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“Intractability” in peptic ulcer
The American Journal VOL.
v
OCTOBER,
of Medicine
1948
No. 4
Editorial “Intractability”
in Peptic
T
HE term “intractable” so frequently used in reference to peptic ulcer is difficult to define. It may refer to the patient, to the ulcer or to complications present. Ordinarily, however, it is used to indicate that the symptoms of ulcer have not been relieved by or have recurred after the use of various therapeutic procedures, usually medical, sometimes surgical. The persistence or reappearance of symptoms is accompanied as a rule by objective roentgenologic or gastroscopic demonstration of the ulcer. Two or three questions inevitably arise: Why they fail to heal? Why the recurrence? Why the refractoriness? These questions are, of course, inseparable from the basic one of the cause of peptic ulcer and from the still older question asked by John Hunter’ of why the stomach does not digest itself. Many details of these phenomena are still unclear, but it is evident that one of the most important factors in the protection of the normal mucosa is the layer of mucus, constantly secreted and renewed. It is also clear that the cause of peptic ulcer, long thought to be unknown, is indeed of “peptic” origin, that it results from the inability of the mucosa to withstand digestion:Very little is known regarding the mucosal factors involved in this process although Konjetzny2 and Biichner” form quite differing points of view and with
Ulcer
conflicting concepts have both described quite well the histologic manifestations. Wangensteen* and his associates have shown that various factors, namely, posthemorrhagic anemia, shock, hemoconcentration, muscular fatigue, age, etc., abet the formation of experimental histamine ulcers in dogs. The extent to which these experiments may be translated into clinical equivalents is perhaps debatable but the principles established do seem valid. Wolf and WolfF observed that in the human stomach with increased vascularity and turgor the surface of the mucosa became more friable and susceptible to injury. This vascularity could be produced in various ways including emotional conflict and frustration. There are doubtless many factors which reduce the susceptibility of the mucosa to digestion. Some of these may explain such phenomena as the location of the lesion, the tendency to recurrence at the same point, the seasonal variation and the precipitating effect of emotional stress and infection. fatigue, However, the feasibility of controlling these mucosal factors by clinical methods seems 4FRIESEN, S. R. and WANGENSTEEN,0. H. Role of hemoconcentration in production of gastric and duodenal ulcer following experimental burns. Proc. S’oc. IT.+. Biol. C3 Med., 64: 81, 1947. LILLEHEI, C. W. and WANGENSTEEN,0. H. Effect of muscular fatigue on histamine-provoked ulcer with observations on gastric secretion. Ibid., 67: 49, 1948. LILLEHEI, C. W., DIXON, J. L. and WANOENSTEEN, 0. H. Relation of anemia and hemorrhagic shock to experimental ulcer production. Ibid, 68: 125, 1948. Effect of age on histamine induced ulcers. Zhid, 68: 129, 1948. 5 WOLF, S. and WOLFF, H. G. Human Gastric Function, An Experimental Study of a Man and His Stomach. New York, 1943. Oxford University Press.
’ HUNTER, J. On digestion of the stomach after death. Phil. 7i. Roy. SIX., 62: 447, 1772. 2 KONJETZNY, G. Die entziindliche Grundlagc de1 Geschwiirsbildung im Magen und Duodenum. Berlin. 1930. Julius Springer. 3 B~~CHNER,F. Die Pathogenese der peptischen Verandrrungen. Jena. 1931. Gustav Fischer. 479
480
Editorial
rather doubtful. Clinicians from Sippy on have, therefore, concentrated upon measures to decrease the acid-pepsin attack rather than hypothetic schemes for protecting 4 the mucosa or increasing mucosal resistance. Through the years there have been students of the ulcer problem who have been unwilling to accept the validity of the concept enunciated by Schwartz’j in 1910 of “no acid, no ulcer.” Their voices have gradually been stilled as it has become established that chronic peptic ulcer occurs only in association with acid gastric juice. If a patient with peptic ulcer develops persistent achlorhydria spontaneously or after roentgen irradiation or as a result of surgery, the ulcers invariably heal and do not recur until or unless the acid gastric secretion returns.’ This fact has led Wangensteen8 to characterize the concept of “intractable ulcer” as a myth; because if sufficient stomach is removed surgically to produce permanent achlorhydria, the lesions do not recur. This brings us back to the question of why some individuals develop peptic ulcer and others do not. Is the fault one of deficient mucosal resistance or of hypersecretion or are both factors operative? Levin’sgs’O studies have shown clearly that with respect to duodenal ulcer there is a profound increase in the fasting or basal gastric secretion of GSCHWARTZ, K. Ueber penetrierende MaEen und Jejunalgeschwiire. Reitr. 5. k&z. Chir., 67: 96, l
