Splenectomy for massive splenomegaly due to myelóid metaplasia

Splenectomy for Massive Splenomegaly dueto Myeloid Metaplasia LEON MORGENSTERN,

Myeloid metaplasia is a myeloproliferative disease of unknown cause, often, but not always, associated with fibrosis of the marrow. Its natural history and clinical manifestations have been well described in the medical literature [1-Z]. Synonyms under which the disease is known include agnogenie myeloid metaplasia, myelofibrosis with myeloid metaplasia, myeloproliferative syndrome, leukoerythroblastic anemia, nonleukemic myelosis, and others. One of the most prominent features of the syndrome is progressive splenomegaly, often reaching massive proportions. The surgical management of such tremendous spleens, usually in patients whose disease is far advanced, presents problems of considerable magnitude. The following report is based on our experience with twenty patients, nineteen of whom were subjected to splenectomy. (Table I.) Preoperative

Preparation

The usual patient referred for surgery is a cachectic, middle-aged person with the symptoms of weakness, easy fatigability, night sweats, and recurrent episodes of fever. The majority of these symptoms are the consequence of hypermetabolism which characterizes this disease, but weight loss and malnutrition may also be secondary to gastric displacement by the enlarged spleen. The most prominent physical finding, in addition to cachexia, is hepatosplenomegaly. The spleen often extends below the iliac crest inferiorly and beyond the midline medially. Hepatic enlargement is generally much less marked. Anemia may be mild, moderate, or severe. Platelets are generally depressed; at times they may be normal in number or increased. The leukocyte count is variable but generally ele-

From the Department of Surgery. Cedars of Lebanon Hospital Division. Cedars-Sinai Medical Center, Los Angeles, California. This work was supported in part by USPHS Grant #E-S01 RR-05468. Reprint reauests should be addressed to Dr Morgenstern, 4833 Fountain Ave.Los Angeles, California 90029. Presented at the Forty-Second Annual Meeting of the Pacific Coast Surgical Association, Mexico City, Mexico, February 14-18, 1971.

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MD, FACS, Los Angeles,

California

vated. Approximately half the patients in this series had been on steroid therapy for control of hemolysis or thrombocytopenic purpura accompanying the syndrome. Several exhibited hyperuricemia of moderate degree. Many required several transfusions per week to offset the severe anemia due to splenic sequestration and hemolysis. Knowledge of these features of the disease is of extreme importance to the surgeon in preparing the patient for operation. Specific problems to be considered are as follows. Cachexia and Malnutrition. Optimal preoperative diet should be encouraged, with the addition of vitamin supplements in therapeutic dosage, In particular, Vitamin C in quantities of 500 to 1,000 mg daily should be given. Fever. Low grade fever is best kept in check by acetaminophen (Tylenol@) rather than aspirincontaining compounds. Occasionally, fever may be marked (103 to 10!9~) and should be controlled by a cooling blanket. Anemia. The hemoglobin level should be raised by transfusion to at least 10.0 gm per cent before operation. These patients are not hypovolemic, hence red cell transfusions are preferable to whole blood lest volume overload precipitate congestive heart failure. Reactions and increased hemolysis are common sequelae of transfusions, requiring meticulous antibody screening technics and careful observation during transfusion. Post-transfusion febrile episodes are not uncommon. At least 4 units of whole blood, some preferably fresh, should be cross matched and available for the operative procedure. Thrombocytopenia. Because of the short life span of transfused platelets, it is generally not advisable to give platelet transfusions in the days prior to operation unless bleeding due to thrombocytopenia is a problem. Six to ten units of platelets should be made available for the operation. For platelet counts over 100,000 per mm3, platelet transfusion is generally not necessary. Occasionally, platelet quality, rather than quantity, is imThe

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paired, constituting another indication for the administration of platelets. Bleeding Tendency. Complete studies for bleeding tendency are required since platelet deficiency may not be the only problem. Hypoprothrombinemia may be present and require correction by vitamin K. Additional tests which are advisable are Ivy bleeding time, partial thromboplastin time, and clot retraction. Steroids. Patients who have been on steroid therapy for temporary control of hemolysis or thrombocytopenia require an increase in steroid dosage for operation. The increased steroid dosage should be begun the evening before surgery by the parenteral route and continued on the morning of surgery. For example, patients who have been receiving prednisone, ‘20 mg daily, should receive a parenteral dosage of 30 mg prednisolone sodium phosphate the evening prior to operation and 20 mg on the morning of operation. Patients receiving steroids Hqperaeidity. should be kept on a bland diet before operation, with regular administration of antacids. The latter should be kept at the bedside. Abnormally high levels of Hgperuricemia. blood uric acid should be corrected well in advance of surgery to prevent postoperative gout and renal deposition of urates. The drug of choice is allopurinol, 100 mg two or three times a day. This may be combined with uricosuric agents such as colchitine (0.6 mg a day) or probenecid (0.6 gm twice daily). Acetazolimide (Diamox@) (260 mg daily) may be given to increase uric acid excretion. Skin Care. Since these patients are generally hospitalized for some time preoperatively, daily pHisoHex@ washes are recommended for at least three days prior to operation. Shaving of the abdomen is unnecessary in female patients ; in hirsute males it is preferable to shave the patient in the operating room rather than induce folliculitis by shaving the evening before. Operative

