Postmortem Demonstration of Esophageal Varices by a Simple Method C A R L O S R. A B R A M O W S K Y , M.D.,
AND A M E R I C O A. G O N Z A L V O ,
M.D.
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710
ABSTRACT
E S O P H A G E A L VARICES constitute a serious complication in a number of clinical situations, most commonly in patients with parenchymal hepatic disease. As they represent a potential source of bleeding with attendant high mortality, it has become necessary to develop refined clinical methods for their detection. Nevertheless, postmortem demonstration of esophageal varices has met with limited success, and the few available methods are cumbersome and Received December 18, 1974; received revised manuscript February 3, 1975; accepted for publication February 3, 1975. Address reprint requests to Dr. Gonzalvo: Department of Pathology, Tampa General Hospital, Tampa,
Florida 33606.
costly. T h e purpose of this report is to describe a simple, inexpensive method used in our department for postmortem demonstration of varices in the esophagus, Clear exposition of submucosal vascularity is achieved in a few minutes, and permanent preparations are easily obtained. In addition, the various vascular patterns observed in esophageal specimens from a selected group and a random group of autopsied patients were correlated with the associated pathologic findings. Materials and Methods r F(
. r J^ I «.• c >r t h e p u r p o s e o f d i r e c t e v a l u a t i o n o f
the method, a group of 40 patients with 672
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Abramowsky, Carlos R., and Gonzalvo, Americo A.: Postmortem demonstration of esophageal varices by a simple method. Am J Clin Pathol 64: 672-677, 1975. T h e usual methods available to demonstrate esophageal varices in postmortem material have met with little success because of their unreliability, difficulty to execute, or cost. A simple, inexpensive method, which consists in separating the esophageal mucosa and submucosa from the muscularis and stretching the former over a suitable absorbent paper, is described. In a few minutes, as the adherent membrane dries, the submucosal vascular pattern gradually develops, and after overnight drying, even the smallest venules are clearly visible. T h e specimen can be stored dry, photographed, or made into a more permanent preparation in a few days. T h e esophageal mucosal vascular patterns in groups of patients who died with a variety of hepatic diseases and other potential causes of esophageal varices were studied and compared with controls. A consistent pattern of prominent venous trunks located towards the distal third of the esophagus was seen in most specimens from cirrhotic patients, predominantly in micronodular forms with severe lobular distortion. Other potential causes of esophageal varices (hepatic tumors, congestion, etc.) resulted in less predictable vascular patterns. (Key words: Esophageal varices: Postmortem demonstration; liver cirrhosis.)
November 1975
673
ESOPHAGEAL VARICES—DEMONSTRATION
Table 1. Distribution of Esophageal Vascular Pattern in Groups of Autopsy Patients Low Vascular Number of Patients
Disease Group
0Trace
1+2 +
Upper Vascular
Diffuse Vascular
3+4 +
1+2 +
Trace 1+
2+3 +
13
Non-cirrhotic hepatic disease
2
0
0
1
7
3
27
Cirrhosis
4
11
8
0
2
2
13
Primary hepatic tumors or metastasis
6
1
0
0
4
2
16
Hepatic congestion
4
0
0
3
3
6
10
Cerebral neoplasms and vascular disease
3
3
0
0
3
1
13
Controls
3
0
0
0
0
0
ment is briskly washed in running water and opened longitudinally following the greater curvature of the attached stomach. (3) T h e opened specimen is laid on a cork block with the mucosa facing upwards and pinned down through the muscularis. The mucosa is then carefully examined. (4) Separation of the mucosa from the underlying muscle can be easily accomplished with sharp scissors and blunt dissection. (5) T h e strip of esophago-gastric mucosa (facing up) is carefully stretched on a suitable strip of absorbent paper. With the aid of a blunt forceps it can be further stretched on the paper until all creases and folds are smoothed out. If a non-absorbent material is used, the specimen will not adhere as it is stretched and will tend to retract and curl. Care must be taken so not to tear the membrane during the stretching procedure. In this study # 1 0 0 Albemarle Blotting Paper (James River Paper Co., Richmond, Va.) was found to be suitable. An excessively wet specimen will saturate the paper to the point that the latter will curl as it dries, and conversely a very dry specimen will not be sufficiently adherent. By pasting the absorbent paper onto cardboard, or by using heavier grades, curling is prevented. (6) The preparation is then placed in a dry area and left overnight, although pre-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
