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

doi:10.21203/rs.3.rs-1972481/v1

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

https://doi.org/10.21203/rs.3.rs-1972481/v1

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published 11 Mar, 2023

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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.

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. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant.

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.

Cholangiocarcinoma

Epidemiology

Risk factors

Systematic Review

Africa

Cholangiocarcinoma (CCA) is a rare and aggressive cancer that arises from the epithelium of the intrahepatic or the extrahepatic bile ducts. CCA can also arise from hepatic progenitor cells (1). Globally, the incidence of cholangiocarcinoma varies from as high as 113 per 100,000 in Northern Thailand, 5.7/100,000 in Southern Thailand, 2.2/100,000 in UK, 1.1/100,000 in USA and 0.3/100,000 in Israel (2). In both males and females, the incidence rises at age 60 to 70 years, rarely diagnosed before age 40 years, with a higher incidence and mortality in men compared to women (2–4). Little is known of CCA in Africa. Patients with CCA can present with jaundice pruritus, acholic stool and steatorrhea depending on tumor location and stage of presentation, but they can also present with abdominal pain and weight loss. Some patients have their CCAs detected as incidentalomas during cross sectional imaging for abdominal symptoms, or during hepatoma screening in those with underlying cirrhosis. Screening programs exist for detection of gall bladder or biliary cholangiocarcinoma in patients with underlying primary sclerosing cholangitis (PSC) using MRCP and CA19-9 (5). The management of CCA is dependent on anatomical location of tumor, staging and histology (6).

Anatomically CCA are classified as: Intrahepatic cholangiocarcinoma (iCCA) if the tumor is located proximal to the secondary branches of the right and left hepatic ducts, perihilar cholangiocarcinoma (pCCA) if located between the secondary branches of the right and left hepatic ducts and the common hepatic duct proximal to the origin of the cystic duct, and distal cholangiocarcinoma (dCCA) if involving the common bile duct but not the ampulla of Vater (2,7). Surgical resection is curative in early iCCA and if R0 resection is achieved, can give up to 36 months disease specific survival. There is a risk of recurrence in up to 62.2% of patients (8). Surgical resection is also curative in dCCA early stage disease for R0 resection which entails a Whipple’s procedure, although the risk of recurrence is high with 5-year survival of 27%.(9) Surgical resection is the treatment of choice for early stage Bismuth-Corlette pCCA, although liver transplantation is emerging as the preferred treatment option with up to 76% 5-year survival with neoadjuvant chemoradiotherapy (10). Neoadjuvant and adjuvant chemotherapy does improve survival in all types of CCA. Hyperbilirubinemia due to biliary obstruction results in a pro-inflammatory state that negatively impacts the post-operative outcomes (11). Palliative treatments include biliary drainage with Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiography (PTC) and stenting depending on tumour location, can improve jaundice in improve survival in pCCA and dCCA. Many patients present with unresectable or metastatic disease, as such the median survival rate is as low as 3 to 6 months in the USA (12).

Risk factors for developing CCA include occupation, which can be due to chemical exposure, chronic biliary inflammation, chronic hepatic inflammation, and cirrhosis of any cause and congenital and acquired causes of cholestasis leading to biliary inflammation. Nonetheless, risk factors are not identifiable in 50% of cases (2). CCA has been documented in workers at printing companies in Japan exposed to high concentrations of 1,2-dichloropropane (1,2-DCP) and dichloromethane (13). CCA has been shown to develop decades after administration of the radiologic contrast medium thorotrast, that was used for cerebral angiography in the 1950s (14). Autoimmune conditions, especially PSC have been associated with increased risk of cholangiocarcinoma in elderly patients in the USA (15). Heavy infestation by liver flukes Clonorchis sinensis and Opisthorchis viverrini due to eating raw fish is a known cause of CCA in Asian countries where these flukes are endemic, including Korea, China, Taiwan, and Vietnam (16). Other liver flukes Fasciola hepatica and Fasciola gigantica, cause fascioliasis in sheep and cattle, and can infest other herbivores, are a known zoonotic cause of human fasciolasis from eating water cress and drinking water with Lymnaeidae snails, that are intermediate hosts, can cause chronic cholestasis (17). Unlike the Clonorchis sinensis and Opisthorchis viverrini, there is no direct causal like between Fasciola hepatica and Fasciola gigantica, to CCA (17). Chronic intrahepatic cholestasis due to pigment stones can occur to due chronic hemolysis associated with hemolytic conditions such as sickle cell disease, thalassemia and red blood cell enzyme disorders such as G6PD deficiency. Although hepatolithiasis is a known risk factor for CCA, a direct link between hemolytic anemia and CCA has not been established (18). Bacterial infections with Helicobacter species causing chronic cholangitis and cholecystitis have been implicated in the etiological role in biliary cancers.(19) Obesity has been associated with the increased risk of cholangiocarcinoma (20). The use of GLP-1 analogues, used in treatment of diabetes is associated with an increased risk of bile duct and gallbladder disease requiring hospital admission including cholelithiasis, cholecystitis, cholangitis. Over the long term as inflammation and cholestasis are associated with CCA, there is a possibility that use of these medications could pose a risk to development of CCA (21). In a recent review of risk factors for CCA in Eastern and Western countries, choledochal cysts, cirrhosis, choledocholithiasis, hepatitis B virus infection have been found to be associated with CCA (2).

