J Gastrointest Surg (2010) 14:8287 DOI 10.

1007/s11605-009-1036-y

ORIGINAL ARTICLE

Evolution of Surgical Treatment of Amebiasis-Associated Colon Perforation

Csar Athi-Gutirrez & Heriberto Rodea-Rosas & Clemente Guzar-Bermdez & Avisa Alcntara & Eduardo E. Montalvo-Jav

Received: 23 May 2009 / Accepted: 2 September 2009 / Published online: 23 September 2009 # 2009 The Society for Surgery of the Alimentary Tract

Abstract Background Amebiasis is a worldwide health problem that mainly affects developing countries. Invasive amebiasis tends to develop complications, and among these, perforation of the colon, although infrequent (1.99.1%), is the most lethal. Surgical treatment in these cases should be carried out in a timely fashion prior to the presentation of systemic repercussions or death. In the present study, we analyzed a total of 122 cases of invasive amebiasis-associated colon perforation. Methods and Study Design We conducted a clinical, retrospective, and observational study and presented cases of colonic perforation observed over the past 30 years at the Medical-Surgical Emergency Service of the Mexico City-based Hospital General de Mxico OD during the 19701999 period. Results During this time, a total of 19,916 emergency abdominal surgeries were performed. One hundred twenty-two of these procedures corresponded to cases of colon perforation by ameba, which represents 0.6%; 80 patients were men (65.6%) and 42 were women (34.4%), with an average age of 48 years. Multiple colon perforation was 74%, with right colon the most affected (90.5%). Depending on the perforations extension and localization, right hemicolectomy with ileostomy were performed in 53 patients (43.45%), subtotal colectomy with ileostomy in 43 (35.25%), left hemicolectomy with transverse colostomy in 12 (9.83%), exteriorization of perforated left colon (stoma) in 13 (10.65%), and primary closure with exteriorization in one patient (0.8%). Post-operative complications were present in 48 patients (39.3%), and 20 cases were related with the creation of a stoma. Eighteen of these cases were due to persistent abdominal sepsis and ten due to toxic colon; the latter correspond solely to patients with initial nonresective treatment. General mortality was 40%, with 32% (17 of 53 cases) of mortality in those submitted to right hemicolestomy, 16.7% (two of 12) of left hemicolestomy, 44.2% (19 of 43) in those in whom a subtotal colectomy was performed, with 76.9% (ten of 13) patients with exteriorization of the perforated right colon, and with 100% (one of one patient) mortality with primary closure. Conclusions Perforation is the most frequent surgical complication of invasive amebiasis of the colon, occurring principally in masculine gender and in the fourth decade of life. Resection and stoma creation is the procedure of choice that can resolve the septic focus from the first surgical procedure, depending on the general status of the patient. However, morbidity and mortality are high, and there is a tendency for these to be lower on comparing initial cases with those with recently conducted surgical procedures.
C. Athi-Gutirrez : H. Rodea-Rosas : C. Guzar-Bermdez : E. E. Montalvo-Jav Servicio de Ciruga General, Hospital General de Mxico, Secretara de Salud (SSA), Mexico City, Mexico E. E. Montalvo-Jav (*) Departamento de Ciruga, Facultad de Medicina, Universidad Nacional Autnoma de Mxico (UNAM), Av. Universidad 3000, Circuito Interior, Edificio D PB, 04510 Mxico, D.F., Mexico City, Mexico e-mail: montalvoeduardo@hotmail.com C. Athi-Gutirrez (*) Puente de Piedra 150-727, C.P.14500 Mxico, D.F., Mxico e-mail: drcesarathie@prodigy.net.mx

A. Alcntara Servicio de Anatoma Patolgica, Hospital General de Mxico, Secretara de Salud, Mexico City, Mexico

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Keywords Colon . Mortality . Perforation . Amebas . Amebiasis . Surgery . Colostomy . Sepsis . Metronidazole . Mexico

Histopathologic Study We systematically reviewed the biopsies performed prior to the procedure with micro- and macrosurgical analyses of the small and large intestine. These samples were added to 10% formol and performed with hematoxylin and eosin stain. Study Population This included all patients with a surgical intervention for acute abdominal pathology during the period from January 1970 to December 1999 with transoperative findings of colon perforation-associated peritonitis.

