Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Total knee arthroplasty is safe for patients aged ≥80 years in Hong Kong.

INTRODUCTION: Total knee arthroplasty (TKA) is an efficacious operation that improves pain and function in patients with knee arthritis. Because of the population ageing trend in Hong Kong, there is a need to determine the safety profile of TKA in older patients. This study examined the age of patients who underwent TKA in the past 10 years in Hong Kong; the aim was to investigate the mortality safety profile and clinical outcomes of TKA in patients aged ≥80 years. METHODS: This study included all patients who underwent primary TKA in the Hospital Authority (HA) from 2010 to 2019. Incidences of 30-day, 90-day, and 1-year mortality were established. Clinical outcomes of patients aged ≥80 years in one cluster of HA hospitals were assessed. RESULTS: Between 2010 and 2019, 25 040 TKA procedures were conducted in all HA hospitals; 2491 were conducted in patients aged ≥80 years. The median age at operation was higher during 2015-2019 than during 2010-2014 (70 vs 69 years; P<0.001); furthermore, an increase was observed in the proportion of patients aged ≥80 years at the time of operation. Incidences of 30-day, 90-day, and 1-year mortality were 0.156%, 0.35%, and 1.09%, respectively. CONCLUSIONS: In this first study to examine the safety profile of TKA in older patients in Hong Kong, the mean age at the time of TKA and proportion of patients aged ≥80 years have steadily risen in the past decade. Even in older patients, TKA is a reasonably safe procedure.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

Effect of SARS and COVID-19 outbreaks on urology practice and training.

INTRODUCTION: The objective was to investigate the changes in urology practice during coronavirus disease 2019 (COVID-19) pandemic with a perspective from our experience with severe acute respiratory syndrome (SARS) in 2003. METHODS: Institutional data from all urology centres in the Hong Kong public sector during the COVID-19 pandemic (1 Feb 2020-31 Mar 2020) and a non-COVID-19 control period (1 Feb 2019-31 Mar 2019) were acquired. An online anonymous questionnaire was used to gauge the impact of COVID-19 on resident training. The clinical output of tertiary centres was compared with data from the SARS period. RESULTS: The numbers of operating sessions, clinic attendance, cystoscopy sessions, prostate biopsy, and shockwave lithotripsy sessions were reduced by 40.5%, 28.5%, 49.6%, 44.8%, and 38.5%, respectively, across all the centres reviewed. The mean numbers of operating sessions before and during the COVID-19 pandemic were 85.1±30.3 and 50.6±25.7, respectively (P=0.005). All centres gave priority to cancer-related surgeries. Benign prostatic hyperplasia-related surgery (39.1%) and ureteric stone surgery (25.5%) were the most commonly delayed surgeries. The degree of reduction in urology services was less than that during SARS (47.2%, 55.3%, and 70.5% for operating sessions, cystoscopy, and biopsy, respectively). The mean numbers of operations performed by residents before and during the COVID-19 pandemic were 75.4±48.0 and 34.9±17.2, respectively (P=0.002). CONCLUSION: A comprehensive review of urology practice during the COVID-19 pandemic revealed changes in every aspect of practice.

Universal haemoglobin A1c screening reveals high prevalence of dysglycaemia in patients undergoing total knee arthroplasty.

INTRODUCTION: Diabetes mellitus is an established modifiable risk factor for periprosthetic joint infection (PJI). Haemoglobin A1c (HbA1c) is a glycaemic marker that correlates with diabetic complications and PJI. As diabetes and prediabetes are frequently asymptomatic, and there is increasing evidence to suggest a correlation between dysglycaemia and osteoarthritis, it is reasonable to provide HbA1c screening before total knee arthroplasty (TKA). The aim of the present study was to determine the prevalence of dysglycaemia in patients who underwent TKA and investigate whether HbA1c screening and optimisation of glycaemic control before TKA affects the incidence of PJI after TKA. METHODS: Patients who underwent primary TKA before and after routine HbA1c screening was introduced in our unit were reviewed. Prediabetes and diabetes were defined according to the American Diabetes Association. Patients with HbA1c ≥7.5% were referred to an endocrinologist for optimisation of glycaemic control before TKA. The incidence PJI, defined according to the Musculoskeletal Infection Society criteria, was recorded. RESULTS: A total of 729 patients (934 knees) had HbA1c screening before TKA. Of them, 17 (2.3%) and 184 (25.2%) patients had known prediabetes and diabetes, respectively, and 265 (36.4%) and 12 (1.6%) had undiagnosed prediabetes and diabetes, respectively. The incidence of PJI was significantly lower in all patients who received HbA1c screening compared with those who did not (0.2% vs 1.02%, P=0.027). CONCLUSION: Screening for HbA1c before TKA provides a cost-effective opportunity to identify undiagnosed dysglycaemia. Patients identified as having dysglycaemia receive modified treatment, significantly reducing the rate of PJI when compared with historical controls.

