Primary central nervous system lymphoma: Comprehension of cell-of-origin subtypes

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Effect on the Prevalence of Various Diffuse Parenchymal Lung Diseases due to Paradigm Change in the Guidelines

Background: Diffuse parenchymal lung diseases (DPLDs) have gone through various changes in nomenclature and classification since they were first described in 1868. Increasing knowledge about their etiopathogenesis has since led to several reclassifications and changes in the nomenclature. This has had a major impact on the prevalence of each interstitial lung disease (ILD) reported by the different registries worldwide. In this study, we attempted to describe the distribution of the different DPLDs in our population and reported changes in prevalence due to changing diagnostic criteria for the disease. Materials and methods: We analyzed retrospective data of 434 patients. For the initial 75 patients, ATS/ERS guidelines published in 2002 were followed in the diagnosis of the ILD (group I). In the later part of the study (359 patients), the diagnosis was based on the computed tomography (CT) patterns defined by ATS/ERS/JPS/ALAT statement on diagnosis of idiopathic pulmonary fibrosis (IPF) and updated 2013 ATS/ERS guidelines (group II). Results: Of the 75 patients in group I, IPF was the most common diagnosis (52%) made at that time, followed by sarcoidosis and connective tissue-related ILD (CTD-ILD) with 12% each. Group II had 359 patients, with IPF again being the most commonly diagnosed ILD with 21.3%. This was followed by CTD-ILD (18.6%), sarcoid (14.7%), and idiopathic nonspecific interstitial pneumonitis (iNSIP; 13.3%). The changing guidelines have an impact on reporting of different DPLD by our multidisciplinary teamover a period of time. Though IPF was the most commonest DPLD reported among both the groups, the diagnosis of IPF had fallen by more than half in the second group. It was paralleled by an increase in the diagnosis of iNSIP and chronic hypersensitivity pneumonitis. These reported changes in the prevalence of DPLDs may reflect the better-defined criteria in the latest guidelines and a better understanding of the fibrotic ILDs other than IPF by the multidisciplinary team. Conclusions: The frequency of diagnosis of the different DPLDs has changed, following the publication of several guidelines in the last decade. It has recognized newer entities with greater clarity, such as idiopathic NSIP and interstitial pneumonia with autoimmune features.

Twice‑weekly palliative radiotherapy for locally very advanced head and neck cancers.

PURPOSE: The purpose of the following study is to evaluate the efficacy of a twice‑weekly hypofractionated palliative radiotherapy schedule in locally very advanced head and neck cancers. MATERIALS AND METHODS: Patients with locally very advanced, head and neck cancers were prospectively evaluated after twice‑weekly palliative radiotherapy regimen of 32 Gy in 8 fractions. Median age was 55.5 years and the predominant primary site was oral cavity (46%). Majority (70.6%) had Stage IV B disease. Disease related distressing symptoms such as pain, bleeding, skin fungation, respiratory symptoms due to tumor burden, were prospectively assessed before the start of treatment, at conclusion and at 6‑12 weeks of completion of treatment. RESULTS: A total of 126 patients were enrolled in the study. Ninety three (73.8%) patients who completed the planned treatment of 32 Gy in 8 fractions were included in the symptom analysis. Overall response rates were 42% at primary disease and 55% at nodal disease. At conclusion of radiotherapy 76.3% of the patients reported improvement in pain scores (P = 0.001) and 42.8% patients reported improvement in anxiety and depression levels (P = 0.001). At first follow‑up after 6‑12 weeks significant improvement in pain scores (P = 0.001) and anxiety/depression levels (P = 0.001) persisted. The median survival of the patients was 5.5 months. Acute grade III mucositis was seen in one patient (1.2%) while none had grade III skin reactions. CONCLUSION: The proposed radiotherapy regimen is effective for sustained symptom palliation with low acute toxicity in locally very advanced head and neck cancers. It delivers a moderately high dose while being logistically simpler for the patient.

Factors predicting 'time to distant metastasis' in radically treated head and neck cancer.

Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.

Cetuximab with radiotherapy in patients with loco-regionally advanced squamous cell carcinoma of head and neck unsuitable or ineligible for concurrent platinum-based chemo-radiotherapy: Ready for routine clinical practice.

Purpose : To report outcomes of cetuximab concurrent with radiotherapy in advanced head-neck cancer unsuitable for platinum-based chemo-radiotherapy. Materials and Methods : Retrospective chart review of 37 patients treated with cetuximab and radiotherapy at a comprehensive cancer centre. Results : Median age of study cohort was 59 years. Thirty four (92%) patients had advanced stage disease (stage III-IV). Reasons for ineligibility for platinum included impaired creatinine-clearance, old age, and/or co-morbidities. Thirty-two (86%) patients completed planned radiotherapy without interruption; 29 (80%) patients received ≥6 cycles of cetuximab. Fifteen patients (40.5%) developed ≥grade 3 dermatitis; 9 patients (25%) experienced ≥grade 3 mucositis. At a median follow-up of 16 months, the 2-year loco-regional control, disease-free survival, and overall survival was 35.5%, 29.5%, and 44.4% respectively. Stage grouping and severe dermatitis were significant predictors of outcome. Conclusions : Cetuximab concurrent with radiotherapy is a reasonable alternative in advanced head-neck cancer patients with acceptable compliance and outcomes, but higher skin toxicity.

