Prognostic Significance of CD163+ and/or CD206+ Tumor-Associated Macrophages Is Linked to Their Spatial Distribution and Tumor-Infiltrating Lymphocytes in Breast Cancer.

Tumor-associated macrophages (TAMs) is a key element in the breast tumor microenvironment. CD163 and CD206 have been utilized for TAM identification, but the clinical implications of TAMs identified by these markers have not been thoroughly explored. This study conducted a comparative analysis of CD163 and CD206 TAMs using digital image analysis, focusing on their spatial distribution and prognostic significance in relation to tumor-infiltrating lymphocytes (TILs). Distinct clinico-pathological and prognostic characteristics were noted between the two types of TAMs. CD163 TAMs were linked to high-grade tumors (p = 0.006), whereas CD206 TAMs were associated with a higher incidence of nodal metastasis (p = 0.033). CD206 TAMs were predominantly found in the stroma, with more cases being stromal CD206-high (sCD206-high) than tumoral CD206-high (tCD206-high) (p = 0.024). Regarding prognostication, patients stratified according to stromal and tumoral densities of CD163 showed different disease-free survival (DFS) time. Specifically, those that were sCD163-low but tCD163-high exhibited the poorest DFS (chi-square = 10.853, p = 0.013). Furthermore, a high sCD163-to-stromal-TILs ratio was identified as an independent predictor of unfavorable survival outcomes (DFS: HR = 3.477, p = 0.018). The spatial distribution and interactions with TILs enhanced the prognostic value of CD163 TAMs, while CD206 TAMs appeared to have limited prognostic utility in breast cancer cases.

Primary Ankle Fusion Using an Antegrade Nail Into the Talus for Early Treatment of OTA Type C3 Distal Tibial Plafond Fractures: A Preliminary Report.

BACKGROUND: Type C3 distal tibial plafond fractures consistently show poor outcomes with high complication rates and significant risk of posttraumatic arthritis. We describe a minimally invasive technique of performing a primary ankle fusion using an anterograde tibial nail and compare our early results to traditional methods of fixation. METHODS: During the acute admission, the patient undergoes an arthroscopic preparation of the ankle joint and insertion of an anterograde nail into the talus. This technique is described in detail and presented alongside a retrospective 5-year review of all adult C3 distal tibial plafond fractures from our center. RESULTS: Twenty-six patients (8 open fractures) had been fixed traditionally using open reduction internal fixation (24 patients) and circular frames (2 patients) with an average follow-up of 20 months. Those internally fixed had protected weightbearing for 3 months. Complications included deep infection (12%), nonunion (8%), malunion (4%), severe posttraumatic osteoarthritis (27%), and the secondary conversion to ankle replacement/fusion (12%) requiring an average of 3 reoperations.Six patients underwent primary fusion (3 open fractures) with an average follow-up of 18 months. Patients were allowed to immediately weightbear. There were no reported complications and the primary fusion group demonstrated shorter hospital stays, faster return to work, and higher mean self-reported foot and ankle score (SEFAS) compared to those treated with ORIF. CONCLUSION: C3 distal tibial plafond fractures are difficult to manage and there has not been a satisfactory method of treating them that allows early return to work, has a low risk of complications, and reduces the risk of posttraumatic tibiotalar arthritis.We present our initial results with a method that uses traditional arthroscopic techniques to prepare the tibiotalar joint together with minimally invasive anterograde tibiotalar nailing. In this initial report of a small group of patients, we found that surgery can be performed once the swelling has subsided after injury and that allowing weightbearing as tolerated did not appear to have a negative effect on initial outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Spatial Distribution and Densities of CD103+ and FoxP3+ Tumor Infiltrating Lymphocytes by Digital Analysis for Outcome Prediction in Breast Cancer.

BACKGROUND: The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined. METHOD: Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient's prognosis were analyzed. RESULTS: CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers. CONCLUSION: The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values.

Trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment.

