Liposomal Bupivacaine Analgesia in Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Retrospective Cohort Study.

Background: Liposomal bupivacaine (LB) can be used for postsurgical analgesia after breast reconstruction. We examined real-world clinical and economic benefits of LB versus bupivacaine after deep inferior epigastric perforator (DIEP) flap breast reconstruction. Methods: This retrospective cohort study used the IQVIA claims databases to identify patients undergoing primary DIEP flap breast reconstruction in 2016-2019. Patients receiving LB and those receiving bupivacaine were compared to assess opioid utilization in morphine milligram equivalents (MMEs) and healthcare resource utilization during perioperative (2 weeks before surgery to 2 weeks after discharge) and 6-month postdischarge periods. A generalized linear mixed-effects model and inverse probability of treatment weighting method were performed. Results: Weighted baseline characteristics were similar between cohorts (LB, n = 669; bupivacaine, n = 348). The LB cohort received significantly fewer mean MMEs versus the bupivacaine cohort during the perioperative (395 versus 512 MMEs; rate ratio [RR], 0.771 [95% confidence interval (CI), 0.677-0.879]; P = 0.0001), 72 hours after surgery (63 versus 140 MMEs; RR, 0.449 [95% CI, 0.347-0.581]; P < 0.0001), and inpatient (154 versus 303 MMEs; RR, 0.508 [95% CI, 0.411-0.629]; P < 0.0001) periods; postdischarge filled opioid prescriptions were comparable. The LB cohort was less likely to have all-cause inpatient readmission (odds ratio, 0.670 [95% CI, 0.452-0.993]; P = 0.046) and outpatient clinic/office visits (odds ratio, 0.885 [95% CI, 0.785-0.999]; P = 0.048) 3 months after discharge than the bupivacaine cohort; other all-cause healthcare resource utilization outcomes were not different. Conclusions: LB was associated with fewer perioperative MMEs and all-cause 3-month inpatient readmissions and outpatient clinic/office visits than bupivacaine in patients undergoing DIEP flap breast reconstruction.

The Use and Technique of Sentinel Node Biopsy for Skin Cancer.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the indications for and prognostic value of sentinel lymph node biopsy in skin cancer. 2. Learn the advantages and disadvantages of various modalities used alone or in combination when performing sentinel lymph node biopsy. 3. Understand how to perform sentinel lymph node biopsy in skin cancer patients. SUMMARY: Advances in technique used to perform sentinel lymph node biopsy to assess lymph node status have led to increased accuracy of the procedure and improved patient outcomes.

New Developments in the Management of Cutaneous Squamous Cell Carcinoma.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. List important prognostic features that affect cutaneous squamous cell carcinoma risk. 2. Summarize the changes to the AJCC Cancer Staging Manual, Eighth Edition, staging system for cutaneous squamous cell carcinoma. 3. Evaluate the draining nodal basin with appropriate imaging modalities. 4. Recommend adjuvant radiation therapy in the correct clinical setting for high-risk tumors. 5. Recognize the currently available treatments for advanced cutaneous squamous cell carcinoma. SUMMARY: This continuing medical education article reviews the features, management, and prognosis of cutaneous squamous cell carcinoma with an emphasis on high-risk squamous cell carcinoma and data from the past 3 years. This review will discuss the primary tumor management, high-risk features of a squamous cell carcinoma, changes to the American Joint Committee on Cancer staging system, and the utility of sentinel lymph node biopsy, and critically review the evidence regarding adjuvant therapy.

Fat Grafting and the Palpable Breast Mass in Implant-Based Breast Reconstruction: Incidence and Implications.

