The Spleen

Since Antiquity, the spleen has been fascinating due to the mysteries of its existence and, to date, this is the organ about which we know the least. The most ancient documentation of the spleen comes from the Chinese. Throughout history, many functions have been attributed to the spleen. For a more didactic presentation, this chapter will be divided into three larger topics, in which the historical aspects of the spleen - Morphology, Physiology and Surgery - will be treated. Great advances in splenic morphology are due to Marcelo Malpighi. His outstanding studies on the spleen, around 1686, resulted in the knowledge of the splenic capsule and its intraparenchymatous insertions, in a trabecular form. The first study on the vascular pedicle of the spleen is attributed to Julius Caesar Arantius, in 1571. The greatest importance attributed to the spleen is the protection of the organism against infections. Hua T'o, had performed a full splenectomy in the second century a.D. in China. The first splenectomy described in detail was carried out by Adrian Zaccarelli, in 1549. The first partial splenectomy may have been performed in 1581. In 1590, Dr. Viard used a string to stitch a segment of the spleen that had come become exposed due to a small abdominal wound and performed the first partial splenectomy. The first description of the splenic implant in the peritoneum, after a human trauma, was reported by H. Albrecht (1896), in Germany. In 1985, Salky et al., considered that the decapsulation of the non-parasitic splenic cyst by laparoscopy was the definitive treatment for this disturbance. The authors of the first total splenectomy executed by laparoscopy most likely belong to Delaitre and Maignien (1991). Only with persistent study can the spleen cease to be, in the words of Galen (second century), “an organ full of misteries”, "mysterii pleni organon".

The spleen receives 5% of the total cardiac output every minute and less than 10% of the blood in the arterial capillaries is emptied directly in the venous sinuses. It is also a major site for the synthesis of tuftsin and properdin, two proteins which serve as opsonins. This organ is the largest lymphoid tissue of the body. Most of the splenic functions of fight against pathogens may be taken over by other organs. The major known functions of spleen are removal of aging erythrocytes and recycling of iron, elicitation of immunity, and supply of erythrocytes after hemorrhagic shock and removes intraerythrocyte inclusions. Up to 30% of platelets are stored within the average spleen and can be released in response to specific stimuli such as epinephrine. Splenic function can be assessed most simply by searching for Howell-Jolly bodies. The spleen can be visualized and its size estimated by scintillation scanning following injection of isotope-labelled, autologous, heat-damaged red cells, which are selectively removed by functional splenic tissue.

Specimen of a spleen is most frequently encountered in centers that deal with autopsy cases. Spleen is not a frequent surgically resected specimen thereby indicating its uncommon presentation with a primary disorder. Most pathologists tend to have a casual approach or consider spleen to be an organ with a difficult or a non-specific morphology. Understanding and interpreting splenic pathology remain a challenge for a pathologist. There are only few diseases which primarily involve the spleen and represent involvement by diseases originating elsewhere. The contribution of a histopathologist in such situation is in confirmation of the clinical diagnosis or exclusion of a suspected pathology. Splenic pathology is of a combined interest to a surgeon, hematologist, histopathologist and an oncologist. There are certain prerequisites for a proper interpretation of splenic pathology like availability of an adequate clinical history, lab investigation, systematic gross examination and studying of sections from a properly fixed specimen. A freshly removed specimen of spleen needs to be thoroughly examined after removal of the attached fat, lymph nodes; splenicule if any and other undesired adherent tissue on the capsule and the hilum. Vessels at hilum are left with adequate length for examination and detail study if need be. After cleaning, the spleen is weighed and measured. The specimen is cut with a sharp knife at an interval of 5 mm thickness along the length exposing the hilum. Any excess blood is shocked with a clean towel and smears can be made. Alternatively, excess blood can be cleaned by washing gently under running tap water. The cut slices are put into fixative and left overnight for fixation. The smears can either be fixed immediately with absolute alcohol or left to dry in the air. Representative sampling can be done immediately in the fresh state or after overnight fixation. Number of blocks to be sampled will depend on the size and gross feature of the specimen. Minimum of two blocks is usually sampled from different area of the spleen including the hilum and capsule.

The spleen is the largest lymphoid organ in the body. It is located in the left hypochondrium and is surrounded by a thick, fibrous capsule that adheres to the parenchyma. In human beings the spleen has an elongated shape and weighs 100-200 grams, with its major diameters measuring 11 x 7 cm. It receives blood mainly through the splenic artery, derived from the celiac trunk, and venous drainage is processed through the splenic vein that leads into the portal vein. When studying the pathologic anatomy of the spleen one should keep in mind the lymphoid and the vascular nature of the organ as well as its shape, size and weight. As we shall see, in most cases the gross anatomy of the spleen is directly or indirectly associated with local and systemic vascular and hemodynamic changes and also with changes of haematolymphopoiesis. Changes in these different systems frequently manifest as modifications of the weight and volume of the spleen.

