A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.

Diabetic foot ulcers, their characteristics, and trends in survival: Real world outcomes at a tertiary care facility in India.

AIMS: Characteristics of diabetes-related foot ulcers (DFU), association with recurrence and amputation are poorly described in the Asian Indian population. METHODS: A prospectively maintained database was reviewed to characterize DFU and its association with amputation and recurrence. RESULTS: Of 200 patients, 63.5 % were male, the median age was 62 years (Min-Max:40-86), and median BMI was 27.90 kg/m2 (Min-Max:18.5-42.7). Median duration of Diabetes mellitus was 15 years (Min-Max:2-43). Complete healing occurred at a median of three months (Min-Max:0.23-37.62). Amputation for the current ulcer was required in 43.4 % of individuals. Ulcer recurrence was documented in 42.4 % instances, 66.1 % evolving on the ipsilateral side. Previous amputation was associated with the risk of subsequent amputation (Adjusted OR-3.08,p-0.047). Median time to ulcer recurrence was 4.23 years among those with amputation, in contrast to 9.61 years in those with healing. Cardiovascular death was the commonest cause of mortality, followed by sepsis. At a median follow up of 6.08 years, mortality at 1,3,5 and 10 years was 2.5 %,2.5 %,8.2 % and 30.9 % respectively among those who underwent amputation versus 0 %,0 %,10.1 % and 24.5 % respectively for those who achieved healing. CONCLUSIONS: Patients with DFU in India incur amputations at rates higher than conventionally described. With previous amputation, subsequent amputation risk triples. Ten-year mortality is 25%-30 %. Underestimates of the burden of recurrence and mortality are consequential of limited follow-up.

Relation of Langerhans cell size to buccal carcinoma.

Oral cancer decreases quality of life despite timely medical management. The carcinogens in tobacco products and their role in tumorigenesis are well documented. Langerhans cells (LCs) are a subset of antigen-presenting cells (APCs) that monitor the tumor microenvironment and engulf carcinogens and foreign bodies. We investigated the distribution and size of LCs and their relation to the mode of tobacco consumption and clinical outcome in patients with buccal carcinoma. We recruited patients with oral cancer who were scheduled for tumor excision and men with urethral stricture undergoing substitution urethroplasty using buccal mucosa. Normal and tumor-adjacent tissues were stained with CD1a antibody. The distribution and mean diameter of 100 LCs/patient were determined. We found significantly smaller LCs in patients who chewed only tobacco compared to those who consumed tobacco by other means. The size of LCs decreased significantly with progressive stages of malignant disease. We found that patients with larger LCs survived longer than those with smaller LCs during an average follow-up of 24 months. We suggest a relation between the size of LCs and clinical outcomes in patients with buccal carcinoma.

Inter- and Intra-rater Reliability of Modified House-Brackmann and Sunnybrook Facial Nerve Grading Systems in Post Parotidectomy Patients.

To compare inter-rater, intra-rater and inter-system reliability of modified House-Brackmann and Sunnybrook grading systems. The study was conducted in a tertiary care hospital with a single cohort of 20 patients and 3 raters. The patients, eligible to be included for the study, were those over 18 years of age planned for nerve sparing parotidectomy. In the postoperative period, patients were video recorded performing specific movements according to the requirements of modified House-Brackmann and Sunnybrook systems. These recordings were used for the grading once recruitment was completed. The inter-rater, intra-rater and inter-system reliability of modified House-Brackmann and Sunnybrook systems were assessed using the intraclass coefficient. The intra-rater reliability was good-to-excellent for both groups with Intra-Class coefficient (ICC) ranging from 0.902 to 0.958 in modified House-Brackmann and in 0.802 to 0.957 Sunnybrook system. The inter-rater reliability was good-to-excellent with ICC ranging from 0.806 to 0.906 in modified House-Brackmann and 0.766 to 0.860 in Sunnybrook system. The inter-system reliability was good-to-excellent with ICC ranging from 0.892 to 0.937. There was no significant difference in the reliability of modified House-Brackmann and Sunnybrook systems. Thus, an interval scale accomplishes the task of grading facial nerve palsy in a reliable way, and the choice of the specific instrument will be based on other factors like expertise involved, ease of administration and generalisability to the incumbent clinical scenario.

Breast reconstruction following mastectomy in Indian women: a neglected entity.

Phyllodes tumour is a rapidly growing neoplasm with a propensity to involve the entire breast tissue. In large tumours, the treatment comprises a wide local excision or a mastectomy. A woman in her 20s from rural India presented with complaints of a recurrent left breast lump. The lump progressed to a large size, limiting her social activities and causing depression. On examination, she had a mass occupying almost the entire left breast, with stretched skin, dilated veins and pressure necrosis. There were no palpable axillary nodes. She was offered a wide local excision and reconstruction with a latissimus dorsi pedicled flap. After much discussion and clarification of some misconceptions around breast reconstruction, she underwent the planned surgery. This was followed by adjuvant radiation therapy as the histopathology was consistent with a complex phyllodes tumour with close margins. She was well at 1-year follow-up and led a good family and social life. Breast conservation and reconstruction are seldom offered as part of cancer treatment in India. All women should be offered surgical options that are oncologically safe while preserving body image, and hence healthcare providers must work towards breaking the barriers that prevent breast reconstruction.

