The Effect of Breast Cancer Subtype on Symptom Improvement Following Palliative Radiotherapy for Bone Metastases.

AIM: To assess the relationship between breast cancer subtypes and patient-reported outcomes (PRO) following palliative radiotherapy for bone metastases. MATERIALS AND METHODS: Prospectively collected PRO for all breast cancer patients treated with palliative, bone metastasis-directed radiotherapy from 2013 to 2016 in the province of British Columbia were analysed. The PRO questionnaire scored pain severity, level of function and symptom frustration at baseline and at 3-4 weeks following palliative radiotherapy using a 12-point scale. The primary outcome was the rate of overall response (any improvement in score); the secondary outcome was the rate of complete improvement in PRO (final PRO score of 0). Multivariate logistic analysis was used to compare response rates between molecular subgroup approximations of luminal A (LumA), luminal B (LumB), HER2-enriched (HER2) and triple negative (TN), as defined by grade and immunohistochemical staining. RESULTS: There were 376 patients who underwent 464 courses of palliative radiation for bone metastases. Subtypes included: 243 LumA, 146 LumB, 46 HER2 and 29 TN. There were 216 multifraction radiotherapy courses (median dose 20 Gy) and 248 single-fraction radiotherapy courses (median dose 8 Gy). The overall response rate was 85% and the complete response rate was 25%. In comparison with LumA breast cancers, TN breast cancers were associated with a lower rate of overall response (69% versus 86%, P = 0.021) and a lower rate of complete response (10% versus 28.8%, P = 0.045) on multivariate analyses. CONCLUSION: Patients with TN breast cancer have lower rates of pain, function and symptom frustration improvement following palliative radiation for bone metastases.

[Cochleo-vestibular lesions and prognosis in patients with profound sudden sensorineural hearing loss: a comparative analysis].

Objective: To investigate the characteristics of cochleo-vestibular dysfunction in patients with profound sudden deafness, and the prognosis of inner ear hemorrhage. Methods: From January 2017 to December 2018, 92 inpatients with profound sudden sensorineural hearing loss were enrolled in the Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University. Our studied patients included 47 males and 45 females, aged 20-78 (39.3±6.1) years. According to the results of inner ear magnetic resonance imaging (MRI), the patients were divided into two groups: inner ear hemorrhage group and non-inner ear hemorrhage group. The clinical features, vestibular tests and audiological examination results during follow up were compared between the two groups. SPSS 22.0 software was used for statistical analysis. Results: The inner ear hemorrhage group consisted of 32 cases (34.8%, 32/92), all of whom complained of vertigo (100%, 32/32). Simultaneous vertigo attack and hearing loss occurred in 78.1% of this group (24/32). Neither semicircular canals function, nor cervical vestibular evoked myogenic potential (c-VEMP), nor ocular vestibular evoked myogenic potential (o-VEMP) in the affected side was normal (100%, 32/32). The rates of benign paroxysmal positional vertigo (BPPV) and disequilibrium were 37.5% (12/32) and 25.0% (8/32) respectively. Hearing improved in 28.1% (9/32) two weeks after treatment, and became stable at one month's follow up. In 60 cases without inner ear hemorrhage, 58.3% of them (35/60) experienced vertigo, which occurred simultaneously with hearing loss in 21 patients (60%, 21/35). The abnormal rates of semicircular canals function, c-VEMP and o-VEMP were 71.6% (43/60), 78.3% (47/60) and 66.7% (40/60), respectively. The incidence of BPPV was 16.7% (10/60) and 8.3% (5/60) in cases with disequilibrium. Hearing improved in 58.3% (35/60) two week after treatment, and became stable at three months' follow up. Significant difference was found in either vertigo rate, or simultaneous vertigo/hearing loss rate, or abnormal c-VEMP/o-VEMP rates, or accompanying BPPV, or disequilibrium rates between the two groups (P<0.05 each). Moreover, we observed better hearing recovery in non-inner ear hemorrhage group in the two weeks, one month, three months and six months' follow up, when compared with those in inner ear hemorrhage groups (P<0.05 each). Conclusions: Inner ear hemorrhage is associated with more severe cochlea-vestibular lesion and poorer prognosis, in comparison to the non-inner ear hemorrhage,in patients with profound sudden sensorineural hearing loss.

