Living with lymphoedema: children's and young people's perspectives.

BACKGROUND: Lymphoedema is a chronic condition that requires lifelong, time-consuming and laborious management. It can have significant effects on physical, psychological and social well-being. Children and young people with lymphoedema require access to expert services to aid early diagnosis and referral for assessment and treatment. AIM: To explore the perspectives of children and young people living with lymphoedema and those of their families, as well as their experiences of the national paediatric lymphoedema service in Wales. METHOD: A qualitative approach was adopted using semi-structured interviews with participants who had been referred to the national paediatric lymphoedema service in Wales. FINDINGS: A total of 15 families were interviewed. Five themes were identified: lack of professional awareness of paediatric lymphoedema; a journey to diagnosis as lost in the system; 'being me' - what it feels like to have lymphoedema; managing lymphoedema and feeling supported; and the benefits of a national paediatric lymphoedema service. Two sub-themes were identified within the 'being me' theme - body image and self-esteem, and loss of control. CONCLUSION: Lymphoedema has a profound effect on daily life, body image and self-esteem. Participants tended to be resilient and determined to continue with their lives. Importantly, they valued being under the care of a service that understood their condition.

Breast cancer-related upper limb lymphoedema: an overview.

Breast cancer-related lymphoedema can be commonly encountered within a community nurse's role. The severity of lymphoedema can range considerably, from those who are considered 'at risk' due to breast cancer treatment, to individuals with highly complex oedema from advanced disease. This article provides an overview of breast cancer-related lymphoedema, including the risk factors for developing lymphoedema and the impact lymphoedema has physically, psychologically and socially. The treatments for lymphoedema, including clinical practical advice and skills, are presented to support ongoing personal development. A collaborative approach between community nurses and lymphoedema clinics is recommended to ensure that patients receive the best care possible.

Pituitary Tumor Transforming Gene 1 Orchestrates Gene Regulatory Variation in Mouse Ventral Midbrain During Aging.

Dopaminergic neurons in the midbrain are of particular interest due to their role in diseases such as Parkinson's disease and schizophrenia. Genetic variation between individuals can affect the integrity and function of dopaminergic neurons but the DNA variants and molecular cascades modulating dopaminergic neurons and other cells types of ventral midbrain remain poorly defined. Three genetically diverse inbred mouse strains - C57BL/6J, A/J, and DBA/2J - differ significantly in their genomes (∼7 million variants), motor and cognitive behavior, and susceptibility to neurotoxins. To further dissect the underlying molecular networks responsible for these variable phenotypes, we generated RNA-seq and ChIP-seq data from ventral midbrains of the 3 mouse strains. We defined 1000-1200 transcripts that are differentially expressed among them. These widespread differences may be due to altered activity or expression of upstream transcription factors. Interestingly, transcription factors were significantly underrepresented among the differentially expressed genes, and only one transcription factor, Pttg1, showed significant differences between all three strains. The changes in Pttg1 expression were accompanied by consistent alterations in histone H3 lysine 4 trimethylation at Pttg1 transcription start site. The ventral midbrain transcriptome of 3-month-old C57BL/6J congenic Pttg1-/- mutants was only modestly altered, but shifted toward that of A/J and DBA/2J in 9-month-old mice. Principle component analysis (PCA) identified the genes underlying the transcriptome shift and deconvolution of these bulk RNA-seq changes using midbrain single cell RNA-seq data suggested that the changes were occurring in several different cell types, including neurons, oligodendrocytes, and astrocytes. Taken together, our results show that Pttg1 contributes to gene regulatory variation between mouse strains and influences mouse midbrain transcriptome during aging.

Severe lower limb lymphoedema successfully treated with a two-stage debulking procedure: a case report.

Lymphoedema is a chronic condition that has significant functional and psychosocial morbidity. We report a case of severe lower limb lymphoedema successfully treated with a two-stage debulking procedure, highlighting the significant improvements in function and quality of life this operation can have with the appropriate multidisciplinary support.

Exploring the impact of lymphoedema on individuals and if lymphatic venous anastomosis surgery effects perceptions on quality of life: A qualitative study.

