Thyroid Nodule Detection and Region Estimation in Ultrasound Images: A Comparison between Physicians and an Automated Decision Support System Approach.

BACKGROUND: Thyroid nodules are very common. In most cases, they are benign, but they can be malignant in a low percentage of cases. The accurate assessment of these nodules is critical to choosing the next diagnostic steps and potential treatment. Ultrasound (US) imaging, the primary modality for assessing these nodules, can lack objectivity due to varying expertise among physicians. This leads to observer variability, potentially affecting patient outcomes. PURPOSE: This study aims to assess the potential of a Decision Support System (DSS) in reducing these variabilities for thyroid nodule detection and region estimation using US images, particularly in lesser experienced physicians. METHODS: Three physicians with varying levels of experience evaluated thyroid nodules on US images, focusing on nodule detection and estimating cystic and solid regions. The outcomes were compared to those obtained from a DSS for comparison. Metrics such as classification match percentage and variance percentage were used to quantify differences. RESULTS: Notable disparities exist between physician evaluations and the DSS assessments: the overall classification match percentage was just 19.2%. Individually, Physicians 1, 2, and 3 had match percentages of 57.6%, 42.3%, and 46.1% with the DSS, respectively. Variances in assessments highlight the subjectivity and observer variability based on physician experience levels. CONCLUSIONS: The evident variability among physician evaluations underscores the need for supplementary decision-making tools. Given its consistency, the CAD offers potential as a reliable "second opinion" tool, minimizing human-induced variabilities in the critical diagnostic process of thyroid nodules using US images. Future integration of such systems could bolster diagnostic precision and improve patient outcomes.

Effect of the nasal airflow inducing manoeuvre on olfaction and quality of life after laryngectomy.

OBJECTIVE: To assess the effectiveness of the nasal airflow inducing manoeuvre or 'polite yawn' technique in improving olfaction and quality of life in laryngectomised patients. METHODS: Using a prospective study design, 42 patients scheduled to undergo laryngectomy at a tertiary care centre were subjected to olfaction testing before surgery and two weeks following the surgery. The nasal airflow inducing manoeuvre was taught, and the olfaction test was repeated with the patient performing the nasal airflow inducing manoeuvre. Quality of life was assessed using the Appetite, Hunger and Sensory Perception questionnaire with calculation of scores after the patient had learnt the nasal airflow inducing manoeuvre. RESULTS: There was a significant reduction in the composite olfaction score, from a mean (standard deviation) baseline value of 4.01 (1.39) to 0.44 (0.51), two weeks after surgery (p < 0.001). After practising the nasal airflow inducing manoeuvre, the olfaction scores increased to 3.05 (1.32) (p < 0.001). Appetite, Hunger and Sensory Perception questionnaire scores ranged from 52 to 110 (normal range, 29-145), suggesting an improvement in the quality of life of patients. CONCLUSION: The nasal airflow inducing manoeuvre, an inexpensive, simple, patient-friendly manoeuvre, can be used in the olfaction rehabilitation of patients undergoing laryngectomy.

Hoarseness: its spectrum, associations and management in a tertiary care centre in India.

OBJECTIVE: To determine the demographic, aetiopathological and diagnostic profiles of patients presenting with hoarseness to a laryngology unit of a tertiary care centre in India. METHODS: A retrospective observational study was conducted. RESULTS: The 1033 patients who presented with dysphonia showed a male predominance (70 per cent), high rates of malignancy (18 per cent), late presentation (mean, 24 months) and poor follow-up trends (53 per cent with 3 months' follow up), which contrasts with data from developed countries. The patient population hailed from different states in India and neighbouring countries around India, serving as a good sample for the subcontinent. The majority (67 per cent) were managed conservatively; however, surgical management was the preferred choice for those who presented with airway stenosis (91 per cent) and laryngeal trauma (75 per cent). Significant associations between vocal professionalism level and co-morbidities and dysphonia aetiopathologies are discussed. CONCLUSION: These findings give insight into the trends of hoarseness in the developing Indian subcontinent, which can aid understanding and management.

