Gallstones: Management of the Sickle Cell Child

Abstract

Gallstone is rare in children; however, sickle cell disease is associated with an increased risk of gallstone formation. We aimed to report particularity of diagnosis and management of gallstones in sickle cell children. We conducted a cross-sectional multicentric study in four hospitals of Dakar, in Senegal, during 18 years. We studied frequency, diagnostic particularities, management, and outcome. Among the 105 pediatric patients managed for gallstones, 87 (82.85%) had sickle cell disease. Among the latter, 18 (17.14%) were asymptomatic. Laparoscopic cholecystectomy was performed in 71 patients (67.62%). Following surgery, sickle cell patients were systematically hospitalized in the intensive care unit for 24 hours. Complications occurred in 7.6% and mortality in 1.9%. Gallstone is frequent in sickle cell children. Its management has good outcomes when taking in account particularities of these patients.

1. Introduction

Cholelithiasis is uncommon in children. Its frequency was estimated to range from 0.13 to 0.22%, and in our settings, it is essentially due to chronic hemolytic diseases [1, 2]. Sickle cell disease (SCD) is the most frequent hemoglobinopathy and is primarily encountered in Africans [3]. According to the World Health Organization (WHO), more than 330,000 children are born with hemoglobinopathy, with 83% affected by SCD [4]. In Sub-Saharan Africa (SSA), namely in Senegal, the increased frequency of SCD is partially due to consanguineous marriages. Its lethality is around 2.6% [5].

In sickle cell (SC) patients, the prevalence of biliary stones increases with age and the severity of hemolysis. It is found in 12% of children aged five to seven, and 23% in those aged eleven to thirteen [6, 7]. Its frequency seems higher in the USA and the West Indies (20%) than in Sub-Saharan Africa.

Sickle cell disease is an autosomal recessive disease in its clinical expression and co-dominant in its biological expression. It is secondary to the beta hemoglobin chain gene mutation, characterized by the substitution of thymine for adenine at the sixth codon, leading to the substitution of valine for glutamic acid in position 6 of the beta chain of hemoglobin, characteristic of the hemoglobin S [7]. The Senegal and Arab-India haplotypes are generally characterized by a more remarkable synthesis of hemoglobin F (fetal) and better tolerance of the disease.

The kind of hemoglobinopathy seems to play a crucial role in the occurrence of gallstones. So, patients with type SC drepanocytosis have less complication, as hemolysis is less frequent in this subgroup [3]. Deoxygenated S hemoglobin forms polymeric intraerythrocytic fibers that lead to sickling of the red blood cell, losing the elasticity needed to pass through small blood vessels. These drepanocytes increase blood viscosity, which alters its circulation within some human organs. The resulting slackness of the blood flow leads to vaso-occlusive crises. Repetition of sickling, vascular occlusion, and hemolysis are responsible for chronic complications of SCD. The frequency of complications of gallstones in SC patients led to the implementation of a protocol of systematic surgical management. A cholecystectomy is indicated in the case of cholelithiasis in a SC child, even in the absence of symptoms [2].

The miniaturization of instruments and the understanding and control of laparoscopy-induced cardiovascular modifications in the child made laparoscopic cholecystectomy a common and safe surgical intervention [8]. Cholecystectomy is one of pediatric surgery’s most frequent laparoscopic surgical interventions [9]. However, this minimally invasive approach is not uniformly performed in Senegalese centers.

2. Epidemiology

Cholelithiasis is rarer in children than in adults but can occur at any age. Sickle cell disease is the most common genetic disease. It is widespread worldwide because of the migration of populations, but it exists mainly in black populations, even if cases have been described in authentic Caucasians, Arabs, or other populations [10]. Its prevalence in Africa varies from 10 to 40%. In Senegal, it is 11% [3, 10].

Some data in the literature report a lower prevalence of cholelithiasis in children with homozygous sickle cell disease living in Africa than in the USA [10].

