Hepatic and splenic infarctions: Complications of therapeutic transcatheter embolization

Hepatic and Splenic Infarctions: Complications of

Therapeutic Transcatheter Embolization

John Q. Trojanowski, MD, PhD,” Boston, Massachusetts

Terence J. Harris& MD, Boston, Massachusetts

Christos A. Athanasoulis, MD, Boston, Massachusetts

Alan J. Greenfield, MD, Boston, Massachusetts

Therapeutic transcatheter Gelfoam@ embolization is widely used to control gastrointestinal hemorrhage

when a well defined bleeding site can be identified. The procedure is generally associated with few serious complications when performed in institutions

with highly skilled personnel familiar with its use. We recently encountered two unusual complications associated with Gelfoam embolization of upper gastrointestinal hemorrhage in two patients, namely massive hepatic infarction and splenic infarction

associated with abscess formation. The former complication was fatal; the latter resulted in a pro- longed hospital stay and additional surgery. In this report these cases are described, the pathophysiology

of the complications is discussed, and suggestions are made for preventing and treating such complica-

tions.

Case Reports

Case I. A 70 year old white man entered the Massa-

chusetts General Hospital (MGH) with a 5 day history of epigastric pain. He had had peptic ulcer disease 10 years earlier but had been asymptomatic until 5 days before admission when epigastric paln occurred, for which he took antacids. On the day of admission, melena and hematem- esis were noted. The patient had been seen initially at another hospital, where he was found to be diaphoretic and cool with no obtainable blood pressure. The hematocrit was 40 percent, and blood was irrigated from the stomach. He was treated with intravenous fluids and whole blood. A blood pressure of 95/50 mm Hg was obtained and he was transferred to the MGH. His medical history included treated hypertension and alcohol abuse in the remote past.

From the Departments of Pathology and Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Supported in part by Grants BRSG-0548613 and lRO1 AM 19611-02 from the U.S. Public Health Service, Bethesda, Maryland.

* Present address and address for reprints: John Q. Trojanowski, MD, Phi? Pathology Department, Division of Neuropathology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.

272

At the MGH the patient was seen to be a thin white man in moderate distress with a blood pressure of 110/O mm Hg, a pulse of 92 beats/min and respirations of 20 breaths/min. The results of abdominal examination were negative, but

he had guaiac-positive stools. The chest x-rays were negative and electrocardiography revealed an old posterior myocardial infarction. On admission the hematocrit was 27.8 percent with a white blood cell count of 16,000/mm3 including 79 percent polymorphonuclear leukocytes, 13 percent lymphocytes and 18 percent monocytes. The prothrombin time was 12.8 seconds, with a control of 11.5 seconds, and the partial thromboplastin time was 31.5 seconds. The serum level of sodium was 135, potassium 3.6, chloride 85 and carbon dioxide 32 mEq/liter. The blood urea nitrogen was 75, creatinine 2.9 and glucose 169 mg/lOO ml; the total protein level was 5.5 (albumin 3.7 and globulin 1.8) g/100 ml. The bilirubin, serum glutamic oxaloacetic transaminase, alkaline phosphatase, amylase, calcium, phosphorus and magnesium levels were normal. Endo- scopic examination revealed fresh blood at the pylorus. Angiographic examination with catheterization of the celiac artery revealed massive bleeding from the gastroduo-

denal artery, which was subsequently successfully embolized with Gelfoam (Figure 1). At this point the hematocrit was 20 percent. By the following morning the patient had received 6 units of packed red cells, 6 units of whole blood and 3 units of fresh frozen plasma. Because of continued bleeding, the patient underwent plication of a bleeding duodenal ulcer with hemigastrectomy, vagotomy and Billroth II gastrojejunostomy on the 2nd hospital day. Postoperatively the patient was ambulatory, the blood pressure was normal, and the hematocrit remained in the low to mid 30 percent range.

