Keywords
gastric varices - portal hypertension
Introduction
Gastric varices (GV) are subepithelial portosystemic collaterals in the stomach that
evolve as a consequence of portal hypertension (PHT). They are seen in around 20%
of all patients with cirrhosis.[1] Bleeding from GVs comprises 10 to 30% all variceal hemorrhages. These bleeds tend
to be more severe, and have higher mortality rates than bleeding from esophageal varices.[1]
GV are heterogenous in terms of their location, morphology as well as risk of bleeding.
Various systems of classification ([Table 1]) have been described for characterization of GVs, mainly based on location.[1]
[2]
[3]
[4]
[5] Only the Hashizume classification takes into account the size and presence of warning
signs of rupture.[2] However, due to its complexity, this system is not very popular.
Table 1
Classification systems for gastric varices
|
Abbreviations: GOV, gastroesophageal varices; IGV, isolated gastric varices; RCS,
red color spot.
|
|
A. Sarin’s classification of gastric varices1
|
|
Gastroesophageal varices
GOV1
GOV2
|
Varices in continuity with esophageal varices
Along the lesser curvature
Along the greater curvature extending toward the gastric fundus
|
|
Isolated gastric varices
IGV1
IGV2
|
Isolated cluster of gastric varices in the gastric fundus
Isolated gastric varices in the other parts of the stomach
|
|
B. Hashizume classification of gastric varices2
|
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Form
|
F1 (tortuous), F2 (nodular) and F3 (tumorous)
|
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Location
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La (anterior), Lp (posterior), Ll (lesser curvature), Lg (greater curvature), Lf (fundus)
|
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Color
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Cw (white), Cr (red)
|
|
RCS
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Glossy, thin-walled focal redness on the varix
|
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C. Hoskins and Johnson’s classification of gastric varices3
|
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Type 1
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Inferior extension of esophageal varices across the squamo-columnar junction
|
|
Type 2
|
Gastric varices located in fundus, which appear to converge to cardia with esophageal
varices
|
|
Type 3
|
Gastric varices in fundus or body in the absence of esophageal varices
|
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D. Arkawa classification of gastric varices4
|
|
Type I
Ia
Ib
|
A single supplying vessel forms a fundic varix
Plural supplying vessels join and form a varix that drains into a single vessel
|
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Type II
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Gastric varices with multiple communications with vessels in stomach wall
|
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E. Mathur’s classification of gastric varices5
|
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Type 1
|
Esophageal varices with lesser curvature varices
|
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Type 2
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Esophageal varices with fundal varices (2a—subcardiac and 2b—diffuse fundal)
|
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Type 3
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Isolated fundal varix (3a—due to splenic vein thrombosis, 3b—due to generalized portal
hypertension)
|
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Type 4
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Lesser curvature gastric varices with esophageal varices with fundal varices
|
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Type 5
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Antral varices
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The mandate of a classification system of GVs is thus limited to description of the
location of the varices in the stomach, which, in turn, dictates the drainage pathway.
The classification by Sarin et al described over two decades back has globally been
the most popular way of categorizing GVs.[1] It is simple to apply, reproduce, and interpret for most cases of GVs, while also
indicating the possible drainage pathway of the varices. It has been endorsed by Baveno-VI
guidelines for PHT and variceal bleeding.[6] Despite its many merits, there is a subset of cases that still remain uncategorized.
We here propose an amendment in this classification based on our experience in past
20 years. It would make the classification more comprehensive and reduce semantic
confusion while maintaining the physiologic description of GV.
Materials and Methods
An observational-analytic study was conducted between 1996 and 2016, where consecutive
patients with PHT presenting to the Department of Hepatology at a tertiary-care institute
for esophagogastroduodenoscopy (EGD) were recruited and their data was prospectively
entered in the record books. The institute caters to more than 40,000 liver patients
in a year from more than eight states in the country. Patients with severe cardiorespiratory
disease, age <18 years, and human immunodeficiency virus infection were excluded.
The patients were evaluated for the presence of varices and findings were noted on
a standardized reporting sheet. The records were analyzed retrospectively to identify
the proportion of patients with esophageal, gastric, gastroesophageal varices (GOV),
and ectopic varices. The grade, location, and stigmata of recent bleed were noted.
Procedures done during EGD including band ligation, sclerosant, or glue injection
were recorded. Clinical details of recruited patients were retrieved from hospital
medical records. Informed consent for EGD was taken from all patients and study was
performed as per the good clinical practice guidelines, and Declaration of Helsinki.