Comparison of four contrast medium delivery protocols in low-iodine and low-radiation dose CT angiography of the aorta.

AIM: To evaluate contrast medium delivery protocols for the optimal enhancement profile of the aorta with both a reduced dose of radiation and contrast medium, called double-low computed tomography (CT) angiography (DLCTA). MATERIALS AND METHODS: DLCTA was performed with 70 kVp and 200 mg iodine/kg in 205 patients following four protocols, namely slow rate (n=52), short duration (n=52), low concentration (n=50), and combined method (n=51), in comparison with a conventional group (120 kVp, 400 mg iodine/kg, n=51). The quantitative measurement of aortic attenuation, homogeneity, and subjective scores were evaluated. RESULTS: Overall, in the four DLCTA groups, the radiation dose was reduced by 62%, and the iodine dose was reduced by 50%. Among the four DLCTA groups, the signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the thoracic aorta were similar, but a significant difference was noted in the abdominal aorta. The short-duration group had the highest peak enhancement, least homogeneity, and worst subjective scores. Good contrast enhancement and good homogeneity were significantly more frequent in the slow-rate (86.6% and 90.4%, respectively) and low-concentration groups (78% and 96.0%, respectively). Subjective scores exhibited a trend of higher scores in the low-concentration group and lower scores in the slow-rate group (p=0.071). CONCLUSION: DLCTA with 70 kVp and 200 mg iodine/kg is feasible for whole-aortic CT angiography. The low-concentration protocol is recommended owing to its most consistent optimal aortic enhancement profile. Alternatively, the slow-rate protocol can be considered for patients with limited venous access.

[Clinical study of inner ear hemorrhage-associated sudden deafness and vertigo].

Objective: To analyze the clinical features and possible pathogenesis of sudden deafenss and vertigo induced by inner ear hemorrhage. Methods: Clinical data of 30 patients with inner ear hemorrhage, from the first affiliated hospital of Sun Yat-sen university during Jan 2016 to May 2017, were retrospectively analyzed. Results: Vergito and profound deafness were seen in all patients. The duration of vertigo ranged from 24 hours to three days in 11 cases, three to 14 days in the remaining 19 cases. Simultaneous occurrence of vergito and deafenss were seen in 24 patients. Semicircular canal hypofunction and abnormal cervical vestibular evoked myogenic potentials(C-VEMP)/ocular vestibular evoked myogenic potentials(O-VEMP) were detected in all cases. Ten patients had benign paroxysmal positional vertigo(BPPV) simultaneously. Hearing recovered in 20% of the cohort posttreatment. Dizziness and balance disturbance disappeared 1 to 2 months after therapy in 16 cases. Long term (6 months) follow up revealed poor hearing outcome and vestibular rehabilitation. Conclusion: Vestibular vertigo and profound sensorineural hearing loss, with unsatisfactory clinical prognosis, constituted the characters of inner ear hemorrhage-associated sudden deafness.

MicroRNA-200 family members are weakly expressed in the neurosensory epithelia of the developing zebrafish (Danio rerio) inner ear.

