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Conservative management of infected necrosis complicating severe acute pancreatitis
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2003 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 98, No. 1, 2003 ISSN 0002-9270/03/$30.00 PII S0002-9270(02)05830-6
Conservative Management of Infected Necrosis Complicating Severe Acute Pancreatitis Douglas G. Adler, M.D., Suresh T. Chari, M.D., Tamela J. Dahl, R.N., Michael B. Farnell, M.D., and Randall K. Pearson, M.D., F.A.C.G. Department of Internal Medicine, Division of Gastroenterology and Hepatology, and Department of Surgery, Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, Minnesota
OBJECTIVES: Patients with severe necrotizing pancreatitis are at risk for infection, a major cause of morbidity and mortality. Most patients with infected pancreatic tissue require surgical intervention (necrosectomy), which is associated with high morbidity and mortality. A subset of these patients can be managed successfully with conservative management combined with prolonged courses of antibiotics. METHODS: Three cases of severe acute pancreatitis seen at our institution are described, in which the patients developed aspirate-proven pancreatic infections. The patients were nonetheless stable from a clinical standpoint and were treated with long courses of antibiotics known to penetrate the pancreas; emergent surgery was deferred. RESULTS: In two patients, surgery was completely avoided, with good clinical outcome. In the third patient, elective surgery was undertaken 12 wk after the episode of acute pancreatitis, to perform necrosectomy on organized pancreatic necrosis and to evaluate the patient’s biliary tree. There were no postoperative complications. CONCLUSIONS: A subset of patients with severe acute pancreatitis complicated by infection can be successfully managed with long term antibiotics and other supportive measures. High risk necrosectomy can, in some instances, be delayed or avoided entirely. (Am J Gastroenterol 2003;98: 98 –103. © 2003 by Am. Coll. of Gastroenterology)
INTRODUCTION Patients with severe necrotizing pancreatitis are at high risk for developing concomitant infections, usually of necrotic tissue or in peripancreatic fluid collections. Standard management dictates urgent surgical debridement and drainage of infected pancreatic necrosis. The morbidity and mortality associated with surgical necrosectomy are high because of the complexity of the surgery and the compromised nature of these patients, many of whom are also experiencing multiorgan failure. In some patients, a protracted course of antibiotics and supportive measures can delay or obviate surgery. We present a series of three patients with proven infected pancreatic necrosis or severe infected peripancre-
atic collections in whom surgical debridement was delayed (n ⫽ 1) or entirely avoided (n ⫽ 2). Case 1 A 74-yr-old woman without a history of alcohol use presented to our institution with 48 h of epigastric abdominal pain without significant nausea or vomiting. Physical examination was remarkable for normal vital signs. Admission temperature was 36.7°C. Physical examination showed an ill-appearing elderly woman with a normal cardiopulmonary examination. She had mild to moderate pain on palpation of her epigastrium, with active bowel sounds and no peritoneal signs. Initial laboratory evaluation revealed: amylase 2156 and lipase 2506 U/L with normal AST, ALT, ALP, bilirubin, creatinine, Hb, and glucose. A CT scan with oral contrast was obtained and revealed edema of the head, uncinate, and proximal body of the pancreas consistent with acute pancreatitis (Fig. 1A). There was no evidence of gallbladder disease or gallstones. The patient was taking a thiazide diuretic for chronic hypertension, and this agent was discontinued as a potential confounding etiology. The patient was managed in the hospital for 6 days without antibiotics and with aggressive hydration, pain management, and gradual reintroduction of oral intake. She was dismissed on a regular diet, which she was tolerating well. She was readmitted 10 days later with recurrent abdominal pain and fever to 38.5°C. Repeat CT scan (with i.v. contrast) showed extensive pancreatic necrosis with gas formation (Fig. 1B). Although febrile, she was otherwise clinically stable. A nasojejunal tube was placed. Treatment with i.v. imipenem, fluids, and nasojejunal feedings led to prompt resolution of fever, and the patient felt well. Based on the CT findings, ultrasound-guided aspiration of an accessible subhepatic collection was performed, which produced copious purulent material and debris that grew Escherichia coli as well as anaerobic Gram negative bacilli species (Fusobacterium and Campylobacter showae). A catheter was placed into a larger collection and an initial drainage of 700 ml of purulent and necrotic material was achieved. General surgical consultation was obtained, and continued conservative therapy was recommended because
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On discharge, the patient was prescribed levofloxacin 500 mg p.o. once daily, and metronidazole 500 mg p.o. q.i.d. for 30 days. After 4 wk, a sinogram demonstrated complete collapse of the collection and the drain was pulled. A repeat CT scan demonstrated marked improvement in the peripancreatic and pancreatic fluid collections (Fig. 1C). The patient has remained pain free and without recurrence of pancreatitis 7 months after presentation. No surgical interventions were performed.
