- Email: [email protected]
Pylephlebitis and liver abscess
Pylephlebitis
and Liver Abscess
H. LOWELL HOFFMAN, M.D., Newport, Rhode Island, PHILIP F. PARTINGTON,M.D., Cleveland, Ohio, ANDALFRED L. DESANCTIS, M.D., Cleveland, Obio From tbe University Cleveland, Cleveland,
Departments of Surgery, Western Reserve School of Medicine, University Hospitals of and Crile Veterans Administration Hospital, Obio.
YLEPHLEBITIS, tirst described by Walter in characterized by suppurative thrombophIebitis of the portal vein, with extension into its intrahepatic branches, and by the formation of single or multipIe liver abscesses mainIy in the right Iobe of the liver. AIthough it may foIIow suppurative disease anywhere in the portal drainage system, and has even been reported from infected hemorrhoids,2s13 it has been associated with suppurative appendicitis in the majority of reported cases. It has been suggested that the suppurative process might reach the portal area through lymphatic drainage,3l4 but most cases can be explained by direct extension5 invoIving the veins of the mesoappendix, iIeocoIic vein and superior mesenteric vein in turn, or by bIood-borne emboIi.g Regardless of the site of the suppurative disease, the responsibIe organism is most frequentIy BaciIIus coIi, with Streptococcus hemolyticus and StaphyIococcus aureus folIowing in that order.13 The present study is based on a series of seventeen cases of pyIephIebitis coIIected from three CIeveIand hospitals: five each from University Hospitals and CriIe Veterans HospitaI, and seven from CIeveIand City HospitaI. The incidence of appendicitis as the source of suppuration was not quite as high as in most reported series. Ten cases, or 59% were preceded by acute gangrenous or perforated appendicitis while the antecedant diseases of the other seven cases, or 41 per cent, were divided equaIIy between the peritonea1 and pIeura1 cavities. (TabIe I.) Of the five patients at University Hospitals, three had had appendectomies for acute appendicitis, one acute and two perforated. They had been operated upon in a series of 6,0 I 4 appendectomies for acute appendicitis thus giving an associated incidence of pyIe-
P 1846,*,lO is a disease
phIebitis of 0.05 per cent. This compares with an incidence of 0.09 per cent reported by Ochsner in 5,293 cases of appendicitis. There were 659 perforated appendices in the University Hospital series giving an associated incidence of pylephlebitis of 3.0 per cent. At SOURCE
TABLE I OF PYLEPHLEBITIS
of Cases
No.
Appendicitis.. Acute........................ Acute perforated.. Acute gangrenous.. Ulcerative enterocolitis. Pubnonary abscess.. Perforated carcinoma, stomach. Emphyema with pneumonia. Perforated duodenum.. Acute pancreatitis.. Carcinomatosis.. :‘. TotaI..
IO 4
5 L I I I I I I 1 17
autopsy Petren found pyIephIebitis was the cause of death in 5 per cent of 1,340 patients dying from appendicitis. l6 The present series is much too smaI1 to permit valid concIusions, but it does present some interesting materia1. PyIephIebitis occurred in a11 decades except the first two and was most prevalent in the third when appendicitis was most common. (Fig. I.) There were five Negro and twelve white patients, demonstrating no raciaI influence. Prior to 1946 there were eIeven cases with eIeven deaths, a mortality rate of I oo per cent. Since I 946 there have been six cases with three deaths, or a mortahty rate of 50 per cent. Autopsies were obtained in a11 but one case which had been confirmed by operation and in which the clinica course had been identica1 to the autopsied cases. The three patients who Iived had adequate Iaboratory data and clinical and operative findings to justify the diagnosis. The diagnosis of pyIephIebitis and Iiver abscess was usuaIIy very diffrcuh to make clinicahy and was aImost aIways belated if
PyIephIebitis
and Liver Abscess days and persisted unti1 the death or recovery of the patient. There was an associated positive cephatin flocculation, and an eIevated thymol turbidity in the six patients tested; in three of the live patients who had serum protein determinations made there was a reversa1 of the A/G ratio. The bIood cuIture was positive in nine of thirteen patients tested. Five of the nine had negative cuItures earIy in the disease but these subsequentIy became positive. The causative organisms were Escherichia coli in three, hemoIytic streptococcus, hemoIytic staphylococcus aureus and Streptococcus viridans in one each, and mixed cuItures in the other three of Staph. aureus, Esch. coli and streptococcus; nonhemolytic streptococcus and staphlococcus; and Esch. coli and Aerobacter aerogenes. It appeared that the bIood cuIture did not become positive unti1 liver abscesses had formed with secondary seeding of the blood stream relativeIy Iate in the disease.3-5 The liver was recorded as enlarged cIinicaIIy in live of the seventeen patients. This may not represent a true incidence as the Iiver is usuahy enIarged at some time during the course of the disease. The spIeen was enIarged in four patients two of whom subsequently were found to have splenic vein thrombosis. Moderate ascites was present in two patients, one with acute appendicitis and the other with perforated carcinoma of the stomach. Ascites is rarely a prominent clinical Iinding with pyIephIebitis.3a4,* The course of pylephlebitis and liver abscess was prolonged Iasting from nine to seventythree days, with an average of thirty-two days in the fata cases. The three patients who lived were hospitaIized thirty-nine, eighty-six and 200 days, respectivety. Treatment before the advent of the antibiotics was chiefly directed toward the undertying disease and consisted of appendectomy, drainage of the appendicea1, subphrenic or other abscesses where indicated, and supportive treatment. Ligation of the ileocolic, superior mesenteric and even porta veins was given up in genera1 as too hazardous after some earIy success with its use.3v4s8Following the availabiIity of potent antibiotic drugs, the natura1 history of the disease seemed to have been aItered.1,11,12,14.18Three patients survived in the present series and the average survivial of the three who died after 1946 was almost doubled.
made at al1 before autopsy. The history of appendicitis was frequentIy so atypica1 that it was overIooked entireIy. In three of the cases of appendicitis, the fever and shaking chili preceded the nausea and abdominal pain by two to six hours. In two other cases of appendi-
II-21
Age Distribution FIG. I. PrevaIence of pyIephIebitis
by decade.