Superdominant right coronary artery with absent left circumflex artery

Noninvasive imaging of coronary artery disease is rapidly replacing angiography as the first line of investigation. Multislice CT is the non-invasive modality of choice for imaging coronary artery disease and provides high speed with good spatial resolution. CT coronary angiography in addition to detecting and characterising atherosclerotic coronary artery disease is also a good imaging tool for evaluating anomalies of coronary arteries. Superdominant right coronary artery with absent left circumflex artery is one such rare coronary artery anomaly which is well evaluated with multislice CT angiography. The authors report one such case of superdominant right coronary artery with absent left circumflex artery imaged with 64-slice MDCT.

Lycopene - tomato's secret weapon against oxidative stress.

Back ground: Lycopene, 40 carbon acyclic carotenoid containing 11 conjugated double bonds, is a phytochemical found in tomatoes and other red fruits. Oxygen derived free radicals are the most reactive species and as an antioxidant lycopene has a singlet oxygen quenching ability twice as high as that of ?-carotene and 10 times higher that of ?-tocoferol, lycopene participate in a host of chemical reactions to protect critical cellular biomolecules including lipid, proteins and DNA. Materials and Methods: The present study include 30 subjects having oxidative stress, age between 40-60 years, nonsmoker, with no history of chronic systemic illness and no medication were taken as patients.30 patients matched healthy subjects were taken as control. All subjects were selected from outpatient department of NSCB Medical College Jabalpur M.P. After estimation of base line antioxidant enzyme and vitamins, we supplement 180 gm of tomato (products like soup, paste. ketchup) contain 12 mg of lycopene to the patient group. After 60 days of lycopene supplementation oxidative stress biomarkers like SOD, GPX, GR, GSH, lipid peroxidation product MDA and other antioxidant vitamins A, vitamin C, vitamin E were estimated in patient's blood sample. Results: The main result of the study revealed that lipid per oxidation product MDA was found to be decreased significantly but after lycopene supplementation levels were improved. The results of SOD , GPX, GR, GSH,Vitamin A ,Vitamin E and Vitamin C were significantly increased after lycopene supplementation, it indicates the improved antioxidant profile after the supplementation of lycopene. Conclusion: There was a significant decrease in oxidative stress after the supplementation of lycopene therefore the study suggest that body's internal production of antioxidant is not enough to neutralize all free radicals, so increased dietary intake of antioxidant lycopene in the form of tomato products is beneficial, which is easily available in developing country like India.

PET/CT-guided radiation therapy planning: From present to the future.

Molecular imaging using 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been successfully used in the diagnosis, initial staging, and response assessment of various malignant tumors. Advances in radiation therapy planning and delivery have ushered in the era of high-precision conformal radiotherapy allowing generation of dose distributions that conform closely to the shape of the target volume while minimizing high-dose regions in the surrounding normal tissues. Traditionally, radiation therapy planning has relied heavily on CT imaging, but recent times have witnessed tremendous enthusiasm for the use of PET/CT-guidance in radiotherapy planning. This has been largely stimulated by widespread availability and integration with treatment planning systems. However, several issues need to be addressed and challenges overcome to realize the full potential of this exciting technology. Integrating PET/CT fusion imaging into routine clinical practice can be challenging due to technical, administrative, financial, geographic, and personnel issues. Concerted efforts are urgently needed for the development of guidelines for appropriate application of this technology using standardized methodology. There is accumulating evidence that incorporating PET/CT imaging in radiotherapy planning for lung cancer, head and neck cancer and cervical cancer has a significant impact. This review highlights the promises and pitfalls of PET/CT imaging in radiotherapy treatment planning with a critical appraisal of the current best evidence for its application in the modern radiotherapy clinic, and provides a sneak preview into the future of such technology.

Donovanosis with auto-amputation of penis in a HIV-2 infected person.

Donovanosis is a slowly progressive, granulomatous ulcerative disease , caused by Klebsiella (Calymmatobacterium) granulomatis. The disease is known to persist for years together, leading to complications. A male patient aged 30 years with underlying HIV-2 infection presented to the department of STD with painful ulceration over the genital region of 5 months duration, with absence of penis. Tissue smear from the ulcer and histopathological examination revealed large histiocytes with intracellular Donovan bodies (Pund cell). A final diagnosis of donovanosis with auto-amputation of penis with HIV-2 infection was made. The old conventional medicines, viz. streptomycin, doxycycline and amoxycillin, were effective. Though HIV-2 infections are milder than HIV-1 infections in all aspects, donovanosis in this HIV-2 infected case presented with complications. However, since the CD4 count was 748 cells/cmm, the severity is attributed to the long standing nature and negligence by the patient, and not to possible immunodeficiency.

