- Email: [email protected]
Primary arterial ligation in resection of cancer of the colon
Primary Arterial Ligation in Resection of Cancer of the Colon Rational and Technic Norman B. Ackerman, MD, PhD, Syracuse, New York
The operative technic for excising a malignant neoplasm must be designed to minimize the dissemination of cancer cells during the procedure. The major routes of dissemination of cancer of the colon are the venous and lymphatic outflow systems. It would appear desirable to decrease the lymphatic and venous outflow early in the operative procedure to prevent a possible “showering” of cancer cells. Present technics of early ligation of arteries and veins or of veins alone may promote an increase flow through marginal veins and lymphatics. By studying the inter-relationships of arterial, venous, and lymphatic flow through mesenteric vessels, we have found that ligation of the arterial system alone results in significant decreases in venous and lymphatic outflow. Accordingly, we are proposing that primary arterial ligation be performed in the early stages of resection for cancer of the colon. Material and Methods Studies on arterial, venous, and lymphatic flow were performed on healthy mongrel dogs weighing 12 to 26 kg. Using intravenously administered Nembutal (pentobarbital) for anesthesia, midline abdominal incisions were made to permit exteriorization of a loop of small intestine. Lymph Flow Lymphatic vessels were identified in the mesentery after injection of a dilute solution of patent blue dye into the intestinal wall. Two to four adjacent lymphatic vessels were cannulated in the area of the mesentery between the intestine and first lymph node systems. The cannula system consisted of a #30 gauge dental needle with fine polyethylene tubing (PE 10) attached to the blunt side of the needle. Lymph was collected during 5 minute periods, pooled, and measured gravimetrically. Stabilization of lymph flow during the control period was observed for 20 From the Departments of Surgery, Veteran’s Administration Hospital and Upstate Medical Center, State University of New York, Syracuse, New York. Reprint requests should be addressed to Norman B. Ackerman, MD, PhD, Department of Surgery, Upstate Medical, Center, State University of New York, Syracuse, New York 13210. Presented at the Seventeenth Annual Meeting of the Society for Surgery of the Alimentary Tract, Miami Beach, Florida, May 25-26, 1976.
Volume 133, January 1977
to 40 minutes. The effects of arterial and venous ligation on lymph flow were measured. Appropriate blood vessels were tied off using fine silk ligatures which had been positioned around the vessels prior to the control period. In six dogs, the total arterial circulation of the intestinal loop was ligated, along with the marginal vessels, both arterial and venous. Lymph flow was measured during the 40 to 45 minutes subsequent to ligation. In the second group of eight dogs, the venous outflow system was ligated, and in all but three the marginal vessels were also tied off. Lymph was measured for 20 to 75 minutes after vessel ligation. In a third group of six dogs, arteries, veins, and marginal vessels were simultaneously ligated. Lymph was measured during the following 40 to 65 minutes after occlusion of the circulation. VenousFlow The measurement of venous flow was carried out with the use of a Carolina electromagnetic flow meter system with vessel occlusive zeroing. A small vein in the mesentery was isolated and a small probe measuring either 3,4, or 5 mm in circumference was positioned around the vein. After stabilization of the system, ligation of the adjacent vessels was carried out in a stepwise fashion, because of the rapid response in venous flow to these acute hemodynamic changes. The intestinal vasculature is depicted in a diagrammatic style in Figure 1 and the terminology used in these studies is depicted. Since there were some variations in the vascular pattern in these experimental animals, minor differences in procedure from experiment to experiment occurred. Response time of venous flow to the changes produced by vessel ligation was rapid, usually well within 2 minutes. The effects of arterial ligation on venous flow were studied in six animals. Left and right lateral arteries were individually ligated as a first step, with ligation of the central artery and finally the arterial and venous marginal vessels following. In some experiments, distant arterial vessels were also ligated in the beginning of the experiment. The effects of occlusion of the adjacent veins on venous flow were studied in six dogs. Left and right lateral veins were ligated individually, followed by ligation of the marginal vessels. Distant veins were occluded in the early phases of some of the experiments. The effects of ligating arteries and veins simultaneously were measured in a third group of six dogs. Right and left lateral arteries and veins were ligated first, followed by occlusion of the marginal vessels. Distant arteries and veins were ligated during the
73
Ackerman
?s--Distant
Figure 1. Diagrammatic representation of the intestinal vasculature.
