Laparoscopic Splenectomy In Patients With Immune Thrompocytopenic Purpura Biology Essay

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Background: Splenectomy remains the single best option to convert a patient with ITP into a "nonpatient," that is, one who is unlikely to need frequent monitoring or intervention. Controversial issues about laparoscopic splenectomy include the ideal surgical technique; prolonged operative time; blood transfusion requirement; and importantly long-term results. The aim of this study was to assess the applicability, safety and efficacy of laparoscopic approach for splenectomy in cases of immune thrombocytopenic purpura (ITP).

Methods: Fourteen patients with Immune Thrombocytopenic Purpra (ITP) indicated for splenectomy during a one year period were included in the study. Laparoscopic splenectomy using the lateral approach was carried out in all patients.

Results: Patients were 10 females (71.4%) and 4 males (28.6%), their age ranged from 17 to 46 year-old with a mean of 28.7±8. Abdominal ultrasound was done to all patients; none of the patients had associated gall stones or other pathologies. Splenules were present in two patients (14.3%). The spleen size ranged between 10 and 15 cm. The operative time ranged from 48 to 90 minutes with mean of 54±2.1. The preoperative platelet count before platelets transfusion had a mean of 9.1±6.4/Cmm. Immediate preoperative and intraoperative platelets transfusion was done for all patients, so the immediate preoperative platelets count ranged from 6.000 to 225.000 with a mean of 71.1±61.3/Cmm. The immediate postoperative platelet count on the first postoperative day had a mean of 135.6±101.3/Cmm. After two months, platelet counts were accepted in all patients (>70.000) with a mean of 90.3±13.2/Cmm.

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Conclusion: Laparoscopic splenectomy, using vascular sealing devices, is applicable, feasible, and safe in cases of ITP.

Key words: Laparoscopic splenectomy, immune thrompocytopenic purpura.

INTRODUCTION

Laparoscopic surgical procedures have progressed at an extraordinary rate over the last years, yet relatively few reports of laparoscopic splenectomy have appeared, this is due to the large and potentially complex blood supply of the spleen combined with splenomegaly. The operative dissection also is made difficult by the remote location of the spleen in the recesses of the left upper quadrant, as well as the intimate relationships with surrounding organs such as the colon, stomach, and pancreas. Technical operative skills and equipment requirements for laparoscopic splenectomy are significantly greater than for other laparoscopic procedures such as cholecystectomy and appendectomy.(1-4)

However, the potential advantages associated with the development of a minimally invasive form of splenectomy are considerable. Avoidance of a major upper abdominal incision decreases postoperative pain and minimizes impairment of pulmonary function; thereby decreasing narcotic use and minimizing pulmonary complications, duration of ileus, and length of postoperative stay.(5-8) Many patients undergoing splenectomy for hematologic diseases are undergoing treatment with cortico-steroid or chemotherapy regimens at the time of operation. These agents are known to impair healing. Avoidance of large incisions in patients who are intentionally immune-suppressed also may decrease the incidence of incisional complications such as infection and dehiscence.(3)

Many patients with hematologic disorders such

as immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hereditary spherocytosis, and others can be cured or their condition can be improved by splenectomy.(9)

Immune thrombocytopenic purpura is an autoimmune disorder characterized by a low platelet count and mucocutaneous bleeding. The estimated incidence is 100 cases per 1 million persons per year.(10) It was long suspected that immune thrombocytopenic purpura is mediated by auto-antibodies. Platelets coated with IgG autoantibodies undergo accelerated clearance through Fc receptors that are expressed by tissue macrophages, predominantly in the spleen and liver. A compensatory increase in platelet production occurs in most patients. In others, platelet production appears to be impaired, as a result of either intramedullary destruction of antibody-coated platelets by macrophages or the inhibition of megakaryocytopoiesis.(11) The level of thrombo-poietin is not increased, reflecting the presence of the normal megakaryocyte mass.(12)

ISSN 1110-0834The first antigen to be identified was recognized on the basis of the failure of immune thrombo-cytopenic purpura antibodies to bind to platelets that were genetically deficient in the glycoprotein IIb / IIIa complex. Antibodies that react with glycoproteins Ib / IX, Ia / IIa, IV, and V and diverse other platelet determinants have since been identified, and the presence of antibodies against multiple antigens is typical. The destruction of platelets within antigen-presenting cells - presumably, although not necessarily, initiated by antibody - may generate a succession of neoantigens, resulting insufficient antibody production to cause thrombocytopenia.(13)

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Splenectomy remains the single best option to convert a patient with ITP into a "nonpatient," that is, one who is unlikely to need frequent monitoring or intervention, and it minimizes interference with

a normal lifestyle. The timing of the procedure depends on disease severity, responsiveness and side effects of therapy, risk of trauma and of the procedure, and patient and doctor preference.(14) If the patient does not wish to temporize, splenectomy is recommended within 3 to 6 months if any therapy (eg, more than 10 mg prednisone/d) is required to maintain a platelet count greater than 30 000 x 109/L. In contrast, some experts recommend a far more protracted period of watchful waiting, with splenectomy reserved for those with a platelet count consistently less than 20 000 x 109/L or in the face of difficult-to-control bleeding.(11)

Controversial issues about laparoscopic splenectomy include the ideal surgical technique; prolonged operative time; blood transfusion requirement; and importantly long-term results.(15) This study aimed at assessing the applicability, safety and efficacy of laparoscopic approach for splenectomy in patients with idiopathic thrombo-cytopenic purpura (ITP).