Management

Operations for this condition frequently must be scheduled for afternoon hours subject to availability of platelets and fresh blood for transfusion. During the preoperative wait, adequate hydration by the intravenous route is desirable to maintain good urine flow. Nasogastric intubation is mandatory, preferably in the operating room. An indwelling urethral catheter should be inserted in the operating room prior to the start of operation, and urinary output should be monitored. In cases of massive splenomegaly we have found it profitVolume 122, August 1971

able to insert two intravenous lines; one for central venous pressure monitoring during the procedure and the other for administration of fluids, platelets, and blood as necessary. Monitoring of central venous pressure during operation has been found especially useful during displacement of massively enlarged spleens, during periods of acute blood loss, and after ligation of the splenic artery with the shift of intrasplenic blood to the general circulation. Platelets, when necessary, should be administered immediately prior to the start of the operation. Six units may be administered rapidly and sequentially while the operative field is being prepared. An additional 2 to 4 units are then given while the spleen is being mobilized. General anesthesia with endotracheal intubation has been preferred by us because of the increased bleeding tendency and better control of respiration during manipulation of massive spleens. However, spinal or epidural anesthesia may be used in suitable cases. For very massively enOperative Technic. larged spleens (2,500 to 6,000 gm) we have found several points in operative technic to be of importance in reducing operative and postoperative difficulties. 1. Incision: A longitudinal incision is preferred. For massive spleens extending to the midline or beyond, the midline incision is excellent. It should extend from the xiphoid to at least 5 cm below the lowermost border of the spleen. For less massively enlarged spleens, the left paramedian incision is favored, extending from the left costal margin to 5 cm below the lowermost splenic border. In our experience transverse or oblique incisions have afforded less adequate exposure, especially critical when sudden bleeding occurs; have increased blood loss, from the divided abdominal muscles; and have been associated with a greater incidence of wound hematomas in the postoperative period. 2. Preliminary ligation of splenic arteries and vasa brevia: Mobilization of the spleen is facilitated and rendered safer if its volume is reduced by preliminary ligation of the splenic artery. Access to the splenic artery is obtained through the lesser sac by division of the gastrocolic omentum. Ligation in continuity with a 1-O silk ligature should be done as close to the splenic hilum as possible, but proximal to the branching of the superior polar artery. Occasionally, large arterial collaterals may be seen arising from the gastroepiploic or omental vessels. These should also be ligated and divided. Finally, the gastrosplenic “liga209

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ment” containing the vasa brevia should be divided as high as is feasible and ligated prior to delivery of the spleen, Otherwise these branches are torn during delivery of the spleen, resulting in troublesome bleeding or intramural gastric hematomas. When massive splenomegaly has existed for some time, the gastroepiploic vessels are huge and should be doubly ligated with 2-O silk. After delivery of the spleen, the main splenic artery and remaining large collateral arterial vessels are ligated with 1-O or 2-O silk from behind the spleen. 3. Ligation of splenic veins: The main splenic veins present two major difficulties : they are huge and they are fragile. Although in some cases it is feasible to commence the venous dissection anteriorly at the hilum, we have found it far easier and safer to isolate, divide, and ligate the veins from behind. This has two advantages: (1) If a large vein is inadvertently entered or torn, the hilum is within grasp and bleeding is more easily controlled. (2) The tail of the pancreas can more easily be visualized and protected. 4. Delivery of the spleen: This is best accomplished by the .surgeon on the right side of the table, after entry by incision or blunt dissection through the parietal peritoneum posterior to the spleen. The right hand should first be passed over the dome of the spleen and slow, gentle traction exerted downward, medially, and eventually anteriorly as the spleen is delivered. Rapid forceful delivery of the spleen can result in major blood loss. 5. Diaphragmatic and retroperitoneal hemostasis: Troublesome bleeding or oozing is often encountered from diaphragmatic or posterior peritoneal collaterals. This is best controlled by temporary packing, by the use of electrocautery, and by the use of hemoclips. Hemoclips are also useful in the control of small fragile venous collaterals in the vicinity of the tail of the pancreas. 6. Lymph node and liver biopsies: Generally, enlarged hilar lymph nodes are present and included with the spleen when the latter is removed. If not, at least one enlarged lymph node from the peripancreatic or para-aortic region should be taken if this can be done safely. Liver biopsy from the easily accessible left lobe should be obtained, as both a wedge biopsy and a Menghini needle biopsy. 7. Drains: We believe firmly in the use of a drain after splenectomies for this condition. A large Penrose drain is placed in the splenic fossa and allowed to exit through a stab wound in the left subcostal region. This allows for the egress of serosanguineous drainage, which may be consid-