Vessels
early stages of the experiments in some studies. The central artery was not ligated in this group of experiments. Arterial Flow
Arterial inflow was measured with the use of a Carolina electromagnetic flow meter system. A probe measuring either 3 or 4 mm in circumference was placed on an appropriate sized artery in the small intestine mesentery. Ligation of the adjacent vessels was carried in a stepwise fashion. Terminology used in these studies is the same as in the venous flow experiments. Response time was short in these experiments permitting relatively brikf periods of observation after vessel ligation. In three dogs, the effects of ligation of the adjacent arteries were observed. The left and right lateral arteries were individually ligated first, followed by occlusion of the marginal vessels. In the second group of three animals,
venous occlusion was studied, ligating the left and right lateral veins first, followed by occlusion of the marginal vessels. In the third group of three experiments, the arteries and veins were ligated simultaneously. Right and left lateral arterial and venous systems were occluded first, followed by ligation of the marginal vessels. TABLE
I Effect of Vascular Ligation on Mesenteric
Lymph
Flow
Ratio Lymph Experimental Study
50.7 73.5
* 9.5 f 35.3
56.5
+ 13.1
*With marginal was 4.59. t With intact ratio was 2.43.
veins arterial
intact,
min)
Maximum Effect
Control
Arterial ligation Venous ligation* Arteriovenous ligation?
74
Flow (mg/5
17.4 423.2 14.6
-
Maximum: Control
f 5.6 k 138.7
0.32 5.76
f 3.6
0.26
maximum:control
collaterals,
maximum:control
ratio
Results Lymph Flow (Table I)
Arterial Ligation. During the control period in these experiments, lymph flow averaged 50.7 mg/5 min. At 10 to 15 minutes after ligation of the arterial and marginal vessels, lymph flow decreased abruptly and ultimately levelled off to an average flow of 17.4 mg/5 min. The ratio of maximum effect to control was 0.32. This represented a significant decrease in flow (p <0.02). In none of the experiments did the lymph flow cease entirely. Venous Ligation. In these experiments, the lymph flow averaged 73.5 mg/5 min during the control periods. Usually within 5 minutes after venous ligation, a substantial increase in ly’mph flow was observed reaching a peak of increased flow at 15 to 20 minutes. Flow rates remained markedly elevated during the entire period of observation, as long as 75 minutes. There was a considerable variation in the extent of increased flow, from 2.4 to more than 24 times control levels, with the flow rates averaging 423.2 mg/5 min. The ratio of the maximum increase/control was 5.76. This was a significantly increased flow (p <0.05). Obvious changes in the intestine were noted during these experiments with hemorrhagic engorgement of intestines and mesentery. The lymph often became blood-tinged. When the marginal vessels were not ligated in three experiments, these changes were not noted. However, significant increases in flow occurred, with an average increase of 4.5 times control levels. Simultaneous Arterial and Venous Ligation. Lymph flow averaged 56.5 mg/5 min during the control periods in these studies. An abrupt decrease in lymph flow occurred within 5 to 10 minutes after
The American Journal 01 Surgery
Arterial
Flow (Table
Simultaneous
II
Effect
II)
of Vascular
Ligation
on Mesenteric
Arterial
Arterial ligation Venous ligation Arteriovenous ligation
TABLE
III
Lateral Vessel Ligation
Control
kffect
2.70 0.97
f 0.63 f 0.18
1.62 1.72
* 0.26 f 0.30
1.98
+ 0.44
4.91
i
of Vascular
Ligation
Venous
Study
Arterial ligation Venous ligation Arteriovenous ligation
Volume 133, January 1977
Control 16.67 21.67 7.33
+ 4.48 + 7.39 * 3.09
Ligation.
Flow Flow (ml/min)
Central Arterial Ligation 0.78
*
f 0.17
Arterial
Ratio
Marginal Arteriovenous Ligation
Maximum Effect
Maximum: Control
0.18 0.75
zk 0.10 i 0.17
0.14 f 0.06 1.91 2 0.33
0.05 1.97
2.22
i 0.58
4.93
2.49
* 1.28
Flow
Arterial
Experimental
Venous
Flow (Table Ill)
1.28
on Mesenteric
and
Arterial Ligation. Arterial blood flow during the control periods averaged 16.67 ml/min. After the lateral vessels were ligated, arterial flow rose to 28.17 ml/min. When the marginal vessels were occluded, arterial flow dropped to levels approximating control values, averaging 17.50 ml/min. The ratio of maximum increased flow to control was 1.69. Venous Ligation. Control levels of arterial flow averaged 21.67 ml/min in these studies. There was
Venous Experimental Study
Arterial
Control flow rates in these studies averaged 1.98 ml/min. Venous flow increased to a mean of 4.91 ml/min after occlusion of lateral arteries and veins. When arterial and venous marginal vessels were ligated, leaving the central artery intact, venous flow returned to control levels. The maximum level of venous flow after ligation of lateral and distant vessels averaged 4.93 ml/min. The ratio of maximum effect to control was 2.49, a significant increase in venous flow (p <0.05).
