World J. Surg 15, 176-187, 1991
Wodd Journal of Surgery 9 1991 by the Soci6t~ lmernationale de Chirurgie
Portal Hypertension in Mansonic Schistosomiasis Silvano Raia, M . D . , P h . D . , Sergio Mies, M . D . , and F e r n a n d o Alfieri, Jr., M.D. Liver Unit (LIM/37), Faculdade de Medicina da Universidade de Silo Paulo, Silo Paulo, Brazil Mansonic schistosomiasis is an endemic disease in Brazil, with an estimated 10--12 million people infested. Among its clinical manifestations, the hepatosplenic form causes portal hypertension which, in turn, brings about severe digestive hemorrhage, the most serious complication of the disease. Normally, the patients are young, and have hepatosplenomegaly, hypersplenism without clinical manifestations, and slightly reduced hepatic function. The angiographic findings are characteristic, differing from those of hepatic cirrhosis. In Brazil, the definitive treatment for gastrointestinal hemorrhage is surgery, which should be done under elective conditions whenever possible. During a short period of time, known as the "risk period" (the time between the hemorrhagic episode and the surgery), propranolol has been used to prevent further bleeding. Surgical treatment is indicated only after the first episode, and never on a prophylactic basis. In 1977, a prospective, randomized trial was begun in order to assess the delayed results of the 3 surgical operations most widely used in this country. The study was interrupted after 94 patients had been operated on due to the high incidence of encephalopathy in the group who underwent classical splenorenal shunt. After a follow-up of at least 60 months and, at most, 130 months, the results showed that classical splenorenal shunt caused encephalopathy in 39.3 % of the cases and distal splenorenal shunt in 14.8%. None of those submitted to esophagogastric devascularization with splenectomy developed encephalopathy. The 3 procedures showed similar rates of hemorrhagic recurrence.
Schistosoma mansoni is a digenetic trematode belonging to the Schistomatidea family. This family includes 4 other species: S. japonicum, S. haematobium, S. mekongi, and S. intercalatum [1, 2]. These species are found in various regions around the world, but only S. mansoni has developed in certain areas of Brazil due to climatic conditions, poor sanitation, and the presence of transmitter snails. Mansonic schistosomiasis is also found in Africa, Asia, and other countries of South America [3]. Brazil is one of the most important foci of this parasitosis, where it is endemic. Estimates are that between 10 and 12 million Brazilians are infested with the disease [3, 4]. The life cycle of S. mansoni takes place in 2 hosts. The eggs, which are eliminated in the feces of contaminated persons, if in contact with water, release the miracidia (ciliated embryos), which infest mollusks of the Planorbidea family of the Biomphalaria genus (intermediate host). Here the miracidia multiply, giving rise to the cercaria (larval form) which are elimiSupported by FIPEC IlI grant no. 10/02007-0. Reprint requests: Silvano Raia, M.D., Ph.D., Rua Peru, 421, 01238 S~o Paulo, Brazil.
nated into the water. Man, in contact with the contaminated water, is actively infested through the skin and mucosa. The larvae, after reaching the bloodstream, migrate to the lungs and then to the portal intrahepatic system where they reach full maturity. Then they descend to the mesenteric veins, reproduce, and, in the finest branches, move to the level of the intestinal submucosa where they lay their eggs, reinitiating the cycle. The eggs are laid principally at the level of the rectum and the sigmoid, extending to the rest of the colon and small bowel in the more massive infestations [5]. Each female of S. mansoni produces approximately 300 eggs per day, 25% of which are eliminated in the feces. The rest are retained in the tissues, especially in the bowels and the liver [5], where they are destroyed. The clinical classification of schistosomiasis is that proposed by the Brazilian Society of Hepatology [5], and consists of 2 phases--the initial and the chronic. The initial phase, in unapparent and acute forms, is self-limiting, and recedes either spontaneously or by means of specific therapeutic measures. Direct evolution to the forms of the chronic phase are rare [5]. Normally, after the initial phase, a relatively asymptomatic period of varying duration occurs, with slow and gradual evolution to chronic forms. In the chronic phase, there are 3 progressively more severe forms: intestinal, hepatointestinal, and hepatosplenic. It is pointed out that the disease is not always progressive, and may remain stationary or even recede, depending on a large number of factors [5]. The only form which causes portal hypertension is the hepatosplenic, which appears between 5 and 10 years after the first infestation [6, 7]. It is estimated that 10% of the infested population develop this form [8]. As a result, approximately 1 million persons in Brazil have or will have portal hypertension caused by this disease. The disease has a complex pathogenesis. The adult worm is well tolerated, and causes neither irritation, inflammation, nor portal obstruction since it has the capacity to "fool" the defenses of the host by incorporating human antigens on its surface [6]. When the worm dies, it is carried to the hepatic parenchyma through the portal vein, causing areas of necrosis and inflammatory reactions which may result in vascular lesions and scar fibrosis (Symmers' fibrosis) [9]. These lesions can also be observed in the lung tissues [3]. The fibrous thickening of the portal tracts causes obstruction of the intrahepatic branches of the portal vein, with intense vascular proliferation of contro-
S. Raia et al.: Schistosomal Portal Hypertension
177
Table 1. Hepatosplenic schistosomiasis: Coagulation factors.
Prothrombin time (%) Fibrinogen (rag %) Factor V (%)
Average and standard deviation (n = 85)
Normal
73.26 + 14.01 288.96 -+ 76.36 68.09 --- 17.09
80/100 130/450 70/100
versial nature (see Hemodynamic aspects) [10, 11]. Other authors believe that the fundamental pathogenesis of the intrahepatic vascular obstructive and inflammatory phenomena are due to the live eggs. These eggs, by means of secretions from the mature miracidia, have a sensitization effect on the host, stimulating immune responses and the formation of granulomas [12, 13]. The development of the lesion may also be related to circulating immune complexes which are probably responsible for progression of the disease [14]. The pathogenesis of Symmers' fibrosis is not satisfactorily explained by the lesions produced, nor by the eggs, dead worms, or immunological factors mentioned. Some authors suggest that soluble products, such as lymphokines, secretions of activated macrophages, or even parasite products, may stimulate the proliferation of fibrous tissue which extends outside the granulomas [15, 16]. Clinical, Laboratory, and Ultrasonographic Features
Patients with schistosomal portal hypertension are young, generally between the ages of 15 and 50 years, in good general health, and without signs of chronic liver disease. Edema, ascites, gynecomastia, spider angiomas, or encephalopathy are rarely observed [17]. In anamnesis, the complaints are noncharacteristic. The first sign of the disease may be an acute episode of digestive hemorrhage, shown by hematemesis or melena [18]. The most frequent finding in the physical examination is hepatosplenomegaly [19]. For reasons not yet fully understood, the liver, principally the left lobe, is enlarged (see Hemodynamic Aspects below). The organ is hardened and displays a rough nodular surface. Splenomegaly, secondary to reticuloendothelial hyperplasia and to passive congestion due to portal hypertension, can be considerable. Mies and associates [20, 21], in an angiographic study of 50 patients with portal hypertension and a history of at least 1 episode of upper digestive hemorrhage, estimated the average weight of the spleen at 1,100 g. Generally, patients withstand bleeding and surgical interventions well, without important signs of hepatic failure (ascites, encephalopathy, or jaundice). Depending on the amount of bleeding, some patients may develop slight jaundice or even ascites which disappear quickly. The hepatorenal syndrome, often present in advanced cirrhosis, is not observed in pure schistosomiasis [! 1]. Laboratory data show moderate hepatic dysfunction. In a series of 38 patients with portal hypertension without bleeding within the previous 15 days, our group observed slight alterations in the levels of transaminases, alkaline phosphatase, and gamma-glutamyl transferase. The protein electrophoresis showed mild hypoalbuminemia with a sizeable increase in the gamma-globulin fraction [11]. Some studies refer to fusion of the beta and gamma fractions in 50% of the patients [22]. Clinically, no important hemorrhagic tendencies were ob-
Table 2. Hepatosplenic schistosomiasis: Hypersplenism (n = 85).
