In the March 1968 issue of Indian Pediatrics, the
published research articles pertained to nephrotic syndrome (clinico-pathological
profile), extrahepatic portal obstruction (EHPO), chromosomal analyses
of children with mental and physical defects, infectious-allergic
myocarditis and megaloblastic anemia. In this write-up, we showcase what
was being done in the 1960’s in management of EHPO in contrast to what
is known and being practised now.
The Past
The study [1] entitled ‘Extrahepatic portal
obstruction in children’ was a case series from Medical College, Nagpur,
and had the objectives of studying the clinical profile of children with
EHPO in terms of presentation, management and outcome. The series
comprised of 12 cases; ages ranging from 9 months to 13 years. The
investigations performed in all children included hemogram, liver
function test, liver biopsy and percutaneous transplenic portal
venography. Esophageal radiographs, barium swallow and intra-splenic
measurement were performed in a few.
The presenting complaint was upper gastrointestinal
(UGI) bleeding in 9 patients and unexplained splenomegaly in 3 patients.
The salient clinical signs observed were splenomegaly in all, mild
hepatomegaly in 6, and ascites in 2 patients. None had any biochemical
evidence of liver dysfunction. Venography revealed extrahepatic block
(at hepatic hilum in 9 and at distal splenic vein in 3 patients),
vascular collaterals and gastro-esophageal varices in all patients.
Initially, all patients were managed conservatively; however, recurrent
hematemesis occurred in five patients. One died and 4 underwent surgery
that comprised of splenorenal shunt with splenectomy in two, and
isolated splenectomy in two patients. The authors concluded that a
diagnosis of EHPO could be made clinically based on hematemesis,
fluctuating splenomegaly (regression of spleen on acute bleed) and the
absence of evidence of hepatocellular failure. However, a splenoportal
venogram and liver biopsy were essential for confirmation and planning
treatment. They advocated conservative management initially, with
surgery reserved only for recurrent UGI bleeding.
Historical background and past knowledge:
In 1868, Balfour, et al. first described the cavernomatous
transformation of the portal vein (PV). Portal hypertension (PHT) was a
known clinical entity by the turn of the century and in 1906, Gilbert,
et al. noted that it was the cause of many cases of UGI
haemorrhage with splenomegaly. In 1955, Gibson, et al. [2]
concluded that the cavernomatous transformation of the PV was secondary
to PV thrombosis, rather than a congenital anomaly. By this time, Indian
researchers had also joined the bandwagon, describing the trans-splenic
portal venography patterns in EHPO. In 1962, Shaldon and Sherlock [3],
on the basis of clinical profile of 16 cases, concluded that
extrahepatic PHT was a syndrome of splenomegaly, gastrointestinal
hemorrhage, anemia and portal thrombosis in the absence of cirrhosis. It
was recognized that it differed from hepatic PHT in terms of clinical
profile, management and outcomes, and that an association with umbilical
sepsis existed.
The Present
Over the years, nomenclature has changed to extra
hepatic portal vein obstruction (EHPVO), with the addition of ‘vein’ to
the pre-existing term. It is reportedly the commonest cause of portal
hypertension in Indian children, unlike in Western countries where
hepatic dysfunction is more common [4]. Though it is widely postulated
that umbilical sepsis, umbilical vein catheterization, abdominal trauma,
surgery, intra-abdominal sepsis, dehydration, congenital agenesis and
portal vein atresia may result in EHPVO, there is still paucity of
strong supportive scientific evidence to substantiate this. Deficiencies
of antithrombotic factors (protein-C, protein-S, anti-thrombin III) have
frequently been found in EHPVO. These have been explained by low
synthesis due to the poor hepatic blood flow resulting from the PV
thrombosis and increased clearance due to the portosystemic shunt [5].
In the late 1970’s and 1980’s, ultrasonography (USG)
replaced visceral angiography for evaluating portal venous system and
porta-systemic anastomoses in most children. Computed tomographic (CT)
portal venography and magnetic resonance imaging (MRI) emerged in the
1990’s as effective and non-invasive tools to visualize the portal
venous system in pre- and post-shunt cases. In the late 1990’s,
ultrasound Doppler superseded conventional USG as a more sensitive
method, and remains the first modality of choice till date. When
inconclusive, a CT portal venography or MRI may be required for
demonstrating portal vein obstruction.