Arterial Ligation. Venous flow averaged 2.70 ml/min in the control period. A sharp decrease in venous flow occurred after ligation of the lateral arteries. Occlusion of the distant arterial vessels had no significant effect on venous flow. Major reductions in venous flow occurred when the central artery was ligated, decreasing to levels 29 per cent of controls. When the marginal vessels were occluded, venous flow decreased further to a mean of 0.18 ml/min and maximum decreased flow after total arterial ligation, including several collateral vessels averaged 0.14 ml/min. The ratio of maximum decrease to control was 0.05 representing a significant decrease (p
in Colon Resection
Venous Ligation. Control venous flow in these experiments averaged 0.97 ml/min. After ligation of the lateral veins, venous flow in the central vein increased to a mean of 1.72 ml/min. Occlusion of distant veins had no significant effects on venous flow. When the marginal vessels were ligated, venous flow decreased to levels averaging 0.75 ml/min. The average maximum venous flow after ligation of lateral and distant veins was 1.91 ml/min. The ratio of maximum increase/control was 1.97, which was significantly higher than controls (p <0.05).
ligation of the arterial and venous circulation including the marginal vessels. Flow rates levelled off to an average of 14.6 mg/5 min. The ratio of maximum effect/control was 0.26 which was not significantly different from the levels observed after arterial ligation. These new levels were significantly different from the controls (p <0.02). Lymph flow did not completely stop in any experiment. In two of the studies, arterial collaterals were inadvertently left intact with pulsation noted in the small vessels of the intestine. In both of these experiments, lymph flow increased until the intact arterial vessels were ligated. At this point, the ratio of lymph flow/control levels was 2.43 and undoubtedly would have increased to higher levels if the collateral vessels were not identified and occluded. Venous
Ligation
Flow (ml/min)
Lateral Vessel Ligation
Marginal Arteriovenous Ligation
28.17 20.00 12.92
17.50 19.67 6.83
+ 3.61 + 6.80 2 4.67
i 4.17 + 5.93 i: 3.34
Ratio Maximum: Control 1.69 0.92 1.76
75
Ackerman
essentially no change in arterial flow when lateral veins were ligated nor when the marginal vessels were occluded, with arterial flow averaging 19.67 ml/min. The ratio of this level to control was 0.92. Simultaneous Arterial and Venous Ligation. The average arterial flow during the control period in these studies was 7.33 ml/min. An increase in arterial flow occurred after lateral arteries and veins were ligated, with arterial flow rates averaging 12.92 ml/min. When the marginal vessels were ligated arterial flow dropped to control levels. The ratio of maximum increase to control was 1.76. Comments
By correlating the findings in the studies on arterial, venous and lymph flow, we are able to make a composite picture of the vascular changes occurring after blood vessel ligation. These findings have been helpful in devising a procedure to minimize venous and lymphatic outflow during the course of resection of cancers of the colon. When arteries in the mesentery are ligated, collateral flow from nearby arteries increases, especially across marginal vessels. However total arterial inflow is probably decreased and there is a decrease in venous outflow. As more arterial vessels are ligated, venous flow decreases, further. When the marginal vessels, acting as pathways of collateral arterial flow, are occluded, venous flow decreases sharply and in some instances may stop completely, and arterial flow in surrounding vessels decreases to a control, preligation rate. During all of this time, as venous flow decreases, the lymph flow also decreases. The changes occurring during vein ligation are considerably different. When one begins to ligate the veins in the mesentery, the flow of arterial blood from nearby vessels does not change appreciably. Consequently, the marginal veins act as a collateral outflow system and venous flow increases via the adjacent intact veins, At this time lymph flow increases, probably as a consequence of an increased venous and tissue pressure, as predicted by Starling’s law. When the marginal vessels are ligated, the venous collateral pathway is eliminated, and the flow in nearby veins decreases back to control, preligation levels. Arterial Bow in adjacent vessels still shows no change. With the loss of major venous outflow pathways, venous and tissue pressure rises and lymphatic flow increases further. When arteries and veins are ligated together, the hemodynamic changes are different than if vessels are ligated individually. As the mesenteric arteries and veins become occluded, an increase in arterial flow in the adjacent vessels occurs with an increased
76
flow through collateral marginal vessels. Venous outflow in adjacent vessels also increases as the marginal veins participate in the drainage of the collateral flow. If the arterial inflow exceeds the capacity for the venous drainage, venous pressure increases and lymphatic flow increases. When marginal vessels are occluded, major pathways of collateral flow are eliminated and arterial flow in the adjacent vessels decreases to control levels, as does venous outflow. As the total blood flow decreases, lymph flow also decreases sharply. On the basis of these studies, primary vein ligation, such as early ligation of the inferior mesenteric veins for left colon cancers, would appear to be an unacceptable operative procedure. An increase in both venous and lymphatic outflow would be expected. Reports by Salsbury et al [1] of an increase in cancer cells in the iliac veins after ligation of the inferior mesenteric veins suggest that an increased flow in the collateral venous circulation occurs. The technic most commonly used in the resection of cancers of the colon includes simultaneous ligation of the mesenteric arteries