METHODS

The current study was carried on 14 patients with idiopathic thrombocytopenic purpura (ITP) indicated for splenectomy during a one year period. All patients were treated first by medications as a first line of treatment for a variable period ranging from one to two years. Treatment modalities included immunosuppressive agents such as steroids and azathioprine, and chemotherapeutic agents such as vincristine, in addition to vitamins (vitamin C, and folic acid).

Abdominal and pelvic ultrasound was done to show the splenic size, presence of splenules and any other pathology. Patients with massive spleno-megaly (more than 20 cm interpolar diameter) and those with cardio-respiratory conditions contra-indicating laparoscopy were excluded. Apart from these exclusions all patients in the study were consecutive.

All patients were subjected to routine laboratory investigations, with stress on platelet count. All patients were negative for hepatitis C virus infection. Patients received immunization against encapsulated bacteria before splenectomy. And a stress dose of parentral corticosteroids (300mg in the day of the operation tapered gradually over a period of three days postoperatively). Preoperative prophylactic antibiotics were given to all patients. Immediate preoperative and intraoperative platelets transfusion (6-12 units) was done for all patients with a mean of 9±1.96.

Operative technique:

Two 10-12 mm and two 5 mm trocars were used. The patient was positioned in the right lateral position with 300 anti-Telendelenburge position. Closed Pneumoperitoneum was done through a subcostal incision in 11 patients (78.6%); while Pneumoperitoneum was created after introduction

of first trocar under vision in 3 patients using transparent trocar (21.4%). The first Trocar was supra-umbilical in position. The locations of the remaining trocars were determined by considering the anatomic configuration in relation to the size of the spleen to be excised, the most common sites were mid-clavicular 5mm, anterior axillary 10-12mm and posterior axillary 5mm. We started all operations by careful exploration of the abdomen

in an anticlockwise manner starting from left hypochondrium searching for accessory spleens. This is done before the initiation of the dissection to avoid obscuring the surgical field with blood or irrigation. Any accessory spleens found were removed immediately. We started the procedure of splenectomy by division of the spleno-colic ligament, and then we used ultrasonic dissecting scalpel or bipolar vascular sealing device to control the terminal branches and tributaries of both the splenic artery and vein. We noticed the change in color of the devitalized splenic segment as we proceeded upward ending with the short gastric vessels. Care was taken to avoid injury of the adjacent organs especially the colon, the pancreas and the stomach. The spleen was placed in an Endocatch or freezer bag, morcellated, and extracted through widening of the anterior axillary line trocar site. Hemostasis was checked and tube drain was inserted in the splenic bed.

Satatistical analysis:

Data were prospectively collected and presented using a simple descriptive analysis (mean, standard deviation, median, and percentage).

RESULTS

Fourteen patients were included in the study. They were 10 females (71.4%) and 4 males (28.6%). Their age ranged from 17 to 46 year-old with a mean of 28.7 ± 9.

Abdominal ultrasound was done to all patients; none of the patients had associated gall stones or other pathologies. Splenules were present in two patients (14.3%). One patient had single splenule at the hilum of the spleen and the other one had two; one at the hilum of the spleen and the other was related to the tail of pancreas. The spleen size ranged between 10 and 15 cm.

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Ultrasonic dissector was used in three patients (21.4%), while the bipolar sealing device was used in the remaining 11 patients (78.6%). Mild bleeding occurred in three patients (21.4%); one of them was due to injury of small pancreatic vessel, controlled by compression and reapplication of vascular sealing device, the second was from branch of the splenic vessel, controlled in the same manner, the third was from the substance of the spleen due to injury of

its capsule by the retracting instrument controlled

by gauze compression. The mean blood loss was 192±150.6 cc (range 40-800 cc) and only one patient required blood transfusion postoperatively.

Extraction of the spleen was done through widening the anterior axillary line trocar site in all patients; Endocatch was used in four patients (28.6%), Freezer bag was used in 10 patients (71.4%). Part of the spleen was lost from the bag during morcellation in one patient; this part was retrieved again immediately. Tube drain was inserted in the splenic bed and left in place for one to three days.

Operative time ranged from 48 to 90 min with mean of 54 ± 2.1 min. All patients had audible peristalsis, started and tolerated oral intake within 24 hours after operation.

There were no operative mortality and no major postoperative complications. Postoperative bleeding was encountered in one patient in the form of trocar site external bleeding treated by compression. Post operative ecchymosis was found in all patients at the site of the trocar widened for splenic extraction. This gradually improved in the postoperative period with return of the platelet count towards normal levels.