STUDY OBJECTIVES: To examine the trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment and to investigate whether psychological, cognitive, and physical factors differentiate trajectories. METHODS: A total of 623 Chinese cancer survivors of diverse cancer types participated in a 2-year-long prospective study after the completion of cancer treatment. Sleep disturbance was measured using Pittsburgh Sleep Quality Index at 3 (T2), 6 (T3), 12 (T4), 18 (T5), and 24 (T6) months after baseline (within 6-months post-treatment; T1). Latent growth mixture modeling identified distinctive sleep disturbance trajectories and tested if these longitudinal patterns were predicted by baseline psychological distress, attentional control, attentional bias and physical symptom distress and T2 cancer-related distress. Fully adjusted multinomial logistic regression then identified whether these factors differentiated trajectories. RESULTS: Two distinct sleep disturbance trajectories were identified, namely stable good sleepers (69.7%) and persistent high sleep disturbance (30.3%). Compared to those in the stable good sleep group, patients in the persistent high sleep disturbance group were less likely to report avoidant (OR=0.49, 95% CI = 0.26-0.90), while more likely to report intrusive thoughts (OR = 1.76, 95% CI = 1.06-2.92) and cancer-related hyperarousal (OR = 3.37, 95% CI = 1.78-6.38). Higher depression scores also predicted persistent high sleep disturbance group membership (OR = 1.13, 95% CI = 1.03-1.25). Attentional bias, attentional control, anxiety, and physical symptom distress did not predict sleep trajectory membership. CONCLUSIONS: One in three cancer survivors experienced persistent high sleep disturbance. Screening and managing depressive symptoms and cancer-related distress in early cancer rehabilitation may reduce risk of persistent sleep disturbance among cancer survivors.

Tubular Adenomas of the Breast Are Cytologically Distinct from Fibroadenomas.

INTRODUCTION: Increasing molecular evidence indicates that tubular adenoma of the breast is distinct from fibroepithelial lesions, leading to its reclassification as an epithelial tumor in the 5th World Health Organization classification of tumors of the breast. However, tubular adenoma remains poorly characterized on fine-needle aspiration cytology (FNAC) and often not distinguished from fibroadenomas. In this study, the largest cohort, to date, of histologically confirmed aspirates of tubular adenomas were reviewed and compared with aspirates of fibroadenomas. Findings from this study further define the cytological features of tubular adenoma and allow differentiation from fibroadenoma. METHODOLOGY: Aspirates of histologically confirmed tubular adenomas were reviewed for features of the background, myoepithelial, epithelial, and stromal components and then compared to a cohort of aspirates of fibroadenomas. RESULTS: Totally, 43 (tubular adenoma) and 94 (fibroadenoma) aspirates were included. Tubular adenomas displayed moderate epithelial cellularity with high cohesiveness, with stromal fragments containing epithelium. Tubules are more common in tubular adenomas (p = 0.009) and "tubular fragments" (tissue fragments containing multiple tubular structures with/without stroma) is a pathognomonic feature of tubular adenoma (p < 0.001). Calcification and fibrocystic changes were variably seen (4.65-13.5%) but without difference to fibroadenomas (p > 0.05). Cytomorphologically malignant features and mitoses were absent in all aspirates of tubular adenoma. Presence of tubules and stromal fragments were independent factors associated with tubular adenomas, whereas a predominance of large epithelial fragments and naked stromal fragments were associated with fibroadenomas. CONCLUSION: Tubular adenomas are not only histologically and molecularly separate from fibroepithelial lesions but also a distinct entity on FNAC.

Return to Work and Work Productivity During the First Year After Cancer Treatment.

