JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Volume 24, Number 0, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/lap.2014.0280

2014 IPEG Paper

Outcomes After Early Splenectomy for Hematological Disorders Nirmal Gokarn, MD,1 Deepa Manwani, MD,2 Patricia Friedmann, MS,3 Steven H. Borenstein, MD,4 Dominique Jan, MD, PhD,4 and Elizabeth Renaud, MD 4

Abstract

Purpose: Acute splenic sequestration crisis is a devastating complication of sickle cell disease that can require prophylactic splenectomy. Historically, splenectomy before 5 years of age was avoided because of fear of overwhelming postsplenectomy sepsis. Recently, splenectomy has been performed as early as 2 years of age, but the safety of this approach is unknown. This study compared outcomes of splenectomy performed in patients under 5 years of age with those 5 years of age and older. Materials and Methods: A retrospective chart review of patients registered in a children’s hospital hematology database was performed to examine intraoperative and postoperative outcomes after splenectomy. Statistical data analysis included Fisher’s exact tests for categorical variables and the nonparametric median test for continuous variables. Results: From 1997 to 2012, 30 sickle cell patients underwent splenectomy. At surgery, 18 of the 30 patients were under 5 years of age (Group 1), and 12 patients were 5 years of age or older (Group 2). Almost all procedures were laparoscopic. Both group had similar operative times, rates of conversion, and frequencies of complications. Both groups had similar lengths of follow-up (median, 62 months for Group 1 versus 63 months for Group 2). No portal vein thromboses or postsplenectomy sepsis events occurred in either group. Conclusions: In this study, there was no evidence that the incidence of complications was higher after splenectomy at a younger age. A large, multicenter study is needed to further evaluate the safety of this practice.

postsplenectomy sepsis in children less than 5 years of age,5–7 previously splenectomy was delayed in young children experiencing ASSC.5,8 Overwhelming postsplenectomy sepsis is the most dreaded complication after splenectomy and is characterized by rapid clinical deterioration resulting from septicemia with an associated high mortality rate.1,6 However, data regarding the risk of postsplenectomy sepsis predate modern antibiotic therapy for prophylaxis and treatment and improvements in immunoprophylaxis. Therefore, they may not accurately reflect the current risk of splenectomy for the younger child. In addition, more recent guidelines have encouraged splenectomy in children younger than 5 years of age who experience ASSC because of the high morbidity and mortality of this condition.2 Although many tertiary pediatric care facilities have adopted this practice, the safety of splenectomy in children under 5 years of age is unknown. Given the lack of information about the outcomes of splenectomy in younger children, we reviewed our experience to

Introduction

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ickle cell disease is a hematological disorder that results in red blood cell deformity and is characterized by recurrent vasoocclusive episodes, accelerated hemolysis, increased susceptibility to infection, and chronic end-organ damage.1,2 Acute splenic sequestration crisis (ASSC) is a life-threatening complication of sickle cell disease that occurs secondary to trapping of deformed cells in the splenic vasculature. The result is rapid splenic enlargement, a compensatory elevation of the reticulocyte count, a decrease in hemoglobin level greater than 2 g/dL from the patient’s baseline level, and potential shock. Mortality for the first episode of ASSC is approximately 12%, and sequestration can recur in up to 50% of patients.2,3 These crises can occur as early as the first year of life. Splenectomy prevents recurrent ASSC.1,3,4 However, because historical data demonstrated a higher likelihood of

Divisions of 1General Surgery and 4Pediatric Surgery, Department of Surgery, Montefiore Medical Center, Bronx, New York. 2 Division of Hematology and Oncology, Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, New York. 3 Department of Surgery, Albert Einstein College of Medicine, Bronx, New York.

