Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) was initially used for locally advanced or inoperable breast cancers. Its extension to early disease has facilitated breast-conserving surgery (BCS). This study investigated the use of NAC in patients registered with the Hong Kong Breast Cancer Registry (HKBCR); it also assessed NAC effectiveness according to rates of pathological complete response (pCR) and BCS. METHODS: Records were retrieved from the HKBCR regarding 13 435 women who had been diagnosed with invasive breast cancer during the period of 2006 to 2017, including 1084 patients who received NAC. RESULTS: The proportion of patients treated with NAC nearly doubled from 5.6% in 2006-2011 to 10.3% in 2012-2017. The increase was most pronounced among patients with stage II or III disease. In terms of biological subtype, substantial increases in the receipt of NAC were evident among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) tumours. The best rates of pCR were observed in patients with HER2-positive (non-luminal) [46.0%] tumours, followed by patients with luminal B (HER2-positive) [29.4%] and triple-negative (29.3%) tumours. After NAC, the rate of BCS was 53.9% in patients with clinical stage IIA disease, compared with 38.2% in patients with pathological stage IIA disease who did not receive NAC. CONCLUSION: The use of NAC in Hong Kong increased from 2006 to 2017. The findings regarding rates of pCR and BCS indicate that NAC is an effective treatment; it should be considered in patients with stage ≥II disease, as well as patients with HER2- positive (non-luminal) or triple-negative breast cancers.

Improving outcomes in breast cancer for low and middle income countries.

Breast cancer is the most common cancer in women world-wide. Incidence rates in low- and middle-income countries (LMICs) are lower than in high income countries; however, the rates are increasing very rapidly in LMICs due to social changes that increase the risk of breast cancer. Breast cancer mortality rates in LMICs remain high due to late presentation and inadequate access to optimal care. Breast Surgery International brought together a group of breast surgeons from different parts of the world to address strategies for improving outcomes in breast cancer for LMICs at a symposium during International Surgical Week in Helsinki, Finland in August 2013. A key strategy for early detection is public health education and breast awareness. Sociocultural barriers to early detection and treatment need to be addressed. Optimal management of breast cancer requires a multidisciplinary team. Surgical treatment is often the only modality of treatment available in low-resource settings where modified radical mastectomy is the most common operation performed. Chemotherapy and radiotherapy require more resources. Endocrine therapy is available but requires accurate assessment of estrogen receptors status. Targeted therapy with trastuzumab is generally unavailable due to cost. The Breast Health Global Initiative guidelines for the early detection and appropriate treatment of breast cancer in LMICs have been specifically designed to improve breast cancer outcomes in these regions. Closing the cancer divide between rich and poor countries is a moral imperative and there is an urgent need to prevent breast cancer deaths with early detection and optimal access to treatment.

What is the relationship between the Glasgow coma scale and airway protective reflexes in the Chinese population?

AIM: To describe the relationship of gag and cough reflexes to Glasgow coma score (GCS) in Chinese adults requiring critical care. METHOD: Prospective observational study of adult patients requiring treatment in the trauma or resuscitation rooms of the Emergency Department, Prince of Wales Hospital, Hong Kong. A long cotton bud to stimulate the posterior pharyngeal wall (gag reflex) and a soft tracheal suction catheter were introduced through the mouth to stimulate the laryngopharynx and elicit the cough reflex. Reflexes were classified as normal, attenuated or absent. RESULTS: A total of 208 patients were recruited. Reduced gag and cough reflexes were found to be significantly related to reduced GCS (p=0.014 and 0.002, respectively). Of 33 patients with a GCS≤8, 12 (36.4%) had normal gag reflexes and 8 (24.2%) had normal cough reflexes. 23/62 (37.1%) patients with a GCS of 9-14 had absent gag reflexes, and 27 (43.5%) had absent cough reflexes. In patients with a normal GCS, 22.1% (25/113) had absent gag reflexes and 25.7% (29) had absent cough reflexes. CONCLUSIONS: Our study has shown that in a Chinese population with a wide range of critical illness (but little trauma or intoxication), reduced GCS is significantly related to gag and cough reflexes. However, a considerable proportion of patients with a GCS≤8 have intact airway reflexes and may be capable of maintaining their own airway, whilst many patients with a GCS>8 have impaired airway reflexes and may be at risk of aspiration. This has important implications for airway management decisions.

Disease severity prediction for nursing home-acquired pneumonia in the emergency department.

