Systematic review of cholangiocarcinoma in Africa: epidemiology, management, and clinical outcomes.

BACKGROUND: The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. METHODS: We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant. RESULTS: A total of 201 citations were identified from the four databases. After excluding duplicates, 133 full texts were reviewed for eligibility, and 11 studies were included. The 11 studies are reported from 4 countries only: 8 are from North Africa (Egypt 6 and Tunisia 2), and 3 in Sub-Saharan Africa (2 in South Africa, 1 in Nigeria). Ten studies reported management and outcomes, while one study reported epidemiology and risk factors. Median age for cholangiocarcinoma ranged between 52 and 61 years. Despite the proportion with cholangiocarcinoma being higher among males than females in Egypt, this gender disparity could not be demonstrated in other African countries. Chemotherapy is mainly used for palliative care. Surgical interventions are curative and prevent cancer progression. Statistical analyses were performed with Stata 15.1. CONCLUSION: The known global major risk factors such as primary sclerosing cholangitis, Clonorchis sinensis and Opisthorchis viverrini infestation are rare. Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies. Surgical intervention was described in at least 6 studies as a curative modality of treatment. Diagnostic capabilities such as radiographic imaging and endoscopic are lacking across the continent which most likely plays a role in accurate diagnosis.

How Would You Manage This Patient With Nonvariceal Upper Gastrointestinal Bleeding? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Nonvariceal upper gastrointestinal bleeding is common, morbid, and potentially fatal. Cornerstones of inpatient management include fluid resuscitation; blood transfusion; endoscopy; and initiation of proton-pump inhibitor therapy, which continues in an individualized manner based on risk factors for recurrent bleeding in the outpatient setting. The International Consensus Group released guidelines on the management of nonvariceal upper gastrointestinal bleeding in 2019. These guidelines provide a helpful, evidence-based roadmap for management of gastrointestinal bleeding but leave certain management details to the discretion of the treating physician. Here, 2 gastroenterologists consider the care of a patient with nonvariceal upper gastrointestinal bleeding from a peptic ulcer, specifically debating approaches to blood transfusion and endoscopy timing in the hospital, as well as the recommended duration of proton-pump inhibitor therapy after discharge.

Endoscopic management and clinical outcomes of obstructive jaundice.

BACKGROUND: This study aimed at evaluating the endoscopic management and clinical outcomes in patients with obstructive jaundice undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) within a newly established apprenticeship teaching model at an academic centre in a resource-limited setting. MATERIALS AND METHODS: We employed an apprenticeship-style model of ERCP training with graded responsibility, multidisciplinary group feedback and short-interval repetition. We collected sociodemographic and clinicopathologic data on consecutive patients who underwent ERCP from March 2018 to February 2020. RESULTS: A total of 177 patients were referred, of which 146 patients had an ERCP performed for obstructive jaundice and 31 excluded during the study period. The median age was 55 years, age range from 8 to 83 years. The most common referral diagnosis was pancreatic head cancer 56/146 (38.1%), followed by choledocholithiasis 29/146 (19.7%), cholangiocarcinoma 22/146 (15.0%) and gall bladder cancer 11/146 (7.5%). In all, 102 patients had a malignant indication for ERCP. The cannulation rate was 92%. The most common site for malignant biliary obstruction was proximal bile stricture in 31/102 (30.4%), followed by distal bile strictures in 30/102 (28.4%), periampullary cancer 20/102 (19.6%) and mid bile duct stricture in 9/102 (8.8%). The common benign obstructive etiology includes choledocholithiasis in 33/44 (75%) and mid duct obstruction from post-cholecystectomy bile duct injury in 3/44 (2.9%) while 2/44 (2.0%) patients had choledochal cyst. Overall complications were post-ERCP pancreatitis (8/146 patients), cholangitis (3/146 patients), stent migration and post-sphincterotomy bleeding (one patient each). Peri-procedural mortality was 5/146 (3.4%). CONCLUSION: ERCP is an effective and safe method of treatment of patients with benign and malignant biliary obstruction. The low morbidity and mortality and its immediate therapeutic benefits, together with the short duration of hospitalization, indicate that this procedure is an important asset in the management of such patients.

