Impact of COVID-19 on 1-Year Survival Outcomes in Hepatocellular Carcinoma: A Multicenter Cohort Study.

INTRODUCTION: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. METHODS: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. RESULTS: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. CONCLUSION: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy.

Improving Operating Room Efficiency: Relocating a Surgical Oncology Program Within a Health Care System.

Background: To meet increased community and regional needs for quality services, our hospital system concluded that its established surgical oncology program-consisting of gynecologic oncology (4 physicians), surgical oncology (2 physicians), and otolaryngologic oncology (2 physicians)-would be best served by the transition of the comprehensive surgical oncology program to a new oncology-naive hospital. We describe the overall strategy and approach involved with this move, its implementation, operating room efficiency results, and physician satisfaction associated with the relocation. Methods: The purpose of the systematic plan for relocation, which was developed and refined during the 2 years preceding the move, was to facilitate a collective awareness and understanding of important patient-centered concepts and essential workflow. All parties involved in direct patient cancer care participated in multiple workgroups to successfully transition the surgical oncology practice. Following the transition to the oncology-naive hospital, components of the operative cases and surgical data were prospectively collected for the initial 6 weeks and compared to retrospective data from the last 8 weeks at the established hospital. The surgical day for each surgeon was deconstructed, and measured variables included total surgical cases, total surgical hours, surgical minutes per case, total anesthesia hours, first case on-time surgical starts, surgical stretcher wheels out to surgical stretcher wheels in, surgical stretcher wheels out to next case start, case end to postanesthesia care unit (PACU), and case end to case start. Results: Five hundred twenty-nine surgical cases encompassing 1,076 anesthesia hours and 710 surgical hours were completed during the 14-week evaluation period. The gynecologic oncologists completed the majority of surgical procedures in both settings. The percentage of first case on-time surgical starts initially decreased during the 6-week interval at the oncology-naive hospital, but interval subset analysis suggested a return to the pre-move norm. Surgical stretcher wheels out to surgical stretcher wheels in had a wide range (9 minutes to 305 minutes) for all surgical sections, but no statistically significant difference was seen overall or for any surgical section. Case end to PACU significantly increased for gynecologic oncology but not for surgical oncology or otolaryngologic oncology. Overall case end to case start times decreased nonsignificantly (63.7 ± 3.1 mean minutes vs 60.3 ± 1.7 mean minutes) following the move. A physician survey found that physicians' expectations were met in terms of the move occurring smoothly without major issues, surgical scheduling and accommodation, anesthesia services, and surgical personnel. Physicians indicated less satisfaction with quality and availability of instrumentation. Conclusion: The transfer of established surgical oncology services to an oncology-naive hospital was associated with early surgeon and operating room staff support, as well as process and programmatic alignment among stakeholders. The success of this transition required transparency, open and honest communication, and problem solving at all levels. The move of a surgical oncology program to an oncology-naive hospital was deemed successful without deterioration of time-related variables associated with operating room efficiency and physician satisfaction. The breakdown and analysis of key components of the surgical day offered additional opportunities for quality improvement in operating room efficiency.

Predictive factors for carboplatin hypersensitivity reactions in gynecologic cancers: Effect of BRCA status.

INTRODUCTION: Carboplatin hypersensitivity reactions have been reported to occur in up to 16% of patients with gynecologic cancers. Several predisposing factors have been suggested including presence of BRCA1/2 mutation, however, contribution of these mutations to reaction development has not been extensively studied. The purpose of this study was to determine if there is an association between BRCA1/2 mutation status and the development of carboplatin hypersensitivity reactions.Methodology: Eligible patients were women aged 18 years or older with a diagnosis of ovarian, fallopian tube, uterine, endometrial, or primary peritoneal cancer who attempted to receive at least one dose of carboplatin. The primary outcome was the effect of BRCA1/2 status on the development of carboplatin hypersensitivity reactions with regard to: reaction frequency, timing, and severity. Secondary outcomes included identification of additional risk factors that may help identify predisposition to carboplatin hypersensitivity reaction. RESULTS: A total of 44 patients were included in this study. Five patients (38%) in the reaction group and 4 patients (31%) in the no reaction group had a documented mutation in one or both BRCA genes (p = 1.00). No significant differences were found in terms of reaction severity or symptoms, and timing of reaction after dose administration. Incidence of thyroid disorder was significantly higher among patients who experienced a hypersensitivity reaction (1 (4%) vs 10 (45%); p = 0.004). CONCLUSION: BRCA mutation status was not associated with an increased risk of carboplatin hypersensitivity in our patient population. Further investigation into thyroid dysfunction as a risk factor for reaction development is warranted.