MicroRNA-200 family members are expressed in the developing mouse inner ear and in zebrafish (Danio rerio) olfactory epithelia, taste buds, and neuromasts, and have also been shown to be associated with differentiation of olfactory and taste buds. However, the role of the miR-200 family in the inner ear of zebrafish had not been studied. We investigated the expression and function of the miR-200 family in the zebrafish inner ear via in situ hybridization and loss-of-function methods. Expression of the miR-200 family was weak and dispersed throughout the developing zebrafish inner ear. After knockdown of miR-200 family members in the developing inner ear, no significant differences in development were observed compared to the controls. Otic vesicles, otoliths, and semicircular canals appeared normal. Compared with less differentiated olfactory filaments in olfactory epithelia, the development of hair cells and statoacoustic ganglion neurons were normal. The kinocilia and stereocilia of hair cells, the innervation of hair cells, and the formation of ribbon synapses were also unaffected. Overall, we conclude that the miR-200 family has a negligible role in the development of zebrafish inner ear; the functions of the miR- 200 family may be organ-specific.

The influence of masticatory hypofunction on developing rat craniofacial structure.

The purpose of this study was to use botulinum neurotoxin type A (BoNT/A) selectively to evaluate the influence of localized masticatory atrophy and paresis on craniofacial growth and development. 60 growing rats, 4 weeks old, weighing approximately 120g, were randomly divided according as follows (Long-Evans, N=15 per group): I (Mb+Tns); II (Mns+Tb); III (Mb+Tb); IV (Mns+Tns), where Mb or Tb is the BoNT/A-injected masseter or temporalis muscles (1.0U/muscle, 2.5ml) and Mns or Tns is the saline-injected muscles (2.5ml). After 7 weeks, the mature rats were killed, the muscles dissected and mean muscle mass recorded. Anthropometric cranial, maxillary and mandibular measurements were taken from the dried skulls. Changes in animal weight during the growth period were not statistically significant. The mean masticatory muscle mass was smaller for the BoNT/A-injected muscles of Mb and Tb. Anthropometric measurements of bony structures inserted by masseter and temporalis muscles revealed a significant treatment effect. The measurements showed a facial morphology typical of a dolichofacial profile: short upper face accompanied by a long lower face with an extended mandibular length and ramus height and constricted bicoronoidal and bigonial widths. The results suggest that induction of localized masticatory muscle atrophy with BoNT/A alters craniofacial growth and development.

Cost-effectiveness of influenza immunization in adult cancer patients in Taiwan.

The aim of this study was to investigate the efficacy of the influenza vaccine among cancer patients in Taiwan. We determined the effect of immunization on the following outcomes of disease: hospitalizations, emergency department visits, hospital outpatient visits, physician office visits, and deaths. Cost-effectiveness was analysed from the perspectives of the healthcare system and society. A decision tree was used, with estimates of disease burden and costs based on data from published and unpublished sources. The model followed 34 112 cancer patients aged 20-64 years who were registered by the Taiwan National Cancer Registry in 2002. An influenza immunization programme for the cancer population would prevent 2555 cases of all types of influenza infection, 660 of which would be serious cases involving hospitalization, emergency department visits and death. From the perspective of the healthcare system, the programme would cost US$7.7 million, providing net savings of US$5.4 million. From a societal perspective, the programme would cost US$28.6 million, providing net savings of US$22.3 million. This corresponds to savings of US$2107 and US$6338 per case averted, from healthcare and societal perspectives, respectively, as well as 110 lives saved. Lesser disease burden, greater vaccine efficacy and lower cost of hospitalizations increased cost-effectiveness. Influenza immunization for cancer patients is cost-saving and cost-effective from a healthcare and societal perspective in Taiwan. We highly recommend annual influenza vaccinations for this patient group.

Traumatic adrenal haematoma: a condition rarely recognised in the emergency department.