and veins. Although this procedure is the simplest way of handling the mesocolon dissection, it has its potential disadvantages. While arteries and veins are being ligated, an increased inflow occurs via collateral arteries with an attendant increase in collateral venous outflow. If collateral arterial flow increases excessively, lymph flow may also increase. There is a possibility of continuing blood flow to and from the area of the malignancy until collateral and marginal vessels are finally eliminated. Only at this time are the lymph and venous flows depressed. Primary arterial ligation appears to offer the most satisfactory technic in the dissection of intestinal cancer. Although collateral arterial flow increases when the arterial circulation is ligated, this is probably of a relatively small magnitude since venous outflow decreases. Lymph flow also decreases at this time. When this is followed by marginal vessel ligation, venous flow drops to a negligable rate, as does lymph flow. High ligation of major mesenteric arteries was advocated in the past as a means of assuring an extensive lymph node resection. Our experimental studies suggest that exposure and ligation of these vessels should be performed as the first steps in the mesocolon dissection as a means of attempting to decrease dissemination of cancer cells through the blood and lymph system. There is no direct evidence that an increased flow of venous blood and lymph results in an increased dissemination of cancer cells and subsequent metastasis. However, since these are the main pathways of spread of cancer and since it is known that malig-
The American Journal of Surgery
Arterial
nant cells can infiltrate into both venous and lymphatic systems, the aim of decreasing flow would appear to be desirable. The reports of Salsbury et al [I] and of Ujiki, Brand, and O’Brien [2] at least suggest the possibilities of increasing the spread of tumor cells in the venous and lymphatic circulations under situations of increased flow. Although it has been accepted that the mere presence of cancer cells in the circulation does not necessarily lead to metastasis, the concentration and numbers of these cells may play an important role. This has been suggested experimentally on numerous studies on tumor “take” in animals by Fisher and Fisher [3], as well as others. Since we do not fully understand nor are able to control the other factors relating to metastasis, including immunologic status, blood flow, specific organ resistance, and others, it appears desirable to keep operative “showering” of cells to a minimum. Accordingly, we believe that manipulation of the tumor should be kept to a minimum with the use of a “no touch” technic similar to that described by Turnbull et al [4]. Earlier studies in our laboratory on lymph flow after manipulating and massage the intestine demonstrated an increased flow of lymph as a consequence [5]. Preliminary studies have also demonstrated an increased venous outflow under these experimental circumstances. Operative Technic An operative technic based on these studies is now being used in the resection of cancer of the colon in patients. After determining the resectability of the tumor, ligation of the appropriate major arteries is carried out as a first step. Marginal vessels located close to the colon are ligated next near the area where intestinal clamps are to be applied. The Doppler ultrasonic flow detector has been useful in identifying arterial channels, particularly in patients with mesocolons heavily infiltrated with fat. The remainder of the mesocolon including lymphatic and venous channels is ligated next, and the standard “no touch” technic is performed with excision of the tumor as a final step.
Volume 133, January 1977
Ligation in Colon Resection
Summary The dynamics of arterial, venous, and lymphatic flow in the mesentery were studied in dogs, using an electromagnetic flowmeter for the blood and cannulation and gravimetric measurement for the lymph. Ligation of veins caused an increased venous outflow in adjacent veins and a marked increase in lymph flow. When marginal vessels were ligated, eliminating the major collateral flow, venous flow decreased, but elevated lymph flow persisted. Simultaneous ligation of arteries and veins resulted in increases of both arterial and venous flow in adjacent vessels. Lymph flow decreased unless excessive arterial collateral flow persisted. When collateral marginal vessel flow was occluded, adjacent venous and arterial blood flow decreased to control levels. With arterial ligation, collateral arterial blood flow increased slightly, but venous and lymph flow decreased sharply. When collateral marginal vessels were eliminated, adjacent arterial blood flow decreased to control levels and venous flow virtually stopped. As a result of these studies, the technic of early primary arterial ligation followed by marginal vessel ligation appears to be the most satisfactory procedure for decreasing venous and lymphatic outflow and hopefully avoiding dissemination of cancer cells during the operation. This technic is now being used as a modification of the “no touch” technic for cancer of the colon.
References 1. Salsbury AJ, McKinna JA, Griffiths JD, Morgan CN: Circulating cancer cells during excision of carcinomas of the rectum and colon with high ligation of the inferior mesenteric vein. Surg Gynecol Obsfet 120: 1266, 1965. 2. Ujiki GT, Brand WN, O’Brien PH: Effects of lymphangiography on metastasis. Radiology 91: 677, 1966. 3. Fisher B, Fisher ER: Experimental studies of factors influencing hepatic metastasis. III. Effect of surgical trauma with special reference to liver injury. Ann Surg 150: 731, 1959. 4. Turnbull RB Jr, Kyle K, Watson FR, Spratt J: Cancer of the colon. Ann Surg 166: 420, 1967. 5. Ackerman NB: The influence of mechanical factors on intestinal lymph flow and their relationship to operations for carcinoma of the intestine. Surg Gynecol Obstet 136: 677, 1974.