Cervical Mesonephric Adenocarcinoma With Novel FGFR2 Mutation.

Mesonephric adenocarcinoma is a rare tumor, accounting for <1% of cervical cancers. Well-differentiated mesonephric adenocarcinoma can be difficult to distinguish from diffuse mesonephric hyperplasia. Herein, we report a case of well-differentiated mesonephric adenocarcinoma with an FGFR2 mutation not previously reported in the literature. Nonselective tyrosine kinase inhibitors or FGFR2 inhibitors may represent options for targeted therapy.

The Model of Mortality with Incident Cirrhosis (MoMIC) and the model of Long-term Outlook of Mortality in Cirrhosis (LOMiC).

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97-3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47-3.38)), elevated bilirubin levels (aHR = 1.38, 1.26-1.51) and low sodium levels (aHR = 2.26, 1.84-2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists.

Imagestream detection and characterisation of circulating tumour cells - A liquid biopsy for hepatocellular carcinoma?

BACKGROUND & AIMS: The lack of progress in developing and delivering new therapies for hepatocellular carcinoma (HCC) is in part attributed to the risk related avoidance of tumour biopsy at diagnosis. Circulating tumour cells (CTCs) are a potential source of tumour tissue that could aid biological or biomarker research, treatment stratification and monitoring. METHODS: An imaging flow cytometry method, using immunofluorescence of cytokeratin, EpCAM, AFP, glypican-3 and DNA-PK together with analysis of size, morphology and DNA content, for detection of HCC CTCs was developed and applied to 69 patient and 31 control samples. The presence of CTCs as a prognostic indicator was assessed in multivariate analyses encompassing recognised prognostic parameters. RESULTS: Between 1 and 1642 CTCs were detected in blood samples from 45/69 HCC patients compared to 0/31 controls. CTCs positive for the epithelial markers cytokeratin and EpCAM were detected in 29% and 18% of patients respectively, while an additional 28% of patients had CTCs negative for all markers other than size and evidence of hyperploidy. CTC number correlated significantly with tumour size and portal vein thrombosis (PVT). The median survival of patients with >1 CTC was 7.5months versus >34months for patients with <1 CTC (p<0.001, log-rank), with significance retained in a multivariate analysis (HR 2.34, 95% CI 1.005-5.425, p=0.049) including tumour size and PVT. CONCLUSIONS: The use of multiple parameters enhanced HCC CTC detection sensitivity, revealing biological associations and predictive biomarker potential that may be able to guide stratified medicine decisions and future research. LAY SUMMARY: Characteristics of tumour tissues can be used to predict outcomes for individual patients with cancer, as well as help to choose their best treatment. Biopsy of liver cancers carries risks, however, and is usually avoided. Some cancer cells enter the blood, and although they are very rare, we have developed a method of finding and characterising them in patients with liver cancer, which we hope will provide a low risk means of guiding treatment.

A novel personal health system with integrated decision support and guidance for the management of chronic liver disease.

A personal health system platform for the management of patients with chronic liver disease that incorporates a novel approach to integrate decision support and guidance through care pathways for patients and their doctors is presented in this paper. The personal health system incorporates an integrated decision support engine that guides patients and doctors through the management of the disease by issuing tasks and providing recommendations to both the care team and the patient and by controlling the execution of a Care Flow Plan based on the results of tasks and the monitored health status of the patient. This Care Flow Plan represents a formal, business process based model of disease management designed off-line by domain experts on the basis of clinical guidelines, knowledge of care pathways and an organisational model for integrated, patient-centred care. In this way, remote monitoring and treatment are dynamically adapted to the patient's actual condition and clinical symptoms and allow flexible delivery of care with close integration of specialists, therapists and care-givers.