OBJECTIVE: To delineate the clinical features of traumatic adrenal haematoma, to help emergency physicians recognise the condition early and so to prevent adrenal crisis. METHODS: Review of the records of all patients admitted to Chi-Mei Medical Center, Tainan, Taiwan, with traumatic torso injuries, between 1 August 2003 and 31 August 2005. Of the 305 patients reviewed, 8 had adrenal haematoma. Injury Severity Scores, hospital course, need for intensive care unit admission and surgery or vascular embolisation, and concomitant injuries, were compared between patients with and without adrenal haematoma. RESULTS: No adrenal haematoma was recognised in the emergency department. No case of adrenal haematoma needed surgery or vascular embolisation, but each had associated injuries to other internal organs. All eight patients with, but only 106 patients without, adrenal haematoma sustained injuries to more than one internal organ (p<0.01). The mean Injury Severity Scores and lengths of hospital and intensive care unit stays among the two groups were not significantly different. There was no statistical significance in the differences in rates of admission to the intensive care unit, mortality, laparotomy or vascular embolisation between the two groups. CONCLUSIONS: Emergency physicians were liable in trauma cases to miss adrenal haematoma, which of itself was a benign condition but was associated with increased internal organ injuries and days in the intensive care unit. Emergency physicians should be aware of the possibility of adrenal haematoma in trauma cases in order not to miss the bilateral condition, which might lead to a deadly adrenal crisis.

Tobacco, betel quid, alcohol, and illicit drug use among 13- to 35-year-olds in I-Lan, rural Taiwan: prevalence and risk factors.

OBJECTIVES: This study determined the prevalence of and risk factors for substance use among rural Taiwanese. METHODS: We used a survey of a representative sample of 6318 participants aged 13 to 35 years in I-Lan, Taiwan, in 1996 through 1997. RESULTS: Perceived use of illicit drugs by peers, tobacco smoking, betel quid chewing, and male gender were the strongest predictors of illicit drug use. The prevalence of illicit drug use ranged from 0.3% among those who did not use any other substance to 7.1% among those using tobacco, betel quid, and alcohol. CONCLUSIONS: Preventive measures should address substance use in general rather than aiming at single substances.

Helicobacter pylori infection induced alteration of gene expression in human gastric cells.

BACKGROUND: Helicobacter pylori, a human pathogen responsible for many digestive disorders, induces complex changes in patterns of gene expression in infected tissues. cDNA expression arrays provide a useful tool for studying these complex phenomena. AIM: To identify genes that showed altered expression after H pylori infection of human gastric cells compared with uninfected controls. METHODS: The gastric adenocarcinoma cell line AGS was cocultivated with H pylori. Growth of infected cells was determined by trypan blue exclusion assay. Complementary DNA probes derived from H pylori treated and untreated cells were hybridised to two identical Atlas human cDNA expression arrays, and those genes with altered expression levels were identified. A real time quantitative reverse transcription-polymerase chain reaction assay was used to better define expression patterns of these genes in endoscopically gastric mucosal biopsies with and without H pylori infection. RESULTS: Over 24 hours, coincubation with H pylori inhibited AGS cell growth but did not cause a noticeable degree of cell death. H pylori treatment altered the pattern of gene expression in AGS cells. We identified 21 overexpressed genes and 17 suppressed genes from the cDNA expression arrays. The majority of genes were transcription factors such as c-jun, BTEB2, and ETR101. Other genes were involved in signal transduction pathways, such as MAP kinase, interleukin 5, and insulin-like growth factor. Genes involved in cell cycle regulation and differentiation, such as CDC25B and NM23-H2, were also identified. In patients with H pylori infection (n=20), there was a significant difference for ERCC3, Id-2, and NM23-H2 mRNA levels in infected gastric mucosa compared with uninfected gastric mucosa in patients without peptic diseases (n=20) (ERCC3 4.75 molecules/10(4) beta-actin mRNA molecules v 13.65, p<0.001; Id-2 16.1 v 23.4, p<0.05; NM23-H2 17.5 v 45.5, p<0.001). There was no significant difference between mRNA levels of c-jun and CDC25B in H pylori colonised gastric mucosa and uninfected mucosa. CONCLUSION: We demonstrated that H pylori infection caused alteration of gene expression in AGS cells. The differential hybridisation technique of Atlas human cDNA expression array is a useful method to identify host genes involved in pathogenic mechanisms in H pylori infection.