The mortality of sickle cell disease is mainly linked to its acute complications. Nevertheless, chronic complications such as cholelithiasis can be the source of acute episodes that can be life-threatening.

The frequency of gallstones in children is estimated between 0.13 and 0.22%. This rate is higher in children with sickle cell disease [1, 11]. Parez in Paris noted a rate of 14% [12]. Almudaibigh reported a 31.4% prevalence of cholelithiasis in Saudi Arabia in children with sickle cell disease [13]. In Senegal, the prevalence rate is 9.4% in children with homozygous sickle cell disease [10].

The mean age of children with cholelithiasis is estimated at ten years. The prevalence and incidence increase with age [14]. Data from the literature indicate that gallstones in children slightly more often occur in females. This difference may be due to hormonal factors.

3. Pathogenesis of gallstones in sickle cell children

Pigmentary gallstones are a classic complication of chronic hemolytic anemia; they differ from cholesterol gallstones by their composition, which must contain less than 25% cholesterol. Thus SCD, like all chronic hemolytic conditions, can be complicated by pigmentary gallstones.

3.1 Bile pigments

Free bilirubin, resulting from the medullary catabolism of the heme from hemoglobin, is captured by the hepatocytes, then glucuronide. This conjugation makes it hydrosoluble. It is then excreted in the bile. A small fraction of bilirubin is excreted in its free form.

3.2 Lithogenesis

The existence of permanent unconjugated hyperbilirubinemia supersaturating the bile and the alteration of the gallbladder functions are the essential factors of this lithogenesis.

During hemolytic anemias, the increase in hemoglobin catabolism increases the fraction excreted in the free form of bilirubin, which precipitates. Another mechanism for forming pigment stones is linked to the hydrolysis of conjugated bilirubin or indirect bilirubin in the bile under bacterial beta-glucuronidase action. The unconjugated bilirubin thus released complexes with the calcium present in the bile. This mechanism is observed in the bile duct, particularly upstream of congenital biliary stenosis.

3.3 Nature of pigment stones

The biochemical analysis makes it possible to distinguish two types of pigmentary lithiasis:

• The lithiasis formed from bilirubin and calcium palmitate is brown, soft, sometimes laminated, and has concentric facets and layers when cut. Its calcium content is low, and it is generally not radiopaque. It is mainly found in the biliary tree, inconstantly associated with cholelithiasis. The frequent existence of an infection of the bile of the subject carrying calcium bilirubin lithiasis has been demonstrated.

• Pure pigmentary lithiasis, or “black stones,” are black, hard, and without any particular structure. It comprises polymers of bilirubin derivatives and is rich in calcium, copper, iron, magnesium, manganese, and calcium carbonate or phosphate. The richness in mineral constituents explains the frequency of their detection on plain radiographs. It is practically found only in the gallbladder. Its formation is linked with increased concentration of unconjugated bilirubin in hemolytic diseases.

4. Diagnosis of gallstones in sickle cell children

The deoxygenated hemoglobin S polymerizes to form intra-erythrocyte fibers, which lead to the sickling of the red blood cells, which thus lose their elasticity properties necessary to pass through the small vessels of the human body. Sickle cells increase the viscosity of blood, which circulates poorly in some organs. The resulting slowing of blood flow promotes the polymerization of hemoglobin S and obstructs the vessels, causing vaso-occlusive crises. Vaso-occlusive crises are acute painful accidents. These are the most frequent manifestations of the disease. Their frequency and intensity vary from one patient to another. When cholelithiasis occurs in children with sickle cell disease, it can be difficult to distinguish it from a simple abdominal vaso-occlusive crisis.