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evaluate the safety of splenectomy performed in patients with hematological disorders less than 5 years of age compared with splenectomy performed in patients 5 years of age and older. To this end, we compared intraoperative, perioperative, and postoperative outcomes between the two age groups. Materials and Methods

This study was a retrospective review of the experience at a single, tertiary-care pediatric hospital. After institutional review board approval, patients with sickle cell disease and treated by the hematology service between 1997 and 2012 were identified from the institution’s pediatric sickle cell patient database. These patients were cross-referenced with the operative logs of the Division of Pediatric Surgery to identify those who had either open or laparoscopic splenectomy. Preoperative vaccination and postoperative antibiotic prophylaxis were administered per the protocols of the Division of Pediatric Hematology. Patients were immunized with the pneumococcal polysaccharide 23-valent vaccine at 2 and 5 years of age, as well as the pneumococcal conjugate vaccine starting in 2000, with catch-up immunizations completed 2 weeks prior to surgery. They also received the meningococcal vaccine. Patients were referred for surgery according to published National Heart, Lung, and Blood Institute guidelines: patients underwent splenectomy after one life-threatening event or two severe events necessitating transfusions as long as the patient was over 2 years of age and had received at least one of the pneumococcal polysaccharide vaccines at 2 years of age. Procedures included laparoscopic and open splenectomy performed by one of six board-certified pediatric surgeons within the stated time period. Postoperatively, patients were maintained on oral penicillin prophylaxis daily. Patients with a temperature of 100.4C or greater postoperatively were evaluated for sepsis with blood cultures and received a minimum of 48 hours of antibiotics. Clinical information for the study was obtained through a retrospective chart review. Patients were analyzed by age, gender, hematologic specific data points, and age at splenectomy. Outcomes examined included operative time, intraoperative and postoperative complications, duration of hospitalization, and occurrence of postsplenectomy sepsis and mesenteric or portal vein thrombosis. Descriptive data were reported using frequencies for categorical variables and means, standard deviations, medians, and ranges for continuous variables. Because of the small sample size of the study and the non-normal distribution of the data, nonparametric statistics were used for analysis. The Wilcoxon test was used to analyze continuous variables. Categorical variables were analyzed using chi-squared and Fisher’s exact tests. Results

Between July 1997 and October 2012, 30 patients underwent splenectomy for hematological conditions. Eighteen patients were under the age of 5 years at the time of splenectomy (Group 1), and 12 patients were 5 years of age or older (Group 2). In Group 1, all 18 patients had splenic sequestration; in Group 2, 11 patients had splenic sequestration, and 1 patient had a diagnosis of immune thrombocytopenic purpura. The median age at splenectomy in Group 1 was 32 months (range, 20–50 months) and the median age in Group 2

FIG. 1. Splenectomies performed by age group by year. Group 1 was younger than 5 years of age, and Group 2 was 5 years of age or older at the time of splenectomy. was 66 months (range, 60–177 months). The two groups were similar in terms of gender (50% males in Group 1, 50% males in Group 2). Patients in Group 1 underwent splenectomy between 1997 and 2012; patients in Group 2 underwent splenectomy between 2002 and 2011 (Fig. 1). Individual patients in Group 1 had more sequestration events before splenectomy than patients in Group 2: median number of events in Group 1, 3 (range, 2–7 events); in Group 2, 2 (range, 0–7) (Pp.032). However, they had a similar number of transfusions and a similar number of admissions before splenectomy (Table 1). Operative records were available for 18 patients in Group 1 and 10 patients in Group 2. All 18 patients in Group 1 underwent successful laparoscopic splenectomy. In Group 2, there were nine laparoscopic splenectomies and one open splenectomy. Of those undergoing laparoscopic splenectomy, there were no conversions to an open procedure in Group 1 and one conversion in Group 2 (conversion due to bleeding) (Pp.36). Operative times were available for 17 patients in Group 1 and 10 patients in Group 2. There was no statistically significant difference in operative times between the groups, although both the median and mean operative times were shorter in Group 1. There was one intraoperative complication in Group 1 (bowel contusion requiring surgical repair) and one intraoperative complication in Group 2 (bleeding) (Table 2). Information on length of postoperative stay was available for 18 patients in Group 1 and 11 patients in Group 2. The median length of stay was 4 days (range, 2–12 days) in Group

Table 1. Events Prior to Splenectomy by Group Group 1 Event Sequestrations Transfusions Admissions

Group 2

Median Range Median Range P value 3 4 6

2–7 2–26 1–25

2 4 4

0–7 1–20 1–22

.03 .96 .32

Group 1 was younger than 5 years of age, and Group 2 was 5 years of age or older at the time of splenectomy.

