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Healing of chronic duodenal ulcers
HEALING OF CHRONIC THEODORE
DUODENAL
ULCERS*
L. BLISS,M.D.
ROCHESTER,
A
MINN.
method by which chronic caIIoused uIcer may hea1. Kennedy9 described a simiIar process of heaIing in an acute duodena1 uIcer in the case of an infant in which signs of meIena neonatorum deveIoped the second day after birth and death occurred on the eighth day of Iife. CayIor described a granuIation bud which was present in the base or under the protecting, overhanging borders in 25 of 30 gastric uIcers in man, which were heaIing at the time the uIcers were resected. Crohn, Weiskopf and Aschner4 aIso described this method of heaIing in chronic peptic uIcers. Stewart’s described a method of heaIing of chronic peptic uIcers which was simiIar to that described by BoIton. He stated that necrotic tissue is an effective barrier to epitheIiaIization and that a cIean base is the prime requisite for the heaIing of chronic peptic uIcer. When heaIing begins the necrotic tissue in the base of the defect sIoughs off and the underIying and surrounding inflammation subsides. A Iayer of epitheIium then grows over the defect from the margin, and from it the mucosa is regenerated and eventuaIIy covers the defect. Stewart14 described the microscopic criteria of the scar of heaIed chronic peptic uIcer as definite and characteristic. Mannll described them in heaIed chronic duodena1 and jejuna1 uIcers which he produced experimentaIIy. There is fibrosis of the muscuIar coats in the area of the scar, which more or Iess compIeteIy repIaces them, depending on the depth of the defect, which extends IateraIIy beyond the defect. There is more or Iess fibrosis of the serosa, and endarteritis and endophIebitis of the bIood vesseIs, even to obliteration of the
FTER Mann and WiIIiamson12 had successfuIIy produced chronic peptic uIcers in experimenta animaIs, they were abIe accurateIy to contro1 the activity and described the method of heaIing. They observed that the process of heaIing begins with the subsiding of the inflammatory reaction around and in the base of the defect, and the sloughing off of the necrotic tissue on the surface of the base. The defect is then covered with a temporary protective Iayer of fibrin beneath which the activeIy proIiferating connective tissue forms a vascular, ceIIuIar, fibrobIastic bud which appears Iike a mushroom in the area of the defect. This granuIation bud is extremeIy friabIe and is easiIy destroyed. As a singIe Iayer of flattened epithelium grows in from the edges of the defect it constricts the base of the granuIation bud at the same time growth is extending up to and over it. A mucous membrane is formed by the proliferation of this Iayer of epithelium and by redupIication it is thrown into folds, which form viIIi. The gIands which regenerate cIoseIy approach in appearance the gIands in the mucosa of the surrounding duodena1 or jejuna1 waI1. As heaIing progresses the staIk of the granuIation bud is progressiveIy constricted, unti1 it is finaIIy pinched off and Iost, and the regeneration of the mucosa continues unti1 the defect is entireIy covered. Mann” observed this course of events in experimenta1 duodena1 and jejuna1 uIcers which were protected and permitted to hea whiIe they were stiI1 in an acute stage; he also observed it in chronic uIcers which were indurated and caIIoused. However, he does not beIieve that this is the onIy
* Abridgment of thesis presented to the FacuIty of the Graduate SchooI of the University of Minnesota in par&I fuIfiIlment of the requirements for the degree of Master of Science in Medicine, June, 1931. Work done in the Section on PathoIogic AnatomS, The Mayo Clinic. 93
94
American
Journal
of Surgery
BIiss-DuodenaI
Iumen, which may or may not be recanaIized. The regenerated mucosa which covers the defect rests directIy on the
UIcers
scopic descriptions of the scar of a heaIed chronic peptic uIcer. A series of chronic duodena1 uIcers,
FIG. I. Beginning heal-ing of a chronic duodena1 ulcer ( X 13).
FIG. 2. HeaIing of a chronic penetrating duodena1 uker (X 12).
base of fibrous tissue, and the muscuIaris mucosae is not regenerated in this area. The connective tissue in the regenerated mucosa is increased, and the gIands and the epitheIium of the mucosa are atypicaL Other observers have given simiIar micro-
which was observed at necropsy, was studied in microscopic sections for evidence of healing. The bud of granuIation tissue, which Mannll and subsequentIy Kennedy, CayIor, Crohn, Weiskopf and Aschner,b and others, described as occurring in a
NEW SERXES VOL. XV, No.