BACKGROUND: Prediction rules exist for the assessment of community-acquired pneumonia but their use in nursing home-acquired pneumonia (NHAP) remains undefined. The objectives of this study were to compare the prognostic ability for severe NHAP of five prediction rules (PSI, CURB-65, M-ATS, R-ATS, España rule), and to evaluate their usefulness to identify patients with less severe disease in the emergency department for outpatient care. METHODS: A prospective observational study of consecutive NHAP patients was conducted at a university teaching hospital emergency department in Hong Kong between January 2004 and June 2005. The primary outcome was severe pneumonia (defined as combined 30-day mortality and/or intensive care unit (ICU) admission). RESULTS: 767 consecutive NHAP patients were included. Mean (SD) age was 83.4 (9.0) years; 350 (45.6%) were male and 644 (84.0%) had coexisting illness. 95 patients died within 30 days (12.4%), five patients were admitted to the ICU (0.7%) and 98 patients had severe pneumonia (12.8%). Sensitivity and specificity of each decision rule ranged from 37.8% to 95.9% and 15.1% to 87.6% respectively. The overall predictive performance of each rule was between 0.627 and 0.712. The negative likelihood ratios of PSI (0.27) and CURB-65 (0.23) were lower than M-ATS (0.71), R-ATS (0.45) and España (0.39). After excluding 204 patients with either poor functional status or those >90 years of age, sensitivities of M-ATS (96.0%) and R-ATS (100%) improved greatly with negative likelihood ratios of <0.1. CONCLUSION: PSI and CURB-65 are useful for identification of patients with less severe NHAP.

A 77-year-old woman with sudden onset of blue discolouration of right third toe.

We report on a 77-year-old woman with a history of peripheral vascular disease who presented with an acute-onset tender blue toe and deteriorating renal function. A clinical diagnosis of blue toe syndrome was made but the patient deteriorated rapidly and died. This case illustrates the rapidly devastating nature and fatality of blue toe syndrome. There is no effective treatment for this condition.

Fine-needle aspiration cytology of mucocelelike tumors of the breast.

Mucocelelike tumors of the breast encompass a spectrum of pathologic lesions, including benign tumor, atypical ductal hyperplasia, carcinoma in situ, and colloid carcinoma. Because the fine-needle aspiration (FNA) cytology of mucocelelike tumors covering this pathologic spectrum is not well defined, a study of 21 cases of mucocelelike tumors was conducted. Benign lesions are likely to be poorly cellular and to contain cohesive clusters of cytologically bland cells arranged in two dimensional sheets in the background of abundant mucoid material. Colloid carcinomas are usually highly cellular and contain loosely cohesive clusters and dissociated cells with nuclei showing minimal to mild atypia. The most discriminating feature between benign and malignant lesions appears to be the presence of many dissociated cells with intact cytoplasm. Cases with atypical ductal hyperplasia, with some bordering on carcinoma in situ as seen in 7 of the 12 benign cases, may be difficult to identify on FNA cytology, possibly because of sampling. As expected, some of the atypical cases have intermediate features of benign and malignant tumors. Because of overlapping features in borderline cases, we recommend excisional biopsy for all mucocelelike lesions. Myxoid fibroadenoma is more cellular than benign mucocelelike lesions and can be distinguished from carcinoma by the absence of dissociation and presence of numerous bare nuclei of bland morphology in the background. The mucoid material of myxoid fibroadenoma stained brightly pink rather than magenta as in mucocelelike tumors using the Diff Quik stain.

The development of the "Cantonese receptive vocabulary test' for children aged 2-6 in Hong Kong.

The study aims to develop a Cantonese receptive vocabulary test to assess 2-6-year-old children in Hong Kong. The test consists of 100 test items. Each target item is accompanied by a phonological distractor, a semantic distractor and an unrelated distractor. A sample of 609 normal children from four Maternal and Child Health Centres and nine kindergartens was selected. The results show that there is a significant effect of age on the correct score. ANOVA was performed to look at the age effect on each distractor individually. It was found that the scores of the three distractors decrease in their own patterns as age increases. With strong content validity, strong construct validity and high correlation coefficients in the split-half reliability, this test could be used as a reliable measurement for the Cantonese-speaking population in Hong Kong.

Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production.