Blood transfusions in total knee arthroplasty: a retrospective analysis of a multimodal patient blood management programme.

PURPOSE: Transfusion is associated with increased perioperative morbidity and mortality in patients undergoing total knee arthroplasty (TKA). Patient blood management (PBM) is an evidence-based approach to maintain blood mass via haemoglobin maintenance, haemostasis optimisation, and blood loss minimisation. The aim of the present study was to assess the effectiveness of a multimodal PBM approach in our centre. METHODS: This was a single-centre retrospective study of patients who underwent primary TKA in Queen Mary Hospital in Hong Kong in 2013 or 2018, using data from the Clinical Data Analysis and Reporting System and a local joint registry database. Patient demographics, preoperative haemoglobin, length of stay, readmission, mean units of transfusion, postoperative prosthetic joint infection, and mortality data were compared between groups. RESULTS: In total, 262 and 215 patients underwent primary TKA in 2013 and 2018, respectively. The mean transfusion rate significantly decreased after PBM implementation (2013: 31.3%; 2018: 1.9%, P<0.001); length of stay after TKA also significantly decreased (2013: 14.49±8.10 days; 2018: 8.77±10.14 days, P<0.001). However, there were no statistically significant differences in readmission, early prosthetic joint infection, or 90-day mortality rates between the two groups. CONCLUSION: Our PBM programme effectively reduced the allogeneic blood transfusion rate in patients undergoing TKA in our institution. Thus, PBM should be considered in current TKA protocols to reduce rates of transfusions and related complications.

Tropism of influenza B viruses in human respiratory tract explants and airway organoids.

Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract.Physiologically relevant ex vivo explant cultures of human bronchus and lung, human airway organoids, and in vitro cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included.The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs.Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.

Emergency attendances and hospitalisations for complications after transrectal ultrasound-guided prostate biopsies: a five-year retrospective multicentre study.

INTRODUCTION: Transrectal ultrasound-guided (TRUS) prostate biopsy is an established procedure for diagnosis of prostate cancer. Complications after TRUS biopsy are not well reported in Hong Kong. This study evaluated the 5-year incidences of TRUS biopsy complications and potential risk factors for those complications. METHODS: This was a retrospective review of biopsies performed from 2013 to 2017 in two local hospitals, using data retrieved from electronic medical records. The primary outcome was the occurrence of complications requiring either emergency attendances or hospitalisations within 30 days after biopsy. Potential risk factors were examined using multiple logistic regression analysis. RESULTS: In total, 1699 men were included (mean age ± standard deviation: 67 ± 7 years; median prostate-specific antigen level: 7.9 µg/L [interquartile range, 5.5-12.6 µg/L]); 4.3% had pre-biopsy bacteriuria. Overall, 5.7% and 3.8% of post-biopsy complications required emergency attendances and hospitalisations, respectively. Gross haematuria and rectal bleeding requiring emergency attendances developed in 2.1% and 0.4% of men; 0.8% and 0.4% required hospitalisations. Furthermore, 1.5% of men developed acute urinary retention requiring hospitalisations; 1.9% and 1.2% had post-biopsy infections requiring emergency attendances and hospitalisations, respectively, and 0.9% had urosepsis requiring hospitalisations. Prostate volume >48 cc was associated with an increased risk of post-biopsy retention (odds ratio 2.75, 95% confidence interval: 1.23-4.17). CONCLUSIONS: The rate of overall complications after TRUS biopsy was low. The most common complications requiring emergency attendances and hospitalisations were gross haematuria and acute urinary retention, respectively. Prostate volume >48 cc increased the risk of post-biopsy urinary retention.