citis, the chiI1 folIowed the onset of nausea and abdomina1 pain by six to twenty-four hours, and in one it occurred six weeks after operation for gangrenous appendicitis. This is in accord with DreviousIv reported cases which foIIowed appendectomy ‘by six and seven weeks.3,4 In anaIyzing 2,841 cases of acute appendicitis, Colp found an incidence of 6.8 per cent of preoperative chiIIs, but pyIephIebitis was usually preceded by muItipIe and protracted chiIIs. The fever of pyIephIebitis was septic after a dramatic onset with chills and ranged up to 40 or 41’~. There was an occasiona decrease in this fever with a change in antibiotics or the use of repeated bIood transfusions, but it usually persisted unti1 the death or recovery of the patient. Nausea was an evident feature of the disease but might have been associated with the primary disease which caused the pylephlebitis. Many of the patients had diarrhea, but the character of the stool was not diagnostic and in no case was it bloody or excessiveIy mucoid. Jaundice was an important cIinica1 manifestation of the disease and a great aid in its diagnosis.3~4~6~s It was present in tweIve of the seventeen cases but was usuaIIy miId with icterus indices of from 19 to 23. Three patients had marked jaundice, however, with icterus indices of so, 43 and 60, respectively. Jaundice usually followed the chills and fever by a few 412
PyIephIebitis
and
Liver
Abscess
in the right upper and Iower abdomen. No masses were felt. Laboratory findings incIuded: a white blood count of 18,000; aIkaIine phosphatase 14.4; serum bilirubin, direct 1.4 mg. per cent, indirect 2.8 mg. per cent; thymo1 turbidity 4.7 units; cephaIin floccuIation 3 +. A bIood cuIture was positive for Esch. coIi on admission. FoIIowing hydration she was operated upon with a diagnosis of empyema of the gaIIbIadder. A perforated appendix with a carcinoid in its proximal third was removed. No observation was made about the appendicea1 or iIeocoIic veins. The patient received terramycin intravenousIy and then peniciIIin and streptomycin. Her condition improved rapidIy and antibiotics were stopped on the sixth postoperative day as her temperature was normaI. On the ninth postoperative day chiIIs and fever to 39.6”c. deveIoped. PeniciIIin and streptomycin were reinstituted but were ineffective. BIood cuIture on the fourteenth day reveaIed StaphyIococcus aIbus sensitive onIy to suIfadiazine and chIoramphenaco1. In spite of large doses of the latter drug, the patient’s condition deteriorated. An attempt to drain a Iiver abscess on the twentieth day demonstrated no Iarge abscess and she died at the cIose of the procedure. Autopsy reveaIed suppurative thrombophIebitis of the porta vein with multipIe smaI1 Iiver abscesses. CASE II. A twenty-eight year oId white man entered the hospita1 with a history of chiIIs, fever, headache and diarrhea of seven days’ duration foIIowing drinking of raw water from a we11 near a privy. The onset of his iIIness had been marked by nausea and vomiting foIIowed in severa hours by a watery stoo1 and shaking chiI1. He had been treated for five days at another hospital with suIfaguanidine, peniciIIin and streptomycin, as we11 as intravenous fluids. On admission he was acuteIy III with a temperature of IO~‘F., a distended abdomen, palpabIe spleen, generaIized Iymphadenopathy and questionabIe rose spots. AggIutination to EbertheIIa typhosa was positive with both 0 and H strains to 1-1280. CephaIin fIoccuIation was 4+ and thymo1 turbidity 6.3. There was an inversion of the A/G ratio. BIood cuIture showed no growth. X-rays reveaIed an inflammatory process in the right Iower Iung fieId and a Iaminated coproIith in the right Iower quadrant of the abdomen. The patient ran a spiking fever up
A variety of the antibiotics and suIfadiazine were employed, with peniciIlin combined with streptomycin being favored unless sensitivity tests run on organisms obtained from the bIood stream or an abscess cavity indicated a different choice. Three of the six patients treated since 1946 incIuding two of the survivors were treated with 40 mg. of heparin intramuscuIarIy every four hours. It was believed that this drug was contraindicated in the other survivor because of hereditary hemorrhagic teIangiectasia of the gastrointestina1 tract. The patient who died in spite of anticoaguIant therapy did not receive it unti1 the eighth week of his illness, two days before death. There was marked but temporary improvement in his cIinica1 condition with a sharp drop in temperature. Operative and autopsy findings in a11 cases revealed a suppurative focus somewhere in the porta drainage system with propagation of the process by direct extension to the portal vein and intrahepatic portal system in thirteen of the patients. In four, there was no involvement of the intervening veins so that it must be postulated that the disease spread by showers of septic emboIi. The liver abscesses were usuaIIy smaI1 measuring I to 2 cm. in diameter. Large and confiuent intrahepatic abscesses and subphrenic abscesses deveIoped Iate in the disease providing that the patient survived Iong enough. Operative intervention for liver abscess proved effective onIy at this stage. Two of the patients who survived had large liver abscesses evacuated. The other survivor had drainage of an appendiceal abscess. The six cases occurring since antibiotic drugs have been avaiIabIe are of specia1 interest and are reported in some detai1. CASE REPORTS CASE I. A twenty-seven year oId Negress entered the hospita1 eight days after the onset of chiIIs and fever which had been foIIowed in one hour by vague upper abdomina1 pain. She had been miIdIy constipated for three days before coming to the hospita1, and two days prior to admission she had become nauseated and had vomited. She had received three injections of peniciIIin during the eight days of her iIIness. On admission her temperature was 3g.I”c., her lungs were clear by physica examination and her abdomen was distended. Spasm and rebound tenderness were present 4’3
PyIephIebitis
and Liver Abscess
