Intronic miR-6741-3p targets the oncogene SRSF3: Implications for oral squamous cell carcinoma pathogenesis.

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro assays and in vivo study in NU/J athymic nude mice. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.

Superior Vena Cava Resection in Locally Advanced Thymoma-Surgical and Survival Outcomes.

This study was aimed at reporting the surgical management of superior vena cava invasion in patients with locally advanced thymoma and to evaluate surgical and survival outcomes. This is a retrospective analysis of 12 patients operated for superior vena cava resection for locally advanced thymoma over 8 years in a thoracic surgery centre in India. An analysis of peri-operative variables including complications was carried out. The influence of various predictors on survival was assessed by log-rank test. Intra-operatively, superior vena cava (SVC) alone was involved in 3 (25%) cases, SVC with BCV involvement was there in 8 cases (66.7%) and in 1 patient, the SVC involvement extended into the right atrium also. In all cases, the tumour was resected en bloc with the involved part of SVC. Repair with primary closure was sufficient in 2 cases (16.6%) in view of < 1/3rd of circumferential involvement. However, in remaining 10 cases, SVC was replaced with PTFE graft (single graft in 6 cases, Y-graft in 2 cases and twin grafts in 2 cases). No peri-operative deaths. Overall survival (OS) at 1, 3 and 5 years was 100%, 91.6% and 83.3%, respectively. Myasthenia gravis and higher Masaoka stage (IV A) of the disease were poor predictors of survival. Superior vena cava resection and reconstruction is a feasible and oncologically superior option in invasive thymoma with SVC involvement. This challenging surgical procedure should only be attempted by an experienced team of thoracic and cardiac surgeons at high-volume centre to achieve best outcomes.

A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

Anencephaly (APH) is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to APH. APH shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of APH has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C > A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive APH in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silico analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared with cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to APH.

The conundrum of deep vein thrombosis prophylaxis in burns in India and review of literature.

OBJECTIVE: The aim is to assess the practice of deep vein thrombosis (DVT) prophylaxis among the plastic surgeons attending National Academy of Burns India Conference 2012 (NABICON 2012). BACKGROUND: DVT prophylaxis in burns is a controversial issue as there is no consensus among the community of burn surgeons about the prevalence of DVT, the incidence of pulmonary embolism, the indications for DVT prophylaxis, dosage and duration of low molecular weight heparins (LMWH) and the complications related to DVT and LMWH. METHODOLOGY: A survey was conducted among plastic surgeons attending the NABICON 2012 held at New Delhi, by circulating a questionnaire. The respondents were divided into two groups based on whether burns constituted more than or less than 50% of their practice. The data thus collected were tabulated and analysed. RESULTS: Almost 70% of all the respondents practice some form of DVT prophylaxis. There was significantly higher incidence of complications related to the use of LMWH among the surgeons whose practice of burns was >50%. There was no significant difference between the two groups in relation to the incidence and complication of DVT or recommendation of DVT prophylaxis. CONCLUSION: Majority of plastic surgeons practice DVT prophylaxis routinely and consider multiple criteria such as percentage of burns, age, lower limb involvement, the degree of burns and associated co-morbidities for starting the LMWH.

