Association of Activity Altering Genotypes - Tyr113His and His139Arg in Microsomal Epoxide Hydrolase Enzyme with Esophageal Squamous Cell Carcinoma.

The study aimed to explore the relationship of microsomal epoxide hydrolase (mEH) exon 3 (Tyr113His) and exon 4 (His139Arg) polymorphisms and predicted mEH activity with esophageal squamous cell carcinoma (ESCC) risk. 482 histologically confirmed cases and equal number of matched controls were analyzed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). Conditional logistic regression models were used to examine the association of polymorphisms with ESCC. We noted exon 3 slow genotype (OR = 6.57; CI 3.43-12.57) as well as predicted low mEH activity (OR = 3.99; CI 2.32-6.85) was associated with the ESCC risk. Elevated ESCC risk estimates were seen in smokers independent of genotypes but the association was stronger among smokers with exon 3 variant (OR = 6.67; 3.29-13.53) and low activity (OR = 7.52; CI 3.46-16.37) genotypes. Positive family history of cancer synergistically increased ESCC risk in the individuals who harbored exon 3 (OR = 13.59; CI 5.63-32.81) or altered mEH activity genotypes (OR = 13.35; CI 5.10-34.94). Significant interaction was seen between mEH exon 3 and exon 4 genotypes (P = 0.006) and between predicted mEH activity and positive family history of cancer (P = 0.018). These findings suggest association of ESCC risk with mEH polymorphisms which get modified by tobacco smoking and positive family history of cancer.

CYP1A2*1F Gene Variant, Alkaline Salt Tea Intake and Risk of Esophageal Squamous Cell Carcinoma.

Unlike many other cancers, the relationship of CYP1A2*1F (rs762551) polymorphism with esophageal squamous cell carcinoma (ESCC) risk has not been assessed so far. To evaluate its association with ESCC, we conducted a case control study in Kashmir, India, a high risk region. We recruited 404 histopathologically confirmed ESCC cases and 404 controls, individually matched for sex, age and residence to the respective cases. Information was obtained on dietary, lifestyle and environmental factors in face to face interviews using a structured questionnaire from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and sequencing randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that mutant genotype (AA) of CYP1A2*1F polymorphism was associated with ESCC risk (OR = 3.11; 95% CI: 1.72-5.36). A very strong ESCC risk was observed in subjects who drank >1250 ml of salt tea daily and harbored mutant genotype of CYP1A2*1F (OR = 14.51; 95% CI: 5.33-39.47). The study indicates that CYP1A2*1F polymorphism is associated with ESCC risk and the risk is modified in salt drinkers. However, more replicative and mechanistic studies are needed to substantiate the findings.

Expression Profiling and Cellular Localization of Stress Responsive Proteins in Squamous Cell Carcinoma of Human Esophagus.

BACKGROUND: The ambiguity in relating expression dynamics of stress response proteins with human esophageal squamous cell carcinoma (ESCC) has sidelined the potential of stress proteins as therapeutic targets. This study was an attempt to unequivocally relate the stress protein dynamics with stage and propensity of ESCC. METHODS: Surgically resected tumor and adjacent histologically normal tissue from 46 patients with esophageal squamous cell carcinoma were investigated in the present study. Expression of HSPs was analyzed by Western blotting and immunohistochemistry. RESULTS: HSP expression was observed in all 46 cases both in adjacent normal and tumor tissues. The expression and the localization of individual HSP showed no significant correlation with depth of invasion, tumor grade, and pathological stage of the tumor. HSP 27 was the most abundant protein followed by HSP 90 and HSP 70. The HSP 27 localized exclusively in the cytoplasm of adjacent normal and tumor cells. HSP 70 showed dispersed expression with predominating nuclear localization in both normal and tumor tissue cells and HSP 90 was localized in cytoplasm of adjacent normal and in nucleus of tumor cells in majority of the cases. CONCLUSION: Our data advocate lack of relationship between stress protein expression and the progression of ESCC. The data renew the prospect of anti-HSP drugs as therapeutic resources in light of the possibility that their use would continue to sensitize cancer cells towards drug induced apoptosis for tumor regression.

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.

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.

Ascaris through a chest tube: a rare presentation.