Objectives: Working-age cancer patients face barriers to resuming work after treatment completion. Those resuming work contend with reduced productivity arising from persisting residual symptoms. Existing studies of return to work (RTW) after cancer diagnosis were done predominantly in Western countries. Given that employment and RTW in cancer survivors likely vary regionally due to healthcare provision and social security differences, we documented rates and correlates of RTW, work productivity, and activity impairment among Chinese cancer survivors in Hong Kong at one-year post-treatment. Methods: Of 1,106 cancer patients assessed at six-months post-cancer treatment (baseline), 593 previously worked; detailed work status, psychological distress (HADS), physical symptom distress (MSAS-SF), supportive care needs (SCNS-SF34-C), health-related quality of life (SF12), and illness perception (B-IPQ) were assessed. Six months later (follow-up), work productivity and activity impairment were assessed (WPAI; n = 402). Descriptive analyses examined RTW rate. Fully adjusted regressions determined RTW, work productivity, and activity impairment predictors. Results: At baseline, 39% (232/593) were working, 26% (153/593) on sick leave, and 35% (208/593) were unemployed. Compared to patients returning to work, unemployed participants were older, likely manual/service-oriented workers, and had lower family income, chemotherapy, fewer unmet health system and information needs, poorer physical functioning, and negative illness perceptions. Sick leave participants were likely service-oriented workers, who had head and neck cancer, chemotherapy, and poor physical functioning. At FU, baseline depressive symptoms, physical symptom distress, and negative illness perceptions predicted presenteeism and work productivity loss; gynecological cancer, fewer unmet health system and information needs, and greater unmet sexuality needs predicted absenteeism; physical symptom distress, negative illness perception, and poor physical functioning predicted activity impairment. Conclusion: Cancer survivors who had more physically demanding jobs and poorer physical functioning delayed RTW. Unmanaged physical symptom and psychological distress hindered work productivity.

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer.

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Patient reported outcomes following non-operatively managed Weber Type A distal fibula fractures.

INTRODUCTION: The outcomes of "Weber A" type fibula fractures treated non-operatively are not well studied. The aims of this study were to investigate patient reported outcomes (PROMs) from such injuries and investigate if different radiological features of the fracture affects such outcomes. METHODS: Patients with conservatively managed Weber A fractures were contacted retrospectively (minimum 11 months) to measure PROMs. PROMs included the use of the Chertsey Outcome Score for Trauma (COST) as well as the time to return to work, physical activity and time to become symptom free. The effect of fracture features such as fracture height and intra-articular extension were analysed for their effect on PROMs. RESULTS: Data was collected from 72 patients from a total of 211 patients presenting with Weber A fractures. The mean COST scores were 83 (range 30-100). Patients reported on average 3.1 weeks (desk based) and 5.7 weeks (labour intensive) to return to work, 10.8 weeks to return to physical activity and 14.8 weeks to become symptom free with 21% of patients still symptomatic at follow-up. Fracture height and fractures with comminution, displacement, intra-articular extension did not appear to be associated with poorer PROMs. CONCLUSION: The outcomes are generally excellent; however, most patients do not return to their baseline before the injury, with a significant proportion of patients remaining symptomatic at follow-up. The reported times to return to work, physical activity and symptom-free are useful to manage patient expectations. Our results dispel any assumption that Weber A type distal fibula fractures are always associated with excellent outcomes.

The timing of closed unstable ankle fracture fixation and major wound complications - an observation from a UK major trauma centre.

OBJECTIVE: A retrospective cohort study was performed at a UK major trauma centre to identify whether timing of surgical fixation of closed unstable ankle fracture affected the rate of major wound complications. METHODS: Consecutive cases of unstable ankle fractures treated with open reduction internal fixation (ORIF) between March 2014 to December 2016 were included in this retrospective cohort study. Data were collected from 2018 onwards allowing a minimum follow-up of 2 years. Patients under the age of 18, polytrauma, open fractures and those requiring external fixation were excluded. Timing of ORIF were categorised into early (within 24 hours of injury) and delayed (after 24 hours of injury). Primary outcome was major soft tissue complications (defined as deep wound infections or wound breakdown that required further surgery). Secondary outcomes included fixation failure, and symptomatic metal work requiring removal. RESULTS: A total of 235 consecutive cases were included. There were 108(46%) patients in the early fixation group, and 127(54%) patients in the delayed fixation group. Seven major wound complications were identified. Five of which were in the early group, and 2 in the late group. There was no statistically significant difference in the major wound complication rates between the early and delayed surgery groups (p = 1.000). CONCLUSIONS: No significant difference was observed in the rate of major soft tissue complications between early and delayed fixation for isolated unstable ankle fractures.

Measurement invariance across gender and age groups, validity and reliability of the Chinese version of the short-form supportive care needs survey questionnaire (SCNS-SF34).

