Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of 'development' and 'validation' cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

Focal therapy for localized prostate cancer in the era of routine multi-parametric MRI.

BACKGROUND: Prostate cancer focal therapy aims to minimize the side-effects of whole gland treatments, such as radical prostatectomy and radiotherapy without compromising oncological efficacy. However, concerns exist regarding the multifocal nature of prostate cancer and the lack of long-term oncological data for this form of treatment. In recent years, the routine adoption of multi-parametric magnetic resonance imaging (mpMRI) of the prostate has improved our ability to select candidates for focal therapy and to accurately deliver this form of prostate cancer treatment. METHODS: We performed a review of the literature to provide a summary of the oncological and functional outcomes of men receiving primary prostate focal therapy. Furthermore, we discuss the impact of the routine implementation of mpMRI as part of the initial prostate cancer diagnostic pathway on the selection of candidates and delivery of focal therapy. Finally, we summarize knowledge gaps in the field and highlight active clinical trials in this arena. RESULTS: Primary focal therapy involves the application of one of a number of energies that ablate tissue, such as cryotherapy and high intensity focused ultrasound (HIFU). Success is principally dependent on highly accurate patient selection and disease localization underpinned in large part by the routine integration of pre-biopsy mpMRI. Prospective medium-term follow-up data for primary HIFU and cryotherapy for men with intermediate-risk disease have shown acceptable cancer control with low risk of side effects and complications. Additional research is needed to clearly define an appropriate follow-up approach and to guide the management of in- and out-of-field recurrences. Multiple comparative trials with randomization against standard care are currently underway in men with intermediate- and high-risk prostate cancer. CONCLUSION: The widespread adoption of prostate mpMRI has led to improved disease localization, enabling the performance of focal therapy as a viable treatment strategy for men with low volume intermediate-risk prostate cancer.

The Demographic Study of Otorhinolaryngological Trauma Among Patients with Head and Neck Trauma and Their Management in a Tertiary Care Centre.

The trauma has been increasing in frequency, especially in recent decades because of the higher number of automobile accidents and violence. The ear, nose and face region is the area in the body that is commonly involved in head and neck injury. Trauma to this region is often associated with mortality and varying degree of physical, functional and psychological damage. To study the demography, aetiology, clinical presentation, outcome of ENT trauma in our tertiary care centre and to compare our study with previous studies to see the changing trends with passage of time. A prospective study was conducted on 200 head and neck patients with ENT injuries during a period of 1 year from July 2014 to July 2015, who were admitted in ENT Department and Trauma Centre of Gajra Raja Medical College and J.A. Group of Hospital, Gwalior. Most of the patients were young adult males of age group 18-40 years (45, 22.5%) with a male:female ratio 1.78:1. Among them 53% patients were from rural area while 47% were from urban area. RTA is the most prevalent cause of ENT trauma (37%), followed by interpersonal violence (25%). 27% of the patients had facial injury and multiple region injury each. Among 200 patients 33% were managed conservatively on the other hand 66% patients required surgical interventions. Mortality rate was 8%. Among all 184 survivors 25.5% suffered from hearing loss, 14.5% had tympanic membrane perforation with hearing loss, 12% had pinna disfigurement, 10% had change in voice, 6.5% had permanent nasal deformity, 2% had facial nerve palsy. Young male adults were the most prevalent victims of ENT trauma, and Road traffic accidents were responsible for majority of the ENT injuries. Screening of all the patients with head and neck injuries for the presence of trauma in the ENT region should be introduced to enable early detection and therefore prevention of complications.

[Urethral centralization and pseudo-glans formation after partial penectomy]. / Zentralisierung der Harnröhre und Pseudoglansbildung nach partieller Penektomie.

The management of penile cancer has altered dramatically over the last decade. Confidence to excise lesions safely with smaller margins has led to the adoption of penile-preserving techniques and in turn improved the functional and cosmetic results. Patients undergoing partial penectomy (PP) find that the urethral meatus is located in an abnormal ventral position. In addition, there is a high risk of meatal stenosis. We describe our novel technique that allows the urethral meatus to be centralised after PP and creation of a pseudo-glans and wide meatus and therefore maintain the cosmetic appearance of the penis after split thickness skin grafting. The UCAPP technique allows the restoration of the normal meatal location and creation of a pseudo-glans in case of partial penectomy and therefore can improve the overall cosmetic appearance and reduce the psychological morbidity.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Prognostic indicators of mortality of mechanically ventilated patients with acute leukemia in a comprehensive cancer center.