Figure 1. (A) Noncontrast CT showing peripancreatic inflammation around the head, uncinate process, and proximal body. (B) Contrast-enhanced CT showing lack of perfusion in the region of the pancreatic head (arrows) and gas-filled fluid collections (star). (C) CT scan demonstrating near total resolution of fluid collections.
of the patient’s lack of fever and improving clinical status. Imipenem was given i.v. for 3 wk on an inpatient basis, with continued clinical improvement. Nasojejunal feedings were discontinued and the patient was gradually advanced to a regular diet.
Case 2 A 52-yr-old woman with a 24-yr history of alcohol abuse presented with abdominal pain and biochemical evidence of acute pancreatitis (amylase 599, lipase 1261 U/L) after drinking approximately 1 L of vodka. Physical examination found the patient to be afebrile but in moderate distress. Her abdomen was tender to palpation over her epigastrium. The remainder of the examination was unremarkable. Transabdominal ultrasound was performed, which was negative for gallstones and revealed a gallbladder that was normal in appearance. Initial CT (Fig. 2A) demonstrated a well perfused pancreas with inflammation and peripancreatic fat necrosis. Conservative treatment, including antibiotic prophylaxis with i.v. imipenem, was instituted. Surgical consultation recommended continued medical therapy in light of clinical improvement. The patient remained in hospital for 4 wk because of intense abdominal pain, which gradually abated. During her admission, she was placed on clear liquids and was eventually able to tolerate a full diet. She was weaned from pain medications before discharge, and was discharged from the hospital to an alcohol rehabilitation program. Six weeks after discharge, the patient again presented to our institution. She complained of fever, nausea, vomiting, and weight loss. Repeat abdominal CT demonstrated persistent pancreatic inflammation with complex, poorly organized peripancreatic fluid collections (Fig. 2B). Despite these findings, the patient seemed to be clinically stable. Ultrasound-guided aspiration of a pancreatic collection demonstrated purulent material that was culture positive for Staphylococcus aureus. Zosyn was administered i.v. for 9 days during hospitalization, which resulted in prompt resolution of fever. The patient was discharged with instructions to take ciprofloxacin (500 mg p.o. b.i.d.) and to receive daily cefazolin (1 g i.v. every 8 h) for 4 wk through our outpatient infusion center. She was compliant with this regimen. After cessation of antibiotics, this patient did well and subsequently gained 15 pounds. One year later, she continues to do well and has not had any recurrences of pancreatitis. Follow-up CT showed resolution of all fluid collections and pancreatitis (Fig. 2C). The patient remains abstinent from alcohol. Case 3 A 70-yr-old woman without significant past medical history presented to an outside hospital after the onset of acute
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Figure 3. (A) Extensive peripancreatic fluid collections containing gas. (B) Organizing pancreatic necrosis containing persistent gas. (C) Fully organized fluid collection. Figure 2. (A) Contrast-enhanced CT scan showing findings of acute pancreatitis with peripancreatic fat stranding and a homogenously, well perfused pancreatic body and tail (arrow). (B) Diffuse, poorly defined peripancreatic fluid collections. (C) Resolution of peripancreatic fluid collections.