Several functions are performed by the spleen, each one correlated with a specific anatomic site in the organ. Most of these functions are usually complementary to those of other organs and thus are not always important in normal adult individuals, but can acquire importance in disease states. The better known functions of the spleen are haematopoiesis, acting as a reservoir of blood elements (mainly platelets), phagocytosis (removal of altered blood cells and other particulate matter), and several roles in the immunologic mechanisms.

Histologically, the spleen can be divided into two distinct regions, i.e., the white pulp and red pulp. These two regions are separated by an ill-defined interphase known as the marginal zone. The white pulp is made up of T and B lymphocytes, the former located along the periarteriolar lymphoid sheath and the latter in the lymphoid follicles, while the red pulp consists of a network of venous sinuses and the Billroth’s cords. The Billroth’s cords contain numerous macrophages which are responsible for the important phagocytic function of the organ. The sinuses are lined with a particular type of endothelial cells forming a discontinuous barrier which allows passage of blood cells between cords and sinuses.

Since ancient times, the spleen is regarded as a mysterious and intriguing organ. It has various functions underscoring its prepoderant relevance as the largest secondary lymphoid organ system. Total splenectomy done at any age and for any reason increases the risk of death from overwhelming postsplenectomy infection (OPSI). The etiologic agents most frequently found in OPSI are Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis, but other bacteria such β-hemolytic Streptococcus, Staphylococcus aureus, and Escherichia coli, Pseudomonas sp., also present a significant risk. Prophylaxis of OPSI is located in three main categories: patient education, immunoprophylaxis, and chemoprophylaxis. Besides these, the realization of heterotopic splenic autotransplantation after splenectomy seems to favor the recovery of some of the functions of the spleen. However, these measures seem to be not sufficient to prevent the higher risk of developing OPSI. Because of this risk, the indication for the realization of total splenectomy in trauma and several diseases has been sharply declining. The objective of this work is to make a description of the aspects that correlate the absence of spleen with the occurrence of sepsis.

[1-4]: Although known for more than 3,000 years, the spleen continues to be one of the most misunderstood human organs, even from a morphological point of view. Its disregard among the majority of doctors and researchers is responsible for the sparse and discontinued anatomical studies regarding the spleen.

The major consequence resulting from the indifference of the scientific and medical worlds towards this organ has occurred in surgery, considering that spleen operations have progressed during the last twenty years more than throughout the history of Medicine. It is not fair to realize that the dogma that still predominates amongst doctors is that spleen surgery results simply in “through out the spleen!”.

This demonstration of medical ignorance and the lack of professional sensibility trend to be modified by the scientific works of recent decades. Discoveries regarding the functioning of the spleen have aided a number of anatomy specialists in improving their efforts regarding the morphology of the spleen. The foundations of these scientific advances have affected new surgical proposals for this organ and its vascular pedicle. The benefits of new surgical proposals have increased the survival rate among many patients as well as reduced the complications that the “spleen removers” once imposed upon their victims.

The portal system includes all veins that carry blood from the abdominal part of the gut, pancreas, gall bladder, and spleen. Portal vein (5-8 cm long) is formed in front of the head of pancreas by the union of superior mesentric and splenic veins, and enters the liver at the porta hepatis in two main branches that have segmental intrahepatic distribution accompanying the hepatic artery and biliary ducts. Portal pressure, like any pressure, is determined by flow rate and resistance. The normal portal pressure and flow are 5 to 7 mm Hg (7-10 cm H2O) and 1000 to 1200 ml/min respectively. Both the increased resistance to portal blood flow (backward component) and the increased splanchnic blood flow (forward component) play major causative roles in the development of portal hypertension (PHT). Portal blood flow can be obstructed before (prehepatic), inside (intrahepatic), or after (posthepatic) the liver. Clinically most important are esophageal varices which are the major causes of morbidity and mortality due bleeding. Many of the mechanisms leading to an enlarged spleen may overlap or coexist in the same condition and in the same patient (infection with congestion with hyperfunction). Splenomegaly is the most important sign of PHT. Thrombosis of the splenic vein increases the venous pressure distal to the obstruction, which leads to left-sided PHT and development of collateral vessels to shunt blood around the occluded splenic vein. Collateral circulation may develop along three pathways. A finding of isolated gastric varices on upper gastrointestinal endoscopy should lead to an evaluation for PHT. Most often is the treatment of the primary disease.