I
BIiss-DuodenaI
heaIing peptic uIcer, was not observed in the sections of the uIcers in this series. Any one of severa reasons wouId expIain
UIcers
American Journal of Surgery
uIcers the bud was destroyed at necropsy, due to handIing, in spite of the care used to prevent it. The granuIation bud was not
FIG. 3. DuodenaI
scar of a chronic
uker
(X
FIG. 4. DuodenaI
scar of a chronic
uIcer
(X 9).
this. The granuIation bud represents one phase of the heaIing process, and in some of the cases death occurred just prior to or subsequent to this phase. Mannll has emphasized the marked ease with which the granuIation bud is destroyed, and since the duodena1 uIcers in this series were not compIeteIy protected, in some of them the bud may have been destroyed prior to or at death. It is aIso possibIe that in some of the
93
15).
seen in one of the uIcers in this series because heaIing was occurring without it. Chronic duodenal uIcer which had ceased to progress and was beginning to heal when death occurred (Fig. I) was found incidentaIIy at necropsy in a man aged sixty-six years. The uIcer was on the posterior waI1 of the duodenum about 3 cm. from the pyIorus. The microscopic section incIuded the margin and sIightIy
96
American Journd
of Surgery
BIiss-DuodenaI
more than haIf of the crater and was cut from the centra1 portion of the uIcer. The crater of the uIcer was not deep and the margin was sIoping, but there were definite pathoIogic changes which denoted chronicity. The base of the defect was composed of connective tissue which had aImost totaIIy repIaced the muscIe coats and extended wider than the Iimits of the defect. The serosa was thickened and there was endarteritis and endophlebitis of the bIood vesseIs. A smaII-sized artery showing the pat.hoIogic changes of endarteritis, and an organizing thrombus were on the surface of the crater. At the margin of the defect the inflammatory process tapered off into the surrounding mucosa and submucosa. In this zone the gIands were activeIy and mitotic figures were proIiferating, seen with a higher magnification. A layer of fibrin covered the protective surface of the crater and indicated the earIiest step in the heaIing of an uIcer after the necrotic tissue had sIoughed off. There were stiI1 many Iymphocytes and some poIymorphonucIear Ieucocytes in the connective tissue base of the crater, the remains of the inflammatory process. A chronic, penetrating duodena1 uIcer, which was in an earIy stage of heaIing when death occurred was situated on the anterior waI1 of the duodenum of a man, aged fortysixty-five seven years. It had perforated days before death. The perforation had been closed surgicaIIy twenty-two hours after its occurrence. The margin of the ulcer was undercut, and the base was composed of a thin Iayer of dense connective tissue which had entirely repIaced the muscIe coats. The centra1 portion of the defect, which at was quite large, had been reinforced operation. SeveraI Iayers of Lieberkchn’s gIands were growing from the margin toward the center of the defect. The gIands were activeIy prohferating, and with higher magnification mitotic figures were seen. The gIands Iay horizontaIIy, and on the surface one end of some of the gIands was open and epitheIium bridged the connective tissue between them, forming rudimentary
UIcers viIIi. A Iayer of Aattened epitheIia1 ceIIs in the form of a syncytium covered the base of the crater nearer the centra1 portion. There were no ceIIuIar remains of the inffammatory process in the base of the crater. Healing in this case was the resuIt of proliferation of the mucosa at the margins directly on a cIean fibrotic base, without the presence of a bud of granuIation tissue. The dense avascuIar fibrous tissue in the base of this crater would not be a fertiIe source for a granuIation bud. In this uIcer satisfactory and permanent heaIing wouId seem questionabIe. A chronic penetrating heaIing duodena1 uIcer which at the time of death was past the stage when a bud of granuIation tissue might have been present (Fig. 2) was noted in the case of a man aged forty-four days after years, who died fifty-three gastroenterostomy had been done for the reIief of symptoms of uIcer. The uIcer was situated on the posterior waI1 about 3 cm. from the pylorus. The microscopic sections were cut through the centra1 portion of the crater and demonstrate the reduction in size that may resuIt from the contraction of the fibrous tissue. The base of the crater consisted of a thin Iayer of connective tissue which had compIeteIy repIaced the muscIe coats and extended beyond the Iimits of the defect. EndophIebitis and endarteritis of the bIood vesseIs, and thickening of the adventitia were noted. The newly forming mucosa which was covering the defect Iay directIy on the fibrous base, and was somewhat macerated before the tissue was fixed. It consisted of ceIIuIar connective tissue which was rich in bIood capiIIaries and was covered by taI1 coIumnar epithelium. The scar of a chronic duodena1 uIcer (Fig. 3) which was situated on the anterior waII of the duodenum about 3 cm. from the pyIorus was found incidentaIIy at necropsy in a man aged thirty-nine years. The site of the uIcer was readiIy recognized. In that area fibrous tissue had compIeteIy repIaced the muscuIar coats, and the serosa was sIightIy thickened. The mucosa, which
NEW SERIES VOL. XV, No.