PURPOSE: Lymphoedema is a chronic condition, a cancer consequence and causes physical, psychological, and social implications. A new super-micro surgical treatment Lymphatic Venous Anastomosis (LVA) may improve the symptoms of lymphoedema. This study aims to explore the impact of lymphoedema on individuals and if LVA Surgery changes perceptions on quality of life. METHOD: Semi-structured interviews were conducted with sixteen individual's pre-LVA surgery and repeated six months later post-LVA with ten of the participants. Transcripts were analysed using thematic analysis. RESULTS: Themes identified pre-LVA included: Impact of Living with Lymphoedema, Being Different, and Future Hopes and Emotions. Participants reported making significant changes to 'normal' life due to living with lymphoedema. Changes included alteration in shopping, cleaning, hobbies, familial roles, employment and sexual intimacy. The wearing of compression garments engendered feelings of being unattractive. Themes found post-LVA were: I am one of the Lucky Ones and Returning to Former Self. Post-LVA, participants described how life had become more normalised with fear and apprehension of developing cellulitis reduced. Positive changes had enabled usual activities of daily living to recommence. Some participants had decreased pain, aching, heaviness, stiffness and were wearing their compression garments less. CONCLUSION: The findings suggest that the real impact of living with lymphoedema is much more challenging than previously identified. The findings suggest that LVA can give a future of greater choice for some of its recipients, but further research should explore longer-term benefits. LVA could offer hope to some people with lymphoedema, but a realistic expectation is essential.

Are you handling genital oedema confidently?

Men, women or children can suffer from oedema (swelling) of the genitalia. When differential diagnosis has excluded acute trauma or pathology and swelling remains, the condition may be diagnosed as genital lymphoedema, a chronic condition that increases the relative risk of cellulitis. Diagnosis of genital oedema is often delayed due to problems with patient and health professional behaviour, in terms of embarrassment, lack of confidence or lack of knowledge. Awareness of this condition and knowledge on how to manage it will go a long way in helping both patients and clinicians overcome the challenges of addressing genital oedema. This article describes the authors' experiences in managing genital oedema. It also briefly discusses a new international project that seeks to identify the knowledge and training that health professionals need to manage this condition more confidently.

Willingness to bear adversity and beliefs about the curability of advanced cancer in older adults.

BACKGROUND: Older patients with advanced cancer who are 100% certain they will be cured pose unique challenges for clinical decision making, but to the authors' knowledge, the prevalence and correlates of absolute certainty about curability (ACC) are unknown. METHODS: Cross-sectional data were collected in a geriatric assessment trial. ACC was assessed by asking patients, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Response options were 100% (coded as ACC), >50%, 50/50, <50%, 0%, and uncertain. The willingness to bear adversity in exchange for longevity was assessed by asking patients to consider trade-offs between survival and 2 clinical outcomes that varied in abstractness: 1) maintaining quality of life (QOL; an abstract outcome); and 2) specific treatment-related toxicities (eg, nausea/vomiting, worsening memory). Logistic regression was used to assess the independent associations between willingness to bear adversity and ACC. RESULTS: Of the 524 patients aged 70 to 96 years, approximately 5.3% reported that there was a 100% chance that their cancer would be cured (ACC). ACC was not found to be significantly associated with willingness to bear treatment-related toxicities, but was more common among patients who were willing to trade QOL for survival (adjusted odds ratio, 4.08; 95% CI, 1.17-14.26). CONCLUSIONS: Patients who were more willing to bear adversity in the form of an abstract state, namely decreased QOL, were more likely to demonstrate ACC. Although conversations regarding prognosis should be conducted with all patients, those who are willing to trade QOL for survival may especially benefit from conversations that focus on values and emotions.

A Randomized Phase II Open-Label Multi-Institution Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients with Advanced Hepatocellular Carcinoma.

OBJECTIVES: To investigate the clinical efficacy and tolerability of the combination of bevacizumab (B) and erlotinib (E) compared to sorafenib (S) as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 90 patients with advanced HCC, Child-Pugh class A-B7 cirrhosis, and no prior systemic therapy were randomly assigned (1: 1) to receive either 10 mg/kg B intravenously every 14 days and 150 mg E orally daily (n = 47) (B+E) or 400 mg S orally twice daily (n = 43). The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), time to progression, and safety and tolerability. RESULTS: The median OS was 8.55 months (95% CI: 7.00-13.9) for patients treated with B+E and 8.55 months (95% CI: 5.69-12.2) for patients receiving S. The hazard ratio (HR) for OS was 0.92 (95% CI: 0.57-1.47). The median EFS was 4.37 months (95% CI: 2.99-7.36) for patients receiving B+E and 2.76 months (95% CI: 1.84-4.80) for patients receiving S. The HR for EFS was 0.67 (95% CI: 0.42-1.07; p = 0.09), favoring B+E over S. When OS was assessed among patients who were Child-Pugh class A, the median OS was 11.4 months (95% CI: 7.5-15.7) for patients treated with B+E (n = 39) and 10.26 months (95% CI: 5.9-13.0) for patients treated with S (n = 38) (HR = 0.88; 95% CI: 0.53-1.46). CONCLUSIONS: There was no difference in efficacy between the B+E and S arms, although the safety and tolerability profile tended to favor B+E over S based on competing risk analysis.