Variables: PHT was defined on imaging (dilated portal vein, splenomegaly, and collaterals),
endoscopic (varices and portal gastropathy) and clinical findings (spider nevi, splenomegaly,
and relevant setting). Etiology of PHT was classified as cirrhosis, based on clinical
(ascites, jaundice, edema, spider nevi), laboratory (low albumin, elevated prothrombin
time, low platelet count), imaging (irregular outline and volume redistribution with
signs of PHT), transient elastography, and biopsy findings; noncirrhotic portal fibrosis
(NCPF) based on PHT with patent dilated splenoportal axis, normal liver stiffness,
and absence of cirrhosis on biopsy[7] extrahepatic portal vein obstruction (EHPVO)[8] based on PHT with evidence of portal cavernoma; and Budd–Chiari syndrome (BCS) based
on imaging findings blocked inferior vena cava (IVC) and/or hepatic veins.[9]
Classification of varices: GV were classified into gastroesophageal varices (GOV 1 and GOV 2) and isolated gastric
varices (IGV 1 and IGV 2) as per Sarin’s classification based on their location and
drainage.[1] We added a new class, GOV3, which included a combination of varices with efferent
drainage to both the superior (SVC) and IVC system simultaneously. Therefore, presence
of varices around the gastroesophageal junction- esophageal varices/GOV1/GOV2 (a majority
of which drain through the periesophageal-azygous-superior vena cava pathway) in combination
with antral and duodenal varices (draining into the posterior gastric-gastrospleno
renal–inferior vena cava pathway) was called GOV3 ([Figs. 1 ]and [2]). Esophageal varices were classified into five grades as described by Paquet,[10] and grades 1 and 2 were considered small varices, and grades 3 and 4 large varices.
Fig. 1 Predominant drainage pathways of gastroesophageal varices. GOV, gastroesophageal
varices; IGV, isolated gastric varices; IVC, inferior vena cava; SVC, superior vena
cava.
Fig. 2 Proposed new classification of gastric varices. “?” denotes inability to categorize
varices with a particular classification. GOV, gastroesophageal varices; IGV, isolated
gastric varices; IVC, inferior vena cava; RCS, red color spot; SVC, superior vena
cava.
Diagnosis of GV: The varices were diagnosed based on endoscopic appearance of dilated venous channel
with blue color on maximum and sustained air insufflation, done or supervised by a
senior endoscopist with more than 30-year experience (VS). The presence of IGV2 in
the body, antrum or duodenum of stomach, was concurred with another independent endoscopist.
The varices were labeled as (a) antral varix: when a single dilated venous column,
linear or polypoidal, is present in the antrum of the stomach, reaching the pyloric
rim and persisting despite full inflation of air in the stomach, (b) duodenal varix:
when one or more distinct, persistent, elevated venous columns are present in the
first or second part of duodenum, running longitudinally or irregularly in the duodenum,
(c) GV in body: when one or multiple column of dilated venous channels are seen in
body of stomach sparing fundus and antrum.
Bleeding from GV: Gastric varices were considered to have bled if active bleeding, oozing, adherent
clot, brownish ulceration, or cherry red spots were seen on the gastric varix or if
there were large GV in a patient with a history of upper gastrointestinal bleed without
esophageal varices or other detectable causes such as portal hypertensive gastropathy,
gastric mucosal lesions, peptic ulceration, or gastric antral vascular ectasia.[1]
Management of bleeding from GV: After initial resuscitation with hydration, airway support, intravenous antibiotics
and vasoactive agents, the GV bleed was managed with either endoscopic sclerotherapy
with absolute alcohol or sodium tetradecyl sulfate or endoscopic variceal obturation
with glue injection.
Statistical Analysis
Numerical data was analyzed as mean with standard deviation (SD) when normally distributed,
and median with interquartile range when not-normally distributed. Categorical data
was represented as number with proportions. Proportions between the two groups were
compared using chi-squared or Fisher’s exact test, and t-test or u-test depending on their applicability. Logistic regression was done for
relationship between variables. A p-value of <0.05 (two-tailed) was considered as significant. The Statistical Package
for Social Sciences (version 22.0 for Windows, SPSS Inc., Chicago, Illinois, United
States) was used for analysis.