On the 4th hospital day the patient developed a temperature of 102’F; the findings on physical examination and chest x-ray were negative. The results of blood, wound and urine cultures were negative, and several sputum cultures revealed abundant Enterobacter aerogenes. The alkaline phosphatase was 3.5 Bodansky units and the amylase 22 units/ml. Keflin administration was begun. On the 6th hospital day the patient was afebrile with stable vital signs and able to eat. On the 8th hospital day the

The American Journal of Surgery

Complications of Transcatheter Embolization

Figure 7. Geffoam emboli- zafion of the gastroduodenal artery to control duodenal ulcer bleeding. Left, a celiac axis arteriogram shows contrast extravasation from the distal gastroduodenal artery ( arrowhead) . Right, the gastroduodenat artery (arrowheads) has been occluded with Gelfoam. There is no contrast ex- tra vasation.

Figure 2. Massive hepatic infarction. Left, photograph at autopsy of the unfixed liver, which is massively infarcted. Right, low power photomicrograph of a central vein with coagulation necrosis of the entire liver parenchyma and no inflammatory infiltrate. (Hematoxylin-eosin stain; magnification X100, reduced 33 percent.)

temperature again rose to 102°F and the patient noted

crampy pain in the left upper abdominal quadrant. He was

jaundiced and the hilirubin level was 9.0 mg/lOO ml. The serum level of serum glutamic oxaloacetic transaminase was 94, lactic dehydrogenase 312 and alkaline phosphatase 7.6 Bodansky units. The results of abdominal examination were negative. On the following day the bilirubin level increased to 13 mg/lOO ml; lactic dehydrogenase increased to 1,288 and alkaline phosphatase to 13.3 Bodansky units. The amylase level was 13 units/ml. On the 10th hospital day, ultrasound examination of the liver revealed a large echogenic area in the right lobe, raising the possibility of a liver abscess. At laparotomy the liver was found to be massively necrotic. Postoperatively the patient’s condition deteriorated rapidly, and he died on the 11th hospital day.

At autopsy the abdominal findings included massive coagulation necrosis of the liver, including both hepato- cy,tes and stroma, with no evidence of inflammation (Figure 2). An organized thrombus containing Gelfoam was found in the gastroduodenal artery, but the remainder of the

extrahepatic portion of the celiac artery and its branches were unremarkable. However, the intrahepatic, proximal portions of the hepatic artery were obstructed hy multiple organizing thrombi containing Gelfoam (Figure 3). The portal vein and hiliary tree appeared normal and the pli- cated duodenum and gastro,jejunostomy were intact. In addition there was acute pancreatitis, colonic ulcerations, mild splenomegaty, fibrinous peritonitis and serous ascit,es. Multiple recent renal infarcts and mild nephrosclerosis were seen as well. Cholesterol emboli were noted in the areas of renal infarction, but no Gelfoam was seen. Both renal arteries and veins appeared normal. The thoracic findings included a fibrinous pericarditis of the portion of

the pericardium lying adjacent to the diaphragm, pulmo- nary edema, mild emphysema, mild cardiomegaly, mild f’ibrocalcific disease of the mitral and aortic valves and an old posterior myocardial infarction with marked athero- sclerosis of the coronary arteries and aorta.

Case II. An obese 44 year old man vomited bright red blood and noticed black stools on the morning of the day

Volume 139, February 1980 273

Trojanowski et al

he entered the hospital. He complained of mid-epigastric and anterior chest pain as well as dizziness. He had a long history of ethanol abuse.

On admission to the MGH blood pressure was 106/80 mm Hg, pulse 110 beats/min and respirations 25 breaths/ min. The abdomen was distended and tenderness noted in the mid-epigastrium. Bowel sounds were present. The

stool was markedly positive for blood. Nasogastric aspi- ration returned bright red blood; the hematocrit was 28 per

cent. Esophagogastroduodenoscopy revealed an erythematous

gastric mucosa and an ulceration in the fundus along the lesser curvature. No other abnormalities were recognized. Selective left gastric and splenic arteriography demonstrated a fundic bleeding site supplied by short gastric

arteries derived from the splenic artery. Vasopressin infusion at 0.2 units/min did not control the bleeding. Transcatheter Gelfoam embolization of the short gastric branches of the splenic artery halted the bleeding (Figure

4). During the next 3 days, pleuritic pain radiating to the

left flank developed in the left upper abdominal quadrant.