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erable. The fluid may be studied for amylase content to ‘detect unsuspected injury to the tail of the pancreas. Drainage should be collected by a plastic collecting bag (stoma1 adhesive type) placed
Management

Patients should be closely observed postoperatively in an intensive care unit. Central venous pressure monitoring should be continued for at least twenty-four hours, after which the central venous catheter ,should be removed if the patient’s condition is hemodynamically stable. The naeogastric tube may be removed on the morning after the operation. Intermittent positive pressure breathing is a useful postoperative adjunct since the left hemidiaphragm is temporarily high and immobile, predisposing to segmental atelectasis particularly on the left. Postoperatively, the temporarily increased steroid dosage in those patients receiving steroids should gradually be tapered and eventually discontinued. Patients on prolonged steroid therapy require more .gradual ,tapering of the dosage and may require a small maintenance dosage. The drain is mobilized at twenty-four hours and removed within forty-eight hours, providing drainage is minimal. Drainage over 100 cc per twenty-four hours should preclude removal of the drain. Early Postoperative

Complications

(to one month)

Postoperative bleeding is rarer than might be anticipated. In two patients in this series it necessitated re-exploration and in another it is suspected as the cause of death, although unproved because of no autopsy confirmation. Septic type fevers without a demonstrable source occurred in five patients, all of whom had a postoperative course also marked by recurrent episodes of unexplained fever. Thrombocytosis was mild to moderate in the great lmajority of cases. In two patients, the platelet count exceeded one million, in one case rising to ,over two million. Both exhibited thrombotic complications, one mild and the other severe. A

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TABLE I Splenectomkr

for Myeloid Metaplasia

Age (yr) and Sex

Steroids

Multiple Preoperative Transfusions

1. DE

44, F

Yes

Yes

2. 3. 4. 5. 6. 7. 8.

CK PM* sc* CR* SF MG HH*

40, 56, 52, 25, 66, 59, 60,

No

No Yes

No No Yes No Yes

Yes Yes

Yes

9. 10. 11. 12. 13. 14.

FV RK* DC* RM HF* HF*

66, F 61, F 68, F 70, F 76, F 58, M

No

Yes

No No No

Yes Yes

Yes

Yes

No

15. 16. 17. 18. 19. 20.

BW JA* wc* BS DH* IM*

48, F 63, M 57, M 73, M 52, M 75, M

Yes Yes No Yes Yes No

Patient

*Author’s

M F M F F M M

Yes Yes

Date of Operation

Weight (gm) of Spleen

10/31/60

630 3,080 2,730 4,650 625 3,000 1,600 2,600

No

g/12/63 6/11/64 7116164 11/10/64 6/09/65 3102166 7122166 (autopsy) l/12/67 2108168 6125168 6113168 12/04/68 4114169

Yes Yes Yes Yes Yes No

8114169 12/01/69 l/29/70 4/14/70 6/01/70 6/03/71

2,100 820 3,695 1,800 3,950 1,575

Yes

Yes

2,400 1,600 1,350 3,700 1,300 4,970

Results Died 10 days postoperatively, sepsis, bleeding diathesis Died 18 hr postoperatively, hemorrhage Died 2.5 yr postoperatively (subtotal splenectomy) Died 8 wk postoperatively, sepsis Living and well 2.5 yr, lost to follow-up study Living and well 5 yr Living and well 5 yr Died 1 day prior to scheduled operation, septic splenic infarction Died 2 yr 7 mo postoperatively Died 5 mo postoperatively, sepsis Died 10 days postoperatively, accidental Living and well 2.5 yr Died 7 mo postoperatively, myocardial infarction Living and well 22 mo, polycythemia and thrombocytosis Died 7 wk postoperatively, bronchopneumonia Died 7 wk postoperatively, sepsis Died 11 mo postoperatively Died 8 mo postoperatively Living and well 8 mo, hilar node enlargement Living and well 2 mo

cases.