Perforated Gastrointestinal Stromal Tumor of the Meckel's Diverticulum: a Case Report and Review of Literature.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, they have a wide spectrum of clinical manifestations, and a small proportion of them present as an acute abdomen due to obstruction, perforation, or hemoperitoneum. We present a case of a perforated GIST of the Meckel's diverticulum and review the current literature on perforated GISTs. We ran a search on Pubmed and Google Scholar with the following terms "perforated GIST," "perforated Meckel's diverticulum," "GIST with peritonitis," and "GIST in Meckel's diverticulum." After selecting the relevant articles, we tabulated our results and analyzed the data. Out of the 45 cases, 32 (71.1 %) were male and 13 (28.8 %) were female. Out of the 45 reported cases, 41 (91.1 %) were from the small intestine, 2 (4.44 %) cases from the stomach, and 2 (4.44 %) from the small bowel. In 15 (33.33 %) cases, the site of perforation was the Meckel's diverticulum (MD). Forty-year-old male, presented with features of peritonitis localized to the right iliac fossa, was diagnosed as acute appendicitis and subjected to a diagnostic laparoscopy. Intraoperatively, a perforated Meckel's diverticulum was found, which on histopathological examination contained a low-grade GIST. Our literature search revealed that in reported cases of perforated GISTs, there is a slight male preponderance. Small bowel appears to be the most common site for a perforated GIST, and a significant proportion (30.23 %) arise from the Meckel's diverticulum. And most importantly, the commonest tumor to cause perforation of a Meckel's diverticulum is a GIST.

Breast Lumps That Do Not Arise from the Breast.

An elderly lady presented to the surgical outpatient with a lump in her breast. On examination, there was a well-defined large lump measuring about 12 × 10 cm, hard in consistency and fixed to the chest wall, the skin appeared to be free, and the nipple-areola complex was normal. A provisional diagnosis of phylloides tumor was made, but digital rectal examination revealed a circumferential rectal growth. To our surprise, biopsy of the rectal growth and the chest wall mass revealed similar adenocarcinoma cells. This image illustrates the possibility that a common clinical entity such as a breast lump can sometimes surprise even the most seasoned clinicians.

Mass in the Left Iliac Fossa-a Diagnostic Dilemma.

Clinical diagnosis of abdominal masses remains a challenge to this day; in spite of the availability of advanced imaging facilities, we fail to reach a definitive diagnosis in a few cases and have to resort to a laparotomy, which reveals unexpected findings. We present a case of a 70-year-old lady who presented with pain abdomen and loss of appetite for 3 months; clinical examination revealed a fixed intra-abdominal firm to hard mass in the left iliac fossa. CT scan of the abdomen showed a large cystic hypodense lesion in the left iliac, lumbar and hypogastric region with no definite organ of origin. The patient underwent an exploratory laparotomy and in toto excision of the cyst; on opening the cyst wall, we found multiple daughter cysts in a pool of thick, purulent fluid. Microscopic examination confirmed the presence of a hydatid cyst Primary peritoneal hydatid cysts are a rare entity and constitute around 2 % of hydatid cysts found in the human body. Very few cases of primary peritoneal hydatid cyst have been reported from non-endemic areas, and this case report highlights the need to maintain a high index of suspicion while evaluating cystic abdominal swellings.

Synchronous malignancies of the gall bladder and common bile duct: a case report.

BACKGROUND: Synchronous malignancies of the gall bladder and common bile duct are a rare entity. Much of our knowledge on this topic comes from Japanese literature. Most of the synchronous carcinomas described in Japanese literature are associated with the presence of an anomalous pancreatic-bile duct junction (APBDJ). CASE PRESENTATION: We report a case of synchronous malignancy of the extrahepatic biliary tree involving the fundus of the gall bladder and the intrapancreatic portion of the common bile duct (CBD). A 50-year-old female patient presented to us with clinical features of obstructive jaundice and on radiological evaluation was diagnosed to have a periampullary carcinoma; the patient underwent a pancreaticoduodenectomy, and histopathological examination revealed adenocarcinoma of the gall bladder and the intrapancreatic portion of the CBD. CONCLUSIONS: Synchronous malignancies have been rarely reported from the Indian subcontinent; therefore, it is essential for the clinician as well as the pathologist to maintain a high index of suspicion while evaluating such lesions and to look for the presence of an anamolous pancreatic-bile duct junction whenever indicated.

Dumbbell-Shaped Neurofibroma Over the External Ear.