When freshly drawn, heparinized human whole blood is incubated with 50 microM calcium ionophore A23187, platelets are stimulated to produce thromboxane B2 (TxB2) by activation of prostaglandin G/H synthase-l (PGHS-1). TxB2 concentration, as measured by immunoassay, is maximal at 20-30 min and declines thereafter. Addition of acetylsalicylic acid (IC50 = 2.8 microM) or other nonsteroidal antiinflammatory drugs (NSAIDs) 15 min or 4.5h prior to 30 min stimulation with ionophore results in concentration dependent inhibition of TxB2 production. When blood is incubated with 0.01-10 micrograms/ml E. colilipopolysaccharide (LPS), PGHS-2 is induced and TxB2 levels become detectable at 3h and continue to increase through 24h. Using a 5h incubation with 10 micrograms/ml LPS, aspirin (10 microM added at 0 h), which is rapidly metabolized to salicylic acid, had no effect on 10 micrograms/ml LPS-induced TxB2, but inhibited TxB2 production by ionophore A23187 added at 4.5h through acetylation of pre-existing PGHS-1. In a 5h assay, NSAIDs added at 0 h were compared for inhibition of TxB2 production stimulated by addition of ionophore A23187 at 4.5h (PGHS-1), or by addition of LPS at 0 h (PGHS-2). Most NSAIDs were more potent against PGHS-1 than PGHS-2. Diclofenac, naproxen and flufenamic acid were equipotent or slightly selective for PGHS-2. Diflunisal and nimesulide were > 4-fold selective for PGHS-2, and NS-398 was > 30-fold selective for PGHS-2.

Pathologic changes of gastric mucosa colonized by Helicobacter pylori.

One hundred eighty-nine consecutive gastric biopsies showing colonization by Helicobacter pylori (HP) were studied. Epigastric pain and bleeding were the clinical presentations in 167 cases (88.4%). Major endoscopic findings were gastritis (n = 72, 38.1%) and ulceration (n = 101, 53.4%). Duodenal ulcer was associated with 32 (44.4%) and 29 (28.7%) cases of gastritis and gastric ulcer, respectively. Histologically, the HP-colonized gastric epithelium showed characteristic degenerative changes that were topographically related to the bacteria but unrelated to the inflammatory infiltrate. Disintegration and loss of apical mucus with formation of epithelial pits was seen in nearly all cases. Other changes included microerosion, conventional erosion, and frank ulceration. Only the disintegration of apical mucus, epithelial pit, and microerosion were specific for HP colonization. These conditions were absent in areas not colonized by HP and in 79 consecutive HP-negative gastric biopsies seen during the same study period. The epithelial degenerative changes in HP-colonized gastric mucosa are easy to recognize in routine hematoxylin-eosin-stained sections and they could serve as histologic guides to the localization of the bacteria. It is proposed that HP-colonized gastric mucosa is a distinct pathologic entity with a pathologic spectrum ranging from active chronic gastritis to erosion and frank ulcer. Damage to the mucin-containing portion of the gastric epithelial cells appears to be the basic cytopathologic effect of HP on the gastric mucosa. As effective specific treatment for HP infection is available, identification of HP colonization in gastric biopsies should be attempted in all cases of gastritis and gastric ulcer.

3-Carboxy-5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide, a new prodrug for the antiarthritic agent 2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide.

The title compound 3-carboxyisoxazole 3 was synthesized by cycloaddition of carbethoxyformonitrile oxide to N-[4-(trifluoromethyl)phenyl]-3-pyrrolidino-2-butenamide (6) with spontaneous elimination of pyrrolidine followed by hydrolysis of the ethyl ester. Compound 3 was shown to be absorbed intact after oral administration to rats. Over 24 h, the compound was metabolized to yield plasma concentrations of the antiinflammatory agent 2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (2), similar to those obtained following an equivalent dose of the established prodrug of 5-methyl-N-[4-(trifluoromethyl)phenyl]isoxazole-4-carboxamide (1).

Epithelial damage by Helicobacter pylori in gastric ulcers.

On review of 136 consecutive biopsies of benign gastric ulcer, Helicobacter pylori was detected in 78 cases (57.3%). The gastric epithelium colonized by Helicobacter pylori showed a characteristic constellation of changes, including loss of apical mucous portion of individual cells, drop-out of epithelial cells, epithelial pits, erosions and cellular tufts, indicative of cellular injury and regeneration. Among the 58 Helicobacter-negative cases, similar changes were not observed in the ulcer edges, except for two cases which exhibited some cellular tufts. Thus, the topographic association of Helicobacter pylori with epithelial damage in the gastric ulcer edges in more than half of the cases suggests that this organism probably plays an aetiological role in ulcerogenesis, at least in these cases. Furthermore, the epithelial changes are so distinctive that they can serve as a helpful histological indicator for the presence of Helicobacter pylori in gastric biopsies.

