Prior administration of chocolate improves the palatability of bitter drugs: The Choc-with-Med study.

AIM: The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. METHODS: A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. RESULTS: Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P < 0.0001 for all comparisons). Dark chocolate was most efficacious for masking the bitter taste of quinine, but the differences in taste masking efficacy between dark, milk and white chocolates were not statistically significant for flucloxacillin and clindamycin. CONCLUSIONS: Prior administration of chocolate results in lower perceived bitterness compared to control tastings of quinine, flucloxacillin and clindamycin solutions; however, there is no clear difference in this effect between the dark, milk and white chocolates used in this study.

Transient C5 Sensory and Motor Blockade After a Unilateral T4 Paravertebral Block: A Case Report.

A thoracic paravertebral block (TPVB) can provide anesthesia for breast cancer surgeries. This case report describes a 58-year-old woman with a prolonged ipsilateral dense C5 dermatomal sensory and motor blockade after receiving a TPVB at T4 with 40 mL of 0.2% ropivacaine for a left total mastectomy, suggesting a high cephalad spread of anesthesia up to C5 paravertebral spaces. The lower extremities and the diaphragm were not involved. It is possible that the large volume of local anesthetic, even at low concentration, combined with her previous neural pathology and surgical laminectomy resulted in unexpected postoperative neurological changes.

Validation of a modified table to map the 1998 Abbreviated Injury Scale to the 2008 scale and the use of adjusted severities.

BACKGROUND: The Abbreviated Injury Scale 2008 (AIS 2008) is the most recent injury coding system. A mapping table from a previous AIS 98 to AIS 2008 is available. However, AIS 98 codes that are unmappable to AIS 2008 codes exist in this table. Furthermore, some AIS 98 codes can be mapped to multiple candidate AIS 2008 codes with different severities. We aimed to modify the original table to adjust the severities and to validate these changes. METHODS: We modified the original table by adding links from unmappable AIS 98 codes to AIS 2008 codes. We applied the original table and our modified table to AIS 98 codes for major trauma patients. We also assigned candidate codes with different severities the weighted averages of their severities as an adjusted severity. The proportion of cases whose injury severity scores (ISSs) were computable were compared. We also compared the agreement of the ISS and New ISS (NISS) between manually determined AIS 2008 codes (MAN) and mapped codes by using our table (MAP) with unadjusted or adjusted severities. RESULTS: All and 72.3% of cases had their ISSs computed by our modified table and the original table, respectively. The agreement between MAN and MAP with respect to the ISS and NISS was substantial (intraclass correlation coefficient = 0.939 for ISS and 0.943 for NISS). Using adjusted severities, the agreements of the ISS and NISS improved to 0.953 (p = 0.11) and 0.963 (p = 0.007), respectively. CONCLUSION: Our modified mapping table seems to allow more ISSs to be computed than the original table. Severity scores exhibited substantial agreement between MAN and MAP. The use of adjusted severities improved these agreements further.

Clinical validation of a customized multiple signature microarray for breast cancer.

PURPOSE: Current histopathologic systems for classifying breast tumors require evaluation of multiple variables and are often associated with significant interobserver variability. Recent studies suggest that gene expression profiles may represent a promising alternative for clinical cancer classification. Here, we investigated the use of a customized microarray as a potential tool for clinical practice. EXPERIMENTAL DESIGN: We fabricated custom 188-gene microarrays containing expression signatures for three breast cancer molecular subtypes [luminal/estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2), and "basaloid"], the Nottingham prognostic index (NPI-ES), and low histologic grade (TuM1). The reliability of these multiple-signature arrays (MSA) was tested in a prospective cohort of 165 patients with primary breast cancer. RESULTS: The MSA-ER signature exhibited a high concordance of 90% with ER immunohistochemistry reported on diagnosis (P < 0.001). This remained unchanged at 89% (P < 0.001) when the immunohistochemistry was repeated using current laboratory standards. Expression of the HER2 signature showed a good correlation of 76% with HER2 fluorescence in situ hybridization (FISH; ratio > or =2.2; P < 0.001), which further improved to 89% when the ratio cutoff was raised to > or =5. A proportion of low-level FISH-amplified samples (ratio, 2.2-5) behaved comparably to FISH-negative samples by HER2 signature expression, HER2 quantitative reverse transcription-PCR, and HER2 immunohistochemistry. Luminal/ER+ tumors with high NPI-ES expression were associated with high NPI scores (P = 0.001), and luminal/ER+ TuM1-expressing tumors were significantly correlated with low histologic grade (P = 0.002) and improved survival outcome in an interim analysis (hazard ratio, 0.2; P = 0.019). CONCLUSION: The consistency of the MSA platform in an independent patient population suggests that custom microarrays could potentially function as an adjunct to standard immunohistochemistry and FISH in clinical practice.

