Contrast-enhanced mammography for surveillance in women with a personal history of breast cancer.

PURPOSE: Women with a personal history of breast cancer have an increased risk of subsequent breast malignancy and may benefit from more sensitive surveillance than conventional mammography (MG). We previously reported outcomes for first surveillance episode using contrast-enhanced mammography (CEM), demonstrating higher sensitivity and comparable specificity to MG. We now report CEM performance for subsequent surveillance. METHODS: A retrospective study of 1,190 women in an Australian hospital setting undergoing annual surveillance following initial surveillance CEM between June 2016 and December 2022. Outcome measures were recall rate, cancer detection rate, contribution of contrast to recalls, false positive rate, interval cancer rate and characteristics of surveillance detected and interval cancers. RESULTS: 2,592 incident surveillance episodes were analysed, of which 93% involved contrast-based imaging. Of 116 (4.5%) recall episodes, 40/116 (34%) recalls were malignant (27 invasive; 13 ductal carcinoma in situ), totalling 15.4 cancers per 1000 surveillance episodes. 55/116 (47%) recalls were contrast-directed including 17/40 (43%) true positive recalls. Tumour features were similar for contrast-directed recalls and other diagnoses. 8/9 (89%) of contrast-directed invasive recalls were Grade 2-3, and 5/9 (56%) were triple negative breast cancers. There were two symptomatic interval cancers (0.8 per 1000 surveillance episodes, program sensitivity 96%). CONCLUSION: Routine use of CEM in surveillance of women with PHBC led to an increase in the detection of clinically significant malignant lesions, with a low interval cancer rate compared to previous published series. Compared to mammographic surveillance, contrast-enhanced mammography increases the sensitivity of surveillance programs for women with PHBC.

Contrast enhanced mammography in breast cancer surveillance.

PURPOSE: Mammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US. METHODS: A retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period. RESULTS: 73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had 'minimal signs' with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented. CONCLUSION: Compared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Evaluation and management of rectal bleeding in pregnancy.

Rectal bleeding occurs in about 40% of pregnant women, and is predominantly attributed to benign perianal pathology (haemorrhoids or anal fissures). More sinister causes of rectal bleeding may be heralded by key red flag clinical and biochemical features. These features should be evaluated in all women with rectal bleeding. Imaging investigations or flexible sigmoidoscopy may be warranted. The latter can be performed safely by experienced operators in pregnant women. Women with evidence of haemodynamic compromise, elevated inflammatory markers, significant anaemia, signs of intestinal obstruction or compromise to the fetus should be evaluated urgently. Providers must be mindful of the changes in normal ranges for common haematological and biochemical parameters in pregnancy compared with the non-pregnant state. Faecal calprotectin is an established tool for identification of intestinal inflammation and is valid in pregnancy. An elevated faecal calprotectin level (≥ 50 µg/g) signifies a need for further diagnostic evaluation. Inflammatory bowel disease may present initially, or with worsening disease activity, in pregnancy. Expedient diagnosis with the use of faecal calprotectin, sigmoidoscopy with or without intestinal ultrasound, exclusion of alternative or compounding infective aetiologies, and institution of appropriate therapy are critical. Medical therapies for management of inflammatory bowel disease can be safely instituted in pregnancy. Colorectal cancer incidence is increasing in younger age groups, but fortunately remains rare. When diagnosed in pregnancy, colorectal cancer can be successfully and safely managed with a collaborative multidisciplinary team approach. Early diagnosis is key to optimising outcomes.

Prospective evaluation of prognostic indicators for early recurrence of cutaneous melanoma.

The majority of melanomas are thin lesions with an excellent prognosis; however, significant tumor heterogeneity exists, and a small percentage of patients with early-stage disease may progress to metastatic recurrence. This study aimed to assess whether prognostic factors previously shown to be significant in predicting stage I and stage II melanoma recurrence were consistent in a large prospectively collected patient cohort, and to identify novel prognostic factors associated with early recurrence to inform follow-up protocols. There were 1029 patients with stage I and stage II melanoma included in the analysis, of whom 123 developed a recurrence during follow-up (median 2.13 years). Multivariable analysis identified ulceration, presence of mitoses, Clark level, presence of lymphovascular invasion, and a history of autoimmune disease as factors independently associated with recurrence. These data identified patients with stage I-II melanoma with very low-risk for recurrence: no ulceration, zero mitoses, a low Clark level, no lymphovascular invasion, and possibly no history of autoimmune disease. These patients do not require intensive follow-up: 12 monthly reviews and full skin checks may be appropriate. Ongoing research into prognostic factors for recurrence in early-stage melanoma is important.

Epithelial-mesenchymal transition and nuclear ß-catenin induced by conditional intestinal disruption of Cdh1 with Apc is E-cadherin EC1 domain dependent.

Two important protein-protein interactions establish E-cadherin (Cdh1) in the adhesion complex; homophilic binding via the extra-cellular (EC1) domain and cytoplasmic tail binding to ß-catenin. Here, we evaluate whether E-cadherin binding can inhibit ß-catenin when there is loss of Adenomatous polyposis coli (APC) from the ß-catenin destruction complex. Combined conditional loss of Cdh1 and Apc were generated in the intestine, intestinal adenoma and adenoma organoids. Combined intestinal disruption (Cdh1fl/flApcfl/flVil-CreERT2) resulted in lethality, breakdown of the intestinal barrier, increased Wnt target gene expression and increased nuclear ß-catenin localization, suggesting that E-cadherin inhibits ß-catenin. Combination with an intestinal stem cell Cre (Lgr5CreERT2) resulted in ApcΔ/Δ recombination and adenoma, but intact Cdh1fl/fl alleles. Cultured ApcΔ/ΔCdh1fl/fl adenoma cells infected with adenovirus-Cre induced Cdh1fl/fl recombination (Cdh1Δ/Δ), disruption of organoid morphology, nuclear ß-catenin localization, and cells with an epithelial-mesenchymal phenotype. Complementation with adenovirus expressing wild-type Cdh1 (Cdh1-WT) rescued adhesion and ß-catenin membrane localization, yet an EC1 specific double mutant defective in homophilic adhesion (Cdh1-MutW2A, S78W) did not. These data suggest that E-cadherin inhibits ß-catenin in the context of disruption of the APC-destruction complex, and that this function is also EC1 domain dependent. Both binding functions of E-cadherin may be required for its tumour suppressor activity.