Systematic review and meta-analysis of esophageal cancer in Africa: Epidemiology, risk factors, management and outcomes.

BACKGROUND: Esophageal cancer (EC) is associated with a poor prognosis, particularly so in Africa where an alarmingly high mortality to incidence ratio prevails for this disease. AIM: To provide further understanding of EC in the context of the unique cultural and genetic diversity, and socio-economic challenges faced on the African continent. METHODS: We performed a systematic review of studies from Africa to obtain data on epidemiology, risk factors, management and outcomes of EC. A non-systematic review was used to obtain incidence data from the International Agency for Research on Cancer, and the Cancer in Sub-Saharan reports. We searched EMBASE, PubMed, Web of Science, and Cochrane Central from inception to March 2019 and reviewed the list of articles retrieved. Random effects meta-analyses were used to assess heterogeneity between studies and to obtain odds ratio (OR) of the associations between EC and risk factors; and incidence rate ratios for EC between sexes with their respective 95% confidence intervals (CI). RESULTS: The incidence of EC is higher in males than females, except in North Africa where it is similar for both sexes. The highest age-standardized rate is from Malawi (30.3 and 19.4 cases/year/100000 population for males and females, respectively) followed by Kenya (28.7 cases/year/100000 population for both sexes). The incidence of EC rises sharply after the age of 40 years and reaches a peak at 75 years old. Meta-analysis shows a strong association with tobacco (OR 3.15, 95%CI: 2.83-3.50). There was significant heterogeneity between studies on alcohol consumption (OR 2.28, 95%CI: 1.94-2.65) and on low socioeconomic status (OR 139, 95%CI: 1.25-1.54) as risk factors, but these could also contribute to increasing the incidence of EC. The best treatment outcomes were with esophagectomy with survival rates of 76.6% at 3 years, and chemo-radiotherapy with an overall combined survival time of 267.50 d. CONCLUSION: Africa has high incidence and mortality rates of EC, with preventable and non-modifiable risk factors. Men in this setting are at increased risk due to their higher prevalence of tobacco and alcohol consumption. Management requires a multidisciplinary approach, and survival is significantly improved in the setting of esophagectomy and chemoradiation therapy.

Lumen apposing metal stents for pancreatic fluid collections: Recognition and management of complications.

For patients recovering from acute pancreatitis, the development of a pancreatic fluid collection (PFC) predicts a more complex course of recovery, and introduces difficult management decisions with regard to when, whether, and how the collection should be drained. Most PFCs resolve spontaneously and drainage is indicated only in pseudocysts and walled-off pancreatic necrosis when the collections are causing symptoms and/or local complications such as biliary obstruction. Historical approaches to PFC drainage have included surgical (open or laparoscopic cystgastrostomy or pancreatic debridement), and the placement of percutaneous drains. Endoscopic drainage techniques have emerged in the last several years as the preferred approach for most patients, when local expertise is available. Lumen-apposing metal stents (LAMS) have recently been developed as a tool to facilitate potentially safer and easier endoscopic drainage of pancreatic fluid collections, and less commonly, for other indications, such as gallbladder drainage. Physicians considering LAMS placement must be aware of the complications most commonly associated with LAMS including bleeding, migration, buried stent, stent occlusion, and perforation. Because of the patient complexity associated with severe pancreatitis, management of pancreatic fluid collections can be a complex and multidisciplinary endeavor. Successful and safe use of LAMS for patients with pancreatic fluid collections requires that the endoscopist have a full understanding of the potential complications of LAMS techniques, including how to recognize and manage expected complications.

The Clinical Implications of Fatty Pancreas: A Concise Review.

Fatty pancreas is a newly recognized condition which is poorly investigated until today as compared to nonalcoholic fatty liver disease. It is characterized by pancreatic fat accumulation and subsequent development of pancreatic and metabolic complications. Association of fatty pancreas have been described with type 2 diabetes mellitus, acute and chronic pancreatitis and even pancreatic carcinoma. In this review article, we provide an update on clinical implications, pathogenesis, diagnosis, treatment and outcomes.

ASA Classification Pre-Endoscopic Procedures: A Retrospective Analysis on the Accuracy of Gastroenterologists.

