The management and outcomes of hepatocellular carcinoma in sub-Saharan Africa: a systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of mortality in sub-Saharan Africa (SSA). This systematic review aimed to appraise all population-based studies describing the management and outcomes of HCC in SSA. METHODS: A systematic review based on a search in PubMed, PubMed Central, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), AfricaWide and Cochrane up to June 2023 was performed. PRISMA guidelines for systematic reviews were followed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration no: CRD42022363955). RESULTS: Thirty-nine publications from 15 of 48 SSA countries were identified; 3989 patients were studied. The majority (74%) were male, with median ages ranging from 28 to 54 years. Chronic Hepatitis B infection was a leading aetiology and non-cirrhotic HCC was frequently reported. Curative treatment (liver resection, transplantation and ablation) was offered to 6% of the cohort. Most patients (84%) received only best supportive care (BSC), with few survivors at one year. CONCLUSION: The majority of SSA countries do not have data reporting outcomes for HCC. Most patients receive only BSC, and curative treatment is seldom available in the region. Outcomes are poor compared to high-income countries.

Novel CABIN score outperforms other prognostic models in predicting in-hospital mortality after salvage transjugular intrahepatic portosystemic shunting.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is now established as the salvage procedure of choice in patients who have uncontrolled or severe recurrent variceal bleeding despite optimal medical and endoscopic treatment. AIM: To analysis compared the performance of eight risk scores to predict in-hospital mortality after salvage TIPS (sTIPS) placement in patients with uncontrolled variceal bleeding after failed medical treatment and endoscopic intervention. METHODS: Baseline risk scores for the Acute Physiology and Chronic Health Evaluation (APACHE) II, Bonn TIPS early mortality (BOTEM), Child-Pugh, Emory, FIPS, model for end-stage liver disease (MELD), MELD-Na, and a novel 5 category CABIN score incorporating Creatinine, Albumin, Bilirubin, INR and Na, were calculated before sTIPS. Concordance (C) statistics for predictive accuracy of in-hospital mortality of the eight scores were compared using area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: Thirty-four patients (29 men, 5 women), median age 52 years (range 31-80) received sTIPS for uncontrolled (11) or refractory (23) bleeding between August 1991 and November 2020. Salvage TIPS controlled bleeding in 32 (94%) patients with recurrence in one. Ten (29%) patients died in hospital. All scoring systems had a significant association with in-hospital mortality (P < 0.05) on multivariate analysis. Based on in-hospital survival AUROC, the CABIN (0.967), APACHE II (0.948) and Emory (0.942) scores had the best capability predicting mortality compared to FIPS (0.892), BOTEM (0.877), MELD Na (0.865), Child-Pugh (0.802) and MELD (0.792). CONCLUSION: The novel CABIN score had the best prediction capability with statistical superiority over seven other risk scores. Despite sTIPS, hospital mortality remains high and can be predicted by CABIN category B or C or CABIN scores > 10. Survival was 100% in CABIN A patients while mortality was 75% for CABIN B, 87.5% for CABIN C, and 83% for CABIN scores > 10.

Aorto-oesophageal fistula after corrosive ingestion: A case report.

BACKGROUND: Aorto-oesophageal fistula (AOF) are uncommon and exceedingly rare after corrosive ingestion. The authors report a case of AOF after corrosive ingestion that survived. A comprehensive literature review was performed to identify all cases of AOF after corrosive ingestion to determine the incidence of this condition, how it is best managed and what the outcomes are. CASE SUMMARY: A previously healthy 30-year-old male, presented with a corrosive oesophageal injury after drain cleaner ingestion. He did not require acute surgical resection, but developed long-segment oesophageal stricturing, which was initially managed with cautious dilatation and later stenting. An AOF was suspected at endoscopy performed two months after the ingestion, when the patient represented with massive upper gastrointestinal bleeding. The fistula was confirmed on computerised tomographic angiography. The initial bleeding at endoscopy was temporised by oesophageal stenting; a second stent was placed when bleeding recurred later the same day. The stenting successfully achieved temporary bleeding control, but resulted in sudden respiratory distress, which was found to be due to left main bronchus compression caused by the overlapping oesophageal stents. Definitive bleeding control was achieved by endovascular aortic stent-grafting. A retrosternal gastroplasty was subsequently performed to achieve gastrointestinal diversion to reduce the risk of stent-graft sepsis. He was subsequently successfully discharged and remains well one year post injury. CONCLUSION: AOF after corrosive ingestion is exceedingly rare, with a very high mortality. Most occur weeks to months after the initial corrosive ingestion. Conservative management is ill-advised.

Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis.

BACKGROUND: The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC. METHODS: A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC). RESULTS: Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery. CONCLUSION: Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.

Defining the advantages and exposing the limitations of endoscopic variceal ligation in controlling acute bleeding and achieving complete variceal eradication.