platelet count over one million is not in itself an indication for anticoagulation. When a platelet count in this range is accompanied by a high hematocrit level, thrombosis is more likely to occur. Major thrombotic phenomena should be treated by the institution of heparin therapy. Leukocytosti: In the majority of cases leukocytosis is mild to moderate (16,000 to 25,000 per mms). In one instance it rose to 250,000 per mms. Persistent marked leukocytosis may require the administration of myelosuppressive therapy with busulfan (Myleran@), 2 to 6 mg a day. Sepsis: Patients with this disease, particularly in advanced stages, are prone to septic complications. Only one patient in this series, however, had an infected subphrenic hematoma. Late Complications

The late postoperative course from the hematologic viewpoint is beyond the scope of this paper and will be dealt with in a separate publication. Progressive, marked hepatomegaly occurred in two patients. It was with the object of preventing this late complication that subtotal splenectomy was performed in one patient. This was proved to be technically feasible [4], but failed to prevent hepatic enlargement .[5].

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Late postoperative sepsis was related to the cause of death in four patients, in one of whom the source of sepsis was never identified. In one patient progressive pulmonary hilar lymphadenopathy has been the cause of intractable cough and recurrent episodes of obstructive pneumonitis. Early Postoperative Mortality (within Thirty Days) No operative deaths occurred in this series. One

patient died within twenty-four hours of operation, presumably due to delayed hemorrhage. Autopsy was not obtained. One patient died ten days after operation of diffuse bleeding tendency and septicemia. Both these deaths occurred early in this series, ten and seven years ago, respectively. The last early postoperative death in this series occurred in a patient with organic brain syndrome who accidentally fell out of bed on the tenth postoperative day, sustaining a fractured skull and brain laceration. Comments

Splenectomy for myeloid metaplasia has been a controversial mode of treatment for myeloid metaplasia since its first use early in this century. Most early series, including the review of Hickling [8] in

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Morgenstern

1937 cited the high operative mortality and low therapeutic benefit of splenectomy as reasons for not resorting to “surgical interference,” More recent series [6-111, however, have lent increasing support to the contention that splenectomy, utilized with the proper indications, is a useful and proper adjunct to therapy. Two of the older notions are still surprisingly evident, however, among otherwise well informed physicians: the first is that removal of the massively enlarged spleen is impossible without grave risk to the life of the patient, and secondly that the spleen is the main blood-forming organ, the removal of which would leave the patient with no effective residual hematopoietic sources. Both notions can now be discounted. With proper attention to the details previously outlined herein, regarding pre-, intra-, and postoperative management, surgical risk in the hands of the well trained surgeon is not excessive. Moreover, even if ferrokinetic studies show the major source of red cell production to be the spleen, auxiliary sources in the liver, lymph nodes, and other sites soon become active. In none of the cases in this seri,es was postoperative aplastic anemia or granulocytopenia a problem. Early mortalities or splenectomy failures occurred almost uniformly in patients desperately ill with the disease prior to operation. It was apparent in this series that patients referred for splenectomy in the earlier phases of treatment failure fared much better in the postoperative period and had an increased chance for more prolonged survival. In contrast, the advanced treatment failures, ravaged by the hypermetabolic syndrome and excessive hemolysis and rendered poorer risks because of cachexia, steroids, and bleeding tendency, were much more likely to become splenectomy failures as well, Certainly splenectomy is not curative, but it most definitely can be palliative. Moreover, by decreasing the need for transfusions and steroids, alleviating the hypermetabolic state, and removing the mechanical burden of a massively enlarged spleen, the progression of the disease may be delayed considerably. In this sense it can be said to have some effect on the natural history of the disease, although the basic myeloproliferative disorder is still present. As a result of the current medical practice of delaying splenectomy until all else has failed, most of the patients in this series were in the “last resort” stage when splenectomy was performed. Nevertheless, more than 50 per cent achieved beneficial palliation from one to five years after operation.