BACKGROUND: Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups-gender and age-which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34. METHODS: The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed. RESULTS: Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach's alpha coefficient ranged from 0.64 to 0.87. CONCLUSIONS: We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.

Illness perceptions as predictors of psychological distress among head and neck cancer survivors: a longitudinal study.

BACKGROUND: Leventhal's commonsense model implies illness perceptions influence illness outcomes. This study examined illness perceptions among head and neck cancer survivors, and whether these predicted subsequent psychological distress. METHODS: A total of 124 survivors of head and neck cancer (87% nasopharyngeal carcinoma; NPC) completed measures of psychological distress (Hospital Anxiety and Depression Scale; HADS), illness perceptions (Brief Illness Perception Questionnaire; B-IPQ), dispositional optimism (revised Chinese version of the Life Orientation Test; C-LOT-R), and clinical and demographic data approximately12.9 months after diagnosis (T1). Six months later (T2) psychological distress (HADS) was again measured. Adjusted multivariate analyses tested whether illness perceptions predicted T2 HADS scores. RESULTS: Illness perception dimensions were significantly intercorrelated (0.01-0.68), explaining 8.0% of anxiety and 4.8% of depression symptom variability at T2. After adjustment for T1 distress, illness identity (ß = 0.270, P < .01) and sex identification as a woman (ß = 0.275, P < .01) predicted T2 anxiety symptoms while illness identity (ß = 0.195, P < .05), unemployment (ß = 0.195, P < .05), and pessimism (ß = -0.227, P < .01) predicted T2 depression symptoms. CONCLUSION: Perceived illness identity predicted psychological distress, accounting for modest levels of distress variance. Unresolved symptoms may exacerbate distress.

Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong.

BACKGROUND: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting. PATIENTS AND METHODS: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance. RESULTS: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses). CONCLUSION: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.

Psychometric assessment of the Chinese version of the brief illness perception questionnaire in breast cancer survivors.

OBJECTIVE: The eight-item Brief Illness Perception Questionnaire (B-IPQ) supposedly evaluates cognitive and emotional representations of illness. This study examined the validity and reliability of a traditional Chinese version of the B-IPQ in Hong Kong Chinese breast cancer survivors. METHODS: 358 Chinese breast cancer survivors who had recently ended their primary treatment completed this B-IPQ Chinese version. Confirmatory factor analysis (CFA) tested the factor structure. The internal consistency, construct, predictive and convergent validities of the scale were assessed. RESULTS: CFA revealed that the original three-factor (cognitive-emotional representations and illness comprehensibility) structure of the B-IPQ poorly fitted our sample. After deleting one item measuring illness coherence, seven-item gave an optimal two-factor (cognitive-emotional representations) structure for the B-IPQ (B-IPQ-7). Cronbach's alpha for the two subscales were 0.653 and 0.821, and for the overall seven-item scale of B-IPQ was 0.783. Correlations of illness perception and physical symptom distress, anxiety, depression and known-group comparison between different treatment status suggested acceptable construct validity. The association between baseline illness perception and psychological distress at 3-month follow up supported predictive validity. CONCLUSIONS: B-IPQ-7 appears to be a moderately valid measure of illness perception in cancer population, potentially useful for assessing illness representations in Chinese women with breast cancer.

Illness perceptions among cancer survivors.