4.1 Circumstances of discovery

Cholelithiasis is often asymptomatic, and it is common to discover it fortuitously during an imaging examination. A vesicular sign is rarely observed; it is:

• Biliary colicky due to tensioning of the gallbladder by the entrapment of one or more stones in the cervico-cystic infundibulum. It is a pain with a sudden onset, of maximum intensity from the outset, evolving in one cycle without remission. It is located in the right hypochondrium or the epigastric region, radiating toward the tip of the right scapula and the back, realizing the classic pain in “suspension.” This pain inhibits deep inspiration. It lasts 15 minutes to several hours but does not exceed six hours without complications, which are inconstantly associated.

• Other signs: nausea, vomiting, dyspepsia, or paralytic ileus.

The clinical picture of sickle cell disease in the intercritical phase is characterized by anemia of variable intensity, jaundice, and splenomegaly in children under five. There is often a delay in stature and weight.

4.2 Physical examination

It can be normal, or find jaundice, pallor related to chronic anemia, tenderness of the right hypochondrium, or sometimes Murphy’s sign. The latter is sought in a patient with dorsal decubitus: deep palpation of the right hypochondrium triggers pain which blocks deep inspiration. One can palpate a tense, sensitive, pear-shaped, dull, and mobile vesicle with the respiratory movements corresponding to the hydrocholecyst, which is already a complicated form.

4.3 Paraclinical examinations

4.3.1 Abdominal ultrasound

Preferably performed in a patient who has been fasting for at least six hours, it allows seeing the gallstone as an oval or rounded, mobile, sloping, and hyperechoic structure with posterior shadowing. It is possible to visualize a vesicular sludge. The gallbladder wall is thin, less than 4 mm. The sensitivity of the examination is at least 95% and allows the visualization of stones from 2 mm in diameter.

4.3.2 Other radiological examinations

Plain abdominal X-ray may show calcified stones in 10 to 30% of cases. They generally appear as rounded opacities, projecting into the right hypochondrium, opposite to the twelfth dorsal vertebra or the first lumbar vertebra. The X-ray may also show reflex ileus.

Abdominal computed tomography is rarely used due to the high sensitivity of ultrasound and due to radiation of computed tomography in children.

Cholangiography preferentially visualizes the common hepatic duct, with renewed interest since the advent of laparoscopic cholecystectomy, which makes intraoperative cholangiography difficult.

4.3.3 Biology

The full blood count shows normochromic, normocytic, and regenerative anemia. The blood smear shows sickle cells. The screening tests are the Emmel test and the Itano test.

Confirmatory exams are:

• Hemoglobin electrophoresis in homozygous sickle cell disease: hemoglobin S is the majority, while hemoglobin A2 is approximately normal, with a variable rate of hemoglobin F.

• The absence of Hb A1 is a fundamental element of the diagnosis.

• The isoelectrofocusing allows antenatal diagnosis and during the neonatal period.

• Molecular biology: PCR allows the detection of the mutated gene.

5. Complications

Even if the evolution is most often asymptomatic, cholelithiasis can cause complications. These are frequent in sickle cell children [15].

5.1 Acute calculous cholecystitis

It is an inflammation of the gallbladder wall due to the entrapment of a gallstone in the cystic duct. In the first phase, the bile is sterile. Secondarily, about 48 to 72 hours after the obstruction, an infection of the bile occurs. The most frequently implicated germs are gram-negative bacilli, essentially Escherichia coli, and more rarely, anaerobes.

The clinical picture includes pain in the right hypochondrium of rapid onset, intense and continuous, hampering breathing, often associated with nausea and vomiting. A fever between 38.5 and 39°C, and minor jaundice found in 15% of patients.

Biology finds polymorphonuclear leukocytosis in 50 to 90% of cases, while bilirubin, transaminases, and alkaline phosphatase are normal or moderately elevated. The sonographic signs are, in addition to the presence of vesicular lithiasis, the thickening of the gallbladder wall greater than five millimeters, gallbladder distension, the existence of a liquid effusion, or a peri-vesicular halo. The occurrence of pain when passing the ultrasound probe over the gallbladder region has little specificity: this is the ultrasound Murphy sign.

