Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Cardiovascular complications and its relationship with functional outcomes in Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is a monophasic disease characterized by acute polyradiculoneuropathy. AIM: This study investigated cardiovascular complications in patients with GBS and their relationship with outcomes. DESIGN AND METHODS: We included 96 patients, who were diagnosed with GBS according to Brighton case definitions. All enrolled patients were evaluated according to a predetermined algorithm, which included nerve conduction studies, cerebrospinal fluid analysis, electrocardiography, 2D echo, cardiac markers and autonomic function testing. RESULTS: We enrolled a total of 96 patients. The mean age of patients was 35.75 ± 17.66 years. Furthermore, 54.2% of patients developed cardiovascular complications, of which changes in electrocardiography (ECG) findings (50%), hypertension (28.12%), labile hypertension (12.5), tachycardia (26.04), bradycardia (13.54%) and a fluctuating heart rate (HR) (11.46) were common. Other cardiovascular complications seen in GBS patients were increased pro-BNP (26.04%), raised troponin T levels (3.12%), acute coronary syndrome (2.08%), heart failure (2.08%) and abnormal 2D echo findings (8.33%). The results of the univariate analysis revealed that a history of preceding infection, a Medical Research Council sum score, neck muscle weakness, facial nerve involvement, bulbar involvement, respiratory failure, cardiovascular complications, autonomic dysfunction, acute motor sensory axonal neuropathy subtype and baseline Hughes score were significantly (P < 0.005) associated with poor outcomes. However, none of these factors were found to be independently associated with poor outcomes in the multivariate analysis. CONCLUSION: A considerable number of patients with GBS developed cardiovascular complications and it needs attention.

Ophthalmological manifestation in patients of tuberculous meningitis.

BACKGROUND: Vision impairment, blindness in particular is a devastating complication in patients with tuberculous meningitis. However, information regarding ophthalmological manifestation and its impact on vision is sparse in the literature. This study evaluated the spectrum of ophthalmological manifestations in tuberculous meningitis, including retinal nerve fiber layer thickness assessment by optic coherence tomography and its correlation with visual and clinical outcome. METHODS: This was a prospective observational study done from October 2015 to March 2017. Consecutive patients of tuberculous meningitis, diagnosed as per consensus case definition were included in the study. The patients were divided into two categories: uncomplicated and complicated tuberculous meningitis. Clinical evaluation, cerebrospinal fluid examination and contrast enhanced MRI of brain was done. Detailed ophthalmological evaluation including optic coherence tomography was done in all patients. All the patients were followed for 6 months. The primary outcome was blindness or low vision after 6 months. The secondary outcome was death or severe disability after 6 months. It was defined as modified Barthel index (MBI) ≤ 12 at 6 months (including disability plus death). Appropriate statistical analysis was done. RESULTS: Out of 101 patients of tuberculous meningitis, 47 patients of TBM belonged to uncomplicated category, while 54 patients were of complicated group. The visual impairment was present in 24 out of 101 (23.76%) patients out of which 20 (19.8%) patients had low vision while 4 (3.96%) had blindness. The visual impairment was more evident in complicated group, low vision 0.03 (1.2-31.5). The most common abnormality on fundus examination was papilledema (22.8%). The complicated group had more incidence <0.0001 (19.6-48). Optic atrophy was found in three patients while choroid tubercles were found in eight patients (all complicated TBM group). RNFL thinning was noted in 10 patients in both the eyes. On univariate analysis, presence of diplopia at baseline, impairment of color vision at baseline, visual impairment at baseline, cranial nerve VIth involvement, optic atrophy and papilledema at baseline, RNFL thinning, abnormal VEP and baseline MBI were associated with poor visual outcome. On multivariate analysis, none of the factors were found to be independently associated with poor visual outcome. On univariate analysis, many factors including baseline MRC staging, altered sensorium, seizure, hemiparesis, basal exudates, infarcts, optochiasmaticarachnoiditis, visual impairment at baseline were found to be associated with poor clinical outcome at 6 months. On multivariate analysis, presence of seizure (P = 0.047, odds ratio = 78.59, 95% confidence interval (1.07-578.72)) was the only factor found to be independently associated with poor outcome. CONCLUSION: Wide spectrum of ophthalmological manifestation was observed in patients of tuberculous meningitis. The visual impairment was more evident in complicated tuberculous meningitis. Ophthalmological findings like optic atrophy, papilledema and RNFL thinning were associated with poor visual outcome on univariate but not multivariate analysis. Visual impairment at baseline, among other factors was associated with poor clinical outcome on univariate analysis, whereas seizure was the only factor independently associated with poor outcome on multivariate analysis.