to 106’~. with frequent chilIs. He was treated with emetine and diodiquin because of a positive compIement fixation test for amebiasis. He also received Iarge doses of penicillin, streptomycin and suIfadiazine without improvement. ExpIoratory Iaparotomy discIosed massive ascites and a huge spleen. Liver biopsy showed acute +oIangitis with acute foca1 inflammation. The icterus index rose to 60 and the patient died on his sixty-sixth hospita1 day. Autopsy reveaIed thrombophIebitis of the porta and superior mesenteric veins with multipIe periporta1 liver abscesses. The appendix was retroceca1 and showed evidence of perforation in the vicinity of a Iarge coproIith. CASE III. A twenty-four year oId white man was transferred from another hospital in the sixth week of an iIIness starting with miId abdominal pain and soon foIIowed by malaise, chiIIs and fever to 103 or 105’~. daily. A diagnosis of “ intestina1 tru” had been made and the patient had been treated with Iarge doses of cathartics. On admission he was acutely iI1, jaundiced, toxic, disoriented and extremeIy weak. There were generaIized purpuric spots; the Iiver was palpabIe 5 cm. below the Costa1 margin and the spIeen was paIpabIe. There was an anemia of 1,800,000 red blood ceIIs, cephaIin tIoccuIation 4+, thymo1 turbidity 6.4 and an inversion of the A/G ratio. BIood culture was positive for Esch. coli with growth inhibited by aureomycin. X-ray of the abdomen showed a coproIith in the right lower quadrant. The patient was treated with suIfadiazine, peniciIIin and streptomycin without improvement. There was dramatic but temporary improvement after aureomycin, and bIood cultures became negative. There was aIso marked temporary improvement after anticoaguIant therapy with heparin was started two days before the patient died on his seventeenth hospita1 day. Autopsy revealed pylethrombophIebitis with multiple abscesses throughout the Iiver. There was an organizing periappendicea1 abscess. CASE IV. A fifty-six year oId white man entered the hospita1 four months after operation for a ruptured appendix with peritonitis. Six weeks Iater epigastric pain, nausea and vomiting developed, and one month after that he commenced to run a fever from IOO to 102~~. which was treated with suIfa drugs at that time. Pain in the right upper back de414
veIoped which was worse with cough and deep breathing. The patient was known to have congenita1 hemorrhagic teIangiectasia of the gastrointestinal and respiratory tracts. On admission he was acuteIy and chronicaIIy iI1, with a temperature of 103’~. There was an inff ammatory process at the base of the right Iung with a high right diaphragm, enIarged spleen, severe anemia with a red bIood count of 1,500,ooo, and mild icterus with an icterus index of 21 rising to 25. The A/G ratio was reversed, cephaIin lloccuIation was 4+, thymo1 turbidity 4.1 and bIood cuItures which were sterile at first grew Str. viridans sensitive to peniciIIin. The patient was treated with peniciIIin, seventy transfusions and surgica1 drainage. SeveraI attempts were necessary before a Iiver abscess measuring 7 cm. in diameter and 4 cm. in depth, and a right subphrenic abscess culturing Proteus vuIgaris, StaphI. albus and A. aerogenes were adequateIy drained. ConvaIescence was proIonged by a homologous serum hepatitis, and the patient was discharged with a draining sinus 200 days after admission. The sinus cIosed four years Iater after further drainage of subphrenic abscesses. CASE v. A twenty-two year old white man entered the hospital with fever and abdominal pain which had started two weeks previousIy associated with headache, maIaise and a chiI1 foIIowed by a fever of 103’~. The duI1 aching abdominal pain had IocaIized in the right abdomen by the third day and had been associated with anorexia. The patient had been treated for amebic dysentery four years previously. On admission he was acuteIy and chronicaIIy iI with a fever of 104~~. The Iungs were clear by physica examination but the right diaphragm did not descend normally. The Iiver was paIpabIe 1.5 cm. beIow the Costa1 margin and was tender. BIood cuItures were steriIe. CephaIin fIoccuIation was 2 +, thymo1 turbidity and A/G ratio were normal, and there was no jaundice. The patient was treated with emetine, but the compIement fixation test for amebiasis proved negative. He ran a septic fever to IO~‘F., and received heparin, peniciIIin and streptomycin. The right diaphragm became high and fixed, and an area of tenderness and edema appeared over the right ninth rib anteriorIy. Two weeks after admission, a twostage drainage of a subdiaphragmatic and a large muItiIocuIated Iiver abscess 2 cm. below
PyIephIebitis
and
the surface of the Iiver was carried out. The pus cuItured non-hemolytic streptococcus. Fever subsided sIowIy and the patient was discharged on the seventy-second hospital day. At appendectomy performed six months later there were many adhesions in the region of the appendix and sections showed healed appendicitis. CASE VI. A twenty-six year oId white man was admitted to the hospita1 with severe abdominal pain and loose watery stools on the tenth day of an iIIness starting with nausea and vomiting. CoIicky pain in the right upper and Iower abdomen had deveIoped twenty-four hours after onset and had localized in the right Iower abdomen after three or four days. There was a past history of two previous attacks of abdomina1 pain diagnosed as appendicitis. The patient was acuteIy III, poorIy nourished and had a fever of 104’F. There was muscIe spasm, acute tenderness and a 6 cm. mass in the right Iower abdomen. The Iiver area was tender and the superficial veins of the abdomina1 waI1 were diIated. The white blood count was 17,000, cephaIin floccuIation 4 +, thymo1 turbidity 2.6, icterus index rg, prothrombin time twenty-four seconds with a contro1 of fifteen seconds. X-ray examination of the abdomen showed free air in the right flank, stepIadder distention of the smaI1 bowel and a coproIith in the right lower abdomen. BIood cuIture was normaI. The patient ran a septic fever to 105~~. daiIy. He was treated with a MiIIer-Abbott tube, Iarge doses of peniciIIin and streptomycin, 250 cc. of whoIe blood daily and intramuscular heparin for the first two weeks of his hospita1 stay. An abscess in the right lower abdomen was drained on the seventh day and the pus cultured Esch. coIi. The patient’s fever subsided. After two cephalin fIoccuIation determinations of 4 +, a negative was obtained a month after admission. The icterus index dropped to 8 and bromsuIfaIein excretion was normaI. The patient was discharged on his twenty-ninth hospita1 day. The appendix was removed four months Iater and showed heaIing appendicitis and periappendicitis. Liver biopsy was normaI. COMMENT