Management includes treatment of variceal bleeding,
and co-morbidities like growth failure, portal biliopathy, hypersplenism
and physical disability. In acute variceal bleeding, hemodynamic
resuscitation should be followed by either endoscopic sclerotherapy
(EST) or endoscopic variceal band ligation (EVL) or both. These
modalities can also prevent further bleeding. The eradication rate of
esophageal varices is 88-100% with EST, but complications like ulcers
and strictures are common. A randomized control trial that compared EVL
versus EST in 49 children with EHPO showed that EVL achieved
variceal eradication more quickly, required fewer sessions, had lower
re-bleeding rate and fewer complications compared with sclerotherapy;
although both were equally effective in arresting acute bleed and had
similar recurrence rate [6].
Conventional shunt (proximal or distal spleno-renal)
surgery is indicated in situations when there is failure of endoscopic
therapy, when gastric or ectopic varices are not amenable to endoscopy,
symptomatic hypersplenism, growth retardation, portal biliopathy,
massive splenomegaly affecting quality of life, or when arranging
immediate blood transfusion is difficult. Presently, endoscopic therapy
is a lifesaving modality in reducing acute variceal bleed related
mortality. It may remain the sole therapy for most patients and serve as
a bridge therapy in those where definitive surgery is warranted.
A major breakthrough that has revolutionized surgical
management in the last decade has been the introduction of the
mesenterico-portal bypass (MPB) or Rex shunt. The internal jugular vein
is used as a conduit to bypass blood from the superior mesenteric vein
to the left branch of the PV, thus closely simulating a physiological
state. This restores hepatic blood flow, corrects PHT and improves
systemic manifestations of EHPVO and linear growth [7]. It is now
emerging as the optimal mode of therapy. The paradigm shift in practice
that has emerged is surgery as soon as the diagnosis is established,
rather than later as an alternative resort. This is because the ability
of the portal venous system to adapt to restored flow is age-dependent
and prolonged deprivation of blood flow may lead to atrophy of
intrahepatic portal veins [8]. However, unfavourable anatomy in a large
number of cases, requirement of an interventional radiologist, and
paucity of surgical experience have limited its application in most
settings at present.
There has been a huge leap forward in the management
of EHPO in the last 50 years, from invasive to non-invasive diagnostic
modalities to the recommendations of early shunt surgery. These have
paved the way for improvement in quality of life and prolonged life
expectancy in these patients. With the availability of greater
resources, wider accessibility and better surgical expertise, the future
certainly appears promising.
References
1. Sur AM, Gupta A, Gharpure VG. Extra hepatic portal
obstruction in children. Indian Pediatr. 1968;5:92-9.
2. Gibson JB, Richards RL. Cavernous transformation
of the portal vein. J Path Bact. 1955; 70:81-96.
3. Shaldon S, Sherlock S. Obstruction to the
extrahepatic portal system in childhood. Lancet. 1962;1:63-8.
4. Poddar U, Thapa BR, Rao KL, Singh K. Etiological
spectrum of esophageal varices due to portal hypertension in Indian
children: is it different from the West? J Gastroenterol Hepatol.
2008;23:1354-7.
5. Dubuisson C, Boyer-Neumann C, Wolf M, Meyer D,
Bernard O. Protein C, protein S and antithrombin III in children with
portal vein obstruction. J Hepatol. 1997;27:132-5.
6. Zargar SA, Javid G, Khan BA, Yattoo GN, Shah AH,
Gulzar GM, et al. Endoscopic ligation compared with sclerotherapy
for bleeding esophageal varices in children with extrahepatic portal
venous obstruction. Hepatology. 2002;36:666-72.
7. Superina R, Bambini DA, Lokar J, Rigsby C,
Whittington PF. Correction of extrahepatic portal vein thrombosis by the
mesenteric to left portal vein bypass. Ann Surg. 2006;243: 515-21.
8. Superina R, Shneider B, Emre S, Sarin S, de Ville
de Goyet J. Surgical guidelines for the management of extra-hepatic
portal vein obstruction. Pediatr Transplant. 2006;10: 908-13.