Pregnancy-related breast cancer: 14-year experience in a tertiary institution in Hong Kong.

BACKGROUND: The incidence of pregnancy-associated breast cancer (PABC) is increasing. Its tumor characteristics and overall survival compared with those in nonpregnant patients remain controversial. While there have been suggestions that PABC patients have a 40 % increase in the risk of death compared to non-pregnant patients, other studies suggested similar disease outcomes. This study aims to review our local experience with PABC. METHODS: Twenty-eight patients diagnosed with PABC and twenty-eight patients diagnosed at premenopausal age randomly selected by a computer-generated system during the same period were recruited. Background characteristics, tumor features, and survival were compared. RESULTS: Among the twenty-eight pregnant patients, seventeen were diagnosed during pregnancy, and eleven were diagnosed in the postpartum period. Compared to the non-pregnant breast cancer patients, they presented with less progesterone receptor-positive tumor (35.7 % vs. 64.2 %, p = 0.03). Although there was no statistically significant difference in tumor size (p = 0.44) and nodal status (p = 0.16), the tumor tended to be larger in size (2.94 +/- 1.82 vs 2.40 +/- 1.69 cm) and with more nodal involvement (35.7 % vs 25.0 %). There was also a trend of delayed presentation to medical attention, with a mean duration of 13.1 weeks in the PABC group and 8.6 weeks in the control group. However, the overall survival did not differ (p = 0.63). CONCLUSION: PABC is increasing in incidence. They tend to have more aggressive features, but overall survival remains similar. A multidisciplinary approach is beneficial for providing the most appropriate care.

Extracellular vesicles as a potential therapeutic for age-related macular degeneration.

Age-related macular degeneration is a major global cause of central visual impairment and severe vision loss. With an aging population, the already immense economic burden of costly anti-vascular endothelial growth factor treatment is likely to increase. In addition, current conventional treatment is only available for the late neovascular stage of age-related macular degeneration, and injections can come with potentially devastating complications, introducing the need for more economical and risk-free treatment. In recent years, exosomes, which are nano-sized extracellular vesicles of an endocytic origin, have shown immense potential as diagnostic biomarkers and in the therapeutic application, as they are bestowed with characteristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells. Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases; however, exosomes as a potential therapy for several retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically. This article will focus on the limited literature available on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures, as well as briefly identify future research directions. Current literature on exosome therapy using age-related macular degeneration rodent models includes laser retinal injury, N-methyl-N-nitrosourea, and royal college of surgeon models, which mimic inflammatory and degenerative aspects of age-related macular degeneration. These have shown promising results in preserving retinal function and morphology, as well as protecting photoreceptors from apoptosis. Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cytokines, mRNAs, and proteins involved in photoreceptor degeneration pathways to exert a therapeutic effect. Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.

Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. OBJECTIVES: We aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. METHODS: In this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. RESULTS: PE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets' expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. CONCLUSIONS: We revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.

Hypercoagulability and Inflammatory Markers in a Case of Congenital Thrombotic Thrombocytopenic Purpura Complicated by Fetal Demise.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder caused by an inherited genetic deficiency of ADAMTS13 and affects less than one per million individuals. Patients who are diagnosed with TTP during pregnancy are at increased risk of maternal and fetal complications including fetal demise. We present a case of a 32-year-old G3P0 (gravida 3, para 0) who presented at 20 weeks gestation with a new diagnosis of congenital TTP (cTTP) and fetal demise. METHODS: We describe the pathophysiology of pregnancy complications in a patient with cTTP using platelet procoagulant membrane dynamics analysis and quantitative proteomic studies, compared to four pregnant patients with gestational hypertension, four pregnant patients with preeclampsia, and four healthy pregnant controls. RESULTS: The cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, suggestive of hypercoagulability. Among 15 proteins that were upregulated, S100A8 and S100A9 were distinctly overexpressed. CONCLUSIONS: There is platelet-neutrophil activation and interaction, platelet hypercoagulability, and proinflammation in our case of cTTP with fetal demise.

Proteomics and Metabolomics Profiling of Platelets and Plasma Mediators of Thrombo-Inflammation in Gestational Hypertension and Preeclampsia.

Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets' contribution to the thrombo-inflammatory states of preeclampsia.

Cognitive Aids for the Management of Thoracic Anesthesia Emergencies: Consensus Guidelines on Behalf of a Canadian Thoracic Taskforce.

A cognitive aid is a tool used to help people accurately and efficiently perform actions. Similarly themed cognitive aids may be collated into a manual to provide relevant information for a specific context (eg, operating room emergencies). Expert content and design are paramount to facilitate the utility of a cognitive aid, especially during a crisis when accessible memory may be limited and distractions may impair task completion. A cognitive aid does not represent a rigid approach to problem-solving or a replacement for decision-making. Successful cognitive aid implementation requires dedicated training, access, and culture integration. Here the authors present a set of evidence-based cognitive aids for thoracic anesthesia emergencies developed by a Canadian thoracic taskforce.

