Endamoeba histolytica

ENDAMOEBA

HISTOLYTICA

INCORRECT DIAGNOSIS AND TREATMENT A POTENTIAL SURGICAL CATASTROPHE

EDGAR P. HOGAN, M.D., BIRMINGHAM,

EDICINE

F.A.C.S.

ALA.

and surgery and the human race are everIastingIy indebted to the Iarge number of abIe investigators who have contributed to our knowIedge of human amebas and the disease caused by Endamoeba histolytica. In 1873, Loesch, of St. Petersburg, Russia, submitted autopsy fmdings of a case in which during the patient’s iIIness amebas were found in the stoo1. Koch, in 1883, demonstrated motiIe amebas in a Iiver abscess and Kartulis, in 1887, CounciIman and Lafleur, in 1891, confirmed his findings. studied the amebas and the autopsy Iesions of Loesch’s case and stated that they are characteristic of those known to be produced by Endamoeba histoIytica. Authorities agree that there are at Ieast five different species of intestina1 amebas beIonging to four distinct genera. WaIker, in IgI I, stated definiteIy that Endamoeba histoIytica is the onIy pathogenic ameba. Sir Leonard Rogers, in 1903, demonstrated that the earIiest amebic muItipIe abscesses of the Iiver commence in the termina1 branches of the porta vein. McDiII, in 191 I, is that abscesses of the Iiver are not more said : “Wonder frequent because amebas and other bacteria reach the Iiver through the bIood-stream more or Iess constantIy during an intestina1 infection.” PracticaIIy a11 authorities agree that the Iiver becomes infected secondariIy from the infected intestine and that the organisms are conveyed to the Iiver through the porta bIood-stream. Some beIieve that the Iymphatics and the peritonea1 cavity may aIso convey the organisms to the Iiver.

M

498

ENDAMOEBA HISTOLYTICA

199

Musgrave, in 1910, stressed the fact that in a Iarge number of cases of amebic infection possibIy haIf of the patients do not present symptoms of diarrhea or dysentery, but on the contrary constipation. He aIso caIIed attention to the protean symptoms in such cases. His observations have been confirmed by practicaIIy a11 investigators and observers of cases of Endamoeba histoIytica infection. Fitz, of Boston, in 1886, singIed out the appendix as the Iocation of the primary Iesion in most acute affections of the right iIiac region. We are stiI1, however, confronted with the fact that the cecum is the predominating Iocation of the infection in some cases producing symptoms and physica and Iaboratory findings which are identica1 with those produced by an infection having its origin in the appendix. MortaIities occur, even in the apparentI!: uncompIicated operative case. It is recognized by surgeons generaIIy that the mortaIity in appendicitis is greater than it shouId be, and that purges shouId not be given to a patient with suspected appendicitis. It is known that there shouId be an earIy diagnosis and prompt operation. Factors that contribute to prevent the earIy diagnosis and operation have been discussed by many surgeons. For years, and especiaIIy recentIy, cases have been reported in which deaths have foIIowed abdomina1 surgica1 operations in which Endamoeba histoIytica infection was shown postoperative and at autopsy to be the cause of death. The writer beIieves that Endamoeba histoIytica infection has been and is the insidious cause of many unaccountabIe medica and surgica1 deaths.

APPENDICITIS

CAUSED

B‘I- ENDAMOEBA

HISTOLl-TICA

INFECTION

McDiII stated in 191 I that “the appendix does not seem to pIay the expected rbIe during intestina1 amebiasis, but many of our cases of chronic appendicitis date from an amebic dysentery, and it has Iong been suspected that Iatency in such

500

EDGAR

P. HOGAN

appendices was perhaps responsibIe for recurrent attacks of amebic coIitis, and aIso perhaps might expIain the Iiver abscesses that occur without discoverabIe Jesions in the boweI, and without any recent history of dysentery, the so-caIIed primary infection of the Iiver. The gross appearance of some of these appendices is a peritonea1 redness from vascuIar injection, with a simiIar zone spreading from the base of the appendix over the surface of the cecum. In spite of the utmost care a11good specimens of these appendices were unfortunateIy ruined for microscopica examination for parasites.” Musgrave, iti 1910, reported the autopsy findings of 3 cases of amebiasis with death from peritonitis foIIowing perforation of the appendix. The perforation of two of them was produced by amebic uIceration, the other by an unknown cause, not amebic. This case shows that a patient with Endamoeba histoIytica infection in the coIon may have an attack of appendicitis not of amebic origin. Lenz, in I 9 I 0, reported one case of appendicitis in amebic dysentery. The appendix was removed, but as far as the report shows, was not examined to determine whether or not amebas were present. Le Roy des Barres, in 1912, reported 3 cases of appendicitis occurring in conjunction with or foIIowing amebic dysentery. Vives, in 1918, stated that true appendicitis may occur in acute dysentery, uIceration of the appendix giving rise to the cIinica1 symptoms of appendicitis. The condition is usually first revealed at necropsy. Lund and Ingram in 1933 reported 4 cases of Endamoeba histoIytica infection. One had typica symptoms and Iaboratory findings of acute appendicitis in which diarrhea was not present unti1 the day foIIowing the operation. Postmortem microscopic examination of the uIcers of the bowe1 reveaIed Endamoeba histoIytica infection. In one case expIoratory Iaparotomy and appendectomy were performed. At autopsy the Iarge intestine was found to be greatIy distended with masses at the cecum, transverse coIon and rectum, sights of Iarge uIcerations. The uIcerated areas showed many amebas. The third patient of Lund’s series is unusuaIIy interesting.

ENDAMOEBA

HISTOLYTICA

501

About July 28, he began to feel tired and feverish and to have a headache. There were no abdomina1 symptoms. The temperature was 102"~. and the Ieucocytes 8000. This condition continued for two weeks when he began to have diarrhea-three or four movements a day. Three days later he had a sudden severe pain in the abdomen and right shouIder with spasm of the entire abdomen and tenderness in the right lower quadrant. Two days later he was taken to a hospita1. The Ieucocyte count was 25,000. A barium enema showed moth-eaten irreguIarities of the cecum and ascending colon. August 19 an abscess in the right Iower quadrant was drained. August 24 a right subphrenic abscess was drained. The patient died August 26. The autopsy showed a Iarge abscess in the right Iobe of the Iiver. The Iiver sections mereIy showed chronic suppurative inflammation. The Iiver abscess waI1 was honeycombed and ragged in appearance. Microscopic examination of recta1 uIcers and the appendix showed invasion by Endamoeba histoIytica, with accompanying ceIIuIar infiItration.

Weinberger, in 1934, reported a case of appendicitis with typica symptoms of an acute attack. The appendix was removed promptIy and the folIowing day the patient deveIoped diarrhea. On stoo1 cuIture BaciIIus dysenteriae was found more than ten days Iater, and about thirty days after the initia1 attack Endamoeba histoIytica was found in the stoo1. Lynch says, “amebic appendicitis is a natura1 extension from the coIon and is usuaIIy continuous with amebic uIceration of the caecum, aIthough it has been reported as occurring independentIy of neighboring ceca1 uIceration.” In the study of some thousands of appendices removed at operation he has never recognized an amebic appendicitis, aIthough amebas have been found in the Iumen. Dr. A. A. Johnson says, “I have seen one patient in CounciI BIuffs, Iowa, whose appendix was removed, the patient went home and returned Iater to the hospita1 with perforation and death within twenty-four hours after admission. The Iaboratory examination by me showed the patient to be infected with Endamoeba histolytica.” Harrison reported a case in which a clinical diagnosis of carcinoma of the colon was made. On operating the hepatic fIexurc, the ascending colon and the first part of the transverse coIon were found to be invoIved in an inAammatory tumor mass. An iIeostomy was

502

EDGAR

P. HOGAN

done and the appendix removed. The appendix showed amebic uIceration. After operation Endamoeba histoIytica was found in the stooI. The patient died and no autopsy was obtained. Asher and Kraemer, in reporting 3 cases of Endamoeba histoIytica infection observed in private practice in New Jersey, found that an earIy appendectomy had been performed on two of them without reIief of symptoms. Dr. James E. Thomas, Second SurgicaI Division, The RooseveIt HospitaI, New York, permits me to report an unpubIished case of his : Case No. B34342g, Second SurgicaI Division, RooseveIt Hospital, New York City. Miss V. L., aged eighteen years, actress. This patient was admitted to RooseveIt HospitaI on August 14, 1934, compIaining of pain in the abdomen, nausea and vomiting. Her past history was essentiaIIy negative aIthough she had had severa attacks of right Iower quadrant pain during the past two years but nothing Iike the present attack. She was aIways constipated and resorted to enemas rather than cathartics for reIief. Her diet has always been IiberaI, but due to her profession she had aIways eaten in hoteIs and restaurants. IncidentaIIy, she had been on the stage since the age of seven. Present Illness: About seven days ago, she began to compIain of gas in the abdomen, which was associated with miId degree of discomfort. However, it did not necessitate confinement to bed. After three days the pain became so severe that she was forced to go to bed. It was associated with genera1 maIaise and she beIieves that she had some fever. The night before admission, because of her constipated state, she was given miIk of magnesia. Two hours Iater she had her first bowel movement which rapidIy deveIoped into a diarrhea and during the remainder of the night she was at stoo1 aImost continuaIIy. The pain in the abdomen increased steadiIy in intensity and became associated with nausea and vomiting. Physical examination, on admission, reveaIed an acuteIy III young gir1, recumbent posture, with thighs flexed on abdomen. Head and neck negative. Teeth in good condition. Tongue coated. Breath fetid odor. Chest and Iungs cIear throughout. Heart of normal size, rate and rhythm. No murmurs. PuIse 120; respiration 22. Abdomen sIightIy distended. There was a definite resistance to the paIpating hand over the whoIe right Iower quadrant, with a suggestion of a mass. Palpation over the whoIe Iower abdomen was excruciatingly tender, with point of maximum intensity over McBurney’s point. Rebound tenderness everywhere.

