Safety and effectiveness of total splenic vessel ligations in paediatric patients with splenomegaly.

BACKGROUNDS: Splenomegaly may contribute to hypersplenism and can result in thrombocytopenia. Many approaches are used to treat splenomegaly; however, the current management of splenomegaly has intrinsic limitations or disadvantages. Now, we initiate a new approach, that of total splenic vessel (artery and vein) ligations (TSVLs) in paediatric patients with splenomegaly. The purpose of our study is to evaluate the results obtained with TVSLs procedure for paediatric patients. PATIENTS AND METHODS: Seventeen paediatric patients with splenomegaly were screened for enrolment into this retrospective analysis. PROCEDURE: We identified and dissociated the splenic vessel. Next, we ligated the splenic artery and we used clips to ligate the vein distally and proximally. RESULT: The mean [standard deviation (SD)] splenic infarction rate of a total of 17 patients was 77.5 (5.1)% in 6 months after operation. After TSVL, the mean count of platelet (PLT) and white blood cell (WBC) increased significantly and reached a steady state in the third month. Both the PLT and WBC had a significance higher than pre-TSVL in a 1-year follow-up.
CONCLUSION: Based on the evidence, we make cautious conclusions that TSVLs are a safe and effective method in the treatment of paediatric patients with splenomegaly, achieving a satisfactory long-term haematological response and benefit.

INTRODUCTION

Splenomegaly is commonly a consequence of the hepatic portal vein system, splenic vein, and hepatic vein thrombosis, which may contribute to hypersplenism and can result in thrombocytopenia. There are several possible reasons that can cause splenomegaly, for example, infectious mononucleosis, subacute infective endocarditis, miliary tuberculosis, gibraltar disease malaria, schistosomiasis, and kala-azar. The common clinical manifestations of splenomegaly include anaemia, infection and bleeding tendency. Many approaches have been applied to treat splenomegaly, for example, surgical splenectomy,[12] splenic embolization,[345] banding or ligation of the splenic artery and placing a percutaneous stent to the splenic artery. Unfortunately, the current management of splenomegaly has intrinsic limitations and disadvantages: Surgical splenectomy can relieve hypersplenism but the morbidity after splenectomy is high,[12] some cases of hypersplenism are not significantly improved following banding or ligation of the splenic artery,[6] splenic embolization is also used to deal with splenomegaly but complications such as portal thrombosis, sepsis and the essential exposure to ray limit its utility.[35] In our clinical practice, we have initiated a new approach, that of total splenic vessel (artery and vein) ligations (TSVLs) in paediatric patients with splenomegaly and our preliminary outcomes indicate the feasibility and safety of the approach. Here we describe 17 patients with splenomegaly who were treated with TSVL. The purpose of this paper is to evaluate the results obtained with the procedure of TSVLs for paediatric patients.

PATIENTS AND METHODS

Study population and ethical considerations

According to the Health Insurance Portability and Accountability Act (HIPPA) guidelines,[7] the protocol was approved by the Institutional Review Board and all patients provided written informed consent. Between June 2011 and July 2013, 17 paediatric patients with splenomegaly caused by hereditary spherocytosis (n = 3), portal hypertension (n = 12), paroxysmal nocturnal haemoglobinuria (n = 1) and thalassemia (n = 1), referred for treatment with TSVL, were screened for enrolment into this retrospective analysis. The diagnosis of splenomegaly was established by inspection of medical history, laboratory examination, ultrasonography and computed tomography (CT) examinations. The eligibility criteria for TSVL included: (1) thrombocytopenia (platelet count of B100,000/mm3), (2) the diagnosis of primary disease was unequivocal, (3) splenomegaly class II or III. Patients with other severe disease (such as liver failure, severe infection) were excluded.

Ligation of total splenic vessel

All ligation procedures were performed by two experienced interventional radiologists who were experienced in conventional laparoscopic surgery. The patient was placed in a supine position and the left upper abdominal region was raised slightly. A laparoscope (STORSE) was placed at the umbilicus and the other three ports were inserted. After opening the gastrocolic ligament and turning up the stomach to expose the pancreatic edge, we identified and dissociated the splenic vessel (one artery and two to three veins, commonly). Next, we ligated the splenic artery with one clip. Then, we separated the distal and proximal parts of the splenic vein, and used clips to ligate the vein distally and proximally. Postoperatively, nearly 90% of the spleen appeared dusky while the remaining 10% of the spleen remained normal, which was an attribute of the patency of the collateral arteries. Antibiotics were administered before and after TSVL in order to avoid infection.

Follow-up protocol

All patients were followed up at our outpatient clinic. Peripheral blood cell parameters, including white blood cell (WBC) count and platelet (PLT) count as well as red blood cell (RBC) count, were measured sequentially 3 days before and 3 days, 2 weeks after TSVL, and subsequently at dates with 3-month intervals during the 1-year follow-up period. We measured and compared the pre-treatment splenic volume by abdominal CT scans. But CT might have radiation hazards, so CT was prudently performed and only applied in 1 week before and 6 month after the operation. The incidence and kind of complications associated with TSVL were also recorded.

RESULT

Baseline demographic and clinical characteristics of patients as well as intraoperative and hospital characteristics are described in Table 1. The mean age of the 17 patients was 6.17 years, and the patients included 11 boys and 6 girls. There were 12 cases of portal hypertension, 3 cases of hereditary spherocytosis, 1 case of paroxysmal nocturnal haemoglobinuria (PNH) and 1 case of thalassemia.