Guidelines to the Practice of Anesthesia - Revised Edition 2021.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2021 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2021 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

RéSUMé: Le Guide d'exercice de l'anesthésie, version révisée 2021 (le Guide), a été préparé par la Société canadienne des anesthésiologistes (SCA), qui se réserve le droit de décider des termes de sa publication et de sa diffusion. Le Guide est soumis à révision et des versions mises à jour sont publiées chaque année. Le Guide d'exercice de l'anesthésie, version révisée 2021, remplace toutes les versions précédemment publiées de ce document. Bien que la SCA incite les anesthésiologistes du Canada à se conformer à son guide d'exercice pour assurer une grande qualité des soins dispensés aux patients, elle ne peut garantir les résultats d'une intervention spécifique. Les anesthésiologistes doivent exercer leur jugement professionnel pour déterminer la méthode d'intervention la mieux adaptée à l'état de leur patient. La SCA n'accepte aucune responsabilité ou imputabilité de quelque nature que ce soit découlant d'erreurs ou d'omissions ou de l'utilisation des renseignements contenus dans son Guide d'exercice de l'anesthésie.

Guidelines to the Practice of Anesthesia - Revised Edition 2020.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2020 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2020 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Guidelines to the Practice of Anesthesia - Revised Edition 2019.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2019 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2019 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Guidelines to the Practice of Anesthesia - Revised Edition 2018.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2018 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2018 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Guidelines to the Practice of Anesthesia - Revised Edition 2017.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2017 (the guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. Because the guidelines are subject to revision, updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2017 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the society cannot guarantee any specific patient outcome. Each anesthesiologist should exercise his or her own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Guidelines to the Practice of Anesthesia - Revised Edition 2016.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2016 (the guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. Because the guidelines are subject to revision, updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2016 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the society cannot guarantee any specific patient outcome. Each anesthesiologist should exercise his or her own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program.

OBJECTIVE: Brain metastasis occurs in 10-15% of metastatic breast cancer patients and is associated with poor prognosis. This study aims to identify tumor characteristics of primary breast cancer, which are related to brain metastases in Hong Kong Chinese patients. METHODS: A retrospective study of patients with invasive breast cancer receiving treatment in a university hospital from January 2001 to December 2008 was performed. The clinicopathological factors of patients with brain metastases were analyzed and compared with those who had no brain metastasis. Risk factors for brain metastasis were identified by univariate analysis first and then by multivariate analysis. RESULTS: A total of 912 patients with invasive breast cancer were treated during the study period. Of these, 30 patients were found to have distant metastases to brain. Patients with brain metastases had more breast tumors of higher histological grade (Grade III, 78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate analysis, only high tumor grading was found to be predictive of developing brain metastasis. CONCLUSION: Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients.

Anesthesia in the pregnant patient with hematologic disorders.

The management of patients with hematologic disorders in pregnancy involves a multidisciplinary approach involving specialists from hematology, obstetrics, and anesthesiology. Whereas regional anesthesia has led to a decline in maternal morbidity and mortality, the presence of uncorrected coagulopathy or the use of anticoagulant or antithrombotic medications pose a special risk for the rare complication of an epidural hematoma after neuraxial anesthesia. This article briefly reviews the common principles of anesthesia for obstetric patients, provides an obstetric anesthesiologist's perspective on the implications of regional anesthesia in obstetrics, and enhances communication between the specialties.

Outcome of laparoscopic resection for colorectal cancer in patients with high operative risk.

BACKGROUND: There is general concern that high-risk patients are more susceptible to the adverse effect of pneumoperitoneum and they are often denied laparoscopic surgery. This study investigated the impact of laparoscopic colorectal cancer resection for patients with high operative risk, which was defined as American Society of Anesthesiologist classes 3 and 4. METHODS: Three hundred thirty-five consecutive high-risk patients who had colorectal cancer resection by open or laparoscopic surgery were included. The patient and tumor characteristics and operative outcomes were recorded prospectively, and comparison was made between the two groups. RESULTS: Compared to open surgery, patients with laparoscopic resection had a shorter hospital stay (8 [6-12] vs. 6 [4-9] days; P < 0.001), less blood loss (200 [100-400] vs. 140 [80-250] mL; P = 0.006), reduced cardiac complication rate (13.2% vs. 3.7%; P = 0.006), overall operative complication rate (36.6% vs. 21.3%; P = 0.006), and a trend toward a lower mortality rate (4.4% vs. 0.9%; P = 0.083). There was no difference in 3-year overall and disease-free survival between two groups. Operative blood loss (P = 0.035; odds ratio = 2.69; 95% confidence interval, 1.00-6.78) and open surgery (P = 0.007; odds ratio = 2.31; 95% confidence interval, 1.26-4.23) were independent factors for occurrence of complication. CONCLUSIONS: Laparoscopic colorectal cancer resection is associated with more favorable short-term results and should be recommended as the preferred treatment option for high-risk patients.