ENDAMOEBA

HISTOLYTICA

Laboratory Findings: Urine yellow, cloudy in appearance, acid reaction. gravity 1.018, trace of albumin. No red bIood ceIIs in urine; no white bIood cells. No casts. BIood findings: u-. B. c. 13,650, polynuclears Specific

89 per cent, mononucIears

minutes.

Diagnosis of acute made,

and operation Gas, oxygen,

1934.

per cent. BIeeding

I I

time three and one-haIf

appendicitis, performed

about

its base

inffammatory three

times

process

was essentiaIIy

but

the

which

its norma

of the ceca1 gIands,

extend

moderate

the

peritoneum

tube,

coIon, fifth

the

Aaxseed

of soft, watery,

where there

in a bottIe

stooIs

serosanguinous

in nature.

The

the peritoneum

appendix

was removed

was and

The

muscles

a

The

ant1 fascia

were

bIack siIk to the skin. Time one-haIf

days

postoperativeIy,

Her abdomen

this time, pouItices

her distention and

enemata.

time

was kept

She

n-as obtained,

in aImost

associated before

dying

On the

the

same

and the material nature,

day, she started

stooIs. On the eighth sis stooIs,

her

ascending

brow-n fIoccuIent

postoperative

with a

death,

hand.

showed

constantIy

was of the same thin watery

and on the day of death

a moderate

and entire

temperature

rather

by means

considerabIe

to the paIpating

the

and had thirteen

passed

unti1 one hour

resistance

distended.

and seemed

was attacked

over the cecum

postoperatively

temperature

daJ- postoperativeIy

brown fecal return that

the

was moderately

backache

fou1 odor. On the seventh

with a real diarrhea August

four

was definite

days

with an extremeIy thirteen

was

pain and severe

From

but a recta1 tube

coIIected

and an

ileum. There

drainage.

was soft and onIy tender

and sixth

range

first

During

dea1 of ffatus.

abdomen

two or

was a considerable

from the ceca1 waI1 for biopsy.

of gas and finaIl>- on the fourth

amount

there

incision,

The

interrupted

of wound

toxic and drowsy.

great

without

103.8” and 101.4’.

She compIained

amount

in an acute

and about

fair.

During

ranged between

of recta1

for some infiI-

coIon.

was removed

was cIosed

except

was invoIved

limited to the cecum itseIf and did not

located.

with pIain catgut,

Course:

14,

the terminal

the usua1 McBurney

pathoIogy

hour; condition:

was

on August

out into its mesentery

fluid,

was entireIy

sized gIand

sutured

extending

gIands about

up aIong the ascending and

cIotting

IOO’F.

IocaI peritonitis,

normal

cecum

In addition,

of free peritoneal

reaction

Procedure: Through opened

was

admission,

its waIIs indurated

thickness.

of the mesenteric

amount

entire

made

enIargement inflammatory

probabIy

two hours after

enlargement a sIight

with

by rectum

ether was given.

Pathology: The appendix tration

time three minutes,

Temperature

day, she had

at g:o$

P.M.

on

23.

On the Iaboratory

fourth

day

postoperativeIy,

for examination

and cuIture

her first but

stoo1 was sent

it was not

to the

unti1 the eighth

so4

EDGAR

P. HOGAN

postoperative day, August 22, that Amoeba histolytica was discovered and was confirmed on subsequent stools. No encysted forms were found and cuhures were negative for any of the forms of baciIIary dysentery. Another interesting finding was a compIete lack of gross blood or mucus in feces at any time throughout the entire course of her iIIness. On August 22, immediateIy foIIowing the discovery of Amoeba histoIytica, I C.C. of emetine hydrochIoride was given subcutaneousIy. On August 23, grain N was given intramuscuIarly. Sigmoidoscopic examination on August 23 reveaIed typical uIcers, at the base of which the amoebas were found. On August 22, foI1owing early circuIatory coIIapse, 500 C.C. of titrated blood were given by the indirect method which was foIlowed by distinct improvement in her general condition and on August 23, when circuIatory collapse again set in, a continuous infusion of saIine with 3 per cent gIucose was instituted which was continued until shortIy before her death.

The preoperative findings in a case operated on by me in Ig 14 were typica of an acute case of appendicitis. The operative findings, the technique of the operation and the postoperative treatment were as usua1 in simpIe appendectomies. The patient did we11 for five days, after which, he, a man thirty-three years of age, a HiIIman Hospital case, began to have intestina1 hemorrhages. He grew progressively worse and died on the seventh postoperative day. An autopsy was performed by Dr. George S. Graham. The findings reported by him are so typicaIIy characteristic of the pathoIogy of Endamoeba histoIytica infection, involving the cecum, Iiver and appendix, they serve IargeIy the purpose of a discussion of the pathoIogy of Endamoeba histoIytica infection. In the right iIiac fossa there was an abscess that was partiaIIy walled off from the general peritonea1 cavity. It contained pus and a smaI1 amount of feca1 material. It appeared to center about an area of perforation in the waI1 of the cecum. On the surface of the cecum there was a recent appendectomy wound. It appeared to be cIean, with norma repair in progress. The mesenteric Iymph nodes were sIightIy enIarged, usuaIIy reddish and occasionaIIy hemorrhagic. The appearance of the cecum was striking. It presented numerous uIcers from 0.5 to 3 cm. in diameter, with soft, necrotic, overhanging waIIs and a centra1 cavity fIIIed with a yeIIowish, or, at times, black, geIatinous materia1. The margina intact mucosa was often extensiveIy undermined, and neighboring uIcer cavities appeared in some cases to be connected by fistuIous tracts extending Iaterally in the deeper IeveIs of the waI1 beneath bridges of intact mucosa. In some cases the undermined

ENDAMOEBA mucosa

HISTOLYTICA

of the large ulcers hung as ragged

or the necrotic a poIypoid

tissue of the uIcer cavity

mass adherent

by a pedicIe to the excavated

tive process

had involved

many

the

cases

appeared formed

inner

to have

the intestina1

muscuIar

been

Section

or even

communicated

through

one of the

undermining

and

destroyed,

at least in part.

so as to form

waIIs. The uIcera-

to varying

was exposed,

depths.

In

occasionaIIy

it

the

serosa

In an uIcer situated

4 cm.

valve there had been compIete

waII. This perforation the right iIiac fossa. characteristic

structures

coat

invaded,

the floor of the uIcer,

below the ileocecal

masses from the uIcer margins,

may have separated

so that

perforation

with the

abscess

of the bowel

already

numerous

uIcers

of the

of the mucosa,

whose

divided

noted

cecum

in

reveaIed

edges partially

covered a cavity fiIIed with faintIy stained tissue debris. The cavity extended IateraIIy

in the submucosa,

progressive more

invoIvement

central

floor consisted

of tissue destruction to infection, mensurate amebas

and toward

the middle part of its Aoor showed

of the outer

coats.

and the resuhing

there

was a surprising

exposure

appeared

found in numbers reaction.

They

in tissues

occurred

Considering

of the subepitheIia1

in other uIcerative

to excite showing

no Ieucocytic

spaces

tissues

reaction

com-

conditions.

The

response,

Iittle or no evidence

in the tissue

the

the amount

Iack of any Ieucocytic

with what wouId be expected

themseIves

In some of the sections,

only of the serosa.

and were

of inAammatory

and frequentIy

in the dilated

Iymph vessels. Only rarely could they be found in the smaIIer blood vessels. The

margina

fibrin

tissues

deposit.

of the

This

floor. Here,

also, there

noteworthy

that

the

cell

leucocytes

of the cecum

showed

The and

appendix

dehydrated

ragged

area

cumference

numerous

invoIving

smalIer

and

of a narrow

uIcers

underlying

and upper submucosa.

The

red ceIIs and ceIIuIar of amebas.

the

the

of fibrin

of the

but it is

lymphocyte.

sections

the

serous

and Ieucocytes,

prominent.

cross

one-quarter downward

of the circuIar

with

a varying Here

cavity

No amebas

the

extending

debris,

mingIed

of the There

of the

inner

irreguIarIy muscuIar

fixed was a cir-

through

Iayer.

