Updates Surg (2013) 65:277–281 DOI 10.1007/s13304-013-0236-x

ORIGINAL ARTICLE

Laparoscopic splenectomy in patients with hereditary spherocytosis: report on 12 consecutive cases R. Vecchio • Eva Intagliata • F. Ferla • S. Marchese • R. R. Cacciola • E. Cacciola

Received: 16 July 2013 / Accepted: 2 October 2013 / Published online: 16 October 2013 Ó Springer-Verlag Italia 2013

Abstract Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency in erythrocyte membrane proteins. Removal of the spleen may reduce the intra-splenic hemolytic process of the disease and, therefore, may correct the anemia. Furthermore, it seems to decrease the levels of serum bilirubin, thus reducing the formation of gallbladder stones. Indications and timing of splenectomy, however, are still debated. Twelve patients with severe hereditary spherocytosis operated on with laparoscopic splenectomy were retrospectively reviewed. Median age at diagnosis was 13.8 years (range 8–25 years). Male to female ratio was 5/7. Indications for laparoscopic removal of the spleen included anemia unresponsive to iron supplementation in eight patients (66.6 %) with increase need for red cells transfusions, and jaundice with symptoms related to cholelitiasis in four patients (33.3 %). Laparoscopic splenectomy was associated in four cases to laparoscopic cholecystectomy. Mean operative time was 50 min (range 40–75 min) with no conversion to open surgery. Mean hospital stay ranged from 3 to 7 days. In a 16-month follow-up, no complications were recorded and a persistent correction of anemia was observed. With the advent of laparoscopic surgery, splenectomy has been performed by this mini-invasive approach in referral centers. Laparoscopic splenectomy is an effective technique, when performed in patients with hereditary spherocytosis. Low complication rate and persistent correction of the

R. Vecchio  E. Intagliata (&)  F. Ferla  S. Marchese Department of Surgery, University of Catania, Catania, Italy e-mail: [email protected] R. R. Cacciola  E. Cacciola Hematologic Unit, Department of Biomedical Science, University of Catania, Catania, Italy

hematologic disorders can be expected after the laparoscopic splenectomy, provided that a proper technique is performed and an experienced surgical team is available. Keywords Laparoscopic splenectomy  Spleen surgery  Hereditary spherocytosis

Introduction Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency in erythrocyte membrane proteins. Removal of the spleen may reduce the intra-splenic hemolytic process of the disease and, therefore, may correct the anemia. Indications and timing of splenectomy, however, are still debated, since surgery is at risk for early and late post-operative infections and portal vein thrombosis [1–3]. With the advent of laparoscopic surgery, splenectomy has been performed by this mini-invasive approach in referral centers [4, 5]. In this study, the authors report on 12 consecutive cases of laparoscopic splenectomy in hereditary spherocytosis. Review of the indications for laparoscopic splenectomy and results are discussed.

Materials and methods Among 119 patients operated on with laparoscopic splenectomy from January 2000 to December 2012 in the Department of Surgery of the University of Catania, the clinical charts of 12 patients with hereditary spherocytosis were retrospectively evaluated. Hereditary spherocytosis was diagnosed on the basis of clinical history, physical examination and laboratory tests.

