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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 44  |  Issue : 1  |  Page : 28-33

Asymptomatic gallstones in patients with sickle cell disease: to wait or to operate?


1 Department of Hematology, Medical Research Institute, Alexandria University, Alexandria, Egypt
2 Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission18-Sep-2018
Date of Acceptance18-Nov-2018
Date of Web Publication27-Sep-2019

Correspondence Address:
Mohamed A.M El-Menoufy
Hematology Department, Medical Research Institute, Alexandria University, Alexandria 21561
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejh.ejh_34_18

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  Abstract 


Background Cholelithiasis (gallstone disease) is found in more than one-half of the patients with sickle cell disease (SCD) by the age of 30 years. Complications of symptomatic cholelithiasis may precipitate to recurrent sickle cell crises, which add to the disease morbidity. Laparoscopic cholecystectomy (LC) is the treatment of choice in patients with symptomatic disease, but the best option for asymptomatic ones is still a source of debate.
Aim To compare the outcome of LC in asymptomatic and symptomatic cholelithiasis in patients with SCD.
Patients and methods The study was performed on 42 patients with SCD having cholelithiasis. A total of 30 (72%) patients with asymptomatic cholelithiasis underwent prophylactic LC and were compared with those [12 (28%) patients] who were operated owing to symptomatic cholelithiasis.
Results The percentage of cholelithiasis was significantly higher in the 12–30 years age group (69%) than in the age groups younger than 12 years and over 30 years (P=0.013). Nine of the 12 (75%) symptomatic patients required emergency cholecystectomy. The mean time of LC procedure and the mean postoperative hospital stay were significantly longer in symptomatic patients when compared with asymptomatic patients (P=0.01 and 0.02, respectively). After LC, a significant reduction in hospital admission rates compared with the rate of admissions during the period before the operation was observed in both groups of patients.
Conclusion Elective (prophylactic) LC is recommended to patients with SCD having asymptomatic cholelithiasis because waiting for the appearance of symptoms worsens the postoperative outcome.

Keywords: asymptomatic cholelithiasis, prophylactic laparoscopic cholecystectomy, sickle cell disease


How to cite this article:
El-Menoufy MA, El-Barbary HM, Raslan SM. Asymptomatic gallstones in patients with sickle cell disease: to wait or to operate?. Egypt J Haematol 2019;44:28-33

How to cite this URL:
El-Menoufy MA, El-Barbary HM, Raslan SM. Asymptomatic gallstones in patients with sickle cell disease: to wait or to operate?. Egypt J Haematol [serial online] 2019 [cited 2019 Oct 23];44:28-33. Available from: http://www.ehj.eg.net/text.asp?2019/44/1/28/268003




  Introduction Top


Sickle cell disease (SCD) is an inherited blood disorder in which the red blood cells undergo sickling when they become deoxygenated, as a result of synthesis of abnormal hemoglobin. Its course is characterized by chronic hemolytic anemia and episodes of pain (vaso-occlusive or painful crises), associated with or without tissue damage. The crisis is usually precipitated by dehydration, physical stresses, exposure to cold weather or hypothermia, acidosis, and infections [1].

Gallstones are frequent complications of SCD owing to enhanced chronic hemolysis and increase bilirubin excretion with subsequent pigment gall stone formation [2].

The development of gallstones in patients with SCD is age dependent: 15% under 10 years of age, 22% between 10 and 14 years of age, and 36% between 15 and 18 years of age, with a reported incidence of 70% by the age of over 30 years [3],[4]. The increased incidence of gall stone in SCD may be − at least partially − owing to increased detection by ultrasound and the increased survival of patients with sickle cell.

Symptoms of cholelithiasis such as biliary colic, vomiting, and infection usually precipitate a sickle cell crisis, which adds more to the morbidity of the disease [5].

Owing to the increased incidence of complications of symptomatic gallstones in patients with SCD (67%) associated with perioperative increased morbidity and mortality, elective laparoscopic cholecystectomy (LC) is offered to these patients, with proper perioperative care, improved anesthesia, and minimally invasive technique [6],[7]. In previous studies, the incidence of postoperative complications was 16% in case of emergency cholecystectomy compared with 6% in elective ones. This was reflected on morbidity and increased hospital stay [3],[8].

