Disease-related complications in patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records. RESULTS: The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission. CONCLUSION: Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system.

Pain Relief After Total Knee Arthroplasty with Intravenous and Periarticular Corticosteroid: A Randomized Controlled Trial.

BACKGROUND: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both. METHODS: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS). RESULTS: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036). CONCLUSIONS: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Arthroscopic approach to the spring (calcaneonavicular) ligament.

BACKGROUND: This research studied the safety and efficacy of a new portal to the spring ligament. This portal is located just plantar to the insertion of the posterior tibial tendon and above the fibrous septum between the posterior tibial and the flexor digitorum longus tendons. METHODS: Twelve fresh frozen foot and ankle specimens were used. The distance between the accessory medial portal and the medial plantar nerve was measured. The relation between the medial plantar nerve and the spring ligament was studied. The depth that can be reached through the portal was also assessed. RESULTS: The average distance between the insertion point of the 3mm diameter metal rod and the medial plantar nerve was 20(6-27)mm. The medial plantar nerve located at lateral third of the ligament in 8 specimens (67%), middle third in 2 specimens (17%) and medial third in 2 specimens (17%). The tip of rod can reach Zone A in all specimens. CONCLUSION: This study demonstrated that arthroscopic approach and repair of the spring ligament can injure the medial plantar nerve. CLINICAL RELEVANCE: The clinical relevance of this cadaver study is that it confirmed the feasibility of arthroscopic approach to the whole span of the spring ligament and alerted the potential risk of injury to the medial plantar nerve during arthroscopic assisted repair of the ligament.

Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of adult tuberculous pleural effusion in Hong Kong.

INTRODUCTION: Pleural fluid adenosine deaminase level can be applied to rapidly detect tuberculous pleural effusion. We aimed to establish a local diagnostic cut-off value for pleural fluid adenosine deaminase to identify patients with tuberculous pleural effusion, and optimise its utility. METHODS: We retrospectively reviewed the medical records of consecutive adults with pleural fluid adenosine deaminase level measured by the Diazyme commercial kit (Diazyme Laboratories, San Diego [CA], United States) during 1 January to 31 December 2011 in a cluster of public hospitals in Hong Kong. We considered its level alongside early (within 2 weeks) findings in pleural fluid and pleural biopsy, with and without applying Light's criteria in multiple scenarios. For each scenario, we used the receiver operating characteristic curve to identify a diagnostic cut-off value for pleural fluid adenosine deaminase, and estimated its positive and negative predictive values. RESULTS: A total of 860 medical records were reviewed. Pleural effusion was caused by congestive heart failure, chronic renal failure, or hypoalbuminaemia caused by liver or kidney diseases in 246 (28.6%) patients, malignancy in 198 (23.0%), non-tuberculous infection in 168 (19.5%), tuberculous pleural effusion in 157 (18.3%), and miscellaneous causes in 91 (10.6%). All those with tuberculous pleural effusion had a pleural fluid adenosine deaminase level of ≤100 U/L. When analysis was restricted to 689 patients with pleural fluid adenosine deaminase level of ≤100 U/L and early negative findings for malignancy and non-tuberculous infection in pleural fluid, the positive predictive value was significantly increased and the negative predictive value non-significantly reduced. Using this approach, neither additionally restricting analysis to exudates by Light's criteria nor adding closed pleural biopsy would further enhance predictive values. As such, the diagnostic cut-off value for pleural fluid adenosine deaminase is 26.5 U/L, with a sensitivity of 87.3%, specificity of 93.2%, positive predictive value of 79.2%, negative predictive value of 96.1%, and accuracy of 91.9%. Sex, age, and co-morbidity did not significantly affect prediction of tuberculous pleural effusion using the cut-off value. CONCLUSION: We have established a diagnostic cut-off level for pleural fluid adenosine deaminase in the diagnosis of tuberculous pleural effusion by restricting analysis to a level of ≤100 U/L, and considering early pleural fluid findings for malignancy and non-tuberculous infection, but not Light's criteria.

Idiopathic Internal Thoracic Artery (ITA) Pseudoaneurysm treated with Endovascular Embolization.

A 44-year-old female was diagnosed with an ITA pseudoaneurysm in the right supraclavicular fossa. She was successfully treated with endovascular embolization. The challenges of diagnosis and treatment are discussed.