Identifying differentially expressed genes associated with metastasis of follicular thyroid cancer by cDNA expression array.

Patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from RNA of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. Genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, DNA damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.

Cytology of small-cell carcinoma arising in Barrett's esophagus.

The cytologic and histologic features of a rare case of small-cell carcinoma arising in Barrett's esophagus are reported. The patient presented with progressive dysphagia and an endoscopy revealed a distal esophageal mass with luminal constriction. The brushing smears showed small-cell carcinoma and dysplastic glandular epithelium. The concomitant biopsy confirmed the diagnosis of small-cell carcinoma arising in Barrett's esophagus.

Expression of sodium iodide symporter in metastatic and follicular human thyroid tissues.

Active iodide uptake across the basal membrane mediated by human sodium iodide symporter (hNIS) has been shown to be a process coupled with the flow of sodium. There is still controversy as to the amount of hNIS expression present in different kinds of human thyroid cancer tissues. In this study, we present a 58-year-old women with follicular thyroid carcinoma with vertebra and skull metastases. 201Tl and 5 mCi 131I scans clearly demonstrated the metastatic lesions in the brain of this patient. Thyroid and metastatic tissues were then obtained for this study, which is aimed at comparing the iodide trapping ability in vivo and in vitro of hNIS, and then comparing their expression in both thyroid tissue and metastatic tissues. Polyclonal antibodies to hNIS and competitive RT PCR were used to analyze the symporter protein and mRNA expressed in follicular human thyroid and metastatic tissues. Positive staining of the symporter protein was performed in the follicular thyroid carcinomas, otherwise, the metastatic tissues could not have demonstrated the protein in the staining. Follicular thyroid carcinoma tissues from thyroid were revealed around 5 pg hNIS expressed in follicular thyroid carcinoma tissues from the thyroid. Otherwise, there was almost an absence of hNIS expression in the metastatic tissue. These discrepancies of the expression in hNIS in vivo and in vitro studies need further investigation.

Subcutaneous tumors of mice treated with rhodamine-123 and laser irradiation.

BACKGROUND: Treatment involving photosensitizers and laser irradiation (LIR) in cancer therapy is known as photodynamic therapy (PDT). The purpose of our study was to assess the therapeutic effect of PDT using rhodamine-123 (Rh123) and LIR on subcutaneous tumors (ST) in mice. METHODS: Sarcoma-180 cells (1 x 10(7)) were implanted subcutaneously into the breast area of strain Cr1:CD-1-ICR (BR) female mice. Mice bearing ST were treated with Rh123 or LIR alone, or a combination of both, once a day for 3 successive days. RESULTS: The best therapeutic effect was observed in the group treated with 7.5 mg Rh123 per kilogram of body weight, combined with 75 J/cm2 laser irradiation energy. The group's mortality rate, tumor control rate, mean survival time, and increase in lifespan within 120 days after treatment were 16.7%, 83.3%, 109.4 days, and 135.8%, respectively. The most inhibitory effect on tumor cells was found in the group treated with 15 mg/kg Rh123 and 90 J/cm2 laser irradiation. The biosyntheses of DNA, RNA, and protein in tumor cells of this group was obviously inhibited. CONCLUSION: PDT with the photosensitizer Rh123 and laser irradiation was therapeutically effective in treating subcutaneous tumors of mice. The tumor cells and the syntheses of DNA, RNA, and protein of the tumor cells in these PDT treated mice were obviously inhibited.

Effects of glycyrrhizae and glycyrrhizic acid on cellular immunocompetence in low-dose gamma-ray irradiated mice.

