•Diaphragmatic stripping is associated with acceptable postoperative morbidity.•The procedure offers significant advantage on patients‘ survival.•The survival benefit seems to be independent of the ...stage at diagnosis or adequacy of tumor debulking.
Diaphragmatic stripping is a standard procedure that is performed in a significant proportion of patients undergoing surgical cytoreduction for advanced ovarian cancer. The objective of the present study is to evaluate morbidity and survival outcomes among patients offered diaphragmatic surgery for primary diagnosed optimally resected ovarian cancer.
We conducted a retrospective cohort study, identifying patients that were offered surgery between 2016 and 2021 for primary diagnosis of ovarian cancer. Cases that had diaphragmatic stripping or partial diaphragmatic resection were selected and compared to cases that did not require this procedure. Kaplan-Meier and Cox-regression analyses were applied to evaluate survival outcomes.
Overall, 61 patients that had diaphragmatic stripping were identified. Severe postoperative complications (Clavien-Dindo 3 + ) were noted in 19 patients (31 %). Survival analyses denoted that the stage of the disease at the time of diagnosis, as well as the timing of the surgical procedure (PDS vs IDS) and the completion of tumor debulking were factors that significantly affected the recurrence free and overall survival of patients. Severe postoperative morbidity was a significant predictor of the overall survival. Multivariate cox-regression analysis that was adjusted for the stage of the disease revealed that preoperative pleural effusion, optimal (compared to complete) tumor resection and the occurrence of postoperative complications significantly affected the overall survival of patients. Compared to patients that did not have diaphragmatic surgery, patients submitted to diaphragmatic stripping or resection had improved progression free and overall survival rates, irrespective of the stage of the disease at diagnosis or the adequacy of resection status.
Diaphragmatic surgery is feasible in advanced ovarian cancer patients with acceptable morbidity that mainly refers to postoperative pleural effusion. Its positive impact on patients‘ survival requires further investigation.
Background
An estimated 5–10% of breast and ovarian cancers are due to hereditary causes such as hereditary breast and ovarian cancer (HBOC) syndrome. Medicare, the third-party payer that covers 44 ...million patients in the United States, has implemented a set of clinical criteria to determine coverage for the testing of the
BRCA1
and
BRCA2
genes. These criteria, developed to identify carriers of
BRCA1/2
variants, have not been evaluated in the panel testing era. This study investigated a series of Medicare patients undergoing genetic testing for HBOC to determine the efficacy of genetic testing criteria in identifying patients with hereditary risk.
Methods
This study retrospectively examined de-identified data from a consecutive series of Medicare patients undergoing genetic testing based on personal and family history of breast and gynecologic cancer. Ordering clinicians indicated whether patients did or did not meet established criteria for
BRCA1/2
genetic testing. The genetic test results were compared between the group that met the criteria and the group that did not. Patients in families with known pathogenic (P) or likely pathogenic (LP) variants were excluded from the primary analysis.
Results
Among 4196 unique Medicare patients, the rate of P/LP variants for the patients who met the criteria for genetic testing was 10.5%, and for those who did not, the rate was 9% (
p
= 0.26).
Conclusions
The results of this study indicate that a substantial number of Medicare patients with clinically actionable genetic variants are being missed by current testing criteria and suggest the need for significant expansion and simplification of the testing criteria for HBOC.
Transformation of endometriosis to malignancy is a rare occurrence. Clear cell ovarian cancer and endometrioid ovarian cancer are the two histotypes most consistently linked to endometriosis. The ...exact pathways leading to malignant transformation of endometriosis remain elusive.
A 41-year-old woman presented to our hospital with a ten days history of abdominal pain which was not responsive to medication. Pathological examination revealed an unexpected finding of bilateral endometriosis associated with distinct malignancies: a clear cell carcinoma in the right ovary and a well-differentiated endometrioid carcinoma in the left ovary. Molecular analysis indicated a shared somatic driver mutation in ING1 in the eutopic endometrium and the bilateral ovaries while simultaneously exhibiting specific genetic alterations unique to each carcinoma. Notably, several common mutation sites were also identified, including previously reported common oncogenes (KRAS, PIK3CA, ARID1A). This finding prompts the hypothesis of a possible monoclonal origin of the two tumours.