Microplastic pollution in the marine waters and sediments of Hong Kong.

The presence of plastic waste with a diameter of less than 5mm ("microplastics") in marine environments has prompted increasing concern in recent years, both locally and globally. We conducted seasonal surveys of microplastic pollution in the surface waters and sediments from Deep Bay, Tolo Harbor, Tsing Yi, and Victoria Harbor in Hong Kong between June 2015 and March 2016. The average concentrations of microplastics in local coastal waters and sediments respectively ranged from 51 to 27,909particles per 100m3 and 49 to 279particles per kilogram. Microplastics of different shapes (mainly fragments, lines, fibers, and pellets) were identified as polypropylene, low-density polyethylene, high-density polyethylene, a blend of polypropylene and ethylene propylene, and styrene acrylonitrile by means of Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy. This is the first comprehensive study to assess the spatial and temporal variations of microplastic pollution in Hong Kong coastal regions.

Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population.

Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations.

Bicycle and motorcycle wheel spoke injury in children.

PURPOSE: To review bicycle and motorcycle wheel spoke injuries around the foot and ankle in 24 children. METHODS: Medical records of 12 boys and 12 girls aged 2 to 11 (mean, 5.3) years who presented with an isolated posterior heel injury caused by wheel spokes of a motorcycle (n=9) or bicycle (n=15) were reviewed. RESULTS: All 9 motorcycle injury patients and 8 of 15 bicycle injury patients had lacerations. The remaining 7 bicycle injury patients had abrasions and developed skin necrosis and ulcerations, with 5 requiring debridement. The most common site of laceration was the posterolateral heel; 7 of these patients had deep soft tissue injury, and in 5 the Achilles tendon was partially cut or completely severed. The mean number of operations was 2.2 in the motorcycle group and 1.3 in the bicycle group. Seven patients with severe skin loss required skin grafting or flap surgery for wound coverage. The mean time from injury to definitive treatment was 8.2 days. The mean length of hospital stay was 18.4 days in the motorcycle group and 8.1 days in the bicycle group. Delayed definitive treatment was associated with more operations (r=0.499, p=0.013) and longer hospital stay (r=0.567, p=0.004). CONCLUSION: Wheel spoke injuries may result in severe soft tissue damage and bony trauma. Poor prognostic factors included high-energy injury, contamination and infection, and delayed treatment.

Computed tomography has low sensitivity for the diagnosis of early colon cancer.

AIM: The accuracy of computed tomography (CT) in detecting local invasion (T status) and nodal metastasis (N status) of colon cancer was determined. METHOD: Data on the preoperative CT scan of 153 lesions from 152 patients with colon cancer were reviewed retrospectively. Evaluation included the T stage and N stage of the TNM system. The results were compared with those obtained by histopathological examination of the resected tumour. RESULTS: Of the 153 tumours, 117 (76.5%) were correctly classified as Stage T1 and T2 (33 tumours) and Stage T3 and T4 (84 tumours) by CT. The sensitivity and specificity were 70.2% and 79.2%, respectively, and the positive and negative predictive values were 85.7% and 60.0%. When analysed according to the individual T stage (Tx/Tis, T1, 2, 3, 4) and N stage (N0, 1, 2), the kappa coefficient with linear weighting was 0.208 (fair agreement) for T stage and 0.154 (slight agreement) for N stage. The estimation of tumour size showed good agreement with histopathology (Spearman correlation coefficient 0.865). CONCLUSION: CT scanning of colonic cancer showed 75% accuracy in identifying T1 and T2 cancers combined, but gave poor agreement between CT and histopathology for individual T stages.

BAG3-related myofibrillar myopathy in a Chinese family.

In contrast to the usual slow disease progression in myofibrillar myopathies, patients with Bag3opathy often have a rapidly progressive and more severe phenotype with a worse prognosis. We describe a Chinese patient, born to non-consanguineous parents, who first presented at age 6 with clumsy walking and difficult climbing staircase. With a history of restrictive lung disease previously diagnosed as asthma, she progressed rapidly with proximal myopathy, rigid spine and bilateral tightening of the Achilles tendons requiring surgical elongation. Hypertrophic cardiomyopathy with restrictive physiology was shown by echocardiogram. Moreover, prolonged QT interval was also noted in the patient. Family history was unremarkable yet her father was incidentally found to have prolonged QT interval. Mutation analysis with genomic DNA of the proband showed heterozygous de novo known mutation c.626C>T (p.Pro209Leu) and a germline variation c.772C>T (p.Arg258Trp) in BAG3. Her father was found to be a carrier of c.772C>T. Muscle biopsy findings were suggestive of myofibrillar myopathy on light microscopy and ultrastructural studies. To our knowledge, this is the first Chinese case of Bag3opathy so far reported.

SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla.

BACKGROUND: Historical studies of lymphatic drainage of the breast have suggested that the lymphatic drainage of the breast was to lymph nodes lying in the antero-pectoral group of nodes in the axilla just lateral to the pectoral muscles. The purpose of this study was to confirm this is not correct. METHODS: The hybrid imaging method of SPECT/CT allows the exact anatomical position of the sentinel lymph node (SLN) in the axilla to be documented during pre-operative lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a series of 741 patients. The Level I axillary nodes were defined as anterior, mid or posterior. This was related to the anatomical location of the primary cancer in the breast. RESULTS: A SLN was found in the axilla in 97.8% of our patients. Just under 50% of SLNs located in the axilla were not in the anterior group and lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a single node field in 460 patients (63%), two node fields in 261(36%), three node fields in 6 and four node fields in 1 patient. CONCLUSION: Axillary lymphatic drainage from the breast is not exclusively to the anterior (or antero-pectoral) group of Level I nodes. SYNOPSIS: SPECT/CT lymphoscintigraphy shows that the breast does not always drain to the anterior group of Level I lymph nodes in the axilla but may drain to the mid axilla and/or posterior group in about 50% of patients with breast cancer regardless of the location of the cancer in the breast. These data redefine lymph drainage from the breast to axillary lymph nodes.

Comparative in vitro cytotoxicity study on uncoated magnetic nanoparticles: effects on cell viability, cell morphology, and cellular uptake.

Magnetic iron oxide nanoparticles (MIONPs) must be biocompatible, and a thorough knowledge on their potential cytotoxicity is crucial for their biomedical applications. However, the detailed study about the effects of iron oxide nanoparticles on cell viability, cell morphology, and cellular uptake of different mammalian cells is still insufficient. In this paper, comparative cytotoxicity study of uncoated magnetite nanoparticles at different concentrations was performed on human cervical cancer cell line (HeLa) and immortalized normal human retinal pigment epithelial cell line (RPE). The size, structure, and magnetic behavior of the MIONPs were characterized using transmission electron microscopy (TEM), X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM) respectively. After 24-hour incubation with the MIONPs, the cell viability was determined by live/dead assay, the cell morphology at high magnification was observed under scanning electron microscopy (SEM), and the cellular uptake of MIONPs was measured under TEM and verified by energy-dispersive X-ray spectroscopy (EDX) analysis. Our results indicate that the uncoated MIONPs at a high concentration (0.40 mg/ml) were toxic to both HeLa and RPE cells. However, the cytotoxicity of uncoated MIONPs at low concentrations was cell-type specific, and RPE cells were more susceptible to these MIONPs than HeLa cells. The effects of the MIONPs on cell morphology and the nanoparticles uptake also showed different features between these two cell lines. Hence cell type should be taken into consideration in the in vitro cytotoxicity study of uncoated MIONPs. Additionally, it should be noticed that the cell morphological changes and the uptake of nanoparticles can take place even though no toxic effect of these MIONPs at low concentrations was reflected in the traditional cell viability assay.

RYR1-related central core myopathy in a Chinese adolescent boy.

Central core myopathy is a rare, inherited neuromuscular disorder with a wide spectrum of phenotypic presentations. It is also considered an allelic disease of malignant hyperthermia. We report a case of central core myopathy in a Chinese adolescent boy presenting with atypical clinical features and a moderately elevated serum creatine kinase level. The diagnosis was made from the histopathological findings of central cores on muscle biopsy, and confirmed by the molecular genetic testing for the RYR1 gene mutation. This is the first case of central core myopathy confirmed by molecular study in our locality.

