Multiplex Gene Profiling of Cell-Free DNA in Patients With Metastatic Melanoma for Monitoring Disease.

Purpose: Hotspot blood cell-free DNA (cfDNA) biomarker assays have limited utility in profiling tumor heterogeneity and burden and in capturing regional metastasis with low disease burden in patients with melanoma. We investigated the utility of a sensitive 54-cancer gene digital next-generation sequencing approach targeting blood cfDNA single nucleotide variants (SNVs) and copy number amplification for monitoring disease in patients with melanoma with regional or distant organ metastasis (DOM).

Patients And Methods: A total of 142 blood samples were evaluated by digital next-generation sequencing across two patient cohorts.

Impact of Laparoscopic Adrenalectomy on Overall Survival in Patients with Nonmetastatic Adrenocortical Carcinoma.

Background: Appropriate use of laparoscopic adrenalectomy (LA) for adrenocortical carcinoma (ACC) remains controversial because complete resection with negative margins is the best chance for potential cure. This study compared the oncologic outcomes and overall survival (OS) of LA and open adrenalectomy (OA) for ACC.

Study Design: A retrospective analysis of the National Cancer Data Base (NCDB) between 2010 and 2014 identified 423 European Network for the Study of Adrenal Tumors (ENSAT) stage I to III ACC patients who had LA (n = 137) or OA (n = 286).

Impact of Completion Lymph Node Dissection on Patients with Positive Sentinel Lymph Node Biopsy in Melanoma.

Background: Whether patients with positive SLNB should undergo complete lymph node dissection (CLND) is an important unanswered clinical question.

Study Design: Patients diagnosed with positive SLNB at a melanoma referral center from 1991 to 2013 were studied. Outcomes of patients who underwent CLND were compared with those who did not undergo immediate CLND (observation [OBS] group).

Predictors and Survival Impact of False-Negative Sentinel Nodes in Melanoma.

Background: The status of the sentinel lymph node in melanoma is an important prognostic factor. The clinical predictors and implications of false-negative (FN) biopsy remain debatable.

Methods: We compared patients with positive sentinel lymph node biopsy (SNB) [true positive (TP)] and negative SNB with and without regional recurrence [FN, true negative (TN)] from our prospective institutional database.

Adrenalectomy for Metastatic Melanoma: Current Role in the Age of Nonsurgical Treatments.

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014.

Attitudes and Perceptions of Surgical Oncology Fellows on ACGME Accreditation and the Complex General Surgical Oncology Certification.

Background: With the first qualifying examination administered September 15, 2014, complex general surgical oncology (CGSO) is now a board-certified specialty. We aimed to assess the attitudes and perceptions of current and future surgical oncology fellows regarding the recently instituted Accreditation Council for Graduate Medical Education (ACGME) accreditation.

Methods: A 29-question anonymous survey was distributed to fellows in surgical oncology fellowship programs and applicants interviewing at our fellowship program.

Sentinel lymph node biopsy and nodal ultrastaging in colorectal cancer.

The tumor status of the regional lymph nodes is the most important prognostic indicator in colorectal cancer (CRC), as it is in other solid tumors. Sentinel lymph node biopsy (SLNB), which has profoundly impacted the treatment of melanoma and breast cancer, has been applied in CRC in an attempt to improve nodal staging accuracy. The challenge lies in identifying patients who have tumor-negative nodes but are at high risk of regional or distant failure and therefore may benefit from adjuvant chemotherapy.

Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome.

Melanoma brain metastasis (MBM) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell-surface glycoprotein CD44 variants during melanoma progression to MBM. High expression of CD44 splicing variant 6 (CD44v6) in primary melanoma (PRM) and regional lymph node metastases from AJCC Stage IIIC patients significantly predicts MBM development.

Management of papillary lesions of the breast: can larger core needle biopsy samples identify patients who may avoid surgical excision?

Background: The ability to distinguish benign from atypical/malignant papillary lesions on core needle biopsy is limited by the representative nature of the biopsy method, thus follow-up excision is usually recommended. We aimed to determine if larger samples of tissue obtained by core needle biopsy can more reliably predict the true benign nature of a papilloma.

Methods: We reviewed the pathology slides and medical records of 51 patients who were diagnosed with benign papillomas on core needle biopsy from 2000 to 2010, who subsequently underwent surgical excision.

Epigenetics of regional lymph node metastasis in solid tumors.

Regional nodal status remains one of the most important prognostic factors in several solid tumors including melanoma, breast cancer, and gastrointestinal malignancies. However, despite the accuracy of lymph node (LN) staging, patients who are LN negative are still at risk for development of recurrence and distant metastasis. As such, numerous molecular studies have focused on genetic and transcriptome changes in primary and metastatic tumors to discover molecular determinants that can predict aggressive metastatic disease and/or correlated to clinical outcomes.

Epigenetic regulation of cancer stem cell genes in triple-negative breast cancer.

Expression of specific breast cancer stem cells (BCSCs) is seen in aggressive tumors, but their regulation is unclear. Epigenetic changes influence gene expression and are implicated in breast cancer progression. We hypothesized that promoter methylation regulates specific BCSC-related genes [CD44, CD133, CD24, MSH1 (alias, Musashi-1), and ALDH1] and that this epigenetic profile can identify aggressive subtypes, such as triple-negative breast cancer (TNBC).

Epigenetics of estrogen receptor-negative primary breast cancer.

Increasingly, breast cancer is being recognized as a heterogeneous disease comprised of molecularly and phenotypically distinct intrinsic tumor subtypes with different clinical outcomes. This biological heterogeneity has significant implications, particularly as it relates to expression profiling of estrogen receptor (ER) status, as classifying breast cancers based on hormone receptor expression impacts not only prognosis but also treatment options and long-term outcomes. Epigenetics has emerged as a promising field for the assessment of hormone receptor status.

Epigenetic biomarkers in skin cancer.

Epigenetic aberrations have been associated with cutaneous melanoma tumorigenesis and progression including dysregulated DNA gene promoter region methylation, histone modification, and microRNA. Several of these major epigenetic aberrations have been developed into biomarkers. Epigenetic biomarkers can be detected in tissue and in blood as circulating DNA in melanoma patients.

Stanniocalcin-1: a novel molecular blood and bone marrow marker for human breast cancer.

Purpose: Very few tumor molecular markers have been identified that are highly specific for breast cancer cells when applied to blood and bone marrow (BM). Stanniocalcin (STC)-1 is a recently discovered human gene that has been implicated in cellular calcium homeostasis and resistance to hypoxia and is located on chromosome 8p in a region associated with amplification in breast cancer. We investigated STC-1 mRNA as a potential molecular marker for detection of breast cancer metastasis in the blood and BM.