Laboratory alterations (89.4%) Leukopenia (• 103/ram3) Platelets (• 103/ram3) Symptomatic hypersplenism Epistaxis Gingival bleeding Purpura Bruising Infections
% 75.3 82.4 12.9 5.8 3.5 2.3 1.3 0
Average and Standard Deviation 3.27 + t.41 75.15 -+ 42.90
served. In our group, the study of coagulation factors in 85 patients with the hepatosplenic form of the disease without digestive bleeding for at least 15 days, showed mild alterations (Table 1). The reduction in prothrombin time, also described by other authors [23], is related either to reduced hepatic synthesis or to increased consumption [24, 25]. Hypersplenism, defined by the number of platelets below 100,000/ram 3, associated or not with a leukocyte count below 4,000/ram 3, was observed in 89.4% of the patients. Clinical manifestations of hypersplenism are rare and occur in only 12.9% of the patients (Table 2). A study of platelet function in 14 patients with the hepatosplenic form of this disease demonstrated that the platelets were functionally normal in spite of their reduced number [26]. Among Brazilian authors, Cerri and associates [27] studied 103 patients with the hepatosplenic forms of schistosomiasis, and described characteristic ultrasonographic alterations. The main findings were hypertrophy of the left lobe of the liver and atrophy of the right lobe (81%), periportal fibrosis (73%), dilated portal vein (73%), dilated splenic vein (68%), and thickening of the gallbladder (60%). Splenomegaly (100%) and collateral vessels (35%) were also found. In pediatric and adolescent patients, a general developmental delay was observed (sexual, psychic, bone age and stature) [28, 29]. Malnutrition has been considered a major contributing factor since the disease is most prevalent among people from lower economic classes [3]. Several authors failed to confirm a possible connection between hypersplenism and hormonal alterations [30, 31]. Hemodynamic and Angiographic Features
Mansonic schistosomiasis produces characteristic angiographic alterations, some of which were described by our group after systematic study of 50 patients with schistosomiasis and a history of gastrointestinal bleeding more than 30 days before the study. The inferior vena cava shows clear retrohepatic constriction in most patients, and generally there is no appreciable venous hypertension [32]. Angiography of the hepatic veins shows characteristic alterations. Dilation is present, with arching of the large branches, reduced dichotomization, radiated images and increased bifurcation angles [32, 33]. The average gradient between the free and wedge pressure is at the upper limit of what is considered normal; however, in about 40% of patients, the gradient is higher [32-34]. The conclusion is that portal hypertension in the majority of patients with hepatosplenic schistosomiasis is of the presinusoidal type. Nev-
178
World J. Surg. Vol. 15, No. 2, Mar./Apr. 1991
Fig. 1. Splenoportographyof a patient with
schistosomiasis. Note the large diameter of the splenic vein (arrow 1), portal vein (arrow 2), and the neoformed vessels around intrahepatic portal branches--"Bogliolo's sign" (black arrows).
ertheless, in approximately 40% of patients, a moderate parasinusoidal block is also observed. The splenic artery is generally tortuous and dilated [20, 21]. The spleen, in the venous phase of the splenic arteriography, is considerably enlarged. A planimetric evaluation and the use of the formula proposed by Blendis and colleagues [35] made it possible to estimate its average weight at 1.1 kg [20, 21]. The splenic and portal veins also show a considerably increased diameter. The portal system presents an intrahepatic pattern which is also characteristic. Although observable in the venous phase of the splenic artery, it can be better analyzed with a direct injection of radiological contrast into the portal system. These alterations, described by Bogliolo in 1956, are characterized by amputation of the large branches and by the development of neoformed vessels around the portal branches, giving origin to what is known as "Bogliolo's sign" (Fig. 1) [36-38]. Another angiographic finding included reduced diameter of the common and proper hepatic arteries, with a greatly altered intrahepatic pattern. Vascular spaces and an increase in the bifurcation angles are also present, showing an aspect of poor arterial supply [20, 21], even though there are no signs of hepatic atrophy (Figs. 2A, 6A); however, some authors claim that in schistosomal patients the liver is more dependent on arterial blood flow [18, 39]. The arterial and portal alterations observed angiographically are compatible with the existence of increased portal blood flow and reduced arterial blood flow to the liver. The interaction between the portal and arterial blood flows in the hepatic blood supply has been described by numerous authors [40, 41]. Recently, the influence of adenosine in the regulation of arterial blood flow to the normal liver has been described. Adenosine, continuously secreted in Mall's space (the physiological representation of the portal tracts), seems to have its local concentration altered by portal blood flow (slower flow, lower wash-
out), bringing about arterial vasodilatation when at high levels. Thus, a reduction in the portal blood flow would result in a greater concentration of adenosine and vasodilation of the hepatic artery and an increase in arterial blood supply to the liver (buffer response) [42]. Consequently, in cirrhosis, the increased diameter of the common and proper hepatic arteries commonly observed in angiography seems to be a consequence of a greater concentration of adenosine in Mall's space, due to the lowering of portal blood flow [42]. In schistosomiasis, on the other hand, the sizeable splenomegaly demands a greater arterial blood supply with a consequent increase in the diameter of the splenic artery. Thus, there seems to be a greater blood flow to the splenic vein, which, in turn, effects an increase in the portal blood flow. Therefore, there would seem to be a reduction in arterial blood flow to the liver secondary to the high splenoportal blood flow, and maintenance of the total hepatic blood flow (Fig. 3). There is some evidence in favor of this hypothesis. Initially, the total hepatic blood flow is normal in schistosomiasis patients [43, 44]. In Brazil, it has been shown by means of angiographic studies, that the common and proper hepatic arteries increase in diameter immediately following occlusion of the splenic artery by means of a balloon catheter [45]. This effect was also observed after splenectomy [20], distal splenorenal shunt (DSRS) [46] and esophagogastric devascularization with splenectomy (EGDS) [47]. It should be noted that all these procedures have in common removal of the splenic component of portal blood flow. Indirectly, the faint visualization of the portal system in the venous phase of the splenic or of the superior mesenteric arteriogram is suggestive of high portal blood flow. In 1980, Raia measured the splenic blood ftow in schistosomiasis by means of an electromagnetic flowmeter. He observed an average splenic blood flow above 500 ml/minute immediately before performing the anastomosis in a DSRS [48]. Thus, it is probable that, in schistosomiasis, the higher portal blood flow determines
S. Raia et al,: Schistosomal Portal Hypertension
179
SPLENC I RETICULO-ENoOTHELIAL HYPERPLASIA
I ~ BLOOD FLOW TO THE sPLEEN
NETWORK OF
9
~N [EOF -ORMEDVESSELS ~ I {BOGLO ' LOS 'SIGN)?
