DNA Methylation Profiling Revealed Promoter Hypermethylation-induced Silencing of p16, DDAH2 and DUSP1 in Primary Oral Squamous Cell Carcinoma

Background: Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC.Methods: DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study.Results: Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients'' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference.Conclusions: The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future.     

Life-threatening angioedema in systemic lupus erythematosus

Life-threatening angioedema involving the upper respiratory tract is an uncommon manifestation in systemic lupus erythematosus (SLE). We report three patients in their late adolescence who had laryngeal oedema causing airway obstruction and requiring mechanical ventilation during active disease following symptoms of a respiratory tract infection. All of them had major organ involvement from lupus and none had a family history of hereditary angioedema (HAE). The mechanisms of angioedema in SLE are heterogeneous. There has been little evidence so far of anti-Cl inhibitor (Cl INH) autoantibody in SLE patients with angioedema. These are the first three cases reported in the literature of life-threatening angioedema following respiratory tract infection in SLE.     

Revision of loop colostomy under regional anaesthesia and sedation

Patients presenting for emergency abdominal procedures often have medical issues that cause both general anaesthesia and central neuraxial blockade to pose significant risks. Regional anaesthetic techniques are often used adjunctively for abdominal procedures under general anaesthesia, but there is limited published data on procedures done under peripheral nerve or plexus blocks. We herein report the case of a patient with recent pulmonary embolism and supraventricular tachycardia who required colostomy refashioning. Ultrasonography-guided regional anaesthesia was administered using a combination of ilioinguinal-iliohypogastric, rectus sheath and transversus abdominis plane blocks. This was supplemented with propofol and dexmedetomidine sedation as well as intermittent fentanyl and ketamine boluses to cover for visceral stimulation. We discuss the anatomical rationale for the choice of blocks and compare the anaesthetic conduct with similar cases that were previously reported.     

A case report of an intracaval extrathoracic solitary fibrous tumour

Solitary fibrous tumours are infrequent neoplasms based in the pleura that are predominantly benign with malignant pathology and behaviour described in 10–36% of cases. Extrathoracic solitary fibrous tumours (ESFTs) have been considered separately to their intrathoracic counterparts and comprise a third of all solitary fibrous tumours. The extrathoracic location was identified as an adverse prognostic factor for local recurrence but not for metastatic disease. So far, there have not been any reports of solitary fibrous tumours demonstrating caval infiltration. We present a case of a benign ESFT infiltrating into the perirenal inferior vena cava. Together with extrauterine leiomyomas, ESFTs should also be considered as a differential diagnosis for the rare benign lesions invading the inferior vena cava.     

Intranodal palisaded myofibroblastoma

Intranodal palisaded myofibroblastoma (IPM) usually presents as a painless, slow-growing inguinal mass. Our review of 42 cases from 13 publications indicates that two thirds of IPMs occur between the ages of 45 and 55 years, the male-female ratio is 2:1, and there is a lack of ethnic predilection. Grossly, the IPM cut surface shows areas of hemorrhage. Five microscopic features are seen: (a) compressed remnants of lymphoid tissue at the periphery; (b) spindle cells with nuclear palisading; (c) intraparenchymal hemorrhage and erythrocyte extravasation; (d) so-called amianthoid fibers; and (e) intracellular and extracellular fuchsinophilic bodies that stain positive for smooth muscle actin. Immunohistochemically, IPM is positive for smooth muscle actin and cyclin D1 and negative for S100, glial fibrillary acidic protein, CD34, and desmin, and it shows a low proliferative index of Ki-67. Electron microscopy demonstrates features of myofibroblasts and smooth muscle cells. Excellent prognosis is seen after surgical treatment, with an approximately 6% recurrence rate and no malignant transformation.     

Cyclophosphamide type I hypersensitivity in systemic lupus erythematosus

Cyclophosphamide is an important immunosuppressive agent in the treatment of many rheumatic diseases. Urticaria and anaphylaxis to intravenous cyclophosphamide (i.v. CYC) have been reported in patients with haematological and solid organ malignancies. This is the first report in the rheumatology literature of a type I hypersensitivity reaction following monthly i.v. CYC. An 18-year-old girl with systemic lupus erythematosus (SLE) developed generalized urticaria (without concomitant angioedema or anaphylaxis) following i.v. CYC. She had previously developed life-threatening angioedema following a respiratory tract infection. She successfully completed regular pulse i.v. CYC with pre-medication with anti-histamine. In the absence of a severe type I hypersensitivity reaction and other suitable immunosuppressive agents, i.v. CYC may be safely continued with pre-medication and careful monitoring during each infusion.