77
The operative technic for excising a malignant neoplasm must be designed to minimize the dissemination of cancer cells during the procedure. The major routes of dissemination of cancer of the colon are the venous and lymphatic outflow systems. It would appear desirable to decrease the lymphatic and venous outflow early in the operative procedure to prevent a possible “showering” of cancer cells. Present technics of early ligation of arteries and veins or of veins alone may promote an increase flow through marginal veins and lymphatics. By studying the inter-relationships of arterial, venous, and lymphatic flow through mesenteric vessels, we have found that ligation of the arterial system alone results in significant decreases in venous and lymphatic outflow. Accordingly, we are proposing that primary arterial ligation be performed in the early stages of resection for cancer of the colon. Material and Methods Studies on arterial, venous, and lymphatic flow were performed on healthy mongrel dogs weighing 12 to 26 kg. Using intravenously administered Nembutal (pentobarbital) for anesthesia, midline abdominal incisions were made to permit exteriorization of a loop of small intestine. Lymph Flow Lymphatic vessels were identified in the mesentery after injection of a dilute solution of patent blue dye into the intestinal wall. Two to four adjacent lymphatic vessels were cannulated in the area of the mesentery between the intestine and first lymph node systems. The cannula system consisted of a #30 gauge dental needle with fine polyethylene tubing (PE 10) attached to the blunt side of the needle. Lymph was collected during 5 minute periods, pooled, and measured gravimetrically. Stabilization of lymph flow during the control period was observed for 20 From the Departments of Surgery, Veteran’s Administration Hospital and Upstate Medical Center, State University of New York, Syracuse, New York. Reprint requests should be addressed to Norman B. Ackerman, MD, PhD, Department of Surgery, Upstate Medical, Center, State University of New York, Syracuse, New York 13210. Presented at the Seventeenth Annual Meeting of the Society for Surgery of the Alimentary Tract, Miami Beach, Florida, May 25-26, 1976.
Volume 133, January 1977
to 40 minutes. The effects of arterial and venous ligation on lymph flow were measured. Appropriate blood vessels were tied off using fine silk ligatures which had been positioned around the vessels prior to the control period. In six dogs, the total arterial circulation of the intestinal loop was ligated, along with the marginal vessels, both arterial and venous. Lymph flow was measured during the 40 to 45 minutes subsequent to ligation. In the second group of eight dogs, the venous outflow system was ligated, and in all but three the marginal vessels were also tied off. Lymph was measured for 20 to 75 minutes after vessel ligation. In a third group of six dogs, arteries, veins, and marginal vessels were simultaneously ligated. Lymph was measured during the following 40 to 65 minutes after occlusion of the circulation. VenousFlow The measurement of venous flow was carried out with the use of a Carolina electromagnetic flow meter system with vessel occlusive zeroing. A small vein in the mesentery was isolated and a small probe measuring either 3,4, or 5 mm in circumference was positioned around the vein. After stabilization of the system, ligation of the adjacent vessels was carried out in a stepwise fashion, because of the rapid response in venous flow to these acute hemodynamic changes. The intestinal vasculature is depicted in a diagrammatic style in Figure 1 and the terminology used in these studies is depicted. Since there were some variations in the vascular pattern in these experimental animals, minor differences in procedure from experiment to experiment occurred. Response time of venous flow to the changes produced by vessel ligation was rapid, usually well within 2 minutes. The effects of arterial ligation on venous flow were studied in six animals. Left and right lateral arteries were individually ligated as a first step, with ligation of the central artery and finally the arterial and venous marginal vessels following. In some experiments, distant arterial vessels were also ligated in the beginning of the experiment. The effects of occlusion of the adjacent veins on venous flow were studied in six dogs. Left and right lateral veins were ligated individually, followed by ligation of the marginal vessels. Distant veins were occluded in the early phases of some of the experiments. The effects of ligating arteries and veins simultaneously were measured in a third group of six dogs. Right and left lateral arteries and veins were ligated first, followed by occlusion of the marginal vessels. Distant arteries and veins were ligated during the
73
Ackerman
?s--Distant
Figure 1. Diagrammatic representation of the intestinal vasculature.