BACKGROUND: Fat grafting is a powerful and increasingly used technique in breast reconstruction. However, fat necrosis can lead to palpable postoperative changes that can induce anxiety and lead to unplanned diagnostic studies. The authors' aim in this study was to evaluate the incidence, type, and timing of these unanticipated studies; the specialty of the ordering provider; and the factors that trigger the ordering process. METHODS: A retrospective chart review was conducted for patients from 2006 to 2015 who underwent fat grafting as part of implant-based breast cancer reconstruction and had at least 1-year follow-up after fat grafting. RESULTS: From 2006 to 2015, 166 patients underwent fat grafting as part of implant-based breast reconstruction. Forty-four women (26.5 percent) underwent at least one imaging procedure. Thirteen women (7.8 percent) underwent 17 biopsies. For a palpable mass, the initial imaging test most commonly ordered was ultrasound, followed by mammography/ultrasound. The percentage of patients with a diagnosis of fat necrosis on mammography, ultrasound, and biopsy was 4.2, 12.7, and 5.4 percent, respectively. Seven patients (4.2 percent) had distant metastases. Tissue diagnosis of local recurrence was never identified. Mean follow-up was 2.4 years. CONCLUSIONS: Fat-grafting sequelae may lead to early unplanned invasive and noninvasive procedures initiated by a variety of providers. In this study, fat grafting had no impact on local recurrence rate. As use of fat grafting grows, communication among breast cancer care providers and enhanced patient and caregiver education will be increasingly important in optimizing the multidisciplinary evaluation and monitoring of palpable breast lesions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Gene expression profiling in melanoma: past results and future potential.

The field of melanoma oncology is rapidly evolving with advances in detection, staging and treatment. There is heterogeneity in all stages of melanoma where some patients fare better than others for reasons currently unknown and it is sometimes unclear which patients warrant closer surveillance, multidisciplinary care, increased imaging, more aggressive surgery or adjuvant therapy. Early studies have shown the predictive ability of gene expression profiling (GEP) and institutions that have adopted GEP for melanoma treatment have demonstrated changes in practice patterns and patient management. The goal of this paper is to review the clinical evidence for a new diagnostic test, DecisionDx-Melanoma, the only GEP test for cutaneous melanoma with prospective studies analyzing its utility.

Utilization of Indocyanine Green to Aid in Identifying Sentinel Lymph Nodes in Merkel Cell Cancer.

BACKGROUND: Merkel cell carcinoma (MCC) is a relatively rare skin cancer with high rates of regional lymph node involvement and metastatic spread. National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for staging purposes. The goal of this study is to report our experience utilizing indocyanine green (ICG) fluorescence-based technology to aid in SLNB detection in MCC. METHODS: Consecutive MCC patients who underwent SLNB with radioisotope lymphoscintigraphy, with intraoperative handheld gamma probe, and ICG-based fluorescence imaging from 2012 to 2017 were prospectively studied (Cohort A). A group of historical controls that underwent SLNB for MCC with radioisotope lymphoscintigraphy and vital blue dye (VBD) (lymphazurin or methylene blue dye) was also analyzed (Cohort B). RESULTS: Twenty-four consecutive patients underwent SLNB with lymphoscintigraphy and ICG-based fluorescence and 11 controls underwent SLNB with lymphoscintigraphy and VBD. The localization rate by node with VBD was 63.6% and ICG-based fluorescence was 94.8%. For two patients, a positive sentinel lymph node (SLN) was detected only by ICG-based fluorescence and the nodes were not detected by gamma probe and one patient's only positive node was identified via ICG fluorescence only. VBD or gamma probe did not identify any unique positive SLNs in either cohort B or either cohort, respectively. CONCLUSIONS: In this study, we indicate that ICG-based fluorescence is not only feasible to augment SLN identification, but it has a higher node localization rate as compared to blue dye and it was able to identify positive SLNs otherwise missed by gamma probe. This study suggests the importance of utilizing two modalities to augment SLN identification and that ICG-based fluorescence may be able to identify nodes that would have been otherwise missed by gamma probe. We will continue to follow these patients and enroll more patients in this prospective study to further determine the role that ICG-based fluorescence has in identifying sentinel lymph nodes in MCC.

Malignant Melanoma: Diagnostic and Management Update.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Summarize the changes to the American Joint Committee on Cancer Eighth Edition Melanoma Staging System. 2. List advances in genetic, molecular, and histopathologic melanoma diagnosis and prognostication. 3. Recommend sentinel lymph node biopsy and appropriate surgical margins based on individualized patient needs. 4. Recognize the currently available treatments for in-transit metastasis and advanced melanoma. 5. Describe current and future therapies for melanoma with distant visceral or brain metastases. SUMMARY: Strides in melanoma surveillance, detection, and treatment continue to be made. The American Joint Committee on Cancer Eighth Edition Cancer Staging System has improved risk stratification of patients, introduced new staging categories, and resulted in stage migration of patients with improved outcomes. This review summarizes melanoma advances of the recent years with an emphasis on the surgical advances, including techniques and utility of sentinel node biopsy, controversies in melanoma margin selection, and the survival impact of time-to-treatment metrics. Once a disease manageable only with surgery, a therapeutic paradigm shift has given a more promising outlook to melanoma patients at any stage. Indeed, a myriad of novel, survival-improving immunotherapies have been introduced for metastatic melanoma and more recently in the high-risk adjuvant setting.

