Mutational Assessment in NKX2-5 and ACTC1 Genes in Patients with Congenital Cardiac Septal Defect (CCSD) from Ethnic Kashmiri Population.

(1) Background globe. The etiology of CHDs is complex and involves both genetic and non-genetic factors. Although, significant progress has been made in deciphering the genetic components involved in CHDs, recent reports have revealed that mutations in Nk2 homeobox5 (NKX2-5) and actin alpha cardiac muscle1 (ACTC1) genes play a key role in CHDs such as atrial and ventricular septum defects. Therefore, the present study evaluates the role of key hotspot mutations in NKX2-5 and ACTC1 genes of congenital cardiac septal defect (CCSD) in ethnic Kashmiri population. (2) Methods: A total of 112 confirmed CHD patients were included in the current study, of which 30 patients were evaluated for mutational analysis for hotspot mutations of NKX2-5 and ACTC1 genes. The total genomic DNA was extracted from the samples (cardiac tissue/blood) and were subjected to amplification for NKX2-5 (exon 1 and 2), and ACTC1 (exon 2) genes by using PCR specific primers to analyze the hotspot mutations in respective exons. The amplified products obtained were sent to Macrogen Korea for sequencing by Sanger's method. (3) Results: Our results confirmed that not a single mutation was found in either hotspot exon 1 and 2 of NKX2-5 and exon 2 of ACTC1 in the patients included in the current study. Interestingly, a novel synonymous nucleotide variation leading to G > C transversion (GCG > GCC) was found in exon 2 of NKX2-5 gene of CCSD patient. (4) Conclusions: The current findings demonstrated the role of NKX2-5 and ACTC1 in cardiac development. The study will provide an insight in understanding the genetic etiology and highlights the role of newly identified mutations in patients with CDS's in ethnic Kashmiri population. In silico findings revealed amino acid changes, splice site variation and the creation of new site. Furthermore, the study warrants complete screening of genes involved in CCSDs.

Characteristics of Pseudoaneurysms in Northern India; Risk Analysis, Clinical Profile, Surgical Management and Outcome.

OBJECTIVE: To determine the risk factors, clinical characteristics, surgical management and outcome of pseudoaneurysm secondary to iatrogenic or traumatic vascular injury. METHODS: This was a cross-sectional study being performed in department of cardiovascular and thoracic surgery skims soura during a 4-year period. We included all the patients referring to our center with primary diagnosis of pseudoaneurysm. The pseudoaneurysm was diagnosed with angiography and color Doppler sonography. The clinical and demographic characteristics were recorded and the risk factors were identified accordingly. Patients with small swelling (less than 5-cm) and without any complication were managed conservatively. They were followed for progression and development of complications in relation to swelling. Others underwent surgical repair and excision. The outcome of the patients was also recorded. RESULTS: Overall we included 20 patients with pseudoaneurysm. The mean age of the patients was 42.1±0.6 years. Among them there were 11 (55%) men and 9 (45%) women. Nine (45%) patients with end stage renal disease developed pseudoaneurysm after inadvertent femoral artery puncture for hemodialysis; two patients after interventional cardiology procedure; one after femoral embolectomy; one developed after fire arm splinter injury and one formed femoral artery related pseudoaneurysm after drainage of right inguinal abscess. The most common site of pseudoaneurysm was femoral artery followed by brachial artery. Overall surgical intervention was performed in 17 (85%) patients and 3 (15%) were managed conservatively. CONCLUSION: End stage renal disease is a major risk factor for pseudoaneurysm formation. Coagulopathy, either therapeutic or pathological is also an important risk factor. Patients with these risk factors need cannulation of venous structures for hemodialysis under ultrasound guide to prevent inadvertent arterial injury. Patients with end stage renal disease who sustain inadvertent arterial puncture during cannulation for hemodialysis should receive compression dressings for 5 to 7 days.

Radical resection of pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare intrathoracic neoplasm of early childhood that occurs in the lung or visceral pleura. We present a case of a 5-year-old boy with a cough, left-sided chest pain and progressive dyspnea on exertion. The patient had had an operation for a congenital lung cyst of the left lower lobe, six months prior to the present admission. A CT showed a heterogeneously enhancing mass lesion filling the left hemithorax. CT-guided fine needle aspiration cytology of the mass was inconclusive. En bloc resection of the mass along with left lower lobe, the involved ribs and left diaphragm was performed. The diaphragmatic defect was repaired using prolene mesh. Histopathology of the resected specimen showed solid and cystic areas consistent with type II PPB. The patient received adjuvent chemotherapy and was doing well 23 months after surgery. Radical resection of the tumor followed by adjuvent chemotherapy provides the only hope of salvaging cases of type II or type III PPB.