Hemoglobin E-beta thalassemia: factors affecting phenotype.

The phenotype of E-beta-thalassemia is affected by several genetic factors. The aim of this study was to analyze severity of E-beta-thalassemia and correlate with HbE, HbF, E/F ratios, beta-mutation and Xmn I polymorphism. Thirty cases of E-beta-thalassemia (23 with childhood onset) were studied. HbE levels were quantitated by HPLC. Xmn1 polymorphism and beta-mutations were studied by PCR-RFLP and ARMS respectively. Commonest features were pallor (100%), splenomegaly (74%), and hepatomegaly (65%), 43% (10/23) were on regular transfusions at diagnosis. One case presented with paraplegia. Patients heterozygous for Xmn I polymorphism (+/-) had later onset (>3 yrs) compared to homozygous (-/-) absence (0.5-2.8 yrs). Most (69.6%) showed beta-mutation IVS 1-5 (G-->C). Negative correlation was found between age of onset and HbE. Thus, presentation is similar to previously reported Thai cases. Heterozygosity of Xmn I polymorphism also delays disease onset. Early diagnosis facilitates appropriate management and prenatal diagnosis.

Spontaneously developing autoantibody to factor VIII in an elderly woman: diagnostic and therapeutic challenges.

An elderly woman with a continuously bleeding small wound was investigated for the presence of antibodies to FVIII using activated partial time-based screening and confirmatory tests. A late acting coagulation factor inhibitor was detected. The same was characterised to be a low titre antibody against FVIII (5.2 Bethesda units). Cryoprecipitate infusions, corticosteroids and topical desmopressin were unsuccessful in controlling the bleeding. Addition of cyclophosphamide brought about stoppage of bleeding and disappearance of the autoantibody.

Dual use of silver for management of chronic bone infections and infected non-unions.

Broad spectrum antibacterial effect of electrically generated silver ions has been fully established. Present work consists of clinical evaluation of beneficial antibacterial effect of silver ions liberated electrically with the help of locally manufactured power pack in 920 proved cases of chronic osteomyelitis with or without pathological fractures and septic non-unions. Wound debridement, silver iontophoresis, proper immobilisation and subsequent wound care yielded not only control of bone infections in 85% cases, but also produced healing of pathological fractures in 83% patients. Results remained unaffected by age or sex of patient, type of bone involved, duration of previous illness or type of previous treatment. Follow-up varied from 6 months to 10 years. This technique is likely to open a new chapter in treatment of chronic resistant bone infections and septic non-unions due to open fractures particularly in developing countries of the world.

Natural family planning--better prospect of contraception.

Natural Family Planning methods are based on naturally occurring signs of fertility by which a couple can prevent or achieve pregnancy. It requires good concept on signs of fertility in female and knowledge of human reproduction. For this reason, successful delivery delivery of NFP services is directly related to literacy rate among users.

Perinatal outcome of pregnancies complicated by threatened abortion.

One hundred and two cases of viable pregnancies with threatened abortion were studied in the department of obstetrics and gynaecology, Kamla Nehru Hospital, IG Medical College, Shimla between November 1987 and February 1989 and their perinatal outcome was evaluated. The pregnancies continued beyond 28 weeks in 61.7% of the cases. The incidence of prematurity was 19.0%. The incidence of low birth weight (LBW) babies was 23.8%. Apgar score was less than 7 in 22.3%. The incidence of neonatal complications was 25.3%. There was no perinatal mortality. In a control group of 50 cases, the incidence of prematurity and LBW was 8% and 4% respectively. Apgar score less than 7 was noted in 4% and neonatal complications were observed only in 4% of newborns.

Effects of intracervical injection of hyaluronidase in primigravidae during labour.

A study was conducted on 75 primigravidae in labour of which 50 were injected with intracervical injection of hyaluronidase and 25 were taken as control. Labour could be accelerated and shortened by an average of 1.95 hours (p < .01) after intracervical injection of hyaluronidase. Its effect was insignificant on the latent phase of labour while it significantly shortened the active phase of labour by 2.09 hours (p < .001). Its effect on maximum rate of cervical dilatation (0.85 cm/hour) was also found to be statistically significant ie, p < .001. Hyaluronidase had no effect on uterine contractions, duration of 2nd and 3rd stages of labour and on involution of the uterus. There was no incidence of cervical tear in any of the cases.

An antilactogenic effect of pyridoxine.

The efficacy of pyridoxine in suppression of lactation was studied. Patients under study included the cases of stillbirths, neonatal deaths and second trimester abortions. The clinical response was good in 80%, fair in 14% and poor in 6% of cases. Administration of pyridoxine only was associated with a rapid and trouble-free suppression of lactation in 94% of cases.

Antiparkinsonian activity and dopamine receptor binding studies of imidazolone derivatives.

Mannich bases and styryl derivatives of imidazolones were evaluated for their antiparkinsonian activity. Two compounds showed potent antiparkinsonian activity. These active compounds also showed binding with dopamine receptors in striatal membrane preparation of rat brain.