The incidence of pyIephIebitis scess has decreased in recent earIier diagnosis and treatment
and Iiver abyears due to , of appendicitis 4’4
Liver
Abscess
and possibIy somewhat to the rather genera1 use of antibiotics. The history of appendicitis, however, may be atypica1 and confusing as in most of the cases in the present series, accounting for a delay in diagnosis. The chiI1 or better muItipIe chiIIs as pointed out by CoIp3v4 are heIpfu1 when present. The presence of a Iaminated coproIith or fecaIith in the right Iower quadrant on a fiat roentgenogram of the abdomen serves to focus attention on the appendix as a possible source of infIammation. There were three coproliths in the six recent cases in this series. In a group of IOO acuteIy inff amed appendices removed consecutively, Remington16 reported that fecaIiths associated with gangrene and rupture of the appendix were more frequent in the twenty-six cases showing thrombosis of the appendicea1 veins. Once a diagnosis of pyIephIebitis is suspected, vigorous supportive therapy is necessary in view of the proIonged and wasting nature of this process. Multiple transfusions heIp combat the anemia and hypoproteinemia which deveIop. Antibiotics can steriIize the bIood stream as evidenced by bIood cuItures becoming negative, and every effort shouId be made to choose the proper drug by sensitivity tests when the causative organism can be cuItured. AnticoaguIant therapy probabIy is useful judging by a very limited experience with it. It may be able to prevent the spread of the thrombosis to the Iarger veins whiIe the antibiotics dea1 with the organisms in the bIood stream. Heparin in 50 mg. doses is probabIy preferable to dicumaro1 in view of the severe toxic depression of the Iiver which is present. In spite of a11 the therapeutic methods avaiIabIe, the mortaIity of pyIephIebitis with Iiver abscess remains high. The prognosis with a singIe Iiver abscess is better than with muItipIe abscesses as shown by 0chsner13 who found a mortality of 37.5 per cent with a singIe compared to g5 per cent for muItipIe abscesses. EIiason6 was of the opinion that a single abscess was due to a septic emboIus from a circumscribed venous infection and had a fairly good prognosis foIIowing surgica1 drainage. Of his fourteen cases of pyIephIebitis with liver abscess, seven had singIe abscesses and lived. Two of the three survivors in the present series had singIe Iarge abscesses in the right lobe of the Iiver though one was multilocuIated. It remains to be shown whether specific antibiotic and anticoaguIant therapy can
PyIephIebitis overcome pyIephIebitis liver abscesses.
with
muItiple
and Liver
small
Abscess REFERENCES
I. D’ABREU, F. Suppurative
SUMMARY
2.
Ten of seventeen cases of pyIephIebitis with Iiver abscess were due to acute gangrenous or perforated appendicitis, an incidence of 5g per cent. The other seven cases were due to other suppurative disease in the pIeura1 or peritoneal cavities. 2. Diagnosis was diffrcuIt to make cIinicaIIy due to the atypica1 history and findings. Shaking chiIIs before or shortIy after the onset of symptoms and a coproIith in the right Iower abdomen by x-ray examination were heIpfu1 when they were present. 3. Jaundice was an important manifestation of the condition being present in tweIve of seventeen cases with icterus indices generalIy from rg to 25. 4. Blood cuItures were positive in nine of the thirteen patients tested with the predominant organism being Esch. coIi foIIowed by hemolytic streptococcus and hemolytic staphlococcus aureus either separately or associated with coIi-aerogenes organisms. 5. Treatment since 1946 consisted of drainage of appendicea1, subphrenic or Iiver abscesses where indicated, antibiotics chosen by sensitivity test when the organism was avaiIabIe for cuIture, anticoagulant therapy with heparin and supportive measures such as frequent blood transfusions. 6. Mortahty in the eleven cases prior to 1946 was IOO per cent whiIe it was 50 per cent in the six cases since that time. Two of the three patients who survived had drainage of singIe abscesses in the right Iobe of the Iiver. I.
3.
4. 5.
pyIeph1ebiti.s with recovery. Proc. Roy. Sot. Med., 39: 309, 1946. ALLEN, W. G. and MURWCK, L. H. PylephIebitis. Tri-State M. J., 9: 1876, 1936-1938. COLP, R. The treatment of pylephlebitis of appendicuIar origin. Surg., Gynec. @ Obst., 43: 627, 1926. COLP, R. The treatment of pyIephIebitis of appendicuIar origin. Ann. Surg., 85: 257, 1927. EITZEN, 0. Acute gangrenous appendicitis complicated by pyIephIebitis. Obio State M. J., 40:
325, ‘944. 6. ELIASON, E. L. PyIephIebitis and Iiver abscess. Surg., Gynec. @ Obst., 42: 5 IO, 1926. 7. HANCOCK, J. D. PyIephIebitis. South. M. J., 34: 647. 1941. 8. HAWKES, S. Z. Thrombophlebitis of the appendicia1 vein complicating acute appendicitis. Surg., Gynec. ti Obst., 66: 62, 1938. 9. KARSNER, H. Human PathoIogy, 6th ed. Philadelphia, 1942. J. B. Lippincott Co, IO. KELLY, H. A. and HURWN, E. The Vermiform Appendix and Its Diseases. PhiIadeIphia, 1905. W. B. Saunders & Co. II. MILLIKEN, N. T. and STRYKER, H. B., JR. Suppurative pyIethrombophIebitis and muItipIe Iiver abscesses following acute appendicitis; report of case with recovery. New England J. Med., 244: 52, 1951. 12. MILLS, J. H. MuItipIe liver abscess. Nortbwest Med., 51: 315, 1952. 13. OCHSNER, A., DEBAKEY, M. and MURRAY, S. Pyogenic abscess of the liver. Am. J. Surg., 40: 292, 1938. IL. (STTENBEKG. R. and BERCK. M. SuIfaniIamide therapy for suppurative pyIephIebitis and Iiver abscesses. J. A. M. A., II: 1374, 1938. 15. PETREN, G. iSber Leberabscess als Komplikation zu akuter Appendicitis. Beitr. z. K&n. Cbir., 94: 225, 19’4. 16. REMINGTON,J. H. and MCDONALD, J. R. Vascular thrombosis in acute appendicitis. Surgery, 24: 787, 1948. 17. THALHIMER, W. ChiIIs occurring earIy in appendicitis before operation and their indication of an operabIe stage of pyIephIebitis. Arch. Surg., 8: 658, ‘924. 18. WILENSKY, A. 0. PyIephIebitis under penicillin and sulfadiazine therapy. New York State J. Med., 45: 2082, 1945.
Acknowledgment: GratefuI acknowIedgment is extended to Dr. F. A. Simeone for permission to examine the records at CIeveIand City Hospital.