I
BIiss-DuodenaI
had covered the defect, rested directIy on the thin connective tissue base, and the muscmaris mucosae had been destroyed in this area. The regenerated mucosa contained a reIativeIy Iarger proportion of connective tissue, and gIands which were atypica1. The contour of the duodenum in this section again indicated the effect of contraction of fibrous tissues in reducing the size of the defect. The scar of another chronic duodenal uIcer (Fig. 4) was found incidentaIIy at necropsy in a man aged forty-nine years. This scar was situated on the posterior waI1 of the duodenum about 3 cm. from the pyIorus, and it might we11 be seIected as the optimal end-resuIt of heaIing of chronic duodena1 uIcer. The uIcer appeared as though it might be permanently and thoroughIy heaIed. The site of the uIcer was readiIy recognized by the fibrosis which had repIaced the muscuIar coats, by the thickening of the serosa, by the endarteritis and endophIebitis of the bIood vesseIs in the serosa, and by the absence of the muscularis mucosae. The mucosa at the site of the defect contained more connective tissue than was present in the mucosa and submucosa adjacent to it, and in the newly-formed mucosa the gIands cIoseIy resembIed and yet differed from the glands in the mucosa and submucosa adjacent to it. Many experimental workers have shown that heaIing begins almost CoincidentaIIy with the formation of acute peptic uIcer. There is active proIiferation of the connective tissue, of the gIands, and of the epitheIium at the margin of the defect in an attempt to hea it. Kennedy described such evidence in an acute duodena1 uIcer occurring in an infant. If the factors which are producing the uIcer, whatever they may be, hoId the baIance of power over the attempts of the duodenum or stomach to hea the uIcer, the uIcer wiI1 progress and in the course of time it wiI1 show evidence of chronicity. Deaver and Reimann, Stewart,15 Connor, Hurst, Levine, HorsIey and many others believe that
UIcers
American
Journal
of Surgery
97
chronic peptic uIcer is an acute uIcer which has persisted in an unheaIed state. As a chronic ulcer progresses there is continued connective tissue proIiferation in an attempt to Iimit its extent as we11 as to prevent its perforation. It is undoubtedly true that the baIance of power aIternates between progression and heaIing, so that a chronic uIcer wiI1 begin to hea and then wiI1 become reactivated repeatedIy. Crohn, Weiskopf and Aschner4J have found that uIcers which are resected during the time the patient is free of symptoms show evidence of heaIing, whereas uIcers that are resected when the patients are having symptoms show evidence of progression. It has been the experience of Deaver and Reimann, however, that every chronic uIcer shows evidence of exacerbation and progression regardIess of whether the patient is having symptoms. They expressed the beIief that chronic ulcers wiI1, and do, hea but they have never encountered such as uIcer. Microscopic sections of chronic indurated and caIIoused peptic uIcers with dense fibrous-tissue base and margins and obIiterated bIood vesseIs, cIearIy show how diffrcuIt it is for them to hea with any degree of permanency. However, when they do hea1, many factors aid in the process. The contraction of the fibrous tissue heIps to reduce the size of the defect. The infIammatory process in the margins subsides, and they become ffattened and are drawn cIoser to the base. The inff ammation in the base subsides and the necrotic tissue sIoughs off so that this barrier to epitheIiaIization is removed. The degree of proIiferation of connective tissue in the base during heaIing depends on its type. If the base is dense fibrous tissue with few bIood capiIIaries, it probabIy wiI1 not form a fibrobIastic bud. If, however, it is not dense and does contain a reasonabte number of bIood capiIIaries, it wil1 undoubtedIy proIiferate to form a IibrobIastic bud, such as MannIl and CayIor have described. The gIands and the epithelium at the margin of the crater wiI1 show more
