Spectrum of Preneoplastic and Neoplastic lesions of intestine in a Tertiary Care Hospital of Karachi, Pakistan.

OBJECTIVES: To present 7 years data mentioning the spectrum of preneoplastic & neoplastic cases of intestine received at Dow Diagnostic Research and Reference Laboratory. METHODS: All the cases of preneoplastic & neoplastic lesions of intestine received during 2009 - 2015 were reviewed. The data obtained were subjected to descriptive statistical analysis using SPSS version 22. Furthermore, the association of diagnosis was seen with various other variables including age, gender & site of the lesion. A p-value of < 0.05 was considered as significant. RESULTS: The total samples were 486, out of which 33 cases were of premalignant and 453 were of malignant lesions. Out of total 33 cases of premalignant lesions of intestine, it consisted adenomatous polyp = 39.4% (n=13), dysplasia = 36.4% (n=12) and adenoma = 24.2% (n=8). From the total of 453 cases diagnosed as malignant lesions; adenocarcinoma as Grade-I were 14.2% (n=64), Grade-II were 7.6% (n=260) and Grade-III were 22% (n=99). Squamous cell carcinoma Grade-I were 0.4% (n=2), Grade-II 1.6% (n=7) and Grade-III 0.9% (n=4). 2.4% (n=11) cases were of metastatic adoncarcinoma, 0.9% (n=4) were diagnosed as neuroendocrine tumors and 0.4% (n=2) as lymphoma. A significant association was seen between site of the tumor and diagnosis, rectum was the commonest site for adenocarcinomas (p=0.001). Moderately differentiated adenocarcinoma was predominantly present in young age (p=0.001). CONCLUSION: Colorectal carcinoma is on rise in Pakistan, predominantly in young males, and rectum being the commonest site. In our study, all the lesions showed male predominance with adenomatous polyp as the commonest premalignant lesion & Grade-II adenocarcinoma the most common malignancy of intestine.

Human epidermal growth factor (Her-2) in gastric and colorectal adenocarcinoma.

Gastrointestinal (GIT) malignancies are a substantial health concern. Most patients present to the clinics with advanced and un-resectable diseases, so it remains difficult to cure with the existing chemotherapeutic regimes. It is therefore extremely important to devise novel therapeutic targets in these neoplasms in order to improve patient's survival. One such target is human epidermal growth factor, also known as Her-2. Although Her-2 expression and the use of a-Her-2 medications in breast cancers is well established, but its expression and potential use as a therapeutic target in gastrointestinal malignancies remains controversial and heavily debated. This review was planned to summarise the available literature extracted from the United States National Library of Medicine (NLM) and Pubmed Central, related to expression of Her-2 in gastric and colorectal adenocarcinomas and their correlation with different parameters. Moreover, we also planned to discuss available data in support of using a-Her-2 in gastric and colorectal malignancies.

Frequency of Her2/neu expression in colorectal adenocarcinoma: a study from developing South Asian Country.

BACKGROUND: Human Epidermal Growth Factor (Her-2/neu) has strong therapeutic implications in certain cancers like breast and gastric cancer. Literature on its frequency in colorectal cancer is scarce. In this study, we have investigated the frequency of Her-2/neu expression in colorectal adenocarcinomas and its association with various clinicopathological variables. METHODS: A total of 95 patients who underwent colonoscopic biopsy or colectomy were studied after Institutional Ethical Approval. Hematoxylin & eosin (H&E) staining was performed on all the tissue sections. Expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. In order to quantify Her-2/neu expression, three criterias were applied that includes the pattern of staining, intensity of staining and percentage of tumor cells stained. Furthermore, its association was seen with various clinicopathological variables including age, gender, histopathological type, grade and stage of the tumor. Data was entered and analyzed using SPSS version 21. A p-value of < 0.05 was considered as significant. RESULTS: From the total of 95 cases, 75 (78.9 %) cases showed Her-2/neu expression. Pattern of Her-2/neu staining was significantly associated with the grade of colorectal cancer depicting cytoplasmic Her-2/neu expression higher in low grade (50 %) while membranous Her-2/neu expression more in high grade colorectal cancer (45 %) (P-value = 0.030). Pattern of Her-2/neu staining was also significantly associated with the type of colorectal cancer representing membranous Her-2/neu expression to be more common in mucinous type (38.5 %) while cytoplasmic Her-2/neu expression to be more frequent in non mucinous type (42.7 %) of colorectal cancer (p-value = 0.024). We observed a significant association between percentage of cells stained & tumor type, with score 3+ maximum in non mucinous type of colorectal cancer (p-value = 0.006). CONCLUSION: Her2/neu is considerably expressed in colorectal adenocarcinoma in Pakistani population. Our findings indicate a significant strong association of cytoplasmic Her-2/neu expression with low grades and membranous Her-2/neu expression with high grades of colorectal cancer. These findings add to the body of information & may help in conducting clinical trials in future to explore its therapeutic significance as well.