sundry hepatic diseases, including 27 who had hepatic cirrhosis, was chosen. An additional group consisted of patients with various other potential causes of portal hypertension. These were all compared with a final group considered to be normal controls, which generally consisted of persons dying fairly rapidly in automobile accidents, homicides, etc. The general breakdown of these groups of patients appears in Table 1. At autopsy, the usual comprehensive sampling of tissues was complemented by a more random and complete selection of tissue blocks from the spleen and liver. All sections of these organs were stained with hematoxylin and eosin, Masson's trichrome, and Wilder's reticulum. They were independently evaluated without knowledge of the clinical history, and various histologic characteristics were recorded. In all cases, the esophagus was prepared as follows: (1) Excision of the esophagus by cutting it as long as possible toward its upper end and including, inferiorly, a segment of proximal stomach. In order to evaluate the major venous branches of the coronary vein, as they ascend into the esophagus, the attached gastric segment should include 7 - 8 cm. of the lesser curvature. (2) The excised esophago-gastric seg-
674
ABRAMOWSKY AND GONZALVO
A.J.C.P. —Vol. 64
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
FIG. 1 (left). Example of a severe form of lower esophageal varix formation (gastric segment is located inferiorly). This is the pattern most consistently associated with hepatic cirrhosis. xO.5. FIG. 2 (right). Another severe form of low varix distribution, where the veins show a corkscrew or helical appearance. xO.5.
November 1975
ESOPHAGEAL VARICES—DEMONSTRATION
675
>. V- \ ' *
•
j , 4
%' ^
"
t •
H
MX .
V1
i
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
' ^
./W
FIG. 3 (/e/i). Diffuse form of venous pattern, which was inconsistently associated with hepatic cirrhosis. x0.5. FIG. 4 (right). Example of a pattern of upper esophageal veins. This was the least frequent and least specific type encountered in patients with hepatic disease, x 0.5.
676
ABRAMOWSKY AND GONZALVO
In addition, in most cases, a photocopy of the dried untreated preparation can be obtained, with good results. This is more effective if the photocopying equipment permits increased contrast, resulting in a quick permanent record that can be included in the autopsy protocol. T h e mucosas so prepared and dried were evaluated as to their vascular patterns, and on the basis of number and size of vessels they were graded on a 0 - 4 + scale. T h e predominant location of the vessels was also r e c o r d e d . Subsequently, clinical data from all patients were recorded together with the associated postmortem findings. Results Observed vascular patterns fit into one of three categories: (1) low esophageal, when the majority of enlarged or tortuous vessels are seen at the distal end of the esophago-gastric junction (Figs. 1 and 2); (2) diffuse pattern, implying an equal distribution, usually of small branches, throughout the length of the esophagus (Fig. 3); upper esophageal, when the vascular branches are more prominent in the proximal end of the esophagus (Fig. 4). In Table 1, the number of patients from each group is tabulated against its corresponding vascular pattern and grade. It can be seen that the 40 patients with
64
hepatic diseases of various types tended to have vascular patterns of all categories except the upper esophageal type. If our observation is restricted to those with cirrhosis (27 of the above-mentioned 40 patients), the predominant pattern is the low esophageal type, with the highest grades of severity being found in this
group. Other groups of patients, including those with hepatic tumors (13 patients) or hepatic congestion (16 patients), which are potential causes of portal hypertension, were examined. T h e vascular patterns observed included most categories except the higher grades of low esophageal distribution. Patients who had cerebral lesions (ten patients, all of them with severe pulmonary congestion) showed a striking prominence of low vascular patterns, without reaching the severity observed in cirrhotic patients. T h e 13 patients classified as controls consistently showed minimal or no vascular dilatation. Observation of various histopathologic characteristics in the livers and spleens from the cirrhotic patients showed some correlation between the form of cirrhosis and the vascular pattern. Thus, micronodular cirrhosis with marked lobular distortion was associated with the severest forms of varix formation in the distal esophagus. Other histologic features such as fatty change, bile stasis, and necrosis did not afford such correlation. No attempt was made to correlate duration of disease with the type of vascular pattern encountered, and in most cases, portal vein pressures were not determined. Discussion Esophageal varices represent a serious complication in patients with hepatic disease. 7 Since their presence is of important prognostic value, their clinical demonstration has been aided by numerous technics. Such is not the case, however, in autopsy specimens. T h e existing methods
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
liminary results can be observed in a few minutes. Too-rapid drying, as in an oven, will cause extreme curling of the preparation. (7) For a more permanent preparation, after complete drying, the excess absorbent paper is trimmed close to the specimen, which is then immersed in xylene for 15 minutes. It is then soaked in a flat dish filled with undiluted Permount (Fisher Scientific Co., Fairlawn, N.J.) for an additional 30 minutes, after which it is removed and suspended in a vertical position, permiting the excess Permount to drain. After air-drying for a few days, a "varnished" glossy preparation is obtained.
