Indocyanine green and fluorescence lymphangiography for sentinel lymph node identification in cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy has become the standard method of determining regional lymph node involvement in cutaneous melanoma. Although traditionally performed via injection of radioisotope tracers and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an attractive alternative. METHODS: Fifty two consecutive patients with cutaneous melanoma of the trunk or extremities underwent SLNB. Preoperative lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC). Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then performed. Successful identification of a sentinel lymph node via each modality was then assessed. RESULTS: A total of 77 lymph nodes were identified from the 52 patients (range 1-3). The majority of melanomas were extremity-based, superficial spreading type, and had SLN localized to the axilla. There were no complications related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6% for ISB, and 88.5% for IcG (P < 0.05 for ICG vs ISB). On univariate logistic regression analysis, no factors were found to be associated with failure of ICG. CONCLUSIONS: Fluorescent lymphangiography using ICG is an effective method of SLN identification in patients with cutaneous melanoma of the trunk and extremities. When ICG and TSC are used in combination, ISB offers no additional advantage and may be safely omitted.

Health behaviors and needs of melanoma survivors.

PURPOSE: Little is known about melanoma survivors' long-term symptoms, sun protection practices, and support needs from health providers. METHODS: Melanoma survivors treated at Stanford Cancer Center from 1995 through 2011 were invited to complete a heath needs survey. We compared responses of survivors by sex, education, time since diagnosis (long-term vs. short-term survivors), and extent of treatment received (wide local excision (WLE) alone versus WLE plus additional surgical or medical treatment (WLE+)). RESULTS: One hundred sixty melanoma survivors (51 % male; 61 % long-term; 73 % WLE+) provided evaluable data. On average, patients were 62 years of age (SD = 14), highly educated (75 % college degree), and Caucasian (94 %). Overall, participants rated anxiety as the most prevalent symptom (34 %). Seventy percent reported that their health provider did not address their symptoms, and 53 % requested education about melanoma-specific issues. Following treatment, women spent significantly less time seeking a tan compared with men (p = 0.01), had more extremity swelling (p = 0.014), and expressed higher need for additional services (p = 0.03). Long-term survivors decreased their use of tanning beds (p = 0.03) and time spent seeking a tan (p = 0.002) and were less likely to receive skin screening every 3-6 months (p < 0.001) compared with short-term survivors. WLE+ survivors reported greater physical long-term effects than WLE survivors (p ≤ 0.001) following treatment. CONCLUSIONS: Melanoma survivors experience continuing symptoms long after treatment, namely anxiety, and they express a need for information about long-term melanoma effects, psychosocial support, and prevention of further skin cancer.

Symbiotic or parasitic? A review of the literature on the impact of fellowships on surgical residents.

OBJECTIVE: We conducted a systematic review of published literature to gain a better understanding of the impact of advanced fellowships on surgical resident training and education. BACKGROUND: As fellowship opportunities rise, resident training may be adversely impacted. METHODS: PubMed, MEDLINE, Scopus, BIOSIS, Web of Science, and a manual search of article bibliographies. Of the 139 citations identified through the initial electronic search and screened for possible inclusion, 23 articles were retained and accepted for this review. Data were extracted regarding surgical specialty, methodology, sample population, outcomes measured, and results. RESULTS: Eight studies retrospectively compared the eras before and after the introduction of a fellowship or trended data over time. Approximately half used data from a single institution, whereas the other half used some form of national data or survey. Only 3 studies used national case data. Fourteen studies looked at general surgery, 6 at obstetrics-gynecology, 2 at urology, and 1 at otolaryngology. Only one study concluded that fellowships have a generally positive impact on resident education, whereas 9 others found a negative impact. The remaining 13 studies found mixed results (n = 6) or minimal to no impact (n = 7). CONCLUSIONS: The overall impact of advanced surgical fellowships on surgical resident education and training remains unclear, as most studies rely on limited data of questionable generalizability. A careful study of the national database of surgery resident case logs is essential to better understand how early surgical specialization and fellowships will impact the future of general surgery education.

The construction of three-dimensional micro-fluidic scaffolds of biodegradable polymers by solvent vapor based bonding of micro-molded layers.

It is increasingly important to control cell growth into and within artificial scaffolds. Tissues such as skin, blood vessels, and cartilage have multi-layer structures with different cells in each layer. With the aid of micro-fabrication technology, a novel scaffolding method for biodegradable polymers such as polylactic acid (PLA), polyglycolic acid (PGA), and the copolymers poly(lactide-co-glycolide)(PLGA), was developed to construct three-dimensional multi-layer micro-fluidic tissue scaffolds. The method emphasizes micro-fluidic interconnections between layers within the scaffolds and maintenance of high-resolution geometries during the bonding process for the creation of multi-layered scaffolds. Micro-holes (10-100 microm), micro-channels, and micro-cavities were all created by micro-molding. Solvent-vapor based bonding of micro-molded layers preserved 20 microm sized structures. Sample scaffolds were constructed for purposes such as channel-directed cell growth and size-based cell sorting. Further extension of these techniques to create a micro-vascular network within or between layers is possible. Culturing of human coronary artery endothelial cells (HCAECs) on the sample scaffolds demonstrated the biocompatibility of the developed process and the strong influence of high-resolution micro-geometries on HCAEC growth.