It has been found that one-half of the patients with asymptomatic stones experience complications within 3–5 years of diagnosis [9]. However, elective removal of asymptomatic gallstones, diagnosed incidentally, is a controversial matter [10],[11], and there are no enough data in the current literature to decide elective cholecystectomy in asymptomatic patients [12],[13].

The aim of this study was to compare the outcome of LC in asymptomatic and symptomatic cholelithiasis in SCD.


  Patients and methods Top


Patients

The study was performed on 42 patients with sickle cell having cholelithiasis and were offered LC in a secondary level hospital in Qatif, Eastern Province KSA, where SCD is endemic.

All patients with sickle cell of both sexes, who underwent LC irrespective of its indications, were included in this study. The median age of the patients was 16.5 years (range: 8–39 years). They were 22 males and 20 females. Informed written consent was obtained in accordance with the Declaration of Helsinki, and the study was approved by the local ethical committee.

Data included age, sex, mode of admission (elective or emergency), indication for LC, and diagnostic investigations.

Patients were divided into two main groups depending on the presence or absence of clinical symptoms of gallstones or their complication(s):
  1. Group A (asymptomatic): included 30 (72%) patients.
  2. Group B (symptomatic): included 12 (28%) patients.


Preoperative investigations and management

A multidisciplinary team was responsible for referral, management, and follow-up of patients with SCD. This team included consultant hematologist, anesthesiologists, and two consultant surgeons with laparoscopic experience who performed the operations.

Patients were required to undergo the standard preoperative investigations including complete blood count, hemoglobin electrophoresis, coagulation profile, liver and kidney function tests, screening for hepatitis, and blood sugar. Hemolytic profiles such as serum bilirubin, lactate dehydrogenase, and reticulocyte count were also included.

Abdominal ultrasonography was routinely performed for all patients to confirm the clinical diagnosis of cholelithiasis and to show the number of stones, their sizes, gallbladder wall thickness, pericholecystic collection, and diameter of common bile duct (CBD).

Then, the hematologist referred these patients with sickle cell with gallstones to the surgeons who performed LC on these patients, whether they were symptomatic or asymptomatic. Informed consent was taken from all patients who agreed for surgery. Patients with suspected CBD stones (choledocholithiasis) ultrasonogrophically (CBD diameter>6 mm) were confirmed by magnetic resonance cholangiopancreatography (MRCP) and followed by emergency LC in the nearest list.

Upon admission, specific perioperative management was started, including intravenous hydration, adequate oxygenation, and intravenous pain killers. Simple packed red blood cell (PRBC) transfusion to get the hemoglobin levels above 10 g/dl and packed cell volume between 30 and 34% is essential. Exchange transfusion was performed to patients who were considered severely ill, based on a history of frequent hospital admissions with sickling crises and presence of sickle-related complications.

All patients received prophylactic intravenous antibiotics, started 2 h before surgery and were continued for 5 days after the procedure. Intravenous pain killers were started in severe pain and then continued on an oral basis; subcutaneous administration of low-molecular-weight heparin in prophylactic doses during the postoperative period was done, and early mobilization was started.

Laparoscopic technique

LC was carried out under general anaesthesia using the standard four-port technique, and the pneumo-peritoneum was created by the closed method using Veress needle in Plamer’s point. Clear identification and division of cystic duct and artery between clips was done, and removal of the gallbladder was performed with the monopolar electrosurgical hook in all cases. Drains were selectively used according to surgeon’s preference. During operation, all patients were kept warm, well hydrated, and well oxygenated, and any acid–base imbalance was corrected to avoid sickling and its complications.

The removed gallbladder in all patients was sent to the laboratory for histopathological examination.

We compared the results observed in the two patient groups who received LC, in terms of duration of the procedure, days of hospital stay, and postoperative morbidity and mortality.

The patients were followed up for 6 months after the operation and the number of postoperative admissions during this period was compared with the number of preoperative admission during the 6 months before operation in both groups of patients.

The outcome was correlated in both groups.

Statistical analysis

Results were tabulated and statistically studied using statistical package for the social sciences (SPSS for Windows, version 16.0; SPSS Inc., Chicago, Illinois, USA) software. χ2-Test, Mann–Whitney test, or Student t-test was used as appropriate. Numerical variables were presented as mean and SD or median and range as appropriate, whereas categorical variables were presented as frequency and percentage. Any difference with P value less than 0.05 was considered statistically significant.