A.J.C.P.—Vol.
November
1975
ESOPHAGEAL VARICES—DEMONSTRATION
seen only infrequently, and was not associated with any specific clinical entity. Preparations from the control group showed minimal or no vascular dilatation. Histopathologic studies of livers and spleens from all patients showed only those with micronodular cirrhosis with higher grades of lobular distortion to be associated with severe forms of the distinctive lower vascular distribution. Acknowledgment. Mr. Carl Bishop and Mr. Bill Boyarski provided photographic assistance.
References 1. Calabresi P, Abellmann WH: Porto-caval and porto-pulmonary anastomosis in Laennec's cirrhosis and in heart failure. J Clin Invest 36 (Part II): 157-165, 1957 2. Chomet B, Hart LM, Reindl FJ: Demonstration of esophageal varices by simple technique. Arch Pathol 69:185-187, 1960 3. Chomet B, Gach BM: Demonstration of Esophageal varices in museum specimens. Am J Clin Pathol 51:793-794, 1969 4. Khaliq SU, Kay JM, Heath D: Porta-pulmonary venous anastomoses in experimental cirrhosis of the liver in rats. J Pathol 107:167-174, 1972 5. Ludwig J: Current methods of autopsy practice, E s o p h a g u s a n d A b d o m i n a l Viscera. Chapter 5. Philadelphia, W.B. Saunders, 1972, pp 129-132 6. Luna A, Meister HP, Szanto PB: Esophageal varices in the absence of cirrhosis. Incidence and characteristics in congestive heart failure and neoplasm of the liver. Am J Clin Pathol 49:710-717, 1968 7. Orloff MJ, Halasz NA, Lipman C, et al: T h e complications of cirrhosis of the liver. Ann Intern Med 66:165, 1967
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
have consisted of variations of vascular injection procedures using different materials, radiopaque 5 or otherwise, 1 or clearing technics in which the vessels are contrasted by rendering the surrounding tissue transparent. 2,3 All these methods are cumbersome and have in common lengthy execution times and high cost. In the present study, a simple, rapid and inexpensive method to demonstrate esophageal varices is described; in order to evaluate its usefulness, specimens from groups of patients with various hepatic diseases and controls were compared. Prominent vascular trunks located toward the distal esophagus represented a distinctive pattern seen most frequently with hepatic cirrhosis and in only some cases of non-cirrhotic hepatic disease (Figs. 1 and 2). Conversely, a diffuse vascular pattern (Fig. 3) was seen in most groups of patients, including those with hepatic disease, but was relatively uncommon in patients with cirrhosis. T h e presence of varices in non-cirrhotic patients who have primary or metastatic tumors or congestion has been described. 6 It is also possible that, in some of these cases, the diffuse vascular network observed corresponds to porta-pulmonary anastomotic channels, 1,4 although local mucosal irritative factors (nasogastric tubes) are not excluded. T h e upper vascular pattern (Fig. 4) was
677
AND A M E R I C O A. G O N Z A L V O ,
M.D.