This case represents an exceedingly rare occurrence of two different histotypes of ovarian endometriosis-associated cancer manifesting simultaneously in bilateral ovaries. Based on genetic analysis, we hypothesize that these malignancies may have a monoclonal origin, providing insights into understanding the different biological mechanisms underlying carcinogenesis.
Ovarian cancer is classified as a gynaecological cancer, but the symptoms present as abdominal and they can be mistaken for those of a bowel condition or bladder problems. Target Ovarian Cancer is ...urging clinicians to recognise the red flags for ovarian cancer, and to never diagnose new-onset irritable bowel syndrome (IBS) or overactive bladder in women over 50 without ruling out ovarian cancer. The symptoms of these are also red flags for ovarian cancer and warrant further investigations. This article covers how to spot these red flags, safety netting and what to do if you suspect a woman's symptoms may be ovarian cancer.
Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for ...early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.
While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for ...novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance. Niraparib was approved regardless of
mutation status, however impact on overall survival is limited. Oliparib was approved for
mutant and
wildtype/homologous recombination deficient patients. This review will focus on current frontline ovarian cancer treatment as well molecularly based approaches to ovarian cancer management.
Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants - 185delAG (c.68_69delAG), 5382insC ...(c.5266dupC), and 6174delT (c.5946delT) - are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings may help inform the discussion around broader access to BRCA genetic testing.
Background
Germline mutations in
BRCA1
and
BRCA2
(
BRCA1/2
) account for the majority of hereditary breast and/or ovarian cancers. Pakistan has one of the highest rates of breast cancer incidence in ...Asia, where
BRCA1/2
small-range mutations account for 17% of early-onset and familial breast/ovarian cancer patients. We report the first study from Pakistan evaluating the prevalence of
BRCA1/2
large genomic rearrangements (LGRs) in breast and/or ovarian cancer patients who do not harbor small-range
BRCA1/2
mutations.
Materials and methods
Both
BRCA1/2
genes were comprehensively screened for LGRs using multiplex ligation-dependent probe amplification in 120
BRCA1/2
small-range mutations negative early-onset or familial breast/ovarian cancer patients from Pakistan (Group 1). The breakpoints were characterized by long-range PCR- and DNA-sequencing analyses. An additional cohort of 445
BRCA1/2
negative high-risk patients (Group 2) was analyzed for the presence of LGRs identified in Group 1.
Results
Three different
BRCA1
LGRs were identified in Group 1 (4/120; 3.3%), two of these were novel. Exon 1–2 deletion was observed in two unrelated patients: an early-onset breast cancer patient and another bilateral breast cancer patient from a hereditary breast cancer (HBC) family. Novel exon 20–21 deletion was detected in a 29-year-old breast cancer patient from a HBC family. Another novel exon 21–24 deletion was identified in a breast-ovarian cancer patient from a hereditary breast and ovarian cancer family. The breakpoints of all deletions were characterized. Screening of the 445 patients in Group 2 for the three LGRs revealed ten additional patients harboring exon 1–2 deletion or exon 21–24 deletion (10/445; 2.2%). No
BRCA2
LGRs were identified.
Conclusions
LGRs in
BRCA1
are found with a considerable frequency in Pakistani breast/ovarian cancer cases. Our findings suggest that
BRCA1
exons 1–2 deletion and exons 21–24 deletion should be included in the recurrent
BRCA1/2
mutations panel for genetic testing of high-risk Pakistani breast/ovarian cancer patients.
Recent molecular genetic findings on endometriosis and normal endometrium suggest a modified model in which circulating epithelial progenitor or stem cells intended to regenerate uterine endometrium ...after menstruation may become overreactive and trapped outside the uterus. These trapped epithelium-committed progenitor cells form nascent glands through clonal expansion and recruit polyclonal stromal cells, leading to the establishment of deep infiltrating endometriosis. Once formed, the ectopic tissue becomes subject to immune surveillance, resulting in chronic inflammation. The inflammatory response orchestrated by nuclear factor-κB signaling is exacerbated by aberrations in the estrogen receptor-β and progesterone receptor pathways, which are also affected by local inflammation, forming a dysregulated inflammation-hormonal loop. Glandular epithelium within endometriotic tissue harbors cancer-associated mutations that are frequently detected in endometriosis-related ovarian cancers. In this review, we summarize recent advances that have illuminated the origin and pathogenesis of endometriosis and have provided new avenues for research that promise to improve the early diagnosis and management of endometriosis.
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