Anti­epidermal growth factor receptor monoclonal antibody therapy in locally advanced head and neck cancer: A systematic review of phase III clinical trials.

The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m2 weekly, instead of the standard doses of 100 mg/m2 every 3 weeks or 40 mg/m2 every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.

Efficacy of a herbal mouthwash for management of periodontitis and radiation-induced mucositis - A consolidated report of two randomized controlled clinical trials.

BACKGROUND: Oral diseases like periodontitis and mucositis often require home care using topical agents in the form of mouthwashes. Many herbal mouthwashes are found to be beneficial; however lack proper scientific evidence to support their use. OBJECTIVES: Study 1 evaluated clinical efficacy of herbal mouthwash in the management of chronic periodontitis in comparison with chlorhexidine mouthwash. Study 2 aimed at assessment of herbal mouthwash in patients of radiation-induced mucosititis. METHODS: The novel herbal mouthwash used in the present study wa prepared from extracts of five plants namely Emblica Officinalis, Terminalia chebula, Terminalia bellerica, Glycyrrhiza glabra, and Azadirachta indica. 50 periodontitis patients were randomly allocated to two groups. As per allocation, they were instructed to use either herbal mouthwash or chlorhexidine mouthwash twice daily for two weeks after nonsurgical periodontal therapy. Similarly, patients with radiation-induced mucositis were randomly given herbal mouthwash and soda saline mouthwash. Intergroup and intragroup comparisons of continuous variables were conducted using paired and unpaired t-tests. Categorical variables were compared using the chi-square test. RESULTS: Significant reductions in gingival bleeding, plaque accumulation, and pocket depth were noticed in periodontitis patients in both groups. Patients reported acceptable taste, freshness, and satisfaction after the use of herbal mouthwash. The herbal mouthwash group noticed a significant reduction in the severity of radiation-induced mucositis and analgesic requirements. The intensity of pain, dryness of mouth, oral hygiene, and need for the use of antibiotic and antifungal during radiotherapy was not significant among the groups. CONCLUSION: The results of this preliminary clinical trial support the use of the tested herbal formulation mouthwash as an adjunct in the treatment of periodontitis as well as radiation-induced mucositis. CLINICAL TRIAL REGISTRATION NUMBER: For Study 1: CTRI/2019/10/021574, Study 2: CTRI/2020/04/024851.

Malignant Peripheral Nerve Sheath Tumour of Uterine Cervix-a Case Report and Review of Literature.

Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of sarcoma occurring in the uterine cervix. Only 16 cases have been reported in literature till date. There is no clear consensus on the treatment due to the rarity of the disease. This is primarily managed by surgery. Here, we present a case of MPNST of the cervix who was treated with preoperative radiotherapy followed by radical hysterectomy and bilateral salpingo-oophorectomy.

Treatment outcomes and prognostic factors of esthesioneuroblastoma-a retrospective study from South India.

Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant neoplasm arising from the neural crest cells of the olfactory epithelium. The optimum treatment for this rare disease is still unclear. Most of the available literature on this rare head and neck tumour is limited to small retrospective series and single institutional reports. We conducted a retrospective study to investigate the clinical profile, treatment outcomes and prognostic factors of patients with ENB treated at a tertiary cancer centre in south India. Patients with a histopathological diagnosis of ENB treated from 2000 to 2019 were included. Patient demographics, tumour characteristics, stage, treatment details and outcome data were identified from medical records. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. The prognostic factors were identified using Cox regression analysis. Forty-two patients underwent treatment for ENB from 2000 to 2019. Twenty-six patients underwent surgery. Twelve patients received radical radiotherapy (RT) while 24 patients underwent adjuvant radiation. After a median follow-up of 71 months, the estimated OS and DFS at 4 years were 64.4% and 54%, respectively. The estimated 4-year OS for modified Kadish A, B, C and D stages was 75.0%, 90.9%, 56.4% and 0%, respectively. Modified Kadish stage, nodal involvement, orbital invasion, intracranial extension, surgery, RT treatment and use of chemotherapy were significant predictors of OS and DFS in univariate Cox regression analysis. Orbital invasion and RT treatment were significant predictors of DFS in the multivariate analysis as well. However, only RT treatment came out to be a significant predictor for OS in multivariate Cox regression analysis. Surgery is the mainstay of treatment. Adjuvant RT may improve local control and survival in advanced cases. Advanced modified Kadish stage, lymph node involvement and orbital invasion are associated with poor outcomes.