Introduction Amebiasis is the second most frequent parasitosis worldwide,1,2 affects approximately 10% of the population,3,4 and is the second or third cause of death due to parasitosis. 5,6 In Mexico, it is considered that the population is the carrier of 20% but that only 2% suffer from the disease; however, it is thought that this number is underestimated because a prevalence has been found of up to 55% in some low-socioeconomic-level zones in Mexico City.2,68 The range of the invasive disease comprises from a clinical symptom of slight diarrhea up to fulminating events of colon and liver; within this range, we find the intestinal and hepatic forms as well as the most important complications for its potential mortality.4 The colon is the main organ affected, and colitis can present in five different forms: asymptomatic colonization, acute amebic colitis, fulminating colitis, appendicitis,9,10 and ameboma.11 Intestinal perforation is the most serious complication of fulminating colitis and can eventually be fatal; fortunately, these cases of fulminating or necrotizing colitis occur in only 1.99.1% of cases; however, they cause very high mortality.12,13 Thus, it is indispensable to suspect the disease, to detect the disease as well as its complications, and to treat the disease in a timely fashion to be able to diminish high morbidity and mortality to the maximum degree. In the present study, we evaluated the frequency of amebaassociated colon perforation, its tendency over the past three decades, and the different surgical procedures utilized for its treatment.

Results We obtained a total of 122 patients who were submitted to ameba perforation-related surgery during a 30-year study period (19701999). These patients represented 0.61% of all abdominal surgery cases with emergency abdominal surgery. With respect to gender, we found 82 men (65%) and 45 women (35%), with an average age of 48 years (range, 1689 years). Regarding antecedents of importance, we found alcoholism in 36% and smoking in 25% of the total number of patients. Preoperative Signs and Symptoms Forms of clinical presentation varied widely, with atypical clinical symptoms predominating with an interval of 525 days of evolution characterized by diarrheic syndrome with bloody mucus in evacuations, rectal straining at stool, rectal tenesmus, an attack on the patients general health status, and abdominal pain. Generalized abdominal pain predominated in 95% of cases, distension in 80%, data on peritoneal irritation in 89%, acute diarrhea in 60%, and chronic diarrhea in 5%. Fever in 30% was quantified as >37.5C, with an average of 5 days prior to hospital admission, with slight dehydration in 20% of patients, severe dehydration in 50%, and type 1 hypovolemic shock-state hemodynamic data in 23% of patients. Radiological Findings Results showed intestinal occlusion in 48% and pneumoperitoneum in 35%, with the former associated with free subdiaphragmatic air, corroborated by X-ray of thorax and abdomen.

Methods There were a total of 19,916 abdominal surgery procedures performed at the Emergency Unit of General del Hospital General de Mxico OD Surgery Service during a 30-year period (19701999). We conducted a retrospective, transversal, and descriptive review of cases of ameba-associated colon perforation confirmed by histopathologic study, found 122 patients with complete records, and studied the following variables: age, gender, socioeconomic condition, preoperative signs and symptoms, surgical procedure, associated complications, preoperative mortality, days of hospital stay, and days in intensive care. Patients were excluded who were <16 years of age and those without a diagnosis confirmed by the pathology.

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Average Days of Hospital Stay There was an average of 10 days of total hospital stay per patient. The average stay in the intensive care unit was 4 days in each patient. We found signs of peritoneal irritation in all cases. Cases of severe colitis (toxic colon or fulminating colitis) were present with systemic repercussion fundamentally with systemic inflammatory response, high blood pressure, and data of abdominal sepsis. Laboratory studies showed leukocytosis, albumin <3 mg/dL in 84% of cases, and 15,00021,000 leukocytes in 76% of cases. Histopathological Study We analyzed biopsies of small intestine and colon, primarily in lesions corresponding, in the great majority, to colon. In their diverse anatomical presentations, we observed macroscopically that initial lesions demonstrated colonic ulcer covered with necrotic material (Fig. 1). Other cases presented extensive destruction of the colonic mucosa with numerous confluent ulcerated areas (Fig. 2). On analyzing the surgical pieces microscopically, we observed an ulcerative lesion that extended to the muscle layer, with diffusion toward the submucosa. In the fundus of the ulcer, there was a group of amebas, as can be appreciated in Fig. 3. With greater augmentation, we were able to observe trophozoites of Entamoeba histolytica, which are characteristic of this type of colon (Fig. 4). Multiple colon perforation was present with greater frequency, corresponding to 75% of cases (92 cases) and unique perforation in 25% (30 cases). Evaluation of surgical risk in all patients was carried out according to American Society of Anesthesiologists (ASA) criteria; we found that cases with surgical procedures were classified as ASA II in 33 patients (27%), ASA III in 55 patients (45%),
Figure 2 Extensive destruction of the colonic mucosa by numerous confluent ulcerated areas.