Early detection of breast cancer through population-based mammographic screening in Asian women: a comparison study between screen-detected and symptomatic breast cancers.

The first nation-wide mammographic screening program in Asia, BreastScreen Singapore (BSS), was launched in Singapore in January 2002. This study compared the presentation and results of screen-detected breast cancers with symptomatic breast cancers in two affiliated high-volume institutions, one of which was an assessment centre for BSS. The medical records of patients diagnosed with primary breast cancer at the Department of General Surgery, Singapore General Hospital and the Department of Surgical Oncology, National Cancer Centre, Singapore, during the period January 2002 to December 2003 were reviewed. Clinical and pathological comparisons were made between screen-detected lesions and symptomatic lesions. Of a total of 767 cases, 640 (83.4%) were invasive carcinomas and 127 (16.6%) were ductal carcinoma in-situ (DCIS) lesions. Only 13.4% of them were screen-detected. Compared to symptomatic cancers, screen-detected lesions were of smaller size (median size 18 versus 23 mm), a lower stage (stages 0-2, 95 versus 83.2%) and histologic grade (grade 1-2, 71 versus 60%), with a higher incidence of DCIS (31.0 versus 14.3%) and had higher rates of breast conservation (45.6 versus 28.2%) (all p-values <0.05). By multivariate analysis, tumor palpability, tumor size >20 mm, nodal involvement, cerbB2 overexpression, and advanced disease stage were independent poor prognostic factors for disease-free survival, whereas nodal involvement, advanced disease, and recurrence predicted poor cancer-specific survival. However, there was no statistically significant difference in disease-free survival or cancer-specific survival between the two groups at a median follow-up of 38 months. Screening mammography has allowed the detection of smaller and hence oncologically more favorable lesions in Asian women. Although no significant survival benefit was demonstrated in our study, a longer period of follow-up is essential before the benefit of mortality reduction, as a result of mammography screening becomes evident in our population.

Managing breast cancer diagnosed in first trimester pregnancy: a case report.

INTRODUCTION: Breast cancer is the most common malignancy in pregnant women, occurring at a rate of about 1 in 3000 pregnancies. Unfortunately, this will sometimes occur during the first trimester of pregnancy and this situation warrants discussion of management options with regard to the mother and child, especially with the current trend of deferring child bearing to a later age. CLINICAL PICTURE: We present a 34-year-old primigravida who had a breast lump prior to confirmation of her pregnancy and received her diagnosis of invasive breast cancer at 7 weeks' amenorrhoea. The oncologic management options of this pregnant patient with breast cancer are discussed. TREATMENT: The patient eventually opted to undergo wide excision of the breast cancer with sentinel lymph node biopsy and possible axillary clearance together with termination of her pregnancy. RESULTS: The patient successfully underwent surgery for her breast cancer and was subsequently treated with adjuvant therapy as per normal protocol for a non-pregnant patient. CONCLUSION: The management of breast cancer and pregnancy occurring concurrently is a complex problem fraught with many dilemmas for both the medical team, the patient and her family. The option chosen must involve a multidisciplinary team and have full informed consent of the patient.

Recurrent phyllodes tumours of the breast: pathological features and clinical implications.

