Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis.

INTRODUCTION: The difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery. METHOD: We conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated. RESULTS: In total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6). CONCLUSION: Right colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.

Porcine dermal collagen mesh (Permacol™) as a bioprosthesis in the ligation of intersphincteric tract (BioLIFT) procedure.

BACKGROUND: Ligation of intersphincteric tract (LIFT) is a sphincter-saving technique used to treat anal fistulas. Incorporation of a bioprosthesis in LIFT (BioLIFT) aims to improve healing. The use of cross-linked porcine dermal collagen mesh Permacol™ in BioLIFT has never been investigated. The aim of this study was to compare the healing rates and outcome of LIFT and BioLIFT for complex anal fistulas using the Permacol™ biological mesh. METHODS: A retrospective analysis of all patients having LIFT or BioLIFT for complex fistulas from January 2010 to November 2019 was performed in a tertiary referral centre. Patient data from a prospectively collected database of all patients having LIFT or BioLIFT were analyzed. RESULTS: LIFT and BioLIFT were performed in 48 (82.8%) and 10 (17.2%) patients, respectively. All BioLIFT patients had previous interventions for their fistulas compared to 30 (62.5%) of patients who had LIFT, p = 0.023. The primary healing rate for LIFT was 87.5% (42/48) compared to 80% (8/10) in BioLIFT, (p = 0.42). Eight (13.8%) patients developed complications, 6 (12.5%) in the LIFT group vs 2 (20%) in the BioLIFT group (p = 0.62). On univariate analysis, the number of previous operations was predictive of complications (p = 0.03). BioLIFT was not associated with complication (OR = 1.75, 95% CI: 0.30-10.3, p = 0.54) or primary healing (OR = 0.57, 95% CI: 0.97-3.36, p = 0.54). There was no significant difference in recurrence (LIFT 12.5% vs BioLIFT 0%, p = 0.58). Kaplan-Meier analysis found no difference in time to recurrence between the two groups (p = 0.65). CONCLUSION: Permacol™ mesh in BioLIFT is feasible and achieves a high primary healing rate of 80%. Prospective evidence is needed to establish the benefits of BioLIFT and determine whether Permacol™ is superior to the non-cross-linked porcine submucosal mesh.

Calculation of the Hadronic Vacuum Polarization Contribution to the Muon Anomalous Magnetic Moment.

We present a first-principles lattice QCD+QED calculation at physical pion mass of the leading-order hadronic vacuum polarization contribution to the muon anomalous magnetic moment. The total contribution of up, down, strange, and charm quarks including QED and strong isospin breaking effects is a_{µ}^{HVP LO}=715.4(18.7)×10^{-10}. By supplementing lattice data for very short and long distances with R-ratio data, we significantly improve the precision to a_{µ}^{HVP LO}=692.5(2.7)×10^{-10}. This is the currently most precise determination of a_{µ}^{HVP LO}.

Effect of Ligand Modification on the Mechanism of Electrocatalytic Hydrogen Production by Ni(pyridinethiolate)3- Derivatives.

The effects of ligand modification on the catalytic mechanism of hydrogen production by Ni(PyS)3- derivatives, made with electron-withdrawing and -donating substitutions to the pyridinethiolate (PyS)- ligands, are studied experimentally and computationally using density functional theory. Thermodynamic data, spin density maps, and frontier molecular orbital diagrams were generated for reaction intermediates. Comparison of computed values for E0 and p Ka with experimental values supports the proposed mechanisms. The rate of electrochemical hydrogen production is correlated with the effect of ligand modification. Notably, the presence of an electron-donating substituent favors an alternative mechanism for hydrogen production. Computationally it was determined that the electron-donating substituent causes deviation from the original chemical-electrochemical-chemical-electrochemical (CECE) mechanism of Ni(PyS)3- to a CCEE mechanism, while the CECE mechanism is maintained for all catalysts substituted with electron-withdrawing groups.

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. METHODS: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. RESULTS: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. CONCLUSIONS: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Comparing the meanings of living with advanced breast cancer between women resilient to distress and women with persistent distress: a qualitative study.