t SPLENOPORTAL BLOOD FLOW
MA N ITENANCEOF TOTAL H EPATC I BLOOD FLOW
$ARTERA I LHEPATC I BLOOD FLOW Fig. 3. Pathophysiology of portal hypertension in schistosomiasis.
Fig. 2. Pre- and postoperative hepatic arteriography of a patient with schistosomiasis (distal splenorenal shunt). A. Preoperative: Note the reduced diameter of the common (arrow 1) and proper hepatic arteries (arrow 2). The in~rahepatic pattern gives an overall appearance of poor arterial supply. B. Postoperative: Note the abundant intrahepatic arterial supply and the increased diameter of the common (arrow 1) and proper hepatic arteries (arrow 2).
a lower concentration of adenosine in Mall's space, resulting in arterial vasoconstriction and the angiographic aspect of a poor intrahepatic arterial pattern, The obstruction of the large intrahepatic portal branches, proper to the disease, would be evidence against this hypothesis; however, an increase in the portal blood flow might be understood if we consider the intense network of neoformed portal vessels observed in the liver (Bogliolo's Sign). It is important to remember that the authors who suggest a greater arterial component in the schistosomal liver made their studies either on cadaver livers or on sptenectomized patients. In these cases, there are no hemodynarnic effects on the regulating balance of the hepatic blood flow altered by the removal of the splenic component or by death [18, 39]. Besides this, in schistosomiasis an increase in the size of the left lobe of the liver is observed. There are studies which demonstrate that there is preferential blood flow in the portal
system, with the right lobe receiving its blood supply chiefly from the superior mesenteric vein and the left lobe chiefly from the splenic vein [49]. A recent study with radioisotopes concluded that portal blood flow in patients with hepatosplenic schistosomiasis is reduced in the right lobe and increased in the left lobe of the liver [50]. The greater portal blood flow to the left lobe is indicative of an increased splenic blood flow. For this reason, it can be supposed that the increase in size of the left lobe of the liver is a consequence of the greater blood flow coming from the splenic vein, which contains a greater quantity of hepatotropic pancreatic hormones. Treatment
The treatment for schistosomiasis is simple, consisting of a single dose of oxamniquine or praziquantel. In spite of some authors having demonstrated a synergistic action with these drugs [51, 52], this association does not necessarily hold true [53, 54]. In Brazil, oxamniquine is used more often, and destruction of the parasite is obtained in 80-90% of the cases [3, 55-57]. This chemotherapy reduces the possibility of evolution to more severe forms of the disease [58-60]. The most severe complication and main clinical manifestation of portal hypertension caused by Schistosoma mansoni is upper gastrointestinal bleeding due to ruptured esophageal varices [46, 61--63]. This complication occurs in 12-20% ofpatients [60, 64] in the few studies published on the natural history of the patient with hepatosplenic schistosomiasis. Some studies have shown that the bleeding is well tolerated and may cease spontaneously or be easily controlled with clinical measures; however, recurrence is frequent and unpredictable [60]. After the initial control of bleeding, there is still the need to prevent its recurrence. Surgical treatment has been the most widely accepted in Brazil [i 1, 46,' 65, 66]. Surgery should only be undertaken, however, when elective conditions are present,
180
World J. Surg. Voi. 15, No. 2, Mar./Apr. 1991 Table 3, Surgical treatment of digestive bleeding in hepatosplenic
a measure which has been shown to reduce more serious complications and mortality [46, 67]. It is important to point out that surgical treatment is generally indicated after the first bleeding episode. Surgery is not prophylactically indicated. In a review of the literature from 1908 to 1976, Raia analyzed 130 publications referring to 4,516 patients submitted to surgery-3,084 of whom were in Brazil~and observed the lack of well controlled studies [46]. Of all the methods proposed, the most frequently used was simple splenectomy (S), followed by EGDS (esophagogastric devascularization with splenectomy) and classical splenorenal shunt (SRS). These procedures made up 81.6% of all the operations performed in different periods in time. In spite of these studies being retrospective, often with partial data, minimum follow-up, and total absence of comparison, they show that recurrence is apparently high only in the patients who have undergone S, while encephalopathy was observed only in those submitted to portosystemic shunts of various types. At that time, it was considered that DSRS (distal splenorenal shunt) would theoretically be the most adequate procedure since it would selectively decompress the gastroesophageal territory responsible for the varices in the esophagus while maintaining the portal blood flow to the liver. In Brazil, this procedure was introduced by Raia and coworkers in 1971 [68].
A continuous suture of the portal vein is then performed with the objective of obtaining anatomic continuity between the superior mesenteric vein and the portal vein. Anastomosis of the splenic vein to the left renal vein, previously dissected and after ligation of the adrenal vein, is then performed in the anatomical position most compatible with a favorable hemodynamic situation (on the cranial surface of the left renal vein, at a 45~ angle).
Prospective Trial
2. Esophagogastric Devascularization with Splenectomy. The
In 1977, our group began a prospective randomized trial comparing the 3 surgical techniques used at that time (EGDS, DSRS, and SRS), with the objective of assessing which was the best procedure for schistosomiasis in terms of recurrence of bleeding, encephalopathy, and mortality. Patients between the ages of 15 and 50 years with portal hypertension and without any digestive bleeding episode for at least 15 days due to rupture of esophageal varices and previous treatment for schistosomiasis were included in the study. Those with portal vein thrombosis, chronic liver disease of any other etiology, or who reported an intake of 100 g of alcohol or more per day for at least 18 months were excluded [11, 61].