BACKGROUND: Phyllodes tumours (PT) of the breast are fibro-epithelial neoplasms that are known to recur locally in up to 19% of patients. The failure to achieve adequate surgical margins is an important risk factor for local recurrence. This, however, is a common problem as PT are clinically similar to the more common fibro-adenoma and are therefore often locally excised without any gross surgical margins. It is still debatable as to whether it is necessary to subject the patient to repeat surgery to obtain pathologically negative margins after a diagnosis of a benign or borderline PT is made. Although the majority of recurrences are histologically similar to the initial tumour, a malignant recurrence is possible. Malignant tumours can metastasize through the haematogenous route and metastases are associated with a poor prognosis as they are poorly responsive to conventional chemotherapy. METHODS: We retrospectively reviewed 37 women who presented with local recurrence over a 10-year period to the Singapore General Hospital. Data, including age at the time of diagnosis, clinical presentation, histological features, type of surgery carried out, clinical progression and characteristics of locally recurrent disease, were analysed. Comparisons were made between those with benign, borderline and malignant tumours, as well as between those who developed a malignant recurrence and those who did not. RESULTS: The mean age at the time of diagnosis was 39.6 +/- 7.4 years and the mean tumour size was 6.0 +/- 5.1 cm. A total of 22 patients were classified as having benign tumour, 9 as having borderline tumour and 6 as having malignant tumour. Tumour grade did not influence the tumour size, the adequacy of surgical margins or the time interval to local recurrence or the number of recurrences. Local recurrence occurred after a median interval of 20 months. Although malignant tumours tended to recur earlier, this was not found to be statistically significant. The majority of recurrent tumours were histologically similar to the initial tumour; however, seven patients (19%) developed a malignant recurrence from an initially benign or borderline tumour. Although these tumours were larger, recurred more frequently and within a shorter interval, no significant predictive factor was found on multivariate analysis. Distant metastasis developed only in patients with malignant tumours and accounted for all three mortalities in the study. CONCLUSIONS: It may be acceptable to use an expectant management towards benign and borderline tumours that are excised without adequate surgical margins. However, surgery for locally recurrent tumours, as well as malignant tumours, should aim to achieve adequate surgical margins to reduce the risk of local recurrence, particularly that of a malignant recurrence.

Correlation between breast tumour size and level of axillary lymph node involvement.

OBJECTIVE: Axillary lymph node dissection (ALND) is important for prognosis but does carry certain morbidities, particularly arm lymphoedema. Our aim was to determine whether tumour size correlates with level of axillary lymph node involvement in order to minimize ALND for small tumours. METHODS: Data were collected prospectively. Patients undergoing breast cancer surgery between May and December 2002 underwent preoperative breast ultrasound to measure the size of the primary tumour. Standard ALND was performed for all patients and levels of lymph nodes were sent separately to determine extent of involvement. RESULTS: Of the 203 cases studied, 91 (44.8%) had T1 tumours (<2 cm). The incidence of level II lymph nodes in T1 tumours was 4.4% (4/91 patients). The greater the T stage, the higher the incidence of level I and II involvement (4.4% in T1, 7.1% in T2 and 36.5% in T3 tumours). No node-positive patients had isolated level II lymph node involvement. Ultrasound-determined tumour size correlated well with final histological size (p<0.0005). CONCLUSION: Based on size, 95.6% (87/91) of patients with T1 tumours did not have level II lymph node metastases, so for these patients, level I axillary dissection is adequate.

Malignant phyllodes tumour presenting as a massive fungating breast mass and silent thrombo-embolism.

INTRODUCTION: We report an unusual case of a massive malignant phyllodes tumour that had almost replaced the entire breast presenting with severe chronic blood loss, extensive deep venous thrombosis (DVT) and a silent pulmonary embolus. PRESENTATION: Long-standing neglected massive fungating ulcerative mass larger than the left haemothorax. DISCUSSION: Phyllodes tumours are rare fibro-epithelial breast lesions that have the propensity to grow rapidly to a large size if neglected. Larger tumours are more likely to be malignant with an overall metastatic rate around 10%. An incidental pulmonary embolus arising from extensive silent lower limb deep vein thrombosis requiring an IVC filter complicated the surgical management. CONCLUSION: Phyllodes tumours are rare and account for approximately 0.3-0.5% of all breast tumours [1]. They have the propensity to be fast growing. However, tumours reaching a massive size (>10cm) are rare with few reports in the literature.

Victims of falls from a height surviving to hospital admission in two Singapore hospitals.

Falls from a height are a common problem in Singapore. However, there has been no analysis of the injury patterns and outcomes of patients who survived initial resuscitation after falls from a height in Singapore. One hundred and thirty-nine patients admitted over a two-and-a-half year period after falls of greater than one storey were studied. The higher the fall, the greater the likelihood of hypotension and neurological injury. The length of stay in hospital, the number of operative procedures and mortality also correlated with the height of the fall. The overall mortality rate was 11% but rose to 47% among patients who were hypotensive on admission. About half of the deaths were due to head injury with haemorrhage being the second most common cause. The majority of patients who fell from five or more storeys did so intentionally, and had more severe torso and extremity injuries compared with those who fell accidentally. These findings suggest that efforts in injury prevention and aggressive evaluation and treatment of fall victims arriving alive at the hospital continue to be important.

