Ari-Nareg Meguerditchian

Interdigitated comb-like electrodes for continuous separation of malignant cells from blood using dielectrophoresis.

In this paper, a method for continuous flow separation of circulating malignant cells from blood in a microfluidic device using dielectrophoresis is discussed. Separation of MDA231 breast cancer cells after mixing with normal blood cells was achieved with a level of accuracy that enabled precise counting of the malignant cells, separation and eventually, sub‐culturing. MDA231 cells were separated from the blood to a daughter channel using two pairs of interdigitated activated comb‐like electrode structures. All experiments are performed with conductivity adjusted medium samples. The electrode pairs were positioned divergent and convergent with respect to the flow. The AC signals used in the separation are 20 V peak‐to‐peak with frequencies of 10–50 kHz. The separation is based on balance of magnitude of the dielectrophoretic force and hydrodynamic force. The difference in response between circulating malignant cells and normal cells at a certain band of alternating current frequencies was used for rapid separation of cancer cells from blood. The significance of these experimental results is discussed in this paper, with detailed reporting on the suspension medium, preparation of cells, flow condition and the fabrication process of the microfluidic chip. The present technique could potentially be applied to identify incident cancer at a stage and size that is not yet detectable by standard diagnostic techniques (imaging and biochemical testing). Alternatively, it may also be used to detect cancer recurrences.

Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans.

Objectives:Dermatofibrosarcoma protuberans (DFSP) is a spindle cell tumor with a high local recurrence rate. Wide excision (WE) has been the standard treatment, but ideal margin width is poorly defined and Mohs micrographic surgery (MMS) has emerged as an alternative procedure. This study examines the use of WE versus MMS for the treatment of primary DFSP at a single institution. Methods:Retrospective review of 48 primary DFSP cases treated from 1971 to 2006. Patient demographics, tumor features, surgical modality (WE vs. MMS), final pathology, and clinical outcome were evaluated. Results:Twenty-eight patients underwent WE versus 20 patients for MMS. Median age was 40 years. Median WE margin width was 2 cm. For MMS, the median number of layers required to clear the tumor was 2. Median maximal defect size was 10 cm for WE versus 9.4 cm for MMS. Advanced closure techniques were required for 18% WE versus 65% MMS (P = 0.001). Median operative time was significantly lower for WE at 77 minutes versus 257 minutes for MMS (P < 0.001). Positive margins were present in 21.4% (6/28) WE versus 0% MMS (P = 0.01). At a median follow-up of 49.9 months for WE and 40.4 months for MMS, local recurrence rates were 3.6% (1/28) and 0%, respectively (P = 1.0). Conclusions:From a surgical standpoint, WE was faster than MMS and resulted in a less complex defect/closure. Although positive margin resection was more common with WE, local control was ultimately similar for the 2 surgical modalities. The choice of WE versus MMS should be based on individualized patients/tumor characteristics and institutional expertise in these modalities.

Anorectal melanoma: diagnosis and treatment.

An increase in the incidence of anorectal melanoma has recently been noted in the United States. Anorectal melanoma is an uncommon and lethal condition, with a median survival of <20 months. Unfortunately, nonspecific symptoms also attributable to common and benign conditions (eg, hemorrhoids) cause significant delay in its diagnosis. Although it has not been validated by clinical trials, abdominoperineal resection has historically been the treatment of choice for this disease. However, for the past 2 decades, a lack of clear survival benefit has led to a shift toward less-mutilating wide local excisions. Controversy still exists regarding the benefit of radiation therapy and chemotherapy. Furthermore, the value of nodal surgery in anorectal melanoma is unclear. In this article, we review the history and current status of management of anorectal melanoma, with a particular focus on surgical controversies and challenges in optimizing survival.

Value of positron emission tomography scan in stage III cutaneous melanoma: A systematic review and meta-analysis

PURPOSE The objective of this study was to review the collective experience and utility of FDG-PET scans (FDG-PET) in the detection of systemic metastases in patients with stage III melanoma. METHODS A systematic search for relevant studies published between 1990 and 2012 was performed. We included English language studies that evaluated melanoma patients with stage III disease, with at least 10 patients per study, and collected statistical data to assess FDG-PET utility in the detection of distant metastases. The SIGN tool was used to evaluate methodological quality and a meta-analysis was performed using Stata statistical software to quantify the clinical utility of FDG-PET. RESULTS The systematic search yielded 9 studies eligible for inclusion in quantitative analyses with a total of 623 patients. The overall sensitivity of FDG-PET in detecting systemic metastases was 89.42% (95% CI: 65.07-97.46), and specificity was 88.78% (95% CI: 77.04-94.91). The pooled positive likelihood ratio was 7.97 (95% CI: 3.58-17.71) and the negative likelihood ratio was 0.12 (95% CI: 0.03-0.47). The area under the summary receiver operating curve (SROC) was 0.94 (95% CI: 0.92-0.96) and the diagnostic odds ratio (DOR) was 66.84 (95% CI: 10.66-418.89). A change in stage and/or management was noted in 22% (126/573) of patients when FDG-PET was utilized. CONCLUSIONS Our findings indicate that FDG-PET may be useful in detecting distant metastases in patients with stage III melanoma. For this highly selected group of patients, FDG-PET has a high sensitivity, specificity and performance, frequently leading to a change in treatment plan.