Indocyanine green fluorescence imaging with lymphoscintigraphy for sentinel node biopsy in head and neck melanoma.

BACKGROUND: Head and neck melanoma is associated with a high false negative (FN) sentinel lymph node biopsy (SLNB) rate. If techniques are developed that can decrease FN SLNBs, better prognostic information will be obtained, and it may be possible to improve overall survival as patients are assigned to the appropriate adjuvant management. Our group previously demonstrated that the combination of lymphoscintigraphy and indocyanine green (ICG) fluorescence-based technology was feasible for SLNB in primary melanoma. METHODS: Consecutive head and neck cutaneous melanoma patients who underwent radioisotope lymphoscintigraphy and ICG-based fluorescence imaging by the senior author (B.G.) from 2012 to 2015 were prospectively enrolled for analysis. Patients were followed postoperatively by the multidisciplinary melanoma team. Main outcome variables were FN rate of SLNB. Length of follow-up was date of surgery to the date of last follow-up/death. RESULTS: There were 10 positive SLNBs, 51 true negative SLNBs, and one FN SLNB. False negative rate was 9.1%, false negative incidence was 1.6%, sensitivity was 91%, and specificity was 100%. Mean follow-up was 27.6, 17.6, and 16.5 mo for true negative, true positive, and FN patients, respectively. CONCLUSIONS: We report the largest cohort of patients with head and neck cutaneous melanoma undergoing SLNB using both a combination of radioactive tracer, gamma probe, and ICG-based fluorescence identification. Our results demonstrate that using concomitant gamma probe-based radioactivity detection and ICG-based fluorescence for SLN identification in head and neck melanoma is reliable, reproducible and, thus far, has produced a low rate of FN SLNB.

Prospective, Randomized, Controlled Comparison of Bupivacaine versus Liposomal Bupivacaine for Pain Management after Unilateral Delayed Deep Inferior Epigastric Perforator Free Flap Reconstruction.

Effective postsurgical analgesia is a critical aspect of patient recovery. The goal of this prospective, randomized, controlled, blinded study was to examine the effect that liposomal bupivacaine delivered by means of a transversus abdominis plane block has on pain control in women undergoing unilateral deep inferior epigastric perforator flap reconstruction. Institutional review board approval was granted for this prospective study. Patients were eligible if they were undergoing unilateral, delayed deep inferior epigastric perforator flap reconstruction. Patients were randomized to one of three groups: liposomal bupivacaine transversus abdominis plane block, or bupivacaine pain pump. Charts were reviewed for demographics, length of stay, and postoperative narcotic use. There were eight patients in the liposomal bupivacaine and bupivacaine transversus abdominis plane block groups and five patients in the pain pump group. A retrospective cohort of six patients who did not receive any intervention was included. Patients who received a liposomal bupivacaine transversus abdominis plane block used statistically significantly less intravenous and total postoperative narcotics in milligrams and milligrams per kilogram per day compared with all other cohorts. They were able to get out of bed at an earlier time point. Overall hospital costs were similar among the groups. This is the first study to investigate liposomal bupivacaine delivered as a transversus abdominis plane block in a prospective, randomized, blinded study in women undergoing unilateral, delayed, abdominally based autologous breast reconstruction. The authors were able to demonstrate a significant reduction in intravenous and total narcotic use when a liposomal bupivacaine transversus abdominis plane block was used. Future studies are needed to prospectively investigate the effect that liposomal bupivacaine would have on immediate and bilateral reconstructions.

Variations in the origins and absence of the common digital arteries of the hand: a cadaveric study.