Systematic review of predictive performance of injury severity scoring tools.

Many injury severity scoring tools have been developed over the past few decades. These tools include the Injury Severity Score (ISS), New ISS (NISS), Trauma and Injury Severity Score (TRISS) and International Classification of Diseases (ICD)-based Injury Severity Score (ICISS). Although many studies have endeavored to determine the ability of these tools to predict the mortality of injured patients, their results have been inconsistent. We conducted a systematic review to summarize the predictive performances of these tools and explore the heterogeneity among studies. We defined a relevant article as any research article that reported the area under the Receiver Operating Characteristic curve as a measure of predictive performance. We conducted an online search using MEDLINE and Embase. We evaluated the quality of each relevant article using a quality assessment questionnaire consisting of 10 questions. The total number of positive answers was reported as the quality score of the study. Meta-analysis was not performed due to the heterogeneity among studies. We identified 64 relevant articles with 157 AUROCs of the tools. The median number of positive answers to the questionnaire was 5, ranging from 2 to 8. Less than half of the relevant studies reported the version of the Abbreviated Injury Scale (AIS) and/or ICD (37.5%). The heterogeneity among the studies could be observed in a broad distribution of crude mortality rates of study data, ranging from 1% to 38%. The NISS was mostly reported to perform better than the ISS when predicting the mortality of blunt trauma patients. The relative performance of the ICSS against the AIS-based tools was inconclusive because of the scarcity of studies. The performance of the ICISS appeared to be unstable because the performance could be altered by the type of formula and survival risk ratios used. In conclusion, high-quality studies were limited. The NISS might perform better in the mortality prediction of blunt injuries than the ISS. Additional studies are required to standardize the derivation of the ICISS and determine the relative performance of the ICISS against the AIS-based tools.

International comparison of regional trauma registries.

BACKGROUND: A regional trauma registry (RTR) collects injury data from multiple hospitals in a given region; however, the differences among RTRs have not yet been thoroughly investigated. AIM: The objective of this study was to identify RTRs worldwide and describe the structural differences, inclusion criteria and demographics among RTRs, as well as to investigate the effect of the inclusion criteria on patient demographics. MATERIALS AND METHODS: We included state, national and multinational trauma registries in this study. We searched for RTRs using the MEDLINE database and a general Internet search engine. We abstracted the funding sources, AIS versions, data submission methods, inclusion criteria and patient demographics of each RTR. We selected the following three outcome measures for comparison: the number of case registrations per year per hospital, proportion of cases with an Injury Severity Score (ISS)>15 and crude mortality rate. We compared the outcome measures for RTRs that included 'an ISS>15', 'an admission to the Intensive Care Unit (ICU)' or 'a transferred patient for higher care' with those of RTRs that did not. RESULTS: We identified 17 RTRs (11 national, 4 state and 2 multinational). Government funding was the most common funding source. The RTRs most frequently used the AIS 98 or AIS 2008. Web-based data submission was the most common. A significantly increased crude mortality rate was seen with 'an admission to the ICU' and 'an ISS>15'. CONCLUSION: We identified 17 RTRs, analysed the differences among RTRs and investigated the effect of the inclusion criteria on patient demographics. These findings may be useful when improving or developing RTRs.

Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008).

The Abbreviated Injury Scale (AIS) was revised in 2005 and updated in 2008 (AIS 2008). We aimed to compare the outcome prediction performance of AIS-based injury severity scoring tools by using AIS 2008 and AIS 98. We used all major trauma patients hospitalized to the Royal Perth Hospital between 1994 and 2008. We selected five AIS-based injury severity scoring tools, including Injury Severity Score (ISS), New Injury Severity Score (NISS), modified Anatomic Profile (mAP), Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). We selected survival after injury as a target outcome. We used the area under the Receiver Operating Characteristic curve (AUROC) as a performance measure. First, we compared the five tools using all cases whose records included all variables for the TRISS (complete dataset) using a 10-fold cross-validation. Second, we compared the ISS and NISS for AIS 98 and AIS 2008 using all subjects (whole dataset). We identified 1,269 and 4,174 cases for a complete dataset and a whole dataset, respectively. With the 10-fold cross-validation, there were no clear differences in the AUROCs between the AIS 98- and AIS 2008-based scores. With the second comparison, the AIS 98-based ISS performed significantly worse than the AIS 2008-based ISS (p<0.0001), while there was no significant difference between the AIS 98- and AIS 2008-based NISSs. Researchers should be aware of these findings when they select an injury severity scoring tool for their studies.