416
and Liver Abscess
H. LOWELL HOFFMAN, M.D., Newport, Rhode Island, PHILIP F. PARTINGTON,M.D., Cleveland, Ohio, ANDALFRED L. DESANCTIS, M.D., Cleveland, Obio From tbe University Cleveland, Cleveland,
Departments of Surgery, Western Reserve School of Medicine, University Hospitals of and Crile Veterans Administration Hospital, Obio.
YLEPHLEBITIS, tirst described by Walter in characterized by suppurative thrombophIebitis of the portal vein, with extension into its intrahepatic branches, and by the formation of single or multipIe liver abscesses mainIy in the right Iobe of the liver. AIthough it may foIIow suppurative disease anywhere in the portal drainage system, and has even been reported from infected hemorrhoids,2s13 it has been associated with suppurative appendicitis in the majority of reported cases. It has been suggested that the suppurative process might reach the portal area through lymphatic drainage,3l4 but most cases can be explained by direct extension5 invoIving the veins of the mesoappendix, iIeocoIic vein and superior mesenteric vein in turn, or by bIood-borne emboIi.g Regardless of the site of the suppurative disease, the responsibIe organism is most frequentIy BaciIIus coIi, with Streptococcus hemolyticus and StaphyIococcus aureus folIowing in that order.13 The present study is based on a series of seventeen cases of pyIephIebitis coIIected from three CIeveIand hospitals: five each from University Hospitals and CriIe Veterans HospitaI, and seven from CIeveIand City HospitaI. The incidence of appendicitis as the source of suppuration was not quite as high as in most reported series. Ten cases, or 59% were preceded by acute gangrenous or perforated appendicitis while the antecedant diseases of the other seven cases, or 41 per cent, were divided equaIIy between the peritonea1 and pIeura1 cavities. (TabIe I.) Of the five patients at University Hospitals, three had had appendectomies for acute appendicitis, one acute and two perforated. They had been operated upon in a series of 6,0 I 4 appendectomies for acute appendicitis thus giving an associated incidence of pyIe-
P 1846,*,lO is a disease
phIebitis of 0.05 per cent. This compares with an incidence of 0.09 per cent reported by Ochsner in 5,293 cases of appendicitis. There were 659 perforated appendices in the University Hospital series giving an associated incidence of pylephlebitis of 3.0 per cent. At SOURCE
TABLE I OF PYLEPHLEBITIS
of Cases
No.
Appendicitis.. Acute........................ Acute perforated.. Acute gangrenous.. Ulcerative enterocolitis. Pubnonary abscess.. Perforated carcinoma, stomach. Emphyema with pneumonia. Perforated duodenum.. Acute pancreatitis.. Carcinomatosis.. :‘. TotaI..
IO 4
5 L I I I I I I 1 17
autopsy Petren found pyIephIebitis was the cause of death in 5 per cent of 1,340 patients dying from appendicitis. l6 The present series is much too smaI1 to permit valid concIusions, but it does present some interesting materia1. PyIephIebitis occurred in a11 decades except the first two and was most prevalent in the third when appendicitis was most common. (Fig. I.) There were five Negro and twelve white patients, demonstrating no raciaI influence. Prior to 1946 there were eIeven cases with eIeven deaths, a mortality rate of I oo per cent. Since I 946 there have been six cases with three deaths, or a mortahty rate of 50 per cent. Autopsies were obtained in a11 but one case which had been confirmed by operation and in which the clinica course had been identica1 to the autopsied cases. The three patients who Iived had adequate Iaboratory data and clinical and operative findings to justify the diagnosis. The diagnosis of pyIephIebitis and Iiver abscess was usuaIIy very diffrcuh to make clinicahy and was aImost aIways belated if
PyIephIebitis
and Liver Abscess days and persisted unti1 the death or recovery of the patient. There was an associated positive cephatin flocculation, and an eIevated thymol turbidity in the six patients tested; in three of the live patients who had serum protein determinations made there was a reversa1 of the A/G ratio. The bIood cuIture was positive in nine of thirteen patients tested. Five of the nine had negative cuItures earIy in the disease but these subsequentIy became positive. The causative organisms were Escherichia coli in three, hemoIytic streptococcus, hemoIytic staphylococcus aureus and Streptococcus viridans in one each, and mixed cuItures in the other three of Staph. aureus, Esch. coli and streptococcus; nonhemolytic streptococcus and staphlococcus; and Esch. coli and Aerobacter aerogenes. It appeared that the bIood cuIture did not become positive unti1 liver abscesses had formed with secondary seeding of the blood stream relativeIy Iate in the disease.3-5 The liver was recorded as enlarged cIinicaIIy in live of the seventeen patients. This may not represent a true incidence as the Iiver is usuahy enIarged at some time during the course of the disease. The spIeen was enIarged in four patients two of whom subsequently were found to have splenic vein thrombosis. Moderate ascites was present in two patients, one with acute appendicitis and the other with perforated carcinoma of the stomach. Ascites is rarely a prominent clinical Iinding with pyIephIebitis.3a4,* The course of pylephlebitis and liver abscess was prolonged Iasting from nine to seventythree days, with an average of thirty-two days in the fata cases. The three patients who lived were hospitaIized thirty-nine, eighty-six and 200 days, respectivety. Treatment before the advent of the antibiotics was chiefly directed toward the undertying disease and consisted of appendectomy, drainage of the appendicea1, subphrenic or other abscesses where indicated, and supportive treatment. Ligation of the ileocolic, superior mesenteric and even porta veins was given up in genera1 as too hazardous after some earIy success with its use.3v4s8Following the availabiIity of potent antibiotic drugs, the natura1 history of the disease seemed to have been aItered.1,11,12,14.18Three patients survived in the present series and the average survivial of the three who died after 1946 was almost doubled.
made at al1 before autopsy. The history of appendicitis was frequentIy so atypica1 that it was overIooked entireIy. In three of the cases of appendicitis, the fever and shaking chili preceded the nausea and abdominal pain by two to six hours. In two other cases of appendi-
II-21
Age Distribution FIG. I. PrevaIence of pyIephIebitis
by decade.