and ASA IV in 34 patients (26.8%). From 1990 on, the Acute Physiology and Chronic Health Evaluation II disease classification was employed in ten patients, who obtained an average score of 18 (range, 529), finding that 50% had a score of >15. Diagnosis of invasive ameba-associated colon perforation was suspected in only 55 cases, that is, in 45% of cases; however, in no case was it suspected that the preoperative diagnosis would be associated with invasive amebiasis, rendering a preoperative diagnostic accuracy of 0% for invasive amebiasis. With regard to surgical treatment for control of intraabdominal septic foci, this was as follows: right hemicolectomy with ileostomy and Hartmann procedure in 53 of 122 patients (43.4%); left hemicolectomy with transversal colostomy of the transverse colon and Hartmann procedure in 12 of 122 patients (9.83%); subtotal colectomy with ileostomy and Hartmann procedure in 43 of 122 patients (35.25%); exteriorization and colostomy at perforation site

Figure 1 Initial lesions, with ulcer covered with necrotic material.

Figure 3 We are able to observe microscopically an ulcer that extends to the muscle layer, with diffusion toward the submucosa. A group of amebas is observed at the fundus of the ulcer.

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Number and cases distributed by decade and their associated mortality are shown in Table 2.

Discussion The frequency of colon perforation by amebiasis in Mexico has diminished considerably according to data provided in the present study on the decades of the 1970s, 1980s, and 1990s. According to our survey, late complications of the surgical event reflect greater mortality at the beginning of the study time period (1970s), reaching alarming numbers of 50% of deaths associated with complications as compared with complications observed in the 1990s of 10%. Among causes for this tendency, we find greater knowledge of amebic pathology, adequate antibiotic scheme (mainly with the use of metronidazole), medical care and advances in intensive therapy, and a colostomyderived surgical procedure, which in the majority of cases have provided a lower rate of mortality and complications in these patients. E. histolytica is a protozoan that evolves in cyst form, which is resistant to gastric secretion up to the trophozoite form and possesses lytic and destructive capacities in the colon. Infection is related with multifactorial mechanisms including the following: (1) the ability for motility and trophozoite phagocytosis and (2) the release of preformed peptides and proteases that produce lethal effects in white cells,14 carried out by means of an adherence sequence, tissue invasion, cytolysis, and inflammatory response.7 The trophozoite adheres to the cells of the mucosa by means of a cell surface protein denominated adherence lectin (Ga1/Ga1 NAc), amebopores, protein kinases that degrade extracellular protein and that give rise to disruption of the colonic mucosa, and the epithelial barrier.1519 Amebapores are polypeptides that are associated with amebic virulence and comprise poreforming cells in the white cell with cytolytic activity that induce the release of Na+, K+, and Ca+ from the soft cell and, finally, cytolysis.18 The inflammatory response is mediated by amebic phospholipases; however, the response is observed to be potentiated by cytolysis of epithelial and inflammatory cells, which add another proinflammatory mechanism.20 Adherence and the inflammatory response is followed by an intracellular increase of calcium in the white cell until their destructionin seconds and up to 20 minof adherence.20 Microscopically, ulcerations are caused that extend into the submucosa, provoking abundant microhemorrhages that progress underneath the mucosa, forming the characteristic shirt-button ulcers.13 Progression of these lesions can result in loss of the mucosa and submucosa and can eventually reach the serose and fracture it. All of these effects interact synergically with the bacterial flora and with the host (susceptibility, age, nutrition, and immunity).4,21

Figure 4 a, b E. histolytica trophozoites are observed in greater detail.