  Results Top


The clinical characteristics of the patients with sickle cell with asymptomatic and symptomatic cholelithiasis were shown in [Table 1]. Three (25%) patients in the symptomatic group had choledocholithiasis with raised serum direct bilirubin, jaundice, and dilated CBD. MRCP followed by emergency LC was performed to these three cases. In the asymptomatic group, one patient had cholelithiasis associated with huge splenomegaly and hypersplenism, to whom we did LC and splenectomy.
Table 1 Clinical, preoperative, and operative characteristics of the patients with sickle cell with cholelithiasis

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Of 42 cases, 12 (28%) cases were investigated because of clinical symptoms of cholelithiasis, whereas 30 patients were diagnosed during routine screening.

The percentage of cholelithiasis was significantly higher in the 12–30 years age group (69%) than in the age groups younger than 12 (9.5%) years and over 30 (21.5%) years (P=0.013); the age of the vast majority of the patients was before 30 years, with a median age of 16.5 years.

There were no significant differences in frequency of cholelithiasis between males and females (52.4 and 47.6%, respectively, P=0.884).

In the symptomatic group, three (25%) patients were electively operated, and nine patients required emergency cholecystectomy, whereas all asymptomatic patients (100%) were electively operated upon (P=0.001). This was reflected on the time of the procedure, postoperative hospital stay, and the occurrence of postoperative complications. No operative or postoperative deaths in either group were observed.

Accordingly, the mean time of the LC procedure and the mean postoperative hospital stay (number of days) were significantly longer in symptomatic patients when compared with those with asymptomatic cholelithiasis (P=0.01 and 0.02, respectively).

The hospital stay was prolonged in the emergency cases; one patient developed severe painful crisis after admission, and postoperative acute chest syndrome which required ICU admission and urgent PRBC exchange transfusion. The other developed a postoperative persistent serous discharge with increased drain output, which had to be removed after 4 days. Three patients had postoperative fever and one had pulmonary atelectasis following a prolonged and difficult cholecystectomy.

On the contrary, we observed a statistically significant reduction in the number of admissions through 6 months after performing LC compared with that of admissions during 6 months before performing LC in both groups of patients with symptomatic and asymptomatic cholelithiasis (P=0.01 and 0.03, respectively; [Table 2]).
Table 2 Mean number of preoperative and postoperative admissions of patients with sickle cell with cholelithiasisa

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Histopathologically, features of cholecystitis were found in three (10%) of the asymptomatic patients and in 10 (83%) of the symptomatic patients.

Our records showed that 67% of admissions of the symptomatic patients before performing LC were related to SCD (mostly owing to recurrent painful crises). Overall, 46% were precipitated by biliary colic and complications of gallstones. On the contrary, 80% of admissions before LC in the asymptomatic group were related to other SCD complications and blood component transfusion therapy.

The reasons for recurrent postoperative admisions in the symptomatic group included LC following MRCP (CBD stones) in three patients, and anemia and PRBC transfusion therapy in nine patients. In the asymptomatic group, recurrent PRBC transfusion therapy was the reason in 10 patients and painful crisis in two.


  Discussion Top


The incidence of cholelithiasis in SCD is age dependent [3],[4]. In the present study, the majority of cases were diagnosed between 12 and 30 years of age. This result matched with that recorded by other authors [3],[4],[5]. Therefore, we suggest that this group of patients should be made aware of the symptoms of gallstones, their risk, and possible complications, and the need for routine preventive measures and regular follow-up.

Complications of symptomatic cholelithiasis may occur as the first presentation, and the proportion of choledocholithiasis in our series was 25% of symptomatic patients. This matched with the finding recorded by Ware et al. [14].

The surgical approach we used is laparoscopic technique which has many advantages over an open surgery, including less surgery-related complications, shorter operative time, less postoperative pain, faster postoperative recovery, and shorter hospital stay [10],[15].

Prophylactic removal of gallstones in asymptomatic sickle cell patients remains a controversial matter as there are no shortcut guidelines for the management of asymptomatic cholelithiasis in SCD. Many experts [10],[11] do not recommend surgery before appearing of symptoms, and episodes of acute cholecystitis have to be treated conservatively with antibiotics, analgesics, and general care until the crisis is over. LC should then be performed. Other authors suggested the benefit of performing LC in asymptomatic patients [13].