To date, no systematic review or meta-analysis of studies on CCA in Africa has been conducted. We address this gap by conducting a comprehensive systematic review on the epidemiology, management, and outcomes of CCA in Africa.

Search strategy and study identification

We searched PubMed, EMBASE, Web of Science, and CINAHL from inception to November 2019 for primary publications. Searches were limited to human studies conducted in Africa and to English-language publications. The following search terms were used in the four databases: (Cholangiocar* OR cholangio cancer OR cholangio tumo*) AND (epidemiology OR incidence OR prevalence OR risk factor* OR treatment OR management OR outcome*) AND (Africa OR East* Africa OR West Africa OR Southern Africa OR North* Africa OR Algeria* OR Angola* OR Benin OR Botswana OR “Burkina Faso” OR Burundi OR Cameroon* OR "Cabo Verde" OR “Cape Verde” OR “Central African Republic” OR Chad OR Comoros OR Congo OR “Cote d`Ivoire” OR Djibouti OR Egypt* OR “Democratic Republic of Congo” OR “Equatorial Guinea” OR Eritrea* OR “Eswatini” OR Swaziland OR Ethiopia* OR Gabon* OR Gambia* OR Ghana* OR Guinea OR “Guinea Bissau” OR Kenya* OR Lesotho OR Liberia* OR Libya* OR Madagascar OR Malawi* OR Mali OR Mauritania* OR Mauritius OR Morocco* OR Mozambique OR Namibia* OR Niger OR Nigeria* OR Rwanda* OR “Sao Tome and Principe” OR Senegal* OR Seychelle* OR “Sierra Leone” OR Somali* OR “South African” OR “South Africa” OR “South African” OR Sudan* OR “North Sudan” OR “South Sudan” OR Tanzania* OR Togo* OR Tunisia* OR Uganda* OR Zambia* OR Zimbabwe*). Citation lists of retrieved articles were manually screened to ensure sensitivity of the search strategy.

Study selection

Studies were included if they (i) provided a quantitative measure of disease occurrence (prevalence, incidence) or mortality (survival, mortality rate), and (ii) had a quantitative association between risk factors and CCA. Studies were excluded if any of these criteria were not met. Titles and abstracts of all articles identified were screened independently by the authors. Full texts were reviewed by the authors, and consensus reached on potential eligibility.

Data extraction

The following information was extracted from each eligible study from the database search: first author; year of publication; country of study; study population; study design; patient characteristics; management and outcomes.

Quality assessment

A modified quality assessment of the final papers included in this systematic review was adapted from the quality assessment tool for systematic reviews of observational studies (QATSO) (22).

Items included in the QATSO tool were: (1) External validity (representativeness of sampling procedures used in each study); (2) Response rate, which we modified to include three categories (> 80%, 60%-80%, < 60% or not reported); (3) Validity of measurement methods and bias in the measurement of the outcomes; and (4) Control for important confounders. The final score was the mean across the items. Studies achieving a final mean score of 60% or above were considered adequate in this review (22).

Statistical analysis

Statistical analyses were performed with Stata 15.1 (Stata Corporation, College Station, TX). Descriptive data were expressed as numbers with proportions. We used the χ2 test to compare proportions. P values < 0.05 were considered significant.