Although there was no evidence of continued gastrointestinal bleeding, the hematocrit gradually decreased from 33 to 24 per cent. The patient was mildly febrile (100.5”F). Tenderness was present over the left posteroinferior chest and the left upper quadrant of the abdomen. Bowel sounds were active. A diagnosis of splenic infarction was made. A liver-spleen scan (technetium-99m sulfur colloid) revealed multiple foci of reduced activity in the spleen (Figure 5). Prothrombin and partial thromboplastin times were normal. After transfusion the hematocrit was 32 per cent.

The patient continued to have fever (100 to 102’F) and pain until 10 days after angiography, when rigors and chills developed. The white blood cell count was 12,900/mmZi with 60 per cent mature neutrophils and 28 per cent lymphocytes. Target cells and reticulocytes were seen easily on peripheral smear. Thrombocytosis of greater than 1 million/mmi of blood was present. Repeated blood cultures were negative.

Eleven days after angiography, a left pleural effusion developed. The white blood cell count was 12,50O/mm:% with 82 per cent mature neutrophils and 11 per cent lymphocytes. Chest x-ray showed elevation of the left hemi-

Figure 3. Left, photograph of the cut surface of the liver revealing mu/tip/e thrombosed infraparenchymai branches of the hepatic artery. Right, low power photomicrograph of one of the infraparenchymai branches of the hepafic artery seen at left, revealing an organizing thrombus obstructing the lumen with Geifoam particles intertwined within the thrombus. ( Hematoxyiin-eosin stain; magnification X37, reduced 33 percent.)

Figure 4. Geifoam emboii- zation of the short gastric arteries to control gastric ulcer bleeding. Left, spienic arferiogram shows contrast exfravasion (arrowhead) from short gastric arteries. Right, spienic arferiogram after franscafheter emboii- zation with Geifoam. Short gastric branches and spienic arterial branches to the upper pole have been occluded ( arrowheads) . There is no exfravasation.

274 The American Journal of Surgery


Figure 5. Radionuclide spleen scan 3 days after emboti- zation shows mu/tip/e areas of reduced activity consistent with the diagnosis of multiple splenic infarcts.

diaphragm with left pleural effusion. Upper gastrointestinal series and chest fluoroscopy subsequently defined a large left subdiaphragmatic air- and fluid-filled cavity co:Gstent with a subphrenic abscess.

Fift,een days after hospital admission, splenectomy and drainage of the left upper abdominal quadrant was per- f‘or,med. A large intrasplenic abscess contained 2,000 cm:{ of’ purulent and necrotic debris. The stomach, colon and liver were adherent to the massively enlarged spleen.

‘I’he surgical specimen was a 15 by 6 by 4 cm spleen that contained in the markedly expanded upper pole a large abscess surrounded by granular necrotic debris. The capsule was granular with gray fibrinous tags and gray-yellow purulent tissue (Figure 6). Within the upper pole segmental branch of the splenic artery, a friable organizing thrombus containing Gelfoam was present. Cultures of the abscess grew Staphylococcus aureus.

The patient did well postoperatively and was discharged cm the 32nd hospital day.

Comments

The cause of death in the patient described in case I was clearly massive hepatic infarction. The remainder of’ the acute pathologic changes may be

co:lsidered secondary to this process and the terminal ca odiovascular deterioration. The best explanation for the hepatic infarction, as elucidated later, is the loss of the gastroduodenal artery as a direct result of the therapeutic embolization procedure and reflux of multiple Gelfoam fragments out of the gastroduodenal artery with embolization of this material to the liver, an unforeseen complication of the therapeutic procedure.

The presence of Gelfoam in the thrombi found wil;hin multiple intraparenchymal branches of the hepatic artery indicates that Gelfoam fragments re- fluxed from the therapeutically embolized gastroduodenal artery and later became lodged in the in- traheptatic branches of the hepatic artery. The point or points in the patient’s hospital course when these events occurred is difficult to ascertain with cer-