in 13 of 122 patients (10.6%), and primary closure in one patient (0.8%). Therefore stoma formation was carried out in 121 cases (99.2%), and in 35 patients (28.7%), two to five multiple reinterventions were performed as needed for control of abdominal sepsis. Mortality according to the surgical procedure conducted was as follows: right hemicolectomy, 32% (17 of 53); left hemicolestomy, 16.7% (two of 12); subtotal colectomy, 44.2% (19 of 43); exteriorization and colostomy, 76.9% (ten of 13), and primary closure in one patient, yielding a general mortality of 49 patients (40%); these can be observed in Table 1 under headings for each decade and according to each surgical procedure. The patient who underwent primary closure was excluded from Table 1 (column 3, total of 121 cases) due to being the sole patient with this treatment type. The general mortality of the present study was 40%, this being a total of 48 patients. According to the ASA classification, two patients were classified preoperatively with ASA II, 16 with ASA III, and 30 cases with ASA IV.

86 Table 1 Mortality by Decade and by Surgical Procedure Surgical procedure Right hemicolectomy Decade 19701979 19801989 19901999 19701979 19801989 19901999 19701979 19801989 19901999 19701979 19801989 19901999 Number of cases 35 15 3 53 4 6 2 12 31 10 2 43 8 4 1 13 121a Mortality (%) 13 4 0 17 1 0 1 2 15 4 0 19 6 3 1 10 (37) (26.7) (0) (32) (25) (0) (50) (16.7) (48.4) (40) (0) (44.2) (75) (75) (100) (76.9)

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Mortality ASA stage 13 patients: ASA II, 1; ASA III, 5; ASA IV, 7 4 patients: ASA III, 1; ASA IV, 3 No deaths 1 patient: ASA IV, 1 No deaths 1 patient: ASA III, 1 15 patients: ASA II, 1; ASA III, 6; ASA IV, 8 4 patients: ASA III, 1; ASA IV, 3 No deaths 6 patients: ASA III, 1; ASA IV, 5 3 patients: ASA III, 1; ASA IV, 2 1 patient: ASA IV, 1 ASA II, 2; ASA III, 16; ASA IV, 30

Total Left hemicolectomy

Total Subtotal colectomy

Total Exteriorization and colostomy

Total Total ASA American Society of Anesthesiologist

a

48 (40)%

The patient who underwent primary closure was excluded due to being the sole patient with this treatment type

These intestinal lesions, characteristic on healing, leave minimal or null scarring.13 The prevalence of amebiasis in our environment continues to be high;5,22 however, we appreciate in this report a progressive diminution of the number of cases of invasive amebiasis with the passing of the decades,23 in agreement with present-day amebiasis in Mexico, possibly related with medical care programs, of medical care, amebiasis detection, and facility of access to antimicrobial drugs. It is considered that approximately 90% of patients with E. histolytica colonization are healthy carriers and can be cured spontaneously; however, 10% of the remaining trophozoites invade the colon and cause colitis in diverse degrees in blind colon, ascendant colon, and/or rectosigmoids, in segmentary fashion and combined, and this can come to affect the entire colon.24,25 Fulminating colitis with perforation takes place in 0.5% of cases and is the most dangerous complication of invasive amebiasis, thus requiring emergency surgical treatment.13,26,27

Surgical treatment was directed toward removing or controlling the infection foci, as well as the effects of the associated peritonitis, and consisted of procedures conducted according to the conditions of the colon and the patients general health status. Right hemicolectomy was carried out in the majority of cases, followed by subtotal colectomy and left colectomy; however, a small group of very grave patients required exteriorization and in-site perforation colostomy as part of damage-control surgery in critical-state patients, who despite maximal-benefit surgery had very high mortality. Progressive diminution is appreciated in mortality from the decade of the 1970s toward lower mortality in the 1990s (Table 2), which is related with timely diagnosis, present-day peri-operative management and intensive therapy, as well as the effectiveness of antiamebic and antimicrobial drugs. In terms of acute clinical symptoms with an evolution time of <48 h, we are able to note that patients presented a smaller percentage of complications and morbimortality.