5.2 Calculous cholangitis

It is an infection of the bile duct, most often due to obstruction of the bile duct by one or more stones. The typical form is characterized by the combination of three signs which follow one another in less than 48 hours: biliary colicky, fever at 39–40°C, and jaundice, which sets in quickly. It is a therapeutic emergency because of the risk of severe complications, including sepsis, gram-negative bacillus septic shock, renal failure, and hepatic abscess.

5.3 Uncomplicated common hepatic duct lithiasis

It is evoked in polymorphic clinical manifestations: simple biliary colicky or atypical abdominal pain, long-term fever, typically variable and intermittent jaundice, recurrent pancreatitis, and intermittent liver function abnormalities. Ultrasound or abdominal CT scan can confirm common hepatic duct stones.

5.4 Residual lithiasis

It is a lithiasis of the bile duct revealed after a cholecystectomy. This is an unrecognized lithiasis during the intervention due to a lack of bile duct exploration. It may not be revealed until several years after surgery. The formation of new stones in situ in the common hepatic duct seems possible but rare.

5.5 Acute biliary pancreatitis

It is due to the obstruction of the sphincter of Oddi by migration of lithiasis in the bile duct, it is recurrent if the lithiasis is not treated. These are often small stones or even micro-lithiasis that are difficult to identify. On the other hand, lithiasis is not responsible for chronic pancreatitis.

5.6 Gallstone ileus

It is a mechanical occlusion of the hail due to the migration of lithiasis due to a bilio-digestive fistula.

6. Treatment of gallstones in children with sickle cell disease

The goal of treatment is to destroy all gallstones, prevent recurrences, and treat complications if they exist.

6.1 Therapeutic means and methods

6.1.1 Surgery

Cholecystectomy is the therapeutic method currently used to manage cholelithiasis in children with sickle cell disease [16, 17]. It consists of completely removing the gallbladder and its contents. Cholecystectomy is feasible either by laparotomy or, at best, by laparoscopic approach.

Laparotomy uses a supra-umbilical midline approach that can be enlarged downward or an elective right subcostal approach.

During laparoscopy, the insufflation pressure varies according to age and weight. The child is installed in the supine position, and the operator stands between the legs of the patient in the French technique, whereas in the so-called American one, they are on the patient’s left. A first trocar of 10 or 5 mm is introduced into the peritoneal cavity at the trans or para-umbilical level by “open laparoscopy.” Three or two other trocars allow the introduction of the instruments. This method allows excellent visualization of the entire abdominopelvic cavity and a precise dissection under visual control through incisions that do not alter the strength or appearance of the abdominal wall.

Biliary tract surgery has certain risks related to anatomical variations and local inflammatory changes.

Iatrogenic incidents are essentially injuries of the bile duct, vascular injuries, and neighboring viscera injuries.

• Common bile duct injury: It is favored by the anatomical variations of the cystico-hepatic junction, which can lead to confusion between the bile duct and the cystic duct. The latter may be absent, with the gallbladder opening directly into the common hepatic duct. The cystic duct can also be confused with a thin bile duct when it is drawn to the right by traction on the gallbladder neck. A partial or complete ductal section is identifiable by bile flow or during intraoperative cholangiography.

• Vascular injuries: They are most often due to anatomical variations of the hepatic pedicle and are essentially arterial ones. The right hepatic artery, which is most often involved, can be injured during dissection of the cystic duct or tied during difficulties in hemostasis of the cystic artery. Its ligature does not cause severe consequences for the liver. When arterial bleeding is significant, the Pringle maneuver’s temporary clamping of the hepatic pedicle can facilitate its control. Venous wounds are rare and often favored by portal hypertension.

• Injury of neighboring viscera: They concern the duodenum and the colon and occur during the dissection of the gallbladder adhering to these viscera. When the injury is recognized, it must be sutured extemporaneously.