There

degree

of destruction

of

tendency

was toward

the

deepIy

Iumen of the appendix

The amebas

section

in diameter.

cm.

about

tissues.

uIcer

1.2

extending

to the inner margins

production

numbers

swoIIen,

measuring

waI1.s and

epitheIium

cytes,

aIways

became

serosa

infiltration,

some

exudate

Ieucocyte

was markedIy

of ulceration

the submucosa were

In

a considerabIe

exposed

Ieucocytic

rare.

a recent

showed

the serosa.

specimen

of the

often in the

was almost

were

and here the poIymorphonucIear were found outside

cavity marked

was a considerable reacting

PoIyrnorphonucIear surfaces

abscess

was especiaIIy

into

the

mucosa

was f3Ied with Ieuco-

with which were considerable

were found in greatest

numbers,

however,

EDGAR

P. HOGAN

immediateIy on the margins of the uIcer cavities. They were present aIso, sometimes in abundance, in the gIanduIar crypts adjacent to the active ulcers; immediateIy beneath intact stretches of epitheIium; and in the connective and Iymphadenoid tissues in the immediate neighborhood of uIcer cavities. They often contained engIobed red bIood cells. The amebas were usuaIIy free in tissue spaces, but in many cases they appeared within the Iumens of diIated Iymph vesseIs. They appeared to excite no reactive inflammatory changes. The uIcer margins usuaIIy showed marked fibrin deposits. In the deepest part of the two Iargest cavities there was active poIymorphonucIear exudation into the cavity and throughout the underIying tissue, where the inflammatory process extended in a wide sector outward to invoIve the muscuIar coat. Here, the intravascular and perivascuIar spaces often showed abundant poIymorphonucIear Ieucocytes. The bIood vesseIs were everywhere diIated and engorged, and there was frequent interstitia1 hemorrhage. SmaII thrombi were frequent. The congestion and hemorrhage became especiaIIy marked at the mesenteric attachment and in the mesenteric tissue itseIf. The serosa showed in some areas we11 marked poIymorphonucIear infiltration, and there was an exudate of fibrin and Ieucocytes on the peritonea1 surface. The Iymph sinuses were diIated and contained numerous lymphocytes, occasional endotheIia1 Ieucocytes and, at times, moderate numbers of red bIood ceIIs. The embedding fibrofatty tissue showed, in pIaces, extensive hemorrhage with considerabIe fibrin deposit and active Iymphocytic infiItration. The centra1 portion of one node was hemorrhagic, and the stroma ceIIs showed weII-marked degenerative changes. CIumps of bacteria were present totiard the centra1 part of the area, and there were numerous poIymorphonucIear Ieucocytes, some of which were breaking up. The liver weighed 2,080 gm. Between the upper surface of the right Iobe and the under surface of the diaphragm there was an abscess cavity 5.3 cm. in diameter, containing a thick red-stained puruIoid material. The cavity extended downward into the Iiver substance to a depth of 4 cm. Here its waII was covered by a soft, yeIIowish, ragged Iayer of fibrin and necrotic tissue, and showed, on section, a surrounding zone of deepIy congested Iiver substance averaging I cm. in width. Deep within the right Iobe was a second abscess cavity of simiIar appearance, 4 by 5 cm. in diameter. In generaI, the cut surfaces of Iiver tissue were reddish brown, the markings sIightIy obscured. The gaI1 bIadder was fiIIed with dark green biIe. Its ducts were patent. Sections through the waI1 of an abscess showed an abrupt erosion of the Iiver tissue associated with a minimum of Ieucocytic reaction and a variabIe amount of fibrin formation. The abscess waI1 was irreguIar, with sharply cut outward extensions of the main cavity, apparentIy of recent origin, whiIe on the other hand there were frequent penin-

ENDAMOEBA HISTOLYTICA

407

s&s of more or less necrotic tissue projecting from the wall outward into the cavity. Here was an expIanation for the ragged appearance presented by the waII in gross. The cavity contained degenerating ceIIular materia1 and debris. Leucocytes were present in very moderate numbers. There were considerable numbers of amebas. Occasiona forms showed two nuclei. They occurred particuIarly aIong the margins of the degenerating Iiver tissue, and occasionaIIy could be found in the superficia1 IeveIs of the more intact parenchyma, where they appeared to lie in the space between the endotheIia1 waII of the sinusoids and the ceIIs of the Ever cords. The eroding process did not invoIve the tissues of the porta cana to more than a sIight degree, but occasiona amebas occurred in the tissue spaces and lymph vesseIs of the connective tissue of the porta canaIs forming portions of the wall of the abscess cavity. The Iiver tissue in the zone surrounding the cavity showed marked concentric flattening of the parenchymat tissues, with diIated and injected sinusoids and more or Iess extensive pressure atrophy of the Iiver ceIIs. The anatomic diagnosis was: amebic colitis with perforation of ceca1 uIcer; abscess of right iliac fossa and generahzed acute peritonitis; amebic abscesses of the liver; sIight puImonary congestion and edema, with possible earIy bronchopneumonia; chronic splenitis; oki adhesive pIeuritis, and recent appendectomy.

The fact that John B. Murphy in the Iate ’80s pIeaded for prompt interference in perityphhtis is evidence that there must have been good reason for Dupuytren, 1827, and others insisting that the cecum was the origin of right iIiac inflammatory masses with accumuIations of pus. They insisted on designating the primary pathoIogy in the right iIiac region by the terms typhihtis and perityphhtis. As we now know Endamoeba histoIytica produces ceca1 uIcers, more extensive pathoIogy of the Iarge bowel and appendicitis, and that right iIiac abscesses are formed in cases that are not operated on as we11 as in cases operated on even at the present time, it is reasonabIe to concIude that such cases existed in much Iarger numbers in the earIy days of abdomina1 surgery than at the present time. The autopsy findings in jo cases reported by Musgrave in 1910, the patients having died of other diseases or compIications of Endamoeba histoIytica infection and in which there

EDGAR

508

P. HOGAN

was no diarrhea and Endamoeba histoIytica infection was not diagnosed, are frequentIy referred to in the Iiterature. TweIve of the deaths and surgica1 compIications were due to Endamoeba histoIytica infection. Thirty-eight of the patients were distinctIy medica cases but the deaths were doubtIess IargeIy due to the primary Endamoeba histoIytica infection with Iesions in the Iarge bowe1. Characteristic amebic Iesions were present at autopsy in a11of the 50 cases. These cases proved the insidious nature of Endamoeba histoIytica infection. Such cases are not onIy potentia1 surgica1 catastrophes, they are aIso potentia1 medica catastrophes. ENDAMOEBA

HISTOLYTICA

GRANULOMAS

OF

THE

LARGE

BOWEL

Gunn and Howard reported 3 cases of granuloma of the Iarge bowe1 caused by Endamoeba histoIytica infection, and caIIed attention to the simiIarity of Endamoeba histoIytica granuIomas to maIignant tumors of the Iarge bowe1 and that the symptoms, physica signs and radioIogic appearance in such cases may be identica1 with those produced by carcinoma. Diagnosis of carcinoma was made in the 3 cases. Recovery foIIowed resection in one case. They have seen severa instances in which amebiasis and carcinoma were present at the same time. KartuIis reported a case of Endamoeba histolytica infection in which the waI1 of the Iarge bowe1 reached the thickness of 22 cm. Four cases showing massive thickening of the ceca1 waI1 were reported by Runyon and Herrick. Harrison reported a case with a cIinica1 diagnosis of carcinoma of the coIon. The hepatic ffexure, ascending coIon and the first part of the transverse coIon were found at operation to be invoIved in an inflammatory tumor mass. IIeostomy and appendectomy were performed. There was amebic uIceration of the appendix. Endamoeba histoIytica was found in the stoo1 after operation. The patient died and no autopsy was obtained. Cope says when the inflammation caused by the Endamoeba histoIytica is subacute, the tissue reaction may be considerabIe, and great

ENDAMOEBA

HISTOLYTICA

$09

edema and swelhng of the bowe1 waII resuIt. Such sweIIing may be evident on paIpation through the abdomina1 waI1 and may cause errors in diagnosis. Lasnier reported severa cases in which paIpabIe abdomina1 tumors were present in Endamoeba histoIytica infection which disappeared under treatment. James and Deeks reported a case in which infiItration had nearIy cIosed the Iumen of the transverse coIon and a cIinica1 and roentgen diagnosis of a maIignant growth was made. Endamoeba histoIytica on repeated examinations of the stoo1 in two hospitaIs in the Canai Zone were not found. Operation for carcinoma was advised but refused. Endamoeba histoIytica was found in the stoo1 three weeks Iater for which the patient was treated with compIete disappearance of the tumor. Two other cases, one invoIving the cecum and the other the sigmoid, cIeared up under treatment. Desjardins reported a case of Endamoeba histoIytica infection resembIing cancer which cIeared up under medica treatment. Through the kindness of Dr. Frank WiIson the foIIowing case report is incIuded: L. S. Jr., Past years

aged thirty-nine.

History.

Usual

diseases

ago. In auto accident

past three

or four years

and on, with constipation.

X-rays

TonsiIIectomy

in October,

December,

days of June,

1932.

1933. Stopped

Present Illness.

digestive

were negative

doctor

childhood.

Appendectomy

ago. Fracture

Began

disturbances:

sIight

Temperature pIained

eIevation IOI’F.

for any gastrointestina1

Went

to Chicago

Was

JuIy

Vincent’s

to St.

Iast ten

and diarrhea

g, had severa

pains in abdomen

Fair

home JuIy 2, 1933.

to have pain in abdomen

of temperature.

HospitaI

JuIy

4,

pain in abdomen bIoody JuIy

stools. Com-

IO.

and diarrhea-six

to eight

hours.

Physical examination

was essentially

ness over right side of abdomen, mum tenderness

disorder.

WorId’s

at HoteI C. Returned

sent

off and

1932, who could find no organic trouble.

Was

of severe cramp-Iike

stooIs in twenty-four

For

gas, hyperacidity

1933. Was seen by Dr. Frank WiIson JuIy 6. Had diarrhea, and

fifteen

of both patelIae.

has had much pain in right side of abdomen

considerable

seen by another

of

five years

negative,

just above oId McBurney

to right flank. Temperature

except for marked

with some muscle incision

spasm.