98
American Journal of Surgery
BIiss-DuodenaI
active evidence of prohferation, with many mitotic nucIei, in an attempt to reduce the size of the defect and to cover it with epitheIium either with or without the aid of a granuIation tissue scaffoId. These various factors wiI1 resuIt in compIete heaIing of a chronic uIcer with the formation of a scar if the uIcer is not reactivated. The microscopic criteria of the scar of a heaIed chronic ulcer, which have been so cIearIy described by Stewart,14 wiI1 remain. This microscopic evidence shouId be correIated with the gross appearance of the scar and the secondary changes in the duodenum. Robertson and Hargis described the changes in the duodenum which are secondary to chronic duodena1 uIcer. They in&de shortening to Iess than the norma average of the distance between the pyIorus and the ampuIIa of Vater, the
UIcers formation of pouches in the duodena1 waII adjacent to the uIcer or the scar, and the distortion of the duodenum. SUMMARY
The microscopic appearance of some of the phases which occur in the heaIing of chronic duodena1 uIcer as observed at necropsy is presented. The various factors which aid in the heaIing of chronic duodena1 uIcer, with the exception of the formation of the granuIation bud described by Mann, are ihustrated in microscopic sections. The microscopic criteria of the scar of chronic duodena1 uIcer as described by Stewart are iIIustrated. The part which the gIands of Lieberkiihn may play in the healing of chronic duodenal uIcer is iIIustrated in microscopic sections.
BIBLIOGRAPHY I. BOLTON, C. Quoted by Stewart. 2. CAYLOR, H. D. The healing process of gastric uIcer in man. Ann. Surg., 86: 905-917, 1927. 3. CONNOR, C. L. The etioIogy and pathology of peptic uIcer. Boston M. @ S. J., 195: 971, 1926. 4. CROHN, B. B., WEISKOPF, S., and ASCHNER, P. W. The Iife cycIe of peptic uIcer. At&. Znt. Med., 35: 405-422, 1925. 5. CROHN, B. B., WEISKOPF, S., and ASCHNER, P. W. The healing of gastric ulcers. Arch. Znt. Med., 37: 217-224, 1926. 6. DEAVER, J. B., and REIMANN, S. P. Pathology and treatment of gastric and duodenal ulcer. AM. J. SURG., 3: 333-339, Oct., 1927. 7. HORSLEY. J. S. Pentic uIcer. Proc. Inter-State PostGrad. M. Assemb. Nortb America, 3: 495, 1927. 8. HURST, A. F. Pathogenesis of gastric and duodenal uIcer. Guy’s Hosp. Rep., 74: 413-431, 1924.
g. KENNEDY, R. L. J. Etiology and heahng process of duodena1 uIcer in meIena neonatorum. Am. J. Dis. Cbild., 31: 631638, 1926. IO. LEVINE, S. EtioIogy and pathoIogy of peptic uIcer. Am. J. Med. SC., 172: 22-45, 1926. I I. MANN, F. C. The chemica1 and mechanica factors in experimentaIIy produced peptic uIcer. S. C&z. North America, 5: 753-775, 1925. 12. MANN, F. C., and WILLIAMSON, C. S. The experimenta1 production of peptic uIcer. Ann. Surg., 77: 409-422, 1923. 13. ROBERTSON, H. E., and HARGIS, E. H. DuodenaI uIcer: an anatomica study. M. Clin. North America, 8: Io65-rogz, 1925. 14. STEWART, M. J. The heaIing of gastric ulcer. Brit. M. J., 2: 1164-1166, 1922. of gastric 15. STEWART, M. J. The morbid-anatomy and duodenal uIcer. Internat. Clin., s. 33, 4: 1-13, 1923.