OBJECTIVES: Before an endoscopic procedure, an evaluation to assess the risk of sedation is performed by the gastroenterologist. To risk stratify based on medical problems, the American Society of Anesthesiologists (ASA) classification scores are used routinely in the preprocedure evaluation. The objective of our study was to evaluate among physicians the ASA score accuracy pre-endoscopic procedures. METHODS: At a single tertiary-care center an institutional review board-approved retrospective study was performed. Upper endoscopies performed from May 2012 through August 2013 were reviewed; data were collected and recorded. Statistical analysis was performed using descriptive statistics and linear weighted kappa analysis for agreement (≤0.20 is poor agreement, 0.21-0.40 is fair, 0.41-0.60 is moderate, 0.61-0.80 is good, and 0.81-1.00 is very good). RESULTS: The mean ASA scores by the gastroenterologist compared with the anesthesiologist were 2.28 ± 0.56 and 2.78 ± 0.60, respectively, with only fair agreement (weighted kappa index 0.223, 95% confidence interval [CI] 0.113-0.333; 48% agreement). The mean ASA scores for gastroenterologists compared with other gastroenterologists were 2.26 ± 0.5 and 2.26 ± 0.44, respectively, with poor agreement (weighted kappa index 0.200, 95% CI 0.108-0.389; 68% agreement). Agreement on ASA scores was only moderate between the gastroenterologist and himself or herself (weighted kappa index 0.464, 95% CI 0.183-0.745; 75% agreement). CONCLUSIONS: Gastroenterologists performing preprocedure assessments of ASA scores have fair agreement with anesthesiologists, poor agreement with other gastroenterologists, and only moderate agreement with themselves. Given this level of inaccuracy, it appears that the ASA score pre-endoscopy is of limited significance.

Pancreatic Cancer Survival Outcomes at a Tertiary Medical Center Based on Sex and Geographic Location.

OBJECTIVES: To describe the survival outcomes of patients with histologically proven primary pancreatic cancer based on geographic location and sex. METHODS: We conducted a retrospective review of medical records from 2009 through 2013 of patients with pancreatic cancer using International Classification of Diseases, Ninth Revision code 157.9 and International Statistical Classification of Diseases, 10th Revision code C 25.9. The variables extracted included demographics, date of diagnosis, mode of diagnosis, duration, treatment methods, family history, history of chronic pancreatitis, and diabetes mellitus. ZIP codes were used to identify the geographic location of each subject, and rural urban commuting area codes were used to further classify the areas as metropolitan, micropolitan, small town, and rural. Population sizes were classified as metropolitan >50,000, micropolitan 10,000 to 49,999, small town 2500 to 9999, and rural <2500. Descriptive analysis and Kaplan-Meier survival for survival outcomes were performed with statistical significance identified as P < 0.05. RESULTS: A total of 400 medical charts were extracted for review, 301 of which belonged to patients with primary pancreatic cancer. Of the 301 cases, we identified 175 men (58%), 125 women (41%), and 1 missing sex data. There were 280 whites (95%), 8 African Americans (2%), 2 Asian Americans (0.64%), 1 Hispanic American (0.34%) and 1 Native American (0.34%), with a mean age of 63.2 ± 12.6 years. Based on geography, there were 34%, 27%, 20%, and 19% in rural areas, metropolitans, small towns, and micropolitans, respectively. No statistically significant difference was noted in sex on survival outcomes (P = 0.85) or geography (P = 0.62). Additional analysis revealed no statistical significant difference between sexes when stratifying by location (P = 0.96). CONCLUSIONS: There is no difference in survival outcomes of patients with primary pancreatic cancer based on sex or geographic location. Our survival outcomes differ from the national survival outcomes, which reveal that mortality in men is higher than it is in women.

Esophageal squamous cell cancer in a highly endemic region.

AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α). METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine. RESULTS: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014). CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.

HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case-control study.