PURPOSE: The purpose of the study is to document in Hong Kong Chinese cancer survivors cross-sectional associations between illness perceptions, physical symptom distress and dispositional optimism. METHODS: A consecutive sample of 1036 (response rate, 86.1%, mean age 55.18 years, 60% female) survivors of different cancers recruited within 6 months of completion of adjuvant therapy from Hong Kong public hospitals completed the Brief Illness Perception Questionnaire (B-IPQ), Chinese version of the Memorial Symptom Assessment Scale Short-Form (MSAS-SF), and the revised Chinese version of Life Orientation Test (C-LOT-R), respectively. Stepwise multiple regression analyses examined adjusted associations. RESULTS: IPQ seriousness, symptom identity, illness concern, and emotional impact scores varied by cancer type (p < 0.01). Stress-related, lifestyle, environment, psychological/personality, and health-related factors were most frequently attributed causes of cancer. After adjustment for sample differences, physical symptom distress was significantly associated with all illness perception dimensions (p < 0.01), excepting control beliefs. Optimism was positively correlated with perceived personal and treatment control (p < 0.01) and illness understanding (p < 0.01), but negatively correlated with other IPQ dimensions (all p < 0.01). IPQ domain differences by cancer type were eliminated by adjustment for sample characteristics. CONCLUSION: Illness perceptions did not differ by cancer type. Greater physical symptom distress and lower levels of optimism were associated with more negative illness perceptions. IMPLICATIONS: Understanding how cancer survivors make sense of cancer can clarify an important aspect of adaptation. This in turn can inform interventions to facilitate adjustment. Knowledge contributions include evidence of physical symptom distress correlating with most dimensions of illness perception. Optimism was also associated with cancer survivors' illness perceptions.

Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).

OBJECTIVES: This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone. METHODS: Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile. RESULTS: A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm. CONCLUSION: AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.

The efficacy of tranexamic acid in hip hemiarthroplasty surgery: an observational cohort study.

Tranexamic acid (TXA) has been shown to reduce perioperative blood loss in elective lower limb arthroplasty surgery. There are potentially even greater physiological benefits in minimising blood loss in hip fracture surgery, however limited evidence exists for TXA use in hemiarthroplasty surgery. This study investigates the effect of TXA use on postoperative transfusion rates and haemoglobin (Hb) levels specifically following hemiarthroplasty surgery for hip fractures. A retrospective cohort study was conducted for consecutive hip hemiarthroplasties for fractures between June 2013 and October 2014 comparing patients with or without prophylactic TXA before incision. During the study, 305 hemiarthroplasties were performed with 271 cases eligible. TXA was given in 84 (31%) cases, and both patient groups were matched for known confounding factors. Patients given TXA had a lower transfusion rate (6% vs. 19%. p=0.005) and less blood loss (Hb drop>20g/L) on day 1 post surgery (26% vs. 42%; p=0.014). One transfusion was prevented with every 8 patients given prophylactic TXA. There were no differences in the 30 and 90-day mortality rates with TXA use. Tranexamic acid is safe, cost-effective and reduces the need for blood transfusion and should be considered in all patients undergoing hip hemiarthroplasty for fractures.

Phase II randomized study comparing the toxicity profile of gemcitabine plus cisplatin with gemcitabine plus oral etoposide in the treatment of advanced non-small cell lung cancer.

OBJECTIVE: This is a randomized phase II study designed to compare the toxicity profile of a non-platinum-based with a platinum-based regimen in the treatment of advanced non-small cell lung cancer. METHODS: Eighty-nine chemotherapy-naïve patients were randomized either to gemcitabine (1,000 mg/m2, 30-min infusion on days 1, 8 and 15) and oral etoposide (50 mg, days 1-14; GE group) or gemcitabine at the same schedule and cisplatin (75 mg/m2 on day 15; GP group). The primary endpoint is toxicity, and secondary endpoints include response rate, survival outcome and quality of life (QOL). RESULTS: The incidence of WHO grade 3 or 4 anemia, neutropenia and thrombocytopenia was 29, 44 and 22% (GE group), and 28, 49 and 23% (GP group), respectively (p = 0.75, 0.95 and 0.87, respectively). The rate of grade 2 or above nausea was numerically higher in the GP arm, but the difference was not statistically significant (GE 15.5%, GP 27.7%, p = 0.20). The rate of vomiting in the GE and GP arms was 20.0 and 20.5%, respectively (p = 0.96). However, subjective changes in QOL scores on nausea and vomiting were significantly higher in the GP arm (p = 0.001). Other symptoms including sore mouth and hair loss were significantly higher in the GE arm (p = 0.003 and 0.007, respectively). There were also significant differences observed in emotional (p = 0.014), cognitive (p = 0.028) and social functioning (p = 0.034) in favor of GP. The differences in tumor response (35.5 and 46.5% for GE and GP, respectively) were not significantly different. Median time to disease progression (33.8 and 40.7 weeks, respectively) and overall survival (41.4 and 57.3 weeks, respectively) were of borderline significance in favor of the GP arm (p = 0.055). CONCLUSION: This toxicity profile of GE is similar to GP, but the apparent inferior efficacy may discourage further investigation.

