Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

COH outcomes in breast cancer patients for fertility preservation: a comparison with the expected response by age

PurposeBreast cancer is the most common cancer diagnosed during childbearing age, and fertility preservation is becoming increasingly more essential. However, recent studies indicate a possible poorer response to controlled ovarian hyperstimulation (COH) in cancer patients than in non-cancer controls and a negative impact of BRCA mutations on female fertility. This study aims to evaluate ovarian response and the number of mature oocytes (MII) vitrified in women with breast cancer, with or without BRCA mutation, comparing them to the expected response according to an age-related nomogram.MethodsThis is a retrospective observational study involving sixty-one breast cancer patients who underwent COH for oocyte cryopreservation. The age-specific nomogram was built using 3871 patients who underwent COH due to oocyte donation, fertility preservation for non-medical reasons, or FIVET for male factor exclusively.ResultsThe mean number of oocytes retrieved was 13.03, whereas the mean number of MII oocytes was 10.00. After the application of the z-score, no statistically significant differences were found compared with the expected response in the general population, neither by dividing patients according to the presence or absence of BRCA mutation nor according to the phase in which they initiated stimulation.ConclusionThe results obtained do not support the notion of a negative impact of the BRCA mutation on the ovarian response of women with breast cancer. Women with breast cancer undergoing COH for fertility preservation can expect the ovarian response predicted for their age.     

彩色多普勒超声诊断卵巢肿瘤蒂扭转的临床意义

目的：探讨彩色多普勒超声诊断卵巢肿瘤蒂扭转的临床意义。方法方便选取2012―2015年该院收治的58例疑似卵巢肿瘤蒂扭转患者作为观察目标，入选病例均应用彩色多普勒超声进行检查，并将检查结果同术后病理检查结果进行比较。结果58例患者中，术后病理证实卵巢肿瘤蒂扭转者51例，彩色多普勒超声共确诊49例，检查准确率为96.1%；囊壁增厚、腹腔或盆腔积液、可见混合型团块是卵巢肿瘤蒂扭转的主要彩超表现。结论卵巢肿瘤蒂扭转应用彩色多普勒超声诊断，可显著提高诊断准确率，具有积极的临床使用和推广价值。     

A rare case of a periorbital respiratory (choristomatous) cyst

Respiratory cysts are benign lesions lined by normal respiratory epithelium. There are few reported cases localized to the orbit, while those of the eyelid are exceedingly rare. Respiratory cysts usually arise either from a non‐hereditary congenital malformation, where they are distinguished as choristomatous, or from trauma. Here, we report a case of a 53‐year‐old man who presented with a large right lower eyelid cyst that was histopathologically diagnosed as a respiratory cyst.     

Symptomatic perineural cyst after spontaneous subarachnoid hemorrhage: A case report

Rationale:Tarlov or perineurial cysts are nerve root lesions often found in the sacral region. Most perineural cysts (PCs) remain asymptomatic throughout a patient''s life. While their pathogenesis is still unclear, trauma resulting in hemorrhaging into subarachnoid space has been put forward as a possible cause of these cysts. Recently, we worked with a patient experiencing symptomatic PCs after spontaneous subarachnoid hemorrhage.Patient concerns:A 45-year-old man had a coil embolization procedure performed after being diagnosed with a subarachnoid hemorrhage from a ruptured anterior communicating artery. His symptoms were relieved after the procedure, but 7 days later he reported worsening pain in the left perineal area. The pain was intermittent at its onset and exacerbated by sitting, walking, and coughing.Diagnoses:Two weeks after the embolization procedure, a lumbar spine MRI revealed 2 PCs at the S1 and S2 level affecting the left S2 root with high signal intensity in T2 and T1 images, suggestive of bleeding within the cyst.Interventions:We operated using a posterior approach. Cyst fenestration was done after S1 laminectomy. We aspirated approximately 1 cc of old blood.Outcomes:His pain was relieved immediately after cyst removal and no neurologic deterioration occurred during the postoperative period.Lessons:Subarachnoid hemorrhage can be the source of the development of pain from asymptomatic PCs, making them symptomatic. Surgical extirpation is 1 treatment option for these symptomatic PCs.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

外泌体在卵巢癌诊疗及转移中的研究进展

卵巢癌是妇科肿瘤领域内的一个热点主题。该种恶性肿瘤疾病的发病率高且隐匿,缺乏有效的早期发现及时诊断并治疗的方式,病情容易加重发生远处转移。因此罹患卵巢癌的女性5年生存率比较低。外泌体属于一类典型的囊性泡样的小体,参与肿瘤的发病及转移机制且在肿瘤疾病的治疗中起着重要作用。本篇综述主要介绍癌细胞外泌体在卵巢恶性肿瘤疾病的诊断、转移及治疗中的研究现状。     

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Transitional care for patients with surgical pediatric hepatobiliary disease: Choledochal cysts and biliary atresia

Choledochal cysts (CDCs) and biliary atresia (BA) are rare pediatric hepatobiliary anomalies that require surgical intervention due to increased risk of malignancy and liver failure, respectively. The underlying disease and operative procedures place patients at risk for long‐term complications, which may continue to affect them into adulthood. Lack of a transitional care model in the health‐care system potentiates the challenges they will face following aging out of their pediatric providers' care. We sought to elucidate the long‐term complications and challenges patients with CDCs and BA face, review the current literature regarding transitioning care, and propose guidelines aiding adult providers in continued care and surveillance of these patients. A literature review was performed to assess short‐term and long‐term complications after surgery and the current standards for transitioning care in patients with a history of CDCs and BA. While transitional programs exist for patients with other gastrointestinal diseases, there are few that focus on CDCs or BA. Generally, authors encourage medical record transmission from pediatric to adult providers, ensuring accuracy of information and compliance with treatment plans. Patients with CDCs are at risk for developing biliary malignancies, cholangitis, and anastomotic strictures after resection. Patients with BA develop progressive liver failure, necessitating transplantation. There are no consensus guidelines regarding timing of follow up for these patients. Based on the best available evidence, we propose a schema for long‐term surveillance.