There is emerging evidence that esophageal cancer occurs in younger adults in sub-Saharan Africa than in Europe or North America. The burden of human immunodeficiency virus (HIV) is also high in this region. We postulated that HIV and human papillomavirus (HPV) infections might contribute to esophageal squamous cell carcinoma (OSCC) risk. This was a case-control study based at the University Teaching Hospital in Lusaka, Zambia. Cases were patients with confirmed OSCC and controls had completely normal upper endoscopic evaluations. A total of 222 patients were included to analyze the influence of HIV infection; of these, 100 patients were used to analyze the influence of HPV infection, alcohol, smoking, and exposure to wood smoke. The presence of HIV infection was determined using antibody kits, and HPV infection was detected by polymerase chain reaction. HIV infection on its own conferred increased risk of developing OSCC (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.0-5.1; P = 0.03). The OR was stronger when only people under 60 years were included (OR 4.3; 95% CI 1.5-13.2; P = 0.003). Cooking with charcoal or firewood, and cigarette smoking, both increased the odds of developing OSCC ([OR 3.5; 95% CI 1.4-9.3; P = 0.004] and [OR 9.1; 95% CI 3.0-30.4; P < 0.001], respectively). There was no significant difference in HPV detection or alcohol intake between cases and controls. We conclude that HIV infection and exposure to domestic and cigarette smoke are risk factors for OSCC, and HPV immunization unlikely to reduce OSCC incidence in Zambia.

Airway assessment of patients undergoing endoscopic procedures.

OBJECTIVES: In advance of endoscopic procedures, an evaluation to assess the risk of sedation is performed by the gastroenterologist. Based on regulations, gastroenterologists are required to perform an airway assessment. At this time, data supporting this regulation are limited; therefore, we evaluated airway assessment accuracy by gastroenterologists before endoscopic procedures. METHODS: A retrospective, single tertiary care center study was performed from May 2012 through August 2013. Patients who underwent an endoscopy or colonoscopy performed at the University of Missouri-Columbia with documented Mallampati scores were included in the analysis. Three primary cohorts of patients were included in our study: gastroenterologist versus anesthesiologist, gastroenterologist versus other gastroenterologists, and gastroenterologists versus themselves. Data were collected and recorded for patient age, body mass index, and Mallampati score. Statistical analysis was performed using descriptive statistics and linear weighted kappa analysis for agreement. RESULTS: For gastroenterologists versus anesthesiologists and versus other gastroenterologists, the agreement on Mallampati scores was poor (weighted kappa index 0.103, 95% confidence interval [CI] -0.0126 to 0.219; percentage of agreement 42% and 0.120, 95% CI -0.0211 to 0.260; percentage of agreement 46%, respectively). For gastroenterologists versus themselves for the same patient, the agreement on Mallampati scores was only moderate (weighted kappa index 0.420, 95% CI 0.119-0.722; percentage of agreement 65%). CONCLUSIONS: Gastroenterologists performing a preprocedure assessment using Mallampati scores have poor agreement with anesthesiologists and colleagues and only moderate agreement with themselves.

Gastric cancer in Africa: current management and outcomes.

Gastric cancer is the fourth most common cancer and second most common cause of cancer death worldwide. Globally, gastric cancer poses a significant public health burden - both economically and socially. In 2008, the economic burden from premature cancer deaths and disability was $895 billion and gastric cancer was the second highest cancer responsible for healthy life lost. With the expected increase in cancer deaths and non-communicable diseases, these costs are expected to rise and impact patient care. World Health Organization, estimates a 15% increase in non-communicable disease worldwide, with more than 20% increase occurring in Africa between 2010 and 2020. Mali, West Africa, is ranked 15(th) highest incidence of gastric cancer worldwide at a rate of 20.3/100000, yet very scarce published data evaluating etiology, prevention or management exist. It is understood that risk factors of gastric cancer are multifactorial and include infectious agents (Helicobacter pylori, Epstein-Barr virus), genetic, dietary, and environmental factors (alcohol, smoking). Interestingly, African patients with gastric cancer are younger, in their 3(rd)-4(th) decade, and present at a late stage of the disease. There is sparse data regarding gastric cancer in Africa due to lack of data collection and under-reporting, which impacts incidence and mortality rates. Currently, GLOBOCAN, an International Agency for Research on Cancer resource, is the most comprehensive available resource allowing comparison between nations. In resource limited settings, with already restricted healthcare funding, data is needed to establish programs in Africa that increase gastric cancer awareness, curtail the economic burden, and improve patient management and survival outcomes.

Characteristics of gastric cancer in Asia.