Early hearing detection and intervention (EHDI) programmes for infants and young children in low-income and middle-income countries in Asia: a systematic review.

BACKGROUND: Early hearing detection and intervention (EHDI) measures initiated in high-income countries (HICs) were attempted in low-income and middle-income countries (L&MICs). However, information regarding the models of EHDI, context-specific adaptations made to strategies and outcomes are not known. AIMS: The aims of this systematic review were to identify the various models of EHDI used in Asian L&MICs in the published scientific literature and to describe their efficacy and validity. METHODS: The studies were eligible if the programme was from Asian L&MICs, implemented for children below 6 years of age and published between 2010 and 2021. Google Scholar, PubMed, Web of Science, Scopus, EBSCOHost and EBSCO-CINAHL were used to find articles. Data were extracted from each selected article, and the risk of bias was assessed. The search results were summarised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. For primary outcomes, narrative synthesis was used, and forest plots were generated for secondary outcomes. RESULTS: In all, 82 studies were included, and these studies were divided into two categories: newborn and infant screening programmes and screening programmes for older children. Predominantly, a two-stage objective otoacoustic emission (Distortion Product/Transient Evoked) or automated auditory brainstem response screening, followed by a detailed auditory brainstem response to confirm the hearing loss, was used in newborn and infant screening programmes. Audiologists were the most frequent screening personnel. Screening of older children was mostly done by otolaryngologists, school instructors and nurses. They performed a single-stage pure tone audiometry screening followed by a detailed examination. CONCLUSION: The screening tools and protocols used were similar to those used in HICs. However, no uniform protocols were followed within each country. Long-term viability of EHDI programmes was not known as there was limited information on impact outcomes such as cost-benefit. PROSPERO REGISTRATION NUMBER: CRD42021240341.

Treatment outcomes of squamous cell carcinoma of the lip: A retrospective study.

Oral and lip cancer is the most common type of cancer among males in India. Early stage tumours of the lip (stages I and II) are treated with single modality treatment, using either radiotherapy [external beam radiotherapy (EBRT) or brachytherapy] or surgery. Locally advanced tumours (stages III and IVa) are treated with surgery followed by adjuvant treatment. The aim of the present study was to retrospectively evaluate the clinical profile and treatment outcomes of patients with squamous cell carcinoma of the lip who were treated with radical intent at the Regional Cancer Centre (Thiruvananthapuram, India). For this purpose, a total of 120 patients treated with radical radiotherapy (brachytherapy or EBRT) or surgery with or without adjuvant treatment between January 2010 and December 2016 were eligible for the analysis. Kaplan-Meier analysis was used to generate the survival outcomes. Univariate and multivariate analyses were performed to determine the impact of various patient- and tumour-related factors and treatment modality on outcomes. At a median follow-up time of 67.6 months, the disease-free survival (DFS) and overall survival (OS) rates at 4 years for the entire cohort were 69.1 and 86.7%, respectively. The 4-year OS rates for patients with stage I, II, III and IV disease were 88.9, 95.2, 86.8 and 75.3%, respectively, and the DFS rates were 83.6, 69.5, 78.8 and 42.9%, respectively. Primary tumour (P=0.025), nodal (P=0.005) and composite clinical (P=0.006) stage were found to be significant factors affecting DFS rates in the univariate analysis. However, only the nodal stage (P=0.005) was found to be a significant factor affecting DFS rates in the multivariate analysis. On the whole, the present study demonstrates that the outcomes of patients with lip carcinoma are favourable when treated at the early stages, and the results from this series are in line with those already published.

Intrathyroidal thymic carcinoma not so indolent a neoplasm?