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710
ABSTRACT
E S O P H A G E A L VARICES constitute a serious complication in a number of clinical situations, most commonly in patients with parenchymal hepatic disease. As they represent a potential source of bleeding with attendant high mortality, it has become necessary to develop refined clinical methods for their detection. Nevertheless, postmortem demonstration of esophageal varices has met with limited success, and the few available methods are cumbersome and Received December 18, 1974; received revised manuscript February 3, 1975; accepted for publication February 3, 1975. Address reprint requests to Dr. Gonzalvo: Department of Pathology, Tampa General Hospital, Tampa,
Florida 33606.
costly. T h e purpose of this report is to describe a simple, inexpensive method used in our department for postmortem demonstration of varices in the esophagus, Clear exposition of submucosal vascularity is achieved in a few minutes, and permanent preparations are easily obtained. In addition, the various vascular patterns observed in esophageal specimens from a selected group and a random group of autopsied patients were correlated with the associated pathologic findings. Materials and Methods r F(
. r J^ I «.• c >r t h e p u r p o s e o f d i r e c t e v a l u a t i o n o f
the method, a group of 40 patients with 672
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Abramowsky, Carlos R., and Gonzalvo, Americo A.: Postmortem demonstration of esophageal varices by a simple method. Am J Clin Pathol 64: 672-677, 1975. T h e usual methods available to demonstrate esophageal varices in postmortem material have met with little success because of their unreliability, difficulty to execute, or cost. A simple, inexpensive method, which consists in separating the esophageal mucosa and submucosa from the muscularis and stretching the former over a suitable absorbent paper, is described. In a few minutes, as the adherent membrane dries, the submucosal vascular pattern gradually develops, and after overnight drying, even the smallest venules are clearly visible. T h e specimen can be stored dry, photographed, or made into a more permanent preparation in a few days. T h e esophageal mucosal vascular patterns in groups of patients who died with a variety of hepatic diseases and other potential causes of esophageal varices were studied and compared with controls. A consistent pattern of prominent venous trunks located towards the distal third of the esophagus was seen in most specimens from cirrhotic patients, predominantly in micronodular forms with severe lobular distortion. Other potential causes of esophageal varices (hepatic tumors, congestion, etc.) resulted in less predictable vascular patterns. (Key words: Esophageal varices: Postmortem demonstration; liver cirrhosis.)
November 1975
673
ESOPHAGEAL VARICES—DEMONSTRATION
Table 1. Distribution of Esophageal Vascular Pattern in Groups of Autopsy Patients Low Vascular Number of Patients
Disease Group
0Trace
1+2 +
Upper Vascular
Diffuse Vascular
3+4 +
1+2 +
Trace 1+
2+3 +
13
Non-cirrhotic hepatic disease
2
0
0
1
7
3
27
Cirrhosis
4
11
8
0
2
2
13
Primary hepatic tumors or metastasis
6
1
0
0
4
2
16
Hepatic congestion
4
0
0
3
3
6
10
Cerebral neoplasms and vascular disease
3
3
0
0
3
1
13
Controls
3
0
0
0
0
0
ment is briskly washed in running water and opened longitudinally following the greater curvature of the attached stomach. (3) T h e opened specimen is laid on a cork block with the mucosa facing upwards and pinned down through the muscularis. The mucosa is then carefully examined. (4) Separation of the mucosa from the underlying muscle can be easily accomplished with sharp scissors and blunt dissection. (5) T h e strip of esophago-gastric mucosa (facing up) is carefully stretched on a suitable strip of absorbent paper. With the aid of a blunt forceps it can be further stretched on the paper until all creases and folds are smoothed out. If a non-absorbent material is used, the specimen will not adhere as it is stretched and will tend to retract and curl. Care must be taken so not to tear the membrane during the stretching procedure. In this study # 1 0 0 Albemarle Blotting Paper (James River Paper Co., Richmond, Va.) was found to be suitable. An excessively wet specimen will saturate the paper to the point that the latter will curl as it dries, and conversely a very dry specimen will not be sufficiently adherent. By pasting the absorbent paper onto cardboard, or by using heavier grades, curling is prevented. (6) The preparation is then placed in a dry area and left overnight, although pre-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