Technical Considerations. Each surgical procedure included in the study had been performed by the same surgeon and the late postoperatory by the same observer during the entire follow-up. The SRS had always been performed according to the technique widely described in the literature. The DSRS and the EGDS deserve special consideration due to the many existing variations and different physiopathological meanings. I. Distal Splenorenal Shunt. Initially, the splenic artery is isolated and temporarily clamped on the upper edge of the body of the pancreas with the objective of preventing splenic engorgement and consequent bleeding when the splenic vein is dissected and clamped in order to perform the anastomosis. The splenic vein is dissected up to the portal vein. At this stage, the right gastroepiploic vein is accessed and ligated at its origin. The retropancreatic portal vein is dissected from behind the pancreas to about half of its extension. The left gastric vein, therefore, is ligated at its origin. The right gastric vein is ligated near the duodenum and the umbilical vein on the umbilical ligament. The splenic vein is sectioned close to the portal vein.
schistosomiasis: Prospective study. SRS No. of patients Loss of follow-up: % (no. of cases) Late mortality: % (no. of cases) Portosystemic encephalopathy: % (no. of cases) Esophageal bleeding recurrence: % (no. of cases)
D S R S E G D S Total p
32 30 12.5 10.0 (4) (3) 42.85 14.81 (12) (4)
32 12.5 (4) 7.14 (2)
94 11.7 (11) 21.68 (18)
39.28 (11)
0
18.07 (15)
14.28 (4)
9.64 (8)
14.81 (4)
10.71 3.70 (3) (1)
= 0.003 = 0.001
aNot done (small no. of patients).
first surgical step consists of a ligature of the splenic artery close to the body of the pancreas, immediately followed by compression of the spleen. The splenic hilum is carefully dissected and its elements are ligated separately. Then the spleen is removed. Generally, the stomach and the terminal esophagus are devascularized starting at the incisura angularis after ligating the left gastric vein on the pancreatic plateau, and by cutting the vagal branches. A longitudinal opening in the anterior surface of the stomach and of the esophagus is made, extending 3 cm below the esophagogastric transition and 7 cm above. The varices are ligated with a continuous catgut suture, starting in the stomach and progressing along the esophagus as high as possible. The esophagogastric incision is closed in 2 layers and recovered with an anterior antireflux valve which includes 270~ of the esophagus. The operation is completed by a pyloroplasty. Hemostasis, particularly in the splenectomy area, should be carefully done, and the cavity is not drained.
Results. After 94 patients had been operated on (32 SRS, 30 DSRS, and 32 EGDS) the study was interrupted for ethical reasons, in view of the high incidence of portosystemic encephalopathy in the SRS group. There was no immediate mortality (up to the 30th postoperative day) in any group. One patient, belonging to the SRS group, died during anesthetic induction and was excluded from the study. In the follow-up of these patients for a minimum of 60 months and a maximum of 130 months (average: 66.16 + 39.31 months, median: 69 months), there was complete loss of follow-up of I I cases (11.7% of the total) (Table 3) [69]. The overall mortality rate in the long-term follow-up was 21.6%. A statistically significant difference was observed only between SRS and the other groups (Table 3). There was a statistically significant incidence of encephalopathy when groups SRS and EGDS were compared; however, no
S. Raia et al.: Schistosoma! Portal Hypertension
statistical significance was observed when the SRS group was compared with the DSRS group, nor the DSRS with the EGDS group. Thus, it was seen that encephalopathy reached excessive rates in the SRS group and intermediate rates in the DSRS group. Of the 4 patients in the DSRS group with encephalopathy, 1 patient developed a severe form of the complication that was controlled with a subtotal colectomy and ileorectal-anastomosis. The rate of bleeding recurrence in the 3 groups, considering all etiologies (esophageal varices, acute gastroduodenitis, peptic ulcer, etc.) was 24.1%, with no statistically significant difference between the groups (p = 0.79). When only recurrence of bleeding from esophageal varices proven by endoscopy was considered, a tendency to lower rates could be seen in the DSRS group and higher rates in the EGDS group. Nevertheless, due to the small number of cases in each group, no statistical analysis was made (Table 3). Indirect hyperbilirubinemia was observed in 52% of the patients of the DSRS group. In 28%, it was above 3 mg/dl. In the SRS group, the increase in indirect bilirubin was seen in 29.6% of the cases, only 3.70% above 3 mg/dl. Nevertheless, no clinical symptoms related to these findings were observed in either of these 2 groups. It is likely that indirect hyperbilirubinemia is due to the persistent hypersplenism in the late follow-up of the patients in the DSRS group, associated with blood flow turbulence in the anastomosis (DSRS and SRS) and reduced clearance by the liver (DSRS and SRS) [11]. In the EGDS group, no hyperbilirubinemia was observed. Postprandial epigastric discomfort, observed immediately after surgery was seen in 28.6% of the patients in the EGDS group and lasted from 2 to 12 months. Dysphagia, reported only by patients of the EGDS group disappeared either spontaneously or after endoscopic examinations performed up to 6 months after surgery. Low rates of ascites in the immediate postoperative period were observed in the 3 procedures (7.1% in the EGDS, 7.1% in SRS, and 14.8% in the DSRS group). Control was easy and there was no recurrence in the late follow-up. Peptic ulcers, especially duodenal, were observed in 12.5% of the DSRS group and in 25% of the SRS, whereas none of those in the EGDS group developed ulcers. These ulcers were diagnosed between 12 and 96 months (average: 44.4 months) after surgery. There was gastrointestinal bleeding due to the ulcer in 33.3% of the patients, with 1 death. In 66.6% of the patients, the ulcers healed after clinical treatment. Arterial hypertension was observed in 37% of the cases in the SRS group, in 29.6% of the EGDS group, and 28% of the DSRS group, without a statistically significant difference. Even though some authors have described structural alterations of the kidney in schistosomiasis patients [70, 71], the etiology of the hypertension is unknown. There are no data available to its incidence among patients who have not undergone surgery. In the analysis of the evolution of the laboratory features, it was observed that the hepatic enzymes and the protein electrophoresis showed no statistically significant alterations in relation to preoperative data for any of the groups. On the other hand, after the surgical procedures, which include splenectomy (EGDS and SRS), increases in the number of leukocytes, platelets, prothrombin activity, factor V, and fibrinogen, were
181
Table 4. Hepatosplenic schistosomiasis: Hemodynamic-angiographic
evaluation in DSRS (n = 39). Preoperative
Postoperative
Hemodynamic WHVP (mmHg) 6.91 -+ 9.96 7.13 -+ 4.81 FHVP (mmHg) 2.92 -+ 2.32 3.25 -+ 3.06 HVPG (mmHg) 4.14 +- 3.25 4.04 +-- 3.42 RAP (mmHg) 0.68 +- 2.05 1.50 +-- 2.45 IVCP (mmHg) 3.97 + 3.13 4.71 -+ 2.86 LRVP (mmHg) 6.9 -+ 6.44 13.03 -+ 7.8 Angiographic CHA (mm) 6.56 -+ 1.32 7.33 -+ 1.23 PHA (mm) 5.34 -+ 1.13 6.34 -+ 1.12 SA (ram) 9.57 --+ 1.94 9.46 -+ 1.74 SV (ram) 18.04 +- 4.41 19.41 - 4.45 PV (ram) 19.96 +- 3.23 15.89 +- 2.94 IVC (ram) 15.85 +- 5.22 19.06 +- 6.13 Splenic area (cm 2) 279.09 -+ 70.33 235.29 -+ 63.99
p
Wodd Journal of Surgery 9 1991 by the Soci6t~ lmernationale de Chirurgie
Portal Hypertension in Mansonic Schistosomiasis Silvano Raia, M . D . , P h . D . , Sergio Mies, M . D . , and F e r n a n d o Alfieri, Jr., M.D. Liver Unit (LIM/37), Faculdade de Medicina da Universidade de Silo Paulo, Silo Paulo, Brazil Mansonic schistosomiasis is an endemic disease in Brazil, with an estimated 10--12 million people infested. Among its clinical manifestations, the hepatosplenic form causes portal hypertension which, in turn, brings about severe digestive hemorrhage, the most serious complication of the disease. Normally, the patients are young, and have hepatosplenomegaly, hypersplenism without clinical manifestations, and slightly reduced hepatic function. The angiographic findings are characteristic, differing from those of hepatic cirrhosis. In Brazil, the definitive treatment for gastrointestinal hemorrhage is surgery, which should be done under elective conditions whenever possible. During a short period of time, known as the "risk period" (the time between the hemorrhagic episode and the surgery), propranolol has been used to prevent further bleeding. Surgical treatment is indicated only after the first episode, and never on a prophylactic basis. In 1977, a prospective, randomized trial was begun in order to assess the delayed results of the 3 surgical operations most widely used in this country. The study was interrupted after 94 patients had been operated on due to the high incidence of encephalopathy in the group who underwent classical splenorenal shunt. After a follow-up of at least 60 months and, at most, 130 months, the results showed that classical splenorenal shunt caused encephalopathy in 39.3 % of the cases and distal splenorenal shunt in 14.8%. None of those submitted to esophagogastric devascularization with splenectomy developed encephalopathy. The 3 procedures showed similar rates of hemorrhagic recurrence.