BACKGROUND: The prognosis for adult acute leukemia patients that require intensive care unit (ICU) admission and invasive mechanical ventilation is poor. We aimed to identify prognostic indicators of 30-day hospital mortality in adult patients who had acute leukemia and respiratory failure, who had received invasive mechanical ventilation in the ICU but who had not received blood and marrow transplantation, were not admitted due to cardiopulmonary arrest or myocardial infarction and, had not recently undergone surgery. METHODS: In this case-control study, we retrospectively reviewed the medical records of relevant patients >16 year old who had been admitted to the ICU at our institution over a 4-year period. The main outcome measure was 30-day hospital mortality. Univariate and multivariate analyses were conducted to determine significant predictors of death. RESULTS: For the 167 patients meeting our eligibility criteria, the median age was 61 years. The majority was admitted due to respiratory insufficiency/failure (69%). The 30-day hospital mortality rate was 62%. Independent predictors of 30-day hospital mortality were advanced disease status (odds ratio [OR]=3.34; 95% confidence interval [CI], 1.65-6.77) and increased organ failure at the time of intubation (OR=1.17; 95% CI, 1.03-1.33) per point increase in the SOFA score. Patients who had received endotracheal intubation within the first 24 h of ICU admission were less likely than others to die (OR=0.46, 95% CI, 0.23-0.91) within the next 30 days after admission to the hospital. CONCLUSION: Advanced disease status and elevated SOFA scores at intubation are strong predictors of 30-day mortality in patients with acute leukemia and respiratory failure. The protective effect of early endotracheal intubation warrants further investigation.

Prevalence of adrenal antibodies in Addison's disease among north Indian Caucasians.

OBJECTIVE: The prevalence of antibodies in different organ-specific autoimmune diseases can vary depending on the racial group studied. Data on the prevalence of antibodies against steroidogenic enzymes in Addison's disease is available only for white Caucasians. We have evaluated the frequency of antibodies against adrenal cytoplasm, 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzyme in a cohort of Indian patients with Addison's disease of idiopathic and granulomatous aetiology. DESIGN: Study of all patients with Addison's disease on whom serum samples were available (84% of total), presenting to the Endocrinology Department in a teaching hospital in India, between 1990 and 1999. PATIENTS: Thirty-eight patients with Addison's disease (19 idiopathic, 19 granulomatous). METHODS: A radiobinding assay using in vitro transcribed and translated recombinant human 35S-labelled 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzymes was utilized to detect the respective antibodies. Adrenal cytoplasmic antibodies were measured by indirect immunofluorescence on cryostatic sections of human adrenal cortex. RESULTS: Of the 19 patients with idiopathic Addison's disease, adrenal cytoplasmic antibodies were present in five (26%) patients, while 21-hydroxylase antibodies were present in four (21%) subjects. The frequency of 21-hydroxylase antibodies was similar among patients with isolated idiopathic Addison's disease (3/13, 23%), and those associated with other organ-specific autoimmune diseases (1/6, 17%). 17-alpha-hydroxylase and side-chain cleavage antibodies were present in four (21%) and three (16%) patients, respectively. Overall, at least one of the three antibodies was present in eight (42%) subjects. All four female patients with premature ovarian failure had antibodies against 17-alpha-hydroxylase and/or side-chain cleavage enzyme. Two (11%) patients with granulomatous Addison's disease had adrenal antibodies. Of these, one patient with enlarged and calcified adrenal gland secondary to tuberculosis had a high titre of antibodies against all three steroidogenic enzymes. CONCLUSIONS: Antibodies to 21-hydroxylase enzyme are less frequent in idiopathic Addison's disease in north Indians, when compared with other Caucasians. In contrast, the prevalence of 17-alpha-hydroxylase and side-chain cleavage enzyme antibodies is similar to those reported. High titre antibodies against steroidogenic enzymes may occasionally be present in patients with clinical evidence of tuberculous Addison's disease.

Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on treatment with selective serotonin reuptake inhibitor antidepressants.