ABSTRACT: Intrathyroidal thymic carcinoma (ITC) is a very rare malignant epithelial tumor of the thyroid gland with thymic epithelial differentiation. Here, we are reporting the case of an eighty-year-old man who at presentation had extrathyroidal spread to the larynx and metastasis to regional lymph nodes. Though the tumor had a relatively low-grade morphology, there were areas of high mitotic activity with areas of necrosis. The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course.

Swift Heavy Ion-Induced Reactivity and Surface Modifications in Indium Thin Films.

As an energetic ion traverses a target material, it loses its energy through the processes of electronic energy loss (S e) and nuclear energy loss (S n). Controlled swift heavy ion (SHI) irradiation on solid targets produces its effects through both of these mechanisms, as a consequence of which modifications occur in the structure, surface morphology, and magnetic and optical properties, apart from ion implantation and ion-induced reactivity. A systematic investigation of these effects can be useful in developing standard protocols for creating desired effects in materials using specific ion beams. In this study, indium films of thickness 25 nm were deposited on silicon substrates and were subjected to 100 MeV O7+ and 100 MeV Si7+ ion irradiation, with the fluences varying from 1 × 1011 to 1 × 1013 ions/cm2. The pristine and SHI-irradiated films were then characterized using glancing incidence X-ray diffraction (GIXRD), Rutherford backscattering spectrometry (RBS), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The motive was to identify the effects of irradiation with different ion species having large variations in electronic and nuclear energy losses. While the RBS results suggest that sputtering is extremely low and that there are no major changes in the film composition due to ion beam-induced mixing, the GIXRD analysis indicates that increasing the ion fluence reduces the crystallinity of the film for both the ions. Ion beam irradiation with O7+ ions, however, results in beam-induced reactivity, as the GIXRD scan shows characteristic peaks from indium oxide (In2O3), which become the predominant peaks at the highest fluence used here. Si7+ ion irradiation results in a narrowing of the particle size distribution on the surface, with no evidence of reactivity. SEM results indicate fusion and fragmentation of grains with the increase in the ion fluences, and AFM images reveal an increase in the surface roughness of a few percent when irradiated with both 100 MeV O7+ and 100 MeV Si7+ ions.

Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination.

Immunoglobulin heavy chain (IgH) locus-associated G-rich long noncoding RNA (SµGLT) is important for physiological and pathological B cell DNA recombination. We demonstrate that the METTL3 enzyme-catalyzed N6-methyladenosine (m6A) RNA modification drives recognition and 3' end processing of SµGLT by the RNA exosome, promoting class switch recombination (CSR) and suppressing chromosomal translocations. The recognition is driven by interaction of the MPP6 adaptor protein with nuclear m6A reader YTHDC1. MPP6 and YTHDC1 promote CSR by recruiting AID and the RNA exosome to actively transcribe SµGLT. Direct suppression of m6A modification of SµGLT or of m6A reader YTHDC1 reduces CSR. Moreover, METTL3, an essential gene for B cell development in the bone marrow and germinal center, suppresses IgH-associated aberrant DNA breaks and prevents genomic instability. Taken together, we propose coordinated and central roles for MPP6, m6A modification, and m6A reader proteins in controlling long noncoding RNA processing, DNA recombination, and development in B cells.

Investigations on Crystalline Perfection, Raman Spectra and Optical Characteristics of Transition Metal (Ru) Co-Doped Mg:LiNbO3 Single Crystals.