Schistosoma mansoni is a digenetic trematode belonging to the Schistomatidea family. This family includes 4 other species: S. japonicum, S. haematobium, S. mekongi, and S. intercalatum [1, 2]. These species are found in various regions around the world, but only S. mansoni has developed in certain areas of Brazil due to climatic conditions, poor sanitation, and the presence of transmitter snails. Mansonic schistosomiasis is also found in Africa, Asia, and other countries of South America [3]. Brazil is one of the most important foci of this parasitosis, where it is endemic. Estimates are that between 10 and 12 million Brazilians are infested with the disease [3, 4]. The life cycle of S. mansoni takes place in 2 hosts. The eggs, which are eliminated in the feces of contaminated persons, if in contact with water, release the miracidia (ciliated embryos), which infest mollusks of the Planorbidea family of the Biomphalaria genus (intermediate host). Here the miracidia multiply, giving rise to the cercaria (larval form) which are elimiSupported by FIPEC IlI grant no. 10/02007-0. Reprint requests: Silvano Raia, M.D., Ph.D., Rua Peru, 421, 01238 S~o Paulo, Brazil.
nated into the water. Man, in contact with the contaminated water, is actively infested through the skin and mucosa. The larvae, after reaching the bloodstream, migrate to the lungs and then to the portal intrahepatic system where they reach full maturity. Then they descend to the mesenteric veins, reproduce, and, in the finest branches, move to the level of the intestinal submucosa where they lay their eggs, reinitiating the cycle. The eggs are laid principally at the level of the rectum and the sigmoid, extending to the rest of the colon and small bowel in the more massive infestations [5]. Each female of S. mansoni produces approximately 300 eggs per day, 25% of which are eliminated in the feces. The rest are retained in the tissues, especially in the bowels and the liver [5], where they are destroyed. The clinical classification of schistosomiasis is that proposed by the Brazilian Society of Hepatology [5], and consists of 2 phases--the initial and the chronic. The initial phase, in unapparent and acute forms, is self-limiting, and recedes either spontaneously or by means of specific therapeutic measures. Direct evolution to the forms of the chronic phase are rare [5]. Normally, after the initial phase, a relatively asymptomatic period of varying duration occurs, with slow and gradual evolution to chronic forms. In the chronic phase, there are 3 progressively more severe forms: intestinal, hepatointestinal, and hepatosplenic. It is pointed out that the disease is not always progressive, and may remain stationary or even recede, depending on a large number of factors [5]. The only form which causes portal hypertension is the hepatosplenic, which appears between 5 and 10 years after the first infestation [6, 7]. It is estimated that 10% of the infested population develop this form [8]. As a result, approximately 1 million persons in Brazil have or will have portal hypertension caused by this disease. The disease has a complex pathogenesis. The adult worm is well tolerated, and causes neither irritation, inflammation, nor portal obstruction since it has the capacity to "fool" the defenses of the host by incorporating human antigens on its surface [6]. When the worm dies, it is carried to the hepatic parenchyma through the portal vein, causing areas of necrosis and inflammatory reactions which may result in vascular lesions and scar fibrosis (Symmers' fibrosis) [9]. These lesions can also be observed in the lung tissues [3]. The fibrous thickening of the portal tracts causes obstruction of the intrahepatic branches of the portal vein, with intense vascular proliferation of contro-
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Table 1. Hepatosplenic schistosomiasis: Coagulation factors.
Prothrombin time (%) Fibrinogen (rag %) Factor V (%)
Average and standard deviation (n = 85)
Normal
73.26 + 14.01 288.96 -+ 76.36 68.09 --- 17.09
80/100 130/450 70/100
versial nature (see Hemodynamic aspects) [10, 11]. Other authors believe that the fundamental pathogenesis of the intrahepatic vascular obstructive and inflammatory phenomena are due to the live eggs. These eggs, by means of secretions from the mature miracidia, have a sensitization effect on the host, stimulating immune responses and the formation of granulomas [12, 13]. The development of the lesion may also be related to circulating immune complexes which are probably responsible for progression of the disease [14]. The pathogenesis of Symmers' fibrosis is not satisfactorily explained by the lesions produced, nor by the eggs, dead worms, or immunological factors mentioned. Some authors suggest that soluble products, such as lymphokines, secretions of activated macrophages, or even parasite products, may stimulate the proliferation of fibrous tissue which extends outside the granulomas [15, 16]. Clinical, Laboratory, and Ultrasonographic Features
Patients with schistosomal portal hypertension are young, generally between the ages of 15 and 50 years, in good general health, and without signs of chronic liver disease. Edema, ascites, gynecomastia, spider angiomas, or encephalopathy are rarely observed [17]. In anamnesis, the complaints are noncharacteristic. The first sign of the disease may be an acute episode of digestive hemorrhage, shown by hematemesis or melena [18]. The most frequent finding in the physical examination is hepatosplenomegaly [19]. For reasons not yet fully understood, the liver, principally the left lobe, is enlarged (see Hemodynamic Aspects below). The organ is hardened and displays a rough nodular surface. Splenomegaly, secondary to reticuloendothelial hyperplasia and to passive congestion due to portal hypertension, can be considerable. Mies and associates [20, 21], in an angiographic study of 50 patients with portal hypertension and a history of at least 1 episode of upper digestive hemorrhage, estimated the average weight of the spleen at 1,100 g. Generally, patients withstand bleeding and surgical interventions well, without important signs of hepatic failure (ascites, encephalopathy, or jaundice). Depending on the amount of bleeding, some patients may develop slight jaundice or even ascites which disappear quickly. The hepatorenal syndrome, often present in advanced cirrhosis, is not observed in pure schistosomiasis [! 1]. Laboratory data show moderate hepatic dysfunction. In a series of 38 patients with portal hypertension without bleeding within the previous 15 days, our group observed slight alterations in the levels of transaminases, alkaline phosphatase, and gamma-glutamyl transferase. The protein electrophoresis showed mild hypoalbuminemia with a sizeable increase in the gamma-globulin fraction [11]. Some studies refer to fusion of the beta and gamma fractions in 50% of the patients [22]. Clinically, no important hemorrhagic tendencies were ob-
Table 2. Hepatosplenic schistosomiasis: Hypersplenism (n = 85).
