Citations

AbstractBackgroundVascularized lymph node transfer (VLNT) is an emerging surgical treatment for lymphedema. However, literature‐comparing outcomes of upper limb lymphedema (ULL) and lower limb lymphedema (LLL) is limited. Hence, the aim of this study is to compare the long‐term clinical outcomes on ULL versus LLL in patients treated with VLNT.MethodsA retrospective study retrieving data from patients with International Society of Lymphology (ISL) stages II–III who underwent different VLNTs from July 2010 to July 2016 in our institution was performed. Demographics preoperatively, and clinical data (limb circumference, infectious episodes, lymphoscintigraphic studies) preoperatively and postoperatively were recorded. Clinical outcomes by extremity were also analyzed.ResultsA total of 83 patients with lymphedema (ULL: n = 30, LLL: n = 53) were included. Mean follow‐up time was 32.8 months (range 24–49 months). Mean circumference reduction was higher in patients with ULL compared to with LLL (28.6 ± 8.6 vs. 22.3 ± 10.1, p < .001), and for patients with secondary lymphedema (24.8 ± 9.6, p < .001) than for patients with primary lymphedema (18.9 ± 14, p > .05). Infectious episodes per year preoperative and postoperative showed that LLL patients had higher reduction on infection rate compared with ULL patients (2.4 ± 1.1 vs. 1.9 ± 1.2, p < .001).ConclusionVLNT is a promising surgical treatment option for patients with lymphedema. This study suggests that VLNT may have a more beneficial outcome in patients with ULL and with secondary lymphedema.

Abstract Lung cancer (LC) is the primary cause of cancer-related deaths in the United States. Whereas smoking and other environmental factors strongly increase LC risk, multiple genetic variants also contribute to risk in smokers. Furthermore, among smokers, some families have been identified with an abnormally high prevalence of LC, suggesting that unknown genetic factors can greatly increase LC risk in smokers. The typically short survival after LC diagnosis impedes collection of detailed genotypic information on any single large family pedigree, impairing the identification of putative high-risk factors. Therefore, the Genetic Epidemiology of LC Consortium has collected epidemiological and genetic data from a number of families with high numbers of LC cases from eight different sites across the US. In this study, we have obtained whole exome sequences (WES) from 290 members of 28 families, including 66 LC cases. We used a gene-based approach to allow for the possibility that different families may contain different variants of the same gene. Variants were filtered for i) allele frequency, ii) functional effect using combined annotation-dependent depletion (CADD), and, iii) affecting a gene with either a known or suspected role in cancer. We further selected variants based on their segregation in family pedigrees in a pattern consistent with a large effect on LC risk. Candidate LC risk genes were then identified as those represented in at least two families by the same or different variants. We further culled the list of genes by requiring the presence of at least one rare, functional variant enriched in the WES of 1060 cases relative to 899 controls from the Transdisciplinary Research on Cancer of the Lung consortium. This analysis narrowed our results to two genes, one being E2A, a member of the E family of bHLH transcription factors. Whereas loss-of-function mutations in E2A drive lymphoid cancers, the E2A protein also participates in an oncogenic heterodimer with TWIST1 that promotes the epithelial-mesenchymal transition and is implicated in multiple cancer types. Furthermore, the E2A/TWIST1 heterodimer is the primary TWIST1-containing complex implicated in oncogenesis, and silencing of E2A in KRAS-mutant non-small cell lung cancer (NSCLC) cell lines results in oncogene-stimulated senescence and apoptosis. Our data identified three distinct E2A variants present in all 10 sequenced LC cases in the 5 families in which those variants are found. Finally, two of these E2A variants are located only 57 nucleotides from each other, immediately adjacent to sequences encoding a transcription activation domain, suggesting that both variants alter the same specific protein function. These data identify E2A variants as likely high risk factors for LC in smokers and validate our general approach for identifying genetic factors with a large impact on LC risk. Citation Format: Claudio W. Pikielny, Anthony M. Musolf, Mariza de Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, yafang Li, Ming You, Richard Wilson, Elena Y. Kupert, Marshall W. Anderson, Ann G. Schwartz, Susan M. Pinney, Ambrose I. Granizo-Mackenzie, Yanhong Liu, Ramaswamy Govindan, James McKay, Rayjean Hung, John K. Field, David C. Christiani, Joan E. Bailey-Wilson, Christopher I. Amos. Familial studies identify variants in the E2A transcription factor as putative risk factors for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-053.

