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1.
J Surg Case Rep ; 2023(10): rjad477, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37846417

ABSTRACT

Cholecystocutaneous fistulas (CCFs) are rare complications of gallbladder disease, wherein chronic inflammation leads the formation of an anomalous fistulous tract between the gallbladder and skin. Widespread availability of imaging modalities and timely access to surgical expertise has caused a marked decline in their incidence. Consequently, there is notable heterogeneity in management approaches to this disease entity, and guidance regarding the best, evidence-based treatment strategy is lacking. Most patients are definitively managed with cholecystectomy and en bloc excision of the adjoining fistula tract. However, there is no guidance on how to manage patients whose comorbidities preclude them from operative intervention. We provide the first report chronicling the stepwise development of a CCF in a 75-year-old woman, complete with pictorial documentation of its evolution. Furthermore, we present the inaugural account of a practical, safe approach to the long-term conservative management of CCFs in patients in whom surgical or endoscopic intervention is prohibitive.

2.
Cancers (Basel) ; 14(8)2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35454786

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy with over 80% of cases already disseminated at diagnosis and facing a dismal five-year survival rate of 35%. EOC cells often spread to the greater omentum where they take-up cholesterol. Excessive amounts of cholesterol can be cytocidal, suggesting that cholesterol efflux through transporters may be important to maintain homeostasis, and this may explain the observation that high expression of the ATP-binding cassette A1 (ABCA1) cholesterol transporter has been associated with poor outcome in EOC patients. METHODS: ABCA1 expression was silenced in EOC cells to investigate the effect of inhibiting cholesterol efflux on EOC biology through growth and migration assays, three-dimensional spheroid culture and cholesterol quantification. RESULTS: ABCA1 suppression significantly reduced the growth, motility and colony formation of EOC cell lines as well as the size of EOC spheroids, whilst stimulating expression of ABCA1 reversed these effects. In serous EOC cells, ABCA1 suppression induced accumulation of cholesterol. Lowering cholesterol levels using methyl-B-cyclodextrin rescued the effect of ABCA1 suppression, restoring EOC growth. Furthermore, we identified FDA-approved agents that induced cholesterol accumulation and elicited cytocidal effects in EOC cells. CONCLUSIONS: Our data demonstrate the importance of ABCA1 in maintaining cholesterol balance and malignant properties in EOC cells, highlighting its potential as a therapeutic target for this disease.

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