Breast cancer screening: clinical, radiologic, and biochemical.

Breast cancer screening is a highly complex and more recently a controversial topic. Conventional screening includes breast self-examination, clinical breast examination, and screening mammography. Several newer imaging modalities have been introduced into the screening armamentarium including breast magnetic resonance imaging and whole-breast automated ultrasound. Novel imaging techniques like positron emission mammography are currently under clinical investigation in the hopes of improving the sensitivity of breast cancer screening. In addition, the development of biochemical assays, which employ minimally invasive sampling are also promising.

Breast Cancer following Augmentation Mammaplasty: A Case-Control Study.

BACKGROUND: The purpose of this study was to determine whether augmentation mammaplasty, implant type, and implant location affect breast cancer detection, stage, and treatment. METHODS: An institutional case-control study was performed of patients with prior breast augmentation undergoing breast cancer treatment from 2000 to 2013. Controls were propensity matched and randomized, and data were retrospectively reviewed. RESULTS: Forty-eight cases and 302 controls were analyzed. Palpable lesions were detected at a smaller size in augmentation patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients were detected by screening mammography (77.8 percent of cases versus 90.7 percent of controls; p = 0.010). Patients with implants were more likely to undergo an excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001), rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p < 0.001). Earlier staging in augmented patients approached but did not reach statistical significance (p = 0.073). Augmented patients had higher mastectomy rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type nor anatomic location affected method of diagnosis, stage, or treatment. CONCLUSIONS: Palpable detection of breast cancer is more likely at a smaller size in augmented patients, yet it is less likely on screening mammography than in controls. Augmentation breast cancer patients have a comparable disease stage and are more likely to undergo mastectomy rather than lumpectomy. Both silicone and saline implants, whether placed submuscularly or subglandularly, have comparable effects on breast imaging, biopsy modality, and surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The role of interleukin 1 in growth and metastasis of human cancer xenografts.

BACKGROUND: Interleukin 1 (IL-1) is a pluripotent cytokine that promotes angiogenesis, tumor growth, and metastasis in experimental models; its presence in some human cancers is associated with aggressive tumor biology. The purpose of these studies was to characterize the role of IL-1 in human cancers and determine if inhibition of IL-1 via its receptor antagonist, IL-1Ra, alters tumor growth and metastatic potential. METHODS: IL-1 mRNA or protein levels were determined in clinical tumor samples, cancer cell lines, and xenografts using quantitative reverse transcription-PCR or ELISA. Biological activity of tumor-derived IL-1 protein was shown via induction of permeability across endothelial cell monolayers. The effects of recombinant IL-1Ra on tumor lines in culture (cell proliferation and IL-8 secretion) and in xenograft models (tumor growth, metastatic potential, and intratumoral levels of IL-8 and VEGF) were characterized. The effects of IL-1Ra-mediated regression of xenograft growth on angiogenic proteins (IL-8 and VEGF) were evaluated in an IL-1-producing melanoma (SMEL) xenograft model. RESULTS: IL-1 mRNA was highly expressed in more than half of all tested metastatic human tumor specimens including non-small-cell lung carcinoma, colorectal adenocarcinoma, and melanoma tumor samples. Constitutive IL-1 mRNA expression was identified in several cancer cell lines; tumor supernatant from these cell lines produced a significant increase in endothelial cell monolayer permeability, a hallmark event in early angiogenesis, in an IL-1-dependent manner. Moreover, systemic recombinant IL-1Ra resulted in significant inhibition of xenograft growth and neovessel density of IL-1-producing, but not non-IL-1-producing, tumor cell lines. Subsequent analysis of SMEL, a melanoma cell line with constitutive IL-1 production, showed that neither exogenous IL-1 nor IL-1Ra altered tumor cell proliferation rates in vitro. Gene expression analyses of IL-1Ra-treated SMEL xenografts showed a >3-fold down-regulation of 100 genes compared with control including a marked down-regulation of IL-8 and VEGF. CONCLUSIONS: These data show that the IL-1 gene is frequently expressed in metastases from patients with several types of human cancers. IL-1Ra inhibits xenograft growth in IL-1-producing tumors but has no direct antiproliferative effects in vitro; decreased tumor levels of IL-8 and VEGF may be an early surrogate of IL-1Ra-mediated antitumor activity. IL-1Ra may have a role alone or with other agents in the treatment of human cancers.

Effect of interleukin 1 receptor antagonist gene transduction on human melanoma xenografts in nude mice.