The Role of Interventional Radiology in the Management of Obstetric and Gynaecological Haemorrhage

Aim We will review our experience of emergent arterial embolization used to treat haemodynamically unstable patients with obstetric and gynaecological haemorrhage. Methods This is a retrospective study of patients with haemodynamically unstable obstetric and gynaecological haemorrhage treated with emergent arterial embolization from 2010 to 2015. Results 22 patients (average age 41 (SD +/-9) years) had emergent arterial embolization. 63% had post-partum haemorrhage (PPH). 82% of cases were performed with conscious sedation and local anaesthesia. Embolization was technically successful in all cases. Embolization was clinically successful in 95% (21/22). In one case of PPH the patient represented six days later with recurrent bleeding and was treated with surgical suturing of the cervix. There were no complications or deaths. Conclusion Arterial embolization is a highly successful treatment of obstetric and gynaecological haemorrhage in unstable patients.

Post-fracture care gap: a retrospective population-based analysis of Hong Kong from 2009 to 2012.

INTRODUCTION: Patients who sustain an osteoporotic fracture are at increased risk of sustaining further osteoporotic fracture. The risk can be reduced by prescription of anti-osteoporosis medication. The aim of the present study was to determine the current practice in Hong Kong regarding secondary drug prevention of fragility fractures after osteoporotic hip fracture. METHODS: Dispensation of anti-osteoporosis medication records from patients with new fragility hip fractures aged ≥65 years were retrieved using the Hospital Authority Clinical Data Analysis and Reporting System from 2009 to 2012. The intervention rate each year was determined from the percentage of patients receiving anti-osteoporosis medication within 1 year after hip fracture. RESULTS: A total of 15 866 patients with osteoporotic hip fracture who met the criteria were included. The intervention rate differed each year from 2009 to 2012, ranging between 9% and 15%. Orthopaedic surgeons initiated 63% of anti-osteoporosis medication, whereas physicians initiated 37%. The anti-osteoporosis drugs being prescribed included alendronic acid (76%), ibandronic acid (12%), strontium ranelate (5%), and zoledronic acid (4%). CONCLUSION: Most patients with hip fracture remained untreated for 1 year after the osteoporotic hip fracture. The Hospital Authority should allocate more resources to implement a best practice framework for treatment of patients with hip fracture at high risk of secondary fracture.

Patterns and Drivers of Costs for Neuroendocrine Tumor Care: A Comparative Population-Based Analysis.

BACKGROUND: Little is known about resource use in the care of neuroendocrine tumors (NETs). This study defined patterns of costs in NET management and compared them with those of a more common malignancy, colon cancer (CC). METHODS: Using a provincial cancer registry (2004-2012), NET patients were identified and matched at a ratio of 1-3 with CC patients. Four phases of care were examined: pre-diagnostic (PreDx: -2 years to -181 days), diagnostic (Dx: -180 days to +180 days), postdiagnostic (PostDx: +181 days to +3 years), and prolonged post-diagnostic (PPostDx: +181 days to +9 years). The mean costs per patient were compared, and cost predictors were analyzed with quintile regression. RESULTS: Of 3827 NETs, 3355 were matched with 9320 CCs. The PreDx mean NET costs were higher than the CC costs ($5877 vs $5368; p = 0.06), driven by nondrug costs. They were lower in the Dx and PostDx phases (both p < 0.01). For PPostDx, the drug costs were higher for NETs ($26,788 vs $7827; p < 0.01), representing 41% of the costs versus 16% of the costs for CC. Older age and comorbidities predicted higher NET costs in all phases. Lower socioeconomic status (SES) predicted higher costs in the initial phases and higher SES costs in the PPost-Dx phase. Gastroenteric NETs were associated with lower costs in the Dx phase [parameter estimate (PE), -$13,644] and pancreatic NETs with higher costs in PostDx phase (PE, $3348). CONCLUSION: Currently, NETs represent a potential important health care burden. The NET cost patterns differed from those for CC, with the highest costs during the PPostDx phase. The SES and primary NET site affected costs differently at different time points. These data can inform resource allocation tailored to the needs for NETs.

Operative outcome of Hong Kong centenarians with hip fracture.