BACKGROUND: For both animals and human beings, it is important to prevent damage from ionizing radiation and to restore immunocompetence following irradiation. The present study was conducted to investigate the effects of glycyrrhizae (GL) and glycyrrhetinic acid (GA) on cellular immunocompetence in low dose gamma-ray-irradiated mice. METHODS: Six- to 8-week-old ICR strain' Crl:CD-1-ICR (BR) strain male mice, bred in the Institute of Cancer Research, U.S.A., were chosen and divided into four groups. Group A was the normal control. Group B, the experimental control, received 1 Gy of whole body gamma-ray irradiation. Groups C and D, the experimental groups, were treated with 500 mg/kg of GL (orally) and 5 mg/kg body weight of GA (i.p.), respectively, once a day, 5 days a week for 2 weeks after gamma-irradiation. The tested mice were killed, at 6 different intervals to measure their leukocyte and differential counts. Cellular immunocompetence was measured by the 3H-thymidine uptake in each group. RESULTS: One gray of gamma-ray irradiation had evident inhibition on the leukocyte and differential counts and the cellular immunity of mice. GL and GA could help to restore the decreased leukocyte counts and the cellular immunocompetence in low dose gamma-irradiated mice. CONCLUSION: GL and GA could help to restore decreased leukocyte counts and the cellular immunocompetence in low-dose gamma-ray-irradiated mice.

Maxillary growth after palatal denudation: an animal experiment.

BACKGROUND: Palate surgery at an early age may cause retardation of maxillary growth. The second intention healing of the raw bone surface created on the palate is considered to be the cause of the growth retardation. The animal experiment in this study was designed to evaluate this effect. METHODS: Four-week-old Sprague-Dawley rats were divided into 3 groups. In the first group, a strip of mucoperiosteum was excised on both sides of the hard palate. A second group of rats received a sham surgery in which bilateral mucoperiosteal flaps were raised and redraped. The third group served as controls with no surgery. Flap elevation with and without excision was performed under an operative microscope to facilitate the delicate manipulation of tissue and to avoid injury to the underlying bone. The animals were killed 11 weeks later and the skulls were prepared for measurements, which included the palatal inter-molar width, maxillary height, and maxillary length. RESULTS: The results revealed statistically significant decreases in palatal width and maxillary length in the experimental group (excision of mucoperiosteum). No differences were observed in the vertical height of the maxilla. CONCLUSION: This study confirms that surgically created bone denudation of the palate causes maxillary growth disturbances.

Causes of death and associated factors among patients with non-insulin-dependent diabetes mellitus in Taipei, Taiwan.

A cohort of 766 patients with non-insulin-dependent diabetes mellitus (NIDDM) from a general teaching hospital in Taipei, Taiwan were followed prospectively to assess survival experience and associated risk factors. Data were abstracted from the medical records and additional information was obtained from patients or their closest relatives using a structured questionnaire. Date and cause of death were determined from death certificates. Standardized mortality ratios were calculated by the direct method. Chi2-Square test and Cox's proportional hazard analysis were used to control for potential confounders. During a median follow-up of 3.5 years (range 1 month to 4.6 years), 131 deaths occurred. Of these, 29.8% were due to cardiopulmonary disease (ICD 401-429), 13.0% due to cerebrovascular disease (ICD 430-438), 13.0% due to acute diabetes metabolic complications (250.1, 250.2), and 11.4% due to nephropathy (580-589). Adjusted for age, people with NIDDM had 2.2 (95% CI 1.6-2.9) times the risk of death than members of the general population, and cause-specific standardized mortality ratios were: CPD 4.6, nephropathy 8.8, cerebrovascular disease 1.9, and neoplasm 0.7. Age, fasting plasma glucose, hypertension, and proteinuria were positively and independently associated with all-cause mortality (P < 0.05 for each). Thus, NIDDM patients have higher mortality rates than the general population in Taiwan, and age, fasting plasma glucose, hypertension, and proteinuria are associated with this excess risk. Proper application of available interventions may control these factors with a consequent reduction in mortality. Particular attention is needed to prevent deaths from the acute metabolic complications of diabetes.