hydrochloric acid. While fasting, normal individuals secrete an average of approximately 680 mg. of hydrochloric acid in twelve hours whereas patients with duodenal ulcer yield an average return of ulcers Kirsner 2,240 mg. In “intractable” and Levin” have found the fasting output of hydrochloric acid to be as high as 6,353 mg. in twelve hours. This hypersecretion, as Dragstedt l2 has shown, is chiefly vagal in origin and can be profoundly reduced by complete bilateral vagotomy; subsequent healing of the ulcer occurs. In gastric ulcer the secretory situation is quite different’” for the output of hydrochloric acid is not greater than that found in normal individuals. Acid gastric juice is invariably present but not in excessive amounts; in fact, there is frequently a definite hyposecretion. It seems evident, therefore, that in gastric ulcer the primary defect is probably one of decreased mucosal resistance arising in some unknown manner: decreased secretion of mucus in a particular area, excessive friability, accidental traumatic mechanical injury of the superficial mucosal cells or some such phenomenon. In the absence of acid gastricjuice such erosions heal promptly; in the presence of acid thyme the regenerative power of the mucosa is still sufficient to bring about healing in the great majority; in a relatively small number peptic digestion transforms the erosion into an ulcer which gradually increases in size and depth. The process may stop at any point for the healing tendency of the mucosa is ever present. Sippy13 considered “the greatest known hindrance to the healing of the peptic ulcer . . . (to be) th e d’lsmtegrating * and digestive action of the gastric juice.” We now know I’ KIRSNER, J. B., LEVIN, E. aid PALMER, W. L. Observations on the excessive nocturnal gastric secretion in patients with peptic ulcer. Gastroenterology, (in press). I2 DRAGSTEDT,L. R. and OWENS, F. M., JR. Supradiaphragmatic section of the vagus nerves in-treatment of duodenal ulcer. Pm. Sot. Exber. Med. & Biol.. 53: 152. 1943. I3 SIPPY, B. W. Gastric and duodenal ulcer: medical cure by an efficient removal of gastric juice corrosion. 7. A. M. A., 64: 1625, 1915.
Editorial that this is the attacking force responsible for the production of the lesion, the stimulus for pain and the cause of failure to heal. The digestive action of the gastric juice depends upon hydrochloric acid and pepsin; it is absent in achlorhydria. The most effective means of controlling the digestive
4-81
attack is by controlling the free acidity. We have not yet found a satisfactory method of control; therein lies the ulcer problem. Intractability would indeed be a myth if complete control could be achieved. \Y.ALTER
LINCOI.~ PALMER, M.D.
v
OCTOBER,
of Medicine
1948
No. 4
Editorial “Intractability”
in Peptic
T
HE term “intractable” so frequently used in reference to peptic ulcer is difficult to define. It may refer to the patient, to the ulcer or to complications present. Ordinarily, however, it is used to indicate that the symptoms of ulcer have not been relieved by or have recurred after the use of various therapeutic procedures, usually medical, sometimes surgical. The persistence or reappearance of symptoms is accompanied as a rule by objective roentgenologic or gastroscopic demonstration of the ulcer. Two or three questions inevitably arise: Why they fail to heal? Why the recurrence? Why the refractoriness? These questions are, of course, inseparable from the basic one of the cause of peptic ulcer and from the still older question asked by John Hunter’ of why the stomach does not digest itself. Many details of these phenomena are still unclear, but it is evident that one of the most important factors in the protection of the normal mucosa is the layer of mucus, constantly secreted and renewed. It is also clear that the cause of peptic ulcer, long thought to be unknown, is indeed of “peptic” origin, that it results from the inability of the mucosa to withstand digestion:Very little is known regarding the mucosal factors involved in this process although Konjetzny2 and Biichner” form quite differing points of view and with
Ulcer
conflicting concepts have both described quite well the histologic manifestations. Wangensteen* and his associates have shown that various factors, namely, posthemorrhagic anemia, shock, hemoconcentration, muscular fatigue, age, etc., abet the formation of experimental histamine ulcers in dogs. The extent to which these experiments may be translated into clinical equivalents is perhaps debatable but the principles established do seem valid. Wolf and WolfF observed that in the human stomach with increased vascularity and turgor the surface of the mucosa became more friable and susceptible to injury. This vascularity could be produced in various ways including emotional conflict and frustration. There are doubtless many factors which reduce the susceptibility of the mucosa to digestion. Some of these may explain such phenomena as the location of the lesion, the tendency to recurrence at the same point, the seasonal variation and the precipitating effect of emotional stress and infection. fatigue, However, the feasibility of controlling these mucosal factors by clinical methods seems 4FRIESEN, S. R. and WANGENSTEEN,0. H. Role of hemoconcentration in production of gastric and duodenal ulcer following experimental burns. Proc. S’oc. IT.+. Biol. C3 Med., 64: 81, 1947. LILLEHEI, C. W. and WANGENSTEEN,0. H. Effect of muscular fatigue on histamine-provoked ulcer with observations on gastric secretion. Ibid., 67: 49, 1948. LILLEHEI, C. W., DIXON, J. L. and WANOENSTEEN, 0. H. Relation of anemia and hemorrhagic shock to experimental ulcer production. Ibid, 68: 125, 1948. Effect of age on histamine induced ulcers. Zhid, 68: 129, 1948. 5 WOLF, S. and WOLFF, H. G. Human Gastric Function, An Experimental Study of a Man and His Stomach. New York, 1943. Oxford University Press.