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The plea for earlier splenectomy should not be misconstrued. Patients with mild symptoms and moderate splenomegaly controlled by medical means are not candidates for splenectomy. However, when steroids and transfusions become necessary to control hemolysis, thrombocytopenia, and anemia and when the hypermetabolic state supervenes, the time to consider splenectomy has arrived. At that time the patient may be offered maximal benefit with minimal risk, as opposed to the converse after months or years of deterioration with heroic medical measures. Summary

From an analysis of these cases and those reported in the recent literature, earlier splenectomy is advocated for patients with myeloid metaplasia. Careful attention to preoperative preparation and “safe” operative technic has reduced the mortality to acceptable levels. Although postoperative mortality and morbidity in this series were high, they reflect primarily the advanced stage of the disease in patients finally referred for surgery. No patient should be denied operation on the basis of risk of operative mortality or on the basis of the spleen being the primary site of hematopoiesis. References 1. Rosenthal DS, Moloney WC: Myeloid metaplasia: a study of 98 cases. Postgrad Med 45: 136, 1969. 2. Bouroncle BA, Doan CA: Myelofibrosis: clinical, hematologic and pathologic study of 110 patients. Amer J _ Med-Sci 243: 697,1962. 3. Hicklinrr RA: Chronic non-leukemic mvelosis. Ouart J < I Mei6: 253, 1937. 4. Morgenstern L, Kahn FH, Weinstein IM: Subtotal splenectomy in myelofibrosis. Surgery 60: 336, 1966. 5. Morgenstern L, Kahn FH, Weinstein IM: Subtotal splenectomy in myelofibrosis: a reappraisal. In preparation. 6. Green TW, Conley CL, Ashburn LL, Peters HR: Splenectomy for myeloid metaplasia of the spleen. New Eng J Med 248: 211,1953. 7. Ashby WB, Ballinger WF II: Indications of splenectomy: changing concepts as a result of advances in hematology. Arch Surg 85: 913, 1962. 8. Sandusky WR, Leave11 BS, Benjamin BI: Splenectomy: indications and results in hematologic disorders. Ann Surg 159: 695, 1964. 9. Jensen MK: Splenectomy in myelofibrosis. Acta Med Stand 175: 533, 1964. 10. Fishman N, Ballinger WF II: Splenectomy for agnogenic myeloid metaplasia and myelofibrosis. Arch Surg 90: 240, 1965. 11. Gomes MR, Silverstein MN, Remine WH: Splenectomy for agnogenic myeloid metaplasia. Surg Gynec Obstet 125: 106.1967.

Discussion MARSHALLJ. ORLOFF(La Jolla, Calif) : We applaud Dr Morgenstern’s thoughtful and meticulous approach

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to the preparation, operative care, and postoperative management of these difficult cases and have only a few minor points of difference regarding the operative technic. We have found the long transverse incision preferable to the longitudinal approach, even when the spleen is massively enlarged. We regularly drain the splenic fossa with a sump catheter attached to suction because of the frequency of postoperative collections of blood, serum, and occasionally pus. Finally, we inject a small amount of epinephrine into the splenic artery before ligating it to shrink the spleen and to give the patient an autotransfusion of blood. Myeloid metaplasia is one of the myeloproliferative diseases and is not an uncommon condition. It is characterized by moderate to massive splenomegaly with active hematopoiesis in the spleen, by abnormalities of the myeloid elements in the peripheral blood, and, in the vast majority of cases, by fibrosis and hypocellularity of the bone marrow. Contrary to what most of us believed previously, fibrosis of the bone marrow is not a contraindication to splenectomy since the spleen is not the only site of hematopoiesis and removal of the spleen is not followed by failure to generate cells of the myeloid series. The use of splenectomy in myeloid metaplasia is still a matter of controversy because removal of the spleen is a palliative rather than a curative procedure, and its influence on long-term survival is not clear. The bulk of evidence indicates that splenectomy produces

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significant palliation in the form of comfort and hematologic improvement when it is used in selected patients. The indications for splenectomy are: (1) severe hemolytic anemia with the demonstration of sequestration of red blood cells in the spleen by studies with radioisotopically labeled iron and red blood cells ; and (2) marked mechanical discomfort from splenomegaly. It must be emphasized that most of the patients are in their fifties, sixties, and seventies, and the risk of operation in many of them is high because of multisystem disorders. Therefore, the decision to perform splenectomy depends to a significant degree on the general condition of the patient. The operative mortality of 1’7 per cent in Dr Morgenstern’s series is not insignificant, but it is in the range of 10 to 20 per cent as reported by others. Doctor Morgenstern’s one year survival rate of about 45 per cent and his over-all eight month to five year survival rate of approximately 33 per cent are not very different from the long-term results of other workers. Silverstein et al at the Mayo Clinic reported that splenect,omy in selected patients produced a four year survival rate of 50 per cent whereas medical treatment of symptomatic patients resulted in a four year survival rate of 34 per cent. We endorse Dr Morgenstern’s contention that splenectomy has a place in the treatment of selected patients with myeloid metaplasia when it i’s performed with meticulous precautions and according to the therapeutic plan that he has outlined.

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