Figure 6. Low power photomicrograph of the splenic abscess wall. A zone of necrosis, polymorphonuclear leuko-

cyte debris and fibrin (right) is surrounded by active granulation tissue ( center). Splenic red pulp shows fibrosis of cords and dilatation of sinusoids (left). (Hematoxylin- eosin stain; magnification X55, reduced 27 percent. )

tainty. The available clinical and laboratory data suggest that the onset of hepatic infarction was on about the 6th or 7t.h postoperative day since the alkaline phosphatase was normal on the 4th postoperative day, the serum glutamic oxaloacetic trans-

aminase was only twice normal on the 8th postoper-

ative day, and the lactic dehydrogenase was still in- creasing on the 9th postoperative day. This conclu-

sion is based on data which indicate that peak ele- vations of the transaminases and lactic dehydrogenase occur within 48 to 72 hours of the onset of hepatic infarction [I ,2]. The onset of hepatic infarction in this case would thus be unrelated to the initial episode of hypotension on admission. This means that reflux could have occurred at the end of the 1st

postoperative week with immediate arterial throm- bosis, or that reflux occurred closer to the time of the

original embolization procedure, perhaps more than once, but that significant arterial occlusion did not occur until about the 6th or 7th postoperative day. Granted that the onset of infarction occurred at this time and given the presence of multiple Gelf’oam emboli in the intrahepatic branches of the hepatic artery in association with the therapeutic embolization of the gastroduodenal artery, one is left to conclude that the loss of these sources of hepatic perfu- sion was the cause of the total hepatic infarction.

The incidence of hepatic infarction in autopsies has been variously reported as 0 in $,iOO to 1 in 50 [%,d]. The cause of hepatic infarction has been as- cribed to arterial or venous occlusion as well as he- modynamic changes due to shock. sepsis, biliary disease or anesthesia [oh’].


Trojanowski et al

There is controversy in the literature with respect to whether occlusion of the hepatic artery can lead to hepatic infarction. Many case reports have documented hepatic infarction due to arterial occlusion, and the subject has been reviewed by several authors

who conclude that hepatic infarction due to arterial occlusion is a definite entity [2,5-71. However, other

authors oppose this view on the basis of the vast number of collateral sources of arterial hepatic per- fusion, the liver’s dual blood supply from the hepatic artery and portal vein and the published reports of

intentional hepatic dearterialization for primary or secondary hepatic neoplasms without total hepatic infarction [8-131.

The controversy is difficult to resolve for several reasons. The dog model has not proved comparable to the human, nor have any good alternatives to the

dog model been developed to date [8]. In addition, the variability of the hepatic arterial supply and the large number of potential collaterals [14] complicates

the analysis of cases and is usually not considered in case reports. Finally, the other aforementioned causes of hepatic infarction are frequently not spe-

cifically excluded in many case reports, making it difficult to draw satisfactory conclusions about the

etiology of the infarction. In the present case, the exclusion of these other

causes of hepatic infarction leads one to the conclu- sion that the constellation of arterial occlusions in the

celiac axis resulting from the Gelfoam embolization described earlier led to hepatic infarction and subsequently to the patient’s death. The emboli to the

intrahepatic branches of the hepatic artery probably resulted from reflux of Gelfoam fragments out of the

gastroduodenal artery, with subsequent embolization to the intrahepatic portions of the hepatic artery.

Although this explanation accounts for the pathologic findings and does not contradict what is known from the clinical history and the literature, it is based

on the exclusion of other known causes of hepatic infarction and cannot be absolutely proven on the

basis of the available data. However, this explanation is supported by a previous report [15] of small non- fatal hepatic infarcts secondary to therapeutic embolization and reversal of flow in the gastroduodenal artery documented angiographically with reflux of embolic material, and by another report [16] of fatal hepatic infarcts with abscess formation after exten- sive embolization of the hepatic artery to reduce in- sulin production by a metastatic islet cell tumor.

In case II, splenic infarction with abscess formation was a complication of transcatheter Gelfoam embolization. In this patient with alcoholic gastritis hemorrhage from short gastric arteries occurred at

the base of an ulcer. Gelfoam embolization of the

short gastric arteries halted the bleeding; however, segmental splenic arteries to the upper pole were also occluded. Multiple small splenic infarctions were associated with fever, pain in the left upper quadrant of the abdomen and tenderness. Thrombocytosis was present and abnormal red cell morphology was noted in peripheral smears.