A rare case of an Ascaris worm emerging through an intercostal chest tube is reported here because of its unusual presentation. A five-year-old male child had a liver abscess, which had ruptured into the right pleural cavity. An intercostal chest tube was inserted for right pleural effusion. On the 5th postoperative day, a 7 cm long worm was noticed emerging through the chest tube. Ascaris lumbricoides infestation can lead to serious complications because of the mobility of the worms. Though complications such as intestinal obstruction, volvulus, gangrene, pancreatitis, biliary obstruction, cholangiohepatitis, and liver abscess have been reported to occur, intrapleural ascariasis is an extremely rare situation. This report describes a clinical situation of intrapleural ascariasis and emphasizes the importance of remaining aware of this rare complication of ascariasis.

LRFN2 gene variant rs2494938 provides susceptibility to esophageal cancer in the population of Jammu and Kashmir.

BACKGROUND: Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease. MATERIALS AND METHODS: In the present case-control study, 166 cases and 459 controls were included. Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003). CONCLUSION: The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.

Transdiaphragmatic migration of forgotten gauze sponge: an unreported entity of lung abscess.

Migration of left in foreign bodies like gauze sponge into intestine, stomach, urinary bladder and their extrusion through umbilicus or rectum is well known. We report a unique case wherein a gauze sponge was left in abdominal cavity 25 years back at the time of initial surgery. This patient who had not undergone any thoracic surgery in the past was recently subjected to posterolateral thoracotomy for a right sided lung abscess and a large sponge gauze was unbelievably recovered from the area of lung abscess.

Prolonged Impacted Denture in the Esophagus: A Case Report and Review of the Literature.

Foreign body ingestion and aspiration is among the most common causes of emergency department visit associated with high morbidity and mortality. Ingested and aspirated denture is rare conditions being scarcely reported in the literature. We herein report a 57-year-old man who presented with 2-day history of liquid and solid dysphagia who was diagnosed to have impacted denture in esophagus since 3 years prior to presentation. He was diagnosed to have esophagus adenocarcinoma and had undergone esophageal radiotherapy. The denture was removed successfully using esophagoscopy and the patient was discharged after 48-hour care with good condition. To prevent accidental ingestion, dentures should be made to fit properly. Damaged or malfitting dentures should be discarded and replaced. Patients should be strongly advised against wearing them during sleep-time.

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.

Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma.

OBJECTIVES: Tumors not only manage to escape from the host immune system, but they effectively contrive to benefit from infiltrating immune cells by modifying their functions so as to create a pro-inflammatory microenvironment favorable for tumor progression and metastasis. In this study we investigated if tectorigenin could suppress lung cancer-induced pro-inflammatory response generated from monocytes. MATERIALS AND METHODS: A549:THP1 co-culture model was set-up favoring release of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Effect of tectorigenin on A549 imparted invasive phenotype of A549:THP-1 co-culture was monitored by cytokine release from monocytes, and metastasis/epithelial-mesenchymal transitiom (EMT) in A549 cells. RESULTS: In a contact A549:THP1 co-culture model, THP-1 cells were activated by A549 cells favoring secretion of pro-inflammatory cytokines, TNF-α and IL-6. However, priming of A549 cells with tectorigenin for 24h repressed A549 cell-induced secretion of TNF-α and IL-6 by THP-1 cells. Tectorigenin induced change in functional phenotype of A549 cells rendered THP-1 cells non-responsive for the secretion of IL-6 and TNF-α in a contact co-culture setup. Additionally, conditioned media from this non-responsive A549:THP-1 co-culture suppressed metastatic potential of A549 cells as confirmed by the wound healing and transwell migration assays. These finding were further corroborated by decrease in expression of Snail with a concomitant increase in E-cadherin, the two signature markers of EMT. CONCLUSION: These results clearly demonstrate the therapeutic potential of tectorigenin to prevent lung cancer elicited inflammatory and pro-metastatic response in monocytes and warrants further investigations to elucidate its mechanism of action.

Comparative proteomics and global genome-wide expression data implicate role of ARMC8 in lung cancer.

BACKGROUND: Cancer loci comprise heterogeneous cell populations with diverse cellular secretions. Therefore, disseminating cancer-specific or cancer-associated protein antigens from tissue lysates could only be marginally correct, if otherwise not validated against precise standards. MATERIALS AND METHODS: In this study, 2DE proteomic profiles were examined from lysates of 13 lung-adenocarcinoma tissue samples and matched against the A549 cell line proteome. A549 matched-cancer-specific hits were analyzed and characterized by MALDI-TOF/MS. RESULTS: Comparative analysis identified a total of 13 protein spots with differential expression. These proteins were found to be involved in critical cellular functions regulating pyrimidine metabolism, pentose phosphate pathway and integrin signaling. Gene ontology based analysis classified majority of protein hits responsible for metabolic processes. Among these, only a single non-predictive protein spot was found to be a cancer cell specific hit, identified as Armadillo repeat-containing protein 8 (ARMC8). Pathway reconstruction studies showed that ARMC8 lies at the centre of cancer metabolic pathways. CONCLUSIONS: The findings in this report are suggestive of a regulatory role of ARMC8 in control of proliferation and differentiation in lung adenocarcinomas.