Vessels
early stages of the experiments in some studies. The central artery was not ligated in this group of experiments. Arterial Flow
Arterial inflow was measured with the use of a Carolina electromagnetic flow meter system. A probe measuring either 3 or 4 mm in circumference was placed on an appropriate sized artery in the small intestine mesentery. Ligation of the adjacent vessels was carried in a stepwise fashion. Terminology used in these studies is the same as in the venous flow experiments. Response time was short in these experiments permitting relatively brikf periods of observation after vessel ligation. In three dogs, the effects of ligation of the adjacent arteries were observed. The left and right lateral arteries were individually ligated first, followed by occlusion of the marginal vessels. In the second group of three animals,
venous occlusion was studied, ligating the left and right lateral veins first, followed by occlusion of the marginal vessels. In the third group of three experiments, the arteries and veins were ligated simultaneously. Right and left lateral arterial and venous systems were occluded first, followed by ligation of the marginal vessels. TABLE
I Effect of Vascular Ligation on Mesenteric
Lymph
Flow
Ratio Lymph Experimental Study
50.7 73.5
* 9.5 f 35.3
56.5
+ 13.1
*With marginal was 4.59. t With intact ratio was 2.43.
veins arterial
intact,
min)
Maximum Effect
Control
Arterial ligation Venous ligation* Arteriovenous ligation?
74
Flow (mg/5
17.4 423.2 14.6
-
Maximum: Control
f 5.6 k 138.7
0.32 5.76
f 3.6
0.26
maximum:control
collaterals,
maximum:control
ratio
Results Lymph Flow (Table I)
Arterial Ligation. During the control period in these experiments, lymph flow averaged 50.7 mg/5 min. At 10 to 15 minutes after ligation of the arterial and marginal vessels, lymph flow decreased abruptly and ultimately levelled off to an average flow of 17.4 mg/5 min. The ratio of maximum effect to control was 0.32. This represented a significant decrease in flow (p <0.02). In none of the experiments did the lymph flow cease entirely. Venous Ligation. In these experiments, the lymph flow averaged 73.5 mg/5 min during the control periods. Usually within 5 minutes after venous ligation, a substantial increase in ly’mph flow was observed reaching a peak of increased flow at 15 to 20 minutes. Flow rates remained markedly elevated during the entire period of observation, as long as 75 minutes. There was a considerable variation in the extent of increased flow, from 2.4 to more than 24 times control levels, with the flow rates averaging 423.2 mg/5 min. The ratio of the maximum increase/control was 5.76. This was a significantly increased flow (p <0.05). Obvious changes in the intestine were noted during these experiments with hemorrhagic engorgement of intestines and mesentery. The lymph often became blood-tinged. When the marginal vessels were not ligated in three experiments, these changes were not noted. However, significant increases in flow occurred, with an average increase of 4.5 times control levels. Simultaneous Arterial and Venous Ligation. Lymph flow averaged 56.5 mg/5 min during the control periods in these studies. An abrupt decrease in lymph flow occurred within 5 to 10 minutes after
The American Journal 01 Surgery
Arterial
Flow (Table
Simultaneous
II
Effect
II)
of Vascular
Ligation
on Mesenteric
Arterial
Arterial ligation Venous ligation Arteriovenous ligation
TABLE
III
Lateral Vessel Ligation
Control
kffect
2.70 0.97
f 0.63 f 0.18
1.62 1.72
* 0.26 f 0.30
1.98
+ 0.44
4.91
i
of Vascular
Ligation
Venous
Study
Arterial ligation Venous ligation Arteriovenous ligation
Volume 133, January 1977
Control 16.67 21.67 7.33
+ 4.48 + 7.39 * 3.09
Ligation.
Flow Flow (ml/min)
Central Arterial Ligation 0.78
*
f 0.17
Arterial
Ratio
Marginal Arteriovenous Ligation
Maximum Effect
Maximum: Control
0.18 0.75
zk 0.10 i 0.17
0.14 f 0.06 1.91 2 0.33
0.05 1.97
2.22
i 0.58
4.93
2.49
* 1.28
Flow
Arterial
Experimental
Venous
Flow (Table Ill)
1.28
on Mesenteric
and
Arterial Ligation. Arterial blood flow during the control periods averaged 16.67 ml/min. After the lateral vessels were ligated, arterial flow rose to 28.17 ml/min. When the marginal vessels were occluded, arterial flow dropped to levels approximating control values, averaging 17.50 ml/min. The ratio of maximum increased flow to control was 1.69. Venous Ligation. Control levels of arterial flow averaged 21.67 ml/min in these studies. There was
Venous Experimental Study
Arterial
Control flow rates in these studies averaged 1.98 ml/min. Venous flow increased to a mean of 4.91 ml/min after occlusion of lateral arteries and veins. When arterial and venous marginal vessels were ligated, leaving the central artery intact, venous flow returned to control levels. The maximum level of venous flow after ligation of lateral and distant vessels averaged 4.93 ml/min. The ratio of maximum effect to control was 2.49, a significant increase in venous flow (p <0.05).