citis, the chiI1 folIowed the onset of nausea and abdomina1 pain by six to twenty-four hours, and in one it occurred six weeks after operation for gangrenous appendicitis. This is in accord with DreviousIv reported cases which foIIowed appendectomy ‘by six and seven weeks.3,4 In anaIyzing 2,841 cases of acute appendicitis, Colp found an incidence of 6.8 per cent of preoperative chiIIs, but pyIephIebitis was usually preceded by muItipIe and protracted chiIIs. The fever of pyIephIebitis was septic after a dramatic onset with chills and ranged up to 40 or 41’~. There was an occasiona decrease in this fever with a change in antibiotics or the use of repeated bIood transfusions, but it usually persisted unti1 the death or recovery of the patient. Nausea was an evident feature of the disease but might have been associated with the primary disease which caused the pylephlebitis. Many of the patients had diarrhea, but the character of the stool was not diagnostic and in no case was it bloody or excessiveIy mucoid. Jaundice was an important cIinica1 manifestation of the disease and a great aid in its diagnosis.3~4~6~s It was present in tweIve of the seventeen cases but was usuaIIy miId with icterus indices of from 19 to 23. Three patients had marked jaundice, however, with icterus indices of so, 43 and 60, respectively. Jaundice usually followed the chills and fever by a few 412
PyIephIebitis
and
Liver
Abscess
in the right upper and Iower abdomen. No masses were felt. Laboratory findings incIuded: a white blood count of 18,000; aIkaIine phosphatase 14.4; serum bilirubin, direct 1.4 mg. per cent, indirect 2.8 mg. per cent; thymo1 turbidity 4.7 units; cephaIin floccuIation 3 +. A bIood cuIture was positive for Esch. coIi on admission. FoIIowing hydration she was operated upon with a diagnosis of empyema of the gaIIbIadder. A perforated appendix with a carcinoid in its proximal third was removed. No observation was made about the appendicea1 or iIeocoIic veins. The patient received terramycin intravenousIy and then peniciIIin and streptomycin. Her condition improved rapidIy and antibiotics were stopped on the sixth postoperative day as her temperature was normaI. On the ninth postoperative day chiIIs and fever to 39.6”c. deveIoped. PeniciIIin and streptomycin were reinstituted but were ineffective. BIood cuIture on the fourteenth day reveaIed StaphyIococcus aIbus sensitive onIy to suIfadiazine and chIoramphenaco1. In spite of large doses of the latter drug, the patient’s condition deteriorated. An attempt to drain a Iiver abscess on the twentieth day demonstrated no Iarge abscess and she died at the cIose of the procedure. Autopsy reveaIed suppurative thrombophIebitis of the porta vein with multipIe smaI1 Iiver abscesses. CASE II. A twenty-eight year oId white man entered the hospita1 with a history of chiIIs, fever, headache and diarrhea of seven days’ duration foIIowing drinking of raw water from a we11 near a privy. The onset of his iIIness had been marked by nausea and vomiting foIIowed in severa hours by a watery stoo1 and shaking chiI1. He had been treated for five days at another hospital with suIfaguanidine, peniciIIin and streptomycin, as we11 as intravenous fluids. On admission he was acuteIy III with a temperature of IO~‘F., a distended abdomen, palpabIe spleen, generaIized Iymphadenopathy and questionabIe rose spots. AggIutination to EbertheIIa typhosa was positive with both 0 and H strains to 1-1280. CephaIin fIoccuIation was 4+ and thymo1 turbidity 6.3. There was an inversion of the A/G ratio. BIood cuIture showed no growth. X-rays reveaIed an inflammatory process in the right Iower Iung fieId and a Iaminated coproIith in the right Iower quadrant of the abdomen. The patient ran a spiking fever up
A variety of the antibiotics and suIfadiazine were employed, with peniciIlin combined with streptomycin being favored unless sensitivity tests run on organisms obtained from the bIood stream or an abscess cavity indicated a different choice. Three of the six patients treated since 1946 incIuding two of the survivors were treated with 40 mg. of heparin intramuscuIarIy every four hours. It was believed that this drug was contraindicated in the other survivor because of hereditary hemorrhagic teIangiectasia of the gastrointestina1 tract. The patient who died in spite of anticoaguIant therapy did not receive it unti1 the eighth week of his illness, two days before death. There was marked but temporary improvement in his cIinica1 condition with a sharp drop in temperature. Operative and autopsy findings in a11 cases revealed a suppurative focus somewhere in the porta drainage system with propagation of the process by direct extension to the portal vein and intrahepatic portal system in thirteen of the patients. In four, there was no involvement of the intervening veins so that it must be postulated that the disease spread by showers of septic emboIi. The liver abscesses were usuaIIy smaI1 measuring I to 2 cm. in diameter. Large and confiuent intrahepatic abscesses and subphrenic abscesses deveIoped Iate in the disease providing that the patient survived Iong enough. Operative intervention for liver abscess proved effective onIy at this stage. Two of the patients who survived had large liver abscesses evacuated. The other survivor had drainage of an appendiceal abscess. The six cases occurring since antibiotic drugs have been avaiIabIe are of specia1 interest and are reported in some detai1. CASE REPORTS CASE I. A twenty-seven year oId Negress entered the hospita1 eight days after the onset of chiIIs and fever which had been foIIowed in one hour by vague upper abdomina1 pain. She had been miIdIy constipated for three days before coming to the hospita1, and two days prior to admission she had become nauseated and had vomited. She had received three injections of peniciIIin during the eight days of her iIIness. On admission her temperature was 3g.I”c., her lungs were clear by physica examination and her abdomen was distended. Spasm and rebound tenderness were present 4’3
PyIephIebitis
and Liver Abscess