Point

tenderof maxi-

scar and extending

IOO’, puIse go, respirations

20,

out

urine essentiaIly

510

EDGAR

P. HOGAN

negative, W.B.C. 28,000, Iymphocytes IO per cent, poIymorphonucIears go per cent, R.B.C. 4,700,ooo. X-rays JuIy IO. Barium enema entered coIon unobstructed reveaIing norma rectum and sigmoid. Descending coIon spastic. SpIenic Aexure in norma position. There is fiIIing defect at junction of dista1 and middIe one-third of transverse colon. Hepatic ffexure is normal. There is Iarge flIing defect in cecum and proxima1 one-third of ascending coIon suggestive of tumor. The cecum is fairIy movabIe with marked tenderness on pressure. Upon ffuoroscopic examination the fiIIing defects produced by muItipIe poIypoid tumors within the Iumen of cecum and coIon couId be easiIy seen upon pressure over this area. Patient continued to have four or five stooIs in twenty-four hours. No macroscopic bIood. Great dea1 of pain in abdomen, particuIarIy in right Iower quadrant. JuIy 12: W.B.C. 41,000, Iymphocytes 7 per cent, Iarge monocytes 2 per cent, poIynucIears 91 per cent. JuIy 13: W.B.C. 45,050, Iymphocytes 5 per cent, poIynucIears g5 per cent; feces occuIt bIood, no amebas found. July 14: feces examined, same. July 15: feces examined, same; W.B.C. 29,350, lymphocytes 8 per cent, large monocytes 2 per cent, poIynucIears go per cent, R.B.C. 3,970,000, hemogIobin 76 per cent. Operation. Patient was operated on, after consultation with Drs. E. M. Mason, S. L. Ledbetter and Magruder. In view of negative stoo1 findings and positive x-ray, diagnosis of carcinoma of cecum and transverse colon was made. Through a low midIine incision, cecum was paIpated and tumor mass easiIy made out. TerminaI iIeum was cut across about 8 inches from iIeoceca1 vaIve and dista1 end cIosed in usua1 manner. ProximaI end was then brought over to sigmoid using Rankin clamp and end-to-side anastomosis was done between proximal end of iIeum and sigmoid. An enterostomy was then done higher up on iIeum bringing tube out through smaI1 Ieft rectus incision. Abdomen cIosed without drainage. Patient showed some improvement for about one week, temperature and W.B.C. faIIing. Enterostomy tube drained we11 but came out on eighth day. On tenth day midIine incision broke down and began draining feces. Patient became graduaIIy worse and died on thirteenth postoperative day. Autopsy by Dr. Geo. S. Graham: Permission Iimited to abdominal examination. The body is that of a white man fairIy we11 nourished. There is a recent Iaparotomy wound and incision is limited to sIight extension of this wound upward. There is a recent enterocoIostomy. When slight traction is made upon the invoIved bowe1, the wound margins separate wideIy and the Iigatures are found to have puIIed through the softened bowe1 tissue. A Iarge amount of thin yeIIow intestina1 contents pours out of the bowe1 Iumen. The Iigated termina1 iIeum is tightly cIosed. The waI1 of the entire Iarge intestine is markedIy friabIe so that it tears readiIy when

ENDAMOEBA

HISTOLE’TICA

traction is put upon it in removaL The smaII intestine and stomach are free of lesions. When the large bowel is opened the mucosa is found to be extensively uIcerated in its whoIe Iength from cecum to rectum. Some uIcers are smaI1 and superficia1, there are patches of yeIIow necrosis invoIving the whole depth of the mucosa but the usua1 Iesion is a Iarge irreguIarIy outIined excavation with overhanging margins and deep floor formed by the submucosa or muscular coats and in a few pIaces by the serosa. In the cecum and ascending coIon there are three deep ulcers that completely perforate the bowe1 waI1 as this is seen after removal. They were covered inside mereIy by a thin deposit of fibrin binding them to adjoining structures. From the margins of some of the uIcers there depend Iong masses of soft dark gray or bIack necrotic tissue. In many parts of the bowe1 there are onIy wideIy scattered isIands of surviving mucosa. No gross changes were found on inspection of the viscera other than the bowe1. The organs were not removed. Fresh preparations made from the bowe1 surface showed the presence of Endamoeba histoIytica and these were seen aIso in eosinhematoxyhn stains. Anatomical Diagnosis: Amebic coIitis. Recent enterocolostomy. Additional Microscopical Description: Sections were taken from a number of areas in the coIon. They show uIcers of varying stage of deveIopment. with more or Iess deep excavation of intestina1 wall. In the infIammatory exudate of the uIcer cavity there are many amebas and they are found aIso wandering outward in the waI1 where they are often present in Iarge numbers. There is typica Iack of inff ammatory reaction in the invaded tissue. In some of the sections there is weII-developed peritoneal exudate.

The foIIowing case was diagnosed and treated by Dr. W. H. Beddow: Mr. R. B., aged forty-four, had practicaIIy always been in good hearth. In rg33 he visited Chicago and stopped at HoteI C., but onIy drank water there. Bloody diarrhea with severe cramping abdomina1 pain deveIoped ten days after the Chicago visit, at first four to five moments daiIy, which increased to eight or ten. Mucus and bIood in the stoo1 were present. Under pahiative treatment the symptoms disappeared in about a week. Endamoeba histolytica infection was not diagnosed at this time. He then took an extensive trip in the Southwest and within a short time the dysenteric and abdomina1 symptoms returned, accompanied by great weakness and exhaustion. These attacks of weakness and exhaustion were thought to be due to a cardiac condition. On his return to Birmingham he consuIted Dr. Beddow. Proctoscopic examination was made which reveaIed

EDGAR

512

P. HOGAN

mceration of the lower bowe1 from which a smear or scraping was obtained for examination. Microscopic examination of this smear and of a warm stoo1 specimen, examined by Dr. George S. Graham, revealed numerous amebas in motile form. The patient was sent to St. Vincent’s HospitaI and emetine, I gr. hypodermicahy, was given daily for tweIve days. Diet of bIand cereaIs onIy. After acute abdomina1 and recta1 symptoms subsided enemas of aIum and gIycerine in water were given. FoIIowing the initia1 emetine treatment stovarso1, 4 grs. t.i.d. by mouth for ten days, was given; Iater anayodin, 4 grs. t.i.d. by mouth bi-weekIy. Patient was in the hospita1 four weeks. After Ieaving the hospita1 weekIy administration of I gr. of emetine hypodermicaIIy aIternating with anayodin 4 gr. t.i.d. were given. Numerous tests of bowe1 excreta since the patient Ieft the hospita1 have been negative. The Iast examination was made November 20, 1934.

Simon, says: “Th e more typical of recta1 uIcer presents a deepIy punched out appearance with ragged overhanging edges. In the vast majority of individuaIs who harbor Endamoeba histoIytica no visibIe evidence of the infection can be found by rectal examination.” McDiII reported perirecta1 abscesses in which motiIe amebas were found. ACUTE

HEPATITIS

AND

ABSCESSES

OF

THE

LIVER

Acute hepatitis was recognized by earIy observers and investigators as being of frequent occurrence in amebic infection. Rogers, in 1gog and 1910, presented vaIuabIe papers on hepatitis and abscesses of the Iiver of amebic origin, stressing the symptoms, diagnosis and treatment of each. He stated that the vast majority of patients that came into the hospita1 with an abscess of the Iiver gave a history of fever with or without pain in the hepatic region for severa weeks and not rareIy for severa months. They had usuaIIy been given quinine and other drugs without avai1, the true nature of the disease onIy becoming apparent with an increased prominence of the Iocalized symptoms. There was uniformly a high Ieucocytosis in acute hepatitis which persisted in cases that deveIoped into liver abscesses. He caIIed attention to the marveIous effect of ipecac and in 1912 of emetine in preventing acute hepatitis deveIoping into Iiver abscesses and said that no case admitted

ENDAMOEBA

HISTOLYTICA

$13

to the hospita1 with acute hepatitis in which this treatment was used had deveIoped a Iiver abscess. He warned against aspiration and operation on Iiver abscess cases in the earl) acute stage and advocated aspiration for deveIoped amebic Iiver abscesses and the immediate treatment of the patient with ipecac and beginning in 1912 with emetine. The emetine treatment aIone sufficed in a Iarge number of amebic abscess of the Iiver. In aspirated cases he injected a soIution of quinine dihydrochIoride, IO gr. to the ounce. He stated that 86 per cent of the abscesses were infected onIy with ameba. In cases of a mixed infection he advocated open operation and drainage. Herrick, in 1910, presented a paper on abscesses of the Iiver before the CanaI Zone MedicaI Association in which he anaIyzed 47 cases which in the main were treated in the Ancon HospitaI, CanaI Zone, Panama, during the previous two years. This paper, aIthough pubIished twenty-five years ago, furnishes authoritative information on the diagnosis, prognosis and treatment of Iiver abscesses. The mortaIity of his series of cases was 23.4 per cent. There were, however, 12 deaths in 13 cases of his series in which dysentery was present before or deveIoped immediateIy after the operation. This record shows the seriousness of operating on a patient in whom there is Endamoeba histoIytica infection. If emetine had been in use at the time Herrick doubtIess wouId have given it before and after operating. He stated that the Iocation of the abscess of the Iiver in the majority of cases can be made out and that one haIf of them must be reached through the chest at the point of eIection in the Iower axiIIary region. in discussing Gessner’s paper, stated that he NoIand, beIieves that: Herrick’s

results were Iargely due to the fact that he abondoned

tory aspiration

of the Iiver transpIeuraIIy

He gave up aspiration of the

number

abscesses many

IargeIy because

of secondary

pIeura1

into the pIeura1 cavity,

cases

muItipIe

abscesses

explora-

far earIier than did most surgeons. of two compIications: infections

and second,

were missed.

foIIowing

because

First,

because

Ieakage

from

of the fact that

His adoption

of exploratory

in

5’4

EDGAR

P. HOGAN

Iaparotomy with carefuI paIpation of the entire Iiver was, I think, a distinct advance. Herrick was abIe to demonstrate immediateIy the exact Iocation of either singIe or muItipIe abscesses. It was then a simpIe matter to cIose the abdomen and to approach the abscess accurateIy if it was in the dome of the Iiver. NoIand beIieves that the method of handIing the pIeura in dome drainage cases had much to do with the exceIIent end resuIts. Herrick earIy gave up any attempt to suture the pIeura, and instead of this he went through the diaphragm making a fairIy free incision, grasped the edge of the diaphragm and brought it up and sutured it to the intercosta1 muscIes before the abscess was opened.