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Complete blood count, blood smear, reticulocytes count, bilirubin concentration, osmotic fragility test and direct Coombs test were studied. Red cell osmotic fragility was evaluated after red blood cell washing in a solution of increasing concentration of sodium chloride. All the patients were screened by abdominal ultrasonography to evaluate spleen size and associated cholelitiasis. Severity of the disease was assessed according to the hemoglobin level, and hereditary spherocytosis was classified as severe, moderate and mild. Severe spherocytosis anemia was classified with a hemoglobin concentration below 80 g/L, while mild disease was considered with a hemoglobin concentration above 110–120 g/L [1, 6–8]. Before splenectomy, all the patients received immunization for Haemophilus influenzae, Streptococcus pneumoniae and Meningococcus at least 15 days ahead the surgical procedure. Penicillin prophylaxis was accomplished with a single-dose pre-operative administration and was continued for at least 2 months after surgery. The laparoscopic procedure was accomplished through the insertion of a Hasson trocar and three other trocars (two of 5 mm and one of 12 mm). With patients lying in the right lateral position with the left flank elevated about 30° above the operating table, the trocars were positioned in the sub-xiphoid region (5 mm trocar), above the transverse umbilical line in the left hypochondrium (Hasson trocar), in the left flank at the level of the transverse umbilical line (12 mm-trocar), and in the left subcostal area in the anterior axillary line (5 mm trocar). An additional 5 mm trocar was introduced in right subcostal line in the anterior axillary line, when associated cholecystectomy was scheduled. After introduction of the trocars, diagnostic laparoscopy and detection of accessory spleens were accomplished. Two patients had accessory spleens which were removed during the operation. The procedure of splenectomy began with the division of the spleno-colic ligament followed by the section of the gastro-splenic ligament by means of the ultrasonic dissector. After division of the spleno-colic and spleno-diaphragmatic ligaments and complete dissection of the splenic hilum from the pancreatic tail, splenic arteries and veins were secured with an endostapler [9]. The spleen was then inserted in a plastic laparoscopic bag, which was pulled through the Hasson trocar site and removed after its fragmentation. Operation was completed by positioning of drainage in the left sub-diaphragmatic region. In four patients with associated cholelitiasis, laparoscopic cholecystectomy was performed before splenectomy. In the traditional fashion, dissection, clipping and division of the cystic artery and duct were accomplished, and gallbladder was dissected from the liver bed and removed in an endobag. Lesions of the common bile duct

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Updates Surg (2013) 65:277–281 Table 1 Clinical data of patients with hereditary spherocytosis operated on with laparoscopic splenectomy Gender Male

5 patients (42 %)

Female

7 patients (58 %)

Median age at diagnosis

13.8 years (range 8–25 years)

Severity classification of the disease Mild (Hb [ 110–120 g/L)

0

Moderate (80 \ Hb \ 110–120 g/L) Severe (Hb \ 80 g/L)

0 12 patients

Indications for laparoscopic splenectomy Increased need of RBC transfusion

8 patients (66.6 %)

Lithiasic cholecystitis

4 patients (33.3 %)

Mean spleen size

15 cm (range 10–18 cm)

Associated laparoscopic cholecystectomy

4 patients

Mean operative time

50 min (range 40–75 min)

Conversion rate

0%

Mean hospital stay

3.5 days (range 3–7 days)

Complications

0%

Department of Surgery, Laparoscopic Surgery Unit, University of Catania, Policlinico V. Emanuele Hospital, Catania, Italy

were avoided by appropriate suspension of the gallbladder and by proper isolation of cystic artery and duct [10].

Results Clinical and laboratory data of the patients with hereditary spherocytosis are shown in Table 1. Median age at the diagnosis was 13.8 years (range 8–25 years). Male to female ratio was 5:7. Main reasons for referral to our Department of Surgery were anemia unresponsive to iron supplementation in eight patients (66.6 %), splenomegaly in seven patients (58.3 %), and jaundice in four cases (33.3 %). All the patients had a severe disease with hemoglobin level below 80 g/L, with a peripheral blood smear showing spherocytic red cells. The median reticulocytes count was 6.5 %. Indirect bilirubin concentration ranged from 1.5 to 3 mg/dL, with a median value of 2.0 mg/dL. A positive red cell osmotic fragility test was recorded in all the patients. Indications to splenectomy were increased need for red cell transfusions in eight patients (66.6 %) and symptoms related to cholelitiasis in four patients (33.3 %). Ultrasonography showed spleen size ranging from 10 to 18 cm (mean 15 cm). Splenectomy was performed in all the patients through the laparoscopic approach. Cholecystectomy was associated with the removal of the spleen in four patients.