Congruent lithium niobate single crystals with a Ru:Mg co-dopant have been successfully grown using the Czochralski technique from the melt containing 0.02 mol % Ru with Mg of two varied concentrations (4.0 and 6.0 mol %). The effects of Ru and Mg co-doping on the crystalline quality were determined by high-resolution X-ray diffractometry, which confirmed that the crystalline quality is good and that the dopants are statistically distributed in the crystal. The Raman scattering analysis shows no change in the lattice vibration except a slight change in the peak width and intensity due to more asymmetry in the molecular charge, which leads to enhancement of the polarizability. The optical transmission spectra indicate that both the crystals have high optical transparency in the visible region, with a shift of the absorption edge toward shorter wavelengths, as compared to un-doped LN. The weak absorption band observed below 400 nm is attributed to Ru ions. The influence of co-doping in the electronic band gap energies is calculated by the Tauc relation. The refractive index is measured by using a prism coupler at two wavelengths (532 and 1064 nm). The calculated absorption coefficients and direct and indirect band gap energies for both the samples are found to be nearly the same within experimental error. A decrease in the birefringence is observed for the Ru:Mg(6 mol %) doped sample. The observed slight reduction in refractive indices with Ru:Mg co-doping is consistent with a rise in band gap energy, which is related to the change in absorption edge to the lower wavelength. The second harmonic generation (SHG) efficiency is measured by the Kurtz and Perry powder method, and a decrease in SHG efficiency for Ru:Mg(6 mol %) is observed.

Prognostic factors and outcomes of nonseminomatous germ cell tumours of testis-experience from a tertiary cancer centre in India.

Germ cell tumour of the testis is the most common cancer in young men in the western world. India has the lowest incidence globally, and hence Indian data are sparse. We report the outcomes of patients with nonseminomatous germ cell tumours of testis treated at a tertiary cancer centre in South India over a period of 10 years. Patients with a histopathological diagnosis of nonseminomatous germ cell tumours of the testis from 1 January 2006 to 31 December 2016 were included in the study. Patient demographics, tumour characteristics and treatment details were retrieved from case records. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox regression model was used to analyse the prognostic factors. One hundred and nineteen patients with nonseminomatous germ cell tumours of the testis were included in the study. The median follow-up was 81 months. The estimated 4-year OS and progression-free survival were 87.1% and 84.5%, respectively. The four-year OS for good, intermediate and poor-risk groups was 93.6%, 87.5% and 52.6%, respectively. The PFS at 4 years was 91.4%, 87.8% and 47.4% for good, intermediate and poor-risk groups, respectively. The presence of nonpulmonary visceral metastasis and biochemical response after chemotherapy were significant predictors for OS and PFS in multivariate cox proportional hazards regression. The survival figures are comparable to the rest of the world except in the poor prognostic risk group. The inferior survival noticed in this group of patients may be due to the lack of good salvage procedures. High-dose chemotherapy with stem-cell support may be considered more often for this group of patients.

Role of Frozen Section in Surgical Management of Ovarian Neoplasm.

OBJECTIVE: Cancers of the adnexae, including ovarian and fallopian tube, constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of ovarian cancer. Intraoperative frozen section diagnosis of ovarian tumors is widely used in making this distinction and to decide the course of surgery. Therefore, the accuracy of this technique is very important. The aim was to determine the overall accuracy, sensitivity, specificity, and predictive values of frozen section for ovarian tumors and to evaluate the role of frozen section in the surgical management of ovarian tumors. MATERIALS AND METHODS: This was a descriptive longitudinal study conducted in the gynecology department of a tertiary care hospital. During the 1 ½ year period of data collection, frozen section was performed among 60 cases of ovarian neoplasms. The overall accuracy, sensitivity, specificity and predictive values of frozen section for benign, borderline and malignant categories of ovarian tumors were studied. RESULTS: Out of the 60 patients of ovarian tumors, frozen section diagnosis showed that 43 (71.7%) tumors were benign, 11 (18.3%) were malignant and 6 (10%) were of borderline nature. Final histopathological diagnosis showed that 45 (75%) tumors were benign, 11 (18.3%) were malignant and 4 (6.7%) were borderline. Frozen section for benign tumors had 95% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 88% negative predictive value (NPV). Malignant tumors had 90% sensitivity, 97% specificity, 90% PPV and 97% NPV with frozen section. However, frozen section had low sensitivity (75%) and PPV (50%) for borderline tumors. Specificity was 94% and NPV 98% in this group of tumors. CONCLUSION: Frozen section was found to be an accurate and useful modality in the intraoperative evaluation of patients with ovarian neoplasm. The results can help to decide the type and extent of surgery.

Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination.

B cells undergo two types of genomic alterations to increase antibody diversity: introduction of point mutations into immunoglobulin heavy- and light-chain (IgH and IgL) variable regions by somatic hypermutation (SHM) and alteration of antibody effector functions by changing the expressed IgH constant region exons through IgH class switch recombination (CSR). SHM and CSR require the B cell-specific activation-induced cytidine deaminase (AID) protein, the transcription of germline noncoding RNAs, and the activity of the 3' regulatory region (3'RR) super-enhancer. Although many transcription regulatory elements (e.g., promoters and enhancers) reside inside the IgH and IgL sequences, the question remains whether clusters of regulatory elements outside IgH control CSR. Using RNA exosome-deficient mouse B cells where long noncoding RNAs (lncRNAs) are easily detected, we identified a cluster of three RNA-expressing elements that includes lncCSRIgA (that expresses lncRNA-CSRIgA). B cells isolated from a mouse model lacking lncRNA-CSRIgA transcription fail to undergo normal levels of CSR to IgA both in B cells of the Peyer's patches and grown in ex vivo culture conditions. lncRNA-CSRIgA is expressed from an enhancer site (lncCSRIgA ) to facilitate the recruitment of regulatory proteins to a nearby CTCF site (CTCFlncCSR) that alters the chromosomal interactions inside the TADlncCSRIgA and long-range interactions with the 3'RR super-enhancer. Humans with IgA deficiency show polymorphisms in the lncCSRIgA locus compared with the normal population. Thus, we provide evidence for an evolutionarily conserved topologically associated domain (TADlncCSRIgA) that coordinates IgA CSR in Peyer's patch B cells through an lncRNA (lncRNA-CSRIgA) transcription-dependent mechanism.

Regulation of long non-coding RNAs and genome dynamics by the RNA surveillance machinery.

Much of the mammalian genome is transcribed, generating long non-coding RNAs (lncRNAs) that can undergo post-transcriptional surveillance whereby only a subset of the non-coding transcripts is allowed to attain sufficient stability to persist in the cellular milieu and control various cellular functions. Paralleling protein turnover by the proteasome complex, lncRNAs are also likely to exist in a dynamic equilibrium that is maintained through constant monitoring by the RNA surveillance machinery. In this Review, we describe the RNA surveillance factors and discuss the vital role of lncRNA surveillance in orchestrating various biological processes, including the protection of genome integrity, maintenance of pluripotency of embryonic stem cells, antibody-gene diversification, coordination of immune cell activation and regulation of heterochromatin formation. We also discuss examples of human diseases and developmental defects associated with the failure of RNA surveillance mechanisms, further highlighting the importance of lncRNA surveillance in maintaining cell and organism functions and health.

Clinicopathological features and outcomes of adrenocortical carcinoma: A single institution experience.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with aggressive behavior. Most of our knowledge about this rare tumor is based on retrospective case series. This study aimed at analyzing the clinicopathological features and outcomes of patients treated at a tertiary cancer center in India. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with ACC registered from January 2006 to December 2015. RESULTS: Thirty-seven patients were included in the study, 20 males and 17 females. Median age was 49 (18-78) years. Hormonal overproduction was noticed in 27% of patients. Median tumor size was 10 cm (2-22). Seventeen patients had metastatic disease and 20 patients were localised at diagnosis. Median follow-up was 22 months and median overall survival (OS) was 23.46 months. OS at 2 years and 5 years was 46.1% and 21%, respectively. The median disease-free survival (DFS) was 20 months. DFS at 2 years and 5 years was 45% and 24%, respectively. Age, sex, tumor size, hormonal overproduction, tumor laterality, and stage of the disease did not influence survival. However, advanced stage was associated with higher risk for recurrence. (P = 0.03). CONCLUSION: ACC is a rare endocrine malignancy with very poor survival rates. Rate of recurrence is high even after complete surgery. Systemic treatment options are limited. Newer agents are needed to improve outcome.

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer.