Results of the Search Strategy

A total of 201 citations were identified from the four databases. After excluding duplicates (n = 33), non-human citations (n = 20), non-English citations (n = 3), and articles that could not be accessed (n = 12), 133 full texts were reviewed for eligibility, and 11 studies were included (Fig. 1).

Description of the Studies and CCA Patients

Of the 11 studies, one reported on the epidemiology and risk factors for CCA and was conducted in Nigeria, (23) and 10 studies reported on management and outcomes of CCA. These 10 studies also reported on patient characteristics that were included in the epidemiology and risk factor analysis below. Of these 10 studies, two studies were conducted in Tunisia, (24,25) two in South Africa (26,27), and six in Egypt (Table 1) (28–33).

Table 1

Summary of studies from systematic review
Number of studies	Nigeria	South Africa	Tunisia	Egypt
Per country	1	2	2	6
Reporting patient characteristics	1	1	2	4
Reporting on chemotherapy	-	-	2	1
Reporting transhepatic self-expanding metal stents	-	2	-	-
Reporting on preoperative biliary drainage	-	-	-	1
Reporting surgery		-	-	6

The 11 studies had a combined total of 1,125 patients with CCA. The study from Nigeria had 13 patients (23). For the two studies from Tunisia, one had 10 patients (24) and the other had 28 patients (25). For the two studies from South Africa, one had 36 patients (26). and the other had 50 patients (27). For the six studies from Egypt, one had 100 patients (28), two studies reported on the same 243 patients, (29,33) one study had 440 patients (30), another had 46 patients (31), and lastly one study had 159 patients (32).

Study Quality

A qualitative assessment of these 11 studies achieved a final score of 77.3% and thus had adequate quality (Table 2).

Table 2

Quality assessment of the 11 studies included in the systematic review
Quality variable	Quality variable categories	Number of studies (%)
External validity	Non-probability	11/11 (100%)
External validity	Probability	0
Response rate or proportion of patients managed for CCA	Above 80%	11/11 (100%)
	Between 60% and 80%	0
	Not reported	0
Validity of measurement methods and bias in the measurement of cholangiocarcinoma	Histology	7/11 (63.6%))
	Enhanced CT and/or MRCP	1
	Not reported	3
Control for important confounders	Yes	5/11 (45.6%)
Control for important confounders	Not reported	6
Final mean % score (mean across the items)		77.3%

Epidemiology and Risk Factors

The risk factors of CCA in Africa remain unclear, most occurring in absence of known risk factors. In a retrospective study done by Babatunde et al., in Nigeria, 13 histologically confirmed specimen of CCA were identified, of which 7 were from males (53.8%) (23). The other studies that reported on gender in the patient characteristics also showed that more males than females had CCA (25,26,28,29,32,33)

The studies from Egypt showed that among patients with CCA, the proportion of males was statistically significantly higher than females. As shown by the wide 95% confidence intervals, the studies from Nigeria, South Africa, and Tunisia had small sample sizes of patients with CCA, and therefore could not demonstrate the significant gender disparity that exists among patients with CCA (Fig. 2).

In studies that reported on age, the median age for CCA was between 52.5 and 61 years (24–26,29,32)

Management and Outcomes

Chemotherapy

Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies (24,25,31). The chemotherapy was also administered as either neoadjuvant or adjuvant therapy (25). In most cases, the first line chemotherapy used was gemcitabine based (24,25). The combined chemotherapies used include gemcitabine-oxaliplatin (GEMOX), gemcitabine-cisplatin (GEMCIS), and folfirinox (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) regimes. The second line chemotherapy used were capecitabine, irinotecan and paclitaxel.^[21] Adjuvant chemotherapy was mainly gemcitabine based (25).

Percutaneous transhepatic self-expanding metal stents (SEMS)

Only two studies reported the use of percutaneous transhepatic SEMS for palliation of malignant biliary obstruction (26,27) In these patients no surgery was planned as the tumor was beyond the surgical margins. Lawson et.al reported that 40% of the SEMS was placed in a single stage procedure while the rest was a two-stage procedure. The biliary obstruction relief and SEMS placement procedure was successful in all the patients. The type of SEMS used was a Boston Scientific 69 mm x 10 mm Wall stent (27).