Anomalous innominate artery complicating tracheal surgical procedures.

OBJECTIVE: To highlight the importance of imaging in reducing an accidental injury to the anomalous brachiocephalic trunk and its branches during tracheal surgery. CASE REPORT: This paper reports two cases of accidental injury to the great vessels in the neck during tracheal surgery. The first incident occurred during a repeat tracheostomy, when the right common carotid artery was injured. On reviewing the computed tomography images, the bifurcation of the brachiocephalic artery was seen to the left of the midline, and the right common carotid artery was adherent just below the tracheostomy site. The second incident happened during surgery for tracheal stenosis, when there was an inadvertent injury to the main brachiocephalic trunk, which was adherent to the trachea in the lower neck region. CONCLUSION: For airway surgeons, radiological assessment of vascular structures in relation to the trachea prior to surgery is as important as the endoluminal airway assessment for the best outcome.

Testicular seminoma: Are clinical features and treatment outcomes any different in India?

AIM: This study aims to identify clinical features, treatment outcomes, and prognostic factors for relapse and survival in patients with testicular seminoma. MATERIALS AND METHODS: Retrospective analysis of all patients with pure seminoma treated at our center during over a decade (January 2005-December 2014) was carried out. Patient demographics, tumor characteristics, and treatment details and pattern of recurrence were recorded in a structured format, and disease-free survival and overall survival were calculated. RESULTS: Sixty-three patients' case records were included in the analysis. Ten patients developed disease in the undescended testis. All patients underwent orchiectomy as the initial treatment procedure. Majority of the patients were Stage I (57.14%) followed by Stage II (39.6%). Among the patients with Stage I, 55.5% received adjuvant chemotherapy while 22.2% received adjuvant radiation and the rest opted for surveillance. The compliance for active surveillance was very poor. Among patients with Stage II disease, majority (80%) were treated with adjuvant chemotherapy and the rest with radiation. At a median follow-up of 49 months, there were four recurrences of which three were salvaged successfully, and one patient remained alive with disease. There were no disease-related deaths. CONCLUSIONS: Testicular seminoma remains to be relatively low and majority of them presented with Stage I disease and single agent carboplatin appeared to be the preferred adjuvant treatment. Advanced disease patients were treated with etoposide and cisplatin/bleomycin, etoposide and cisplatin chemotherapy and the clinical outcome is comparable with the Western literature.

Current therapeutic protocols for chronic granulomatous fungal sinusitis.

BACKGROUND: The treatment of chronic granulomatous fungal sinusitis (CGFS), a rare form of invasive fungal sinusitis, is controversial. AIM: To assess the response to postoperative antifungal therapy in patients with CGFS and suggest an effective treatment protocol. METHODOLOGY: Clinical records of patients with CGFS who had undergone excisive surgery followed by antifungal therapy were reviewed to assess current disease status. RESULTS: Fourteen male and 4 female patients were diagnosed with CGFS, based on typical histopathological and fungal smear/ culture results. Aspergillus flavus was isolated from 88.9% cases. Stage 1 patients had resectable sinonasal disease, stage 2 had additional spread to orbit/palate and stage 3 had extensive disease. Follow-up ranged from 6 months to 8 years. Residual disease was seen in all but one patient who received amphotericin B as first line therapy and in none of those who received itraconazole or voriconazole. Even those who received azoles as second line therapy were disease free at last follow-up. CONCLUSION: Surgery followed by itraconazole or voriconazole for Stage 1 and 2 disease and voriconazole for stage 3 disease is recommended for a good outcome. Amphotericin B is not recommended as first line therapy for CGFS.

Velopharyngeal incompetence in patients with cleft palate, flexible video pharyngoscopy and perceptual speech assessment: a correlational pilot study.