Gastric cancer (GC) is the fourth most common cancer in the world with more than 70% of cases occur in the developing world. More than 50% of cases occur in Eastern Asia. GC is the second leading cause of cancer death in both sexes worldwide. In Asia, GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer. Although the incidence and mortality rates are slowly declining in many countries of Asia, GC still remains a significant public health problem. The incidence and mortality varies according to the geographic area in Asia. These variations are closely related to the prevalence of GC risk factors; especially Helicobacter pylori (H. pylori) and its molecular virulent characteristics. The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H. pylori seroprevalence rates leading to a reduction in the GC incidence. However, GC remains a significant public health and an economic burden in Asia. There has been no recent systemic review of GC incidence, mortality, and H. pylori molecular epidemiology in Asia. The aim of this report is to review the GC incidence, mortality, and linkage to H. pylori in Asia.

Gastric cancer in Zambian adults: a prospective case-control study that assessed dietary intake and antioxidant status by using urinary isoprostane excretion.

BACKGROUND: Gastric cancer is increasingly recognized in Zambia. Although nutritional factors contribute to gastric cancer risk, their effect in Zambia is unknown. OBJECTIVE: The objective was to investigate the association between intake of dietary antioxidants, urinary 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress, and gastric cancer. DESIGN: This was a case-control study at the University Teaching Hospital in Zambia. Gastric cancer cases were compared with age- and sex-matched controls. Urine 8-iso PGF2α was measured primarily by ELISA, and by gas chromatography-mass spectrometry in a subset, expressed as a ratio to creatinine. Blood was collected for Helicobacter pylori, HIV serology, gastrin-17, and pepsinogen 1 and 2 concentrations. Clinical and dietary data were collected by using questionnaires. Food items were broadly classified into 7 major categories (fruit, vegetables, fish, meat, insects, cereals, and starches). RESULTS: Fifty cases with gastric cancer (mean age: 61 y; n = 31 males) and 90 controls (mean age: 54 y; n = 41 males) were enrolled. Median urinary 8-iso PGF2α excretion was higher in cases (0.014; IQR: 0.008-0.021) than in controls (0.011; IQR: 0.006-0.018; P = 0.039). On univariate analysis, habitual fruit intake was lower in cases than in controls during the dry season (P = 0.02). On multivariate analysis, smoking (OR: 7.22; IQR: 1.38-37.9) and gastric atrophy (OR: 2.43; IQR: 1.12-5.13) were independently associated with cancer, and higher fruit intake was protective (OR: 0.44; IQR: 0.20-0.95). Isoprostane excretion was inversely correlated with total fruit intake (ρ = -0.23; n = 140; P = 0.006). CONCLUSION: Urinary 8-iso PGF2α excretion was associated with the risk of gastric cancer, as were smoking and gastric atrophy, but increased fruit intake conferred protection. This trial was registered at www.pactr.org as ISRCTN52971746.

Gastric cancer in Africa: what do we know about incidence and risk factors?

Gastric cancer is a major contributor to mortality worldwide, yet its incidence varies widely around the world in a way which our current understanding of aetiology cannot fully explain. Incidence data from Africa are weak, reflecting poor diagnostic resources, but there are firm data on intestinal metaplasia and gastric atrophy which are important steps in the carcinogenesis pathway. The available registry data suggest that incidence is unlikely to be dramatically different from Europe or North America. Helicobacter pylori infection is an important permissive factor in the development of cancer, but H. pylori seroprevalence is high all over Africa and cannot clearly be correlated with cancer. However, there is evidence that specific bacterial virulence genes, particularly vacA and iceA allele1, do contribute to cancer risk. Intestinal metaplasia and gastric atrophy have been the focus of twelve studies and are common in Africa. Epstein-Barr virus, which causes 10% of cancer worldwide, is the focus of only one African study. Work in other continents demonstrates that other risk factors apply only to one or other of the two major histological types, intestinal and diffuse. Diet, smoking, alcohol and salt intake predispose to the intestinal type of cancer, but genetic factors predispose to the diffuse type. There is a pressing need for information on the histological types occurring in Africa, and their associated risk factors. Most urgently, information on dietary predisposition to cancer is required to inform public health policy with respect to the demographic transition (urbanisation and lifestyle changes) which is occurring all over the continent.