IntroductionManagement after total pharyngolaryngectomy with free ileocolon flaps can be challenging. Adequate postoperative surgical guidelines are essential to avoid complications. Factors, such as agitation, hypotension, or prolonged mechanical ventilation, might compromise final outcomes. Herein, we describe our experience in the early postoperative care of patients after total pharyngolaryngectomy with immediate reconstruction using the free ileocolon flap.MethodsThis is a retrospective review of all patients who underwent total pharyngolaryngectomy and immediate reconstruction using the free Ileocolon flap. Demographics, etiology of resection, neoadjuvant therapy, surgical time, method of sedation, postoperative use of vasopressors, length of intensive care unit (ICU) stay, time of discontinuation of mechanical ventilation, and complications were recorded and analyzed.ResultsBetween 2010 and 2015, a total of 34 patients underwent total pharyngolaryngectomy and immediate reconstruction using the free Ileocolon flap. The most common cause of total pharyngolaryngectomy was cancer. Twenty-eight patients had neoadjuvant therapy (radiation). The average surgical time was 11.5 hours (range, 8–14.5 hours), average length of ICU stay was 3 days (range, 2–15 days) with an average time for mechanical ventilation cessation of 3 days (range, 1–20 days). Midazolam and dexmedetomidine were the most common sedatives used during surgery and in the ICU period. Three patients required vasopressors due to hypotension, 2 had unplanned self-extubation from the tracheostomy site, 2 experienced postoperative bleeding, 1 had pneumonia, 4 required unplanned return to the operating room, 2 had partial flap loss, and 1 had complete flap loss.ConclusionsOverall, a majority of patients recovered well postoperatively with minimal complications and low rate of reoperation. Our research provides a foundation to develop a risk-stratified approach to determine the need for an ICU admission or early transfer to floor care.

1562 Background: In Caucasian-predominant populations, overweight or obese NSCLC pts (BMI≥25-kg/m2) have better prognosis while underweight (BMI≤18.5-kg/m2) pts have a worse prognosis. A large pooled sample allowed us to evaluate the role of ethnicity in this BMI-NSCLC OS relationship. Methods: Using individual data, survival analysis was performed on 15 ILCCO studies, assessing the interactions between ethnicity and BMI on overall survival (OS). Adjusted Hazard Ratios (aHR) from Cox models and adjusted penalized smoothing spline plots were generated. Results: Among 13416 (77%) Caucasian, 2975 (17%) Asian, and 935 (5%) Black NSCLC pts analyzed, we confirmed that for all pts, being underweight at NSCLC diagnosis was associated with worse OS (aHR=1.68, CI 1.5-1.8, p<0.001), while overweight/obese pts had improved survival (aHR 0.89, CI 0.8-0.9, p<0.001), when compared to pts with normal BMI. In general, Black pts had poorer OS than Caucasian pts (aHR 1.26 CI 1.1-1.4, p<0.001). However, the BMI-OS relationship differed according to ethnicity (BMI-ethnicity interaction, p=0.009): Caucasian underweight pts had poorer OS (aHR 1.67, CI 1.5-1.8, P<0.001) while overweight/obese pts had improved OS (aHR 0.89, CI 0.8-0.9, P<0.001). In Asian pts, these two associations were aHR 1.15, CI 0.8-1.5, P=0.33, and aHR 0.91, CI 0.7-1.1, P=0.32, respectively. In Black pts, these two associations were aHR 1.06, CI 0.7-1.5, p=0.73 and 0.75, CI 0.6-0.8 p<0.001, respectively. For overweight/obese patients, as BMI rises from 25-kg/m2 through 45-kg/m2, the prognosis worsens for Caucasian pts, remains stable for Asian pts, but improves for Black pts. Conclusions: InCaucasian pts, being underweight had a greater negative impact on OS than for Asian or Black pts, while being obese had a greater beneficial impact in Blacks than in other ethnic groups. These ethnic differences likely reflect genetically-informed muscle/adipose tissue distributions, where Black pts may have less sarcopenic obesity than other ethnicities. In future prognostic studies, BMI relationships must account for ethnic differences.