As benign, non-traumatic, splenic diseases are extremely rare, the practicing surgeon very occasionally deals with patients suffering from such conditions. A number of these diseases, such as congenital splenic cyst, may present themselves with mild symptomatology, thereby creating diagnostic uncertainty. Others however, such as hydatid cyst, when unprofessionally managed, may still be dangerous and even prove lethal. Therefore, the diagnosis and management of benign non-traumatic splenic diseases remain a challenge for the clinician. Benign splenic diseases, which are discussed in this chapter, include non-parasitic cysts (primary or true and secondary or false cysts), inflammatory cystic masses (hydatid cyst, bacterial and fungal abscesses), benign vascular neoplasms (haemangioma, littoral cell angioma, lymphangioma and hamartoma), benign vascular pathology (splenic infarction, splenic artery and vein aneurysm, intrasplenic pseudoaneurysm, splenic arteriovenous fistula and splenic vein thrombosis), and other benign disorders such as inflammatory pseudotumour of the spleen, splenic peliosis, Gandy- Gamna’s bodies and ectopic or wandering spleen. Their signs and symptoms are vague, non-specific and often confusing, delaying and often making diagnosis difficult. Clinical findings and blood analysis are often of little help. Sonography, computed tomography and magnetic resonance imaging are the most valuable imaging techniques. Besides being a therapeutic procedure, surgery may be indicated when the diagnosis is in doubt. While splenectomy was the treatment of choice for a long period of time, during the last decades, more conservative management has been advocated for benign non-traumatic splenic disorders after the recognition of the significant function of the spleen. Additionally, improvement in available equipment and an increasing experience of interventional radiologists under emergent conditions has led to increased application of endovascular techniques in the treatment of diseases of the splenic vessels and subsequent preservation of splenic function.

Chronic lymphocytic leukemia (CLL) is a clonal malignancy that results from expansion of the mature lymphocyte compartment and is the most common leukemia in adults. The survival period from the time of diagnosis of CLL varies between 2 and more than 10 years. At the time of diagnosis, most patients with chronic lymphocytic leukemia does not need to be treated with chemotherapy until the patient is symptomatic. Chlorambucil and cyclophosphamide were the main therapy in CLL. Cyclophosphamide is usually combined with other agents, such as vincristine and prednisone, and incorporated into combination regimens. High response rates were also seen with anthracycline regimens. Purine analogues are currently used in CLL. Because of the difficulty in eradicating CLL cells from bone marrow peripheral blood, autologous transplantation is widely used. Rituximab, an anti-CD20 monoclonal antibody, has recently provoked interest for the treatment of CLL. Perhaps the most potent regimen for CLL is the combination of the most effective single chemotherapeutic agent with the most effective monoclonal antibody. Splenectomy is helpful in the management of selected patients with CLL, who do not present adequate response to clinical therapy in an attempt to reduce the resistance to drugs and to alleviate the symptoms provoked by the huge size of the spleen. Besides the advantages of splenectomy, it must be stressed that in most cases this procedure is accompanied by a greater morbidity and mortality. Thus a conservative procedure that reduces the spleen size may have a similar effect to that of total spleen ablation for treatment of CLL, without losing the important functions of this organ. Subtotal splnectomy or splenic autotransplants after total splenectomy are worth to be considered as surgical options in presence of a symptomatic giant spleen or a refractory patient to chemotherapy.

Malignant diseases of the spleen occur rather frequently. However, most of these cases are malignant diseases of the lymphatic and haematopoietic systems, but not local malignant neoplasms of the spleen. Most frequently, such diseases come with an enlargement of both the entire spleen and the lymph nodes of the splenic hilum. A systematic treatment of the underlying disease should be given priority over a splenectomy, which may be applied in particular cases only. It should be noted, that in order to diagnose properly or stage the systemic disease a splenectomy including the removal of the splenic hilum may become inevitable. Notwithstanding, in most of today’s cases, imagining diagnostics is an appropriate means to identify an affection of the spleen. Malignant neoplasms in the spleen are very rare. Most tumours can be identified and categorised through the use of anamnesis, imaging, chemical and laboratory examinations. If malignant neoplasms have isolatedly affected the spleen, splenectomy can be applied to cure the organ. Generally, the splenectomy can be conducted in a laparoscopic way. The use of splenectomy is not reasonable in patients with more organs affected; such cases require a systemic therapy.