BACKGROUND: Bleeding esophageal varices (BEV) is a potentially life-threatening complication in patients with portal hypertension with mortality rates as high as 25% within six weeks of the index variceal bleed. After control of the initial bleeding episode patients should enter a long-term surveillance program with endoscopic intervention combined with non-selective ß-blockers to prevent further bleeding and eradicate EV. AIM: To assess the efficacy of endoscopic variceal ligation (EVL) in controlling acute variceal bleeding, preventing variceal recurrence and rebleeding and achieving complete eradication of esophageal varices (EV) in patients who present with BEV. METHODS: A prospectively documented single-center database was used to retrospectively identify all patients with BEV who were treated with EVL between 2000 and 2018. Control of acute bleeding, variceal recurrence, rebleeding, eradication and survival were analyzed using Baveno assessment criteria. RESULTS: One hundred and forty patients (100 men, 40 women; mean age 50 years; range, 21-84 years; Child-Pugh grade A = 32; B = 48; C = 60) underwent 160 emergency and 298 elective EVL interventions during a total of 928 endoscopy sessions. One hundred and fourteen (81%) of the 140 patients had variceal bleeding that was effectively controlled during the index banding procedure and never bled again from EV, while 26 (19%) patients had complicated and refractory variceal bleeding. EVL controlled the acute sentinel variceal bleed during the first endoscopic intervention in 134 of 140 patients (95.7%). Six patients required balloon tamponade for control and 4 other patients rebled in hospital. Overall 5-d endoscopic failure to control variceal bleeding was 7.1% (n = 10) and four patients required a salvage transjugular intrahepatic portosystemic shunt. Index admission mortality was 14.2% (n = 20). EV were completely eradicated in 50 of 111 patients (45%) who survived > 3 mo of whom 31 recurred and 3 rebled. Sixteen (13.3%) of 120 surviving patients subsequently had 21 EV rebleeding episodes and 10 patients bled from other sources after discharge from hospital. Overall rebleeding from all sources after 2 years was 21.7% (n = 26). Sixty-nine (49.3%) of the 140 patients died, mainly due to liver failure (n = 46) during follow-up. Cumulative survival for the 140 patients was 71.4% at 1 year, 65% at 3 years, 60% at 5 years and 52.1% at 10 years. CONCLUSION: EVL was highly effective in controlling the sentinel variceal bleed with an overall 5-day failure to control bleeding of 7.1%. Although repeated EVL achieved complete variceal eradication in less than half of patients with BEV, of whom 62% recurred, there was a significant reduction in subsequent rebleeding.

Factors leading to loss of patency after biliary reconstruction of major laparoscopic cholecystectomy bile duct injuries: an observational study with long-term outcomes.

BACKGROUND: Small sample size and a lack of standardized reporting for patients requiring reconstruction for laparoscopic cholecystectomy bile duct injuries (LC-BDI) have limited investigation of factors contributing to loss of patency. METHODS: Using a prospective database, patient characteristics, pre-repair investigations, Strasberg-Bismuth level of injury, timing of reconstruction and postoperative complications were compared in successful index reconstruction and revision patients. Multivariate analysis was performed to determine independent predictors of loss of patency. RESULTS: Of 131 patients analysed, 103 had a successful index reconstruction and 28 required revision. There were no statistically significant differences in patient characteristics between the two groups. Days to referral and reconstruction were significantly different (p < 0.001, p = 0.001). Patients with incomplete biliary imaging more often required a revision (p < 0.001). The only independent predictor of loss of patency was incomplete depiction of the biliary tree prior to initial reconstruction (p = 0.035, OR 10.131, 95% CI 1.180-86.987). Primary and secondary patency were 98.1% and 96.4%, respectively with no differences in 30-day complications. CONCLUSIONS: Incomplete depiction of LC-BDI before index reconstruction was independently associated with loss of patency requiring revision. Despite the complexity of repeat biliary reconstruction, outcomes in an HPB unit were similar to that of an index reconstruction.

Evolution of bile duct repair in a low and middle-income country (LMIC): a comparison of diagnosis, referral, management and outcomes in repair of bile duct injury after laparoscopic cholecystectomy from 1991 to 2004 and 2005-2017.