Abstract Lymphedema refers to the accumulation of protein-rich fluid in the interstitial spaces. This can occur secondary to congenital malformation of the lymphatic channels or nodes or as a result of an insult that damages appropriately formed channels and nodes. Stagnant, protein-rich lymph initiates an inflammatory response that leads to adipocyte proliferation, fibrous tissue deposition, and increased susceptibility to infections. The end result is permanent disfigurement and dermal changes. Early and accurate diagnosis is essential, since lymphedema is a chronic and progressive problem. When lymphedema affects the lower extremity, it is important to manage it in a way that preserves function and mobility. Early diagnosis also allows for a proactive rather than reactive approach to treatment and utilization of novel physiologic procedures, such as lymphovenous anastomosis and vascularized lymph node transfer. Such interventions slow down disease progression and reduce morbidity by allowing the surgeon to salvage the remaining functional lymphatic channels. When physiologic procedures fail or when faced with a delayed presentation, the addition of excisional procedures can provide a more comprehensive treatment of this debilitating disease. The aim of this article is to review the most current concepts in the surgical management of lower extremity lymphedema.

We provide a case report of reconstruction of a massive chest wall defect after recurrent phyllodes tumour resections. The reconstruction used a bipedicled groin and latissimus dorsi flap, with composite rib autologous reconstruction. The patient successfully recovered from the operation. Our case illustrates the applicability of this flap in the armamentarium of anterior chest wall reconstructive options.

Abstract Background: Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations. Methods: Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry. Results: Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer. Conclusions: Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data. Impact: Our work demonstrated the importance of rare and common variants in pancreatic cancer risk.

Abstract Purpose: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized. Experimental Design: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression. Results: In mixed tumors, gynecologic-type carcinoma components demonstrated lineage-characteristic and lineage-specific alterations, with choriocarcinomatous components sharing some of these as well as demonstrating novel alterations, supporting a clonal relationship with divergent differentiation of the choriocarcinoma from the somatic carcinoma. TP53 mutation only occurred in nongestational tumors. Diffuse PD-L1 expression was characteristic of choriocarcinoma in both pure and mixed tumors but not seen in the gynecologic-type carcinoma components. Conclusions: Given that the somatic carcinomatous and choriocarcinomatous components of mixed tumors have distinct genetic alterations and biomarker expression, separate analysis of these components is required to guide targeted therapy. High PD-L1 expression suggests a role for checkpoint inhibitor–based immunotherapy in tumors with a choriocarcinoma component. The underlying mechanisms by which cancer stem cells reprogram and initiate trophoblastic retrodifferentiation in some somatic tumors warrant further investigation.

AbstractObjectiveTo investigate whether physician–patient agreement of potential patient problem areas impacts subsequent patient enrollment in an interdisciplinary pain management program.DesignRetrospective chart review of 544 patients who underwent evaluation of their chronic pain. Physicians and their patients endorsed perceived patient problems during the evaluation. The potential problems included 7 clinical domains: pain, sleep, mood, physical functioning, ability to cope with pain, ability to manage pain flare‐ups, and pain medication effectiveness.ResultsResults indicated statistically significant levels of agreement among the physicians and their patients (free‐marginal kappa range, 0.19 to 0.94, P's < 0.001). The highest agreement occurred for pain and the lowest for pain medication effectiveness. Patients who enrolled in a recommended program did not differ from those who did not enroll based on either levels of agreement or average number of physician–patient agreements for the 7 clinical domains (P's > 0.05). Patients recommended for higher‐intensity programs were perceived by their evaluating physician to have a significantly greater number of problematic clinical domains than those recommended for less intense pain programs.ConclusionThe level of physician–patient agreement regarding the patients’ current difficulties did not appear to influence patients’ decisions to participate in interdisciplinary pain management. Extraneous, nonclinical factors may have had a greater impact on participation in interdisciplinary pain management than physician–patient agreement. Future research should focus on identifying these factors and their impact. Also, studying the impact of physician–patient agreement beyond enrollment status (eg, on successful program completion) may be helpful in potentially enhancing patient outcomes.