Columnar cell carcinoma of the thyroid. Fine needle aspiration findings in a case.

Columnar cell carcinoma is a recently described rare tumor of the thyroid. The fine needle aspiration cytologic findings of one example are reported. In the smears, the tumor fragments showed papillary and glandular patterns. The tumor cells were columnar and exhibited pseudostratification of the nuclei. The nuclei were oval to elongated and possessed stippled chromatin and inconspicuous nucleoli; occasional ones exhibited longitudinal grooving. It is important to distinguish this tumor from papillary carcinoma of thyroid because of its much more aggressive behavior, from metastatic adenocarcinoma for obvious treatment considerations, and from medullary carcinoma.

Thyroxine suppressive therapy of benign solitary thyroid nodules: a prospective randomized study.

Patients with solitary thyroid nodules that are benign on aspiration biopsy are often treated nonsurgically. To find out if thyroxine therapy is effective, 74 patients were randomized to receive levothyroxine treatment or nothing. There were 8 males and 66 females. Their mean age was 39 years. The mean nodule size was 3.6 cm and the mean nodule duration was 11 months. All patients had normal serum thyroxine and thyroid stimulating hormone (TSH) levels, and positive thyrotropin releasing hormone (TRH) tests. The dose of thyroxine was adjusted until the TRH test was negative. Patients were followed at 6-month intervals in the first 2 years and yearly thereafter, with measurement of the nodule diameter. The mean follow-up period was 1.5 years. In the 37 patients receiving thyroxine therapy, 8 had disappearance of nodules, 6 had greater than 50% reduction in nodule size. In 19, the nodules were unchanged and in 4, the nodules were enlarged. In the 37 patients receiving no drug, 8 had disappearance of nodules, 5 had greater than a 50% reduction in nodule size, 17 had nodules unchanged, and 7 had enlarged nodules (p greater than 0.9). The mean reduction in nodule diameter at various follow-up periods was greater in the thyroxine group, but the difference did not reach statistical significance. Carcinoma was found in 1 patient in each group and both of them experienced nodule enlargement. We conclude that an adequate suppressive dose of levothyroxine does not alter the natural course of benign solitary thyroid nodules. An enlargement of the nodule or a change in its consistency should be further investigated to exclude malignancy.

Right atrial extension of adrenocortical carcinoma. Surgical management using hypothermia and cardiopulmonary bypass.

A patient with right adrenocortical carcinoma extending into the inferior vena cava and right atrium is presented. Tumor extension was demonstrated by magnetic resonance imaging (MRI) preoperatively. Successful resection of the adrenal tumor and its intravascular extension was achieved with the help of cardiopulmonary bypass and hypothermia. The patient was maintained on mitotane (o,p'-DDD), and was well for 12 months after surgery. It was concluded that intravascular extension of adrenocortical carcinoma is not a contraindication to radical surgery.

Strategy in reoperative surgery for hyperparathyroidism.

Eighty-three patients undergoing reoperations for hyperparathyroidism were studied. Preoperative diagnosis was reviewed, and localization was employed in selected patients. Cervical reexploration was carried out in a systematic manner, and mediastinotomy was required in 11 patients. Sixty patients had had previous parathyroid exploration. Missed adenomas were found in 34, of which 28 were single and 6 were double adenomas. Fourteen single adenomas were in normal locations and 14 were in ectopic locations. Seventeen patients had hyperplasia; 6 were wrongly diagnosed as adenoma, 3 had inadequate excision, 2 had supernumerary glands, and 6 had remnant hypertrophy. Three patients had recurrent carcinoma. Two had wrong diagnoses and 4 had uncertain diagnoses. Reoperation eliminated hypercalcemia in 71 patients (85.5%). Eight patients developed permanent hypoparathyroidism, and 1 had a permanent recurrent nerve palsy. Reoperative parathyroid surgery can be minimized with thorough initial cervical exploration, correct pathologic interpretation, and adequate parathyroid resection.

Carney's complex of primary pigmented nodular adrenocortical disease and pigmentous and myxomatous lesions.