In 191 I McDiII made the foIIowing statement: “The most striking proof of this passing of dysentery, in ManiIa at Ieast, is that the Iiver abscess compIication formerIy so frequent is rareIy encountered now and then onIy in negIected cases.” This he attributed to the advent of pure drinking water and to better public understanding of the fact that the cause is taken in by the mouth. He advocated the transpIeura1 operation for aspiration and drainage of Iiver abscesses. He made a curviIinear incision in the anterior or posterior axiIIary Iine from the ninth rib to the eIeventh and resected the tenth rib and cIosed over by suture the area of the resected rib. The incision was made just beIow the resected portion of the tenth rib, the pIeura being eIevated and the peritonea1 cavity was entered through the diaphragm which was sutured to the intercosta1 muscIes. The greatest care was exercised during the procedure to prevent air entering the pIeura1 cavity. It seems that most cases operated on by McDiII had formed adhesions which he beIieved was the ruIe. When adhesions had not formed, he packed the cavity and aspirated Iater, or if indicated waIIed the point of aspiration off with gauze, and if pus was Iocated by aspiration immediate drainage was provided. McDiII did not give his mortaIity in such cases. Cort, in reporting 530 cases of Endamoeba histoIytica infection, caIIed attention to the fact that 97 had hepatic invojvement with definite Iiver abscess deveIopment in 17. He confirmed Rogers’ findings in that treatment with emetine brought about ameIioration and reduction in the size of the

ENDAMOEBA HISTOLYTICA

515

liver within two to four days. “So specific,” said he, “do we consider this action that we have used emetine as a therapeutic test in doubtfu1 cases of inflammation of the Iiver in which the history and microscopic observations are negative. If after three days of treatment there is not a definite reduction in the size of the Iiver and a great ameIioration of symptoms, we beIieve that an abscess due to Endamoeba histoIytica can be ruIed out.” Of the 97 cases there was onIy one death. In some of the cases Iiver duIIness extended from the seventh intercosta1 space to beIow the umbiIicus and to the Ieft Costa1 cartiIages. In onIy 2 cases was more than one aspiration done. In one of these there was a tendency to reIapse and in the other the abscess had ruptured into the pIeura1 cavity. The case of the patient that died was comphcated by cardiorenal disease with ascites. Diagnosis was made too Iate in this case and no emetine was given. The series of 19 cases of abscess of the liver reported by BoIand, with a mortaIity of 33.7 per cent, is most interesting from the standpoint of thorough study, diagnosis and medica He used a11 means of diagnosis, and surgica1 treatment. abdomina1 and transpIeura1 drainage, and instituted emetine treatment in diagnosed amebic abscess cases both before and after operation. In pyogenic abscesses he stated that the usua1 operative procedure shouId be carried out in two stages as in operating upon Iung abscess. If this ruIe had been foIIowed consistentIy in his series he thinks probabIy 2 deaths wouId have been avoided. The criticism which BoIand made of his own operative technique is extremeIy vaIuabIe. It may be, as he stated, the determining factor in the prognosis. In 6 patients the approach to the Iiver was through the abdomina1 waI1 and in 6 by rib resection. The pIeura was incised in 3 patients, once accidentaIIy with a fata outcome. This point in the technique of the transpIeura1 operation is aIso of the greatest importance, as forcibIy emphasized by Herrick in 191 o and by McDiII in 191 I. Two stages were empIoyed in 3 cases, an area being isoIated by adhesions for the opening of the abscess

516

EDGAR

P. HOGAN

twenty-four hours later. LocaI anesthesia was used. Of the 14 amebic cases there were 5 deaths, mortahty 35.7 per cent. There were 5 patients with abscess due to pyogenic organism with 2 recoveries, a mortahty of 60 per cent. The 5 cases of pyogenic Iiver abscess with mortaIity of 60 per cent show cIearIy that patients with Iiver abscesses due to Endamoeba histoIytica and pyogenic organisms associated offer a very unfavorabIe prognosis as was emphasized by Major C. C. Spencer, Professor of MiIitary Surgery, RoyaI Army MedicaI CoIIege, CaIcutta, India, in Igog and by many others. Spencer says the great majority of amebic abscesses are steriIe when first opened. The patient does we11 the first few days after operation and then infection occurs. The temperature goes up again and death from septic poisoning sIowIy but sureIy foIIows. With the improvement in surgica1 technique it is doubtIess true that secondary infections do not so frequentIy occur as when Spencer made his observation. Gessner anaIyzed g6 verified cases of amebic ibscess of the Iiver in the Charity HospitaI of New OrIeans from 1918 to 1932 with a mortaIity of 39.58 per cent. He correctIy states that surgeons are interested in earIy diagnosis and effective treatment. Diagnosis, he says, is based on a Iarge and tender Iiver, usuaIIy attended with fever and Ieucocytosis. There may be chiIIs, jaundice, pain in the shouIder, a history of antecedent diarrhea or dysentery. X-ray fiIms show an eIevated right Ieaf of the diaphragm, with the angIes cIear. He reviewed the different methods of treatment of Iiver abscess and he referred to Leonard Rogers’ report of 2661 cases in 1922 treated by open operation between 1893 and 1907 with I 3 I I deaths, a 56.7 per cent mortaIity. Rogers stated that after the change from open operation to aspiration and washing out with I :5oo quinine suIphate soIution and Iater without irrigation in a series of I I I cases there were onIy 16 deaths, a mortaIity of 14.4 per cent. A pupi of Rogers, K. K. Chathrji, is quoted by him as reporting 186 Iiver abscesses treated by aspiration qnd emetine, combined with irrigation of the cavity through the

ENDAMOEBA

HISTOLYTICA

417

aspirating needIe with the remarkabIy Iow mortaIity of 1.6 per cent. Matas stated that during the period I 884-1909 a tota of 536 cases of abscess of the Iiver were treated in the Charit HospitaI, New OrIeans, with an average genera1 mortality of 40 per cent. He referred to 79 cases of abscess of the Iiver under his persona1 care. The mortaIity in the earIy years was about 40 per cent. After 1898 it graduaIIy decreased unti1 in Iater years it feI1 to 13 and IO per cent. This improvement he attributes to the earIy diagnosis of the primary coIonic infection and its better treatment, to the better type of patients and to the immense benefit of medication with emetine which has sufficed in severa cases to cure the abscess with the aid of simpIe and repeated aspiration. In j cases reported by Lund, Iiver abscesses were found in 2 cases postmortem. In the g cases diagnosed earIy and treated by Ikeda, the Iiver was enIarged in one case. In May 1933, Ikeda encountered a case of Iiver abscess rupturing into the with metastatic puImonary and cerebral pIeuraI cavity, abscesses, and termina1 emboIic abscesses in the spIeen and the waI1 of the smaI1 intestine, in which the onIy demohstrable primal->- amebic Iesion in the coIon was represented by a smaI1 infected diverticuIum Iocated in the sigmoid, though the stooIs contained at times Endamoeba histoIytica in Iarge numbers and activeIy motiIe. This case is an exampIe of a chronic amebic carrier who had never experienced any intestina disorders but succumbed to a widespread systemic In one of Simon’s cases presenting heaIed compIication. hepatic abscess he was abIe to trace the amebic invasion back forty-three years. with or without a history of Brown says any patient, diarrhea, who begins to compIain of pain in the upper right abdomina1 quadrant and who has an irreguIar fever and IeucocJ-tosis, must be suspected of having a hepatic abscess. Hasty surgica1 interference in such a case is attended by high mortaIity, as has been attested to in the past few months.