Arterial Ligation. Venous flow averaged 2.70 ml/min in the control period. A sharp decrease in venous flow occurred after ligation of the lateral arteries. Occlusion of the distant arterial vessels had no significant effect on venous flow. Major reductions in venous flow occurred when the central artery was ligated, decreasing to levels 29 per cent of controls. When the marginal vessels were occluded, venous flow decreased further to a mean of 0.18 ml/min and maximum decreased flow after total arterial ligation, including several collateral vessels averaged 0.14 ml/min. The ratio of maximum decrease to control was 0.05 representing a significant decrease (p
in Colon Resection
Venous Ligation. Control venous flow in these experiments averaged 0.97 ml/min. After ligation of the lateral veins, venous flow in the central vein increased to a mean of 1.72 ml/min. Occlusion of distant veins had no significant effects on venous flow. When the marginal vessels were ligated, venous flow decreased to levels averaging 0.75 ml/min. The average maximum venous flow after ligation of lateral and distant veins was 1.91 ml/min. The ratio of maximum increase/control was 1.97, which was significantly higher than controls (p <0.05).
ligation of the arterial and venous circulation including the marginal vessels. Flow rates levelled off to an average of 14.6 mg/5 min. The ratio of maximum effect/control was 0.26 which was not significantly different from the levels observed after arterial ligation. These new levels were significantly different from the controls (p <0.02). Lymph flow did not completely stop in any experiment. In two of the studies, arterial collaterals were inadvertently left intact with pulsation noted in the small vessels of the intestine. In both of these experiments, lymph flow increased until the intact arterial vessels were ligated. At this point, the ratio of lymph flow/control levels was 2.43 and undoubtedly would have increased to higher levels if the collateral vessels were not identified and occluded. Venous
Ligation
Flow (ml/min)
Lateral Vessel Ligation
Marginal Arteriovenous Ligation
28.17 20.00 12.92
17.50 19.67 6.83
+ 3.61 + 6.80 2 4.67
i 4.17 + 5.93 i: 3.34
Ratio Maximum: Control 1.69 0.92 1.76
75
Ackerman
essentially no change in arterial flow when lateral veins were ligated nor when the marginal vessels were occluded, with arterial flow averaging 19.67 ml/min. The ratio of this level to control was 0.92. Simultaneous Arterial and Venous Ligation. The average arterial flow during the control period in these studies was 7.33 ml/min. An increase in arterial flow occurred after lateral arteries and veins were ligated, with arterial flow rates averaging 12.92 ml/min. When the marginal vessels were ligated arterial flow dropped to control levels. The ratio of maximum increase to control was 1.76. Comments
By correlating the findings in the studies on arterial, venous and lymph flow, we are able to make a composite picture of the vascular changes occurring after blood vessel ligation. These findings have been helpful in devising a procedure to minimize venous and lymphatic outflow during the course of resection of cancers of the colon. When arteries in the mesentery are ligated, collateral flow from nearby arteries increases, especially across marginal vessels. However total arterial inflow is probably decreased and there is a decrease in venous outflow. As more arterial vessels are ligated, venous flow decreases, further. When the marginal vessels, acting as pathways of collateral arterial flow, are occluded, venous flow decreases sharply and in some instances may stop completely, and arterial flow in surrounding vessels decreases to a control, preligation rate. During all of this time, as venous flow decreases, the lymph flow also decreases. The changes occurring during vein ligation are considerably different. When one begins to ligate the veins in the mesentery, the flow of arterial blood from nearby vessels does not change appreciably. Consequently, the marginal veins act as a collateral outflow system and venous flow increases via the adjacent intact veins, At this time lymph flow increases, probably as a consequence of an increased venous and tissue pressure, as predicted by Starling’s law. When the marginal vessels are ligated, the venous collateral pathway is eliminated, and the flow in nearby veins decreases back to control, preligation levels. Arterial Bow in adjacent vessels still shows no change. With the loss of major venous outflow pathways, venous and tissue pressure rises and lymphatic flow increases further. When arteries and veins are ligated together, the hemodynamic changes are different than if vessels are ligated individually. As the mesenteric arteries and veins become occluded, an increase in arterial flow in the adjacent vessels occurs with an increased
76
flow through collateral marginal vessels. Venous outflow in adjacent vessels also increases as the marginal veins participate in the drainage of the collateral flow. If the arterial inflow exceeds the capacity for the venous drainage, venous pressure increases and lymphatic flow increases. When marginal vessels are occluded, major pathways of collateral flow are eliminated and arterial flow in the adjacent vessels decreases to control levels, as does venous outflow. As the total blood flow decreases, lymph flow also decreases sharply. On the basis of these studies, primary vein ligation, such as early ligation of the inferior mesenteric veins for left colon cancers, would appear to be an unacceptable operative procedure. An increase in both venous and lymphatic outflow would be expected. Reports by Salsbury et al [1] of an increase in cancer cells in the iliac veins after ligation of the inferior mesenteric veins suggest that an increased flow in the collateral venous circulation occurs. The technic most commonly used in the resection of cancers of the colon includes simultaneous ligation of the mesenteric arteries