Preoperative Biliary Drainage (PBD)

This is a preoperative procedure done to relieve the patient from the jaundice and improve the patient’s general and liver functional state before any definitive surgery. The type of PBD reported in a single study includes percutaneous transhepatic drainage (PTD), and endoscopic retrograde cholangiopancreatography (ERCP) with stent placement (28).

Surgery

This is the only known curative treatment for cholangiocarcinoma. There were six studies in which patients underwent surgery for curative intent (28–33). In each of these studies the choice of the surgical procedure done was dependent on the patients’ general status and tumor extension. Major hepatectomy with or without caudate lobectomy was reported in two studies (31,32). In all these studies, extrahepatic biliary resection and lymphadenectomy of locoregional lymph nodes was done. For patients with eCCA which was localized, local resection of the bile duct with or without minor hepatectomy was performed (31). Hepaticojejunostomy with or without a stent was done for biliary enteric anastomosis (32). In one case-control study that compared patients that had both CCA and cirrhosis, with those that had CCA but without cirrhosis, the incidence of early postoperative liver cell failure was significantly higher in the cirrhotic group. Also, cirrhosis was associated with significantly lower overall survival (33). However, not all surgery was for curative intent, in some cases palliative bypass surgery was done to relieve patient from jaundice secondary to malignant obstruction (26).

Assessment of Outcomes and Overall Survival

The best median patient survival time reported was 36 months in patients who underwent surgery with curative intent. This was in patients that underwent major hepatectomy with caudate lobectomy (32). Patients who underwent palliative bypass surgery had a reported survival rate of 54.5% in one year and the longest survival period of 28 months (26). Two other studies with sample sizes of 10 and 28 CCA patients reported a median survival period of 10 months and 12 months, respectively (24,25). A single center experience study with a study population of 100 patients showed a higher median survival period of 19.7 months in patient who did not undergo pre-operative biliary drainage compared to those who underwent it prior to hepatectomy (28).

Palliative chemotherapy was used in patients whose CCA was beyond the surgical margins. Two studies on palliative chemotherapy with a combined study population of 68 patients had the same median survival period of 9 months (24,25). Also, two studies on palliative treatment of malignant biliary obstruction using a percutaneous transhepatic self-expanding metal stents had a median survival period of seven months and a 20% survival rate in six months (26,27)

This is the first systematic review to assess risk factors, epidemiology, and management of cholangiocarcinoma in Africa. We have not identified a comprehensive study on the incidence of CCA across the whole continent of Africa. An Egyptian study has identified male gender (1.7:1), farming and rural residency, cirrhosis, hepatitis C infection (54%), Schistosomiasis (66.5%), chronic typhoid infection (52%) and gallstone disease as possible risk factors for hilar cholangiocarcinoma (34). However, in a retrospective study done by Babatunde et al in Nigeria, 37 patients had biliary tract carcinomas (representing 0.18% of all cancers in Ibadan), with more female than male patients (26 versus 11) (23). Twenty females and four males had gallbladder carcinoma, while 6 females and 7 males had cholangiocarcinoma (p = 0.02). Gallstones (33%) and dysplasia (42%) were also risk factors for developing biliary type cancers (23).

CCAs express different types of mucin as a marker of differentiation and probable metastatic potential. MUC1, MUC1 core, MUC2, MUC3, MUC4, MUC5AC, and MUC6, were studied (35). Extensive MUC3 expression was significantly associated with well-differentiated tumors, whilst there was an approaching significance between the extensive expression of MUC1 and metastasis in CCA (35). Depot-medroxyprogesterone acetate (DMPA) is not a risk factor for the development of either hepatocellular carcinoma or cholangiocarcinoma according to a study conducted in Thailand and Kenya (36). PSC, a major risk factor in the west, is rare especially in sub-Saharan Africa as is ulcerative colitis. A study on PSC has been conducted in South Africa, with a total of 69 patients attending Charlotte Maxeke Johannesburg Academic Hospital of which 22 were black (37). The risk of CCA among this population in Johannesburg has not been stated. 3 out of 4 Afro Caribbean women on the UC database at St Bartholomew’s Hospital in London developed of PSC (38). Segal reported a series of the first 46 patients treated at Baragwanath Hospital with ulcerative colitis which is a known risk factor for PSC (39).