518

EDGAR

P. HOGAN

Lynch says the occurrence of an apparentIy primary Iiver abscess shouId Iead to investigation of the stoo1 and intestine, no matter what the geographic origin of the case may be. The foIIowing is quoted from a persona1 Ietter from Dr. Car1 F. Jordan, Director of CommunicabIe Diseases, of Iowa: Dr. AIdis A. Johnson, of CounciI BIuffs, Iowa, caIIed attention to an unusua1 number of xases of Endamoeba histoIytica infection originating at Pacific Junction, Iowa. “I know of two cases,” he said, “from this community that had Iiver abscesses, one operated in Omaha and died, one is now Iiving.” A case operated on by Dr. J. M. Mason is of interest. This patient, Miss V. G., a young white schoo1 gir1, aged fifteen, was admitted to HiIIman HospitaI JuIy 25, 1930 after having been sick for eight days. IIIness began with epigastric pain, cramping in character, nausea and vomiting. She had a chiI1 the second day of her iIIness and in the morning and afternoon of .the third day. Vomiting had been more frequent during the forty-eight to seventy-two hours before admission to the hospita1. Physicai examination was negative except for pain in the epigastrium. No rigidity. Leucocyte count 19,400, neutrophils 85 per cent. This patient was studied thoroughIy by the MedicaI Service and referred to the SurgicaI Service after the Iiver had been aspirated and about 2 C.C. of thick pus had been obtained. Microscopic and cuItura1 examination of the pus was negative. Dr. Mason examined the patient the day the pus was obtained by aspiration and made the diagnosis of abscess of the Iiver and operated. He did the Herrick and McDiII operation. Pus was Iocated about 2 inches from the surface of the Iiver. The abscess was opened and drained with one rubber tube and rubber tissue. The aspirated pus on microscopic examination and cuIture was negative. Smears of the Iiver abscess waI1 were positive for Endamoeba histoIytica. The patient was immediateIy put on emetine treatment, I gr. daiIy hypodermicaIIy for tweIve days. She made an uneventfu1 recovery. LABORATORY

EXAMINATION HISTOLYTICA

AND

DIAGNOSIS

OF

ENDAMOEBA

INFECTION

Those who have read Magath’s paper on the Iaboratory diagnosis of amebiasis reaIize the great importance and the

ENDAMOEBA

complicated thoroughIy Endamoeba

technique in reaching histoIytica

HISTOLYTICA

519

which may have to be carried out a decision that a patient has or has not infection.

The differentiation of Endamoeba histolytica from other amebas should be attempted only by those qualified by specia1 training and experience. Unfortunately, at the present time comparativeIy few clinical pathologists and technicians heve received adequate training in this field. NO one shouId be considered satisfactoriIy quahfied unIess he or she has received adequate training under a qualified instructor. The conclusive diagnosis of amebiasis depends on the demonstration of Endamoeba histoIytica in the stool, discharges or tissues of the suspected person. A negative report, however, does not necessarily mean absence of infection with Endamoeba histoIytica.

Professor

Lemierre

says :

The diagnosis is not so diffIcuIt as it appears at first. One cannot count on discovering pathogenic amebas other than in cases of typica intestinal amebiasis. The discovery of a hyperIeucocytosis with neutrophil poIynucIeosis wiI1 be of great aid in distinguishing febriIe hepatitis, without characteristic IocaI symptoms, from maIaria, typhoid or paratyphoid fever, tubercuIosis and undulant fever. But the strongest proof of the amebic nature of the symptoms, when their character permits onIy a supposition, is the specific action of treatment with injection of emetine. In the apparently hopeIess cases, emetine works wonders, estabIishing thus, at the same time, the diagnosis. On the slightest suspicion therefore, the physician should not hesitate to institute an emetine test treatment, which wiI1 be harmIess if it has no curative effect. The onIy thing that one need fear is faiIure to recognize amebiasis when it presents itseIf. X-RAY I keda

EX_4MIN_4TION

AS

AN

AID

IN

DIAGNOSIS

says :

The roentgen appearance of the colon varies considerabIy, depending In the earIiest stages no appreciabIe upon the stage of the infection. changes are noted. Later, fine saw-tooth projections which probabIy represent smaI1 superficia1 uIcerations may deveIop aIong the walls. Fine feathery or thorny fiIIing defects on the indurated waIIs signify a Iater stage of the Iesion in which the submucosa and muscuIaris are invoIved in an extensive inff ammatory process. During the subacute or earIy chronic stage roentgen examination reveaIs a somewhat characteristic deformity of the cecum and

$20

EDGAR

P. HOGAN

ascending coIon with an apparent shortening or contraction of the bowe1 waII and induration and fiIIing defects of varying degree. On the institution of emetine treatment these changes rapidIy disappear. When the Iesion is sharpIy IocaIized and Ieads to obstruction it may be confused with cancer of the bowe1, but such confusion is not IikeIy in cases of advanced Iesions which are diffuse and extensive. X-ray examination of the coIon in amebic dysentery is of vaIue more as a guide to treatment than a means of positive diagnosis. It constitutes a positive means of determining the Iocation, extent, and degree of the invoIvement.

In Iiver abscesses the fiIms and Auoroscopic views usuaIIy show the diaphragm eIevated on the right side. In advanced cases it may be fixed and the Iiver density may be increased. BoIand says : Sometimes it seems diffIcuIt to determine whether the pathoIogy is beIow or above the diaphragm. A IateraI thoracic roentgenogram shouId aIways be taken. It brings out the compIete curve of the diaphragm, and seIdom faiIs to differentiate between disease beIow and above the muscle. In some cases both such pathoIogica1 conditions may co-exist.

The pathoIogy may appear to be onIy above the diaphragm and may be interpreted as due to tubercuIosis as in a case recentIy reviewed by the writer. Autopsy showed a Iarge Iiver abscess with extensive abdomina1 and Ieft thoracic invoIvement. INCIDENCE

Various IocaI and institutiona surveys have been made, especiaIIy since the WorId War by various investigators in order to ascertain approximateIy the incidence of Endamoeba histoIytica as a Iumen dweIIing or infective human parasite. StiIes and Boeck found the incidence to be 4. I per cent in more than 8000 persons examined. The Freshman class of the University of PennsyIvania had an infestation of the same percentage. The specia1 committee that investigated the recent Chicago epidemic stated that the incidence is possibIy 3.9 per cent. Others state that the percentage is higher. The surveys

ENDAMOEBA

HISTOLYTICA

$21

made in this country, in France and in EngIand indicate that the incidence of the infestation or infection in the three countries is about the same. The reported cases of Endamoeba histoIytica infection and deaths caused by this organism for the years 1932, 1933 and for six to eight months of 1934 were received by the writer from the heaIth departments of 45 states. In 1932 there were 730 cases reported with 188 deaths; in 1933 there were I 982 cases reported with 248 deaths ; in 1934, first six to eight months, there were 1585 cases reported with g3 deaths. The mortahty of 25.7 per cent in 1932, 12 per cent pIus in 1933 and 58 per cent the first six to eight months of 1934 is remarkabIe in that the reduction is no doubt due to the fact that the profession has recentIy been on the Iookout for cases of Endamoeba histoIytica infection, and cases have been more promptIy diagnosed and treated. It is most important that this intense interest in the diagnosis and treatment of Endamoeba histoIytica infection be continued and that a11 possibIe means of preventing the infection be instituted and used. If this is done Iives wiI1 be saved and surgery wiII be immenseIy benefited because an infection with this organism in a surgica1 case if undiagnosed and treated may be the cause of the patient’s death, even though at the time of the operation there was every reason to expect an uneventfu1 recovery. It should not be necessary for the symptoms, physica and laboratory findings, and possibIe pathology produced by Endamoeba histoIytica to be considered in the picture of a surgical case. TREATMEKT The subject of the treatment of amebiasis-Endamoeba histoIytica infection, has recentIy been fuIIy discussed Reed. He says:

by

Surgical compIications are not at a11 uncommon. Proper treatment rests on early diagnosis especiaIIy before or at the time of surgical intervention in the abdomen. Intensive emetine treatment is to be avoided before operation because of the danger of weakening the myocardium.

522

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CarefuI diagnosis wiII often decide whether a moderate course, not to exceed 5 or IO grains of emetine, shouId be given or whether the emetine shouId be begun immediateIy before or after operation. OnIy good cIinica1 judgment with dear recognition of the possibiIity of amebic Iesions in the absence of discovering amebas in the stoo1 wiI1 enabIe the physician to decide on wise therapy. We must have in mind the frequency with which amebic Iesions simuIate peptic uIcer, choIecystitis, perforation, appendicitis, gangrene, new-growth and the extreme danger of operations invoIving the gastrointestina1 tract when amebic Iesions are present and untreated. In this group of surgica1 compIications emetine is the drug of choice because of quickness of action, to be foIIowed at the earliest safe moment by carbarsone. . . . SurgicaI compIications may appear earIy in a first acute attack or Iate in cases insuffIcientIy treated. They may aIso be discovered unsuspected at operation or operation may be done without recognition of Endamoeba histoIytica infection or under a wrong or incompIete diagnosis. James and others have advised wide-open cecostomy and thorough irrigations through the cecostomy and through the rectum as weI1. It is found to be very effective in the acute fuIminating types and aIso in the chronic types that did not yieId to treatment. DougIas Smith, of San Francisco, strongIy advocates cecostomy.