Prophylactic cholecystectomy of asymptomatic gallstones may diminish SCD-related postoperative complications that usually happen in emergency or even elective operations in patients with symptomatic cholelithiasis [3],[8],[16],[17],[18]. It has been reported that emergency cholecystectomy is usually associated with a high risk of operative and postoperative complications in patients with sickle cell [19].

Similar findings were reported by the present study, as we observed major postoperative complications in 42% of patients with symptomatic cholelithiasis, whereas only 13% of patients with asymptomatic cholelithiasis developed minor postoperative complications and the vast majority of patients progressed satisfactorily after surgery. It was also noticed that the mean total hospital stay was significantly higher in patients who underwent emergency cholecystectomy.

Furthermore, the frequent vaso-occlusive (painful) crisis precipitated by the frequently occurring biliary colics and acute cholecystitis added more to the morbidity of disease [12]. This was the case in six of our symptomatic patients as they developed a painful crisis on admission owing to persistent biliary colic and they were too sick to wait for elective surgery, as even potent narcotic analgesics failed to improve symptoms and they had to be operated immediately. No operative or postoperative mortality in either group was reported. The perioperative measures that were implemented may explain these results.

Although the removed gallbladders of asymptomatic patients were normal in most of our cases apart from the presence of pigment gallstones, gallbladders of most of symptomatic patients showed histopathological features of chronic inflammation (chronic cholecystitis). It is well known that inflammation and infection may precipitate a sickle or hemolytic crisis by inducing the release of inflammatory mediators (interleukin-1, interleukin-6, and tumor necrosis factor-α) [20]. In addition, a number of viruses and bacteria (Papovirus B 19, Epstein–Barr virus,  Salmonella More Details spp., Pneumococci, and Streptococci) are also implicated.

In addition, the presence of the gallbladder in an inflammatory state makes its dissection and exposure of the cystic duct and artery more difficult with subsequent longer operative time [19],[21]. This was particularly evident in three of our patients in whom we had to operate upon in the presence of acute cholecystitis. Subsequently, the operative time and postoperative hospital stay were prolonged in these patients.

Thus, prophylactic cholecystectomy should be considered for patients with SCD with asymptomatic cholelithiasis for various reasons: first, the procedure excludes the biliary complications in the presence of painful crisis because both of conditions have similar presenting symptoms, otherwise the diagnosis and management would be difficult.

Second, the natural history of cholelithiasis in patients with sickle cell seems to be different from that of the general population in which cholelithiasis affects only 10% of adults by the age of 60 years [22]. In patients with sickle cell, cholelithiasis usually occurs at a younger age, with higher incidence as 70% of patients with sickle cell older than 30 years have cholelithiasis [4].

Third, 50% of patients with asymptomatic cholelithiasis develop biliary complications within 3–5 years of diagnosis [9],[22]. The onset of symptoms itself is considered a complication that should be avoided, as emergency surgery in patients with sickle cell can be associated with high morbidity and mortality [18],[19],[20],[21],[22],[23]. In addition, potential complications in emergency cholecystectomy in patients with sickle cell may be also related to the general anesthesia and the inability to implement the recommended perioperative care such as exchange PRBC transfusion and proper hydration [12].

Fourth, the frequency of hospital admissions in children with sickle cell having gallstones is twice as high as that of normal children with gallstones [13]. The present study demonstrated that the frequency of admission after cholecystectomy was significantly reduced when compared with that before operation in both groups of patients.

Fifth, the postoperative SCD-related complications were less frequent for asymptomatic patients who experienced prophylactic LC [18]. This fact was evident in our study as the postoperative complications were present in only 13% of asymptomatic patients versus 42% of the symptomatic group. This procedure, when performed with adequate perioperative management, is safe and helps to avoid emergency operations in case of exposure to acute complications such as cholecystitis, cholangitis, and choledocholithiasis.

Sixth, prophylactic LC significantly reduced the operative hospital stays when compared with symptomatic group. Similar results were reported by Muroni et al. [10].

Thus, we proposed prophylactic LC for patients with asymptomatic cholelithiasis. The favorable postoperative outcome we noticed in these cases is encouraging. Considering the potential complications of SCD, it becomes clear that prophylactic LC should be offered when cholelithiasis is discovered by abdominal ultrasonography.


  Conclusion Top


Based on our results, we can safely recommend prophylactic LC with proper perioperative management to patients with SCD if cholelithiasis is diagnosed by ultrasonography even if they are asymptomatic because the occurrence of symptomatic cholelithiasis worsens postoperative outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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