SMAD4 - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene

<p>Abstract</p> <p>Background</p> <p>The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the <it>SMAD4 </it>gene mutations with <it>KRAS </it>mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of <it>SMAD4 </it>gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and <it>KRAS </it>mutant genotype.</p> <p>Methods</p> <p>We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of <it>SMAD4 </it>and exon 1 of <it>KRAS </it>by PCR-SSCP and/or PCR-Direct sequencing.</p> <p>Results</p> <p>The overall mutation rate of mutation cluster region (MCR) region of <it>SMAD4 </it>gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the <it>SMAD4 </it>gene mutants were found to have mutations in <it>KRAS </it>gene as well. The association between the <it>KRAS </it>mutant genotype with <it>SMAD4 </it>mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the <it>SMAD4 </it>gene (P =< 0.05).</p> <p>Conclusion</p> <p>Our study suggests that <it>SMAD4 </it>gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the <it>KRAS </it>mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.</p

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Goiter prevalence and iodine deficiency disorder among school-age children (6–12 years) in district Ganderbal of Kashmir valley

BACKGROUND: Iodine deficiency is a major cause of brain damage in childhood which can be prevented. Dietary deficiency of iodine is mainly responsible for iodine deficiency. This study was done to determine the prevalence of goiter among school-aged group of 6–12 years in district Ganderbal. MATERIALS AND METHODS: This was a cross-sectional study done among children of 6–12 years in district Ganderbal. RESULTS: Out of 2700 children examined, Grade 1 goiter was found in 90 (3.3%) children and Grade 2 goiter was found in 6 (0.3%) with a total goiter rate (sum of grade first and grade second) of 3.6%. On analyzing the urine samples, about 19.1% of the children had mild to moderate iodine deficiency. CONCLUSION: The study showed mild goiter prevalence in school-aged children of 6–12 years in the Ganderbal district of Kashmir valley. Continuous periodic surveys to assess the magnitude of the iodine deficiency disorders (IDD) should be undertaken to ensure that we achieve sustainable elimination of IDD in India

Case Report Total Esophageal Avulsion at the Esophagogastric Junction after Blunt Trauma

Total avulsion and transection of the esophagus at the esophagogastric junction are very rare after blunt trauma, and their management is challenging. Here, we present the case of a boy with this injury. To date, only two cases have been reported in children. One was treated successfully and the other died. The initial emergency operation should aim to save the life and native esophagus. Therefore, a primary or early thoracal end esophagostomy with gastrostomy should be performed, while primary repair should not be

Burden of Goitre and Urinary Iodine Status among Primary School Children in Kashmir, India—Evidence from a Population-Based Iodine Deficiency Disorder Survey

Introduction: Iodine deficiency is the leading cause of preventable brain damage, with 30% of the world’s population suffering from iodine deficiency disorders (IDDs). The objectives of the study are to estimate the prevalence of goitre among schoolchildren in the age group of 6–12 years, to find out the proportion of households with adequately iodised salt, and to assess the dietary iodine intake by measuring urinary iodine levels in the urine samples of school-going children. Methods: A cross-sectional study was conducted in four pre-selected districts of the Kashmir division of Jammu and Kashmir in school-going children aged 6 to 12 years. Multi-stage 30 cluster sampling was used to select the study sample. For the selection of 30 clusters in each district, probability proportional to size (PPS) was employed. From each cluster, 90 children were selected. From a sub-sample of children in each district, 540 salt samples and 270 urine samples were also collected. Results: A total of 10,800 children aged 6–12 years were examined. Grade I goitre was present in 1382 (12.8%) and 116 (1.07%) which were having Grade II goitre. The weighted prevalence of goitre for four districts was 12.6%, lowest for district Ganderbal and highest for district Shopian. Half of the population in all the districts consumed salt with iodine levels of <15 ppm. Urinary iodine levels <99.9 mg/L were present in 15.7% indicating mild to moderate iodine deficiency. Conclusion: Though the present survey showed some decline in the total goitre rate (TGR) from a prevalence of 14.8% in 2017 to 12.6% in 2022, it continues to be a public health problem of mild to moderate intensity in Kashmir. The salt consumed at the household level was inadequately iodised. Hence, efforts in IDD elimination activities need to be scaled up further with emphasis on iodised salt quality control and intensive education at the community level