Endometrial cancer: a review and current management strategies: part I.

Endometrial carcinoma is the most common gynecologic malignancy. A thorough understanding of the epidemiology, pathophysiology, and management strategies for this cancer allows the obstetrician-gynecologist to identify women at increased risk, contribute toward risk reduction, and facilitate early diagnosis. The Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the literature and created evidence-based practice recommendations for diagnosis and treatment. This article examines: • Risk factors, including genetic predisposition • Diagnostic and metastatic evaluation • Surgical management of early and advanced cancer, including lymphadenectomy in early cancer.

Endometrial cancer: a review and current management strategies: part II.

Endometrial carcinoma is the most common gynecologic malignancy. A thorough understanding of the epidemiology, pathophysiology, and management strategies for this cancer allows the obstetrician-gynecologist to identify women at increased risk, contribute toward risk reduction, and facilitate early diagnosis. The Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the literature through March of 2014 and created evidence-based practice recommendations for diagnosis and treatment. The level of recommendations used is based on the method used by the U.S. Preventive Services Task Force (A: There is good evidence to support the recommendation, B: There is fair evidence to support the recommendation, C: There is insufficient evidence to support the recommendation; however, the recommendation may be made on other grounds, D: There is fair evidence against the recommendation, E: There is good evidence against the recommendation.). It is not the purpose of this document to provide a complete review of the literature on all aspects of endometrial cancer. This article examines: • Adjuvant therapy, including radiation, vaginal brachytherapy, and chemotherapy • Therapy for advanced disease, including chemotherapy and radiation therapy alone and in combination as well as hormone therapy • Treatment for synchronous endometrial and ovarian cancer • Fertility-sparing treatment • Post-treatment patient surveillance • The role of hormone replacement therapy in the development of endometrial carcinoma • Novel targeted therapies.

A prospective study evaluating the clinical relevance of a chemoresponse assay for treatment of patients with persistent or recurrent ovarian cancer.

OBJECTIVE: Use of in vitro chemoresponse assays for informing effective treatment selection is a compelling clinical question and a topic of debate among oncologists. A prospective study was conducted evaluating the use of a chemoresponse assay in recurrent ovarian cancer patients. METHODS: Women with persistent or recurrent ovarian cancer were enrolled under an IRB-approved protocol, and fresh tissue samples were collected for chemoresponse testing. Patients were treated with one of 15 protocol-designated treatments empirically selected by the oncologist, blinded to the assay results. Each treatment was classified by the assay as: sensitive (S), intermediate (I), or resistant (R). Patients were prospectively monitored for progression-free survival (PFS) and overall survival (OS). Associations of assay response for the physician-selected treatment with PFS and OS were analyzed. RESULTS: A total of 262 evaluable patients were enrolled. Patients treated with an assay-sensitive regimen demonstrated significantly improved PFS and OS while there was no difference in clinical outcomes between I and R groups. Median PFS was 8.8 months for S vs. 5.9 months for I+R (hazard ratio [HR]=0.67, p=0.009). The association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate analysis (HR=0.66, p=0.020). A statistically significant14-month improvement in mean OS (37.5 months for S vs. 23.9 months for I+R, HR=0.61, p=0.010) was demonstrated. CONCLUSIONS: This prospective study demonstrated improved PFS and OS for patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer treated with assay-sensitive agents.

Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer.

BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients. METHODS: Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures.

Improving breast care: providing, guiding, expertise, and leadership.

Optimal healthcare blends timeless doctor-patient values with state-of-the-art medical knowledge. The physician's role varies from delivering therapies to guiding patients through the healthcare maze to their best decisions. Breast care should not be parceling out of anatomic parts, as if biological relationships do not exist. Instead, it should stem from an understanding of the "total woman"--biological and otherwise--and how important that unity is for quality of life, even when confronting breast cancer. Breast fellowships for gynecologic and general surgeons create superior clinicians and better patient advocates -essential in advancing women-centric care and healthcare leadership.