Mammography Among Women With Severe Mental Illness: Exploring Disparities Through a Large Retrospective Cohort Study.

OBJECTIVE: This study examined mammogram screening rates among women with severe mental illness by using a socioecological framework. Because it has been shown that people with severe mental illness receive less preventive health care overall, the analysis included psychosocial predictors of mammogram screening rates in a cohort of women with severe mental illness. METHODS: This retrospective cohort study (N=14,651) used existing statewide data for women ages 48-67 in California with Medicaid insurance who received treatment in the specialty mental health care system. The primary outcome of interest was evidence of breast cancer screening via mammogram. The associations of each predictor of interest with mammogram screening were evaluated by using Poisson models with robust standard errors. RESULTS: Across all demographic and diagnostic categories, rates of breast cancer screening in this cohort of women with severe mental illness fell below the national average. Only 26.3% (3,859/14,651) of women in the cohort received breast cancer screening in the past year. This study replicated previous findings that women with schizophrenia spectrum disorder and those with a comorbid substance use disorder are less likely to receive screening than those with other types of mental illness. In this cohort of women with severe mental illness, evidence of nonpsychiatric health care utilization was strongly associated with breast cancer screening (adjusted risk ratio=3.30, 95% confidence interval=2.61-4.16, p<.001). CONCLUSIONS: The findings can inform efforts to improve breast cancer screening among women with severe mental illness, such as targeted outreach to population subsets and colocation of primary care services in mental health treatment settings.

Pilot evaluation of the management of chronic oedema in community settings project.

AIMS: The aim of this economic analysis was to estimate the economic impact of the On the Ground Education Programme (OGEP) within one local University Health Board (UHB) in Wales. BACKGROUND: The burden of managing chronic oedema can be considerable to the NHS. Developing innovative solutions to the care and management of patients with chronic oedema has the potential to deliver prudent, cost-effective and high quality care within NHS Wales. DESIGN: The study was a pilot Evaluation of the OGEP using retrospectively and prospectively collected patient recalled data. METHODS: A questionnaire collected health care service use data prior to receiving the OGEP (baseline) and at 3 months follow-up from 97 patients during the period June 2016 and January 2017. In addition, we analysed a patient reported health outcome using the EQ-5D 5L, which was completed by patients at the same two assessment points. RESULTS/FINDINGS: The total cost of managing chronic oedema in the 97 patients recruited was £563 729 (mean patient cost £5812 SD (£5870) at baseline and £445 098 (including the addition of intervention costs) (mean patient cost £4589 (SD £5465) at 3 months follow-up. Improvements in the EQ-5D 5L score increasing from 0.40 (SD 0.25) at baseline to 0.54 (SD 0.23) at 3 months follow-up. CONCLUSIONS: Our research show health care resource use and costs decreased, while health-related quality of life scores increased.

Evaluation of the economic impact of a national lymphoedema service in Wales.

Lymphoedema Network Wales has focused on maximising the impact of its service through the effective use of available resources to ensure high-quality and consistent care for people with lymphoedema across Wales. The aim of this evaluation was to estimate the economic impact of a national lymphoedema service on the NHS Wales budget. Work was undertaken to determine the care pathway within Lymphoedema Network Wales and develop a hypothetical 'world without' the service as a comparator. The four groups of patients that made up the pathways were group 0: 'at risk', group 1-2: 'uncomplicated lymphoedema', group 3: 'complicated/complex' and group 4: 'palliative care'. Overall resource utilisation between 6 months pre- and 6 months post-entry indicated that there were significant cost reductions to be seen after lymphoedema service entry for all patients in each group. This evaluation provides estimates that suggest that the service is likely to be cost saving when people with lymphoedema are managed within Lymphoedema Network Wales rather than in a 'world without' the service.

Managing chronic oedema and wet legs in the community: a service evaluation.