A complex of primary pigmented nodular adrenocortical hyperplasia associated with myxomatous masses and pigmented lesions of the skin was recently described by Carney. Herein, we describe three patients with Carney's complex seen at our institution. Two patients presented with Cushing's syndrome and one patient with atrial myxoma. The diagnosis was revealed in all three because of an awareness of the disease in association with primary adrenocortical hyperplasia. Because Cushing's syndrome and atrial myxomas are life-threatening components of the disease and can occur metachronously, an early diagnosis in combination with the appropriate treatment is mandatory, and follow-up measures should be taken to define the natural course of events in the disease.

Flow cytometric measurements of nuclear DNA and ploidy analysis in Hürthle cell neoplasms of the thyroid.

Nuclear DNA content and nuclear DNA ploidy were measured in 36 Hürthle cell neoplasms (HCNs) to better define their potential roles in predicting the clinical behavior of these lesions. An EPICS V flow cytometer (Coulter Electronics, Hialeah, Fla) was used. Measurements were taken from paraffin-embedded tissue. Isolated nuclei were stained with propidium iodide. The study was conducted in a blinded fashion. Observed NDC and PDY patterns were classified as diploid, aneuploid, or suspicious. Twenty-nine lesions (81%) were diploid and seven (19%) were aneuploid. Twelve (33%) HCNs were malignant, 23 (64%) were benign, and one (3%) was indeterminate. Eight (67%) of 12 malignant HCNs were diploid and four (33%) of 12 were aneuploid. In comparison, 20 (87%) of 23 benign lesions were diploid and three (13%) of 23 were aneuploid. The indeterminate neoplasm was diploid. There were three deaths in this group of patients; all three had aneuploid neoplasms, and all had locally recurrent disease with distant metastases. There was a significant cross correlation between histologic features and DNA content with regard to outcome. These preliminary data suggest that NDC and PDY are not helpful in distinguishing histologically benign from malignant HCNs; however, they may be useful in determining prognosis.

Primary hyperparathyroidism: its clinical pattern and results of surgical treatment in Hong Kong Chinese.

Primary hyperparathyroidism has been increasingly diagnosed among whites since the advent of the biochemical autoanalyzer. However, the condition remains uncommon among Orientals. Our experience with 31 patients at the Queen Mary Hospital, University of Hong Kong, in the periods before and after we began to use the biochemical autoanalyzer was reviewed. The prevalence of primary hyperparathyroidism rose slightly from 3.1 to 3.7 per 100,000 hospital population. In both periods skeletal manifestation was the major clinical presentation, followed by hypercalcemic symptoms and urologic disease. Asymptomatic hypercalcemia occurred in three of 31 patients despite the use of the biochemical autoanalyzer. Preoperative localization was carried out in 27 patients and was helpful in nine (33.3%) of them. The surgeon explored all four parathyroids, removed the diseased gland(s), and examined a biopsy specimen of one normal-appearing gland. There were 27 adenomas, two carcinomas, one four-gland hyperplasia, and one sarcoidosis. Twenty-eight patients had transient hypocalcemia after parathyroidectomy and required calcium supplements for variable periods. Before and after we began to use the biochemical autoanalyzer, there was minimal change in the prevalence and clinical pattern of primary hyperparathyroidism seen in our hospital. In our experience, successful parathyroidectomy depends more on the surgeon's operative technique than on preoperative localization.

Frank rectal bleeding: a prospective study of causes in patients over the age of 40.

In order to determine the frequency of tumours in patients presenting with frank rectal bleeding, a prospective study was carried out in 337 patients over the age of 40 attending our Proctology Clinic. After making a clinical diagnosis, flexible sigmoidoscopy followed by barium enema was performed. Excluding 7 digitally palpable rectal cancers, there were 30 cancers (9.1%), 34 polyps (10.3%), 7 proctocolitis (2.1%) and 25 diverticula (7.6%) detected, giving a total diagnostic yield of 29.1%. A clinical diagnosis of bleeding sources other than haemorrhoids was made in 80% of the cancers. Flexible sigmoidoscopy detected 93.3% of the cancers and 88.2% of the polyps. Barium enema diagnosed the remaining cancers and polyps but there was a false-positive rate of 3.8%. From our results, we conclude that patients with frank rectal bleeding should be screened routinely for left-colon cancer irrespective of the clinical diagnosis. The flexible sigmoidoscope is a quick and useful tool. However, barium enema should be recommended to individuals with strong clinical suspicion of rectal bleeding other than haemorrhoids.