EARLY SPLENECTOMY FOR HEMATOLOGICAL DISORDERS

Table 2. Operative Outcomes by Group Group 1

Group 2

n 18 10 Laparoscopic/open 18/0 9/1 Conversion to open 0 1 Operating room time (minutes) Median 140 (n = 17) 175 (n = 10) Mean 143.1 (n = 17) 184.3 (n = 10) Intraoperative 1 1 complications

P value .36 .36 .15 1.0

Group 1 was younger than 5 years of age, and Group 2 was 5 years of age or older at the time of splenectomy.

1 and 6 days (range, 4–37 days) in Group 2 (Pp.10). There were three postoperative complications in Group 1: one pneumonia, one acute chest syndrome with pneumonia, and one silent infarct. There were two in Group 2: one Clostridium difficile infection and one acute chest syndrome (Pp1.0). There were no episodes of mesenteric or portal vein thrombosis in either group. The length of postsplenectomy follow-up was similar for both groups: median length of follow-up for Group 1, 62 months (range, 10–193 months); for Group 2, 63 months (range, 27–128 months) (Pp.73). There were no episodes of postsplenectomy sepsis in either group during the follow-up period. Discussion

Surgeons and hematologists historically have delayed surgery for splenectomy in children with sickle cell disease because of the technical considerations of operating on a small child, limitations imposed by laparoscopic equipment, and the increased risk of overwhelming postsplenectomy sepsis. Overwhelming postsplenectomy sepsis is potentially lethal and believed to be more likely in patients who undergo splenectomy before the fifth birthday and prior to the development of a mature humoral immune system. Over the last decade, advancements in laparoscopic equipment and technique have enabled successful completion of complex laparoscopic procedures in patients as small as newborns; therefore, the technical limitations of laparoscopy in smaller children have become less of a concern. The last few decades also have witnessed advances in vaccinations and antibiotic treatments which may reduce the risk of postsplenectomy sepsis.6,9 However, previous studies have not compared the outcomes of splenectomy in sickle cell patients under 5 years of age with those of older children in order to determine the safety of this practice. As shown, the procedures in this study occurred over a similar time range. Therefore, the comparisons between groups should be unaffected by factors such as laparoscopic experience of the surgeons, advances in laparoscopic instrumentation, and changes in medication and vaccinations that may have occurred during this time period. The number of preoperative sequestration events was greater in Group 1. This is not surprising as patients with greater severity of sequestration were referred earlier for splenectomy according to the practice of the center’s hematology group, which followed published National Heart,