Splice site and Germline variations of the MGMT gene in Esophageal cancer from Kashmir Valley: India.

OBJECTIVES: The aim of our investigation was to detect mutation or genetic polymorphisms in MGMT gene of esophageal cancer patients from Kashmir Valley (India). METHODOLOGY: The genetic polymorphisms or mutations in the coding exons 2, 3, 4 and 5 of MGMT gene were searched for in DNA samples from the frozen tumor tissues of 30 esophageal cancer patients from Kashmir. The PCR products were sequenced with fluorescently labelled terminators and separated on automatic sequencer. We developed a new PCR based RFLP approach for genotyping c.459A>G (p.Gly153Gly) variation in 71 esophageal cancer patients and 60 healthy controls. RESULTS: Two somatic variations c.274 +4G>A and c.274 + 22G>A were identified in Exon3-intron 4 boundary. A novel germline variation c.459A>G (p.Gly153Gly) was found in the exon 5 of an esophageal cancer patient. This germline variation was not found in any of the studied esophageal cancer patients and healthy controls except the patient where it has been found by direct sequencing. CONCLUSION: We identified novel sequence variants of the MGMT gene in esophageal cancer patients from Kashmir valley-India.

The Etiology, Associated Injuries and Clinical Presentation of Post Traumatic Diaphragmatic Hernia.

OBJECTIVES: The aim of this study was to evaluate the etiology, associated injurers and clinical presentation of post traumatic diaphragmatic hernia. METHODS: This study was a cross-sectional study being conducted in the department of Cardiovascular, thoracic surgery (CVTS) and Pediatric Surgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Kashmir, India. All patients of post traumatic diaphragmatic hernia who were admitted in the department of CVTS and Pediatric Surgery, SKIMS, during the course of study (May 2009 to Nov. 2011) were included. RESULTS: From the commencement of the study 21 patients had traumatic diaphragmatic hernia. Most common presenting symptoms in traumatic diaphragmatic hernia were, chest discomfort and pain abdomen presented in 81% of patients, followed by breathlessness in 61.9% and vomiting in 47.6%. Common associated injuries in traumatic diaphragmatic hernia in our study group were, rib fracture in 47.6%, splenic injury in 28.6%, head injury in 23.8%, soft tissue injury in 23.8%, gut perforation in 19%, limb fracture in 14.3%, liver injury in 9.5%, pancreatic injury in 4.8% and renal injury in 4.8%. CONCLUSION: Usually the patients of Post traumatic diaphragmatic hernia presents as emergency, early recognition and prompt surgical treatment is needed for better outcome. The Incidence of post traumatic diaphragmatic hernia when associated with blunt trauma abdomen and chest is very high (81%). A high level of suspicion is needed in these injuries. The 9.5% of traumatic diaphragmatic hernia may have delayed presentation. Early diagnosis of traumatic diaphragmatic hernia is most difficult when herniation is delayed.

Mediastinal bronchogenic cyst compressing left recurrent laryngeal nerve.

A 15-year-old boy developed recurrent laryngeal nerve compression by a bronchogenic cyst, causing recurrent choking. Bronchogenic cyst compressing the recurrent laryngeal nerve is unusual. The patient had a normal voice and occasional choking with periods of normalcy in between. A left posterolateral thoracotomy was performed and cyst was excised. Histopathology revealed bronchogenic cyst.

Native arterio-venous fistula is the vascular access of choice for hemodialysis in end stage renal disease.