BACKGROUND: Patients with depressive disorders smoke tobacco more often than the population at large and find quitting more difficult. Furthermore, when they quit smoking, they are more likely to suffer a relapse of depression. We evaluated the addition of bupropion sustained release (SR) for smoking cessation among patients with a history of depressive disorders being maintained in a euthymic state with selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD: Twenty-five adults with DSM-IV major depressive disorder or depressive disorder NOS currently receiving SSRI maintenance treatment and smoking > or = 15 cigarettes per day participated in the 9-week study. Bupropion SR, 150 mg/day, was added to SSRI treatment and increased to 300 mg/day. Subjects were counseled on smoking cessation measures and chose a target quit date 2 or 4 weeks after the initiation of bupropion SR. Self-reported smoking status, expired carbon monoxide (CO) measurements, Hamilton Rating Scales for Depression and Anxiety scores, and weight were measured at each visit. Subjects were abstinent if they reported not smoking during the prior 7 days, confirmed with an expired-air CO value of < or = 10 ppm. RESULTS: Eight (32%) of 25 subjects were abstinent after 9 weeks. At 3-month follow-up, 3 subjects remained abstinent, 3 relapsed, and 2 were lost to follow-up. Eleven subjects (44%) were nonresponders, and 6 (24%) dropped out prior to 3 weeks of treatment due to side effects (N = 3) or were lost to follow-up (N = 3). Mean weight gain was approximately 0.5 lb (0.2 kg) for those completing 9 weeks of bupropion SR treatment. During the 9-week study and the 3-month follow-up, there was no evidence of emergent depression in any subject. Four subjects (16%) spontaneously reported an improvement in SSRI-associated sexual dysfunction. CONCLUSION: These open data suggest modest effectiveness for and the safety of bupropion SR as a smoking cessation agent in individuals with depression maintained on treatment with SSRIs. Minimal weight gain, lack of emergent depressive episodes, and improvement of SSRI-associated sexual dysfunction are added advantages.

Androgen receptor mutations in prostate cancer.

We analyzed the frequency and relevance of mutations in the coding region of the androgen receptor (AR) in genomic DNA extracted from 137 specimens of prostate cancer. The specimens were obtained from the primary tumors of patients affected by stage B disease [15 nonmicrodissected (group 1A) and 84 microdissected (group 1B)] and from the metastatic deposits of individuals with stage D1 disease [8 nonmicrodissected (group 2A) and 30 microdissected (group 2B)] who had not undergone androgen ablation therapy. The study was conducted by PCR-single strand conformational polymorphism (SSCP) analysis of exons 2-8 in the four groups and direct sequence analysis of exon 1 in group 1B. As positive and negative controls, we used genomic DNA extracted from genital skin fibroblasts of patients affected by various forms of androgen resistance with known mutations in the AR. To control for genetic instability, PCR-SSCP analysis of exon 2 of the human progesterone receptor was carried out on each specimen. The overall number of mutations detected was 11 (8%). No mutations were detected in any of the 99 patients with stage B disease. Eleven mutations were detected in exons 2-8 in 8 of the 38 patients with stage D1 disease (all in group 2B). Simultaneous analysis of exon 2 of the progesterone receptor was carried out, and no SSCP changes were identified. These data suggest that AR mutations are rare and presumably do not play a role in the initial phase of prostatic carcinogenesis. The presence of a significant number of AR mutations in metastatic disease indicates that mutations of this molecule may play a role in the most advanced phases of the natural history of this disease, either by facilitating growth or acquisition of the metastatic phenotype.

Treatment of dual diagnosis patients: a relapse prevention group approach.

The authors describe the successful use of an adjunctive group psychotherapy for substance-abusing patients with major psychiatric disorders (bipolar, schizophrenia, schizoaffective, psychotic depression, and atypical psychosis). The group utilizes a psychoeducational approach that focuses on substance abuse causes and consequences, principles of recovery, and relapse prevention strategies. Eight patients with prolonged histories of abuse of cocaine, alcohol, marijuana, or other drugs were enrolled in this weekly group treatment at a community mental health center drug treatment program, while continuing in treatment with their current case manager or primary therapist. Six of the eight patients achieved periods of stable abstinence, documented by self-report, urine toxicology screens, continued group attendance, and improved social functioning. Case examples are utilized to illustrate the group process.

Chronic myelogenous leukemia presenting in the blastic phase and its association with a 45 XO Ph1 karyotype.

A 58-yr-old male patient presented in the blastic phase of chronic myelogenous leukemia (CML). Cytogenetic studies revealed a 45 XO Ph1 chromosome pattern in bone marrow cells during a short remission and again in the blastic phase of the disease. The patient expired 8 mo following diagnosis. The blastic phase of CML can stimulate acute myelogenous leukemia (AML) clinically and hematologically; CML can be differentiated by the presence of the Ph1 chromosome and the stigmata of CML. Absence of the Y chromosome from the bone marrow in CML is a recently described finding. Previous reports indicating the prevention of the blastic phase in patients with this karyotype could not be confirmed by our or other recently reported cases.