We have not seen any published evidence of risk of PSC and CCA in Africa. Fish borne zoonotic liver flukes Clonorchis sinensis and Opisthorchis viverrini are not a problem in Africa. There is a case report of infestation among Egyptian family who had the practice of consumption of imported fish from the Far East (40). Whereas, this is not a risk factor among native Africans, it will be an increasing risk with Chinese migration onto the continent of Africa. It is estimated up to 12.5 million Chinese are infected by Clonorchis sinensis (41).

Other liver flukes causing fasciolasis affect cows and sheep in almost all countries in Africa (42). Although there is a similar lifecycle and pathogenesis with Clonorchis sinensis and Opisthorchis viverrini, there is not definite causal effect for CCA. Gall stones have been identified as a risk factor for CCA. However, no direct cause link has been attributed to hemolytic anemias which causes pigment stones.

Eleven studies report on the management of CCA in Africa, 6 in Egypt, 2 in South Africa, 2 in Tunisia and 1 in Senegal. Although liver transplantation is emerging as treatment of choice in localized hCCA, this has not been reported in Africa. Six Egyptian and 2 Tunisian studies have reported on surgical resection of CCA with curative intent. In Egypt, Wahab reported that major hepatectomy with excision of the extrahepatic bile duct system and caudate lobe resection may be recommended for the surgical treatment of central cholangiocarcinoma in selected cases (31).

In a study published in 2012 Wahab concluded that caudate lobe resection in combination with major hepatectomy did not affect operative or postoperative morbidity and mortality but led to higher rates of margin-negative resections and significantly improved survival (32).

El- Hanafy et al found that preoperative biliary drainage by PTC and ERCP in selected patients with cholangitis and long-standing jaundice increased morbidity, transfusion requirements and hospital stay (28). However biliary drainage was associated with better outcomes in patients with malnutrition and renal impairment prior to liver resection in hCCA. But in these patients, there was higher complication risk including bile leak and collections, increased transfusion requirement, wound infection and pneumonia. In another study El Wahab et al treated 243 patients with hCCA with resection of which 173 were with curative intent (29).

There was a 14% five-year survival. Factors influencing survival were young age at diagnosis, resection with caudate lobe resection, well differentiated tumor, negative resection margins, negative nodal metastases, and absence of cirrhosis. A bilirubin of less than 10mg/dL and HCV negative status in a non-cirrhotic liver predicted a better prognosis in resection on hCCA (43).

Of the two Tunisian studies, the treatments were multimodal with different tumor locations. Romdhane et al, (24) treated 17 patients: 41% gall bladder, 35.5% pHCCA, 23.5% dCCA. Five patients were treated with curative intent, of which 3 had adjuvant chemotherapy (the subtype of CCA is not described), with rest treated with chemotherapy. Median survival for surgical resection was 10 months and 9 months for the chemotherapy group. Labidi S et al also reports of treatment outcomes of 51 patients in Tunisia: 45% gall bladder, 22% hCCA, 20% iCCA 14.5% dCCA.(25) Of these, 9 were treated with curative resection 5 of whom also had adjuvant chemotherapy (subtype unclear). Again, the outcome was 12 months median survival for surgical resection with curative intent group, and 9 months in the chemotherapy only group.

Two South African studies report on palliative management of obstructing hCCA (26,27), Clarke DL et al report on a total of 36 deeply jaundiced patients with hilar obstruction (26). Twenty-two had surgical biliary bypass, and 14 had PTC, the surgical group had higher morbidity, but both had good symptomatic relief of jaundice. There was no significant benefit of survival in the 2 groups, concluding that PTC would be treatment of choice in this group of patients. Lawson AJ et al evaluated the use of PTC self-expanding metal stents to palliate malignant biliary obstruction as an alternative to surgical bypass or when ERCP is not feasible (27). This study involved 50 patients. Although the mortality rate was high in this very high-risk group of patients, PTC placed SEMS achieved satisfactory palliation (27).

While the risk factors exist across the continent, it is unlikely that these data can be extrapolated across the whole of Africa. The changing demographics on the African continent with changing migration from the Far East should increase the awareness of Clonorchis sinensis and Opisthorchis viverrini as risk factors for CCA. The prevalence of PSC in Africa is unknown, as it is the only condition that warrants surveillance elsewhere in the world. Research is also required to determine if Fasciola.hepatica and Fasciola.gigantica are indeed not a risk factor for CCA, as they have a similar life cycle and cause cholestatic disease as do Clonorchis sinensis and Opisthorchis viverrini.