OBJECTIVES: To assess the role of video endoscopy in evaluating velopharyngeal incompetence and investigate a possible relationship between velopharyngeal incompetence type and speech defect in cleft palate patients. METHODS: A prospective study of 28 pre- or post-operative cleft palate patients with speech defects who attended Plastic Surgery-Cleft Palate and ENT out-patient clinics was performed. The velar defect type was determined using a flexible endoscope and findings were video recorded. Speech pathology was assessed using the cleft palate audit protocol for speech. RESULTS: A significant, clinically relevant relationship was noted between the perceived characteristics of hypernasality and velopharyngeal insufficiency type. Hypernasal speech was a definite clinical indicator of velopharyngeal incompetence, and the type 1 velopharyngeal defect was most common. Type 1 velopharyngeal coronal-type dysfunction was strongly associated with hypernasality (p < 0.05). When speech substitution was noted, type 2 velopharyngeal (or sagittal) incompetence could be predicted (p < 0.05). CONCLUSION: In the management of cleft palate patients, it is important that surgical correction of the defect and achieving velopharyngeal competency for speech are performed simultaneously. Pre-operative velopharyngeal endoscopy with speech assessment will define the anatomical and functional bases for velopharyngeal correction and assist in planning and tailoring the pharyngeal flap.

Recent synchronous radiation of a living fossil.

Modern survivors of previously more diverse lineages are regarded as living fossils, particularly when characterized by morphological stasis. Cycads are often cited as a classic example, reaching their greatest diversity during the Jurassic-Cretaceous (199.6 to 65.5 million years ago) then dwindling to their present diversity of ~300 species as flowering plants rose to dominance. Using fossil-calibrated molecular phylogenies, we show that cycads underwent a near synchronous global rediversification beginning in the late Miocene, followed by a slowdown toward the Recent. Although the cycad lineage is ancient, our timetrees indicate that living cycad species are not much older than ~12 million years. These data reject the hypothesized role of dinosaurs in generating extant diversity and the designation of today's cycad species as living fossils.

Chitosan enhances mineralization during osteoblast differentiation of human bone marrow-derived mesenchymal stem cells, by upregulating the associated genes.

OBJECTIVES: Chitosan is widely used as a scaffold for bone tissue engineering. However, up-to-date, no previous detailed study has been conducted to elucidate any mechanism of osteogenesis by chitosan itself. Here, we have evaluated effects of chitosan-coated tissue culture plates on adhesion and osteoblast differentiation processes of human mesenchymal stem cells (hMSCs), isolated from adult bone marrow. MATERIALS AND METHODS: Tissue culture plates coated with chitosan at different coating densities were used to evaluate the effects on hMSC adhesion and osteoblast differentiation. hMSCs were induced to differentiate into osteoblasts on the chitosan-coated plates and were evaluated using established techniques: alkaline phosphatase assay, demonstration of presence of calcium and real time PCR. RESULTS: The cells adhered to plates of lower coating density of chitosan, but formed viable cell aggregates at higher coating density (100 µg/sq.cm). Coating density of 25 µg/sq.cm, supporting cell adhesion was chosen for osteoblast differentiation experiments. Differentiating hMSCs showed higher mineral deposition and calcium content on chitosan-coated plates. Chitosan upregulated genes associated with calcium binding and mineralization such as collagen type 1 alpha 1, integrin-binding sialoprotein, osteopontin, osteonectin and osteocalcin, significantly. CONCLUSIONS: We demonstrate for the first time that chitosan enhanced mineralization by upregulating the associated genes. Thus, the study may help clinical situations promoting use of chitosan in bone mineralization, necessary for healing non-union fractures and more.

Alpha-fetoprotein as a tumor marker in hepatocellular carcinoma: investigations in south Indian subjects with hepatotropic virus and aflatoxin etiologies.

