Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations.

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Diagnostic Differentiation between Pancreatitis and Pancreatic Cancer: A Scoping Review.

Pancreatitis, encompassing acute and chronic forms, and pancreatic cancer pose significant challenges to the exocrine tissue of the pancreas. Recurrence rates and complications following acute pancreatitis episodes can lead to long-term risks, including diabetes mellitus. Chronic pancreatitis can develop in approximately 15% of cases, regardless of the initial episode's severity. Alcohol-induced pancreatitis, idiopathic causes, cigarette smoking, and hereditary pancreatitis contribute to the progression to chronic pancreatitis. Chronic pancreatitis is associated with an increased risk of pancreatic cancer, with older age at onset and smoking identified as risk factors. This scoping review aims to synthesise recent publications (2017-2022) on the diagnostic differentiation between pancreatitis and pancreatic cancer while identifying knowledge gaps in the field. The review focuses on biomarkers and imaging techniques in individuals with pancreatitis and pancreatic cancer. Promising biomarkers such as faecal elastase-1 and specific chemokines offer non-invasive ways to assess pancreatic insufficiency and detect early biomarkers for chronic pancreatitis. Imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), and positron emission tomography (PET), aid in differentiating between chronic pancreatitis and pancreatic cancer. However, accurately distinguishing between the two conditions remains a challenge, particularly when a mass is present in the head of the pancreas. Several knowledge gaps persist despite advancements in understanding the association between pancreatitis and pancreatic cancer, including the correlation between histopathological grading systems, non-invasive imaging techniques, and biomarkers in chronic pancreatitis to determine the risk of progression to pancreatic cancer, as well as differentiating between the two conditions. Further research is necessary to enhance our understanding of these aspects, which can ultimately improve the diagnosis and management of pancreatitis and pancreatic cancer.

Laparoscopic splenectomy for immune thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy has become the preferred method of splenectomy for refractory immune thrombocytopenic purpura (ITP). We present our experience with the introduction of laparoscopic splenectomy for ITP. METHODS: Over a 2-year period, retrospective and prospective data were collected on all patients undergoing laparoscopic splenectomy for ITP at our institution. We analysed demographic data, peri-operative courses, platelet count responses and complications. RESULTS: Twenty laparoscopic splenectomies were performed. There were 2 conversions to an open procedure. The average operating time was 100 minutes (range 30 - 170 minutes), and mean blood loss was 106 ml (range 50 - 200 ml). There were no deaths or major complications. The mean follow-up period was 7 months. Ninety-five per cent of patients had a complete or partial response to splenectomy. CONCLUSION: Laparoscopic splenectomy can be introduced safely with an acceptable conversion rate, and is an effective treatment for ITP on short-term follow-up.

Processing and Analysis of Tissue Samples from Esophageal Cancer Patients in an African Setting.

Although infectious diseases continue to present a major health care problem in Africa, the incidence of cancer is increasing rapidly on the African continent and this merits an increased investment in cancer research in low to medium resource settings. Esophageal squamous cell carcinoma (ESCC) has a high incidence in Eastern and Southern Africa, with late clinical presentation and a very poor prognosis. There is limited research on the molecular pathology of this cancer in Africa, partly as a result of a lack of infrastructure for biobanking and sample processing in many African countries. The aim of this study was to establish a practical and robust workflow to collect, store, and process esophageal cancer samples such that both the tissue architecture and quality of the samples would be preserved and suitable for future genomic research. We developed a workflow that allows storage of fresh biopsy tissue in sterile Eppendorf tubes containing RNAlater, an efficient RNAse inhibitor. We collected 142 ESCC biopsy samples and showed that storage in RNAlater for up to 18 months did not alter tissue morphology, thus allowing histologic assessment by experienced pathologists and determination of tumor content in each biopsied sample. DNA and RNA extracted from tissue samples was assessed for purity, molecular size, and yield. The quantity and quality of nucleic acids obtained were suitable for genomic applications, and whole-exome sequencing of DNA from tumor tissues produced sequence data with a high proportion of both usable reads and correct base calling. We conclude that this workflow may be applicable to a wide range of malignancies for future genomic research in low-resource settings.

Gender Differences in Oesophageal Squamous Cell Carcinoma in a South African Tertiary Hospital.

(1) Oesophageal squamous cell carcinoma is common in Africa and has a male preponderance. The gender-based differences in clinical presentation and risk factor exposure are poorly studied in the African context. Our aim was to compare males and females with this disease. We analyzed the differences in clinical features and risk factor exposure between males and females with oesophageal cancer. (2) Data from patients presenting to a tertiary hospital in South Africa with oesophageal squamous cell carcinoma were analyzed. Data collected included patient demographics, clinical presentation, pathology and risk factor exposure. (3) Three hundred and sixty three patients were included in the study. The male to female ratio was 1.4:1. The mean age was 66 years for females and 61 years for males (p < 0.0001). A significantly larger percentage of males were underweight compared to females (60% vs. 32%, p < 0.001). There were no differences between the genders with regards to performance status, dysphagia grade and duration and tumor length, location and degree of differentiation. There were significant differences between risk factor exposure between the two genders. Smoking and alcohol consumption was an association in more than 70% of males but in less than 10% of females There was no difference survival. (4) Female patients with oesophageal squamous cell carcinoma (OSCC) are older and have a higher body mass index (BMI) than their male counterparts. Traditionally purported risk factors of smoking and alcohol consumption are infrequent associations with OSCC in female patients and other environmental risk factors may be more relevant in this gender.

Self-expanding metal stent placement for oesophageal cancer without fluoroscopy is safe and effective.

BACKGROUND: Self-expanding metal stents (SEMS) are widely used to palliate patients with oesophageal cancer. Placement is usually done under endoscopic and fluoroscopic guidance. We have developed an exclusively endoscopic technique to deploy these stents. This article documents the technique and periprocedural experience. PATIENTS AND METHODS: All patients who had SEMS placement for oesophageal cancer at Grey's Hospital, Pietermaritzburg, South Africa, over a 5-year period (2007-2011) were reviewed. Stenting was performed without radiological guidance using the technique documented in this article. At endoscopy, the oesophageal lesion was identified, dilated over a guidewire if necessary, and a partially covered stent was passed over the wire and positioned and deployed under direct vision. Data were captured from completed procedure forms and included demographics, tumour length, the presence of fistulas, stent size and immediate complications. RESULTS: A total of 480 SEMS were inserted, involving 453 patients, of whom 43 required repeat stenting. There were 185 female patients (40.8%) and 268 male patients (59.2%). The mean age was 60 years (range 38 - 101). There were 432 black patients (95.4%), 15 white patients (3.3%) and 6 Indian patients (1.3%). The reasons for palliative stenting were distributed as follows: age>70 years n=95 patients, tumour>8 cm n=142, tracheo-oesophageal fistula (TOF) n=29, and unspecified n=170. One patient refused surgery, and one stent was placed for a post-oesophagectomy leak. Repeat stenting was for stent migration (n=15), tumour overgrowth (n=26) and a blocked stent and a stricture (n=1 each). Complications were recorded in six cases (1.3%): iatrogenic TOF (n=2), false tracts (n=3) and perforation (n=1). All six were nevertheless successfully stented. There was no periprocedural mortality. CONCLUSION: The endoscopic placement technique described is a viable and safe option with a low periprocedural complication rate. It is of particular use in situations of restricted access to fluoroscopic guidance.