CCA remains a late presenting disease in Africa. The best median survival outcome of 36 months were for patients who had undergone hepatectomy with caudate lobectomy. Outcomes were improved when patients did not undergo preoperative biliary drainage. Where surgical resection with curative intent was planned, the data does not show that was based on modern radiological staging techniques and preoperative histology, and this may explain the poor 5-year survival. In a single high-volume center in Egypt, curative surgery results in 14% 5-year survival. At this center, factors positively influencing survival were identified as: caudate lobe resection, bilirubin of less than 10mg/dL, absence of cirrhosis and young age. There are no obvious risk factors on which to formulate surveillance programs in Africa. PTC based SEMS can be used to palliate jaundice in obstructing tumors as can ERCP stenting of dCCA. This would require investment in expertise and equipment in those African countries lacking such equipment.

Chemotherapy was used for palliative intent in most studies, except a select group from the Tunisian studies when it was neoadjuvant to curative resection (24,25).

The earlier studies were Gemcitabine based, either with Oxaliplatin (GEMOX) or Cisplatin (GEMCIS). The Folfirinox (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) regime has also been used. The numbers in these study groups were small and there was not significant survival advantage in those who received chemotherapy and neoadjuvant chemotherapy.

Study limitations include the few number of included studies; inability to rule duplicate publication as similar author’s group published a few of the included studies, the data reviewed is reported from 4 countries only. Given the small number of studies, our review highlights the need for more research to understand epidemiology and aid with development of management strategies.

Funding: none

Conflicts of interest: None

Author contributions: Asombang AW, Chishinga N, Banda L, Dua KS designed and conceptualized the review; Asombang AW, Chishinga N, Mohamed M, Nkhoma A, Chipaila J, Nsokolo B, Manda-Mapalo M, Montiero JFG were involved in data acquisition and analysis; all authors contributed to data interpretation, drafting the initial manuscript, reviewing and approving the final manuscript as submitted.