OBJECTIVES: THE AIM OF THE STUDY WAS: Is primary Arterio-venous fistula the vascular access of choice for adequate dialysis and better patient outcome in end stage renal disease. MATERIALS AND METHODS: The present study was done in the department of cardiovascular and thoracic surgery at Sher-i-Kashmir institute of medical sciences, Soura, Srinagar Kashmir. Native Arterio-Venous (AV) fistulas were made in the patients with end stage renal disease for performing hemodialysis. They were followed for patency and adequacy of blood flow during hemodialysis. All the patients were operated under local anesthesia. RESULTS: The results showed that 77% of the AV fistulas based on radial artery with side-to-side anastomosis and 80% of those with end-to-side anastomosis were functionally patent after one year. After two years, the patency rate in side-to-side and end-to-side anastomosis was 50% and 55%, respectively. In addition, the patency rate was 90% in brachial artery based AV fistula with end-to-side anastomosis, whether done primarily or secondarily, at the end of one year. However, a rapid decline was observed in the patency rate during the third year in both radial artery based and brachial artery based AV fistulas. CONCLUSIONS: We concluded that Arterialised arm superficial veins after primary AV fistula was the optimal and rational vascular access for hemodialysis providing adequate blood flow during this process. Besides, failure of primary AV fistula should be replaced by secondary AV fistula preferably based on brachial artery.

Delayed presentation of traumatic diaphragmatic hernia: a diagnosis of suspicion with increased morbidity and mortality.

BACKGROUND: Diaphragmatic rupture due to blunt or penetrating injury may be a missed diagnosis in an acute setting and can present with a delayed complication with significantly increased morbidity and mortality. OBJECTIVES: The objective of this study is to better understand why diaphragmatic tears with delayed presentation and diagnosis are so often missed and why traumatic diaphragmatic tears are difficult to diagnose in emergency settings and how they present with grievous complications. PATIENTS AND METHODS: Eleven patients with diaphragmatic hernias with delayed presentation and delayed diagnosis were operated within the last five years. All patients presented with different complications like gut gangrene or respiratory distress. RESULTS: Out of eleven patients who were operated on for diaphragmatic hernia, three patients (27%) died. Three patients required colonic resection, one patient needed gastrectomy and one patient underwent esophagogastrectomy. CONCLUSIONS: A small diaphragmatic tear due to blunt trauma to the abdomen is difficult to diagnosis in acute settings due to ragged margins and possibly no herniated contents and usually present with a delayed complication. Therefore a careful examination of the entire traumatized area is the best approach in treating delayed presentation of traumatic diaphragmatic hernia prior to development of grievous complications.

Lung Contusion: A Clinico-Pathological Entity with Unpredictable Clinical Course.

Lung contusion is an entity involving injury to the alveolar capillaries, without any tear or cut in the lung tissue. This results in accumulation of blood and other fluids within the lung tissue. The excess fluid interferes with gas exchange leading to hypoxia. The pathophysiology of lung contusion includes ventilation/perfusion mismatching, increased intrapulmonary shunting, increased lung water, segmental lung damage, and a loss of compliance. Clinically, patient's presents with hypoxiemia, hypercarbia and increase in laboured breathing. Patients are treated with supplemental oxygen and mechanical ventilation whenever indicated. Treatment is primarily supportive. Computed tomography (CT) is very sensitive for diagnosing pulmonary contusion. Pulmonary contusion occurs in 25-35% of all blunt chest traumas.

The Pattern, Presentation and Management of Pardah Pin Inhalation: Report from a Single Center in Northern India.

OBJECTIVE: To describe the clinical characteristics, presentation and management of Pardah pin inhalation in female teenagers of single center in northern India. METHODS: This was a prospective cross-sectional study being performed in department of cardiovascular and thoracic surgery of Sher-i-Kashmir institute of medical sciences located in northern India from January 2009 to December 2012. We included 36 female patients with Pardah pin inhalation who were admitted to our center during the study period. All patients underwent rigid bronchoscopy under local or general anesthesia. We recorded the baseline characteristics including the demographic information, the site of the pin and clinical findings as well as the management strategies and the outcome of these patients. RESULTS: All patients were female using scarf to wrap their head and neck as religious obligation. Mean age of the patients was 14.3 ± 3.6 years. The most common symptom was chocking followed by cough being reported in all (100%) and 31 (86.1%) patients respectively. Bronchoscopy was successful in removing the pin in 31 (86.1%) patients. Pins were located in right main bronchus in 20 (55.5%) patients, and in left main bronchus in 10 (27.7%) patients. There was no mortality in our series. Pin was removed in 31 (86.1%) patients with the help of bronchoscope, but 5 (13.9%) patients needed bronchotomy for removal of the pin. Average hospital stay was 12.43 ± 1.6 hours. CONCLUSION: Rigid bronchoscopy is an ideal approach in management of Pardah pin inhalation. However some patients may need bronchotomy to remove the Pardah pin.

Lack of influence of MGMT codon Leu84Phe and codon Ileu143Val polymorphisms on esophageal cancer risk in the Kashmir Valley.

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.