DUODENAL
ULCERS*
L. BLISS,M.D.
ROCHESTER,
A
MINN.
method by which chronic caIIoused uIcer may hea1. Kennedy9 described a simiIar process of heaIing in an acute duodena1 uIcer in the case of an infant in which signs of meIena neonatorum deveIoped the second day after birth and death occurred on the eighth day of Iife. CayIor described a granuIation bud which was present in the base or under the protecting, overhanging borders in 25 of 30 gastric uIcers in man, which were heaIing at the time the uIcers were resected. Crohn, Weiskopf and Aschner4 aIso described this method of heaIing in chronic peptic uIcers. Stewart’s described a method of heaIing of chronic peptic uIcers which was simiIar to that described by BoIton. He stated that necrotic tissue is an effective barrier to epitheIiaIization and that a cIean base is the prime requisite for the heaIing of chronic peptic uIcer. When heaIing begins the necrotic tissue in the base of the defect sIoughs off and the underIying and surrounding inflammation subsides. A Iayer of epitheIium then grows over the defect from the margin, and from it the mucosa is regenerated and eventuaIIy covers the defect. Stewart14 described the microscopic criteria of the scar of heaIed chronic peptic uIcer as definite and characteristic. Mannll described them in heaIed chronic duodena1 and jejuna1 uIcers which he produced experimentaIIy. There is fibrosis of the muscuIar coats in the area of the scar, which more or Iess compIeteIy repIaces them, depending on the depth of the defect, which extends IateraIIy beyond the defect. There is more or Iess fibrosis of the serosa, and endarteritis and endophIebitis of the bIood vesseIs, even to obliteration of the
FTER Mann and WiIIiamson12 had successfuIIy produced chronic peptic uIcers in experimenta animaIs, they were abIe accurateIy to contro1 the activity and described the method of heaIing. They observed that the process of heaIing begins with the subsiding of the inflammatory reaction around and in the base of the defect, and the sloughing off of the necrotic tissue on the surface of the base. The defect is then covered with a temporary protective Iayer of fibrin beneath which the activeIy proIiferating connective tissue forms a vascular, ceIIuIar, fibrobIastic bud which appears Iike a mushroom in the area of the defect. This granuIation bud is extremeIy friabIe and is easiIy destroyed. As a singIe Iayer of flattened epithelium grows in from the edges of the defect it constricts the base of the granuIation bud at the same time growth is extending up to and over it. A mucous membrane is formed by the proliferation of this Iayer of epithelium and by redupIication it is thrown into folds, which form viIIi. The gIands which regenerate cIoseIy approach in appearance the gIands in the mucosa of the surrounding duodena1 or jejuna1 waI1. As heaIing progresses the staIk of the granuIation bud is progressiveIy constricted, unti1 it is finaIIy pinched off and Iost, and the regeneration of the mucosa continues unti1 the defect is entireIy covered. Mann” observed this course of events in experimenta1 duodena1 and jejuna1 uIcers which were protected and permitted to hea whiIe they were stiI1 in an acute stage; he also observed it in chronic uIcers which were indurated and caIIoused. However, he does not beIieve that this is the onIy
* Abridgment of thesis presented to the FacuIty of the Graduate SchooI of the University of Minnesota in par&I fuIfiIlment of the requirements for the degree of Master of Science in Medicine, June, 1931. Work done in the Section on PathoIogic AnatomS, The Mayo Clinic. 93
94
American
Journal
of Surgery
BIiss-DuodenaI
Iumen, which may or may not be recanaIized. The regenerated mucosa which covers the defect rests directIy on the
UIcers
scopic descriptions of the scar of a heaIed chronic peptic uIcer. A series of chronic duodena1 uIcers,
FIG. I. Beginning heal-ing of a chronic duodena1 ulcer ( X 13).
FIG. 2. HeaIing of a chronic penetrating duodena1 uker (X 12).
base of fibrous tissue, and the muscuIaris mucosae is not regenerated in this area. The connective tissue in the regenerated mucosa is increased, and the gIands and the epitheIium of the mucosa are atypicaL Other observers have given simiIar micro-
which was observed at necropsy, was studied in microscopic sections for evidence of healing. The bud of granuIation tissue, which Mannll and subsequentIy Kennedy, CayIor, Crohn, Weiskopf and Aschner,b and others, described as occurring in a
NEW SERXES VOL. XV, No.