Laboratory alterations (89.4%) Leukopenia (• 103/ram3) Platelets (• 103/ram3) Symptomatic hypersplenism Epistaxis Gingival bleeding Purpura Bruising Infections
% 75.3 82.4 12.9 5.8 3.5 2.3 1.3 0
Average and Standard Deviation 3.27 + t.41 75.15 -+ 42.90
served. In our group, the study of coagulation factors in 85 patients with the hepatosplenic form of the disease without digestive bleeding for at least 15 days, showed mild alterations (Table 1). The reduction in prothrombin time, also described by other authors [23], is related either to reduced hepatic synthesis or to increased consumption [24, 25]. Hypersplenism, defined by the number of platelets below 100,000/ram 3, associated or not with a leukocyte count below 4,000/ram 3, was observed in 89.4% of the patients. Clinical manifestations of hypersplenism are rare and occur in only 12.9% of the patients (Table 2). A study of platelet function in 14 patients with the hepatosplenic form of this disease demonstrated that the platelets were functionally normal in spite of their reduced number [26]. Among Brazilian authors, Cerri and associates [27] studied 103 patients with the hepatosplenic forms of schistosomiasis, and described characteristic ultrasonographic alterations. The main findings were hypertrophy of the left lobe of the liver and atrophy of the right lobe (81%), periportal fibrosis (73%), dilated portal vein (73%), dilated splenic vein (68%), and thickening of the gallbladder (60%). Splenomegaly (100%) and collateral vessels (35%) were also found. In pediatric and adolescent patients, a general developmental delay was observed (sexual, psychic, bone age and stature) [28, 29]. Malnutrition has been considered a major contributing factor since the disease is most prevalent among people from lower economic classes [3]. Several authors failed to confirm a possible connection between hypersplenism and hormonal alterations [30, 31]. Hemodynamic and Angiographic Features
Mansonic schistosomiasis produces characteristic angiographic alterations, some of which were described by our group after systematic study of 50 patients with schistosomiasis and a history of gastrointestinal bleeding more than 30 days before the study. The inferior vena cava shows clear retrohepatic constriction in most patients, and generally there is no appreciable venous hypertension [32]. Angiography of the hepatic veins shows characteristic alterations. Dilation is present, with arching of the large branches, reduced dichotomization, radiated images and increased bifurcation angles [32, 33]. The average gradient between the free and wedge pressure is at the upper limit of what is considered normal; however, in about 40% of patients, the gradient is higher [32-34]. The conclusion is that portal hypertension in the majority of patients with hepatosplenic schistosomiasis is of the presinusoidal type. Nev-
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World J. Surg. Vol. 15, No. 2, Mar./Apr. 1991
Fig. 1. Splenoportographyof a patient with
schistosomiasis. Note the large diameter of the splenic vein (arrow 1), portal vein (arrow 2), and the neoformed vessels around intrahepatic portal branches--"Bogliolo's sign" (black arrows).
ertheless, in approximately 40% of patients, a moderate parasinusoidal block is also observed. The splenic artery is generally tortuous and dilated [20, 21]. The spleen, in the venous phase of the splenic arteriography, is considerably enlarged. A planimetric evaluation and the use of the formula proposed by Blendis and colleagues [35] made it possible to estimate its average weight at 1.1 kg [20, 21]. The splenic and portal veins also show a considerably increased diameter. The portal system presents an intrahepatic pattern which is also characteristic. Although observable in the venous phase of the splenic artery, it can be better analyzed with a direct injection of radiological contrast into the portal system. These alterations, described by Bogliolo in 1956, are characterized by amputation of the large branches and by the development of neoformed vessels around the portal branches, giving origin to what is known as "Bogliolo's sign" (Fig. 1) [36-38]. Another angiographic finding included reduced diameter of the common and proper hepatic arteries, with a greatly altered intrahepatic pattern. Vascular spaces and an increase in the bifurcation angles are also present, showing an aspect of poor arterial supply [20, 21], even though there are no signs of hepatic atrophy (Figs. 2A, 6A); however, some authors claim that in schistosomal patients the liver is more dependent on arterial blood flow [18, 39]. The arterial and portal alterations observed angiographically are compatible with the existence of increased portal blood flow and reduced arterial blood flow to the liver. The interaction between the portal and arterial blood flows in the hepatic blood supply has been described by numerous authors [40, 41]. Recently, the influence of adenosine in the regulation of arterial blood flow to the normal liver has been described. Adenosine, continuously secreted in Mall's space (the physiological representation of the portal tracts), seems to have its local concentration altered by portal blood flow (slower flow, lower wash-
out), bringing about arterial vasodilatation when at high levels. Thus, a reduction in the portal blood flow would result in a greater concentration of adenosine and vasodilation of the hepatic artery and an increase in arterial blood supply to the liver (buffer response) [42]. Consequently, in cirrhosis, the increased diameter of the common and proper hepatic arteries commonly observed in angiography seems to be a consequence of a greater concentration of adenosine in Mall's space, due to the lowering of portal blood flow [42]. In schistosomiasis, on the other hand, the sizeable splenomegaly demands a greater arterial blood supply with a consequent increase in the diameter of the splenic artery. Thus, there seems to be a greater blood flow to the splenic vein, which, in turn, effects an increase in the portal blood flow. Therefore, there would seem to be a reduction in arterial blood flow to the liver secondary to the high splenoportal blood flow, and maintenance of the total hepatic blood flow (Fig. 3). There is some evidence in favor of this hypothesis. Initially, the total hepatic blood flow is normal in schistosomiasis patients [43, 44]. In Brazil, it has been shown by means of angiographic studies, that the common and proper hepatic arteries increase in diameter immediately following occlusion of the splenic artery by means of a balloon catheter [45]. This effect was also observed after splenectomy [20], distal splenorenal shunt (DSRS) [46] and esophagogastric devascularization with splenectomy (EGDS) [47]. It should be noted that all these procedures have in common removal of the splenic component of portal blood flow. Indirectly, the faint visualization of the portal system in the venous phase of the splenic or of the superior mesenteric arteriogram is suggestive of high portal blood flow. In 1980, Raia measured the splenic blood ftow in schistosomiasis by means of an electromagnetic flowmeter. He observed an average splenic blood flow above 500 ml/minute immediately before performing the anastomosis in a DSRS [48]. Thus, it is probable that, in schistosomiasis, the higher portal blood flow determines
S. Raia et al,: Schistosomal Portal Hypertension
179
SPLENC I RETICULO-ENoOTHELIAL HYPERPLASIA
I ~ BLOOD FLOW TO THE sPLEEN
NETWORK OF
9
~N [EOF -ORMEDVESSELS ~ I {BOGLO ' LOS 'SIGN)?