The development of splenic abscess was heralded by fever, chills, left pleural effusion and sudden

marked granulocytosis. An air-fluid level was demonstrated in the left upper quadrant. Surgery revealed a large splenic upper pole abscess that grew Staphylococcus aureus.

Splenic abscesses may be classified in two cate- gories [17]. Multiple small abscesses are usually discovered at autopsy and are the result of an over- whelming septic inoculum or immunodepression of the patient. Solitary large abscesses arise secondarily in intrinsic disruptions of splenic architecture, such as hematomas or infarcts. Inoculation occurs via low level bacteremia that is usually not clinically ap-

parent. Gram-negative bacteria are the most com- monly isolated organism (24 per cent), and staphy- lococci the second most common (21 per cent) [18]. The spleen may also be involved by extension of adjacent septic processes such as pancreatic or peripheral abscesses.

Large solitary splenic abscesses are challenging clinical problems and occur in diseases where splenic infarction is common, such as certain hemoglobino-

pathies. Experimental work has given validity to the clinical association of splenic infarction and abscess. Caldarera [19] was only able to produce splenic ab-

scess after intravenous injection of Staphylococcus aureus in healthy rabbits when the spleen had been traumatized or a terminal branch of splenic artery

had been ligated before injection. Dalton and West [20] noted a paucity of gross and

microscopic changes within the spleens of three dogs after ligation of the main splenic artery. The fact that

ligation of the splenic artery in healthy dogs does not significantly alter splenic structure was confirmed

by Tsapogas et al [21], who also demonstrated rela- tively preserved functional integrity. The collateral arterial supply of short gastric arteries and spleno- renal arteries were intact. When the spleen is com- pletely dearterialized, marked scarring and atrophy occur. Reflux of blood from the portaisystem and the subsequent development of collateral circulation from the omentum may play a role in the mainte- nance of residual splenic tissue [ZO]. Therefore, occlusion of the large arterial supplies to the spleen may leave residual functional splenic tissue. The small

276 The American Journal of Surgery


arteries of the spleen are essentially end arteries that st~pply a wedge-shaped area the base of which is di-

rected toward the capsule 1221. Occlusion of one of these vessels. as occurred in our case II, leads to local infarction, providing fertile ground for subsequent

aijscess formation.

icopathologic study of seven cases. Arch Pathol Lab Med

1976; 100:32.

4. Seeley TT, Blumenfeld CM, lkeda R, Knapp W, Rueben BH.

Hepatic infarction, Hum Pathol 1976; 3:265. 5. Park& RGF. Arterial infarction of the liver in man. J Pathol

Bacterial 1955; 70:521. 6. Carroll R. Infarction of the human liver. J Clin Pathol 1963;

16:133.

‘1’1, o\lr knowledge. this is the first reported case of splenic infarction with abscess formation as a complication of (:eifoam embolization for gastric bleeding. However, splenic infarction and subsequent aljscess is a well known hazard of therapeutic em-

1) )lization of’ the spleen in hypersplenism [S’S26’1. Recently, investigators have devised a method of tr,anscatheter splenic embolization associated with

a lower incidence of serious complications [27]. These authors have devised protocols for successful *’ nedical splenectomy” using embolization proce-

dures that depend on scrupulous asepsis, antibiotic u;e and post,embolization management. When splenic infarction is suspected as a complication of a therapeutic embolization procedure, the rapid in- st itution of such an approach to patient management rr.ight preclude the development of an abscess. A

similar approach might prove of some value in cases 01 hepatic infbrction since it can also be complicated

b:q abscess formation [IS], although such was not the case in t,he patient we described. However, the prevent ion of’ reflux appears to be the best remedy for the c~omplications reported herein. A technique using balloon-tipped catheters has been developed at our ir.stitution and has been successfully used to prevent ref’lux during transcatheter embolization [28].

Summary

‘I’wo cases are described in which therapeutic transcatheter Gelfoam embolization was complicated by fat.al hepatic infarction in one patient and splenic infarction with abscess formation in another patient. These are unusual complications of this widely used therapeutic technique. The probable pathophysiology of’ these complications is discussed and sugges- ti/)ns for managing and avoiding them are made.

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Hepatic and splenic infarctions: Complications of therapeutic transcatheter embolization