BACKGROUND: There is a paucity of data from the developing world regarding laparoscopic cholecystectomy (LC) bile duct injuries (BDIs), despite the fact that most of the world's population live in a developing country. We assessed how referral patterns, management and outcomes after LC-BDI repair have evolved over time in patients treated at a tertiary referral center in a low and middle-income country (LMIC). METHODS: Patients with LC-BDIs requiring hepaticojejunostomy were identified from a prospective database. Clinical characteristics, geographic distance from referral hospital, timing of referral and repair, and post-operative outcomes were compared in two cohorts treated during 1991-2004 and 2005-2017. RESULTS: Of 125 patients, 32 underwent repair in the early period, 93 in the latter. There was no difference in demographic or clinical characteristics, but a 45.6% increase in geographically distant referrals in the 2005-2017 period. Time from diagnosis to referral and referral to repair increased significantly (p = 0.031, p < 0.001), necessitating more intermediate repairs. Despite this, the number of severe complications decreased (p = 0.022) while long-term outcomes remained unchanged. CONCLUSION: In this study from an LMIC, geographic and logistic constraints necessitated deviation from accepted algorithms devised for well-resourced countries. When appropriately adapted, results comparable to those reported from developed countries are achievable.

An analysis of early postoperative complications following biliary reconstruction of major bile duct injuries using the Modified Accordion and Anatomic, Timing Of and Mechanism classifications.

BACKGROUND: Few studies have reported patient outcome after surgical repair of bile duct injury using a standardized, validated classification system. This is the first analysis to investigate the correlation between the Anatomic, Timing Of and Mechanism classification of bile duct injury and severity of postoperative complications classified using the Modified Accordion Grading System. METHODS: Patients undergoing index hepaticojejunostomy repair of bile duct injury in laparoscopic cholecystectomy at a tertiary referral center from 1993-2018 were included. Patient demographics, geographic distance from referral center, time to referral, Anatomic, Timing Of and Mechanism classification and highest Modified Accordion Grade complication were retrieved from a prospective database. The primary outcome was determined using correlation statistics to assess the relationship between level of injury and severity of postoperative complication. RESULTS: One hundred and twenty-eight patients were included. There was no correlation between level of injury and severity of postoperative complication (r s (128) = -0.113, P = .203). Seventy (54.7%) patients had an injury less than 2 cm from the hepatic duct bifurcation and 52% of patients developed a postoperative complication, most mild to moderate in severity. Geographic distance resulted in substantial delays in referral (P < .001) but did not affect complication rate (P = .523). CONCLUSION: In this prospective analysis the short-term complication rate was higher than previous retrospective reports, but the distribution of the severity of complications and spectrum of injury type were similar. There was no correlation between severity of injury and postoperative complications. Geographic distance from referral center resulted in substantial differences in referral delay but had no statistically significant effect on outcome.

Resection of complex pancreatic injuries: Benchmarking postoperative complications using the Accordion classification.

AIM: To benchmark severity of complications using the Accordion Severity Grading System (ASGS) in patients undergoing operation for severe pancreatic injuries. METHODS: A prospective institutional database of 461 patients with pancreatic injuries treated from 1990 to 2015 was reviewed. One hundred and thirty patients with AAST grade 3, 4 or 5 pancreatic injuries underwent resection (pancreatoduodenectomy, n = 20, distal pancreatectomy, n = 110), including 30 who had an initial damage control laparotomy (DCL) and later definitive surgery. AAST injury grades, type of pancreatic resection, need for DCL and incidence and ASGS severity of complications were assessed. Uni- and multivariate logistic regression analysis was applied. RESULTS: Overall 238 complications occurred in 95 (73%) patients of which 73% were ASGS grades 3-6. Nineteen patients (14.6%) died. Patients more likely to have complications after pancreatic resection were older, had a revised trauma score (RTS) < 7.8, were shocked on admission, had grade 5 injuries of the head and neck of the pancreas with associated vascular and duodenal injuries, required a DCL, received a larger blood transfusion, had a pancreatoduodenectomy (PD) and repeat laparotomies. Applying univariate logistic regression analysis, mechanism of injury, RTS < 7.8, shock on admission, DCL, increasing AAST grade and type of pancreatic resection were significant variables for complications. Multivariate logistic regression analysis however showed that only age and type of pancreatic resection (PD) were significant. CONCLUSION: This ASGS-based study benchmarked postoperative morbidity after pancreatic resection for trauma. The detailed outcome analysis provided may serve as a reference for future institutional comparisons.

Surgical Management and Outcomes of Combined Pancreaticoduodenal Injuries: Analysis of 75 Consecutive Cases.