BACKGROUND: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. OBJECTIVES: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2) concurrently with radiation in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: This phase IIb trial randomized 56 patients with Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and acute toxicity. DFS and OS were estimated using Kaplan-Meier method, and log-rank test was used to assess the difference in these distributions with respect to treatment. RESULTS: The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%, respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B, respectively (P = 0.61). There were no significant differences in acute hematological, renal, or mucosal toxicities between the two arms. CONCLUSION: This study showed a nonsignificant improvement in DFS and OS in the 3 weekly cisplatin arm over the weekly arm with comparable toxicities. The trial is registered with Clinical Trial Registry of India (CTRI registration number: CTRI/2013/05/003703, URL-http://ctri.nic.in).

Renal metastasis from papillary carcinoma thyroid detected by whole body iodine scan: A case report and review of the literature.

Papillary carcinoma is the most common thyroid malignancy. Usual sites of metastasis include lungs and bone, but renal metastasis is very rare. Here we present a case of a follicular variant of papillary carcinoma with renal and lung metastasis at presentation.

Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease.

Cytokines play crucial roles in coordinating the activities of innate and adaptive immune systems. In response to pathogen recognition, innate immune cells secrete cytokines that inform the adaptive immune system about the nature of the pathogen and instruct naïve T cells to differentiate into the appropriate T cell subtypes required to clear the infection. These include Interleukins, Interferons and other immune-regulatory cytokines that exhibit remarkable functional redundancy and pleiotropic effects. The focus of this review, however, is on the enigmatic Interleukin 12 (IL-12) family of cytokines. This family of cytokines plays crucial roles in shaping immune responses during antigen presentation and influence cell-fate decisions of differentiating naïve T cells. They also play essential roles in regulating functions of a variety of effector cells, making IL-12 family cytokines important therapeutic targets or agents in a number of inflammatory diseases, such as the CNS autoimmune diseases, uveitis and multiple sclerosis.

Self Regressing Epitheloid Haemangioendothelioma of Tibia in an Infant-A rare case report and review of literature.

INTRODUCTION: Epitheloid hemangioendothelioma is a rare vascular soft tissue tumour of intermediate malignant potential. The tumor affects any age group, and liver is the commonest internal organ affected. Bones as calvarium, spine, tibia and femur may also be affected. The lesion can be multifocal in the liver or the same bone itself and can metastasise to lungs. Here we report a rare case of epithelioid hemangioendothelioma involving tibia in a male infant, which regressed by itself without any treatment, after incisional biopsy over a period of one and half years. CASE REPORT: A 7 month old male baby was presented with incessant cry, fever and swelling in left upper leg of 2 weeks duration. X-ray of leg showed a well demarcated lytic lesion in the meta diaphysial region of left tibia. Magnetic resonance imaging showed an irregular lytic lesion with intramedullary extension. Incisional biopsy showed a vascular tumor, epithelioid hemangioendothelioma grade 1. Meanwhile the patient became asymptomatic and subsequent follow ups showed regression in the size of the tumor and complete disappearance after one and half years. This points towards the need of a wait and watch policy in such intermediate grade vascular tumours even though the lesion is so extensive. This is the first case report of an extensive self regressing epithelioid hemangioendothelioma of tibia in an infant to our knowledge. CONCLUSION: Intermediate grade vascular tumors can undergo spontaneous regression which points towards the need of a wait and watch policy in such tumors thus avoiding extensive surgeries, especially in young patients.

The interplay between the intestinal microbiota and the immune system.

The relationship between commensal microbes and their hosts has been studied for many years. Commensal microorganisms are known to have a significant role in regulating the physiology of their hosts and preventing pathogenic infections while the hosts' immune system is important in determining the composition of the microbiota. More recently, specific effects of the intestinal microbiota on the local and distal immune systems have been uncovered with important consequences for health and disease, and alterations in intestinal microbial composition has been associated with various disease states. Here, we will review the current understanding of the microbiota/immune system crosstalk, highlight the clinical consequences of changes in the microbiota and consider how to harness this symbiotic relationship to improve public health.