BACKGROUND: Most women with advanced breast cancer (ABC) show little distress, but about one in ten show persistent distress over time. It remains unclear if meanings ascribed by patients to ABC differentiate these distress trajectories. STUDY AIMS: This qualitative study (a) compared illness meanings of ABC between women with persistent psychological distress and those with low/transient distress, and (b) examined how illness meanings might influence coping strategies. METHODS: The sample was drawn from a prior quantitative study exploring psychological distress trajectories following ABC diagnosis. Overall, 42 Cantonese- or Mandarin-speaking Chinese women diagnosed with locally advanced or metastatic ABC were recruited based on their distress trajectory status (low-stable, transient, or persistent distress). Interviews were recorded, transcribed, and analyzed following grounded theory approach using simultaneous analysis. RESULTS: Women with persistent distress viewed their diagnosis as another blow in life, the illness was global, permeating every aspect of their life. Maladaptive rumination and thought suppression were common responses to illness demands. These women had poor social support. A sense of demoralization stood out in their narratives. In contrast, women with transient/low-stable distress encapsulated the illness, with minimum impacts of their life. They did not evidence dysfunctional repetitive thoughts. Living in a supportive environment, they were able to accept and/or live in the present-moment. CONCLUSIONS: Rumination, thought suppression, social constraints, and pre-existing exposure to life stress may be potential risks for chronic distress in response to advanced breast cancer. Persistent and transient distress responses to cancer may have different underpinnings. Copyright © 2016 John Wiley & Sons, Ltd.

Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer.

Optimal interval between neoadjuvant chemoradiotherapy (CRT) and surgery is not elucidated for esophageal squamous carcinoma. The aim of this study is to evaluate the impact of this time interval on patient outcome. Patients treated with neoadjuvant CRT followed by surgery between 2002 and 2009 were analyzed. Patients were divided into two groups based on the median interval to surgery (64 days): A  64 days (n = 53). A second analysis was performed by re-classifying patients into three interval groups: A* ≤ 40 days (n = 16); B* 41-80 days (n = 60); C* > 80 days (n = 31). Operative outcome, pathological data, and long-term survival were analyzed. One hundred and seven (n = 107) patients were analyzed. Five patients (9.4%) in group B had an anastomotic leak compared with no leakage from group A (P < 0.021). The complete pathological response was comparable in groups A and B (35% vs. 24.5%, p = 0.23). R0 was significantly lower in group A* (A*: 56.3%, B*: 90%, C*: 74.2%, P = 0.006). In patients with R0 resection, 5-year survival was significantly better in group A than B (71.7% vs. 51%, P = 0.032) and in group A* (A* 100% vs. B* 60.2% & C* 48.3%; A* vs. B*, P = 0.036; A* vs. C*, P = 0.019). Complete pathological response was an independent predictor of survival. Early surgery with R0 resection following neoadjuvant CRT may lead to a better outcome. Further prospective studies are still necessary to provide better insight into the issue. At present, timing of surgery should be individualized and performed at the earliest opportunity.

Post-esophagectomy gastric conduit cancers: treatment experiences and literature review.

Esophagectomy remains the mainstay of treatment for esophageal cancer. The stomach is the commonest organ used to restore intestinal continuity after esophagectomy. Metachronous gastric cancer in the gastric conduit after esophagectomy is rare; the etiology remains unclear. Possible risk factors include Helicobacter pylori infection, biliary or pancreatic reflux and prior radiotherapy. Prognosis of these patients remains poor. Treatment of this particular entity poses unique challenges to the surgeon and oncologist. Early diagnosis by endoscopy may allow endoscopic excision such as endoscopic mucosal resection or endoscopic submucosal dissection. In more advanced cancers, surgery is difficult, reconstruction is complicated, and further radiation may not be feasible because of previous neoadjuvant therapy. In this report, four patients who developed gastric conduit cancers are presented. They were treated with either surgery alone or combined with chemoradiotherapy. All four patients were still alive after at least 21 months, with three patients currently still alive (21-48 months). The literature is also reviewed, in particular addressing the incidence, possible underlying causes, prognosis and options of treatment for this specific clinical scenario.

Subtyping of triple-negative breast cancers: its prognostication and implications in diagnosis of breast origin.