Kraemer and Asher suppIement the emetine treatment with a course of vioform, gr. 4 in capsuIes t.i.d. for ten days, repeated at intervaIs of one week, one month, and three months, even though the patient is free from symptoms. PREVENTION

Endamoeba histoIytica infection has, does and will continue to exist just to the extent that human beings take into the intestina1 tract through the mouth or in any way food, water or anything which is contaminated with human excreta. The prevention of the infection is an educationa1, pubIic heaIth, sanitary engineering, and buiIding and pIumbing probIem. The source of potabIe water must not onIy be free from contamination, but it must be conveyed to the consumer free of contamination. Any water for human consumption must be absoIuteIy free from contamination with human excreta. If this is done, and each individua1 is taught the importance of and practices what is necessary in the way of using soap and

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water frequently for cIeansing the hands and if food is free from contamination, the means of becoming infected by the Endamoeba histoIytica organism wiI1 be reduced to the vanishing point. With the present recognition of the importance of the disease, it is reasonabIe that there wiI1 be continuous united effort on the part of the medica profession and citizens generaIIy to protect the peopIe from this insidious disease. Such work is truIy preventive medicine and surgerv. IMPORTANCE

OF

AUTOPSIES

The importance of autopsies is indicated by the folIowing quotations from Ietters received recentIy from state heaIth departments : I. No deaths were reported in which surgical operation was performed. In the case of Mr. M. R. on whom an operation was performed the nature of the disease was not determined at the time of the operation nor at the time of death but was determined from pathoIogica1 specimens after attention was caIIed to the possibility of the infection from the Chicago outbreak. 2. So far as our records show acute surgical conditions were diagnosed in 5 instances (Endamoeba histoIytica infection) and were foIIowed by operation. Three cases terminated fatally. AI1 were in our 1933 series. 3. In 1933 there were 9 reported deaths due to Endamoeba histoIytica infection in 4 of whom operations were performed. 4. One death has been reportecl recentIy for the current year. This patient had a choIecystectomy on JuIy 28. Subdiaphragmatic abscess was opened on August 7 and the patient died August 24 after a rather stormy period. The diagnosis of amebiasis was made at autopsy. Another case recentIy reported had a Iiver abscess opened and a diagnosis of amebiasis made three days Iater. This patient is recovering. 5. Male, aged forty-seven, died June 7, 1933.Amebic dysentery one or two years. Amebic abscess of brain two or three months. Amebic abscess of liver eight to ten months. May 3, 1933admitted to hospita1. May I:, 1933, E. histoIytica found in stoo1 specimen. May 28, 1933 operation for Iiver abscess performed. 6. MaIe, aged fifty-nine, died October 25, 1933, first symptoms JuIy 15, 1933. October 24, 1933, admitted to hospita1. October 25, 1933 operation for intestinal obstruction performed. November 18, 1933 gross examination

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EDGAR P. HOGAN

of jejunum revealed, muItipJe abscessing ulcers, undoubtedly caused by E. histoIytica even though organisms were not found in microscopic sections. 7. About a year ago a patient became ilI after having visited Chicago. An operation for appendicitis was performed and the patient died. Endamoeba histoIytica infection was suspected but carefu1 study of the appendix faiIed to discIose the amebas. CONCLUSIONS I. From the practica1 experience of surgeons and autopsy findings there is decisive evidence that a patient may have an acute, subacute or chronic abdomina1 condition in which an operation is or seems to be indicated and yet the symptoms, physica findings, Iaboratory and x-ray findings may be due entireIy to Endamoeba histoIytica infection, or a compIication of the infection. It may not be possibIe during the Iife of the patient or unti1 Iate postoperativeIy to prove that the patient is infected with Endamoeba histoIytica. If there is a suspicion of such an infection in a surgica1 case the patient shouId be given emetine promptly. In some cases if this treatment is postponed unti1 the organisms can be demonstrated the opportunity for the therapeutic effect of emetine may be Iost and possibIy aIso the Iife of the patient. 2. Up to the present a very high percentage of patients with intestina1 pathoIogy due to Endamoeba histoIytica infection that were operated on died. In most of these patients who died the rea1 cause of death was not known and wouId not have been known if an autopsy had not been heId. 3. It is of the greatest importance that autopsies be secured. The vaIue of the information obtained therefrom cannot be overestimated. 4. Endamoeba histoIytica infection is the probIem of pubIic heaIth agencies, of the citizens generaIIy, and of medicine and surgery. AI1 can contribute to the prevention of deaths due to this cause, by: (a) The pubIic heaIth agencies and the citizens generaIIy can see to it that the known means of preventing the disease are instituted and used.

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$24

(b) The medica and surgica1 profession in cooperation with pathoIogists and laboratory workers can use a11 means for the correct earIy diagnosis and proper treatment of infected cases. In suspected cases where the laboratory cannot prove that the infection does or does not exist some authorities state, and the writer thinks wiseIy, t.hat the emetine test which may be the first step in the cure of the patient shouId be used promptly. 3. It is agreed by authorities that most cases of acute hepatitis of amebic origin respond to emetine treatment and do not go on to abscess formation. Some authorities state that even Iarge amebic abscesses foIIowing the emetine treatment do not. have to be drained and get weI1. If the emetine treatment hypodermicaIIy and aspiration and irrigation when indicated, as advocated by Rogers, secure the remarkabIe resuIts that he reports and that have been reported by Cort, Cathrji and others, it is a remarkabIy good method of treatment. ,4 case of suspected or diagnosed amebic abscess can be given the emetine hypodermicaIIy both as a therapeutic test and for a curative purpose. Aspiration or operation can be performed when indicated if the patient does not respond satisfactoriIy to the emetine treatment. Amebic abscesses of the Ii\-er, promptIy diagnosed, timeIy and appropriateIy operated on, treated immediateIy with emetine hypodermicaIIy and given the proper postoperative care, resuIt in a comparativeIy low mortaIity, as shown in cases operated on and treated in this way by a number of surgeons. TimeIy and appropriate surgery with emetine treatment and the proper postoperative care may decide the question of Iife or death Authorities agree that pyogenic abscesses for the patient. shouId be drained by an open operation at the point of IocaIization, and that this shouId be done earIy and appropriateIy. REFERENCES I. CRAIG, C. F. Unrecognized infections in the production of carriers of pathogenic organisms. J. A. M. A., 77: 827 (Sept. IO) 1921. 2. BOKH, W. C., and STILES, C. W. Bull. 133, Hyg. Lab., U. S. P. H. S. 1923, p. 12.

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3. MUSGRAVE, W. E. Pbilippine J. Science, s. B. 5: 220, rgro. 4. KAPLAN, B., WILLIAMSON, C. S., and GEIGER, J. C. Amebic

dysentery

in Chicago.

J. A. M. A.; 88: 977 (March 26) 1927.

9. IO.

II.

12. 13. 14. ‘5. 16.

WILLIAMS, C. S., KAPLAN, B., and GEIGER, J. C. A survey of amebic dysentery in Chicago. J. A. M. A., ga.: 528 (Feb. 16) rg2g. CHIC, C. F. The amebiasis probIem. J. A. M. A., 98: 615 (May 7) 1932. JOHNSTONE, H. G., DAVID, M. A., and REED, A. C. A protozoa1 survey of one thousand persons. J. A. M. A., IOO: 728 (March I I) 1933. CRAIG, C. F. The symptomoIogy of infection with Endamoeba histoIytica in carriers. J. A. M. A., 88: Ig (Jan. 21) 1927. TONNEY, F. O., HOEF~, G. L., SPECTOR, and KAPLAN, B. The threat of amebiasis in the food handler. J. A. M. A., IOI: 1638 (Nov. 18) 1933. BUNDESEN, H. N., RAWLINGS, I. D., and FISHBEIN, W. L. The heaIth hazard of I amebic dysentery. J. A. M. A., IOI: 1636 (Nov. 18) 1933. LUND, C. C., and INGHAM, T. R. Four fata cases of unsuspected amebiasis: preIiminary report of one aspect of the recent Chicago epidemic. J. A. M. A., IOO: 1720 (Nov. 25) 1933. COUNCILMAN,W. T., and LAFLEUR, H. A. Amebic dysentery. Jobns Hopkins Hosp. Rep., 2: 393, 1891. RILEY, W. A. Protozoa1 infestation of ex-service men in Minnesota. J. A. M. A., 92: 1661-1662 (May 18) 1929. EditoriaI. Further evidences of the distribution of intestina1 amebas. J. A. M. A., 102: 934 (Mar. 24) 1934. CRAIG, C. F. The epidemioIogy of amebiasis. CIinicaI lecture at CIeveIand session. J. A. M. A., 103: 1061 (Oct. 6) 1934. SIMON, S. K. The cIinica1 diagnosis of amebiasis. CIinicaI Iecture at CIeveIand session. J. A. M. A., 103: 1063 (Oct. 6) 1934.

17. WEINBERGER, H. L. Dysentery. J. A. M. A., 102: 916 (March 24) 1934. 18. MCCOY, G. W., and CHESLEY, A. J. ControI of amebic dysentery. CIinicaI Iecture at

CIeveIand session. J. A. M. A., 103: 1145 (Oct. 14) 1934. M. Prolonged inffuences and complications of intestina1 amebiasis. CIinicaI Iecture at CIeveIand session. J. A. M. A., 103: I 147 (Oct. 13) 1934. MELENEY, H. E. The pathoIogy of amebiasis. CIinicaI Iecture at CIeveIand session. J. A. M. A., 103: 1213 (Oct. 20) 1934. MAGATH, T. B. The Iaboratory diagnosis of amebiasis. CIinicaI Iecture at CIeveIand session. J. A. M. A., 103: 1218 (Oct. 20) 1934. REED, A. C. Treatment of amebiasis. CIinicaI Iecture at CIeveIand session. J. A. M. A., 103: 1224 (Oct. 20) 1934. CORT, E. C. Amebiasis of the Iiver. J. A. M. A., go: 205 (June 23) 1928. GUNN, H., and HOWARD, N. J. Amebic granuIomas of the Iarge bowe1. J. A. M. A., 97: 166 (JuIy 18) rg3r. SUMERLIN, H. S. Amebiasis: incidence in private practice. J. A. M. A., 102: 363

19. LYNCH, K.

20. 21. 22. 23. 24. 25.