False-negative rate of abdominal sonography for detecting hepatocellular carcinoma in patients with hepatitis B and elevated serum alpha-fetoprotein levels.

OBJECTIVE: Routine screening for hepatocellular carcinoma among chronic carriers of hepatitis B virus using a combination of abdominal sonography and serum alpha-fetoprotein levels is widely practiced. Negative results on an abdominal sonogram generally indicate the absence of hepatocellular carcinoma despite the elevation of alpha-fetoprotein levels, but the false-negative rate of abdominal sonography has not been established prospectively. SUBJECTS AND METHODS: In our screening program, we routinely investigated patients with Lipiodol (iodized oil) CT when they presented with alpha-fetoprotein levels above 20 ng/mL or a focal lesion as depicted on abdominal sonography. Lipiodol CT comprised a hepatic angiogram with injection of Lipiodol selectively in the hepatic arteries, followed by an unenhanced CT scan 10 days later. Positive findings on Lipiodol CT were confirmed histologically by biopsy or surgical resection. We defined false-negative as histologic diagnosis of hepatocellular carcinoma within 3 months of normal findings on screening abdominal sonography. RESULTS: One hundred three patients with elevated alpha-fetoprotein levels were investigated with Lipiodol CT within 2 months of abdominal sonography. Of these, three of 70 patients with negative abdominal sonography had histologically confirmed hepatocellular carcinoma. Thus, abdominal sonography has a false-negative rate of 4.3%. Lipiodol CT is associated with a significant false-positive rate of 43.7%. The sensitivity, specificity, and positive predictive value of abdominal sonography for early detection of hepatocellular carcinoma among hepatitis B virus carriers with elevated alpha-fetoprotein levels was 85.7%, 81.7%, and 54.5%, respectively. CONCLUSION: Negative results on a screening abdominal sonogram among hepatitis B virus carriers with elevated alpha-fetoprotein levels does not rule out the presence of small hepatocellular carcinoma. Routine use of Lipiodol CT as a supplementary screening tool is not recommended.

Comprehensive proteomic profiling identifies serum proteomic signatures for detection of hepatocellular carcinoma and its subtypes.

BACKGROUND: Detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is difficult. We investigated the use of comprehensive proteomic profiling of sera to differentiate HCC from CLD. METHODS: Proteomes in sera from 20 CLD patients with alpha-fetoprotein (AFP) <500 microg/L (control group) and 38 HCC patients (disease group) were profiled by anion-exchange fractionation (first dimension), two types (IMAC3 copper and WCX2) of ProteinChip Arrays (second dimension), and time-of-flight mass spectrometry (third dimension). Bioinformatic tests were used to identify tumor-specific proteomic features and to estimate the values of the tumor-specific proteomic features in the diagnosis of HCC. Cross-validation was performed, and we also validated the models with pooled sera from the control and disease groups, serum from a CLD patient with AFP >500 microg/L, and postoperative sera from two HCC patients. RESULTS: Among 2384 common serum proteomic features, 250 were significantly different between the HCC and CLD cases. Two-way hierarchical clustering differentiated HCC and CLD cases. Most HCC cases with advanced disease were clustered together and formed two subgroups that contained significantly more cases with lymph node invasion or distant metastasis. For differentiation of HCC and CLD by an artificial network (ANN), the area under the ROC curve was 0.91 (95% confidence interval, 0.82-1.01; P <0.0005) for all cases and 0.954 (95% confidence interval, 0.881-1.027; P <0.0005) for cases with nondiagnostic serum AFP (<500 microg/L). At a specificity of 90%, the sensitivity was 92%. Both cluster analysis and ANN correctly classified the pooled serum samples, the CLD serum sample with increased AFP, and the HCC patient in complete remission. CONCLUSION: Tumor-specific proteomic signatures may be useful for detection and classification of hepatocellular cancers.