Perceived Value of a Program to Promote Surgical Resident Well-being.

OBJECTIVE: The demands of surgical residency are intense and threaten not only trainees' physical wellness, but also risk depression, burnout, and suicide. Our residency program implemented a multifaceted Balance in Life program that is designed to improve residents' well-being. The purpose of this study was to evaluate the program utilization and perceived value by residents. DESIGN, SETTING, PARTICIPANTS: Residents (n = 56, 76% response rate) were invited to participate in a voluntary survey from December 2013 to February 2014 regarding utilization, barriers to use, and perceived value of 6 program components (refrigerator, After Hours Guide, psychological counseling sessions, Resident Mentorship Program, Class Representative System, and social events). They were also asked questions about psychological well-being, burnout, grit, and sleep and exercise habits before and after implementation of the program. RESULTS: The most valued components of the program were the refrigerator (mean = 4.61) and the psychological counseling sessions (mean = 3.58), followed by social events (mean = 3.48), the Resident Mentorship Program (mean = 2.79), the Class Representative System (mean = 2.62), and the After Hours Guide (mean = 2.10). When residents were asked how they would allocate $100 among the different programs, the majority was allocated to the refrigerator ($54.31), social events ($26.43), and counseling sessions ($24.06). There was no change in psychological well-being or burnout after the program. Residents had higher levels of grit (ß = 0.26, p < 0.01) and exercised (ß = 1.02, p < 0.001) and slept (ß = 1.17, p < 0.0001) more after the program was implemented. CONCLUSIONS: This study demonstrated that a multifaceted program to improve the well-being of trainees is feasible, highly valued, and positively perceived by the residents. Further research is needed to quantify the effectiveness and longitudinal impact such a program has on resident depression, burnout, and other psychological factors.

Grit as a predictor of risk of attrition in surgical residency.

BACKGROUND: Grit, a measure of perseverance, has been shown to predict resident well-being. In this study we assess the relationship between grit and attrition. METHODS: We collected survey data from residents in a single institution over two consecutive years. All residents in general surgery were invited to participate (N = 115). Grit and psychological well-being were assessed using validated measures. Risk of attrition was measured using survey items. RESULTS: 73 residents participated (63% response rate). Grit was positively correlated with general psychological well-being (r = 0.30, p < 0.05) and inversely correlated with depression (r = -0.25, p < 0.05) and risk of attrition (r = -0.37, p < 0.01). In regression analyses, grit was positively predictive of well-being (B = 0.77, t = 2.96, p < 0.01) and negatively predictive of depression (B = -0.28 t = -2.74, p < 0.01) and attrition (B = -0.99, t = -2.53, p < 0.05). CONCLUSIONS: Attrition is a costly and disruptive problem in residency. Grit is a quick, reliable measure which appears to be predictive of attrition risk in this single-institution study.

Prevalence and predictors of depression among general surgery residents.

BACKGROUND: Recent resident suicides have highlighted the need to address depression among medical trainees. This study sought to identify the prevalence and predictors of depression among surgical residents. METHODS: Surgical residents at a single institution were surveyed. Depression and personal traits were assessed using validated measures; participant demographics were also obtained. RESULTS: 73 residents completed the survey (response rate 63%). 36% met criteria for at least mild depression, of which 20% met criteria for moderate to severe depression. In multivariate linear regression analyses controlling for demographic factors, trait emotional intelligence alone was a significant inverse predictor of depression (ß = -0.60, p < 0.001). CONCLUSIONS: Depression is prevalent among general surgery residents. Identifying protective factors and at-risk populations may allow for effective initiatives to be developed to address depression, and optimize the mental health of trainees.

Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer.

PURPOSE: To determine the efficacy of concurrent 5-fluorouracil (5-FU) and intensity-modulated radiotherapy (IMRT) followed by body stereotactic radiosurgery (SRS) in patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: In this prospective study, all patients (19) had pathologically confirmed adenocarcinoma and were uniformly staged. Our treatment protocol consisted of 45 Gy IMRT with concurrent 5-FU followed by a 25 Gy SRS boost to the primary tumor. RESULTS: Sixteen patients completed the planned therapy. Two patients experienced Grade 3 toxicity (none had more than Grade 3 toxicity). Fifteen of these 16 patients were free from local progression until death. Median overall survival was 33 weeks. CONCLUSIONS: Concurrent IMRT and 5-FU followed by SRS in patients with locally advanced pancreatic cancer results in excellent local control, but does not improve overall survival and is associated with more toxicity than SRS, alone.

Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections.