I
BIiss-DuodenaI
heaIing peptic uIcer, was not observed in the sections of the uIcers in this series. Any one of severa reasons wouId expIain
UIcers
American Journal of Surgery
uIcers the bud was destroyed at necropsy, due to handIing, in spite of the care used to prevent it. The granuIation bud was not
FIG. 3. DuodenaI
scar of a chronic
uker
(X
FIG. 4. DuodenaI
scar of a chronic
uIcer
(X 9).
this. The granuIation bud represents one phase of the heaIing process, and in some of the cases death occurred just prior to or subsequent to this phase. Mannll has emphasized the marked ease with which the granuIation bud is destroyed, and since the duodena1 uIcers in this series were not compIeteIy protected, in some of them the bud may have been destroyed prior to or at death. It is aIso possibIe that in some of the
93
15).
seen in one of the uIcers in this series because heaIing was occurring without it. Chronic duodenal uIcer which had ceased to progress and was beginning to heal when death occurred (Fig. I) was found incidentaIIy at necropsy in a man aged sixty-six years. The uIcer was on the posterior waI1 of the duodenum about 3 cm. from the pyIorus. The microscopic section incIuded the margin and sIightIy
96
American Journd
of Surgery
BIiss-DuodenaI
more than haIf of the crater and was cut from the centra1 portion of the uIcer. The crater of the uIcer was not deep and the margin was sIoping, but there were definite pathoIogic changes which denoted chronicity. The base of the defect was composed of connective tissue which had aImost totaIIy repIaced the muscIe coats and extended wider than the Iimits of the defect. The serosa was thickened and there was endarteritis and endophlebitis of the bIood vesseIs. A smaII-sized artery showing the pat.hoIogic changes of endarteritis, and an organizing thrombus were on the surface of the crater. At the margin of the defect the inflammatory process tapered off into the surrounding mucosa and submucosa. In this zone the gIands were activeIy and mitotic figures were proIiferating, seen with a higher magnification. A layer of fibrin covered the protective surface of the crater and indicated the earIiest step in the heaIing of an uIcer after the necrotic tissue had sIoughed off. There were stiI1 many Iymphocytes and some poIymorphonucIear Ieucocytes in the connective tissue base of the crater, the remains of the inflammatory process. A chronic, penetrating duodena1 uIcer, which was in an earIy stage of heaIing when death occurred was situated on the anterior waI1 of the duodenum of a man, aged fortysixty-five seven years. It had perforated days before death. The perforation had been closed surgicaIIy twenty-two hours after its occurrence. The margin of the ulcer was undercut, and the base was composed of a thin Iayer of dense connective tissue which had entirely repIaced the muscIe coats. The centra1 portion of the defect, which at was quite large, had been reinforced operation. SeveraI Iayers of Lieberkchn’s gIands were growing from the margin toward the center of the defect. The gIands were activeIy prohferating, and with higher magnification mitotic figures were seen. The gIands Iay horizontaIIy, and on the surface one end of some of the gIands was open and epitheIium bridged the connective tissue between them, forming rudimentary
UIcers viIIi. A Iayer of Aattened epitheIia1 ceIIs in the form of a syncytium covered the base of the crater nearer the centra1 portion. There were no ceIIuIar remains of the inffammatory process in the base of the crater. Healing in this case was the resuIt of proliferation of the mucosa at the margins directly on a cIean fibrotic base, without the presence of a bud of granuIation tissue. The dense avascuIar fibrous tissue in the base of this crater would not be a fertiIe source for a granuIation bud. In this uIcer satisfactory and permanent heaIing wouId seem questionabIe. A chronic penetrating heaIing duodena1 uIcer which at the time of death was past the stage when a bud of granuIation tissue might have been present (Fig. 2) was noted in the case of a man aged forty-four days after years, who died fifty-three gastroenterostomy had been done for the reIief of symptoms of uIcer. The uIcer was situated on the posterior waI1 about 3 cm. from the pylorus. The microscopic sections were cut through the centra1 portion of the crater and demonstrate the reduction in size that may resuIt from the contraction of the fibrous tissue. The base of the crater consisted of a thin Iayer of connective tissue which had compIeteIy repIaced the muscIe coats and extended beyond the Iimits of the defect. EndophIebitis and endarteritis of the bIood vesseIs, and thickening of the adventitia were noted. The newly forming mucosa which was covering the defect Iay directIy on the fibrous base, and was somewhat macerated before the tissue was fixed. It consisted of ceIIuIar connective tissue which was rich in bIood capiIIaries and was covered by taI1 coIumnar epithelium. The scar of a chronic duodena1 uIcer (Fig. 3) which was situated on the anterior waII of the duodenum about 3 cm. from the pyIorus was found incidentaIIy at necropsy in a man aged thirty-nine years. The site of the uIcer was readiIy recognized. In that area fibrous tissue had compIeteIy repIaced the muscuIar coats, and the serosa was sIightIy thickened. The mucosa, which
NEW SERIES VOL. XV, No.