Does histoid leprosy represent a locally hyperimmune variant of lepromatous leprosy?

BACKGROUND: Histoid leprosy is a subtype of leprosy with distinct clinical presentation and histologic features. It accounts for <4% of leprosy cases. The exact location of histoid leprosy along the immune spectrum and its relation to other subtypes is unclear. AIM: To evaluate the local immune phenomenon which define histoid leprosy. DESIGN: Parallel skin biopsies from histoid lesions and from unremarkable skin in patients with histoid leprosy were evaluated and the histologic findings compared. METHODS: Formalin fixed, paraffin embedded tissue sections from lesional and non-lesional biopsies were assessed for changes in epidermis and dermis; type and extent of infiltrate, presence or absence of pseudocapsule and associated reactions. Bacillary index was evaluated using Wade Fite stain for lepra bacilli. RESULTS: Amongst 208 leprosy cases, six cases of histoid leprosy were identified (2.88%). The cases showed presence of nodules, patches and plaques overlying clinically unremarkable skin. Fourteen skin biopsies were evaluated of which the lesional biopsies showed equal proportion of fusocellular, fusocellular epithelioid and fusocellular-vacuolated histology. A greater circumscription was noted in lesional biopsies; however the cellular content of the infiltrate was similar in lesional and non-lesional biopsies. A case of erythema nodosum leprosum in histoid leprosy was also seen. CONCLUSIONS: Ours is the first study comparing normal and lesional skin in histoid leprosy. Though the histoid lesions appear to have a derivation from lepromatous leprosy, the local histologic and clinical alterations may be a result of heightened local immunity or reactive local modifying factors.

Study of interleukin-6 and interleukin-8 levels in patients with neurological manifestations of dengue.

CONTEXT: Pro-inflammatory markers play a key role in the pathogenesis of various Flavivirus infection. AIM: In this study, we evaluated the role of these markers in neurological manifestations of dengue. SETTINGS AND DESIGNS: Consecutive dengue cases with different neurological manifestations who presented between August 2012 and July 2014 were studied in hospital-based case-control study. MATERIALS AND METHODS: Interleukin (IL-6) and IL-8 level were measured in serum and cerebrospinal fluid (CSF) of dengue cases with different neurological manifestations and also in age- and sex-matched controls. Level was analyzed with various parameters and outcomes. STATISTICAL ANALYSIS: Statistical analysis was done using SPSS version 16.0 by applying appropriate statistical methods. P < 0.05 considered statistically significant. RESULTS: Out of the 40 enrolled cases of dengue with neurological manifestations, 29 had central nervous system and 11 had peripheral nervous system (CNS/PNS) manifestations. In CNS group, both IL-6 and IL-8 (CSF and serum) were significantly elevated (P < 0.001), whereas CSF IL-6 (P = 0.008), serum IL-6 (P = 0.001), and serum IL-8 (P = 0.005) were significantly elevated in PNS group. CSF IL-6, serum IL-6, and IL-8 were significantly elevated in poor outcome patients in CNS group (P < 0.05). CSF IL-6 and IL-8 were significantly elevated in CSF dengue positive cases as compared to CSF negative patients (P < 0.05). Cytokine level was not significantly correlated with neuroimaging abnormality in CNS group. Nine patients died and the remainder recovered. CONCLUSION: Elevated level of IL-6 and IL-8 is associated with different neurological manifestations and poor outcome, but whether they are contributing to neuropathogenesis or simply a correlate of severe disease remains to be determined.

Cocaine Abuse: An Unusual Association.

Cocaine addiction is a common problem in the adolescent and the young adults, pharmacologic interventions to reverse the effects of which do not exist. Neurological complications of cocaine abuse, such as seizures, headache, ischemic or hemorrhagic stroke, or subarachnoid hemorrhage, can be disastrous as a result of uncontrolled vasoconstriction and vasculitic damage. The lone occurrence of subdural hematoma in the absence of any other intracranial hemorrhagic complication is rarely seen in patients of cocaine abuse. We wish to share our experience of one such patient who presented to us with an unusual combination of the widespread cerebral infarction and subdural hematoma.