Effectiveness of immediate preoperative injection of radiopharmaceutical and blue dye for sentinel node biopsy in patients with breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) in breast cancer conventionally utilises a preoperative radioisotope injection and lymphoscintigraphy, which is time consuming and painful. The aim of this study was to evaluate a potentially more efficient and practical technique of immediate preoperative injection of blue dye and radiopharmaceutical by the surgeon (without involvement of a nuclear medicine department). METHOD: One hundred and sixty three clinically node negative patients with invasive breast cancer undergoing breast-conserving surgery were included. The radiopharmaceutical was delivered to the operating suite and injected by the surgeon in the subareolar region immediately after induction of anaesthesia. Sentinel node biopsy was performed in conjunction with removal of any palpable axillary lymph nodes (axillary node sampling). RESULTS: Sentinel nodes (SNs) were detected in 161 of 163 women. On average, 3.0 sentinel nodes were identified. Twenty nine patients had involved nodes of whom 28 had a positive sentinel node. Of the two patients with failed identification, one had involved axillary lymph nodes on sampling and the other had an involved intramammary lymph node. CONCLUSION: This method produces results identical to those obtained with other techniques. This study shows that sentinel node biopsy can be performed safely without involvement of a nuclear medicine department with the added benefits of no preoperative injection and improved efficiency in the operating suite.

Factors affecting the palpability of breast lesion by self-examination.

INTRODUCTION: This study aims to assess the accuracy of detection of breast lesion by breast self-examination and to assess different factors affecting the accuracy. METHODS: All consecutive Chinese female patients, who attended our breast imaging unit in 2001, completed our questionnaire, had retrievable hard copy films, and had more than three years clinical follow-up, were recruited for this study. Different factors, such as age, menopausal status, previous experience of breastfeeding, family history of breast cancer, previous history of mastectomy or lumpectomy, hormonal therapy, oral contraceptive pills and previous history of mammography, were correlated with accuracy in self-detection of breast lesions retrospectively. The nature, size and location of the lesion, and breast size based on imaging, were also correlated with the accuracy in self-detection of breast lesions. RESULTS: A total of 163 questionnaires were analysed. 111 patients detected a breast lesion themselves and 24 of these lesions were false-positives. A total of 173 lesions (27 cancerous, 146 benign lesions) were documented by either ultrasonography and/or mammography, and confirmed by either histology or three-year clinical follow-up. The overall sensitivity in detecting both benign and malignant breast lesions was 71% when number of breast lesions was used as the denominator, and up to 78% sensitivity was achieved when number of patients was used as the denominator. History of mastectomy, and size and nature of the lesions were found to affect the accuracy of self-detection of breast lesions. CONCLUSION: Overall, breast self-examinations were effective in the detection of breast lesions and factors such as size of lesion, nature of the lesion and history of mastectomy affect the accuracy of the detections. Breast self-examination should be promoted for early detection of breast cancer.

Cloning and differential expression of manganese superoxide dismutase (Mn-SOD) of Trichinella pseudospiralis.

The complete coding sequence of manganese superoxide dismutase (Mn-SOD) of Trichinella pseudospiralis (Tp) was obtained and characterized for the first time by degenerative reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of complementary DNA ends (RACE) reactions. The open reading frame of Tp Mn-SOD contained 663 nucleotides, encoding 220 amino acid residues. This included the conserved histidine and aspartate residues for metal binding, cysteine residues for disulfide bond formation, and arginine residue for directing the superoxide ion to the protein. The presence of mitochondrial transit peptides and maturation cleavage site suggest that the cloned Tp Mn-SOD gene is a mitochondrial enzyme. It is a single copy gene containing three introns. Northern blotting suggested that the expression level of Mn-SOD is lower than Cu/Zn SOD in infective stage larvae. Semi-quantitative RT-PCR demonstrated that a single dominant transcript of Tp Mn-SOD was highly expressed in the infective-stage larvae but not in adult worms. The information provides a better understanding of the highly compartmentalized superoxide dismutases of adenophorean nematodes.

Epidermoid cyst of the testis.

Epidermoid cysts, though having a variable sonographic appearance, may present with an onion peel configuration, that is, concentric rings of alternating hyperechogenicities and hypoechogenicities. The absence of vascular flow on colour Doppler sonography is also consistent with the avascular nature of these lesions. By combining these two sonographic features and the absence of biochemical tumour marker, preoperative diagnosis of epidermoid cyst is possible and may prompt a testis sparing surgery rather than orchidectomy.