I
BIiss-DuodenaI
had covered the defect, rested directIy on the thin connective tissue base, and the muscmaris mucosae had been destroyed in this area. The regenerated mucosa contained a reIativeIy Iarger proportion of connective tissue, and gIands which were atypica1. The contour of the duodenum in this section again indicated the effect of contraction of fibrous tissues in reducing the size of the defect. The scar of another chronic duodenal uIcer (Fig. 4) was found incidentaIIy at necropsy in a man aged forty-nine years. This scar was situated on the posterior waI1 of the duodenum about 3 cm. from the pyIorus, and it might we11 be seIected as the optimal end-resuIt of heaIing of chronic duodena1 uIcer. The uIcer appeared as though it might be permanently and thoroughIy heaIed. The site of the uIcer was readiIy recognized by the fibrosis which had repIaced the muscuIar coats, by the thickening of the serosa, by the endarteritis and endophIebitis of the bIood vesseIs in the serosa, and by the absence of the muscularis mucosae. The mucosa at the site of the defect contained more connective tissue than was present in the mucosa and submucosa adjacent to it, and in the newly-formed mucosa the gIands cIoseIy resembIed and yet differed from the glands in the mucosa and submucosa adjacent to it. Many experimental workers have shown that heaIing begins almost CoincidentaIIy with the formation of acute peptic uIcer. There is active proIiferation of the connective tissue, of the gIands, and of the epitheIium at the margin of the defect in an attempt to hea it. Kennedy described such evidence in an acute duodena1 uIcer occurring in an infant. If the factors which are producing the uIcer, whatever they may be, hoId the baIance of power over the attempts of the duodenum or stomach to hea the uIcer, the uIcer wiI1 progress and in the course of time it wiI1 show evidence of chronicity. Deaver and Reimann, Stewart,15 Connor, Hurst, Levine, HorsIey and many others believe that
UIcers
American
Journal
of Surgery
97
chronic peptic uIcer is an acute uIcer which has persisted in an unheaIed state. As a chronic ulcer progresses there is continued connective tissue proIiferation in an attempt to Iimit its extent as we11 as to prevent its perforation. It is undoubtedly true that the baIance of power aIternates between progression and heaIing, so that a chronic uIcer wiI1 begin to hea and then wiI1 become reactivated repeatedIy. Crohn, Weiskopf and Aschner4J have found that uIcers which are resected during the time the patient is free of symptoms show evidence of heaIing, whereas uIcers that are resected when the patients are having symptoms show evidence of progression. It has been the experience of Deaver and Reimann, however, that every chronic uIcer shows evidence of exacerbation and progression regardIess of whether the patient is having symptoms. They expressed the beIief that chronic ulcers wiI1, and do, hea but they have never encountered such as uIcer. Microscopic sections of chronic indurated and caIIoused peptic uIcers with dense fibrous-tissue base and margins and obIiterated bIood vesseIs, cIearIy show how diffrcuIt it is for them to hea with any degree of permanency. However, when they do hea1, many factors aid in the process. The contraction of the fibrous tissue heIps to reduce the size of the defect. The infIammatory process in the margins subsides, and they become ffattened and are drawn cIoser to the base. The inff ammation in the base subsides and the necrotic tissue sIoughs off so that this barrier to epitheIiaIization is removed. The degree of proIiferation of connective tissue in the base during heaIing depends on its type. If the base is dense fibrous tissue with few bIood capiIIaries, it probabIy wiI1 not form a fibrobIastic bud. If, however, it is not dense and does contain a reasonabte number of bIood capiIIaries, it wil1 undoubtedIy proIiferate to form a IibrobIastic bud, such as MannIl and CayIor have described. The gIands and the epithelium at the margin of the crater wiI1 show more