Drug resistance and associated genetic mutations among patients with suspected MDR-TB in Uttar Pradesh, India.

SETTING: Programmatic Management of Drug-Resistant Tuberculosis (PMDT) programme in 32 districts of Uttar Pradesh (UP), India. OBJECTIVE: To provide epidemiological status of multidrug-resistant tuberculosis (MDR-TB) and associated microbial genetic mutations among suspected cases in UP. DESIGN: We retrospectively studied and tested using line-probe assay (LPA) 4895 retreatment patients with suspected MDR-TB who were enrolled for PMDT during 2012-2015. The demographic characteristics of cases, LPA-determined drug resistance, the genetic mutation profile, trends in drug resistance over the study period as well as the comparative performance of LPA and phenotypic drug susceptibility testing (DST) were analysed. RESULTS: MDR-TB and rifampicin-resistant TB (RR-TB) were confirmed in respectively 34.5% and 40.3% cases. The RR-TB detection rate (a valid proxy for MDR-TB) initially declined during the study period. Age â©¿30 years and implemented MDR-TB suspicion criteria were independent predictors for RR-TB (P < 0.01). LPA indicated predominant distribution of S531L (1483/1970, 75.3%) and S315T1 (1981/2116, 93.6%) mutations in the rpoB and katG genes, respectively, and had >94.0% agreement with phenotypic DST in determining rifampicin/isoniazid resistance. CONCLUSION: MDR-TB prevalence in retreatment cases is very high, highlighting the need to reduce the development and transmission of drug-resistant TB.

Spinal cord involvement in tuberculous meningitis.

OBJECTIVES: To summarize the incidence and spectrum of spinal cord-related complications in patients of tuberculous meningitis. SETTING: Reports from multiple countries were included. METHODS: An extensive review of the literature, published in English, was carried out using Scopus, PubMed and Google Scholar databases. RESULTS: Tuberculous meningitis frequently affects the spinal cord and nerve roots. Initial evidence of spinal cord involvement came from post-mortem examination. Subsequent advancement in neuroimaging like conventional lumbar myelography, computed tomographic myelography and gadolinium-enhanced magnetic resonance-myelography have contributed immensely. Spinal involvement manifests in several forms, like tuberculous radiculomyelitis, spinal tuberculoma, myelitis, syringomyelia, vertebral tuberculosis and very rarely spinal tuberculous abscess. Frequently, tuberculous spinal arachnoiditis develops paradoxically. Infrequently, spinal cord involvement may even be asymptomatic. Spinal cord and spinal nerve involvement is demonstrated by diffuse enhancement of cord parenchyma, nerve roots and meninges on contrast-enhanced magnetic resonance imaging. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis. Anti-tuberculosis therapy is the main stay of treatment for tuberculous meningitis. Higher doses of corticosteroids have been found effective. Surgery should be considered only when pathological confirmation is needed or there is significant spinal cord compression. The outcome in these patients has been unpredictable. Some reports observed excellent recovery and some reported unfavorable outcomes after surgical decompression and debridement. CONCLUSIONS: Tuberculous meningitis is frequently associated with disabling spinal cord and radicular complications. Available treatment options are far from satisfactory.

Outcome assessment in conservatively managed patients with cervical spine tuberculosis.

STUDY DESIGN: Cervical spine tuberculosis is a relatively less frequent form of spinal tuberculosis. Cervical spine tuberculosis has a greater propensity to involve the spinal cord and results in major sensory motor deficit. In this prospective study, we aimed to evaluate the clinical and imaging predictors of outcome in conservatively managed patients. METHODS: In this study, 42 patients of cervical spine tuberculosis were included. Patients were subjected to a detailed clinical evaluation and magnetic resonance imaging. Patients were treated with antituberculosis treatment and were followed up for 18 months. The Modified Barthel index (MBI) was used to assess the disability. Good outcome was defined as MBI >12 and poor outcome as MBI ⩽12. Clinical and imaging characteristics were used to analyze the predictors of outcome, using univariate and multivariate analysis. RESULTS: Four (9.5%) patients required surgery. Data from 38 patients, who were conservatively managed, were analyzed for predictors of outcome. Among conservatively managed patients, at presentation, 29 patients had an MBI score of ⩽12. At 18 months, the majority of patients (81.6%) had a good outcome. On univariate analysis, a duration of illness >3 months, a major motor deficit, bladder involvement, flexor spasms, significant cord compression and spinal extension of the abscess were significantly associated with a poor outcome. However, on multivariate analysis significant cord compression (P=0.003) and spinal extension (P=0.02) showed a significant correlation with a poor outcome. CONCLUSION: Medical management was effective in cervical spine tuberculosis. Patients with significant cord compression and spinal extension of the abscess showed poorer outcome.