6.1.2 Medical means

6.1.2.1 Preoperative evaluation

In children with SCD, the vital organs are generally poorly affected. The specific search for cardiomyopathy or pulmonary involvement must be made by history taking and clinical examination.

The homozygous form of the disease is more prone to acute attacks. Children with frequent painful crises, and a fortiori multiple hospitalizations, are more exposed to perioperative crises. Paraclinical examinations must be adapted to the history and clinical findings (Table 1).

Investigation	Indication
Hematocrit	Signs of dehydration
Azotemia and creatininemia	Oligo-anuria
Hematuria and proteinuria	Urinary tract infection
Functional respiratory tests, blood gazes, Oxygen saturation, thorax plain x-ray	Clinical signs of chronic respiratory insufficiency
Search for irregular agglutinins	Patients with multiple transfusions
Cerebral imaging	Psychomotor retardation

Table 1.

Preanesthetic investigations.

6.1.2.2 Perioperative transfusions

Its indications are the correction of anemia, the compensation of hemorrhagic losses, and the prevention or treatment of the manifestations of the disease.

• Prevention of disease complications: The dilution of hemoglobin S with normal blood lowers its level and prevents the occurrence of vaso-occlusive crises. This transfusion is indicated when the concentration of hemoglobin S is greater than 30%, and the hematocrit is less than 30%.

• Improved oxygen transport: The existence of an acute chest syndrome or chronic respiratory failure can compromise the delivery of oxygen. Homozygous sickle cell patients are often carriers of anemia, which they tolerate relatively well thanks to compensatory mechanisms.

Transfusion can be done in two ways:

• Simple transfusion if the hemoglobin level is low. It is performed one to three weeks, or just before surgery, maintaining a hematocrit level < 30%. The quantity to be transfused is 3 ml/Kg of red blood cells or 6 ml/Kg of whole blood to obtain a gain of 1 g/dl of hemoglobin.

• Transfusion exchange if baseline hemoglobin is higher. It is performed 24 to 48 hours before the operation and consists of subtracting 45 ml/kg of the patient’s blood and transfusing them with 30 ml/Kg of red blood cells in three stages. The blood used ideally comes from a single donor; it must be leukocyte-depleted and phenotyped. Approximately, half a blood mass exchange lowers hemoglobin S by 35–40%.

6.1.2.3 Perioperative oxygenation

As with all anesthetic procedure, hypoxia should be avoided in these children, but there is no need to maintain hyperoxia intraoperatively beyond the time limit that would be applied to a normal subject.

6.1.2.4 Perioperative hydration

Intracellular dehydration promotes sickling by raising the level of intralobular hemoglobin. Prolonged preoperative fasting should be avoided. The compensation of water losses is made by reflex vasoconstriction. Placing a urinary catheter allows the monitoring of diuresis and blood volume.

6.1.2.5 Perioperative thermal regulation

The intraoperative method of preventing hypothermia in sickle cell patients is the same as in normal children.

6.1.2.6 Perioperative acid: Base balance

In vitro, plasma acidification promotes the deformation of red blood cells. However, no clinical argument demonstrates the role of acidosis in triggering the complications of sickle cell disease.

6.1.2.7 Postoperative care

In children with homozygous sickle cell disease, postoperative monitoring is carried out in an intensive care unit for at least 24 hours. Febrile episodes represent underlying complications in these patients: vaso-occlusive crises and acute chest syndrome. Their treatment is based on oxygen therapy, hydration, antibiotic therapy, and sometimes transfusion. Alkalinization seems unsuitable.

6.2 Indications

Curative treatment is surgical.

6.2.1 Uncomplicated presentations

Laparoscopic cholecystectomy, commonly practiced in adults since 1987, has seen its indications extend to children. The adaptation of laparoscopic instruments to patients under sixteen allows the treatment of all uncomplicated cholelithiasis in children by laparoscopy. The indications for conventional surgery now depend on the limitations of laparoscopy.