Due to associated diseases, the function of the spleen may be modified, in turn causing certain complications, such as anaemia, altered coagulation, malnutrition and organ failure. Preoperative management of patients must take these two possibilities into account. In non-traumatic splenectomies, blood samples are necessary to screen for thrombophilia: antithrombin III deficiency, protein C deficiency, protein S deficiency and dysplasminogenemia. Complete blood count, AST, ALT, serum amylase, C-reactive protein, thrombin-AT-III complex and D-dimer also become necessary perioperatively. The preoperative management of anaemia must evaluate the risk and benefits of blood transfusion. Malnutrition increases the risk of postoperative complications. Antibiotics are recommended for patients who are immunosuppressed and in trauma. In the classical form of spleen surgery, pain is a frequent symptom, with variable intensity, mostly due to the pressure applied to the ribs. If the pain is not well managed by specific pills, it is better to make an anaesthetic block of the thoracic nerves. Thrombosis extending into the portal vein is rare; with an overall risk of 3.3%. Infection is the most common postoperative complication. Fever commonly appears between the fourth and seventh day after surgery. The risk of thromboembolic events and pulmonary arterial hypertension varies greatly, depending on the underlying condition for which the splenectomy is performed and its association with intravascular haemolysis. The most serious septic complication after splenectomy is the (OPSI), which brings about a prohibitory mortality rate of 50% to 90%. Prevention of postsplenectomy sepsis has occurred through the use of greater efforts to avoid splenectomies.

The spleen is a very important organ with many essential functions, not only in the defense of the organism, but also in its metabolism and immunological and the haematological systems. The most common manifestations of the splenic disturbances include the splenomegaly and a decrease, in the number of blood elements. After the removal of the spleen, 2% of adults present severe sepsis, while 5 % of children, the elderly people and patients with severe chronic diseases are at risk of death due to septic conditions. Most of splenic diseases may be treated conservatively. Operative procedures should be considered in special conditions, when all conservative options have been unsuccessfully depleted. Even in the presence of a severe trauma to the spleen or advanced haematological diseases, the best approach is a non-operative procedure. When the operation is unavoidable, partial (preserving the splenic vascular pedicle) or subtotal (preserving the upper splenic pole, being supplied only by the splenogastric vessels) splenectomies should be preferred. When a conservative procedure on the spleen is unfeasible, the best option is a total splenectomy combined with the transplant of autogenous splenic tissue on to the greater omentum. The technological advances and the progressive development of new surgical devices are responsible for surgical approaches with less pain, faster postoperative recovery and better aesthetical results without decreasing the therapeutic efficacy. The conservative splenic approach, whether clinical or surgical, is the best way to prevent postsplenectomy infection, by preserving the spleen immune role. The surgeon should choose the best surgical procedure and the size of the splenic remnant, remembering that at least 25 % of a normal spleen should be left.

Since the first description of laparoscopic splenectomy (LS) in 1991, this technique has been adopted as the standard procedure for most indications for splenectomy throughout the world. The utility of LS in the treatment of hematologic diseases such as hereditary spherocytosis, immune thrombocytopenic purpura, and autoimmune hemolytic anemia is well established. LS has become the gold standard approach for normal or slightly enlarged spleens and is currently considered the procedure of choice. The benefits of laparoscopic removal of the spleen are evident to patients and surgeons alike. This approach is superior to open splenectomy in terms of postoperative pain, shorter postoperative hospital stay, perioperative complications, and an improved cosmetic result. Additionally, the period of convalescence is brief, with an early return to work or normal activities. The results of large series around the world are similar, with an operating time of between 60 and 90 minutes, hospital stay of between 1 and 2 days and morbidity of less than 10% [1,2,3,4,5].

While laparoscopic splenectomy has become the standard procedure for the surgical treatment of hematologic splenic disorders, the role of robotic splenectomy is still a matter of debate. The robotic equipment is expensive, still bulky and the surgical team needs special training. However, there are some limitations of laparoscopy in difficult splenectomies (massive splenomegaly, portal hypertension, partial/subtotal splenectomy and splenic malignancies) which can be overcome by the robotic system by means of better visualization, maneuverability and motion control allowing a better dissection of the splenic vessels and precise and timeefficient intracorporeal maneuvers.

The spleen is one of the most frequently injured solid organs in blunt abdominal trauma [1]. In the history of trauma care, however, injuries of the spleen have received but scant attention compared to those of the liver and the kidney. Splenectomy has long been the preferred and standard treatment for bleeding from the spleen caused by blunt trauma, because the spleen was regarded as to have no vital function [2]. Owing to the pioneering article of King and Schumacher on the correlation between asplenia and overwhelming infection, the role of the spleen as an immunologic organ particularly in children, came to be widely recognized in the 1960s [3-6]. Then, splenic preservation treatment such as splenorrhaphy, partial splenectomy, and splenic embolisation, became the optimal management techniques for blunt splenic injury [7,8]. Due to the advances in CT imaging and angiography, nonoperative management (NOM) became the optimal management techniques for blunt splenic injury, and splenic embolisation is a valuable adjunct to the NOM [9,10].