Claims data linked to hospital registry data enhance evaluation of the quality of care of breast cancer

Complete treatment data is central to evaluation and improvement of cancer care quality. Cancer registries vary in completeness of radiation (RT), chemotherapy (CT), and hormone therapy (HT) data. Administrative claims from health payers may supplement these registries. This study assesses the ability to link private payer claims to the National Cancer Data Base (NCDB) and the extent of additional treatment data identified in claims.

Hyperthermic isolated limb perfusion for extremity soft tissue sarcomas: Systematic review of clinical efficacy and quality assessment of reported trials

Extremity soft tissue sarcomas (STS) are managed with radiotherapy and limb‐sparing surgery however aggressive or recurrent cases require amputation. Hyperthermic isolated limb perfusion (HILP) has been proposed as an alternative. Our aim was to systematically review phase II HILP trials, assess tumor response, limb salvage (LS), and quality of scientific publications on this technique.

Do physician communication skills influence screening mammography utilization

BackgroundThe quality of physician communication skills influences health-related decisions, including use of cancer screening tests. We assessed whether patient-physician communication examination scores in a national, standardized clinical skills examination predicted future use of screening mammography (SM).MethodsCohort study of 413 physicians taking the Medical Council of Canada clinical skills examination between 1993 and 1996, with follow up until 2006. Administrative claims for SM performed within 12 months of a comprehensive health maintenance visit for women 50–69 years old were reviewed. Multivariable regression was used to estimate the relationship between physician communication skills exam score and patients’ SM use while controlling for other factors.ResultsOverall, 33.8 % of 96,708 eligible women who visited study physicians between 1993 and 2006 had an SM in the 12 months following an index visit. Patient-related factors associated with increased SM use included higher income, non-urban residence, low Charlson co-morbidity index, prior benign breast biopsy and an interval >12 months since the previous mammogram. Physician-related factors associated with increased use of SM included female sex, surgical specialty, and higher communication skills score. After adjusting for physician and patient-related factors, the odds of SM increased by 24 % for 2SD increase in communication score (OR: 1.24, 95 % CI: 1.11 - 1.38). This impact was even greater in urban areas (OR 1.30, 95 % CI: 1.16, 1.46) and did not vary with practice experience (interaction p-value 0.74).ConclusionPhysicians with better communication skills documented by a standardized licensing examination were more successful at obtaining SM for their patients.

Thick primary melanoma has a heterogeneous tumor biology: an institutional series

BackgroundThick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up.Methods155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS).ResultsMedian patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients - 15.4%), elective lymph node dissection (ELND) (24 patients - 17.6%) or SLNB (91 patients - 67%). 75% of ELNDs and 53% of SLNBs were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively).ConclusionWithin the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).

Use of hormonal therapy in senior breast cancer patients treated with or without radiotherapy

PURPOSE Breast cancer treatment guidelines state that radiotherapy (rt) can reasonably be omitted in selected women 70 years of age and older if they take adjuvant endocrine therapy (aet) for 5 years. We aimed to assess persistence and adherence to aet in women 70 years of age and older, and to examine differences between rt receivers and non-receivers. METHODS Quebecs medical service and pharmacy claims databases were used to identify seniors undergoing breast-conserving surgery (1998-2005) and initiating aet. Cox proportional hazards models were used to identify predictors of aet non-persistence. RESULTS Of 3180 women who initiated aet (mean age: 77.5 years), 28% did not receive rt. During the subsequent 5 years, 32% of patients who initiated aet did not persist, 2% filled only a single prescription, and 22% switched medications. Compared with rt receivers, non-receivers discontinued more often (35.5% vs. 30.1%) and earlier (1.4 years vs. 1.6 years). They also became nonadherent earlier (medication possession ratio < 80% at year 3 vs. at year 5). Predictors of nonpersistence included rt omission [hazard ratio (hr): 1.26; 95% confidence interval (ci): 1.09 to 1.46]; age (hr per decade increase: 1.15; 95% ci: 1.01 to 1.31); new medications (hr per medication: 1.01; 95% ci: 1.00 to 1.02); and hospitalizations during aet, (hr per hospitalization: 1.08; 95% ci: 1.05 to 1.11). In a subanalysis of rt non-receivers, significant predictors included hospitalizations (hr: 1.07; 95% ci: 1.02 to 1.12) and medications at aet start (hr: 0.94; 95% ci: 0.91 to 0.97). CONCLUSIONS Suboptimal use of aet was observed in at least one third of women. In rt non-receivers, aet use was worse than it was in rt receivers. Initiation of new medications and hospitalizations increased the risk of non-persistence.

Soft tissue tumors of the anorectum: rare, complex and misunderstood

Anorectal soft tissue tumors are uncommon and often present both diagnostic and therapeutic challenges. Although many of these tumors are identified with imaging performed for unrelated reasons, most present with nonspecific symptoms that can lead to a delay in diagnosis. Historically, radical surgery (abdominoperineal resection) has been the mainstay of treatment for both benign and malignant anorectal soft tissue tumors. However, a lack of proven benefit in benign disease along with changes in technology has called this practice into question. In addition, the role of radiation and/or chemotherapy remains controversial. In this manuscript, we review the history and current status of anorectal soft tissue tumor management, with a particular focus on challenges in optimizing survival.