BACKGROUND: Triple-negative breast cancer (TNBC) subtyping by gene profiling has provided valuable clinical information. Here, we aimed to evaluate the relevance of TNBC subtyping using immunohistochemistry (IHC), which could be a more clinically practical approach, for prognostication and applications in patient management. METHODS: A total of 123 TNBC cases were classified using androgen receptor (AR), CD8, Forkhead box C1 protein (FOXC1), and doublecortin-like kinase 1 (DCLK1) into luminal androgen receptor (LAR), basal-like immunosuppressive (BLIS), mesenchymal-like (MES), and immunomodulatory (IM) subtypes. The IM cases were further divided into the IM-excluded and IM-inflamed categories by CD8 spatial distribution. Their clinicopathological and biomarker profiles and prognoses were evaluated. RESULTS: LAR (28.6%) and MES (11.2%) were the most and least frequent subtypes. The IHC-TNBC subtypes demonstrated distinct clinicopathological features and biomarker profiles, corresponding to the reported features in gene profiling studies. IM-inflamed subtype had the best outcome, while BLIS had a significantly poorer survival. Differential breast-specific marker expressions were found. Trichorhinophalangeal syndrome type 1 (TRPS1) was more sensitive for IM-inflamed and BLIS, GATA-binding protein 3 (GATA3) for IM-excluded and MES, and gross cystic disease fluid protein 15 (GCDFP15) for LAR subtypes. CONCLUSIONS: Our findings demonstrated the feasibility of IHC surrogates to stratify TNBC subtypes with distinct features and prognoses. The IM subtype can be refined by its CD8 spatial pattern. Breast-specific marker expression varied among the subtypes. Marker selection should be tailored accordingly.

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study.

BACKGROUND: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. METHODS: Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. RESULTS: Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. CONCLUSION: Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms.

Challenges in oncology career: are we closing the gender gap? Results of the new ESMO Women for Oncology Committee survey.

BACKGROUND: Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. MATERIALS AND METHODS: The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. RESULTS: The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work-life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. CONCLUSIONS: Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.

The potency of allospecific Tregs cells appears to correlate with T cell receptor functional avidity.

CD4(+) CD25(+) regulatory T cells (T(reg) cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T-cell receptor (TcR) activation is critical for T(reg) function, suggesting that the TcR avidity of T(reg) cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of T(reg) lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. T(reg) lines generated from CD4(+)CD25(+) T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced T(reg) lines was confirmed in vitro. T(reg) lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro. Furthermore, the same T(reg) lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these T(reg) cells, together with anti-CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received T(reg) lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for T(reg) function. It highlights the fact that strategies to select T(reg) with higher functional avidity might be beneficial for immunotherapy in transplantation.

Validation of the Chinese version of the short-form Supportive Care Needs Survey Questionnaire (SCNS-SF34-C).

BACKGROUND: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). METHODS: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. RESULTS: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). DISCUSSION: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types.

Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong.

We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p < 0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p = 0.01) and received more ß-lactam antibiotics in the preceding 3 months compared with the controls (p = 0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p < 0.001) and the rate of positive detection from 4.17% to 6.28% (p < 0.001) between period 1 (2004-2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027.

[Application of three-staged paramedian forehead flap in reconstruction and repair of full-thickness nasal defect].

Objective: To evaluate the application of three-staged paramendian forehead flap technique in reconstruction of severe full-thickness nasal defect. Methods: Clinical data of 7 cases with nasal reconstruction by three-staged forehead flap technique in the First Affiliated Hospital of Xinjiang Medical University and HongKong University Shenzhen Hospital between June 2016 and October 2019 was retrospectively reviewed. All were males aged from 10 to 71 years. There were 4 cases of basal cell carcinoma of the external nose, 2 cases of traumatic nasal defects and 1 case of large rhinophyma. All the operations were performed with the paramedian forehead flap in three stages. In stage Ⅰ, full layered forehead flap was transposed to the nasal detect. Lining flaps were reconstructed with folded forehead skin (n=4), turn-over flap plus septal chondro mucosal pivotal flap (n=2), or bipedicled vestibular skin and nasal mucosa advancement flap (n=1). According to the reconstruction mode of the lining flaps, whether to implant cartilage to reconstruct the external nasal stent at stage Ⅰ was determined. At stage Ⅱ, the folded flaps were partly or completely separated from the covering flaps along the free edges of nasal alar. All the excess soft tissue including subcutaneous fat and frontalis muscle were excised, cartilage grafts were placed or sculpted to make an ideal nasal contour. The covering flaps were then returned on the recontoured, three-dimensional recipient bed. At stage Ⅲ, the pedicles were divided. Descriptive statistical method was used to analyze the data. Results: In all cases, restoration of the nasal contour was remarkably good, no flap necrosis occurred. All patients were followed up for 6 months to 2 years, and the appearance and function of the nose recovered well. All patients were satisfied with their final aesthetic results. Conclusions: Three-staged paramedian forehead flap technique ensures maximal blood supply for the lining flap and the inserted cartilage graft, and restores an ideal three-dimensional nasal contour for reconstruction of large full thickness nasal defects.