Dumbbell-shaped swellings in neurofibroma have been commonly described in the spine, thorax, cranial cavity, and pelvis; however, dumbbell-shaped swellings in the peripheries are rare. Here, we report a dumbbell-shaped neurofibroma over the pinna in an 18-year-old female patient, its successful surgical management, and its association with Hashimoto thyroiditis. To the best of our knowledge, this is the first ever case to be reported of a dumbbell-shaped neurofibroma over the external ear and only the fourth case of neurofibromatosis type 1 (NF1) to be associated with Hashimoto thyroiditis.

Chondroid Syringoma of the Philtral Dimple.

A chondroid syringoma (CS) is an exceedingly rare mixed tumor of the skin. These tumors are relatively common in the head and neck area. Occurrence of these tumors in the philtrum is rare, with only two documented cases in English literature to the best of our knowledge. This paper presents a case of CS of the philtral dimple with aesthetically excellent philtrum reconstruction.

Anti-NMDAR limbic encephalitis--a clinical curiosity.

BACKGROUND: Neurological paraneoplastic syndromes are rarely the first manifestation of an underlying cancer. A high index of suspicion is thus needed to diagnose such conditions. Paraneoplastic limbic encephalitis is one such entity which is well described in association with small cell lung cancers, testicular germ cell tumors, breast cancers and ovarian tumors. This article describes the entity being associated with an ovarian tumor. CASE: A 36-year-old female presented with abnormal behaviour, mood swings and delusions. She was evaluated for her psychiatric symptoms and found to have an underlying ovarian tumor. Anti-NMDA receptor titers were strongly positive. She underwent oophorectomy, and post-operatively there was a significant improvement in her psychiatric symptoms. CONCLUSIONS: Ovarian tumors like teratomas are implicated in the pathogenesis of paraneoplastic limbic encephalitis. An underlying ovarian tumor must be evaluated in all young females presenting with sudden onset of psychiatric symptoms.

Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature.

PURPOSE: Congenital hereditary endothelial dystrophy 2 (CHED2) is an autosomal recessive disorder caused by mutations in the solute carrier family 4, sodium borate transporter, member 11 (SLC4A11) gene. The purpose of this study was to identify the genetic cause of CHED2 in six Indian families and catalog all known mutations in the SLC4A11 gene. METHODS: Peripheral blood samples were collected from individuals of the families with CHED2 and used in genomic DNA isolation. PCR primers were used to amplify the entire coding region including intron-exon junctions of SLC4A11. Amplicons were subsequently sequenced to identify the mutations. RESULTS: DNA sequence analysis of the six families identified four novel (viz., p.Thr262Ile, p.Gly417Arg, p.Cys611Arg, and p.His724Asp) mutations and one known p.Arg869His homozygous mutation in the SLC4A11 gene. The mutation p.Gly417Arg was identified in two families. CONCLUSIONS: This study increases the mutation spectrum of the SLC4A11 gene. A review of the literature showed that the total number of mutations in the SLC4A11 gene described to date is 78. Most of the mutations are missense, followed by insertions-deletions. The present study will be helpful in genetic diagnosis of the families reported here.

Clinical phenotype and the lack of mutations in the CHRNG, CHRND, and CHRNA1 genes in two Indian families with Escobar syndrome.

The objective of this study was to report the clinical phenotype and genetic analysis of two Indian families with Escobar syndrome (ES). The diagnosis of ES in both families was made on the basis of published clinical features. Blood samples were collected from members of both families and used in genomic DNA isolation. The entire coding regions and intron-exon junctions of the ES gene CHRNG (cholinergic receptor, nicotinic, gamma), and two other related genes, CHRND and CHRNA1, were amplified and sequenced to search for mutations in both families. Both families show a typical form of ES. Sequencing of the entire coding regions including the intron-exon junctions of the three genes did not yield any mutations in these families. In conclusion, it is possible that the mutations in these genes are located in the promoter or deep intronic regions that we failed to identify or the ES in these families is caused by mutations in a different gene. The lack of mutations in CHRNG has also been reported in several families, suggesting the possibility of at least one more gene for this syndrome.