Multisystem Inflammatory Syndrome in Neonates Associated with COVID-19 in Neonatal ICU of a Tertiary Care Hospital.

OBJECTIVE: Neonatal multisystem inflammatory syndrome (MIS-N) is a unique disease of neonates described in several case reports from all over the world with a myriad of presentations and the emergence of new cases. STUDY DESIGN: Retrospective case series. Place and Duration of the Study: Department of Paediatrics, Fazaia Medical College, Pakistan Air Force Hospital, Islamabad, Pakistan, from December 2021 to November 2022. METHODOLOGY: The study was conducted on neonates who were managed as MIS-N in the neonatal ICU. Data were collected and analysed on SPSS version 24. RESULTS: Patients in this study ranged from newborns to 13 days of age with a mean age of 3.27 ± 4.29 days and average gestational age of 35.18 ± 3.67 weeks. Among these neonates, 7 (63.6%) had bleeding diathesis, 11 (100%) had seizures, 8 (72.2%) presented with haemodynamic instability and shock, and 7 (63.3%) had signs of heart failure. All neonates (100%) had markedly raised SARS-CoV2 IgG antibodies, CRP, ferritin, D-dimers, interleukin 6, procalcitonin, 10 (90.9%) had hypoalbuminemia, and 7 (63.3%) had deranged coagulation profile. Cardiac involvement was seen in all neonates (100%) with raised proBNP and myocardial dysfunction on echocardiography. Pulmonary hypertension was present in 6 (54.4%) neonates. High mortality was observed at 6 (54.5%) among which 4 (66.6%) were premature neonates. CONCLUSION: MIS-N is a new disease entity which is still under research. There is a high propensity for cardiovascular system involvement and higher mortality among preterm neonates. KEY WORDS: Neonatal multisystem inflammatory syndrome (MIS-N), Multisystem inflammatory syndrome in children (MIS-C), SARS-CoV2 infection, SARS-CoV2 spike protein, SARS-CoV2 IgG antibodies.

Role of Alanine Transaminase and Transient Elastography in Categorising Nonalcoholic Fatty Liver Disease Subgroups.

OBJECTIVE: To investigate the association of alanine transaminase (ALT) with transient elastography grades to define various nonalcoholic fatty liver disease (NAFLD) groups for disease status. STUDY DESIGN: Cross-sectional, descriptive study. Place and Duration of the Study: Gastroenterology Outpatient Clinic, Ziauddin Hospital, from January to December 2022. METHODOLOGY: This study included 194 NAFLD patients. Demographic data, body mass index, enzymes, and transient elastography (TE) findings were recorded. NAFLD patients were categorised as nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), steatofibrosis (significant fibrosis F2-F3 with normal ALT), and cirrhosis using TE grades. RESULTS: The median age of the patients was 44 [IQR 18.25] years; 146 (75.3%) were males. Out of 194 NAFLD patients, 21 (10.8%) were NAFL, 116 (59.8%) were NASH, 14 (7.2%) showed steatofibrosis, and 43 (22.2%) were cirrhotic. On transient elastography, the majority were with S3 steatosis (n=107, 55.2%) and 59 (30.2%) had F0-F1 fibrosis. There was a statistically significant difference in the mean rank of age, ALT, AST, and GGT levels within 4 groups of NAFLD (p <0.001). Most of the patients with all the stages of fibrosis had increased ALT levels (p=0.034). CONCLUSION: This study concluded that a combination of ALT levels and transient elastography findings could be considered for differentiating uncomplicated steatosis from NASH, steatofibrosis, and cirrhosis, hence limiting the use of liver biopsy. This may prove a reliable way to measure the severity of the disease. KEY WORDS: Nonalcoholic fatty liver disease, Cirrhosis, Transient elastography.

Adoption of Digital Pathology in Developing Countries: From Benefits to Challenges.

Digital pathology and the use of artificial intelligence constitute undisputedly the future of modern pathology. The outcomes and benefits of the whole slide imaging are beyond the scope of traditional microscopy, which the pathologists were using for decades. COVID-19 pandemic has further highlighted the importance of digital pathology as it offers the pathologists to work from their place of comfort and bridges the gap of physical barriers. In addition to the many advantages, there are certain limitations and challenges, which have to be overcomed particularly in the developing world. The major issue is the cost of scanners and technical support and training of staff. However, despite all these problems and challenges that exist, these can be resolved with the passage of time, where the role of world leader organisations will be of great importance in resolving these challenges. Key Words: Digital pathology, Artificial intelligence, Whole slide imaging.

Cardiovascular Sequelae and Genetics of Familial Mediterranean Fever: A Literature Review.