and veins. Although this procedure is the simplest way of handling the mesocolon dissection, it has its potential disadvantages. While arteries and veins are being ligated, an increased inflow occurs via collateral arteries with an attendant increase in collateral venous outflow. If collateral arterial flow increases excessively, lymph flow may also increase. There is a possibility of continuing blood flow to and from the area of the malignancy until collateral and marginal vessels are finally eliminated. Only at this time are the lymph and venous flows depressed. Primary arterial ligation appears to offer the most satisfactory technic in the dissection of intestinal cancer. Although collateral arterial flow increases when the arterial circulation is ligated, this is probably of a relatively small magnitude since venous outflow decreases. Lymph flow also decreases at this time. When this is followed by marginal vessel ligation, venous flow drops to a negligable rate, as does lymph flow. High ligation of major mesenteric arteries was advocated in the past as a means of assuring an extensive lymph node resection. Our experimental studies suggest that exposure and ligation of these vessels should be performed as the first steps in the mesocolon dissection as a means of attempting to decrease dissemination of cancer cells through the blood and lymph system. There is no direct evidence that an increased flow of venous blood and lymph results in an increased dissemination of cancer cells and subsequent metastasis. However, since these are the main pathways of spread of cancer and since it is known that malig-
The American Journal of Surgery
Arterial
nant cells can infiltrate into both venous and lymphatic systems, the aim of decreasing flow would appear to be desirable. The reports of Salsbury et al [I] and of Ujiki, Brand, and O’Brien [2] at least suggest the possibilities of increasing the spread of tumor cells in the venous and lymphatic circulations under situations of increased flow. Although it has been accepted that the mere presence of cancer cells in the circulation does not necessarily lead to metastasis, the concentration and numbers of these cells may play an important role. This has been suggested experimentally on numerous studies on tumor “take” in animals by Fisher and Fisher [3], as well as others. Since we do not fully understand nor are able to control the other factors relating to metastasis, including immunologic status, blood flow, specific organ resistance, and others, it appears desirable to keep operative “showering” of cells to a minimum. Accordingly, we believe that manipulation of the tumor should be kept to a minimum with the use of a “no touch” technic similar to that described by Turnbull et al [4]. Earlier studies in our laboratory on lymph flow after manipulating and massage the intestine demonstrated an increased flow of lymph as a consequence [5]. Preliminary studies have also demonstrated an increased venous outflow under these experimental circumstances. Operative Technic An operative technic based on these studies is now being used in the resection of cancer of the colon in patients. After determining the resectability of the tumor, ligation of the appropriate major arteries is carried out as a first step. Marginal vessels located close to the colon are ligated next near the area where intestinal clamps are to be applied. The Doppler ultrasonic flow detector has been useful in identifying arterial channels, particularly in patients with mesocolons heavily infiltrated with fat. The remainder of the mesocolon including lymphatic and venous channels is ligated next, and the standard “no touch” technic is performed with excision of the tumor as a final step.
Volume 133, January 1977
Ligation in Colon Resection
Summary The dynamics of arterial, venous, and lymphatic flow in the mesentery were studied in dogs, using an electromagnetic flowmeter for the blood and cannulation and gravimetric measurement for the lymph. Ligation of veins caused an increased venous outflow in adjacent veins and a marked increase in lymph flow. When marginal vessels were ligated, eliminating the major collateral flow, venous flow decreased, but elevated lymph flow persisted. Simultaneous ligation of arteries and veins resulted in increases of both arterial and venous flow in adjacent vessels. Lymph flow decreased unless excessive arterial collateral flow persisted. When collateral marginal vessel flow was occluded, adjacent venous and arterial blood flow decreased to control levels. With arterial ligation, collateral arterial blood flow increased slightly, but venous and lymph flow decreased sharply. When collateral marginal vessels were eliminated, adjacent arterial blood flow decreased to control levels and venous flow virtually stopped. As a result of these studies, the technic of early primary arterial ligation followed by marginal vessel ligation appears to be the most satisfactory procedure for decreasing venous and lymphatic outflow and hopefully avoiding dissemination of cancer cells during the operation. This technic is now being used as a modification of the “no touch” technic for cancer of the colon.
References 1. Salsbury AJ, McKinna JA, Griffiths JD, Morgan CN: Circulating cancer cells during excision of carcinomas of the rectum and colon with high ligation of the inferior mesenteric vein. Surg Gynecol Obsfet 120: 1266, 1965. 2. Ujiki GT, Brand WN, O’Brien PH: Effects of lymphangiography on metastasis. Radiology 91: 677, 1966. 3. Fisher B, Fisher ER: Experimental studies of factors influencing hepatic metastasis. III. Effect of surgical trauma with special reference to liver injury. Ann Surg 150: 731, 1959. 4. Turnbull RB Jr, Kyle K, Watson FR, Spratt J: Cancer of the colon. Ann Surg 166: 420, 1967. 5. Ackerman NB: The influence of mechanical factors on intestinal lymph flow and their relationship to operations for carcinoma of the intestine. Surg Gynecol Obstet 136: 677, 1974.
77