Impact of thyroidectomy on quality of life in benign goitres: results from a prospective cohort study.

PURPOSE: Benign thyroid diseases encompass a large spectrum of conditions that are chronic and subtle in nature. A majority of patients choose non-surgical management and continue living their daily lives with subconscious impairment of optimal functioning. We studied the effect of thyroidectomy on the quality of life (QoL) in patients with benign goitres. METHODS: A prospective study was conducted on 50 patients between January 2017 and August 2018 using the ThyPRO 39 questionnaire. This is a disease-specific health-related questionnaire administered the day before surgery and 6 months following surgery. Data analysis was performed using EpiData Manager and EpiData Entry Client (v 3.1). RESULTS: The mean age of the cohort was 43.30 years ± 11.61, with a female preponderance (34:16). The most common indications for surgery were suspicion of malignancy and compressive symptoms in 34% and 30%, respectively. The most common histopathology reported was nodular/adenomatous hyperplasia (56%). Prior to surgery, the most common domains affected were emotional susceptibility and tiredness. Following surgery, a significant improvement in all domains of the ThyPRO 39 questionnaire were seen except for psychological well-being (p=0.126). In addition, the composite scores significantly improved (p<0.001). Younger age, female gender, and longer duration of goitre were the factors that significantly affected the outcomes in various domains. CONCLUSION: Patients with benign goitres have subtle impairment of QoL which showed significant improvement following thyroidectomy.

Transcutaneous Partial Pressure of Oxygen Measurement in Advanced Chronic Venous Insufficiency as a Marker of Tissue Oxygenation.

PURPOSE: Determination of oxygen concentration in tissues affected by chronic venous insufficiency (CVI) has shown inconsistent results over the years and has confounded the pathophysiology of venous diseases. This study measured transcutaneous partial oxygen pressure (TcPO2) levels in patients with CVI to assess oxygenation and variation in oxygenation according to CVI stage. Materials and. METHODS: A prospective study was performed on consecutive patients with unilateral CVI. TcPO2 of diseased and unaffected limbs was measured in the supine and dependent positions. A single TcPO2 value was measured at the site of greatest skin change or at the edge of the ulcer. The TcPO2 values were analyzed and compared according to stage. RESULTS: A total of 96 patients were included in the study with C4 (24.0%), C5 (19.8%), and C6 (56.3%) disease. The mean age was 44.7 years, and 85 (88.5%) were male. There was a statistically significant (P<0.01) difference in mean TcPO2 levels between the unaffected limb (supine, 32.1 mmHg; dependent, 50.7 mmHg), C5 diseased limb (supine, 16.6 mmHg; dependent, 35.5 mmHg), and C6 diseased limb (supine, 24.2 mmHg; dependent, 40.4 mmHg). In the supine and dependent positions, the mean TcPO2 in the affected limb was significantly lower (P<0.01) than that in the unaffected limb. CONCLUSION: TcPO2 in advanced CVI can be used as a marker of oxygenation status. This is the first study in an Indian population looking at the relevance of TcPO2 in the prognostication of advanced CVI.

Palatal flap in bilateral inferior partial maxillectomy.

Maxillectomy is done for a variety of disease conditions. Reconstruction following maxillectomy is done to restore the form and function. One of the important goals that are to be achieved in reconstruction is the separation of the oral and nasal cavities. In this article, we report the use of palatal flap by preserving the descending palatine artery during bilateral inferior partial maxillectomy, for separating the nasal cavity from the oral cavity. This technique eliminates the need for an obturator or another free or local flap for this purpose.

Myoepithelial Tumors of Salivary Gland: A Clinicopathologic and Immunohistochemical Study of 15 Patients with MIB-1 Correlation.

Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological features, immunohistochemical profile and biological behavior are not well characterized and pose a diagnostic challenge. A total of 15 myoepithelial tumors, diagnosed during 2012 and 2019 were subcategorized and correlated with MIB-1 labeling index (LI) and various histological parameters. Immunohistochemical stains for MIB-1 and other antibodies were performed. Statistical analysis was done by chi-square test, Fisher's exact test and Kaplan Meier curve. Nine patients were male and six were female with the median age of 44 years (range 21-83 years). Of the 15 patients, 6 cases were classified as myoepithelioma (ME) and 9 cases as myoepithelial carcinoma (MECA). Parotid gland was the most common site (46.7%) followed by the palate. MEs showed well circumscribed tumor borders whereas MECAs exhibited focal capsular to extensive invasion into adjacent tissues. Epithelioid cell morphology was most common followed by mixed cell morphology. MIB-1 LI was significantly associated with invasive tumor borders, necrosis and high mitosis. Increased frequency of recurrence was noted with high MIB-1 LI, though it was not statistically significant. MIB-1 LI was high in nearly all MECAs with focal capsular to extensive invasion while low in MEs. Myoepithelial tumor with multinodular growth pattern and focal capsular invasion may have an indolent behavior if mitotic activity and MIB-1 LI is low. Early diagnosis and treatment of MECAs significantly improves the patient's survival and prognosis.