INTRODUCTION: International clinical guidelines recommend early surgical treatment for geriatric patients with hip fracture. There are, however, few data concerning the operative outcome of centenarians. This study aimed to report the epidemiology of hip fracture and postoperative mortality rate, and to discuss whether operation is justified in centenarians in Hong Kong. METHODS: This observational study was carried out in all public hospitals of Hong Kong. All patients aged 100 years or above who underwent hip fracture surgery in any public hospital between 1 January 2010 and 31 December 2013 were included. Their postoperative mean and median survival time was recorded. RESULTS: Of 114 centenarians, 96 (84%) were female. The age of patients ranged from 100 to 109 years, with the largest number (44%) aged 100 years. The follow-up interval ranged from 5 to 1619 days (median, 412 days; interquartile range, 683 days). The 1-month, 6-month, and 1-year mortalities were 8%, 25%, and 37%, respectively. By Kaplan-Meier analysis, the postoperative mean survival was 2 years 2 months (95% confidence interval, 680-936 days) and the median survival time was 2 years (interquartile range, 1234 days). CONCLUSION: The 1-year mortality among Hong Kong centenarians with hip fracture was 37%, which is lower than the 41.1% in the general centenarian population in Japan. The median survival time after hip fracture surgery was 2 years, suggesting that surgery even at an extreme age is worthwhile to maintain quality of life. Extreme age should not be a barrier to operative treatment.

Intravenous lignocaine infusion facilitates acute rehabilitation after laparoscopic colectomy in the Chinese patients.

INTRODUCTION: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery. METHODS: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay. RESULTS: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days. CONCLUSIONS: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.

Examining the medical resource utilization and costs of relapsed and refractory chronic lymphocytic leukemia in Ontario.

PURPOSE: The purpose of the present study was to collect medical resource utilization data and costs in Ontario for the management of patients with relapsed or refractory chronic lymphocytic lymphoma (cll) who have undergone at least 1 treatment course and have been stratified by Rai staging. METHODS: This retrospective longitudinal cohort study, conducted by chart review, analyzed anonymized patient records from two cancer centres in Ontario. Comprehensive records of 86 patients meeting the inclusion criteria were used to obtain resource utilization, which, multiplied by unit costs, were used to determine overall and mean costs. Descriptive statistics are presented for patient demographics, medical resource utilization, and costing data. RESULTS: The total cost for the cohort was $2.2 million over a mean follow-up period of 4.7 years. The mean total cost per patient (regardless of follow-up) was $25,736. In terms of Rai staging, overall mean costs were highest for stage iv patients. Almost 50% of the total cost was attributable to cll treatments, among which fludarabine-based treatments had the highest utilization. CONCLUSIONS: For this Canadian cll cohort, medical resource utilization and costs were determined to be $2.2 million, with cll treatments accounting for about half the cost. Costs generally increased with Rai stage.

Improvement in nitrogen fixation capacity could be part of the domestication process in soybean.

Biological nitrogen fixation (BNF) in soybeans is a complex process involving the interplay between the plant host and the symbiotic rhizobia. As nitrogen supply has a crucial role in growth and development, higher nitrogen fixation capacity would be important to achieve bigger plants and larger seeds, which were important selection criteria during plant domestication by humans. To test this hypothesis, we monitored the nitrogen fixation-related performance in 31 cultivated and 17 wild soybeans after inoculation with the slow-growing Bradyrhizobium diazoefficiens sp. nov. USDA110 and the fast-growing Sinorhizobium (Ensifer) fredii CCBAU45436. Our results showed that, in general, cultivated soybeans gave better performance in BNF. Electron microscopic studies indicated that there was an exceptionally high accumulation of poly-ß-hydroxybutyrate bodies in bacteroids in the nodules of all wild soybeans tested, suggesting that the C/N balance in wild soybeans may not be optimized for nitrogen fixation. Furthermore, we identified new quantitative trait loci (QTLs) for total ureides and total nodule fresh weight by employing a recombinant inbred population composed of descendants from a cross between a cultivated and a wild parent. Using nucleotide diversity (θπ), divergence index (Fst) and distribution of fixed single-nucleotide polymorphisms as parameters, we found that some regions in the total ureides QTL on chromosome 17 and the total nodule fresh weight QTL on chromosome 12 exhibited very low diversity among cultivated soybeans, suggesting that these were traits specially selected during the domestication and breeding process.