Patients with chronic oedema and 'wet legs' are frequently seen in the community setting, with research indicating that more than half of community nurses' caseloads are patients with chronic oedema. However, a lack of nurse education and standardised care pathways for this condition has been identified. In June 2016, the Welsh Government supported the development of the On the Ground Education Project (OGEP), which aimed to raise community nurses' awareness and recognition of chronic oedema and wet legs, to improve the management of these conditions, and to support the efficient use of community nurses' time and resources. AIM: To investigate the potential economic benefits of the OGEP and its effects on patients' quality of life. METHOD: The OGEP was implemented between June 2016 and March 2017. During this time, 725 patients were assessed and chronic oedema was diagnosed in 426 (59%) of them. Of these, 100 patients were purposively recruited and 97 completed the pilot service evaluation. Data were collected observationally before and after the OGEP was implemented. Baseline measurements of resources, costs and outcomes were captured at the time the patients were initially identified and at a follow-up review three months later. The EQ-5D-5L tool was used to measure patients' health-related quality of life before and after the OGEP was implemented. Data were analysed using Microsoft Excel and SPSS Version 22. RESULTS: Following implementation of the OGEP, there was a significant decrease in the number of district nurse home visits, (P=<0.001), GP surgery appointments (P=0.003) and episodes of cellulitis (P=<0.001). The EQ-5D-5L utility scores showed that patients' quality of life improved after the OGEP was implemented, from a baseline of 0.401 (SD 0.254) to 0.537 (SD 0.231) at the three-month follow-up review. CONCLUSION: The OGEP may support the efficient use of community nurses' time and resources, reduce costs to the NHS, and improve the quality of life of patients with chronic oedema and wet legs.

Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer.

BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from the peripheral blood of HLA-A2+ patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin (SRV.A2). Patients received four intradermal injections of 1 × 107 peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42). Concurrently, patients received intramuscular administration of Poly-ICLC at 30 µg/Kg on vaccination days (i.e., day 0, 14, 28, and 42), as well as on days 3, 17, 21, 31, 37, and 45. Our key objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells. RESULTS: Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I -tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease. CONCLUSION: Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and induces a measurable tumor specific T cell population in patients with advanced PC. TRIAL REGISTRATION: NCT01410968 ; Name of registry: clinicaltrials.gov; Date of registration: 08/04/2011).

A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors.

Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of ABC294640, a first-in-class orally available inhibitor of SK2.Experimental Design: Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid, and 750 mg bid, continuously in cycles of 28 days. Serial blood samples were obtained to measure ABC294640 concentrations and sphingolipid profiles.Results: Twenty-two patients were enrolled, and 21 received ABC294640. The most common drug-related toxicities were nausea, vomiting, and fatigue. Among the 4 patients at 750 mg bid, one had dose-limiting grade 3 nausea and vomiting, and 2 were unable to complete cycle 1 due to diverse drug-related toxicities. The 500 mg bid dose level was established as the recommended phase II dose. ABC294640 administration resulted in decreases in S1P levels over the first 12 hours, with return to baseline at 24 hours. The best response was a partial response in a patient with cholangiocarcinoma at 250 mg qd, and stable disease was observed in 6 patients with various solid tumors across dose levels.Conclusions: At 500 mg bid, ABC294640 is well tolerated and achieves biologically relevant plasma concentrations. Changes in plasma sphingolipid levels may provide a useful pharmacodynamic biomarker for ABC294640. Clin Cancer Res; 23(16); 4642-50. ©2017 AACR.

Rates of Cervical Cancer Screening Among Women With Severe Mental Illness in the Public Health System.

OBJECTIVE: This study aimed to determine cervical cancer screening rates among women with severe mental illness. METHODS: California Medicaid administrative records (2010-2011) for 31,308 women with severe mental illness were examined. Participants received specialty mental health services and were not dually eligible for Medicare. Poisson models assessed association between selected predictors and cervical cancer screening. RESULTS: Overall, 20.2% of women with severe mental illness received cervical cancer screening during the one-year period. Compared with white women, Asian women (adjusted risk ratio [ARR]=1.23), black women (ARR=1.10), and Hispanic women (ARR=1.11) (p<.001) were more likely to have been screened. Women ages 28-37 were more likely than those ages 18-27 to have been screened (ARR=1.31, p<.001). Evidence of other health care use was the strongest predictor of screening (ARR=3.07, p<.001). CONCLUSIONS: Most women in the sample were not regularly screened for cervical cancer. Cervical cancer screening for this high-risk population should be prioritized.

Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells.