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Mean operative time was 50 min (range 40–75 min). Neither intra-operative complications nor conversion to open surgery was recorded. The mean amount of operative bleeding was 50 mL (range 0–150 mL). Mean hospital stay was 3.5 days (range 3–7 days). At a mean follow-up of 16 months, neither early nor late local or systemic infections were observed. All the patients who were splenectomised were subjected to prophylaxis for portal vein thrombosis and pulmonary embolism with a daily single dose of low-weightmolecular heparin, which was prolonged for at least 3 weeks. Post-operative hematologic surveillance showed a persistent correction of the anemia in the follow-up period.

Discussion Hereditary spherocytosis is a worldwide disease and is the most common inherited anemia in Northern Europe and North America, where it affects 1/2,000 persons [6]. In most cases the hereditary transmission is autosomal dominant, and in 25–35 % of cases there are no hematological abnormalities in the parents. Approximately 65 % of cases are diagnosed during the neonatal period. However, the age of onset and the severity are highly variable; both sexes can be affected in equal measure [6]. The disease is caused by de novo mutations or by the transmission of an autosomal recessive mutation in a gene of the alpha-spectrin. The primary lesion is the loss of surface area of the red cell membrane, resulting in decreased deformability, due to defects in membrane proteins such as ankyrin, band 3, beta-spectrin, alpha-spectrin or protein 4.2 [6, 8, 11]. Because of the round shape that the erythrocytes assume, they are called spherocytes. Hemolysis is associated with an increase in the turnover of red blood cells and with an increase of bilirubin load to the liver. This can cause gallstones in the first or second decade of life, and the risk increases with the co-presence of Gilbert’s syndrome [12]. The patients may show several degree of anemia with mild, moderate and severe forms. Hemoglobin levels above 110 g/L in women and children and above 120 g/L in men should be considered mild spherocytic anemia. A hemoglobin concentration below 80 g/L is classified as severe spherocytic anemia [1]. The clinical presentation of patients with hereditary spherocytosis is quite variable. Generally, symptoms are jaundice, splenomegaly and hemolytic anemia [1, 6]. The jaundice is the first clinical sign observed in infants and is associated with anemia due to the inability to compensate completely the hyperhemolysis. Repeated

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episodes of jaundice and biliary colic, due to the increased metabolism of bile pigments, are often the first indicators of the existence of a state of hyperhemolysis. Gallstones are known in at least 5 % of children under 10 years of age, the percentage of which rises to 40–50 % in the second decade and beyond [6, 11]. Clinical manifestations of the disease also include signs and symptoms related to lithiasic cholecystitis and splenomegaly, reticulocytosis and spherocytes on peripheral blood smear [11]. Splenomegaly, caused by a high splenic sequestration of erythrocytes, has been reported in more than 75 % of patients with hereditary spherocytosis [11]. The diagnostic approach to hereditary spherocytosis is based on traditional blood tests, and investigations through biochemical and molecular biology techniques [8, 13, 14]. In the peripheral blood a decrease in erythrocyte count and hemoglobin level is almost always detectable. High increase of reticulocytosis in the absence of bleeding is also pathognomonic. Total bilirubin and the lactic-dehydrogenases are increased, but the haptoglobin is usually decreased. The test of the osmotic fragility of erythrocytes allows the definitive diagnosis, since the fragility is characteristically increased in patients with the disease [8, 13]. According to the guidelines revised by members of Haematology Task Force of the British Committee for Standards in Haematology, patients affected by hereditary spherocytosis should be selected for splenectomy on the basis of clinical symptoms and in the presence of complications such as gallstones, not only on the basis of diagnosis of spherocytosis. Therefore, indication to splenectomy in patients with hereditary spherocytosis, according to these guidelines, is not related to the preoperative length of the diagnosed disease, and timing for surgery is dictated by the onset of complications and/or worsening of the clinical and hematologic condition of the patients. Splenectomy should be performed in children aged C6 years with moderate or severe hemolysis and anemia, with or without associated gallstones. In children with no evidence of cholelithiasis, there is no indication to remove the gallbladder at the time of splenectomy. Once the spleen is removed, individuals with hereditary spherocytosis do not develop pigmentary gallbladder stones. Symptoms of cholelithiasis remain the first reason for carrying out a splenectomy in hereditary spherocytosis. In patients undergoing splenectomy, the gallbladder should be removed at the same time if there is symptomatic cholelithiasis. If gallstones are an incidental finding without symptoms, the value of cholecystectomy remains controversial. If there is symptomatic cholelithiasis in patients undergoing splenectomy, the gallbladder should be removed during the same surgery.