’ HUNTER, J. On digestion of the stomach after death. Phil. 7i. Roy. SIX., 62: 447, 1772. 2 KONJETZNY, G. Die entziindliche Grundlagc de1 Geschwiirsbildung im Magen und Duodenum. Berlin. 1930. Julius Springer. 3 B~~CHNER,F. Die Pathogenese der peptischen Verandrrungen. Jena. 1931. Gustav Fischer. 479
480
Editorial
rather doubtful. Clinicians from Sippy on have, therefore, concentrated upon measures to decrease the acid-pepsin attack rather than hypothetic schemes for protecting 4 the mucosa or increasing mucosal resistance. Through the years there have been students of the ulcer problem who have been unwilling to accept the validity of the concept enunciated by Schwartz’j in 1910 of “no acid, no ulcer.” Their voices have gradually been stilled as it has become established that chronic peptic ulcer occurs only in association with acid gastric juice. If a patient with peptic ulcer develops persistent achlorhydria spontaneously or after roentgen irradiation or as a result of surgery, the ulcers invariably heal and do not recur until or unless the acid gastric secretion returns.’ This fact has led Wangensteen8 to characterize the concept of “intractable ulcer” as a myth; because if sufficient stomach is removed surgically to produce permanent achlorhydria, the lesions do not recur. This brings us back to the question of why some individuals develop peptic ulcer and others do not. Is the fault one of deficient mucosal resistance or of hypersecretion or are both factors operative? Levin’sgs’O studies have shown clearly that with respect to duodenal ulcer there is a profound increase in the fasting or basal gastric secretion of GSCHWARTZ, K. Ueber penetrierende MaEen und Jejunalgeschwiire. Reitr. 5. k&z. Chir., 67: 96, l
hydrochloric acid. While fasting, normal individuals secrete an average of approximately 680 mg. of hydrochloric acid in twelve hours whereas patients with duodenal ulcer yield an average return of ulcers Kirsner 2,240 mg. In “intractable” and Levin” have found the fasting output of hydrochloric acid to be as high as 6,353 mg. in twelve hours. This hypersecretion, as Dragstedt l2 has shown, is chiefly vagal in origin and can be profoundly reduced by complete bilateral vagotomy; subsequent healing of the ulcer occurs. In gastric ulcer the secretory situation is quite different’” for the output of hydrochloric acid is not greater than that found in normal individuals. Acid gastric juice is invariably present but not in excessive amounts; in fact, there is frequently a definite hyposecretion. It seems evident, therefore, that in gastric ulcer the primary defect is probably one of decreased mucosal resistance arising in some unknown manner: decreased secretion of mucus in a particular area, excessive friability, accidental traumatic mechanical injury of the superficial mucosal cells or some such phenomenon. In the absence of acid gastricjuice such erosions heal promptly; in the presence of acid thyme the regenerative power of the mucosa is still sufficient to bring about healing in the great majority; in a relatively small number peptic digestion transforms the erosion into an ulcer which gradually increases in size and depth. The process may stop at any point for the healing tendency of the mucosa is ever present. Sippy13 considered “the greatest known hindrance to the healing of the peptic ulcer . . . (to be) th e d’lsmtegrating * and digestive action of the gastric juice.” We now know I’ KIRSNER, J. B., LEVIN, E. aid PALMER, W. L. Observations on the excessive nocturnal gastric secretion in patients with peptic ulcer. Gastroenterology, (in press). I2 DRAGSTEDT,L. R. and OWENS, F. M., JR. Supradiaphragmatic section of the vagus nerves in-treatment of duodenal ulcer. Pm. Sot. Exber. Med. & Biol.. 53: 152. 1943. I3 SIPPY, B. W. Gastric and duodenal ulcer: medical cure by an efficient removal of gastric juice corrosion. 7. A. M. A., 64: 1625, 1915.
Editorial that this is the attacking force responsible for the production of the lesion, the stimulus for pain and the cause of failure to heal. The digestive action of the gastric juice depends upon hydrochloric acid and pepsin; it is absent in achlorhydria. The most effective means of controlling the digestive
4-81
attack is by controlling the free acidity. We have not yet found a satisfactory method of control; therein lies the ulcer problem. Intractability would indeed be a myth if complete control could be achieved. \Y.ALTER
LINCOI.~ PALMER, M.D.