Transthoracic versus transhiatal esophagectomy for esophageal carcinoma: experience from a single tertiary care institution.

BACKGROUND: There is a lot of controversy about the best surgical treatment for esophageal carcinoma. METHODS: In this retrospective study, 382 patients with carcinoma of the mid-to-distal esophagus underwent transthoracic or transhiatal esophagectomy. Early morbidity and mortality were compared. Principal endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 177 patients underwent transthoracic esophagectomy, and 205 patients underwent transhiatal esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative and postoperative morbidity was higher after transhiatal esophagectomy. In-hospital mortality was also higher after transhiatal esophagectomy. The median follow-up was 4.3 years. Estimated 3-year DFS rates were 44.63 and 31.21%, whereas the 3-year OS rates were 57.06 and 41.46% for the transthoracic and transhiatal groups, respectively (statistically significant). Also, the estimated 5-year DFS rates were 26.55 and 21.46%, whereas the 5-year OS rates were 32.76 and 30.24% for the transthoracic and transhiatal groups, respectively (statistically not significant). CONCLUSIONS: Transhiatal esophagectomy was associated with higher perioperative and postoperative morbidity and in-hospital mortality than transthoracic esophagectomy. The DFS and OS were higher in the transthoracic group and were statistically significant at 3 years but statistically insignificant at 5 years.

Unusual metastasis to all the digits of both hands in a patient previously operated on for esophageal carcinoma.

Metastatic malignancies to the hand, although rare, usually develop from lung, breast, and kidney tumors. Very rarely the origin is the gastrointestinal system. Metastases to the bones of the hand can cause pain, swelling, soft tissue ulceration, and osteolytic destruction. We present a patient with metastatic tumors to all digits of both hands 2.5 years after being operated on for esophageal carcinoma. The patient underwent amputation of the left little finger followed by systemic chemotherapy. The histopathological diagnosis was consistent with that of the primary tumor. This case is being presented for being the rarest of its kind and may even be the first of its nature in the world's literature as an extensive search has not shown another of its kind to date.

Association of cyclin D1 gene polymorphisms with risk of esophageal squamous cell carcinoma in Kashmir Valley: a high risk area.

Investigation of potential association of SNPs (G870A, rs9344; G1722C, rs678653) of cyclin D1 gene (CCND1) with susceptibility to esophageal squamous cell carcinoma (ESCC) in Kashmir valley (India). The study included 302 subjects comprising 151 ESCC cases and 151 controls. PCR-RFLP and direct sequencing were employed for genotyping. The G870A polymorphism, the individuals carrying GA + AA genotype was having 2.80-fold increased risk for development of ESCC (OR 2.8, 95% CI = 1.77-4.4; P = 0.0001) compared to GG genotype. Further a significantly higher risk was observed in individuals who consume >3 cups per day of salted tea (OR = 5.1; 95% CI = 1.6-16.7; P = 0.0016) and had smoking habits (OR = 6.3; 95% CI = 2.9-13.9; P = 0.0005). We also demonstrate for the first time in CCND1 1722 locus, the CC genotype was strongly associated with increased risk of developing ESCC (OR = 2.58; 95% CI = 1.61-4.15; P = 0.0001). In addition, the frequency of polymorphic C allele was also found to be higher in cases (OR = 1.92; 95% CI = 1.37-2.69; P = 0.0002). There appears to be an influence of CCND1 G870A/G1772C genotypes on genetic susceptibility to ESCC.

Clinical profile and surgical outcome for pulmonary aspergilloma: nine year retrospective observational study in a tertiary care hospital.