98
American Journal of Surgery
BIiss-DuodenaI
active evidence of prohferation, with many mitotic nucIei, in an attempt to reduce the size of the defect and to cover it with epitheIium either with or without the aid of a granuIation tissue scaffoId. These various factors wiI1 resuIt in compIete heaIing of a chronic uIcer with the formation of a scar if the uIcer is not reactivated. The microscopic criteria of the scar of a heaIed chronic ulcer, which have been so cIearIy described by Stewart,14 wiI1 remain. This microscopic evidence shouId be correIated with the gross appearance of the scar and the secondary changes in the duodenum. Robertson and Hargis described the changes in the duodenum which are secondary to chronic duodena1 uIcer. They in&de shortening to Iess than the norma average of the distance between the pyIorus and the ampuIIa of Vater, the
UIcers formation of pouches in the duodena1 waII adjacent to the uIcer or the scar, and the distortion of the duodenum. SUMMARY
The microscopic appearance of some of the phases which occur in the heaIing of chronic duodena1 uIcer as observed at necropsy is presented. The various factors which aid in the heaIing of chronic duodena1 uIcer, with the exception of the formation of the granuIation bud described by Mann, are ihustrated in microscopic sections. The microscopic criteria of the scar of chronic duodena1 uIcer as described by Stewart are iIIustrated. The part which the gIands of Lieberkiihn may play in the healing of chronic duodenal uIcer is iIIustrated in microscopic sections.
BIBLIOGRAPHY I. BOLTON, C. Quoted by Stewart. 2. CAYLOR, H. D. The healing process of gastric uIcer in man. Ann. Surg., 86: 905-917, 1927. 3. CONNOR, C. L. The etioIogy and pathology of peptic uIcer. Boston M. @ S. J., 195: 971, 1926. 4. CROHN, B. B., WEISKOPF, S., and ASCHNER, P. W. The Iife cycIe of peptic uIcer. At&. Znt. Med., 35: 405-422, 1925. 5. CROHN, B. B., WEISKOPF, S., and ASCHNER, P. W. The healing of gastric ulcers. Arch. Znt. Med., 37: 217-224, 1926. 6. DEAVER, J. B., and REIMANN, S. P. Pathology and treatment of gastric and duodenal ulcer. AM. J. SURG., 3: 333-339, Oct., 1927. 7. HORSLEY. J. S. Pentic uIcer. Proc. Inter-State PostGrad. M. Assemb. Nortb America, 3: 495, 1927. 8. HURST, A. F. Pathogenesis of gastric and duodenal uIcer. Guy’s Hosp. Rep., 74: 413-431, 1924.
g. KENNEDY, R. L. J. Etiology and heahng process of duodena1 uIcer in meIena neonatorum. Am. J. Dis. Cbild., 31: 631638, 1926. IO. LEVINE, S. EtioIogy and pathoIogy of peptic uIcer. Am. J. Med. SC., 172: 22-45, 1926. I I. MANN, F. C. The chemica1 and mechanica factors in experimentaIIy produced peptic uIcer. S. C&z. North America, 5: 753-775, 1925. 12. MANN, F. C., and WILLIAMSON, C. S. The experimenta1 production of peptic uIcer. Ann. Surg., 77: 409-422, 1923. 13. ROBERTSON, H. E., and HARGIS, E. H. DuodenaI uIcer: an anatomica study. M. Clin. North America, 8: Io65-rogz, 1925. 14. STEWART, M. J. The heaIing of gastric ulcer. Brit. M. J., 2: 1164-1166, 1922. of gastric 15. STEWART, M. J. The morbid-anatomy and duodenal uIcer. Internat. Clin., s. 33, 4: 1-13, 1923.