Libbrecht L, Roskams T. Hepatic progenitor cells in human liver diseases [Internet]. Semin. Cell Dev. Biol. 2002;13:389–396.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/12468238/.
Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: Epidemiology and risk factors [Internet]. Liver Int. 2019;39:19–31.[cited 2022 Mar 17] Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/liv.14095.
Patel T. Worldwide trends in mortality from biliary tract malignancies [Internet]. BMC Cancer 2002;2[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/11991810/.
Charbel H, Al-Kawas FH. Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis [Internet]. Curr. Gastroenterol. Rep. 2011;13:182–187.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/21271364/.
Razumilava N, Gores GJ. Surveillance for Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis: Effective and Justified? [Internet]. Clin. liver Dis. 2016;8:43–47.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/27822365/.
Forner A, Vidili G, Rengo M, et al. Clinical presentation, diagnosis and staging of cholangiocarcinoma [Internet]. Liver Int. 2019;39 Suppl 1:98–107.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/30831002/.
Blechacz B, Komuta M, Roskams T, et al. Clinical diagnosis and staging of cholangiocarcinoma [Internet]. Nat. Rev. Gastroenterol. Hepatol. 2011;8:512–522.[cited 2022 Mar 17] Available from: https://pubmed.ncbi.nlm.nih.gov/21808282/.
Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection [Internet]. Ann. Surg. 2008;248:84–96.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/18580211/.
DeOliveira ML, Cunningham SC, Cameron JL, et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution [Internet]. Ann. Surg. 2007;245:755–762.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/17457168/.
Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma [Internet]. Liver Transpl. 2018;24:294–303.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/29024405/.
Kimmings AN, Deventer SJH, Van, Obertop H, et al. Inflammatory and immunologic effects of obstructive jaundice: pathogenesis and treatment. [Internet]. J. Am. Coll. Surg. 1995;181:567–581.[cited 2022 Mar 17] Available from: https://europepmc.org/article/med/7582236.
Cunningham SC, Choti MA, Bellavance EC, et al. Palliation of hepatic tumors [Internet]. Surg. Oncol. 2007;16:277–291.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/17935975/.
Mimaki S, Totsuka Y, Suzuki Y, et al. Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes [Internet]. Carcinogenesis 2016;37:817.[cited 2022 Mar 16] Available from: /pmc/articles/PMC4967217/.
Site-Specific Cancer Incidence and Mortality after Cerebral Angiography with Radioactive Thorotrast on JSTOR [Internet]. [cited 2022 Mar 16] Available from: https://www.jstor.org/stable/3580998.
McGee EE, Castro FA, Engels EA, et al. Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults [Internet]. Int. J. cancer 2019;144:707–717.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/30155920/.
Kim TS, Pak JH, Kim JB, et al. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review [Internet]. BMB Rep. 2016;49:590–597.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/27418285/.
Mas-Coma S, Bargues MD, Valero MA. Fascioliasis and other plant-borne trematode zoonoses. Int J Parasitol. 2005;35:1255–78.
Kim HJ, Kim JS, Joo MK, et al. Hepatolithiasis and intrahepatic cholangiocarcinoma: A review [Internet]. World J. Gastroenterol. 2015;21:13418.[cited 2022 Mar 16] Available from: /pmc/articles/PMC4690170/.
Thun MJ, Linet MS, Cerhan JR, et al. Schottenfeld and fraumeni Cancer epidemiology and prevention, fourth edition. Schottenfeld Fraumeni Cancer Epidemiol. Prev. Fourth Ed. 2017;1–1308.
Li JS, Han TJ, Jing N, et al. Obesity and the risk of cholangiocarcinoma: a meta-analysis [Internet]. Tumour Biol. 2014;35:6831–6838.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/24729126/.
Faillie JL, Yu OH, Yin H, et al. Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes Mellitus [Internet]. JAMA Intern. Med. 2016;176:1474–1481.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/27478902/.
Wong WCW, Cheung CSK, Hart GJ. Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours [Internet]. Emerg. Themes Epidemiol. 2008;5[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/19014686/.
Pattern of biliary tract carcinoma at the University College Hospital. Ibadan. | Semantic Scholar [Internet]. [cited 2022 Mar 16] Available from: https://www.semanticscholar.org/paper/Pattern-of-biliary-tract-carcinoma-at-the-College-To-Jo/70269d41cbc5b12b706c2f6598f8d5478eced64f.
Romdhane Y, Ben, Labidi S, Meganem H, et al. P-138 Biliary tract cancers: epidemiology and prognosis [Internet]. Ann. Oncol. 2015;26:iv39.[cited 2022 Mar 16] Available from: http://www.annalsofoncology.org/article/S0923753419506718/fulltext.
Labid S, Nasri M, Benna H, El, et al. 265P Epidemiology, outcome and prognostic factors of biliary tract cancer in the Tunisian population. Ann Oncol. 2016;27:ix82–3.