6.2.2 Complicated presentations

Acute calculous cholecystitis requires cholecystectomy after the disappearance of the inflammatory phenomena. Its initial management is medical and urgent and occurs in a hospital setting. In the case of gallstone ileus, surgery allows the obstruction treatment by removing the lithiasis. It is the same in the case of cholecysto-choledochal fistula. In the case of cholangitis, the endoscopic sphincterotomy allows rapid drainage of the bile duct and extraction of stones.

6.3 Specific biliary complications

6.3.1 Biliary leaks

The occurrence of a biliary leak is the fear of any surgeon practicing classical or laparoscopic biliary surgery. It can most often come from the cystic stump, and the clip can migrate, having been loosely tightened, from the bile duct due to a per-operative injury or by secondary fall of eschar of coagulation. Finally, leaks can originate from the vesicular bed either by section of a small segmental canal flowing into the gallbladder or by oozing attributed to the intrahepatic canals.

6.3.2 Bile duct stenosis

Stenosis of the bile duct can occur either immediately by placing a clip on the bile duct or secondarily by a mechanism that is not unequivocal: evolution of scarring stenosis after lesion of the common hepatic duct taken for cystic, stenosis of ischemic origin by the diffusion of electricity during the abusive use of monopolar coagulation.

6.3.3 Residual lithiasis of the common hepatic duct

It can result from the migration of a cystic or vesicular stone.

7. Outcomes

To make an evaluation of epidemiology, diagnosis, management, and outcomes of gallstones in sickle cell children, we conducted a multicentric retrospective descriptive study in Dakar.

7.1 Patients and methods

We conducted a retrospective multicentric study in four university teaching hospitals (UTHs) in Dakar. These included two departments of pediatric surgery and two departments of general surgery at Aristide Le Dantec Hospital, Albert Royer Children’s Hospital, and Idrissa Pouye General Hospital. All SC patients under 16 years old surgically managed for gallstones were included. We considered 18 years from January 2002 to December 2020.

At Albert Royer Children’s Hospital, the follow-up of SC patients has been organized since January 1991 and is coordinated by a Professor of Pediatrics specialist in hematology. For SC children, an abdominal ultrasound (US) is systematically ordered in those aged five years and over, and in all cases of recurrent abdominal pain or right upper quadrant pain on physical examination.

Once a gallstone diagnosis is made, patients are referred to the surgery department for management. So, we selected all patients suitable for general anesthesia and whom hospitalization was required a day before, without any particular premedication.

1. Preoperative Evaluation

   It consisted with a standard investigation (full blood count and coagulation tests), confirmation of absence of infection (C-reactive protein), and abdominal ultrasound 24 to 48 hours to verify permeability of the bile duct.

2. Blood Transfusion

   A preoperative blood transfusion was indicated when hemoglobin concentration was lower than basic hemoglobin rate of the patient, usually lower than 9 g/dl.

3. Surgery

   The surgical approach used in our study is elective cholecystectomy. Children hospitalized for acute cholecystitis initially benefited from medical treatment using antibiotics and analgesics, then cholecystectomy was performed after regression of inflammatory phenomenon, confirmed by biological investigations.

We studied the frequency of SCD in patients with gallstones, their age, diagnostic particularity, treatment, and outcomes in these patients.

7.2 Results

During 18 years, 105 patients of less than 16 years benefited from cholecystectomy for gallstones. Among them, 87 (82.85%) were homozygote for SCD. There were 46 boys and 41 girls, determining a sex ratio of 1.12. Mean age was 11.3 years, ranging from 7.3 to 15 years. The range from 11 to 15 years represented 68.96% of our patients. Figure 1 depicts the repartition of patients according to age.

Figure 1.

Patients’ age categories.

Forty-one children (47.12%) had at least one hospitalization for acute cholecystitis when gallstone was asymptomatic and discovered fortuitously during routine US in 18 SC patients (17.14%). Table 2 illustrates the variable circumstances of the discovery of gallstones. Preoperative US screening for bile duct stones was realized in 14 patients (16.01%) 24 to 48 hours prior to surgical intervention.