to 106’~. with frequent chilIs. He was treated with emetine and diodiquin because of a positive compIement fixation test for amebiasis. He also received Iarge doses of penicillin, streptomycin and suIfadiazine without improvement. ExpIoratory Iaparotomy discIosed massive ascites and a huge spleen. Liver biopsy showed acute +oIangitis with acute foca1 inflammation. The icterus index rose to 60 and the patient died on his sixty-sixth hospita1 day. Autopsy reveaIed thrombophIebitis of the porta and superior mesenteric veins with multipIe periporta1 liver abscesses. The appendix was retroceca1 and showed evidence of perforation in the vicinity of a Iarge coproIith. CASE III. A twenty-four year oId white man was transferred from another hospital in the sixth week of an iIIness starting with miId abdominal pain and soon foIIowed by malaise, chiIIs and fever to 103 or 105’~. daily. A diagnosis of “ intestina1 tru” had been made and the patient had been treated with Iarge doses of cathartics. On admission he was acutely iI1, jaundiced, toxic, disoriented and extremeIy weak. There were generaIized purpuric spots; the Iiver was palpabIe 5 cm. below the Costa1 margin and the spIeen was paIpabIe. There was an anemia of 1,800,000 red blood ceIIs, cephaIin tIoccuIation 4+, thymo1 turbidity 6.4 and an inversion of the A/G ratio. BIood culture was positive for Esch. coli with growth inhibited by aureomycin. X-ray of the abdomen showed a coproIith in the right lower quadrant. The patient was treated with suIfadiazine, peniciIIin and streptomycin without improvement. There was dramatic but temporary improvement after aureomycin, and bIood cultures became negative. There was aIso marked temporary improvement after anticoaguIant therapy with heparin was started two days before the patient died on his seventeenth hospita1 day. Autopsy revealed pylethrombophIebitis with multiple abscesses throughout the Iiver. There was an organizing periappendicea1 abscess. CASE IV. A fifty-six year oId white man entered the hospita1 four months after operation for a ruptured appendix with peritonitis. Six weeks Iater epigastric pain, nausea and vomiting developed, and one month after that he commenced to run a fever from IOO to 102~~. which was treated with suIfa drugs at that time. Pain in the right upper back de414
veIoped which was worse with cough and deep breathing. The patient was known to have congenita1 hemorrhagic teIangiectasia of the gastrointestinal and respiratory tracts. On admission he was acuteIy and chronicaIIy iI1, with a temperature of 103’~. There was an inff ammatory process at the base of the right Iung with a high right diaphragm, enIarged spleen, severe anemia with a red bIood count of 1,500,ooo, and mild icterus with an icterus index of 21 rising to 25. The A/G ratio was reversed, cephaIin lloccuIation was 4+, thymo1 turbidity 4.1 and bIood cuItures which were sterile at first grew Str. viridans sensitive to peniciIIin. The patient was treated with peniciIIin, seventy transfusions and surgica1 drainage. SeveraI attempts were necessary before a Iiver abscess measuring 7 cm. in diameter and 4 cm. in depth, and a right subphrenic abscess culturing Proteus vuIgaris, StaphI. albus and A. aerogenes were adequateIy drained. ConvaIescence was proIonged by a homologous serum hepatitis, and the patient was discharged with a draining sinus 200 days after admission. The sinus cIosed four years Iater after further drainage of subphrenic abscesses. CASE v. A twenty-two year old white man entered the hospital with fever and abdominal pain which had started two weeks previousIy associated with headache, maIaise and a chiI1 foIIowed by a fever of 103’~. The duI1 aching abdominal pain had IocaIized in the right abdomen by the third day and had been associated with anorexia. The patient had been treated for amebic dysentery four years previously. On admission he was acuteIy and chronicaIIy iI with a fever of 104~~. The Iungs were clear by physica examination but the right diaphragm did not descend normally. The Iiver was paIpabIe 1.5 cm. beIow the Costa1 margin and was tender. BIood cuItures were steriIe. CephaIin fIoccuIation was 2 +, thymo1 turbidity and A/G ratio were normal, and there was no jaundice. The patient was treated with emetine, but the compIement fixation test for amebiasis proved negative. He ran a septic fever to IO~‘F., and received heparin, peniciIIin and streptomycin. The right diaphragm became high and fixed, and an area of tenderness and edema appeared over the right ninth rib anteriorIy. Two weeks after admission, a twostage drainage of a subdiaphragmatic and a large muItiIocuIated Iiver abscess 2 cm. below
PyIephIebitis
and
the surface of the Iiver was carried out. The pus cuItured non-hemolytic streptococcus. Fever subsided sIowIy and the patient was discharged on the seventy-second hospital day. At appendectomy performed six months later there were many adhesions in the region of the appendix and sections showed healed appendicitis. CASE VI. A twenty-six year oId white man was admitted to the hospita1 with severe abdominal pain and loose watery stools on the tenth day of an iIIness starting with nausea and vomiting. CoIicky pain in the right upper and Iower abdomen had deveIoped twenty-four hours after onset and had localized in the right Iower abdomen after three or four days. There was a past history of two previous attacks of abdomina1 pain diagnosed as appendicitis. The patient was acuteIy III, poorIy nourished and had a fever of 104’F. There was muscIe spasm, acute tenderness and a 6 cm. mass in the right Iower abdomen. The Iiver area was tender and the superficial veins of the abdomina1 waI1 were diIated. The white blood count was 17,000, cephaIin floccuIation 4 +, thymo1 turbidity 2.6, icterus index rg, prothrombin time twenty-four seconds with a contro1 of fifteen seconds. X-ray examination of the abdomen showed free air in the right flank, stepIadder distention of the smaI1 bowel and a coproIith in the right lower abdomen. BIood cuIture was normaI. The patient ran a septic fever to 105~~. daiIy. He was treated with a MiIIer-Abbott tube, Iarge doses of peniciIIin and streptomycin, 250 cc. of whoIe blood daily and intramuscular heparin for the first two weeks of his hospita1 stay. An abscess in the right lower abdomen was drained on the seventh day and the pus cultured Esch. coIi. The patient’s fever subsided. After two cephalin fIoccuIation determinations of 4 +, a negative was obtained a month after admission. The icterus index dropped to 8 and bromsuIfaIein excretion was normaI. The patient was discharged on his twenty-ninth hospita1 day. The appendix was removed four months Iater and showed heaIing appendicitis and periappendicitis. Liver biopsy was normaI. COMMENT