Flow cytometry and laser scanning cytometry, a comparison of techniques.

OBJECTIVE: Flow and laser scanning cytometry are used extensively in research and clinical settings. These techniques provide clinicians and scientists information about cell functioning in a variety of health and disease states. An in-depth knowledge and understanding of cytometry techniques can enhance interpretation of current research findings. Our goal with this review is to reacquaint clinicians and scientists with information concerning differences between flow and laser scanning cytometry by comparing their capabilities and applications. METHODS: A Pubmed abstract search was conducted for articles on research, reviews and current texts relating to origins and use of flow and laser scanning cytometry. Attention was given to studies describing application of these techniques in the clinical setting. RESULTS: Both techniques exploit interactions between the physical properties of light. Data are immediately and automatically acquired; they are distinctly different. Flow cytometry provides valuable rapid information about a wide variety of cellular or particle characteristics. This technique does not provide the scanned high resolution image analysis needed for investigators to localize areas of interest within the cell for quantification. Flow cytometry requires that the sample contain a large amount disaggregated, single, suspended cells. Laser scanning cytometry is slide-based and does not require as large of a sample. The tissue sample is affixed to a slide allowing repeated sample analyses. These cytometry techniques are used in the clinical setting to understand pathophysiological derangements associated with many diseases; cardiovascular disease, diabetes, acute lung injury, hemorrhagic shock, surgery, cancer and Alzheimer's disease. CONCLUSIONS: Understanding the differences between FCM and LSCM can assist investigators in planning and design of their research or clinical testing. Researchers and clinicians optimize these technique capabilities with the cellular characteristics they wish to measure delineating molecular and cellular events occurring in health and disease. Discovery of mechanisms in cells using FCM and LSCM provide evidence needed to guide future treatment and interventions.

Surgically (laparotomy/laparoscopy) guided placement of high dose rate interstitial irradiation catheters (LG-HDRT): technique and outcome.

OBJECTIVE: To describe and evaluate the technique and the clinical outcome of a new modality for the treatment of women with persistent or recurrent pelvic malignancies utilizing surgically (laparotomy or laparoscopic) guided high dose rate (HDR) catheters to complete high dose rate interstitial irradiation therapy (LG-HDRT). METHODS: Between 6/2000 and 6/2004, 14 women with histologic evidence of postradiation persistent (3 patients) or recurrent (11 patients) pelvic disease underwent LG-HDRT. Five patients (36%) received treatment for a 2nd, 3rd or 4th recurrence. Preoperative clinical and radiologic evaluation to exclude evidence of extrapelvic disease was routine. Initial intraoperative evaluation included intraabdominal inspection and or biopsy to determine the extent of disease. A two "team" approach was used to place the 100 cm Teflon after loading HDR catheters. Each catheter had its open ends closed with bone wax prior to placement. Using a 14 gauge intravenous catheter as a guide, each HDR catheter was individually placed transvaginally. The tumor bed (treatment volume) was marked circumferentially with clips to facilitate treatment planning. Dosimetry was typically completed on the day of surgery and HDR therapy was started within the initial 24 postoperative hours. The catheters were removed transvaginally, without anesthesia following completion of therapy. RESULTS: Mean patient age was 63.1 years and weight was 138.2 lb. Squamous cell cancer of the vagina or cervix was the most common (64%) diagnosis. The mean time from initial diagnosis to LG-HDRT was 67.9 months. The procedure was completed laparoscopically in 71% of patients, with 4 patients requiring laparotomy (3 conversions from laparoscopy). The mean duration of surgery was 94.9 min and the mean hospital stay was 4.8 days. Only 2 patients (14%) were discharged prior to the completion of therapy. The mean number of catheters placed was 6.1 and the mean dose delivered was 20 Gy over a mean of 5 fractions. There were no major intraoperative complications. Postradiation complications were limited to DVT (1), bladder bleeding (1),