Disseminated mycobacterial septicemia presented as acute abdomen: a surgeon's perspective on Landouzy's sepsis.

A 20-year-old man presented in emergency with fever, abdominal pain and obstipation. On evaluation, he was found to have an acute abdomen with septic shock. The cross-sectional abdominal imaging revealed hepatosplenomegaly, pleural effusion and ascites with retroperitoneal lymphadenopathy. He was resuscitated and started on broad-spectrum antibiotics. There was no other source of infection identified elsewhere. While bacterial and fungal cultures were negative, the sputum, blood, bone marrow and ascitic fluid were positive for Mycobacterium tuberculosis following which he was started on antituberculosis therapy. Despite therapy, the patient's clinical condition continued to deteriorate requiring critical care. In view of Landouzy's sepsis, pulse steroid therapy was started. However, the patient's clinical condition continued to deteriorate and developed systemic inflammatory response syndrome and multi-organ dysfunction syndrome. Despite the best efforts, the patient expired.

Non-dendritic Langerhans cells: A new entity in normal and malignant buccal mucosa

Langerhans cells (LCs) are the most effective antigen presenting cells against foreign bodies and carcinogens. Since the oral cavity is a portal of entry for these antigens, the aim of this study was to morphologically classify CD1a+ LCs, quantify them in the normal and malignant buccal mucosa, and evaluate their relation to the age of patients. Healthy buccal mucosal samples collected from 16 patients undergoing reconstructive operation, and malignant samples obtained from 15 patients undergoing radical oncological resection. were processed for immunohistochemistry four- to fivemicron thick sections were stained with CD1a antibody (CD1a). At 40X magnification, CD1a+ LCs were morphologically classified and quantified manually for a 25mm length of basement membrane using Cellsens image analysing software and the data was analysed. Two categories of CD1a+ LCs were identified in the normal and malignant buccal mucosa a) typical dendritic LCs and b) non-dendritic LCs (a new entity). Non-dendritic LCs were of significantly higher number compared to the typical dendritic LCs in the normal tissues (p -0.001). In the malignant group, the non-dendritic CD1a+ LCs were significantly fewer in number (p0.004), when compared to the normal group. Nondendritic LCs were also significantly fewer (p0.026) in patients over 60 years of age. This is the first report of non-dendritic Langerhans cells in normal buccal mucosa and malignant buccal mucosa using the CD1a marker. The significantly higher number of these cells in normal tissues and younger individuals supports their role as accessory antigen presenting cells

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Malignant Peripheral Nerve Sheath Tumour of the Small Bowel Presenting with Intussusception and Perforation: a Double Jeopardy?

Malignant peripheral nerve sheath tumours (MPNST) are rare soft tissue sarcomas which largely occur in the extremities and the head and neck region. The tumours are aggressive with a high rate of recurrence. Radical surgical resection remains the treatment of choice with adjuvant radiation therapy and chemotherapy still failing to demonstrate a clear benefit. The gastrointestinal tract is an exceedingly rare site for these tumours. We report an unusual case of a young male with an MPNST of the small bowel who presented with an ileocolic intussusception and sigmoid perforation.

Colonic metastasis in mucoepidermoid carcinoma of the parotid: a rare occurrence.

We present a case of intermediate-grade mucoepidermoid carcinoma of the parotid with late local recurrence and colonic metastasis. A 69-year-old man who had undergone right total conservative parotidectomy followed by adjuvant radiotherapy for intermediate-grade mucoepidermoid carcinoma 10 years prior, presented with a recurrent swelling in the postoperative site and cardiac failure. On evaluation, he was found to have severe anaemia with positive stool occult blood. Colonoscopic evaluation revealed a globular submucosal bulge with erosion 40 cm from the anal verge, the biopsy of which was consistent with mucoepidermoid carcinoma. The presentation, diagnostic details and management of this rare case are discussed.

Amyand's Hernia: Case Report -Current Dilemma in Diagnosis and Management.

Amyand's hernia is an extremely rare condition, often misdiagnosed as a strangulated inguinal hernia, in which the inguinal hernial sac contains the vermiform appendix. It is often a surgical surprise. The reported incidence is approximately 1% of all adult inguinal hernia cases. Acute appendicitis in the Amyand's hernia is even less common. We report a rare presentation of acute appendicitis associated with Amyand's hernia managed by en masse reduction of the hernia followed by laparoscopic appendicectomy and open Lichtenstein's tension free inguinal hernioplasty.