Circumstance	Number	Percentage
Acute cholecystitis	41	47.12
Cholestatic syndrome	5	5.74
Biliary colic	23	26.44
Asymptomatic (discovered fortuitously through screening US)	18	17.14
Total	87	100

Table 2.

Circumstances of discovery of the gallstone.

Laparoscopic cholecystectomy was performed in 71 cases (67.62%). The American layout, the patient laid on their back, legs together, and the surgeon on the left with two assistants was used in most cases. Surgery using three or four ports was used in all cases. The surgical approach using three ports is shown in Figure 2.

Figure 2.

Laparoscopic approach using three trocarts. In (1), the umbilical port, in (2), the epigastric trocart, and in (3), the latéro-umbilical trocart.

Open surgery was used in 16 patients (18.39%) due to a lack of equipment or the absence of qualified surgeons to perform laparoscopy. The cholecystectomy was retrograde in 64 patients (73.56%) and anterograde in 23 cases (26.44%). The mean duration of the laparoscopic surgical intervention was 33.88 minutes, ranging from 15 to 80 minutes. The duration progressively decreased from the beginning of the study period to its end. Longer durations were due to inflammatory gallbladder and adhesions to neighboring structures. Preoperative incidents were noted: difficult dissection due to adherent gallbladder in seven patients (8.01%) and a case of extrahepatic duct wound (1.14%). Accidental opening of the gallbladder was encountered in 6 patients with bile leaking, without loss of stones in the abdominal cavity.

Postoperatively, all patients were admitted to the intensive care unit (ICU) for 24 hours. The mean length of stay (LOS) was 7.9 days, ranging from 2 to 90 days. After a mean follow-up of five years (ranging from 1.3 to 8.5 years), no complication was encountered in 94.25% of patients. Morbidity rate was found in 5.75%. These included a case of sepsis due to Klebsiella, 2 cases (2.29%) of bile duct residual lithiasis, and 2 cases (2.29%) of cholestatic syndrome due to bile duct stenosis among children who benefited from laparoscopic and open cholecystectomy. Both benefited from a biliary derivation using hepatica-jejunal anastomosis with the Roux-en-Y technique. One represents the single mortality (1.14%) registered in our patients.

7.3 Discussion

Gallstones are rare in children; their frequency ranges from 0.13 to 0.22%, and it is mainly secondary to anomalies of the hemoglobin [1, 2]. Rarity of gallstones in Africa was reported for all ages despite the high incidence of SCD on the continent. In high-income countries (HICs) and Northern Africa, the prevalence of gallstone is probably linked to food, obesity, and hypercholesterolemia. Therefore, the global prevalence of gallstones in SC patients varies from country to country. In Senegal, it is around 9.4%; in France: 14%; in Italy, it is 22% in children from 10 to 14 years old; and in Jamaica, it is 23% of SC patients from 11 to 13 years old [9, 12, 18]. Its frequency in SSA and Senegal is due to the high frequency of SCD.

The evolution of SCD is characterized by recurrence of vaso-occlusive crises and chronic anemia. Several complications may occur during this evolution [19, 20]. Acute complications are mainly vascular thrombosis, infections, and acute anemia.

According to the WHO, 500,000 children are born yearly with the SCD gene, so the organization recommends neonatal screening and early treatment. In Senegal, it is estimated that 1700 newborns are affected each year. It is why screening and management of chronic complications such as gallstones were implemented during SC patients’ follow-up. For that, yearly abdominal US in SC patients older than five years was recommended [2, 12, 21]. Gallstone is the primary chronic complication [22]. SCD was present in 82.85% of children with gallstones in our study. Abdul Rahman in Saudi Arabia found 75% of SC patients among 72 children with gallstones [23], thus, gallstone is a well-known complication of chronic hemolysis secondary to SCD [12]. The Senegal haplotype leads to a more important synthesis of fetal hemoglobin with a better tolerance of the disease [24]. In our series, other hemoglobinopathies were not searched for due to their low prevalence in our settings and the low socioeconomic level, which was a constraint to realization of such investigations. When complications of SCD mainly occur before 10 years [25], gallstones mainly occur from six years. Majority of our patients had more than 10 years. These results are similar to the literature, where the prevalence of gallstones increases with age [2, 12, 21].