OBJECTIVES: The prevalence of hepatitis B virus (HBV) is reportedly the main cause of hepatocellular carcinoma (HCC) in India, where hepatitis C virus (HCV)-associated HCC is believed to be relatively less prevalent. We verified the usefulness of alpha-fetoprotein (AFP) as a tumor marker and analyzed the influence of viral etiology on AFP levels in HCC. METHODS: Of a total of 1012 cases with liver disease, 202 were investigated for the presence of AFP (142 HCC cases, 30 cirrhosis cases, and 30 chronic liver disease (CLD) cases). In addition, serum samples from 30 healthy patients, 30 hepatitis B surface antigen (HBsAg) carriers, and 30 acute viral hepatitis cases were included as controls. AFP was quantitatively determined using a commercial ELISA (Quorum Diagnostics, Canada). Out of the 142 HCC cases screened for AFP, aflatoxin B1 (AFB1) detection was carried out in 38 HCC cases using an in-house immunoperoxidase test. RESULTS: In HBV and HCV co-infected HCC cases, the AFP positivity was 85.7%. In HBV alone-associated HCC, the positivity was 62.9%, and 54.5% of AFB1 positive HCC cases showed AFP positivity. In HBV and HCV negative HCC cases, the positivity was 20.5%, and in HCV-associated HCC it was 17.6%. The HBV/HCV co-infected group and HBV alone positive HCC cases had significantly elevated levels of AFP. When AFP positivity was analyzed based on the marker profile of HBV, 89.7% of AFP positive cases were HBV-DNA positive. CONCLUSIONS: The overall positivity pattern of AFP in HCC does indicate that higher levels of AFP are observed with hepatitis virus positivity, especially with HBV. Further studies must be carried out to correlate the serum levels of AFP with the size, number, and degree of differentiation of HCC nodules.

Oral manifestations of Sjögren's syndrome.

Sjögren's syndrome is a common autoimmune rheumatic disease. The most common symptoms of Sjögren's syndrome are extreme tiredness, along with dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). Saliva plays an essential role in numerous functions of the mouth. Xerostomia can be caused by medications, chronic diseases like Sjögren's syndrome, and medical treatments, such as radiation therapy and bone marrow transplant. Xerostomia can eventually lead to difficulty in swallowing, severe and progressive tooth decay, or oral infections. Despite having excellent oral hygiene, individuals with Sjögren's syndrome have elevated levels of dental caries, along with the loss of many teeth, early in the disease. Sjögren's syndrome alters the protein profile and brings about a change in the composition of saliva. There is an increase in the levels of lactoferrin, beta(2)-microglobulin, sodium, lysozyme C, and cystatin C, and a decrease in salivary amylase and carbonic anhydrase. Up to 90% of individuals with Sjögren's syndrome have antibodies targeting the Ro 60 and La autoantigens. Natural aging, regardless of Sjögren's syndrome, is also another factor that brings about a significant change in the composition of saliva. The most prevailing cause of xerostomia in elderly persons is the use of anticholinergic medications. Currently, there is no cure for Sjögren's syndrome, and treatment is mainly palliative.

Prevalence of aflatoxin B1 in liver biopsies of proven hepatocellular carcinoma in India determined by an in-house immunoperoxidase test.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death in the world. The incidence of HCC in India is reportedly low and varies from 0.2 to 1.9 %. Aflatoxins, secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus, are potent human carcinogens implicated in HCC. The prevalence of aflatoxin B1 (AFB1) as co-carcinogen was analysed using an in-house immunoperoxidase test in 31 liver biopsies and 7 liver-resection specimens from histopathologically proven HCC, and in 15 liver biopsies from cirrhosis patients (control group). Serum was tested for hepatitis B and C serological markers using commercial assays, and for AFB1 using an in-house ELISA with a sensitivity of approximately 1 ng ml(-1) for AFB1. In spite of positive AFB1 immunostaining in HCC cases, all serum specimens, from both HCC and the control groups, were AFB1-negative. There were 18 (58.1 %) HCC cases that revealed AFB1 in liver biopsies; 68.8 % (n=11) of non-B non-C hepatitis cases with HCC and 46.1 % (n=6) of the hepatitis B surface-antigen-positive subjects were positive for AFB1. Out of the two hepatitis B/hepatitis C virus co-infected cases, one was positive for AFB1. Of seven tumour-resection samples, six were positive for AFB1. Only one case revealed AFB1 in the non-tumour area of the resected material. Thus AFB1 staining was significantly associated with tumour tissue (P=0.03). Aflatoxins proved to have a significant association with HCC in this peninsular part of the subcontinent. The impact seems to be a cumulative process, as revealed by the AFB1 deposits in HCC liver tissue, even though the serum levels were undetectable.