Clarke D, Thomson S, Anderson F, et al. Palliation of malignant hilar obstruction at a single centre–review of operative and non-operative techniques - PubMed [Internet]. S Afr J Surg 2007;45:12–16.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/17969772/.
Lawson AJ, Beningfield SJ, Krige JEJ, et al. Percutaneous transhepatic self-expanding metal stents for palliation of malignant biliary obstruction [Internet]. S. Afr. J. Surg. 2012;50:54–60.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/22856436/.
El-Hanafy E. Pre-operative biliary drainage in hilar cholangiocarcinoma, benefits and risks, single center experience [Internet]. Hepatogastroenterology. 2010;57:414–419.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/20698200/.
ElWahab MA, Nakeeb A, El HE, El, et al. Predictors of long term survival after hepatic resection for hilar cholangiocarcinoma: A retrospective study of 5-year survivors [Internet]. World J Gastrointest Surg. 2016;8:436..[cited 2022 Mar 16] Available from: /pmc/articles/PMC4919711/.
Abdel Wahab M, Fathy O, Elghwalby N, et al. Resectability and prognostic factors after resection of hilar cholangiocarcinoma - PubMed [Internet]. Hepatogastroenterology 2006;53:5–10.[cited 2022 Mar 16] Available from: https://pubmed.ncbi.nlm.nih.gov/16506367/.
Wahab MA, Sultan A, Elgwalby N, et al. Outcome after resection of central cholangiocarcinoma: preliminary experience with 46 patients in a single center. [Internet]. Hepatogastroenterology. 2003;50:337–341.[cited 2022 Mar 17] Available from: https://europepmc.org/article/med/12749216.
Abdel-Wahab M, Sultan AM, Salah T, et al. Caudate lobe resection with major hepatectomy for central cholangiocarcinoma: is it of value? [Internet]. Hepatogastroenterology. 2012;59:321–324.[cited 2022 Mar 17] Available from: https://pubmed.ncbi.nlm.nih.gov/22328268/.
Abdelwahab M, Nakeeb A, El, Salah T, et al. Hilar cholangiocarcinoma in cirrhotic liver: a case-control study [Internet]. Int. J. Surg. 2014;12:762–767.[cited 2022 Mar 17] Available from: https://pubmed.ncbi.nlm.nih.gov/24909136/.
Abdel Wahab M, Mostafa M, Salah T, et al. Epidemiology of hilar cholangiocarcinoma in Egypt: single center study. [Internet]. Hepatogastroenterology. 2007;54:1626–1631.[cited 2022 Mar 17] Available from: https://europepmc.org/article/med/18019680.
Mall A, Hall P, Barnard R, et al. The expression of mucin in cholangiocarcinoma. An immunohistochemical study [Internet]. J. Hepatol. 2002;36:211.[cited 2022 Mar 17] Available from: http://www.journal-of-hepatology.eu/article/S016882780280753X/fulltext.
Mati JG, Kenya P, Kungu A, et al. Depot-medroxyprogesterone acetate (DMPA) and risk of liver cancer [Internet]. Int. J. Cancer 1991;49:182–185.[cited 2022 Mar 17] Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.2910490206.
Primary Sclerosing Cholangitis in a cohort of South African patients with Inflammatory Bowel Disease. at Charlotte Maxeke Johannesburg Academic Hospital | South African Gastroenterology Review [Internet]. [cited 2022 Mar 17] Available from: https://journals.co.za/doi/10.10520/EJC-12926aa0ff.
Kelly P, Patchett S, McCloskey D, et al. Sclerosing cholangitis, race and sex [Internet]. Gut 1997;41:688–689.[cited 2022 Mar 17] Available from: https://gut.bmj.com/content/41/5/688.
Segal I. Ulcerative colitis in a developing country of Africa: The Baragwanath experience of the first 46 patients. Int J Colorectal Dis. 1988;3:222–5.
Morsy ATA, Al-Mathal EM. Clonorchis sinensis a new report in Egyptian employees returning back from Saudi Arabia. [Internet]. J. Egypt. Soc. Parasitol. 2011;41:221–225.[cited 2022 Mar 17] Available from: https://europepmc.org/article/med/21634255.
Shin HR, Oh JK, Masuyer E, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors [Internet]. Cancer Sci. 2010;101:579–585.[cited 2022 Mar 17] Available from: https://pubmed.ncbi.nlm.nih.gov/20085587/.
Phiri AM, Phiri IK, Sikasunge CS, et al. Prevalence of fasciolosis in Zambian cattle observed at selected abattoirs with emphasis on age, sex and origin [Internet]. J. Vet. Med. B. Infect. Dis. Vet. Public Health 2005;52:414–416.[cited 2022 Mar 17] Available from: https://pubmed.ncbi.nlm.nih.gov/16283922/.
Abdel Wahab M, Fathy O, Elghwalby N, et al. Resectability and prognostic factors after resection of hilar cholangiocarcinoma. [Internet]. Hepatogastroenterology. 2006;53:5–10.[cited 2022 Mar 17] Available from: https://europepmc.org/article/med/16506367.

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

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Journal Publication

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Abstract

BACKGROUND:

METHODS:

RESULTS:

CONCLUSION:

Figures

Background

Materials And Methods

Search strategy and study identification

Study selection

Data extraction

Quality assessment

Statistical analysis

Results

Results of the Search Strategy

Description of the Studies and CCA Patients

Study Quality

Epidemiology and Risk Factors

Chemotherapy

Percutaneous transhepatic self-expanding metal stents (SEMS)

Preoperative Biliary Drainage (PBD)

Surgery

Assessment of Outcomes and Overall Survival

Discussion

Conclusion

Declarations

References

Status:

Journal Publication

Version 1