Abdominal pain is the most frequent revealing sign of gallstones [26]. Approximately a third of our patients had biliary colicky when a complication revealed gallstones in half of the cases, such as acute cholecystitis or cholestatic syndrome. Despite our gallstones screening protocol in SC children, a significant number of patients presented with acute cholecystitis prior to the date for elective surgery. Before surgery, abdominal US was the only investigation to explore the common bile duct. Its sensitivity is variable. However, liver US gives orientation to the intraoperative exploration of the bile duct. In our patients, it allowed the diagnosis of lithiasis of the common hepatic duct in our series.

Children scheduled for elective cholecystectomy without symptoms, with normal liver function tests and normal amylasemia, without biliary duct dilatation on abdominal US do not need preoperative nor on-table cholangiography [27, 28]. Moreover, in a patient with bile duct lithiasis associated with gallstones, we opted for safe surgery with a laparoscopic exploration, followed by a right subcostal mini-laparotomy. This was motivated by our lack of experience in laparoscopic surgery of the bile duct and the lack of dedicated equipment.

Most of our patients benefited from retrograde cholecystectomy: 69.56% and 20.43% from anterograde cholecystectomy. Identification of the cystic duct allowed us to make its section before the artery; when identifying the cystic artery prior to the cystic duct allowed us to avoid arterial injury by excessive traction on the cystic duct. Performing on retrograde or anterograde cholecystectomy depends on the surgeons’ habits.

A biliary duct injury was reported in two cases (2.29%). One was in a patient with an anatomical variation with an hepato-cystic accessory duct, confused with the embryological remnant of the Luschka’s hepato-vesicular duct. The existence of an anatomical variation of the extrahepatic biliary ducts is a well-documented cause of biliary duct injury during laparoscopic cholecystectomy [29]. There are many anatomical [30], radiological [31] or intraoperative [29] description of hepato-cystic ducts. Their low frequency, estimated to range from 1 to 2% can explain the poor knowledge of these anatomical variations.

Authors reported a higher risk of biliary tract injury during laparoscopic cholecystectomy [21]. During an open cholecystectomy, a patient presented with cholestasis secondary to a biliary tract injury. No matter the surgical approach, identifying the extrahepatic biliary tract must be meticulous before attempting any section.

Complications were encountered in 5.74% of patients, with a case of sepsis due to Klebsiella, probably secondary to bile duct lithiasis. Therefore, postoperative infections in these patients should be avoided, which justifies close monitoring in ICU immediately after surgery. Additionally, SC children with recurrent painful crises and multiple hospitalizations have an increased risk for perioperative crises [9]. Preoperative US must be done in each case, which could allow identification of bile duct lithiasis discovered after surgery.

8. Conclusion

Gallstones are frequent in adults; however, they are also encountered in children younger than 16. Their discovery in the child must lead to investigations about the underlying cause, namely comorbidity with chronic hemolysis.

Sickle cell disease is the most common cause of gallstones in children from SSA. It is a congenital disease representing a major public health problem in this part of the continent.

The risk of complications such as acute cholecystitis, and common biliary tree calculous that are true emergencies, and the high risk of postoperative complication in emergent cholecystectomy show the importance of gallstone screening with liver US in SC patients from 5 years. Consequently, systematic cholecystectomy before the discovery of any gallstone should be performed.

Laparoscopic cholecystectomy has good outcomes when precautions due to SCD are applied.