t SPLENOPORTAL BLOOD FLOW
MA N ITENANCEOF TOTAL H EPATC I BLOOD FLOW
$ARTERA I LHEPATC I BLOOD FLOW Fig. 3. Pathophysiology of portal hypertension in schistosomiasis.
Fig. 2. Pre- and postoperative hepatic arteriography of a patient with schistosomiasis (distal splenorenal shunt). A. Preoperative: Note the reduced diameter of the common (arrow 1) and proper hepatic arteries (arrow 2). The in~rahepatic pattern gives an overall appearance of poor arterial supply. B. Postoperative: Note the abundant intrahepatic arterial supply and the increased diameter of the common (arrow 1) and proper hepatic arteries (arrow 2).
a lower concentration of adenosine in Mall's space, resulting in arterial vasoconstriction and the angiographic aspect of a poor intrahepatic arterial pattern, The obstruction of the large intrahepatic portal branches, proper to the disease, would be evidence against this hypothesis; however, an increase in the portal blood flow might be understood if we consider the intense network of neoformed portal vessels observed in the liver (Bogliolo's Sign). It is important to remember that the authors who suggest a greater arterial component in the schistosomal liver made their studies either on cadaver livers or on sptenectomized patients. In these cases, there are no hemodynarnic effects on the regulating balance of the hepatic blood flow altered by the removal of the splenic component or by death [18, 39]. Besides this, in schistosomiasis an increase in the size of the left lobe of the liver is observed. There are studies which demonstrate that there is preferential blood flow in the portal
system, with the right lobe receiving its blood supply chiefly from the superior mesenteric vein and the left lobe chiefly from the splenic vein [49]. A recent study with radioisotopes concluded that portal blood flow in patients with hepatosplenic schistosomiasis is reduced in the right lobe and increased in the left lobe of the liver [50]. The greater portal blood flow to the left lobe is indicative of an increased splenic blood flow. For this reason, it can be supposed that the increase in size of the left lobe of the liver is a consequence of the greater blood flow coming from the splenic vein, which contains a greater quantity of hepatotropic pancreatic hormones. Treatment
The treatment for schistosomiasis is simple, consisting of a single dose of oxamniquine or praziquantel. In spite of some authors having demonstrated a synergistic action with these drugs [51, 52], this association does not necessarily hold true [53, 54]. In Brazil, oxamniquine is used more often, and destruction of the parasite is obtained in 80-90% of the cases [3, 55-57]. This chemotherapy reduces the possibility of evolution to more severe forms of the disease [58-60]. The most severe complication and main clinical manifestation of portal hypertension caused by Schistosoma mansoni is upper gastrointestinal bleeding due to ruptured esophageal varices [46, 61--63]. This complication occurs in 12-20% ofpatients [60, 64] in the few studies published on the natural history of the patient with hepatosplenic schistosomiasis. Some studies have shown that the bleeding is well tolerated and may cease spontaneously or be easily controlled with clinical measures; however, recurrence is frequent and unpredictable [60]. After the initial control of bleeding, there is still the need to prevent its recurrence. Surgical treatment has been the most widely accepted in Brazil [i 1, 46,' 65, 66]. Surgery should only be undertaken, however, when elective conditions are present,
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World J. Surg. Voi. 15, No. 2, Mar./Apr. 1991 Table 3, Surgical treatment of digestive bleeding in hepatosplenic
a measure which has been shown to reduce more serious complications and mortality [46, 67]. It is important to point out that surgical treatment is generally indicated after the first bleeding episode. Surgery is not prophylactically indicated. In a review of the literature from 1908 to 1976, Raia analyzed 130 publications referring to 4,516 patients submitted to surgery-3,084 of whom were in Brazil~and observed the lack of well controlled studies [46]. Of all the methods proposed, the most frequently used was simple splenectomy (S), followed by EGDS (esophagogastric devascularization with splenectomy) and classical splenorenal shunt (SRS). These procedures made up 81.6% of all the operations performed in different periods in time. In spite of these studies being retrospective, often with partial data, minimum follow-up, and total absence of comparison, they show that recurrence is apparently high only in the patients who have undergone S, while encephalopathy was observed only in those submitted to portosystemic shunts of various types. At that time, it was considered that DSRS (distal splenorenal shunt) would theoretically be the most adequate procedure since it would selectively decompress the gastroesophageal territory responsible for the varices in the esophagus while maintaining the portal blood flow to the liver. In Brazil, this procedure was introduced by Raia and coworkers in 1971 [68].
A continuous suture of the portal vein is then performed with the objective of obtaining anatomic continuity between the superior mesenteric vein and the portal vein. Anastomosis of the splenic vein to the left renal vein, previously dissected and after ligation of the adrenal vein, is then performed in the anatomical position most compatible with a favorable hemodynamic situation (on the cranial surface of the left renal vein, at a 45~ angle).
Prospective Trial
2. Esophagogastric Devascularization with Splenectomy. The
In 1977, our group began a prospective randomized trial comparing the 3 surgical techniques used at that time (EGDS, DSRS, and SRS), with the objective of assessing which was the best procedure for schistosomiasis in terms of recurrence of bleeding, encephalopathy, and mortality. Patients between the ages of 15 and 50 years with portal hypertension and without any digestive bleeding episode for at least 15 days due to rupture of esophageal varices and previous treatment for schistosomiasis were included in the study. Those with portal vein thrombosis, chronic liver disease of any other etiology, or who reported an intake of 100 g of alcohol or more per day for at least 18 months were excluded [11, 61].