Has COVID-19 had a greater impact on female than male oncologists? Results of the ESMO Women for Oncology (W4O) Survey.

BACKGROUND: European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. METHODS: A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. RESULTS: Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). CONCLUSIONS: The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.

Female leadership in oncology-has progress stalled? Data from the ESMO W4O authorship and monitoring studies.

BACKGROUND: Exploratory research showed that female oncologists are frequently under-represented in leadership roles. European Society for Medical Oncology (ESMO) Women for Oncology (W4O) therefore implemented gender equality programs in career development and established international studies on female representation at all stages of the oncology career pathway. METHODS: For 2017-2019, data were collected on (i) first and last authorship of publications in five major oncology journals and (ii) representation of women in leadership positions in oncology-as invited speakers at National/International congresses, board members or presidents of National/International societies and ESMO members. The 2015/2016 data from the first published W4O Study were incorporated for comparisons. RESULTS: Across 2017-2019, female oncologists were significantly more likely to be first than last authors (P < 0.001). The proportion of female first authors was similar across years: 38.0% in 2017, 37.1% in 2018, 41.0% in 2019 (P = 0.063). The proportion of female last authors decreased from 30.4% in 2017 to 24.2% in 2018 (P = 0.0018) and increased to 28.5% in 2019 (P = 0.018). Across 2015-2019, invited speakers at International/National oncology congresses were significantly less likely to be female than male (P < 0.001; 29.7% in 2015 to 36.8% in 2019). Across 2016-2019, board members of International/National oncology societies were significantly less likely to be female than male (P < 0.001; 26.8% in 2016 to 35.8% in 2019). There were statistically significant increasing trends in female speakers and board members across the study periods (P < 0.001 for both). Societies with a female president had a higher proportion of female board members across these periods (P = 0.026). CONCLUSIONS: Reported progress towards gender equality in career development in oncology is real but slow. Women in leadership positions are essential for encouraging young women to aspire to and work towards similar or greater success. Therefore, continued monitoring is needed to inform ESMO W4O initiatives to promote gender balance at all stages of the career pathway.

Generation of multi-functional antigen-specific human T-cells by lentiviral TCR gene transfer.

T-cell receptor (TCR) gene transfer is an attractive strategy to generate antigen-specific T-cells for adoptive immunotherapy of cancer and chronic viral infection. However, current TCR gene transfer protocols trigger T-cell differentiation into terminally differentiated effector cells, which likely have reduced ability to mediate disease protection in vivo. We have developed a lentiviral gene transfer strategy to generate TCR-transduced human T-cells without promoting T-cell differentiation. We found that a combination of interleukin-15 (IL15) and IL21 facilitated lentiviral TCR gene transfer into non-proliferating T-cells. The transduced T-cells showed redirection of antigen specificity and produced IL2, IFNgamma and TNFalpha in a peptide-dependent manner. A significantly higher proportion of the IL15/IL21-stimulated T-cells were multi-functional and able to simultaneously produce all three cytokines (P<0.01), compared with TCR-transduced T-cells generated by conventional anti-CD3 plus IL2 stimulation, which primarily secreted only one cytokine. Similarly, IL15/IL21 maintained high levels of CD62L and CD28 expression in transduced T-cells, whereas anti-CD3 plus IL2 accelerated the loss of CD62L/CD28 expression. The data demonstrate that the combination of lentiviral TCR gene transfer together with IL15/IL21 stimulation can efficiently redirect the antigen specificity of resting primary human T-cells and generate multi-functional T-cells.