Neuroimaging features and predictors of outcome in eclamptic encephalopathy: a prospective observational study.

BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome is associated with eclampsia. We assessed the distribution and nature of typical and atypical cranial MR imaging findings in these patients and their correlation with clinical and laboratory data and predictors of outcome. MATERIALS AND METHODS: Forty-five clinically confirmed cases of eclampsia were included in this prospective observational study. Subjects with hemolysis, elevated liver enzymes, and low platelets syndrome (n = 9) and pre-existing neurologic conditions (1 with cerebral solitary cysticercus granuloma) were excluded. Patients underwent blood investigations and cranial MR imaging. RESULTS: Twenty-seven patients had abnormal while 8 had normal MR imaging findings. Involvement of brain regions was as follows: frontal, 88.89%; temporal, 44.44%; parietal, 100%; occipital, 100%; deep gray matter, 29.63%; cerebellum, 22.22%; brain stem, 14.81%. Cytotoxic edema was present in 33.33% of cases; 66.67% of patients had mild posterior reversible encephalopathy syndrome; 25.92% had moderate posterior reversible encephalopathy syndrome; and 7.41% had severe posterior reversible encephalopathy syndrome. Abnormal neuroimaging findings were significantly associated with altered sensorium; visual disturbances; status epilepticus; and elevated serum creatinine, uric acid, and lactate dehydrogenase (P=.006, P=.018, P=.015, P=.019, P=.003, and P=.001, respectively). Serum creatinine, uric acid, and lactate dehydrogenase values and the presence of moderate or severe posterior reversible encephalopathy syndrome were significantly associated with mortality (P<.001, P<.001, P=.009, and P=.027, respectively). CONCLUSIONS: Neuroimaging in eclampsia demonstrates a higher incidence of atypical distributions and cytotoxic edema than previously thought. Altered sensorium; visual disturbances; status epilepticus; and elevated serum uric acid, lactate dehydrogenase, and creatinine are associated with abnormal neuroimaging findings. Higher serum creatinine, uric acid, and lactate dehydrogenase levels and moderate and severe forms of posterior reversible encephalopathy syndrome are possible predictors of poor outcome.

Neurovascular antropylorus perineal transposition using inferior rectal nerve anastomosis for total anorectal reconstruction: preliminary report in humans.

BACKGROUND: Technical feasibility of inferior rectal nerve anastomosis to the anterior vagus branch of the perineally transposed antropyloric valve for total anorectal reconstruction has been previously demonstrated in cadavers. To the best of our knowledge, the present study is the first report of using this procedure in humans. METHODS: Eight patients [mean age 35.5 years (range 15-55 years); (male/female = 7:1)] underwent the procedure. The antropyloric valve with its anterior vagus branch was mobilized based on the left gastroepiploic arterial pedicle. The antral end was anastomosed to the distal colon. The anterior vagus nerve was anastomosed by epineural technique to the inferior rectal nerve in the perineum. A diverting proximal colostomy was maintained for 6 months. Anatomical integrity of the graft (on magnetic resonance imaging scans), its arterial pedicle (on computed tomography angiogram) and neural continuity (on ultrasound and pyloric electromyography) were assessed. Functional assessment was performed using barium retention studies, endoscopy, manometry and fecal incontinence scores. RESULTS: Tension-free end-to-end anastomosis of the anterior vagus nerve to the right (n = 7) and left (n = 1) inferior rectal nerve was achieved. An intact left gastroepiploic pedicle, a healthy graft and neural continuity were visualized on perineal ultrasound. Electromyographic activity was noticed on neural stimulation. Endoscopy and barium studies showed voluntary antral contraction and contrast retention, respectively, in all patients. The mean resting and squeeze pressures were 26.25 mmHg (range 16-62 mmHg) and 50.25 mmHg (range 16-113 mmHg), respectively. St. Mark's incontinence scores varied between 7 and 12. There were no major surgical complications. CONCLUSIONS: Pudendal (inferior rectal) innervation of the perineally transposed antropylorus in total anorectal reconstruction is feasible and may improve outcomes in selected patients with end-stage fecal incontinence.