Table 1

Baseline demographic and clinical characteristics of patients

Perioperative outcomes

All paediatric patients were successfully performed TSVL without the need for conversion to open operation or splenic embolization. The mean operative time was 50.9 min (range: 32.1-70.3) and mean blood loss was 10 mL (range: 5-20). The mean postoperative hospital stay was 5.6 ± 1.7 days (range: 4-12 days). The average duration of full diet resumption was 1.80 ± 1.62 days. Surgery-related death did not occur. After operation 16 patients developed transient fever and were treated by intravenous fluids, and abdominal pain occurred in all 17 patients. Pleural effusion was observed in three patients and those three patients were responsive to conservative management. No hernias were found at the port sites during our follow-up [Table 1].

Degree of splenic infarction after total splenic vessel ligation splenic infarction rate

The mean [standard deviation (SD)] splenic infarction rate of a total of 17 patients was 77·5 (5.1)% 6 months after operation. We next analysed our data in different aetiologies and we found the mean (SD) splenic infarction rate in patients with portal hypertension; other aetiologies were 78.5 (5.4) % and 75.0 (3.2)%. There was no significant difference in the splenic infarction rate among the aetiological groups indicating that the effectiveness of TSVL may be independent of aetiologies [Figures 1 and 2].

Figure 1

Splenic infarction rate of paediatric patients

Figure 2

Post-procedure CT scans with contrast (a) normal spleen (b) infarcted spleen

Chronological changes of peripheral blood counts

Figure 3 showed the chronological changes of peripheral blood count before TSVL and 3 days to 1 year after TSVL. After TSVL, the mean counts of PLT and WBC increased significantly and reached the peak level on the second week and on 3 days after TSVL, respectively. Then the counts of PLT and WBC gradually fell, reaching a steady state in the third month. Both the PLT and WBC were significantly higher than pre-TSVL in the 1-year follow-up. As for the RBC counts, no significant chronological change was found either subsequent to TSVL or during the follow-up period.

Figure 3

Follow-up of (a) PLT count, (b) WBC count, and (c) RBC count in paediatric patients subjected to total splenic vessel ligations. *Significant change (a), (b) and (c) at the time point in comparison to pre-operation

DISCUSSION

Splenomegaly often contributes to hypersplenism and can result in severe thrombocytopenia and/or leucocytopenia. The management of hypersplenism includes several possible approaches such as surgical splenectomy,[12] splenic embolization,[345] banding or ligation of the splenic artery and placing a percutaneous stent to the splenic artery. Unfortunately, all those managements of splenomegaly have limitations and disadvantages, and we have not found the ideal method to deal with splenomegaly. Although surgical splenectomy may effectively improve blood cell destruction caused by hypersplenism, the morbidity of severe complications after splenectomy is still high, ranging from 9.6% to 26.6%.[2] In addition, splenectomy can affect the body's immune function, increasing the risk of septic events.[128] The effect of ligation of the splenic artery in some hypersplenism cases is not significant.[6] Percutaneous placement of a stent into the splenic artery seemed to be a promising technique in the treatment of splenomegaly and hypersplenism;[9] however, ensuring a sustained and long-term increase in PLT and WBC counts was difficult as the splenic artery was incompletely occluded.[10] Splenic embolization was first performed by in 1979,[11] which might preserve spleen function but high complications associated with splenic embolization such as post-embolization syndrome, splenic abscess, splenic rupture, pneumonia, portal thrombosis and the essential exposure to ray limit its utility.[4121314]

Here, we developed a new approach, total splenic vessel ligation (TSVL), for splenomegaly. In our knowledge, this is the first study to evaluate the results obtained with TSVLs for paediatric patients. Previously, we only ligated the splenic artery but the effect was not significant, especially thrombocytopenia that was often recurrent in long-term follow-up, which was in accordance with the published article.[6] So in 2011, we started to ligate total splenic vessel including the splenic artery and vein. In this study, we retrospectively analysed our original experience of 17 paediatric patients who underwent TSVL. In 17 patients followed up for more than 1 year, we found that the mean splenic infarction rate of total 17 patients was 77.5%, and the counts of PLT and WBC increased significantly, indicating that the effectiveness of TSVLs was satisfactory and favourable. On the other hand, we found the mean splenic infarction rate in patients with portal hypertension and other aetiologies to be 78.5% and 75.0%, respectively. There was no significant difference in the splenic infarction rate among the aetiological groups indicating the effectiveness of TSVL may be useful for splenomegaly independent of aetiology.

In this study, TSVL was technically successful in all paediatric patients, with no operation-related complication. Although transient post-TSVL occurred in most paediatric patients, no death or other major complication was observed. These results indicate that TSVL is a safe approach in the treatment of paediatric patients with hypersplenism.

As TSVL was performed by laparoscopic operation, the potential advantages of this approach are associated with improved cosmetic outcomes, incisional hernias, less risks for haemorrhage, and fewer wound complications, organ injuries, and less postoperative incisional pain.

Limits

There are limitations to this study, which should not be ignored. First, the sample size of the study included in the analysis was small and no control group was included; the power to detect the outcomes was limited. Randomized controlled trial comparing TSVL and other approaches for splenomegaly are needed in order to determine the risk of complications involved in the treatment of splenomegaly and long-term clinical efficacy. Second, the follow-up time in our study was not very long; so a longer follow-up was needed. Last, the potentially existent significant risk of measurement bias might have more or less affected the accuracy of the results.

CONCLUSION

Although our study including several demerits, further expanded follow-up studies are needed. Based on the evidence, we make cautious conclusions that TSVLs are safe and effective in the treatment of paediatric patients with splenomegaly, achieving a satisfactory long-term haematological response and benefit. TSVLs may be an important factor for reducing the risk of major complications such as splenic rupture, pneumonia, and refractory ascites, and may serve as an alternative to surgical splenectomy or splenic embolization.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.