The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept. METHODS: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24. RESULTS: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points. CONCLUSION: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.

Early management of pathological fractures in children.

The management of pathological fractures in children remains controversial. The indications for surgical treatment are unclear and the need for histological diagnosis before or after definitive treatment is not clearly defined. We reviewed retrospectively the records of all patients under the age of 16 years who presented over the past 7 years with a fracture as the first manifestation of bone pathology. There were 23 patients (16 boys and 7 girls) of an average age of 12 years and 2 months (range 4.1-15.8 years). There were nine cases of fracture through a simple bone cyst, five cases of fibrous dysplasia, two giant cell tumours, three aneurysmal bone cysts, one chondroblastoma, and three cases of Ewings sarcoma. After review of our cases we propose a simple algorithm for the safe early management and assessment of paediatric pathological fractures. We recommend that primary fixation of pathological fractures should be avoided until histological diagnosis is obtained. Most lesions should eventually be biopsied. However, if radiographic appearances are reassuringly benign, biopsy can be delayed until conservative fracture management is completed. Definitive treatment of benign lesions with protective intra medullary nailing or curettage and grafting can follow frozen section under the same anaesthetic.

A phase I study of oral ZD 1839 given daily in patients with solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), the biological active (BA) dose and the pharmacokinetics (PK) of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa) when administered continuously as a once daily dose in patients with advanced, incurable solid tumours. PATIENTS AND METHODS: Twenty-eight patients were enrolled in cohorts of three from three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) centers. ZD1839 was given at doses from 150 to 800 mg daily orally and patients underwent a pretreatment and a 28 day post treatment tumor biopsy, while PK sampling was performed on days 8, 15, 22, 29, and a toxicity assessment every 28 days. RESULTS: All twenty-eight patients were evaluable for non-hematological and hematological toxicity. Twenty-seven were evaluable for response. The MTD was not reached but DLT included reversible rash and diarrhea. One patient with urachal cancer had a transient 55% decrease in tumor size and two other patients (breast and non-small cell lung cancer) had minor responses; three additional patients had pharmacodynamic evidence of target effect. PK demonstrated steady state within the first 2 weeks of dosing and dose dependent exposure. CONCLUSION: It appears that ZD 1839 at a dose of 800 m/day was tolerable, although some patients required dose modification for diarrhea. Doses above 250 m/day demonstrate biologic activity and could be consider for future study in a variety of EGFR positive tumor types.

Cumulative risk and trends in prostate cancer incidence in Mumbai, India.

BACKGROUND: Information relating to cancer incidence trends in a community forms the scientific basis for the planning and organization of prevention, diagnosis and treatment of cancer. We here estimated the cumulative risk and trends in incidence of prostate cancer in Mumbai, India, using data collected by the Bombay Population-based Cancer Registry from the year 1986 to 2000. METHODS: During the 15 year period, a total of 2864 prostate cancer cases (4.7% of all male cancers and 2.4% of all cancers) were registered by the Bombay Population-based Cancer Registry. For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the evaluation. Cumulative incidence rates percentages were calculated by adding up the age specific incidence rates at single ages and then expressed as a percentage. RESULTS: Analysis of the trends in age-adjusted incidence rates of prostate cancer during the period 1986 to 2000 showed no statistically significant increase or decrease and the rates proved stable across the various age groups (00-49, 50-69 and 70+) also. The probability estimates indicated that one out of every 59 men will contract a prostate cancer at some time in his whole life and 99% of the chance is after he reaches the age of 50. CONCLUSION: The stability in age adjusted-incidence rates indicates that there are no changes in the etiological factors for prostate cancer in Mumbai, India. These findings may be of general interest because changes in diagnostic practices are confounded in the time trends of prostate cancer change in many western countries preventing inferences on the changes in risk.