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Partial splenectomy in hereditary spherocytosis finds some indication, and it is theoretically associated with a decreased risk for post-splenectomy sepsis, but it is possible that additional surgery may be necessary for recurrence of the hematological disease. The partial splenectomy can be useful, but at present the effectiveness of partial splenectomy should be evaluated by further studies [6, 7, 13, 15–21]. In our series, in four cases surgical treatment consisting in laparoscopic splenectomy and cholecystectomy was proposed because of gallstone disease. In these cases, we performed cholecystectomy as first step, before laparoscopic splenectomy. The rationale is that the conversion rate during cholecystectomy is very low and if conversion is needed during the following steps of splenectomy, a left sub-costal incision could be performed avoiding large abdominal incisions. This occurred in one case of a series of laparoscopic splenectomy and cholecystectomy reported by us elsewhere [22]. Splenectomy in hereditary spherocytosis is associated with a reduction of hemolysis, with red blood cells’ life prolongation and it seems to decrease the levels of serum bilirubin, thus reducing the formation of gallbladder stones [15, 23]. These data were confirmed in our series, where correction of anemia was achieved and no sign of gallbladder stones were observed in the follow-up. Since its introduction in 1992 [24], laparoscopic splenectomy has become the technique of choice for surgical removal of the spleen [25], due to the well-recognized benefits [26, 27]. The procedure, which can be performed also in the hand-assisted fashion [28] and by a single access laparoscopy [29], is associated with risks and complications. Although the incidence of intraoperative complications is unknown, intraoperative risks in patients undergoing laparoscopic splenectomy are not uncommon. They consist mainly of intra- or post-operative bleeding, reported in 4.8 % of patients [30], and abdominal organs injuries. Knowledge of anatomical details and appropriate surgical skills are the sine-qua-non conditions to reduce, like in our series, significantly the incidence of these complications. Complications in post-operative phase can also be observed [11, 12]. Portal vein thrombosis (PVT) is the most fearsome lifethreatening complication after splenectomy. Risk factors of PVT are not completely clarified, although it is more commonly observed in patients operated on with splenectomy and malignant hematologic disease. We have observed this complication in four cases operated on with splenectomy, but in no one in this reported series of patients affected by hereditary spherocytosis [2, 18]. Another harmful post-operative complication is the overwhelming post-splenectomy sepsis, which is

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responsible of mortality in approximately 40–50 % of affected patients. With vaccinations and antibiotic prophylaxis in the described follow-up of 16 months, we never observed this complication [2, 18]. In the Literature, laparoscopic splenectomy was associated with a significantly (P \ 0.001) lower risk of pulmonary (3.8 vs. 9 %), wound (1.6 vs. 4.3 %), and infectious (1.0 vs. 3.8 %) complications, as well as subphrenic abscess (0.1 vs. 2.4 %), when compared with open surgery [30].

Conclusions Laparoscopic splenectomy is an effective technique, when performed in patients with hereditary spherocytosis. Proper technique and adequate surgical team training and experience are essential to perform the procedure in a safe way [31]. Indications may be selected and guidelines for prevention of sepsis and thromboembolism must be followed. Our data, in the indications to surgery we followed in our patients, should be compared with that of other future studies. This study, with the low complication rate reported with the laparoscopic approach, might encourage the clinicians to propose splenectomy earlier in the clinical history of patients with hereditary spherocytosis. Conflict of interest of interest.

The authors declare that they have no conflict

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Laparoscopic splenectomy in patients with hereditary spherocytosis: report on 12 consecutive cases.

Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency in erythrocyte membrane proteins. Removal of the spleen may reduce th...
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