The preoperative platelet count before platelets transfusion ranged from 1000 to 20.000/Cmm with a mean of 9.1±6.4/Cmm. After preoperative platelets transfusion, the immediate preoperative platelets count ranged from 6000 to 225000 with the mean of 71.1 ± 61.3 / Cmm. The platelet count on the first postoperative day had a mean of 135.6 ± 101.3 / Cmm. After two months platelet counts were accepted in all patients (>70.000) with a mean of 90.3 ± 13.2/Cmm (Table I).

Hospital stay ranged from 2 to 4 days, with a mean of 3.1±0.7 days. Resumption of normal daily activity ranged from 7 to 14 days, with a mean of 11.6 ± 2.459 days.

Table I: Platelet count/Cmm in patients with ITP before

and after laparoscopic splenectomy.

Mean ± SD

Median

On admission

9.1±6.4

8

Immediate Preoperative

71.1±61.3

76

Postoperative day 1

135.6±101.3

121.5

After 2 month

90.3±13.2

90

DISCUSSION

The size of the spleen is an important determinant of the feasibility of laparoscopic splenectomy. It has been suggested that laparoscopic splenectomy can be performed if the greatest dimension of the spleen is 20 cm.(16,17) In patients with ITP, the spleen is generally small and there is no surrounding fibrotic reaction or hypervascularity rendering it more readily amenable to laparoscopic removal. However, with increasing experience, larger spleens (in other diseases) may be removed laparoscopically. In our study, the size of the spleen was not exceeding 15 cm, so we didn't find any technical difficulty during dissection or retrieval of the spleen.

The presence of an accessory spleen is of particular importance because it may cause recurrence of disease unless recognized and excised. In a large study on open splenectomies for ITP, the disease recurred in 9% of the patients because of an unrecognized accessory spleen.(18) The prevalence

of an accessory spleen in our group was 14.3%, near to that reported by other authors (7%-12%),(19-21)

but it has been reported as high as 39%.(16) Notably, in a comparative study between laparoscopic splenectomy and open splenectomy, an accessory spleen was found 3 times more often in open splenectomy vs. laparoscopic splenectomy (24% vs. 8%).(22) This observation shows the need for a systematic search for accessory spleens during laparoscopic splenectomy and the importance of preoperative CT scan. Laparoscopic splenectomy allows exploration of the splenic hilum, tail of

the pancreas, the splenocolic and gastrosplenic ligaments, and the greater omentum. Other sites may be poorly visualized in the semidecubitus position, but they are rare locations for accessory spleens. Long-term follow-up will be the only true way to tell if clinically significant accessory spleens are missed.

In other studies, clips were used to ligate individual vessels, the inferior polar branches are divided using clips or the harmonic shears. Michel(23) described two main modes for distribution of the splenic blood supply; the distributed mode and the magistral mode. In the distributed mode of blood supply, multiple branches arise from the main trunk approximately 2 to 3 cm from the hilum. In the magistral mode, the pedicle formed by the artery

and vein enters the hilum as a compact bundle. Katkhouda et al(24) used clips to control the terminal branches in distributed mode while in the magistral mode, a linear stapler were used to control the main bundle in block. Once the hilum has been controlled, the remaining short gastric vessels at the superior pole of the spleen and the ligamentous phrenic attachments are divided with the harmonic shears, completing the splenic mobilization.(24) In our study we depended on controlling the splenic vessels as close as possible to the spleen, so that we were applying the vascular sealing device to the smaller vessels, this allowed safe effective vascular control

I all patients. We noticed the change in color of

the devitalized splenic segment and proceeded upward ending with the short gastric vessels. In

the last two patients in our series we found that it was easier to start with the inferior polar vessels, then the short gastric vessels, ending by the splenic hilum.

Removal of the spleen by morcellation has been criticized for 2 main reasons. The first concern is that disruption of the bag could lead to splenosis. However, if morcellation is performed with care, avoiding application of undue force and pressure on the specimen, disruption should not occur. Part of the spleen was lost from the bag during morcellation in one patient, this part was retrieved immediately, and this patient was followed for one year without evidence of splenosis. The second concern is the lack of an intact specimen for pathologic review. This is certainly legitimate when splenectomy is performed for a neoplastic condition (i.e., Hodgkin disease), in which case the spleen should be removed either with the open technique or by enlarging one of the laparoscopic incisions. However, most splenectomies are performed for conditions the diagnosis of which is based on preoperative hematologic studies and tissue confirmation is not necessary, such as ITP and spherocytosis.(15)

Katkhouda et al(24) reported an immediate positive response in 83% of all patients with various hematologic disorders and long-term good results in 77.6% of the patients with ITP. In our study, laparoscopic splenectomy showed an immediate positive response in all patients with ITP with an accepted platelet count (more than 70.000/ Cmm) after two months.

Conclusion

Laparoscopic splenectomy, using vascular sealing devices, is applicable, feasible, and safe in cases of ITP.