Cost comparison of femoral head banking versus bone substitutes.

PURPOSE: To compare the costs of femoral head banking versus bone substitutes. METHODS: Records of femoral head banking from 1998 to 2008 were reviewed. The cost of allogenic cancellous bone graft was calculated by estimating the direct expenditure of femoral head procurement, screening tests, and storage, and then divided by the amount of bone harvested. RESULTS: 326 females and 141 males (mean age, 80.3 years) donated 470 femoral heads. Each transplantable femoral head costs US$978. Each gram of transplantable allogenic bone graft costs US$86, compared with US$9 to 26 per gram for commercially available bone substitutes. CONCLUSION: Compared with bone substitutes, femoral head banking in Hong Kong was less economical. Unless allografts yield superior outcomes, harvesting femoral heads for general usage (such as filling bone voids for fresh fractures) is not justified from a financial perspective, especially in banks dedicated to procuring bone from femoral heads only.

Flowmetry-based portal inflow manipulation for a small-for-size liver graft in a recipient with spontaneous splenorenal shunt.

We report a case of living donor liver transplantation using a small-for-size graft (SFSG) with graft to estimated standard liver volume of only 28% in a recipient with spontaneous splenorenal shunt and demonstrate the value of intraoperative ultrasonic flowmetry. Despite an SFSG, the graft was underperfused. This was recognized by flowmetry and was rectified by ligation of the splenorenal shunt.

Differences in measured mammographic density in the menstrual cycle.

BACKGROUND: In premenopausal women, the sensitivity of screening mammography for detecting breast cancer has been reported to be greater in the follicular phase than in the luteal phase of the menstrual cycle, which may be due to differences in mammographic density. To examine this possible effect, we compared mammographic density in premenopausal women who had mammograms at different phases of the menstrual cycle. METHODS: We recruited premenopausal women ages 40 to 49 years from two mammography units in Toronto, recorded the first day of the last menstrual period (LMP) and measured mammographic density using Cumulus software. We classified the time of the mammography examination as having occurred in one of four intervals, 1 (first week after LMP), 2 (second week after LMP), 3 (third week after LMP) and 4 (>3 weeks after LMP), and compared mammographic density across intervals. RESULTS: Of the 936 women included in the analysis, 620 were examined by film and 316 by digital mammography. There were small and statistically nonsignificant variations in breast dense, nondense area, and percent density over the menstrual cycle in women examined by film mammography. Marginally significant variation in percent density was observed in the digital subset due to significant differences in the amount of nondense tissue over the menstrual cycle. CONCLUSION: Variations in mammographic density over the menstrual cycle were small and nonsignificant for women examined by either film or digital mammography. Thus, timing of mammography in menstrual cycle is unlikely to have a significant influence in breast cancer detection by screening mammography.

Breast-conserving surgery in Hong Kong Chinese women.

BACKGROUND: Since the introduction of breast-conserving surgery (BCS), it has been increasingly accepted as the standard surgical option for suitable breast cancer patients in Western countries. However, there have been reports suggesting striking ethnic variations in those undergoing BCS. This study aimed to review the rate of BCS in Hong Kong Chinese breast cancer patients and the possible clinicopathologic and psychosocial factors that may have affected the choice of surgery. METHODS: Patients in a university academic surgical center with early-stage breast cancer (stage I/II invasive carcinoma and carcinoma in situ) who underwent definitive surgery from January 2001 to December 2005 were studied. BCS was considered feasible for those with (1) the optimal tumor size for which an acceptable cosmetic outcome can be achieved after surgery, (2) unifocal disease, and (3) no contraindication for postoperative radiotherapy. The proportion of women undergoing BCS or mastectomy were compared. Factors affecting the choice of surgery were correlated. RESULTS: Six hundred eighty female patients with early-stage breast cancer underwent surgery during the study period; 495 (72.8%) mastectomies, 149 (21.9%) BCS, and 36 (5.3%) mastectomies with immediate reconstruction were performed. For those patients who had mastectomies, 54.8% (271/495) had considered BCS as the initial surgical option. Among these, 19.6% (53/271) failed to have BCS performed due to margin involvement or extensive disease, and 80.4% (218/271) declined BCS and opted for mastectomy only. Age, marital status, and educational level were found to be independent significant factors affecting the choice of BCS. CONCLUSION: The rate of BCS in Hong Kong is relatively low compared to that of Western countries. Patients who opted for mastectomies tended to be older, married, and have a lower educational level. Prospective studies on how sociocultural, clinicopathologic, and other factors important in treatment decision-making processes and psychosocial impact of choice of surgery are important so that an ethnic-specific assessment can be made. Suitability and acceptance of BCS by Chinese women should increase with better understanding and education.