was procedural safety issues. The rate of technical success of drainage device installation was 100%. Most patients experienced improvements in symptom control after ascites drainage. When analyzed together, 19.7% (255/1297) of patients experienced any complication and 6.2% (81/1297) experienced serious adverse events during MA drainage. Complications were reported for every drainage method; however, the least occurred after PC or central venous catheter, while the most serious occurred after peritoneovenous shunts. Adverse events were as follows: catheter obstruction: 4.4%, infection: 4.1%, leakage: 3.5%, catheter dislodgment: 2.3%, hypotension: 0.6%, injuries during device insertion: 0.6%, renal impairment: 0.5%, electrolyte imbalance: 0.2%, other: 3.6%. PRO and QOL endpoints were available for 12 studies. When PRO were measured using an interview, a significant improvement in symptom control and QOL was reported in almost all patients. Once standardized questionnaires were used, improvements in symptomatic scores and role functioning were observed. Deterioration was observed in cognitive and emotional subscales. MA drainage is a safe and effective method to control symptoms associated with ascites, and should be perceived as a supportive care, that can be applied for those who need it at any time of their cancer trajectory. Patient selection should be performed using a thorough assessment of symptoms and QOL, and should not be delayed.

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Constitutional loss-of-function pathogenic variants in the tumor suppressor genes BRCA1 and BRCA2 are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the BRCA1/2 pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the BRCA1/2 and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the BRCA1/2 pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs*74) and c.3700_3704del (p.Val1234Glnfs*8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with NBN and CHEK2 reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in APC, 1/333 in ATM, 2/333 in BLM, 1/333 in BRIP1, 1/333 in MRE11A, 2/333 in PALB2, 1/333 in RAD50, and 1/333 in RAD51C, accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals.

Only approximately 50% of all familial breast cancers can be explained by known genetic factors, including mutations in BRCA1 and BRCA2. One of the most extensively studied candidates for breast and/or ovarian cancer susceptibility is BARD1. Although it was suggested that large mutations may contribute substantially to the deleterious variants of BARD1, no systematic study of the large mutations in BARD1 has been performed. To further elucidate the role of large mutations in BARD1, we designed a multiplex ligation-dependent probe amplification (MLPA) assay and performed an analysis of 504 women with a familial breast and/or ovarian cancer and 313 patients with ovarian cancer. The investigation did not reveal any large mutations in the BARD1 gene. Although the analysis was not focused on identification of small mutations, we detected seven deleterious or potentially deleterious point mutations, which contribute substantially to the total number of BARD1 mutations detected so far. In conclusion, although we cannot exclude the presence of large mutations in BARD1, our study indicates that such mutations do not contribute substantially to the risk of breast and/or ovarian cancer. However, it has to be noted that our results may be specific to the Polish population.

Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. We investigated the expression of several druggable targets (phospho-S6 ribosomal protein, PTEN, PDGFR-α, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6, was tested in patient-derived xenograft (PDX) leiomyosarcoma models. In uterine sarcomas and STUMPs, S6 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade ( = 0.001) and recurrence ( = 0.019), as shown by logistic regression. In addition, p-S6 correlated with shorter progression-free survival ( = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6 expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6 in response prediction to PI3K/mTOR inhibition. Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6 expression is a potential predictive biomarker for response to treatment. .

The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9 %) mutations, where 65 % (n = 13) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35 %) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n = 5/12; 41 %) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65 %) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered.

The endometrial cancer (EC)-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-EN24), was developed and validated in one study. We independently validated and assessed the psychometric properties of the instrument. Two hundred and eight women with EC before surgery, during adjuvant treatment and follow-up; in three different cancer centres completed the EORTC QLQ-C30 and the EN24. The questionnaire's completion rate was 100%, except sexuality items, that were answered by 35% of patients.All item-scale correlations for the multi-item scales exceeded the .4 criterion and correlated well with their own scale, while correlations with the other scales were low.The internal consistency of all multi-item scales were satisfactory (Cronbach's alpha coefficients ranging from .77 to .97). Discriminance for single-item scales was low. The QLQ-EN24 module discriminated well between clinically different patients, and there were no differences in quality of life questionnaire scales between patients with body mass index ≤30 when compared to those with >30. This validation study supports the reliability, as well as convergent and divergent validity of the EORTC QLQ-EN24. The module is a useful instrument for the assessment of QOL in patients with EC. However, data concerning sexuality should be interpreted with caution. K E Y W O R D Sendometrial cancer, quality of life, questionnaire, validation

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