Results
Out of 3,476 patients with PHT who underwent EGD, 400 patients (11.4%) had varices
in the stomach or duodenum. Patients with GV presented at a mean age of 42.7 (SD:
15.7) years and were predominantly males (299, 74.7%) ([Table 2]). Etiology of PHT among patients with GV was cirrhosis in 301 (75.2%), EHPVO in
78 (19.5%), NCPF in 18 (4.5%), and BCS in 3 (0.75%) patients. Among patients with
cirrhosis, 33 patients (10.9%) had ascites, 4 patients (1.3%) had hepatic encephalopathy,
and 21 patients (6.9%) had jaundice. Diabetes and hypertension were present in 4 (1.0%)
and 40 patients (10.0%), respectively.
Table 2
Baseline characteristics of patients with gastric varices in the study population
|
Sr. no.
|
Parameters
|
n = 400
|
|
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; BCS, Budd–Chiari
syndrome; EHPVO, extrahepatic portal venous obstruction; INR, international normalized
ratio; NCPF, noncirrhotic portal fibrosis; TLC, total leucocyte count.
Data was represented as number (%) or median (interquartile range) or mean (standard
deviation).
|
|
1
|
Age
|
42.7 (15.7)
|
|
2
|
Gender (males)
|
299 (74.7%)
|
|
3
|
Etiology of portal hypertension
|
|
Cirrhosis
|
301 (75.2%)
|
|
EHPVO
|
78 (19.5%)
|
|
NCPF
|
98 (4.5%)
|
|
BCS
|
3 (0.8%)
|
|
4
|
Investigations
|
|
Hemoglobin—g/dL
|
10.0 (8.6–11.9)
|
|
Platelet count—x109/L
|
83 (63–143)
|
|
TLC—per mm3
|
5400 (3,700–7120)
|
|
Serum creatinine—mg/dL
|
0.83 (0.36–1.10)
|
|
Bilirubin—mg/dL
|
1.7 (1.0–2.7)
|
|
ALT—U/L
|
34.5 (26.0–59.1)
|
|
ALP—U/L
|
165 (102–246)
|
|
Protein—g/dL
|
6.9 (6.4–7.8)
|
|
Albumin—g/dL
|
3.6 (2.9–4.2)
|
|
INR
|
1.25 (1.10–1.38)
|
The distribution of GV as per Sarin’s classification was GOV1 in 170 patients (42.5%),
GOV2 in 154 patients (38.5%), IGV1 in 17 patients (4.3%), IGV2 in 5 patients (1.3%),
and combined GOV1 with GOV2 in 12 patients (3.0%). Forty-two patients (10.5%) were
not classified by Sarin’s classification and were labeled GOV3. The distribution of
GV including GOV1, 2, IGV and GOV3, mechanistic drainage, and classification scheme
was described in [Figs. 1 ]
[2]
[3 ]. Patients with GOV3 had esophageal varices with antral varices (3.3%) or duodenal
varices (1.5%), GOV1 with antral varices (2.3%), GOV2 with antral varices (1.5%),
and combined GOV1 with GOV2 with antral varices (2.0%). Out of 336 patients with GOV,
199 (59.2%) patients had small esophageal varices, while 137 (40.7%) had large esophageal
varices.
Fig. 3 Distribution of gastric varices in our population depicting efferent drainage. Shaded
areas denote dual drainage varices (GOV3). GOV 2 can drain into IVC (44%), SVC (38%), or both (18%). GOV, gastroesophageal varices;
IGV, isolated gastric varices; IVC, inferior vena cava; SVC, superior vena cava.
Among patients with GVs, 93 (23.5%) patients presented with gastrointestinal bleed.
There was no difference in mean age, gender, and etiology of cirrhosis in bleeders
and nonbleeders ([Table 3]). As compared with nonbleeders, bleeders had a higher frequency of GOV2 (odds ratio
[OR]: 2.04, 95% confidence interval [CI]: 1.27–3.29; p < 0.001), lower GOV1 (OR: 0.43, 95% CI: 0.26–0.69]; p = 0.006), and lower GOV3 (OR: 0.35, 95% CI: 0.15–0.80; p = 0.011). There was no difference in the frequencies of isolated GV in bleeders and
nonbleeders. There was no relationship between presence of GOV3 and age, gender, etiology,
or grade of esophageal varices. Bleeding due to GV was managed with either sclerotherapy
with absolute alcohol or sodium tetradecyl sulfate in 18 (19.4%) patients and glue
injection in 75 (80.6%) patients.