Table 2 Number of Cases by Decade and Their Mortality

Decade 19701979 19801989 19901999 Totals

Number of cases 76 37 9 122

Number of deaths 36 8 1 45

Mortality (%) 47.3 21.6 11 36.9

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87 salmonellosis in the General Hospital of Mexico, from 1975 to 1990. Analysis of 4,679 cases. Cir Gen 2008;30:136140. Guzmn-Valdvia G. Acute amebic appendicitis. World J Surg 2006;30:10381042. Rodea-Rosas H, Athi-Gutirrez C, Padilla MAD, Montalvo-Jav E, Guzae-Bermdez C. The behavior of amebomas during the last 4 decades, experience at the Hospital General of Mexico. Cir Gen 2008;30:7073. Ozdogan M, Baykal A, Aran O. Amebic perforation of the colon: rare and frequently fatal complication. World J Surg 2004;28:926929. Takahashi T, Gamboa-Domnguez A, Gmez-Mndez TJ, Remes JM, Rembis V, Martnez-Gonzlez D, Gutirrez-Saldvar J, Morales JC, Granados J, Sierra-Madero J. Fulminant amebic colitis: analysis of 55 cases. Dis Colon Rectum 1997;40:13621367. Tsutsumi V, Anaya-Velzquez F, Martnez-Palomo A. Experimental intestinal amebiasis: invasion and extension of the amebic lesion. Arch Invest Med (Mex) 1990;21(Suppl 1):4752. Ravdin JI, Guerrant RL. Role of adherence in cytopathogenic mechanisms of Entamoeba histolytica. Study with mammalian tissue culture cells and human erythrocytes. J Clin Invest 1981;68:13051313. Lpez-Vancell R, Montfort I, Prez-Tamayo R. Galactose-specific adhesin and cytotoxicity of Entamoeba histolytica. Parasitol Res 2000;86:226231. Das P, Debnath A, Muoz ML. Molecular mechanisms of pathogenesis in amebiasis. Indian J Gastroenterol 1999;18:161 166. Zhang X, Zhang Z, Alexander D, Bracha R, Mirelman D, Stanley SL Jr. Expression of amoebapores is required for full expression of Entamoeba histolytica virulence in amebic liver abscess but is not necessary for the induction of inflammation or tissue damage in amebic colitis. Infect Immun 2004;72:678683. Que X, Reed SL. Cysteine proteinases and the pathogenesis of amebiasis. Clin Microbiol Rev 2000;13:196206. Said-Fernndez S. Virulence factors of Entamoeba histolytica. Arch Invest Med (Mex) 1990;21:253262. Diamond LS. Amebiasis: nutritional implications. Rev Infect Dis 1982;4:843850. Lejeune M, Rybicka JM, Chadee K. Recent discoveries in the pathogenesis and immune response toward Entamoeba histolytica. Future Microbiol 2009;4:105118. Conde-Bonfil MC, de la Mora-Zerpa C. Entamoeba histolytica: a standing threat. Salud Publica Mex 1992;34:335341. Hsu YB, Chen FM, Lee PH, Yu SC, Chen KM, Yao YT, Hsu HC. Fulminant amebiasis: a clinical evaluation. Hepatogastroenterology 1995;42:109112. Essenhigh DM, Carter RL. Massive necrosis of the colon due to amoebiasis. Gut 1966;7:444447. Hasan M, Islam MA, Siddiqua SS, Shuvra MR. Colonic perforation due to necrotizing amoebic colitis. Mymensingh Med J 2003;12:6163. Shimada S, Mizumoto T, Nishioka R, Fukami K, Kuramoto M, Nomura K, Aoki N, Ogawa M. Acute fulminant necrotizing colitis caused by amebiasis: report of a case. Surg Today 2002;32:738741.

In conclusion, the invasion of the colon by amebas is a frequently found disease in Mexico and in countries with a high incidence of amebiasis. However, as described in the present study, a diminution has been observed in the number of cases of amebiasis in recent years. Colon perforation is the most serious complication. The most frequent data that characterize this pathology were severe systemic response, hypoperfusion, and abdominal sepsis. Colon perforation is the result of the necrosis on the colony wall, with destruction of the colonic mucosa and the presence of amebas. We must consider that a sole patient died, this a case with unique perforation that was sutured with primary closure, given that the remainder of the mucosa was found to be eroded in the postmortem study, with necrosis, tissue invasion, cytolysis, and microhemorrhagic zones that at the very short term ended in colon perforation. Thus, surgical treatment is wide resection of colon and stoma, not carrying out primary anastomosis, and primary closure of the perforation is contraindicated in general. In very grave patients with high trans-operative risk, we found very high mortality despite loop colostomy at the perforation site and later programmed reintervention.

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