Extrathyroidal cancers could potentially be targeted with (131)I, if the Na(+)/I(-) symporter (NIS) were functional. Using immunohistochemical methods we probed 1278 human samples with anti-NIS antibody, including 253 thyroid and 169 breast conventional whole tissue sections (CWTS). Four high density tissue microarrays containing a wide variety of breast lesions, normal tissues, and carcinoma cores were tested. The results of the normal microarray were corroborated in 50 CWTS. Nineteen of 34 normal tissues, including bladder, colon, endometrium, kidney, prostate, and pancreas, expressed NIS. Nineteen of 25 carcinomas demonstrated NIS immunopositivity; 55.7% of 479 carcinoma microarray cores expressed NIS, including prostate (74%), ovary (73%), lung (65%), colon (62.6%), and endometrium (56%). NIS protein was present in 75% benign thyroid lesions, 73% thyroid cancers, 30% normal-appearing, peritumoral breasts, 88% ductal carcinomas in situ, and 76% invasive breast carcinoma CWTS. Comparatively, breast microarray cores had lower immunoreactivity. Plasma membrane immunopositivity was confirmed in thyrocytes, salivary ductal, gastric mucosa, and lactating mammary cells. In other tissues, immunoreactivity was predominantly intracellular, particularly in malignant lesions. Thus, NIS is present in many normal epithelial tissues and is predominantly expressed intracellularly in many carcinomas. Elucidating the regulatory mechanisms that render NIS functional in extrathyroidal carcinomas may make (131)I therapy feasible.

A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male.

We report a rare synchronous presentation of adrenocortical carcinoma (ACC) and papillary thyroid carcinoma (PTC). A 31-year-old male first presented with a large left adrenal mass that was identified during the workup for refractory hypertension due to hyperaldosteronism. The mass was removed surgically with pathology showing ACC. The patient was then treated with adjuvant radiation therapy and mitotane chemotherapy. Four months post ACC resection, metastatic ACC to the right upper lung and PTC in the left lobe of the thyroid were found in surveillance imaging. He subsequently developed pulmonary, contralateral adrenal and brain metastases from his ACC. Li Fraumeni syndrome and Multiple Endocrine Neoplasia Type I (MEN I) were considered, but testing of both P53 and menin genes showed no mutation. We also performed a review of the literature and found three similar cases, however gene mutation analysis was not performed..

Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. METHODS AND MATERIALS: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. RESULTS: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). CONCLUSION: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers.

A programmable and biodegradable drug delivery device is desirable when a drug needs to be administered locally. While most local drug delivery devices made of biodegradable polymers relied on the degradation of the polymers, the degradation-based release control is often limited by the property of the polymers. Thus, we propose micro-geometry as an alternative measure of controlling drug release. The proposed devices consist of three functional layers: diffusion control layer via micro-orifices, diffusion layer, and drug reservoir layers. A micro-fabrication technology was used to shape an array of micro-orifices and micro-cavities in 85/15PLGA layers. A thin layer of fast degrading 50/50PLGA was placed as the diffusion layer between the 85/15PLGA layers to prevent any burst-type release. To modulate the release of the devices, the dimension and location of the micro-orifices were varied and the responding in vitro release response of tetracycline was monitored over 2 weeks. The release response to the different micro-geometry was prominent and further analyzed by FEM simulation. Comparison of the experiments to the simulated results identified that the variation of micro-geometry influenced also the volume-dependent degradation rate and induced the osmotic pressure.

Neutrophil survival on biomaterials is determined by surface topography.

PURPOSE: Cardiovascular device-centered infections are a major cause of hospital morbidity, mortality, and expense. Caused by opportunistic bacteria, this phenomenon is thought to arise because of a defect in neutrophil bacterial killing. We have shown that neutrophils that adhere to polystyrene remain viable, whereas neutrophils that adhere to the vascular biomaterials expanded polytetrafluoroethylene (ePTFE) and Dacron undergo a rapid nonapoptotic death. This study was designed to test the hypothesis that surface topography is a determinant of the nonapoptotic death response of neutrophils to biomaterials. METHODS: We took advantage of the ease with which a polystyrene surface can be manipulated to examine the effect of surface topography on neutrophil viability. Neutrophils were exposed to smooth or roughened polystyrene surfaces both in vivo and in vitro. Changes in cell membrane permeability and production of reactive oxygen species by individual cells were monitored with fluorescent dyes. RESULTS: Host cells and isolated human neutrophils died rapidly after adhesion to roughened polystyrene. Neutrophils adherent to roughened surfaces produced more reactive oxygen intermediates than those adherent to smooth surfaces and were first to die. The cell death response precipitated by expanded polytetrafluoroethylene, Dacron, or the roughened surfaces was significantly reduced with treatment of the neutrophils with catalase, diphenylene iodonium, or the src kinase inhibitor PP2 before adhesion. CONCLUSIONS: Neutrophil adhesion to roughened materials triggers rapid production of reactive oxygen species and precipitates a nonapoptotic cell death. Understanding the material properties that trigger these responses is essential to development of the next generation of implantable biomaterials.