(Feb. 3) 1934. BUNESDEN, H. N., TONNEY, F. O., and RAWLINGS, I. D. Outbreak of amebiasis in Chicago during 1933: sequence of events. J. A. M. A., 102: 367 (Feb. 3) 1934. 27. Report of Special Committee on Chicago Epidemic: Amebiasis outbreak in Chicago. J. A. M. A., 102: 367 (Feb. 3) 1934. 28. LEMIERRE. Amebiasis in Paris. J. A. M. A., 103: 1079 (Oct. 6) 1934. 29. ROGERS, L. The prevention and treatment of amebic abscess of the Iiver. Pbilippine J. Science, s. B. 5: 21g-228, rgro. 26.

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30. MCDILL, J. R. TropicaI infections of the derivatives of the primitive gut: their complications and treatment. Surg., Gynec. Obst., 13: 523-557 (Nov.) 191 I. 37. BROWN, P. W. Amebic dysentery: diagnosis and treatment. Proc. Sta$ Meetings Ma.yo Clin., 25: 262, 1933. 32. IKEDA, K. Roentgenological observations of the colon in amebic dysentery. Abstr. Surg. Gynec. Obst., 59: 405-406 (Nov.) 1934. 33. GESSNER, H. B. Abscesses of the liver. Am. J. Surg., 20: 683 (June) 1933. 34. BOLAND, F. K. Abscesses of the Iiver. Ann. Surg., 94: 766 (Dec.) 1931. 35. HERRICK, A. B. Abscess of the liver. Surg. Gynec. Obst., 5: 472 (Nov.) 19x0. 36. AYNESWORTH, K. H. Abscess of the Iiver, chronic form. Am. J. Surg., LO: 672 (June) 1933. 37. KRAEMER, M. and ASHUR, M. Amebic dysentery and the genera1 practitioner in New Jersey. Repr. from J. M. Sot. New Jersey, 1934. 38. HOGAN, E. P. Appendicitis caused by Endamoeba histoIytica. J. A. M. A., 75: 727 (Sept. II) 1920. DISCUSSION

DR. J. S. HORSLEY, Richmond, Va.: I wish to report a case of the same type as described in Dr. Hogan’s paper. Miss A. B., aged seventeen, had been ill with diarrhea for six weeks before entering the hospita1. Numerous examinations of stooIs failed to show amebae, and there was no history of contact with amebae. She had been given, however, a smaI1 amount of emetine, and a transfusion of bIood. Three days after admission to the hospita1 there were symptoms of distention, pain, and increased temperature and p&e rate, with muscIe spasm, that appeared to indicate perforation of some hoIIow viscus. She was operated upon as an emergency March 19, 1934. There was apparentIy general peritonitis. Most of the termina1 iIeum was swoIIen, covered with lymph Aakes, and rather doughy. The cecum and ascending colon appeared normaI. There was no definite perforation in the iIeum, though because of the Iymph flakes and sweIIing it was diffIcuIt to determine any actua1 area of perforation. The termina1 iIeum was resected, with an end-to-side union of the iIeum to the cecum. It was then observed that there was apparently some Ieakage from the upper portion of the abdomen, and a search showed a perforation on the under surface of the transverse coIon. This was sutured. There was very IittIe exudate about the perforation. An enterostomy was done, and drainage was instituted. The patient died five days after the operation. Necropsy showed genera1 peritonitis and adhesions. There was Ieakage of fecal matter from around the sutured perforation, and there were many abscesses in the Ioops of bowe1. The anastomosis of the iIeum to the cecum was in good condition. The ascending, transverse and descending coIon were opened and showed Iimited areas of necrosis and ulceration. The sigmoid and rectum showed superficia1 uIcerations scattered throughout,

528

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P. HOGAN

but most of the tissue was normaI, the Iargest ulceration being not more than about 0.5 cm. in diameter. HistoIogic examination of the areas of the coIon showed Endamoeba histoIytica imbedded in the bowe1 waI1. The case is interesting because of the inability of the Iaboratory to demonstrate Endamoeba histoIytica after numerous examinations, because of marked invoIvement of the Iower iIeum, and the finding of the endamoebae in abundance buried deep in the bowe1 waI1. DR. ALTON OCHSNER, New Orleans, La.: Amebiasis is interesting to surgeons because of the Iesions in the right side of the coIon which produce symptoms referabIe to the upper intestina1 tract and the stomach. The reason amebiasis is more IikeIy to produce Iesions simuIating surgical conditions is because in cases with right-sided Iesions there is no diarrhea, whereas the patient with Iesions on the Ieft side of the coIon wiI1 have diarrhea, the stoo1 containing mucus and bIood. Dr. DeBakey and I found in 73 cases of amebic Iiver abscess admitted to the Charity HospitaI and the Touro Infirmary in New OrIeans that diarrhea was absent in 80 per cent of the cases at the time of entrance to the hospital, and 40.3 per cent gave no history of diarrhea at any time. We have found in going over 4594 reported cases that in those cases with Iiver abscess treated by open drainage the mortaIity was 47.2 per cent, whereas foIIowing conservative treatment it was onIy 6.9 per cent. Rogers showed that the mortaIity couId be reduced from 56.8 per cent to 14 per cent by conservative treatment. Emetine undoubtedIy is an exceIIent drug in the fuIminant type of amebiasis, but is dangerous if given in Iarge doses and must be used cautiousIy. Emetine shouId be used in amebic hepatitis, however, because most of the other amebacides are aIso Iiver toxins. I beIieve that in a11 patients, especiaIIy here in the South, who give an indefinite history of chronic appendicitis, the possibiIity of amebiasis shouId be considered. FrequentIy a stoo1 examination wiI1 make an operation unnecessary. DR. LLOYD NOLAND, Birmingham, AIa.: I am Iucky enough to be one of the four survivors of the origina medica group that started work on the Panama CanaI. We found a country in which the genera1 popuIation had never had much in the way of medicaI care. Amebiasis was, of course, endemic and cases in a11stages of the infection were a matter of aImost daiIy observation. I do not beIieve that I am exaggerating when I say that in the first two or three years perforations of the rectum and sigmoid occurred frequentIy with ordinary recta1 tube irrigation. Dr. Hogan has spoken of the difhcuIty of diagnosis because of frequent negative stoo1 reports. I think that part of this troubIe is due to Iack of experience and fauIty technique on the part of the Iaboratory workers, but there is no question that aImost

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an>- case of fairly advanced amebiasis can be diagnosed by the use of a proctoscope with the coIlection of scrapings from almost aIways e\-ident ulcers. Dr. Ochsner has spoken of the aspiration treatment in Iiver abscess. If Iiver abscess were aIways singIe and if the abscess were aIways Iocated in the dome of the liver, this treatment might be,permissibIe, but the facts are that amebic abscess of the liver is frequently multipIe, and no simple aspiration treatment can, of course, be effective in such cases. In addition to this fact, aspiration of the dome of the Iiver necessitates passage of the needle through the pIeura. When the needIe is withdrawn the pIeural cavity is necessariIy infected; aIso, frequently the puncture in the Ii\-er wiI1 leak into the abdominal cavity. Both of these comphcations we have observed on a number of occasions. I am not competent to discuss the emetine treatment of amebiasis or its complications, but I would like once more to strongIy advocate simple abdomina1 expIoration through a high incision in cases of suspected Iiver abscess. The location of even smaI1 abscesses is extremeIy easy by palpation, and one is then prepared to institute the simplest and safest type of drainage. If drainage of the dome is necessary, a short rib resection directIy over the site of the abscess, with boId section of the pIeura and diaphragm, foIIowed by simple suture of the cut edges of the diaphragm to the intercostal muscIes, thus thoroughIy waIIing off the pIeura1 cavity before the abscess is opened and aIIowing easy access for a gauze waII-off to protect the genera1 abdomina1 cavity, will, I beIieve, give far better resuIts than any haphazard method of aspiration. AIthough this technique was independentIy worked out in Panama, credit for it must go to George G. Davis of Chicago, who practiced it in the PhiIippines at the same time we were using it in Panama and who published the first articIe on the subject many years ago in Surgery, Gynecoloc and Obstetrics. DR. LOMAX GWATHMEY, NorfoIk, Va.: Our attention

to amebiasis was aroused many years ago, and we did a fair number of appendicostomies, washing out the coIon with a11 sorts of preparations. Since that time we have seen amebiasis of a11 types, which were readiIy reIieved by emetine. Carrying out Dr. Hogan’s idea, we have at present 2 cases in the hospita1. Both were diagnosed as subphrenic abscess by x-ray and so on. On exploration we found a subdiaphragmatic abscess in one case, and I suggested that we investigate the stooIs. There had been no diarrhea but we found the ameba. This patient aIso had gaIIstones but I think the origin was the Endamoeba histoIytica. The second case was interesting. It was aIso diagnosed as subphrenic abscess. We expIored from in front, but found it so far back that we thought

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best to cIose the abdomen and approach by rib resection from the back. In Iooking over the abdomen I noticed that the appendix was quite red and congested and suggested that we shouId take it out and see if it contained amebas. We did so and within a few minutes the report came back that amebas were present. There had been no diarrhea, but I think in cases suggestive of appendicitis we wouId probabIy find amebas if we examined the contents of the appendix when it was first removed.