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Lung, and Blood Institute guidelines. In addition, as patients may experience sequestration at any age, patients in Group 2 may have been older at the time of their first event and referred for surgery soon after, thereby limiting the number of preoperative sequestration events in this group. The retrospective nature of this review limited analysis of this outcome. In addition, there were similar numbers of transfusions and admissions before surgery in each group; this outcome may also reflect the practice of referring those patients with recurrent sequestration for surgery regardless of age. Although the difference in operative time between groups was not statistically significant, the median operative time was 35 minutes shorter in Group 1, the patients less than 5 years of age. This could be considered of clinical significance. This result reflected the trend in operative times and was not influenced by outliers. The small number of study patients limited the statistical analysis in this study. From a clinical standpoint, why operative time was shorter for patients less than 5 years of age was unclear, but may be due to splenic enlargement in older patients, which increased the difficulty of the procedure. Again, analysis was limited by the retrospective nature of this study. The two groups had similar postoperative outcomes. Although previous reports cite a prevalence of mesenteric or portal venous thrombosis as high as 5% after laparoscopic splenectomy,10,11 this major complication did not occur in any of the 30 patients. In addition, there were no admissions for sepsis seen in either group. As the median length of follow-up was over 5 years for each group and the risk of overwhelming postsplenectomy sepsis is highest in the first 2 years after surgery,7 it is unlikely that episodes were missed. Therefore, the occurrence of sepsis after splenectomy at this institution was much lower than the frequency of 10% quoted previously.6,12 The patient sample size for this study was relatively small, which limited the statistical analysis of the data and our ability to examine specific outcomes such as C. difficile infection and intraoperative bleeding. In addition, data collection was retrospective. Several patient records had gaps and incomplete details that limited further analysis of the results. In conclusion, our data provide no evidence of an increase in surgical complications for patients with hematological disorders who were under 5 years of age at the time of splenectomy compared with patients 5 years or older at the time of procedure. Although limited by a small sample size and the retrospective nature of the study, this result has not been previously reported. Large, prospective, multicenter studies are needed to further assess the safety of this surgical practice in a younger patient population. In order to rule out the possibility of a 5% difference between groups in either rate of sepsis or in surgical complications, we would need approximately 700 patients per group. Given the large sample size needed vis-a`-vis the relatively low rates of complications reported in the literature and the relatively small numbers of patients with acute splenic sequestration, the feasibility of conducting such a large trial seems at the very least a challenge. Certainly the logistics, cost, and time involved would be significant. We therefore sought to report on our singlecenter experience until such multicenter data become available. Until then, our outcomes may assist physicians when considering the clinical options for a young patient with sickle cell disease and sequestration.

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Disclosure Statement

No competing financial interests exist. References

1. Lesher AP, Kalpatthi R, Glenn JB, Jackson SM, Hebra A. Outcome of splenectomy in children younger than 4 years with sickle cell disease. J Pediatr Surg 2009;44:1134–1138. 2. Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health. The Management of Sickle Cell Disease, 4th ed. NIH Publication Number 02-2117. Bethesda, MD: National Institutes of Health, 2002, pp. 119–121. 3. Topley JM, Rogers DW, Stevens MCG, Serjeant GR. Acute splenic sequestration and hypersplenism in the first five years in homozygous sickle cell disease. Arch Dis Child 1981;56:765–769. 4. Al Salem AH, Qaisaruddin S, Naserullah Z, Al Dabbous I, Abu Srair H, Al Jam’a A. Splenectomy and acute splenic sequestration crises in sickle cell disease. Pediatr Surg Int 1996;11:26–28. 5. Diamond LK. Splenectomy in childhood and the hazard of overwhelming infection. Pediatrics 1969;43:886–889. 6. Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: Actual versus perceived risks. Br J Surg 1991;78:1031–1038. 7. Jugenburg M, Haddock G, Freedman MH, Ford-Jones L, Ein SH. The morbidity and mortality of pediatric splenectomy: Does prophylaxis make a difference? J Pediatr Surg 1999;34:1064–1067.

8. Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. 9. McCavit TL, Xuan L, Zhang S, Flores G, Quinn CT. Hospitalization for invasive pneumococcal disease in a national sample of children with sickle cell disease before and after PCV7 licensure. Pediatr Blood Cancer 2012;58: 945–949. 10. Oomen MWN, Minden M, van Rijin RR, Peters M, Heij HA. Implementation of laparoscopic splenectomy in children and the incidence of portal vein thrombosis diagnosed by ultrasonography. J Pediatr Surg 2013;48:2276–2280. 11. Soyer T, Ciftci AO, Tanyel FC, Senocak ME, Buyukpamukcu. Portal vein thrombosis after splenectomy in pediatric hematologic disease: Risk factors, clinical features, and outcome. J Pediatr Surg 2006;41:1899–1902. 12. Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood 2013;122: 4782–4790.

Address correspondence to: Elizabeth Renaud, MD Division of Pediatric Surgery Department of Surgery Montefiore Medical Center 111 East 210th Street Bronx, NY 10467 E-mail: [email protected]

Outcomes after early splenectomy for hematological disorders.

Acute splenic sequestration crisis is a devastating complication of sickle cell disease that can require prophylactic splenectomy. Historically, splen...
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