sundry hepatic diseases, including 27 who had hepatic cirrhosis, was chosen. An additional group consisted of patients with various other potential causes of portal hypertension. These were all compared with a final group considered to be normal controls, which generally consisted of persons dying fairly rapidly in automobile accidents, homicides, etc. The general breakdown of these groups of patients appears in Table 1. At autopsy, the usual comprehensive sampling of tissues was complemented by a more random and complete selection of tissue blocks from the spleen and liver. All sections of these organs were stained with hematoxylin and eosin, Masson's trichrome, and Wilder's reticulum. They were independently evaluated without knowledge of the clinical history, and various histologic characteristics were recorded. In all cases, the esophagus was prepared as follows: (1) Excision of the esophagus by cutting it as long as possible toward its upper end and including, inferiorly, a segment of proximal stomach. In order to evaluate the major venous branches of the coronary vein, as they ascend into the esophagus, the attached gastric segment should include 7 - 8 cm. of the lesser curvature. (2) The excised esophago-gastric seg-
674
ABRAMOWSKY AND GONZALVO
A.J.C.P. —Vol. 64
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
FIG. 1 (left). Example of a severe form of lower esophageal varix formation (gastric segment is located inferiorly). This is the pattern most consistently associated with hepatic cirrhosis. xO.5. FIG. 2 (right). Another severe form of low varix distribution, where the veins show a corkscrew or helical appearance. xO.5.
November 1975
ESOPHAGEAL VARICES—DEMONSTRATION
675
>. V- \ ' *
•
j , 4
%' ^
"
t •
H
MX .
V1
i
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
' ^
./W
FIG. 3 (/e/i). Diffuse form of venous pattern, which was inconsistently associated with hepatic cirrhosis. x0.5. FIG. 4 (right). Example of a pattern of upper esophageal veins. This was the least frequent and least specific type encountered in patients with hepatic disease, x 0.5.
676
ABRAMOWSKY AND GONZALVO
In addition, in most cases, a photocopy of the dried untreated preparation can be obtained, with good results. This is more effective if the photocopying equipment permits increased contrast, resulting in a quick permanent record that can be included in the autopsy protocol. T h e mucosas so prepared and dried were evaluated as to their vascular patterns, and on the basis of number and size of vessels they were graded on a 0 - 4 + scale. T h e predominant location of the vessels was also r e c o r d e d . Subsequently, clinical data from all patients were recorded together with the associated postmortem findings. Results Observed vascular patterns fit into one of three categories: (1) low esophageal, when the majority of enlarged or tortuous vessels are seen at the distal end of the esophago-gastric junction (Figs. 1 and 2); (2) diffuse pattern, implying an equal distribution, usually of small branches, throughout the length of the esophagus (Fig. 3); upper esophageal, when the vascular branches are more prominent in the proximal end of the esophagus (Fig. 4). In Table 1, the number of patients from each group is tabulated against its corresponding vascular pattern and grade. It can be seen that the 40 patients with
64
hepatic diseases of various types tended to have vascular patterns of all categories except the upper esophageal type. If our observation is restricted to those with cirrhosis (27 of the above-mentioned 40 patients), the predominant pattern is the low esophageal type, with the highest grades of severity being found in this
group. Other groups of patients, including those with hepatic tumors (13 patients) or hepatic congestion (16 patients), which are potential causes of portal hypertension, were examined. T h e vascular patterns observed included most categories except the higher grades of low esophageal distribution. Patients who had cerebral lesions (ten patients, all of them with severe pulmonary congestion) showed a striking prominence of low vascular patterns, without reaching the severity observed in cirrhotic patients. T h e 13 patients classified as controls consistently showed minimal or no vascular dilatation. Observation of various histopathologic characteristics in the livers and spleens from the cirrhotic patients showed some correlation between the form of cirrhosis and the vascular pattern. Thus, micronodular cirrhosis with marked lobular distortion was associated with the severest forms of varix formation in the distal esophagus. Other histologic features such as fatty change, bile stasis, and necrosis did not afford such correlation. No attempt was made to correlate duration of disease with the type of vascular pattern encountered, and in most cases, portal vein pressures were not determined. Discussion Esophageal varices represent a serious complication in patients with hepatic disease. 7 Since their presence is of important prognostic value, their clinical demonstration has been aided by numerous technics. Such is not the case, however, in autopsy specimens. T h e existing methods
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
liminary results can be observed in a few minutes. Too-rapid drying, as in an oven, will cause extreme curling of the preparation. (7) For a more permanent preparation, after complete drying, the excess absorbent paper is trimmed close to the specimen, which is then immersed in xylene for 15 minutes. It is then soaked in a flat dish filled with undiluted Permount (Fisher Scientific Co., Fairlawn, N.J.) for an additional 30 minutes, after which it is removed and suspended in a vertical position, permiting the excess Permount to drain. After air-drying for a few days, a "varnished" glossy preparation is obtained.