Clinical outcome of neoadjuvant chemoradiation in locally advanced rectal cancer at a tertiary hospital.

OBJECTIVES: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome. METHODS: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented. RESULTS: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery. CONCLUSIONS: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

The experiences of cancer survivors while transitioning from tertiary to primary care.

PURPOSE: In current fiscally constrained health care systems, the transition of cancer survivors to primary care from tertiary care settings is becoming more common and necessary. The purpose of our study was to explore the experiences of survivors who are transitioning from tertiary to primary care. METHODS: One focus group and ten individual telephone interviews were conducted. Data saturation was reached with 13 participants. All sessions were audio-recorded, transcribed verbatim, and analyzed using a qualitative descriptive approach. RESULTS: Eight categories relating to the main content category of transition readiness were identified in the analysis. Several factors affected participant transition readiness: how the transition was introduced, perceived continuity of care, support from health care providers, clarity of the timeline throughout the transition, and desire for a "roadmap." Although all participants spoke about the effect of their relationships with health care providers (tertiary, transition, and primary care), their relationship with the primary care provider had the most influence on their transition readiness. CONCLUSIONS: Our study provided insights into survivor experiences during the transition to primary care. Transition readiness of survivors is affected by many factors, with their relationship with the primary care provider being particularly influential. Understanding transition readiness from the survivor perspective could prove useful in ensuring patient-centred care as transitions from tertiary to primary care become commonplace.

Follow-up care for survivors of lymphoma who have received curative-intent treatment.

OBJECTIVE: This evidence summary set out to assess the available evidence about the follow-up of asymptomatic survivors of lymphoma who have received curative-intent treatment. METHODS: The medline and embase databases and the Cochrane Database of Systematic Reviews were searched for evidence published between 2000 and August 2015 relating to lymphoma survivorship follow-up. The evidence summary was developed by a Working Group at the request of the Cancer Care Ontario Survivorship and Cancer Imaging programs because of the absence of evidence-based practice documents in Ontario for the follow-up and surveillance of asymptomatic patients with lymphoma in complete remission. RESULTS: Eleven retrospective studies met the inclusion criteria. The proportion of relapses initially detected by clinical manifestations ranged from 13% to 78%; for relapses initially detected by imaging, the proportion ranged from 8% to 46%. Median time for relapse detection ranged from 8.6 to 19 months for patients initially suspected because of imaging and from 8.6 to 33 months for those initially suspected because of clinical manifestations. Only one study reported significantly earlier relapse detection for patients initially suspected because of clinical manifestations (mean: 4.5 months vs. 6.0 months, p = 0.042). No benefit in terms of overall survival was observed for patients depending on whether their relapse was initially detected because of clinical manifestations or surveillance imaging. SUMMARY: Findings in the present study support the importance of improving awareness on the part of survivors and clinicians about the symptoms that might be associated with recurrence. The evidence does not support routine imaging for improving outcomes in this patient population.

BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts.

BACKGROUND: Germline mutations of the BRCA tumour suppressors have been associated with increased risk of pancreatic cancer. Clinical evidence suggests that these patients may be more sensitive to treatment with cisplatin. As the frequency of germline BRCA mutations is low, definitive experimental data to support the clinical observations are still missing. METHODS: We tested gemcitabine and cisplatin sensitivity of four BRCA1 and BRCA2 mutant and three BRCA1 and BRCA2 wild-type (WT) patient-derived pancreatic cancer xenografts. RESULTS: We observed treatment sensitivity to gemcitabine and cisplatin in the BRCA WT and mutant models. The BRCA1 and BRCA2 mutant xenografts were significantly more sensitive to cisplatin although these models also showed sensitivity to gemcitabine. The BRCA1 and BRCA2 WT models showed sensitivity to gemcitabine but not cisplatin. Treatment sensitivity in the xenograft models closely resembled treatment response in the corresponding patients. DISCUSSION: We have characterised a panel of xenografts derived from pancreatic cancer patients carrying germline BRCA mutations, and shown that their genetic features resemble the patient donor. Our results support further clinical testing of treatment regimens combining gemcitabine and platinum drugs in this patient population, as well as preclinical research aiming to identify mechanisms of cisplatin resistance in BRCA mutant pancreatic cancers.