Pattern of esophageal injuries and surgical management: A retrospective review.

BACKGROUND: The consequence of significant injury to the esophagus is devastating. The initial management when timely and appropriate is rewarding and often prevents lethal complications. The objective of this study is to describe the etiology of esophageal injury in our institution, the management procedures and the mid-term results. METHOD: Consecutive patients diagnosed and managed for esophageal injury from January 2005 to March 2015 were retrospectively reviewed. RESULTS: One hundred and eleven patients were seen and treated during this period; 85 (76.6%) predominantly children were corrosive esophageal injuries who accidentally ingested caustic soda and 26 (24.4%) were traumatic esophageal injuries. Patients with corrosive esophageal injuries were predominantly male (2:1), mean age 12.8 ± 14.2 years (2-58 years) and predominantly children (53% ≤5 years; 18.8% ≥ 18 years). Patients with non-corrosive esophageal injury were also predominantly male (4:1) with a mean age of 34.4 ± 20.1 years (1-73 years). The treatment procedures for corrosive esophageal injuries included esophagocoloplasty 64 (75.3%), colopharyngoplasty 10 (11.8%), colon-flap augmentation pharyngo-esophagoplasty 4 (4.7%), colopharyngoplasty with tracheostomy 4 (4.7%) and esophagoscopy and dilatation 3 (3.5%). Mortality was 5.9% and 5 patients were lost to follow-up. In patients with noncorrosive esophageal injury, esophageal perforation from instrumentation accounted for 14 (53.9%), foreign body impaction 11 (42.3%) and spontaneous perforation 1 (3.8%) making up the rest. Management of these patients included esophagotomy and removal of foreign body 7 (26.9%), esophagectomy, cervical esophagostomy and feeding gastrostomy 10 (38.6%), primary repair 7 (26.9%), Ivor Lewis procedure 1 (3.8%) and emergency esophagectomy with colon replacement 1 (3.8%). Mortality in this group of patients was 7.7% and 4 patients were lost to follow-up. CONCLUSION: Corrosive esophageal injuries were the most frequent form of esophageal injury at our center due to unrestricted access to corrosive substances. Generally, appropriate surgical intervention in patients with esophageal injury based on individualization of care yields excellent early and mid-term results.

The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal.

Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.

Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal.

The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings.

Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor.

BACKGROUND: Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP) centers for patients with CML. METHODS: A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses. RESULTS: Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity. CONCLUSIONS: Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.

African dust clouds are associated with increased paediatric asthma accident and emergency admissions on the Caribbean island of Trinidad

Objective: To determine if there is any association between paediatric Accident & Emergency (A&E) asthma admissions and Saharan dust cloud cover Methods: A retrospective ecological study of paediatric asthma patients who attended the A&E department of the Eric Williams Medical Sciences Complex in relation to Saharan dust visibility andother climactic variables for the period May 23 2001 to May 13 2002. A quasi-likelihood approach was used to develop a statistical model for the relationship between acute paediatric asthma A&Evisits and Saharan dust cover.Results: 2655 A&E visits for acute asthma during the study period. There were significant associations between paediatric admissions and two climate variables; Saharan dust levels (p <0.05)and barometric pressure (p <0.01). In the absence of dust however, barometric pressure by itself hadno predictive power. Dust cover & barometric pressure were most strongly associated with increased admissions the day after dust cover Conclusions: Saharan dust cloud cover over Trinidad was associated with an increase inpaediatric asthma A&E visits on the following day. The dust effect was strongly influenced by prevailing barometric pressure; heavy dust cover and low pressure were most strongly associated with increased acute asthma visits.

African dust clouds are associated with increased paediatric asthma accident and emergency admissions on the Caribbean island of Trinidad.

A retrospective ecological study of paediatric asthma patients who attended the Accident and Emergency (A and E) department of the Paediatric Priority Care Facility at the Eric Williams Medical Sciences Complex in relation to Saharan dust visibility and other climatic variables for the period 23 May 2001 to 13 May 2002 was undertaken to determine if there is an association between paediatric A and E asthma visits and Saharan dust cloud cover. A Poisson regression model was used to determine the statistical relationship between acute paediatric asthma A and E visits and Saharan dust cover with and without other variables such as climatic parameters and month. During the study period, there were 2,655 A and E visits for acute asthma. There was an association between increased paediatric asthma admissions and increased Saharan dust cover. The best fitting model estimated that in one month, such as June, a deterioration of visibility due to increased Saharan dust cover from no dust (visibility =16 km) to very dusty (visibility =7 km) would increase a daily admission rate of 7.8 patients to 9.25 when climate variables such as barometric pressure and humidity were kept constant.

Novel glycolipids of Mycobacterium avium and related M. paratuberculosis strains of relevance to AIDS and Crohn's disease.

The polar glycolipid fractions of several mycobacterial strains of the closely related species M. avium and M. paratuberculosis have been analysed by thin layer chromatography (TLC), high pH anion exchange chromatography (HPAEC), gas-liquid chromatography (GC) and nuclear magnetic resonance (NMR) spectroscopy. The upper phase of a Folch partitioning (rather than the lower phase analysed by others) was subjected to TLC in solvent system chloroform-methanol-water 50:40:10 v/v/v. A major band was purified from each mycobacterial strain. Monosaccharide analysis of that from M. avium A14 (from an AIDS patient) contained Glc, Ara, Man, Gal in ratios 7:4:3:2. whereas one strain of M. paratuberculosis (316F) had low levels of Ara, Gal and Man with major monosaccharides being Glc and two unidentified monosaccharides. A second M. paratuberculosis strain (J10) had a single TLC band containing only Glc. These known strains were compared to two slow growing mycobacterial isolates, one from a Crohn's patient and one isolated from armadillo. These were similar to J10 in only having Glc present: the former also had a similar NMR spectrum to J10, whereas the latter had a different NMR spectrum from any of the other strains analysed. The results therefore indicate that M. paratuberculosis strain 316F is more closely related to M. avium (from an AIDS patient) than it is to the classical M. paratuberculosis strain J10 and a Crohn's isolate.