The incidence of pyIephIebitis scess has decreased in recent earIier diagnosis and treatment
and Iiver abyears due to , of appendicitis 4’4
Liver
Abscess
and possibIy somewhat to the rather genera1 use of antibiotics. The history of appendicitis, however, may be atypica1 and confusing as in most of the cases in the present series, accounting for a delay in diagnosis. The chiI1 or better muItipIe chiIIs as pointed out by CoIp3v4 are heIpfu1 when present. The presence of a Iaminated coproIith or fecaIith in the right Iower quadrant on a fiat roentgenogram of the abdomen serves to focus attention on the appendix as a possible source of infIammation. There were three coproliths in the six recent cases in this series. In a group of IOO acuteIy inff amed appendices removed consecutively, Remington16 reported that fecaIiths associated with gangrene and rupture of the appendix were more frequent in the twenty-six cases showing thrombosis of the appendicea1 veins. Once a diagnosis of pyIephIebitis is suspected, vigorous supportive therapy is necessary in view of the proIonged and wasting nature of this process. Multiple transfusions heIp combat the anemia and hypoproteinemia which deveIop. Antibiotics can steriIize the bIood stream as evidenced by bIood cuItures becoming negative, and every effort shouId be made to choose the proper drug by sensitivity tests when the causative organism can be cuItured. AnticoaguIant therapy probabIy is useful judging by a very limited experience with it. It may be able to prevent the spread of the thrombosis to the Iarger veins whiIe the antibiotics dea1 with the organisms in the bIood stream. Heparin in 50 mg. doses is probabIy preferable to dicumaro1 in view of the severe toxic depression of the Iiver which is present. In spite of a11 the therapeutic methods avaiIabIe, the mortaIity of pyIephIebitis with Iiver abscess remains high. The prognosis with a singIe Iiver abscess is better than with muItipIe abscesses as shown by 0chsner13 who found a mortality of 37.5 per cent with a singIe compared to g5 per cent for muItipIe abscesses. EIiason6 was of the opinion that a single abscess was due to a septic emboIus from a circumscribed venous infection and had a fairly good prognosis foIIowing surgica1 drainage. Of his fourteen cases of pyIephIebitis with liver abscess, seven had singIe abscesses and lived. Two of the three survivors in the present series had singIe Iarge abscesses in the right lobe of the Iiver though one was multilocuIated. It remains to be shown whether specific antibiotic and anticoaguIant therapy can
PyIephIebitis overcome pyIephIebitis liver abscesses.
with
muItiple
and Liver
small
Abscess REFERENCES
I. D’ABREU, F. Suppurative
SUMMARY
2.
Ten of seventeen cases of pyIephIebitis with Iiver abscess were due to acute gangrenous or perforated appendicitis, an incidence of 5g per cent. The other seven cases were due to other suppurative disease in the pIeura1 or peritoneal cavities. 2. Diagnosis was diffrcuIt to make cIinicaIIy due to the atypica1 history and findings. Shaking chiIIs before or shortIy after the onset of symptoms and a coproIith in the right Iower abdomen by x-ray examination were heIpfu1 when they were present. 3. Jaundice was an important manifestation of the condition being present in tweIve of seventeen cases with icterus indices generalIy from rg to 25. 4. Blood cuItures were positive in nine of the thirteen patients tested with the predominant organism being Esch. coIi foIIowed by hemolytic streptococcus and hemolytic staphlococcus aureus either separately or associated with coIi-aerogenes organisms. 5. Treatment since 1946 consisted of drainage of appendicea1, subphrenic or Iiver abscesses where indicated, antibiotics chosen by sensitivity test when the organism was avaiIabIe for cuIture, anticoagulant therapy with heparin and supportive measures such as frequent blood transfusions. 6. Mortahty in the eleven cases prior to 1946 was IOO per cent whiIe it was 50 per cent in the six cases since that time. Two of the three patients who survived had drainage of singIe abscesses in the right Iobe of the Iiver. I.
3.
4. 5.
pyIeph1ebiti.s with recovery. Proc. Roy. Sot. Med., 39: 309, 1946. ALLEN, W. G. and MURWCK, L. H. PylephIebitis. Tri-State M. J., 9: 1876, 1936-1938. COLP, R. The treatment of pylephlebitis of appendicuIar origin. Surg., Gynec. @ Obst., 43: 627, 1926. COLP, R. The treatment of pyIephIebitis of appendicuIar origin. Ann. Surg., 85: 257, 1927. EITZEN, 0. Acute gangrenous appendicitis complicated by pyIephIebitis. Obio State M. J., 40:
325, ‘944. 6. ELIASON, E. L. PyIephIebitis and Iiver abscess. Surg., Gynec. @ Obst., 42: 5 IO, 1926. 7. HANCOCK, J. D. PyIephIebitis. South. M. J., 34: 647. 1941. 8. HAWKES, S. Z. Thrombophlebitis of the appendicia1 vein complicating acute appendicitis. Surg., Gynec. ti Obst., 66: 62, 1938. 9. KARSNER, H. Human PathoIogy, 6th ed. Philadelphia, 1942. J. B. Lippincott Co, IO. KELLY, H. A. and HURWN, E. The Vermiform Appendix and Its Diseases. PhiIadeIphia, 1905. W. B. Saunders & Co. II. MILLIKEN, N. T. and STRYKER, H. B., JR. Suppurative pyIethrombophIebitis and muItipIe Iiver abscesses following acute appendicitis; report of case with recovery. New England J. Med., 244: 52, 1951. 12. MILLS, J. H. MuItipIe liver abscess. Nortbwest Med., 51: 315, 1952. 13. OCHSNER, A., DEBAKEY, M. and MURRAY, S. Pyogenic abscess of the liver. Am. J. Surg., 40: 292, 1938. IL. (STTENBEKG. R. and BERCK. M. SuIfaniIamide therapy for suppurative pyIephIebitis and Iiver abscesses. J. A. M. A., II: 1374, 1938. 15. PETREN, G. iSber Leberabscess als Komplikation zu akuter Appendicitis. Beitr. z. K&n. Cbir., 94: 225, 19’4. 16. REMINGTON,J. H. and MCDONALD, J. R. Vascular thrombosis in acute appendicitis. Surgery, 24: 787, 1948. 17. THALHIMER, W. ChiIIs occurring earIy in appendicitis before operation and their indication of an operabIe stage of pyIephIebitis. Arch. Surg., 8: 658, ‘924. 18. WILENSKY, A. 0. PyIephIebitis under penicillin and sulfadiazine therapy. New York State J. Med., 45: 2082, 1945.
Acknowledgment: GratefuI acknowIedgment is extended to Dr. F. A. Simeone for permission to examine the records at CIeveIand City Hospital.
416