INTRODUCTION: Familial Mediterranean fever (FMF) is an autoinflammatory fever syndrome distinguished by recurrent attacks of spontaneous peritonitis, pleuritis, fever, and arthritis. It is specifically seen in the ethnic groups of Mediterranean origin, but sporadic cases have been reported in Eastern Europe and America due to migrations. There is a number of cardiac manifestations associated with FMF. METHODS: Using PubMed as the search engine, the literature search was done for articles published between 1958 and 2020. To summarize the body of available evidence, a scoping review was carried out to find relevant articles and case reports in patients of FMF with cardiovascular manifestations. RESULTS: In the literature, there is a number of mechanisms explaining the cause of cardiac involvement in FMF, including the subclinical inflammation and secondary (AA) amyloid deposition in the vessels and the myocardium. There is a variable and often spurious course of these manifestations and it can be associated with a poor prognosis such as an acute myocardial infarction. In FMF patients, polyarteritis nodosa and Henoch-Schönlein purpura are seen more significantly as compared to the general population with increased frequency of mutations in Mediterranean fever (MEFV) gene. Through unclear mechanisms, Behçet's disease is associated with MEFV gene mutations and shares vascular manifestations with FMF. There is an interplay of IL-1 and MEFV gene, which impart an important role in inflammatory attacks of FMF. There is an intima-media thickening of blood vessels AA to persistent inflammation which can lead to atherosclerotic plaque formation resulting in atherosclerotic cardiovascular disease. CONCLUSION: FMF and its associated cardiovascular diseases are interlinked to 2 main mechanisms: subclinical atherosclerosis and amyloid deposition, and colchicine is the primary treatment of patients with FMF which shows the regression of amyloid deposits and prevents cardiovascular sequelae.

Coronary Artery Calcium Score: Assessment of SYNTAX Score and Prediction of Coronary Artery Disease.

Background With the advent of modern imaging technologies, non-invasive assessment of the coronary system is not only possible but its complexity and plaque burden can be quantified. This study aims to determine whether calcium score on computed tomography coronary angiography (CTCA) can be associated with the complexity of coronary artery disease (CAD), which is determined by the SYNTAX score on coronary angiography, as well as to determine which cut-off value of coronary artery calcium (CAC) score can predict severe CAD in our population. Methodology This was a cross-sectional study conducted at the Rawalpindi Institute of Cardiology, Pakistan from January 2019 to March 2020. The calcium score of all patients with low-to-intermediate pretest probability of CAD was calculated on CTCA. All patients who had significant disease on CTCA were subjected to conventional coronary angiography and SYNTAX score was calculated, which was later used to determine the association between calcium and SYNTAX score. Results A total of 90 patients were included in the study. CAC and SYNTAX score were found to be positively correlated (Pearson coefficient [r] = 0.354; p = 0.001). The total CAC score with a cut-off value of 212 recognized patients with the SYNTAX score of >27. The sensitivity was 66.7% and specificity was 70.5% with an area under the curve of 0.743. The mean calcium score of patients in our study group was 223, with the maximum score of 1,216 and the minimum score of zero. Conclusion A CAC score greater than 212 is associated with a high SYNTAX score indicating complex disease. Only age is an independent predictor of calcium score.

Gastric adenocarcinoma expressing human epidermal growth factor receptor in South Asian population.

BACKGROUND/AIM: Gastric cancer is the third leading cause of cancer mortality worldwide. Human epidermal growth factor (Her-2/neu) has shown strong therapeutic implication in breast cancer. Although the prevalence of Her-2/neu over-expression in gastric cancer has been reported across the world, it is still unknown from South Asia. The aim of this study is to evaluate Her-2/neu expression in gastric adenocarcinomas and to correlate with various clinicopathological variables. PATIENTS AND METHODS: A total of 95 consecutive patients undergoing endoscopic biopsy or gastrectomy were recruited in this study. Clinicopathological parameters of all patients were recorded and hematoxylin and eosin (H and E) staining was performed. Over-expression of Her-2/neu was investigated by immunohistochemistry using α-Her-2 antibody. To quantify Her-2/neu over-expression, the Hofmann validation scoring system was used and further its association was seen with age, gender, histopathological type, grade, and stage of the tumor. Data were entered and analyzed using SPSS version 21. A P value of <0.05 was considered as significant. RESULTS: Overall, 21 (22.1%) cases were positive for Her-2/neu overexpression from the total of 95 gastric adenocarcinomas. Her-2/neu was significantly expressed in low-grade gastric cancer (grade I = 50%, grade II = 34.5%, grade III = 14.5%; P = 0.030). Although there was insignificant difference between Her-2/neu over expression and other variables, Her-2/neu score 3+ was predominantly seen in females, age >60 years, Laurens intestinal type, and IIIC stage tumors. CONCLUSION: Her-2/neu is over-expressed in a limited group of gastric cancer patients in our population and indicates a significant strong association with low grades of gastric cancer.