Interleukin (IL)-1 is a pleiotropic inflammatory cytokine that promotes angiogenesis and enhances tumor growth and metastases. We evaluated the effects of IL-1 receptor antagonist (IL-1ra) on tumor growth and metastases in human melanoma xenografts. We selected two human melanoma lines (SMEL and PMEL) with differential (high versus low, respectively) constitutive production of IL-1 by ELISA. The IL-1ra gene was isolated from monocyte RNA by PCR and retrovirally transduced into SMEL and PMEL. In vitro cell proliferation was evaluated using a WST-1 assay. Athymic nude mice received s.c. or i.v. injection with parental, vector-transduced, or IL-1ra-transduced melanoma cells, and tumor growth, lung metastases, and histology were characterized. IL-1 was produced by SMEL in vitro and ex vivo (117 and 67 pg/ml/10(6) cells/24 h, respectively), but not by PMEL (15 and 0 pg/ml/10(6) cells/24 h, respectively). Neither made IL-1ra natively. Gene-transduced cell lines secreted >1000 pg/ml/10(6) cells/24 h of IL-1ra by ELISA. In vitro proliferation of each parental cell line was comparable to the proliferation rate of each transduced cell line. IL-1ra-transduced SMEL (SMEL/IL-1ra) showed significantly slower tumor growth compared with null-transduced and parental cell lines (P < 0.001, ANOVA-Bonferroni/Dunn). There was no difference in growth rates between PMEL and IL-1ra-transduced PMEL (PMEL/IL-1ra). A mixing study of SMEL and SMEL/IL-1ra showed significant inhibition of tumor growth at various ratios (P < 0.001, ANOVA-Bonferroni/Dunn). There were significantly fewer lung metastases with SMEL/IL-1ra versus SMEL (P < 0.002). IL-1ra decreases in vivo growth and metastatic potential of a human melanoma xenograft that constitutively secretes IL-1. This effect may be exploitable using clinically available IL-1ra for the treatment of human cancers.

Giant juvenile fibroadenoma: a systematic review with diagnostic and treatment recommendations.

BACKGROUND: Currently, there is a lack of clear guidelines regarding evaluation and management of giant juvenile fibroadenomas. The purpose of this study was to conduct a systematic review of giant juvenile fibroadenomas and to evaluate the most common diagnostic and therapeutic modalities. METHODS: A systematic literature search of PubMed and MEDLINE databases was conducted in February 2014 to identify articles related to giant juvenile fibroadenomas. Pooled outcomes are reported. RESULTS: Fifty-two articles (153 patients) met inclusion criteria. Mean age was 16.7 years old, with a mean lesion size of 11.2 cm. Most patients (86%) presented with a single breast mass. Imaging modalities included ultrasound in 72.5% and mammography in 26.1% of cases. Tissue diagnosis was obtained using a core needle biopsy in 18.3% of cases, fine-needle aspiration (FNA) in 25.5%, and excisional biopsy in 11.1% of patients. Surgical treatment was implemented in 98.7% of patients (mean time to treatment of 9.5 months, range, 3 days to 7 years). Surgical intervention included excision in all cases, of which four were mastectomies. Breast reconstruction was completed in 17.6% of cases. There were no postoperative complications. CONCLUSIONS: Diagnosis and treatment of giant juvenile fibroadenoma is heterogeneous. There is a paucity of data to support observation and non-operative treatment. The most common diagnostic modalities include core needle or excisional biopsy. The mainstay of treatment is complete excision with an emphasis on preserving the developing breast parenchyma and nipple areolar complex. Breast reconstruction is uncommon, but may be necessary in certain cases.

Treatment of patients with unresectable primary hepatic malignancies using hyperthermic isolated hepatic perfusion.

Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Isolated hepatic perfusion (IHP) is a regional treatment technique that isolates the organ to allow delivery of high-dose chemotherapy, biological agents, and hyperthermia directly to unresectable cancers confined to the liver. This study presents our experience using IHP with melphalan with or without tumor necrosis factor (TNF) to treat patients with hepatocellular carcinoma or adenocarcinoma of hepatobiliary origin. Nine patients with unresectable primary hepatic malignancies underwent a 60-minute IHP with 1.5 mg/kg melphalan with or without 1.0 mg TNF. Four patients failed one or more previous treatment regimens, and the mean hepatic replacement by tumor was 41% (range 10% to 75%). Patients were monitored for response, toxicity, time to recurrence, and survival. Six (67%) of nine patients experienced greater than 50% regression of tumor by objective radiographic imaging and an additional patient had a 45% reduction in tumor burden. Mean time to progression was 7.7 months for those who responded to treatment. Patients who had a response to therapy had an average overall survival of 16.3 months. IHP can be performed safely and has significant antitumor activity in patients with unresectable primary hepatic malignancies. Hepatic progression continues to be the dominant factor influencing survival in this group of patients.

Nipple-sparing mastectomy for prophylactic and therapeutic indications.