Laparotomy for acute complications of gastrointestinal metastases from lung cancer: is it a worthwhile or futile effort?

PURPOSE: Complications of gastrointestinal tract (GIT) metastases from lung cancer are rare and the optimal management remains controversial. Whereas some authors advocate a nonoperative policy due to the poor prognosis, others recommend aggressive surgery as it offers effective palliation. The aim of this study is to present our experience with nine patients who underwent a laparotomy for complications of GIT metastases and to determine their outcome. METHODS: Between 1995 and 2005, nine patients who underwent a laparotomy for complications of pathologically proven GIT metastases secondary to lung cancer were retrospectively reviewed. RESULTS: All patients were male with a median age of 63 years (range, 40-70 years) at initial presentation. The sites of symptomatic GIT metastases include the ileum (n = 3), jejunum (n = 3), cecum (n = 1), duodenum (n = 2) and stomach (n = 2) and the patients presented with obstruction (n = 2), hemorrhage (n = 3), intussusception (n = 3) and perforation (n = 1). The median time of symptomatic GIT metastases from initial presentation was 2 months (range, 0-8 months) and the histological subtypes of the lung cancer were squamous cell carcinoma (n = 3), large cell carcinoma (n = 3), adenocarcinoma (n = 1), pleomorphic carcinoma (n = 1) and pleomorphic with adenocarcinoma (n = 1). All patients underwent an exploratory laparotomy and the definitive surgical procedure was dependent on the site and extent of disease. These included a small bowel resection with primary anastomosis (n = 5), a subtotal gastrectomy with an extended right hemicolectomy (n = 1), a gastrojejunostomy (n = 1), a right hemicolectomy (n = 1), and an ulcerectomy with under-running of ulcers (n = 1). Eight of the nine patients (89%) recovered from surgery and were then discharged from hospital at a median time of 9.5 days (range, 6-24 days). All these eight patients survived for more than 30 days and the median survival was 6 months (range, 2-13 months). Four of the 8 patients (50%) lived for more than 6 months and all eight patients died of advanced metastatic lung cancer with multiple sites of metastases at the time of death. CONCLUSION: Gastrointestinal tract metastases should always be considered in the differential diagnosis of lung cancer patients presenting with an acute abdomen. Aggressive surgical treatment is worthwhile in a selected group of patients as it provides effective palliation.

Use of the extended V-Y latissimus dorsi myocutaneous flap for chest wall reconstruction in locally advanced breast cancer.

The extended V-Y latissimus dorsi myocutaneous flap described by Micali and Carramaschi provides an innovative method of closing large anterior chest defects after resection of breast cancer. The technique provides robust chest wall coverage that is able to withstand immediate postoperative radiotherapy. The aim of this article is to confirm the usefulness of the flap's design and describe modifications to the technique. The modifications to technique include: a curvilinear design that recruited more skin for closure in patients with wounds extending laterally or superiorly, routine transposition of latissimus dorsi insertion inferio-medially onto the chest wall to maximize pedicle reach, and the use of small split skin grafts or delayed primary closure if there was tension in closing. Twelve patients who underwent resection of locally advanced breast cancer had immediate chest wall reconstruction with the extended V-Y latissimus dorsi musculocutaneous flap. The V to Y design of the flap's cutaneous island allowed primary closure of chest wound and donor defect. There were no instances of chest wound dehiscence. The chest wounds healed, allowing patients to undergo adjuvant radiotherapy in a mean time interval of 6 weeks after surgery.

Traumatic pneumorrhachis.

Traumatic pneumorrhachis is extremely rare, and a review of the English literature has revealed only 31 reported cases. We review the cause and pathophysiology of this unique entity in trauma patients. We also discuss the significance of this entity to the trauma specialist, paying special attention to the differences between air in the subarachnoid space versus air in the epidural space.