A.J.C.P.—Vol.
November
1975
ESOPHAGEAL VARICES—DEMONSTRATION
seen only infrequently, and was not associated with any specific clinical entity. Preparations from the control group showed minimal or no vascular dilatation. Histopathologic studies of livers and spleens from all patients showed only those with micronodular cirrhosis with higher grades of lobular distortion to be associated with severe forms of the distinctive lower vascular distribution. Acknowledgment. Mr. Carl Bishop and Mr. Bill Boyarski provided photographic assistance.
References 1. Calabresi P, Abellmann WH: Porto-caval and porto-pulmonary anastomosis in Laennec's cirrhosis and in heart failure. J Clin Invest 36 (Part II): 157-165, 1957 2. Chomet B, Hart LM, Reindl FJ: Demonstration of esophageal varices by simple technique. Arch Pathol 69:185-187, 1960 3. Chomet B, Gach BM: Demonstration of Esophageal varices in museum specimens. Am J Clin Pathol 51:793-794, 1969 4. Khaliq SU, Kay JM, Heath D: Porta-pulmonary venous anastomoses in experimental cirrhosis of the liver in rats. J Pathol 107:167-174, 1972 5. Ludwig J: Current methods of autopsy practice, E s o p h a g u s a n d A b d o m i n a l Viscera. Chapter 5. Philadelphia, W.B. Saunders, 1972, pp 129-132 6. Luna A, Meister HP, Szanto PB: Esophageal varices in the absence of cirrhosis. Incidence and characteristics in congestive heart failure and neoplasm of the liver. Am J Clin Pathol 49:710-717, 1968 7. Orloff MJ, Halasz NA, Lipman C, et al: T h e complications of cirrhosis of the liver. Ann Intern Med 66:165, 1967
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
have consisted of variations of vascular injection procedures using different materials, radiopaque 5 or otherwise, 1 or clearing technics in which the vessels are contrasted by rendering the surrounding tissue transparent. 2,3 All these methods are cumbersome and have in common lengthy execution times and high cost. In the present study, a simple, rapid and inexpensive method to demonstrate esophageal varices is described; in order to evaluate its usefulness, specimens from groups of patients with various hepatic diseases and controls were compared. Prominent vascular trunks located toward the distal esophagus represented a distinctive pattern seen most frequently with hepatic cirrhosis and in only some cases of non-cirrhotic hepatic disease (Figs. 1 and 2). Conversely, a diffuse vascular pattern (Fig. 3) was seen in most groups of patients, including those with hepatic disease, but was relatively uncommon in patients with cirrhosis. T h e presence of varices in non-cirrhotic patients who have primary or metastatic tumors or congestion has been described. 6 It is also possible that, in some of these cases, the diffuse vascular network observed corresponds to porta-pulmonary anastomotic channels, 1,4 although local mucosal irritative factors (nasogastric tubes) are not excluded. T h e upper vascular pattern (Fig. 4) was
677