We studied anomalies of the common digital arteries by dissecting 33 fresh cadaver hands under magnification. In the majority of the dissected hands (25 hands), common digital arteries took off from the superficial palmar arch and ran superficial and parallel to the flexor tendons. Variations were found in eight out of 33 hands. In four hands the common digital artery to the second web space was replaced by an atypical vessel, originating from the deep palmar arch, that crossed posterior to the index flexor tendons proximal to the A1 pulley. In eight hands, the common digital artery to the fourth web space was replaced by an atypical deeper vessel, originating from the superficial palmar arch and crossing posterior to the little finger flexors. No nerve anomalies were identified. Unrecognized, these atypical arteries to the second and/or fourth web spaces could lead to vascular complications during surgery, especially pollicization.

Aggressive digital papillary adenocarcinoma: treatment with Mohs micrographic surgery and an update of the literature.

BACKGROUND: Aggressive digital papillary adenocarcinoma (ADPA) is a rare adenocarcinoma of the sweat glands. AIMS: We wish to report the treatment of two cases of ADPA with Mohs micrographic surgery and review the presentation, management, and prognosis of this rare malignancy. MATERIALS & METHODS: Cases of ADPA were identified from recent surgery logs. Demographic, tumor, and treatment characteristics were extracted. A PubMed database search for English language full-text articles of aggressive digital papillary adenocarcinoma was performed, and relevant articles were summarized. RESULTS: Two cases of ADPA were identified. A 53-year-old man presented with ADPA on his right third fingernail, and a 65-year-old man presented with ADPA on his right thumb. Both patients underwent Mohs micrographic surgery and negative sentinel lymph node biopsy, remaining recurrence free at 34 and 9 months, respectively. DISCUSSION: ADPA frequently presents as a solitary mass on the digit. Treatment of ADPA with local excision or amputation has historically been fraught with high recurrence rates. Regional lymph node spread and distant metastasis have been reported. Mohs micrographic surgery may be an alternative treatment for ADPA. CONCLUSION: Mohs micrographic surgery is a viable option for ADPA and warrants further exploration. Long-term follow-up is important, and additional studies will need to identify the role of sentinel lymph node biopsy.

A novel approach to training students in delivering evidence-based obesity treatment.

BACKGROUND AND OBJECTIVES: Obesity is a major public health concern because of its prevalence, serious health consequences, and costs. Many health care providers believe they have been inadequately trained to treat obesity and, as a result, often do not address patients' weight. Despite recommendations to improve knowledge and skills so they can more effectively address obesity, health care educational curricula are already overburdened with content and have been slow to respond to these recommendations. METHODS: Interprofessional health care students voluntarily participated in an extracurricular service-learning opportunity to learn about the evidence-based treatment of obesity. A multidisciplinary team of weight management professionals taught didactic lessons and oversaw the service-learning component of training. An essential element of the training was the students' delivery of a free 10-week weight management intervention to low-income overweight and obese community residents. RESULTS: Patients in both the student-led (n=25) and professional-led (n=21) programs lost a statistically and clinically significant amount of weight. Additionally, there was no significant difference in weight loss between the two programs, even after taking into account differences in attendance between the two programs. CONCLUSIONS: An extracurricular service-learning program pairing brief didactic instruction with experiential learning appears to be a viable strategy for accomplishing the important dual objectives of preparing health care students to treat obesity and providing much-needed treatment to those in our community who are least able to afford it.

Characterization of a novel two-component system in Burkholderia cenocepacia.

Two-component systems are important regulatory systems that allow bacteria to adjust to environmental conditions, and in some bacteria are used in pathogenesis. We identified a novel two-component system in Burkholderia cenocepacia, an opportunistic pathogen that causes pneumonia in cystic fibrosis (CF) patients. The putative operon encodes BceS, a sensor kinase, and BceR, a response regulator. Our studies indicated that the bceR mutant showed a statistically significant decrease in protease, swimming motility, and quorum sensing when compared to the wild-type, but there was no significant difference in phospholipase C activity, swarming, and biofilm formation. In addition, the mutant showed a statistically significant reduction in virulence compared to the wild-type using the alfalfa plant model. Examination of the Burkholderia cepacia complex (a group of organisms that are phenotypically similar, but genotypically distinct) revealed that this system is prevalent in B. ambifaria, B. multivorans, B. vietnamiensis and B. dolosa. Interestingly, all these organisms have been associated with CF patients. The collective results indicate that BceSR influences various activities important in Burkholderia physiology and possibly pathogenesis. This information could be important in the design of novel therapeutics for Burkholderia infections.