BACKGROUND: Combined pancreaticoduodenal injuries (CPDI) are complex and result in significant morbidity and mortality. Survival in CPDI after initial damage-control laparotomy (DCL) and pancreaticoduodenectomy was evaluated in a large cohort treated in a Level I trauma center. We hypothesized that bivariate analyses would accurately identify factors influencing morbidity and mortality. STUDY DESIGN: The records from a prospective database of 453 consecutive patients treated for pancreatic injuries between January 1990 and April 2015 were reviewed to identify those with CPDI. Primary and secondary end points assessed were death and morbidity. RESULTS: Seventy-five patients (69 men, median age 27 years, range 14 to 56 years) with CPDI, underwent 161 operations (range 1 to 9 operations). Twenty-nine patients with complex CPDI underwent a DCL and 46 had definitive treatment during the initial operation. Nineteen had a pancreaticoduodenectomy, either during the initial operation (n = 13) or after the DCL (n = 6). Postoperative complications occurred in 63 (84%) patients. Twenty-one (28%) patients died, including 15 (43%) of 35 patients with associated vascular injuries. Sixteen (84%) of the 19 patients who had a pancreaticoduodenectomy survived. Significantly more complications related to bleeding, disseminated intravascular coagulation, and hypovolemic shock occurred in those patients who eventually died and significantly more abdominal sepsis and fistulas occurred in patients who survived. Mortality was related to associated vascular injuries overall (p < 0.01), major visceral venous injuries (p < 0.011), and the combination of vascular plus the total number of associated organs injured (p < 0.046). CONCLUSIONS: Despite using DCL in CPDIs, morbidity (84%) and mortality (28%) remain substantial. Careful selection of patients undergoing pancreaticoduodenectomy resulted in 84% survival. Associated vascular injuries, major visceral venous injuries, and combined vascular and associated organs injured influenced outcomes and mortality.

Outcome in decompensated alcoholic cirrhotic patients with acute variceal bleeding.

BACKGROUND: Variceal bleeding (VB) is the leading cause of death in cirrhotic patients with oesophageal varices. We evaluated the efficacy of emergency endoscopic intervention in controlling acute variceal bleeding and preventing rebleeding and death during the index hospital admission in a large cohort of consecutively treated alcoholic cirrhotic patients after a first variceal bleed. METHODS: From January 1984 to August 2011, 448 alcoholic cirrhotic patients (349 men, 99 women; median age 50 years) with VB underwent endoscopic treatments (556 emergency, 249 elective) during the index hospital admission. Endoscopic control of initial bleeding, variceal rebleeding and survival after the first hospital admission were recorded. RESULTS: Endoscopic intervention alone controlled VB in 394 patients (87.9%); 54 also required balloon tamponade. Within 24 hours 15 patients rebled; after 24 hours 61 (17%, n=76) rebled; and 93 (20.8%) died in hospital. No Child-Pugh (C-P) grade A patients died, while 16 grade B and 77 grade C patients died. Mortality increased exponentially as the C-P score increased, reaching 80% when the C-P score exceeded 13. CONCLUSION: Despite initial control of variceal haemorrhage, 1 in 6 patients (17%) rebled during the first hospital admission. Survival (79.2%) was influenced by the severity of liver failure, with most deaths occurring in C-P grade C patients.

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

BACKGROUND: Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. METHODS: Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. RESULTS: Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. CONCLUSIONS: Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices.

OBJECTIVE: This study tested the validity of the hypothesis that eradication of esophageal varices by repeated injection sclerotherapy would reduce recurrent variceal bleeding and death from bleeding varices in a high-risk cohort of alcoholic patients with cirrhosis. SUMMARY BACKGROUND DATA: Although banding of esophageal varices is now regarded as the most effective method of endoscopic intervention, injection sclerotherapy is still widely used to control acute esophageal variceal bleeding as well as to eradicate varices to prevent recurrent bleeding. This large single-center prospective study provides data on the natural history of alcoholic cirrhotic patients with bleeding varices who underwent injection sclerotherapy. METHODS: Between 1984 and 2001, 287 alcoholic cirrhotic patients (225 men, 62 women; mean age, 51.9 years; range, 24-87 years; Child-Pugh grades A, 39; B, 116; C, 132) underwent a total of 2565 upper gastrointestinal endoscopic sessions, which included 353 emergency and 1015 elective variceal injection treatments. Variceal rebleeding, eradication, recurrence, and survival were recorded. RESULTS: Before eradication of varices was achieved, 104 (36.2%) of the 287 patients had a total of 170 further bleeding episodes after the first endoscopic intervention during the index hospital admission. Rebleeding was markedly reduced after eradication of varices. In 147 (80.7%) of 182 patients who survived more than 3 months, varices were eradicated after a mean of 5 injection sessions and remained eradicated in 69 patients (mean follow-up, 34.6 months; range, 1-174 months). Varices recurred in 78 patients and rebled in 45 of these patients. Median follow-up was 32.3 months (mean, 42.1 months; range, 3-198.9 months). Cumulative overall survival by life-table analysis was 67%, 42%, and 26% at 1, 3, and 5 years, respectively. A total of 201 (70%) patients died during follow-up. Liver failure was the most common cause of death. CONCLUSION: Repeated sclerotherapy eradicates esophageal varices in most alcoholic cirrhotic patients with a reduction in rebleeding. Despite control of variceal bleeding, survival at 5 years was only 26% because of death due to liver failure in most patients.