Sphingosine kinase 2 (Sphk2) has an oncogenic role in cancer. A recently developed first-in-class Sphk2 specific inhibitor ABC294640 displays antitumor activity in many cancer models. However, the role of Sphk2 and the antitumor activity of its inhibitor ABC294640 are not known in cholangiocarcinoma. We investigated the potential of targeting Sphk2 for the treatment of cholangiocarcinoma. We found that Sphk2 is overexpressed in five established human cholangiocarcinoma cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient-derived cholangiocarcinoma cell line (LIV27) compared to H69 normal cholangiocytes. Inhibition of Sphk2 by ABC294640 inhibited proliferation and induced caspase-dependent apoptosis. Furthermore, we found that ABC294640 inhibited STAT3 phosphorylation, one of the key signaling pathways regulating cholangiocarcinoma cell proliferation and survival. ABC294640 also induced autophagy. Inhibition of autophagy by bafilomycin A1 or chloroquine potentiated ABC294640-induced cytotoxicity and apoptosis. In addition, ABC294640 in combination with sorafenib synergistically inhibited cell proliferation of cholangiocarcinoma cells. Strong decreases in STAT3 phosphorylation were observed in WITT and HuCCT1 cells exposed to the ABC294640 and sorafenib combination. These findings provide novel evidence that Sphk2 may be a rational therapeutic target in cholangiocarcinoma. Combinations of ABC294640 with sorafenib and/or autophagy inhibitors may provide novel strategies for the treatment of cholangiocarcinoma.

Expression of insulin-like growth factor I receptor as a biomarker for predicting prognosis in biliary tract cancer patients.

Carcinomas of the gallbladder (GBCa) and bile ducts are aggressive tumors with poor survival and it is, therefore, essential to elucidate the molecular mechanisms of the various signaling pathways in order to develop effective therapies. In this study, tumor specimens from 40 GBCa patients, 12 extrahepatic bile duct carcinoma patients and 26 intrahepatic bile duct carcinoma patients from the USA and Japan were investigated for insulin-like growth factor I receptor (IGF-IR), mammalian target of rapamycin (mTOR) and rapidly accelerated fibrosarcoma-1 (Raf-1) expression by immunohistochemistry; in addition, the correlations with histological type, pathological stage and patient outcome were analyzed. Positive expression of IGF-IR, mTOR and Raf-1 were identified in 68, 73 and 85% of the specimens, respectively. There was no association with histological type and pathological stage, although the positive expression rate of Raf-1 was higher in advanced-stage GBCa. Moreover, patients with positive expression of IGF-IR exhibited significantly reduced survival compared to those with negative IGF-IR expression. In conclusion, IGF-IR, mTOR and Raf-1 were highly expressed in biliary tract cancer and targeted therapy against IGF-IR may be an effective strategy. Among these molecules, IGF-IR expression was found to be a useful biomarker for identifying patients who may benefit from additional treatment.

SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma.

PURPOSE: The role of postoperative therapy in extrahepatic cholangiocarcinoma (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate 2-year survival (overall and after R0 or R1 resection), pattern of relapse, and toxicity in patients treated with this adjuvant regimen. PATIENTS AND METHODS: Eligibility criteria included diagnosis of EHCC or GBCA after radical resection, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine (1,000 mg/m(2) intravenously on days 1 and 8) and capecitabine (1,500 mg/m(2) per day on days 1 to 14) every 21 days followed by concurrent capecitabine (1,330 mg/m(2) per day) and radiotherapy (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable patients, results would be promising if 2-year survival 95% CI were > 45% and R0 and R1 survival estimates were ≥ 65% and 45%, respectively. RESULTS: A total of 79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%); it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively. The most common grade 3 to 4 adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%), lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI hemorrhage. CONCLUSION: This combination was well tolerated, has promising efficacy, and provides clinicians with a well-supported regimen. Our trial establishes the feasibility of conducting national adjuvant trials in EHCC and GBCA and provides baseline data for planning future phase III trials.

HER2/neu-directed therapy for biliary tract cancer.

BACKGROUND: Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown. PATIENTS AND METHODS: We retrospectively reviewed cases of advanced gallbladder cancer and cholangiocarcinoma with HER2/neu genetic aberrations or protein overexpression who received HER2/neu-directed therapy between 2007 and 2014. Clinical data were retrieved from medical records, and imaging studies were independently reviewed. RESULTS: Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period. In the gallbladder cancer group, HER2/neu gene amplification or overexpression was detected in eight cases. These patients experienced disease stability (n = 3), partial response (n = 4), or complete response (n = 1) with HER2/neu-directed therapy. One patient had HER2/neu mutation and experienced a mixed response after lapatinib therapy. The duration of response varied from 8+ to 168 weeks (median 40 weeks), and three patients are still on therapy. One patient developed HER2/neu amplification as a secondary event after FGFR-directed therapy for FGF3-TACC3 gene fusion. The cholangiocarcinoma cases treated in this series had a higher proportion of HER2/neu mutations, and no radiological responses were seen in these patients despite HER2/neu-directed therapy. CONCLUSIONS: HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.