Green tea polyphenol epigallocatechin 3-gallate, contributes to the degradation of DNMT3A and HDAC3 in HCT 116 human colon cancer cells.

BACKGROUND: Colon cancer is still the second leading cause of cancer deaths in the United States. Epigenetic gene silencing involving DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) plays an important role in the progression of colon cancer. MATERIALS AND METHODS: In the present study we found that the sensitivity of colon cancer cells to methylation plays a role in its response to alternative therapy involving the green tea polyphenol, epigallocatechin 3-gallate. HDAC and DNMT protein expression were reduced when methylation-sensitive HCT 116 human colon cancer cells was treated with EGCG, but was relatively stable in the HT-29 cell line. This decrease in expression may be partially explained by our finding that DNMT3A and HDAC3 are degraded in the methylation-sensitive colon cancer cells in part by inhibiting their association with the E3 ubiquitin ligase, UHRF1. CONCLUSION: These findings provide a rationale for the development of a targeted therapy for methylation-sensitive colon cancer that can include EGCG in combination with other DNMT and HDAC inhibitors.

Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis.

The anti-inflammatory actions of vitamin D have long been recognized and its importance in modulating colon cancer and colitis development is becoming apparent. The vitamin D receptor (VDR) is downregulated in human ulcerative colitis and colitis-associated cancer (CAC); however, its status in murine models of colitis has yet to be explored. Snail and Snail2, zinc-finger transcription factors regulated by inflammatory pathways and able to transcriptionally silence VDR, are upregulated in human Ulcerative Colitis and are associated with localized VDR silencing. To signal, VDR must heterodimerize with retinoid X receptor α (RXRα). If either VDR or RXRα are compromised, vitamin D cannot regulate inflammatory pathways. RXRα is downregulated in human colorectal cancer, yet its expression in human and murine colitis has yet to be investigated. To explore the importance of vitamin D and VDR in murine colitis, we used acute and chronic azoxymethane/dextran sulfate sodium models of murine colitis. VDR was downregulated early in the onset of colitis, whereas RXRα downregulation only occurred as colitis became chronic and developed into CAC. Receptor downregulation was associated with an early increase in the expression of the inflammatory markers, Snail and Snail2. The acute colitis model induced in combination with a vitamin D-deficient diet resulted in increased morbidity, receptor downregulation, inflammatory marker expression, and Snail and Snail2 upregulation. These experiments show the importance of vitamin D and VDR in modulating murine colitis development.

Epigenetic mechanisms underlying diet-sourced compounds in the prevention and treatment of gastrointestinal cancer.

The development of colon cancer, the third most diagnosed cancer and third leading cause of cancer deaths in the United States, can be influenced by genetic predispositions and environmental exposures. As 80% of colon cancer cases are sporadic in nature, much interest lies in determining risk factors that may foster its development, as well as identifying compounds that could inhibit colon cancer development or halt progression. A major risk factor for sporadic colon cancer is a high fat, Western diet which has been linked to a cancer-prone, pro-inflammatory state. Cultures which place an emphasis on fresh fruits and vegetables demonstrate lower colon cancer incidences. Diet not only has the potential to encourage colon cancer development, but recent evidence demonstrates that certain dietary natural products can halt colon cancer development and progression via epigenetic regulation. Epigenetic dysregulation may contribute to inflammation-driven diseases, such as cancer, and can lead to the inappropriate silencing of genes necessary to inhibit cancer development. Natural compounds have shown the ability to reverse epigenetic dysregulation in in vitro and in vivo models. As current allopathic medicines aimed at reversing epigenetic silencing are accompanied with the risk of toxicity and side effects, much interest lies in being able to harness the disease preventing properties in natural products. Here, we discuss the epidemiology of colon cancer, describe the need for natural approaches to inhibit disease development and highlight natural products which have been shown to inhibit gastrointestinal cancer initiation and progression in vitro or in vivo through epigenetic modulation.