Table 3
Characteristics of gastric variceal bleeders compared with nonbleeders
|
Parameters
|
Bleeders (n = 93)
|
Nonbleeders (n = 307)
|
p-Value
|
|
Abbreviations: BCS, Budd–Chiari syndrome; EHPVO, extrahepatic portal venous obstruction;
F, female; GOV, gastroesophageal varices; IGV, isolated gastric varices; M, male;
NCPF, noncirrhotic portal fibrosis; PHT, portal hypertension.
Data represented as mean (standard deviation) and number (%).
|
|
Age (years)
|
42.0 ± 14.2
|
42.9 ± 16.1
|
0.622
|
|
Gender (M:F)
|
74:19
|
225:82
|
0.222
|
|
Etiology of PHT
|
|
Cirrhosis
|
63 (67.7%)
|
238 (77.5%)
|
0.099
|
|
EHPVO
|
26 (28.0%)
|
52 (16.9%)
|
|
NCPF
|
4 (4.3%)
|
14 (4.6%)
|
|
BCS
|
0 (0.0%)
|
3 (1.0%)
|
|
Type of gastric varices
|
|
GOV1
|
31 (33.3%)
|
152 (49.5%)
|
0.006
|
|
GOV2
|
56 (60.2%)
|
111 (36.2%)
|
<0.001
|
|
GOV3
|
3 (3.2%)
|
38 (12.4%)
|
0.011
|
|
IGV1
|
3 (3.2%)
|
11 (3.6%)
|
0.230
|
|
IGV2
|
0 (0.0%)
|
5 (1.6%)
|
0.216
|
Discussion
In the present study, GV were found in 11.5% adult patients with PHT. GV had been
reported heterogeneously (2–100%) in literature possibly due to heterogenous selection
criteria, referral bias, and diagnostic criteria.[1]
[2]
[3]
[4]
[5] About 23% presented with bleed, the rest were incidentally diagnosed on screening
endoscopy. The distribution of etiology was similar between bleeders and nonbleeders.
GOV1 was less likely to present with bleed. GOV2, on the other hand, presented with
bleed more often.
Of all the patients, about one in ten remained uncategorized by the existing system
of classification. This classification is based on the location of the varix in the
stomach, which ultimately dictates its drainage. Nearly all esophageal varices and
GOV1 drain into the azygous system via the periesophageal plexus.[11] In most cases, GOV2 drains either via the azygous vein to SVC (~44%) or via the
inferior phrenic vein or gastro-spleno-renal shunt (~38%) into the IVC.[11]
[12] IGVs drain almost exclusively into the IVC territory, either via the gastrosplenorenal
shunt, or in few cases, via the pericardiophrenic (inferior phrenic) veins.[13]
The drawback of the current classification system is that it leaves about a tenth
of the GV unclassified. These are often described in the endoscopy report as various
combinations of gastric and esophageal varices, which can sometimes be confusing.
Moreover, isolated GV may be associated with GOV1 or GOV2 in upto 59% of cases, rendering
the term “isolated gastric varices” technically incorrect.[13]
To avoid this, while retaining the physiological essence of the classification, we
suggest that a separate category, GOV3, should be added. This terminology refers to
cases where varices are present both in the SVC and IVC draining territories, and
covers the previously unclassified cases. Moreover, this will prevent duplicate coding
of an individual for epidemiological purposes, especially when a patient exhibits
both GOV1/2/esophageal and antral/duodenal varices. Moreover, GOV3 can further be
supplemented by the description of location of varices.
The category of GOV3 was able to include the previously uncategorized varices. These
varices have two separate drainage systems: those around the gastroesophageal junction
have their efferent into the central or right portal system, draining into the SVC
via azygous vein. The relatively distal gastric part has efferent into the left portal
system, draining via the splenogastrorenal shunt or the pericardiophrenic veins, into
the IVC.[12] GOV3 were three times less likely to present with bleed than other GV. This may
have been due to a more effective decompression of the portal system by way of both
left and right portal collaterals. Thus, the addition of GOV3 led to complete classification
of all varices seen on EGD, while giving some insight on the portal hemodynamics.
However, this will have to be confirmed in larger studies.
Due to its retrospective nature, our study was prone to certain biases. Moreover,
the lack of follow-up data restricts the information about the natural history and
progression of GV. However, we were able to address a lacuna in the categorization
of GVs and provide a rational addendum to the nomenclature. We propose that a category
GOV3 may be added to the existing Sarin’s classification. Addition of GOV3 in Sarin’s
classification will make it more comprehensive, uniform, and reproducible for future
studies. Further prospective studies are needed to discern the outcomes in patients
with GOV3 and angiographic studies are required to demonstrate their drainage pathways.