BACKGROUND: Nipple-sparing mastectomy remains controversial and its adoption has been slow because of oncologic and surgical concerns. METHODS: A retrospective study evaluated all nipple-sparing mastectomies performed at a single institution for therapeutic or prophylactic indications for which records were available. RESULTS: Between 1989 and 2010, 162 nipple-sparing mastectomies were performed in 101 women. Forty-nine (30 percent) were performed for therapeutic purposes on 48 patients. A subareolar biopsy specimen was taken in 39 of 49 breasts (80 percent); four (10 percent) revealed ductal carcinoma in situ, and the nipple or nipple-areola complex was later removed. Four of 49 breasts (8 percent) in the therapeutic group had ischemic complications involving the nipple-areola complex, one of which (2 percent) was excised. With a mean follow-up of 2 years 6 months (range, 5 months to 9 years 5 months), no patients developed cancer in the nipple-areola complex. The remaining 113 mastectomies (70 percent) were performed prophylactically on 80 patients. The subareolar tissue was biopsied in 80 breasts (71 percent). One biopsy revealed lobular carcinoma in situ; none had ductal carcinoma in situ or invasive cancer. Two nipple-areola complexes (1.8 percent) were ischemic and excised. With a mean follow-up of 3 years 7 months (range, 5 months to 20 years 6 months), no patients developed new primary cancers in the nipple-areola complex. CONCLUSIONS: Nipple-sparing mastectomy can be safe in properly selected patients. A subareolar biopsy can effectively identify nipple-areola complexes that may harbor cancerous cells. Ischemic complications resulting in nipple loss can be minimized, and long-term follow-up suggests that this technique deserves further investigation in properly selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Interferon gamma-inducible protein 10 selectively inhibits proliferation and induces apoptosis in endothelial cells.

BACKGROUND: Interferon gamma-inducible protein 10 (IP-10) has antitumor effects in various murine models. The IP-10 receptor has two distinct splice variants, CXCR3A and CXCR3B, that have paradoxical effects after ligand-receptor interaction. METHODS: To characterize the putative antiangiogenic effects of IP-10, we measured proliferation rates and apoptosis in human umbilical vein endothelial cells (HUVECs), fibroblasts, and A375 melanoma or WIDR adenocarcinoma cell lines after exposure to the recombinant protein. CXCR3A (activating) and CXCR3B (inhibitory/proapoptotic) messenger RNA (mRNA) expression levels in fibroblasts, 2 human tumor cell lines, T lymphocytes, and HUVECs of varying cell densities were characterized. RESULTS: IP-10 resulted in dose-dependent and selective inhibition of proliferation and countered the proliferative effects of vascular endothelial growth factor in HUVECs but did not affect fibroblasts or 2 human tumor cell lines. In addition, IP-10 resulted in potent and selective induction of apoptosis in HUVECS but had no effect on fibroblasts or A375 melanoma. Confluent HUVECs had a predominance of mRNA for the CXCR3B splice variant by reverse transcriptase-polymerase chain reaction, and the ratio of CXCR3B to CXCR3A mRNA was >40 in HUVECs, compared with

Regional treatment options for patients with ocular melanoma metastatic to the liver.

Ocular melanoma is the most common primary ocular malignancy and has a significant predilection for metastasis to the liver. More than 40% of patients have hepatic metastases present at initial diagnosis, and the liver becomes involved in up to 95% of individuals who develop metastatic disease. The median survival of patients after diagnosis of liver metastasis ranges from 2 to 7 months. Metastatic disease localized to the liver has proven to be resistant to most available chemotherapy and immunotherapy regimens. Recognition of the grave prognosis associated with liver metastasis from ocular melanoma has led to the evaluation of new regional treatment modalities primarily designed to control tumor progression in the liver, including hepatic arterial chemotherapy, hepatic artery chemoembolization, regional immunotherapy, isolated hepatic perfusion, and percutaneous hepatic perfusion. This article reviews the efficacy, outcomes, and morbidities of the multiple locoregional therapies available today.

Pseudo-Meigs' syndrome secondary to isolated colorectal metastasis to ovary: a case report and review of the literature.

INTRODUCTION: Pseudo-Meigs' syndrome is a syndrome that includes hydrothorax and/or ascites secondary to ovarian neoplasms other than benign primary tumors. Gastrointestinal malignancies, including colorectal or gastric adenocarcinoma, are rare etiologies for this syndrome. CASE REPORT: In this report, we present the case of a 49-year-old woman with metastatic colon cancer who acutely developed a massive pleural effusion and ascites coincident with a rapidly enlarging adnexal mass and a rising CA-125 level. DISCUSSION: Seven cases of pseudo-Meigs' syndrome secondary to gastrointestinal primaries have been reported to date. This case highlights the difficulty in discerning the diagnosis of pseudo-Meigs' syndrome from that of disseminated colorectal cancer or a new primary ovarian neoplasm and the importance in making the distinction to initiate appropriate therapy.