DTI correlates of cognition in conventional MRI of normal-appearing brain in patients with clinical features of subacute combined degeneration and biochemically proven vitamin B(12) deficiency.

BACKGROUND AND PURPOSE: Vitamin B12 deficiency may cause neural injury that results in cognitive deficits. The main purpose of our study was to evaluate morphometric and microstructural changes in the brain and relate them to cognition in subacute combined degeneration of the spinal cord and patients with biochemically deficient vitamin B12. MATERIALS AND METHODS: Fifty-one patients were recruited and underwent nerve-conduction velocity tests and routine hematologic examinations. Serum vitamin B12 and homocystine levels were also measured. All patients and 46 age- and sex-matched controls underwent cervical spine and brain MR imaging along with cognition tests. MR imaging included conventional scans and DTI. Voxel-based morphometry was performed for determining the WM and GM volumes, based on T1-weighted images. DTI measures that included fractional anisotropy, ADC, radial diffusivity, and axial diffusivity were determined by using tract-based statistics. RESULTS: None of the patients showed any abnormality on conventional MR imaging. No significant changes in GM and WM volumes were observed in patients compared with controls. Significant reductions in the fractional anisotropy and an increase in ADC and radial diffusivity values were observed in multiple brain regions in patients compared with controls. These changes were confirmed on the region-of-interest analysis. Neuropsychological scores were significantly different in patients compared with controls and showed significant correlation with fractional anisotropy and radial diffusivity in a few brain regions. CONCLUSIONS: Microstructural changes are seen in WM regions on DTI in patients with vitamin B12 deficiency and correlate with cognition scores. DTI can be used for objective assessment of microstructural changes in the brain in vitamin B12 deficiency.

Janus activated kinase inhibition in myelofibrosis.

Janus Activated Kinase (JAK) 2 plays an important role in the pathogenesis of myelofibrosis (MF). Ruxolitinib (INCB018424, Jakafi) is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.

SU-E-T-452: Impact of Abdominal Compression on the Tumor Motion in the Treatment of NSCLC Using Stereotactic Body Radiosurgery.

PURPOSE: Involuntary motion of the tumor during the treatment of NSCLC using stereotactic body radiosurgery presents its own unique challenges. In this study, we quantify the impact of abdominal compression technique to minimize tumor motion as a function of location of tumor in a patient. METHODS: 25 patients (5 in each lung lobe viz. RUL, RML, RLL, LUL and LLL) were retrospectively analyzed. A 4DCT study encompassing the tumor was used on a 16 slice GE CT scanner along with Varian RPM gating system. The images were retrospectively binned in 10 phases. The motion of tumor was analyzed phase by phase in transverse, sagittal & coronal projections of the 3D image. This gave us 2 values for anterior-posterior, superior-inferior and lateral-medial motions each and was averaged out. RESULTS: Analysis of data reveals that the motion (mean ± 1SD) in the superior-inferior direction was 1.8 ± 0.9, 4.2±2.8, 7.4±2.3, 1.5±0.8, 3.1±2.8 mm for tumors located in RUL, RML, RLL, LUL and LLL, respectively. Along the anterior-posterior direction the respective values were 2.5 ± 1.9, 2.4 ± 1.1, 2.7 ± 1.3, 1.4 ± 0.2 and 1.8 ± 1 mm. Similarly, along the lateral direction, the respective values were 2.1 ± 1.1, 1.9 ± 1.1, 1.6 ± 1.3, 1.1 ± 0.3 and 1.8 ± 0.7 mm. When the data was analyzed removing the location of the tumor in the thorax, the median displacement along the superior-inferior, anterior-posterior, lateral direction was 2.3, 1.6 and 1.5 mm, respectively while the respective maximum value were 9.2, 5 & 3.8 mm. CONCLUSIONS: The use of abdominal compression provides a simple inexpensive yet easily tolerable device to control the motion of the tumor in the management of NSCLC for SBRT treatments. This will allows the treatment of the tumor without resorting to complex and time consuming gated treatments.