BACKGROUND: The indications and the outcome of surgery for pulmonary aspergilloma remain highly controversial. This retrospective observational study was conducted to study the clinical profile, indications, post-operative complications and long term outcome of patients having pulmonary aspergilloma. METHODS: From January 2000 to October 2008, 52 patients underwent surgery for pulmonary aspergilloma at our tertiary care institute. RESULTS: The group consisted of 32 males and 20 females with a mean age of 39.3 ± 11.2 years. The most common indication for surgery was hemoptysis (96.15%). The underlying lung diseases were tuberculosis (75%), bronchiectasis (5.76%), and lung abscess (5.76%). In one patient (2%), concomitant ruptured lung hydatid cyst and an aspergilloma was present. The procedures performed were lobectomy (n = 43), bilobectomy (n = 3). pneumonectomy (n = 3), segmental resection (n = 3). The post-operative mortality was 1.92% (one patient). Overall complications occurred in 12 (23.07%) patients. The complications included prolonged air leak (n = 6), bleeding (n = 3), empyema (n = 1), repeated pneumothorax (n = 1), and wound dehiscence (n = 1). The mean follow-up period was 38 ± 18.6 months. There was no recurrence of disease or hemoptysis. CONCLUSION: Pulmonary aspergilloma is common in developing countries like India in which there is high prevalence of pulmonary tuberculosis. Surgical resection of pulmonary aspergilloma is effective in preventing recurrence of symptoms including hemoptysis. We recommend early surgical resection of symptomatic aspergilloma with reasonable complications. Pre-operative preparation of the patients, meticulous surgical technique and post-operative chest physiotherapy reduces the rate of complications. Complications may still occur and are largely related to the underlying lung pathology; however, the long term outcome is good.

Nontraumatic massive right-sided Bochdalek hernia in an adult: an unusual presentation.

Diaphragmatic hernias in adults usually pose a diagnostic challenge; the presentations are varied and range from acute abdominal pain with features of gut obstruction, pleuritic chest pain, breathlessness, to a pregnant woman with pain abdomen. The usual cause in adults is posttraumatic. Because of varied presentations, the diagnosis is often delayed. We present a case of a young woman who presented with sudden-onset breathlessness with similar episodes in the past and no history of trauma, who proved to be having a right-sided diaphragmatic hernia. This case is reported not only because of rarity of nontraumatic right-sided Bochdalek hernias in adults, but also because of peculiar presentation and history.

Hydatid embolism from a thoracic aortic pseudoaneurysm presenting as gangrenous toes.

Cystic echinococcosis (hydatid cyst), caused by Echinococcus granulosus, has worldwide distribution and poses a health problem in endemic areas. Embolization of hydatid cysts into the vascular tree is an unusual manifestation of the disease. The hydatid embolism results from spontaneous or traumatic rupture of the cyst, and rare case reports of this kind are not well documented in the literature. We report a case of a hydatid embolism from a ruptured hydatid in a pseudoaneurysm of the thoracic aorta. A 45-year-old woman presented with gangrenous changes of the toes of her right foot. After embolectomy, the histopathology of the embolus was doubtful about its being blood clots around hydatid membranes. Postoperatively, computed tomography (CT) of the chest revealed a pseudoaneurysm of the descending thoracic aorta. Definitive surgery for the pseudoaneurysm was done during a second operation. Numerous hydatid cysts were evacuated from the pseudoaneurysm. This report emphasizes the need for an early diagnosis and treatment of echinococcosis before disabling and life-threatening complications occur.

Missile vascular injuries: 19-year experience.

BACKGROUND: Missile vascular injuries have reached an epidemic proportion in Kashmir valley since the eruption of militancy. The present study was undertaken to analyze the mode, pattern, presentation, and management of missile vascular injuries. METHODS: A retrospective study of patients with missile vascular injury from January 1990 to October 2008 was undertaken. Five hundred eighty patients with missile vascular injury were studied. All patients with vascular injury due to causes other than missiles were excluded from the study. RESULTS: Most of the patients were treated by interpositional saphenous vein graft or end-to-end anastomosis. The most common complication was wound infection (22.7%) followed by graft occlusion (3.8%). The amputation rate was 3.3% and was higher in patients with a delay of >6 hours to revascularization and associated fractures. CONCLUSION: Missile vascular injury requires prompt resuscitation and revascularization. Preoperative angiography is seldom necessary. Doppler study may sometimes be needed to aid in the diagnosis.

Transcription factor AP-1 in esophageal squamous cell carcinoma: alterations in activity and expression during human Papillomavirus infection.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high-risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection. METHODS: Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively. RESULTS: A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues. CONCLUSION: Differential AP-1 binding activity and expression of its specific proteins between HPV--positive and HPV--negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis.

Pulmonary lymphangioleiomyomatosis: a rare presentation.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare idiopathic, cystic disease. We report a case of LAM who presented with nonchylous, bilateral pleural effusion and progressive respiratory failure.