Technical Considerations. Each surgical procedure included in the study had been performed by the same surgeon and the late postoperatory by the same observer during the entire follow-up. The SRS had always been performed according to the technique widely described in the literature. The DSRS and the EGDS deserve special consideration due to the many existing variations and different physiopathological meanings. I. Distal Splenorenal Shunt. Initially, the splenic artery is isolated and temporarily clamped on the upper edge of the body of the pancreas with the objective of preventing splenic engorgement and consequent bleeding when the splenic vein is dissected and clamped in order to perform the anastomosis. The splenic vein is dissected up to the portal vein. At this stage, the right gastroepiploic vein is accessed and ligated at its origin. The retropancreatic portal vein is dissected from behind the pancreas to about half of its extension. The left gastric vein, therefore, is ligated at its origin. The right gastric vein is ligated near the duodenum and the umbilical vein on the umbilical ligament. The splenic vein is sectioned close to the portal vein.
schistosomiasis: Prospective study. SRS No. of patients Loss of follow-up: % (no. of cases) Late mortality: % (no. of cases) Portosystemic encephalopathy: % (no. of cases) Esophageal bleeding recurrence: % (no. of cases)
D S R S E G D S Total p
32 30 12.5 10.0 (4) (3) 42.85 14.81 (12) (4)
32 12.5 (4) 7.14 (2)
94 11.7 (11) 21.68 (18)
39.28 (11)
0
18.07 (15)
14.28 (4)
9.64 (8)
14.81 (4)
10.71 3.70 (3) (1)
= 0.003 = 0.001
aNot done (small no. of patients).
first surgical step consists of a ligature of the splenic artery close to the body of the pancreas, immediately followed by compression of the spleen. The splenic hilum is carefully dissected and its elements are ligated separately. Then the spleen is removed. Generally, the stomach and the terminal esophagus are devascularized starting at the incisura angularis after ligating the left gastric vein on the pancreatic plateau, and by cutting the vagal branches. A longitudinal opening in the anterior surface of the stomach and of the esophagus is made, extending 3 cm below the esophagogastric transition and 7 cm above. The varices are ligated with a continuous catgut suture, starting in the stomach and progressing along the esophagus as high as possible. The esophagogastric incision is closed in 2 layers and recovered with an anterior antireflux valve which includes 270~ of the esophagus. The operation is completed by a pyloroplasty. Hemostasis, particularly in the splenectomy area, should be carefully done, and the cavity is not drained.
Results. After 94 patients had been operated on (32 SRS, 30 DSRS, and 32 EGDS) the study was interrupted for ethical reasons, in view of the high incidence of portosystemic encephalopathy in the SRS group. There was no immediate mortality (up to the 30th postoperative day) in any group. One patient, belonging to the SRS group, died during anesthetic induction and was excluded from the study. In the follow-up of these patients for a minimum of 60 months and a maximum of 130 months (average: 66.16 + 39.31 months, median: 69 months), there was complete loss of follow-up of I I cases (11.7% of the total) (Table 3) [69]. The overall mortality rate in the long-term follow-up was 21.6%. A statistically significant difference was observed only between SRS and the other groups (Table 3). There was a statistically significant incidence of encephalopathy when groups SRS and EGDS were compared; however, no
S. Raia et al.: Schistosoma! Portal Hypertension
statistical significance was observed when the SRS group was compared with the DSRS group, nor the DSRS with the EGDS group. Thus, it was seen that encephalopathy reached excessive rates in the SRS group and intermediate rates in the DSRS group. Of the 4 patients in the DSRS group with encephalopathy, 1 patient developed a severe form of the complication that was controlled with a subtotal colectomy and ileorectal-anastomosis. The rate of bleeding recurrence in the 3 groups, considering all etiologies (esophageal varices, acute gastroduodenitis, peptic ulcer, etc.) was 24.1%, with no statistically significant difference between the groups (p = 0.79). When only recurrence of bleeding from esophageal varices proven by endoscopy was considered, a tendency to lower rates could be seen in the DSRS group and higher rates in the EGDS group. Nevertheless, due to the small number of cases in each group, no statistical analysis was made (Table 3). Indirect hyperbilirubinemia was observed in 52% of the patients of the DSRS group. In 28%, it was above 3 mg/dl. In the SRS group, the increase in indirect bilirubin was seen in 29.6% of the cases, only 3.70% above 3 mg/dl. Nevertheless, no clinical symptoms related to these findings were observed in either of these 2 groups. It is likely that indirect hyperbilirubinemia is due to the persistent hypersplenism in the late follow-up of the patients in the DSRS group, associated with blood flow turbulence in the anastomosis (DSRS and SRS) and reduced clearance by the liver (DSRS and SRS) [11]. In the EGDS group, no hyperbilirubinemia was observed. Postprandial epigastric discomfort, observed immediately after surgery was seen in 28.6% of the patients in the EGDS group and lasted from 2 to 12 months. Dysphagia, reported only by patients of the EGDS group disappeared either spontaneously or after endoscopic examinations performed up to 6 months after surgery. Low rates of ascites in the immediate postoperative period were observed in the 3 procedures (7.1% in the EGDS, 7.1% in SRS, and 14.8% in the DSRS group). Control was easy and there was no recurrence in the late follow-up. Peptic ulcers, especially duodenal, were observed in 12.5% of the DSRS group and in 25% of the SRS, whereas none of those in the EGDS group developed ulcers. These ulcers were diagnosed between 12 and 96 months (average: 44.4 months) after surgery. There was gastrointestinal bleeding due to the ulcer in 33.3% of the patients, with 1 death. In 66.6% of the patients, the ulcers healed after clinical treatment. Arterial hypertension was observed in 37% of the cases in the SRS group, in 29.6% of the EGDS group, and 28% of the DSRS group, without a statistically significant difference. Even though some authors have described structural alterations of the kidney in schistosomiasis patients [70, 71], the etiology of the hypertension is unknown. There are no data available to its incidence among patients who have not undergone surgery. In the analysis of the evolution of the laboratory features, it was observed that the hepatic enzymes and the protein electrophoresis showed no statistically significant alterations in relation to preoperative data for any of the groups. On the other hand, after the surgical procedures, which include splenectomy (EGDS and SRS), increases in the number of leukocytes, platelets, prothrombin activity, factor V, and fibrinogen, were
181
Table 4. Hepatosplenic schistosomiasis: Hemodynamic-angiographic
evaluation in DSRS (n = 39). Preoperative
Postoperative
Hemodynamic WHVP (mmHg) 6.91 -+ 9.96 7.13 -+ 4.81 FHVP (mmHg) 2.92 -+ 2.32 3.25 -+ 3.06 HVPG (mmHg) 4.14 +- 3.25 4.04 +-- 3.42 RAP (mmHg) 0.68 +- 2.05 1.50 +-- 2.45 IVCP (mmHg) 3.97 + 3.13 4.71 -+ 2.86 LRVP (mmHg) 6.9 -+ 6.44 13.03 -+ 7.8 Angiographic CHA (mm) 6.56 -+ 1.32 7.33 -+ 1.23 PHA (mm) 5.34 -+ 1.13 6.34 -+ 1.12 SA (ram) 9.57 --+ 1.94 9.46 -+ 1.74 SV (ram) 18.04 +- 4.41 19.41 - 4.45 PV (ram) 19.96 +- 3.23 15.89 +- 2.94 IVC (ram) 15.85 +- 5.22 19.06 +- 6.13 Splenic area (cm 2) 279.09 -+ 70.33 235.29 -+ 63.99
p