abdominal pain accompanied by nausea and vomiting. Initial laboratory tests were remarkable for an amylase of 3,800, lipase of 14,000 U/L, and white blood cell count of 25,000. A CT scan was performed and confirmed the diagnosis of acute pancreatitis, revealing significant pancreatic and peripancreatic inflammation. The patient was admitted
to the hospital and was managed conservatively for 5 days, with marked clinical improvement. She was discharged home feeling well with only trace abdominal discomfort. One month later, the patient presented to our institution with gradually escalating abdominal pain, nausea, vomiting, and fevers. A CT scan showed a large necrotic sequestrum containing air, extrinsically compressing the patient’s stomach and duodenum (Fig. 3A). She was febrile but clinically stable. Imipenem (1 g i.v. every 8 h) was begun because of a strong suspicion of infection with prompt resolution of fever. Her abdominal symptoms improved with conserva-
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tive management. The patient was slowly advanced to a regular diet, which was well tolerated. Imipenem was administered i.v. for 1 wk on an inpatient basis. Subsequently, CT-guided aspiration of the fluid collection yielded 310 ml of purulent fluid that was culture positive for E. coli. (Fig. 3B). A drainage catheter was not placed, as the radiologist believed that the collection was not suitable for CT-guided drainage. Of note, air was seen in the biliary tree. Based on her otherwise stable clinical appearance, our surgical colleagues advised against immediate surgical intervention. A 6-wk outpatient course of oral levofloxacin (500 mg p.o. once daily) was initiated on discharge from the hospital. Subsequent CT-guided aspiration fluid collection after completion of antibiotic therapy produced necrotic debris that was culture negative. Three months after this patient’s initial presentation to our institution, an abdominal CT scan (Fig. 3C) showed consolidation of the sequestrum into a thickwalled structure. An elective necrosectomy and cholecystectomy was then performed, and the patient had an uneventful postoperative course. The surgery was prompted, in part, by a wish to perform a concomitant surgical evaluation of the biliary system, as the patient was seen to have air in the biliary tree on a CT scan. The referring surgeon was concerned about a possible fistula between the infected pancreatic collection and the biliary tree, which, if present, could lead to chronic biliary infection or biliary lithiasis. At surgery, a cholecystoduodenal fistula was found and repaired. Gram stain of the necrotic pancreatic tissue revealed that there were no organisms present at the time of surgery.
DISCUSSION Infection is the most dreaded late complication of acute pancreatitis. Early mortality (within 2 wk) is primarily due to the systemic inflammatory response syndrome leading to multisystem organ failure. Late mortality in the setting of acute pancreatitis is usually a consequence of bacterial infection of necrotic pancreatic parenchyma (1). Although the majority of patients with acute pancreatitis will not have any infectious complications, up to 12% of patients with acute pancreatitis will develop some pancreatic or peripancreatic infection during the course of disease, the majority of whom will also have developed some degree of pancreatic necrosis (2). Tissue samples from patients with infected pancreatic necrosis typically yield Gram negative organisms of intestinal origin such as E. coli, Klebsiella, and Enterococcus species. Less commonly seen organisms include Enterobacter species, staphylococci, anaerobic organisms, and fungi (3). Oral bowel decontamination is sometimes used as a prophylactic agent in patients with severe acute pancreatitis to prevent bacterial translocation from the gut. Antibiotic therapy with agents that penetrate the pancreas (cefuroxime, imipenem, and quinolone agents) are thought to decrease the rate of infection and to increase survival in patients with severe acute pancreatitis with pancreatic ne-
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crosis (4 – 6). Although encouraging, these studies were not double-blinded in design, and definitive proof of efficacy is lacking. Furthermore, there is concern about the emergence of fungal superinfections with the use of broad-spectrum antibiotics (e.g., imipenem) (7). Despite these limitations, prophylactic broad-spectrum antibiotics are widely used in the setting of acute necrotizing pancreatitis. The standard approach to the management of infected necrosis complicating acute pancreatitis is early surgical drainage and debridement (8 –11). Surgical management has been shown to significantly decrease overall mortality (12), despite the fact that many patients with infected pancreatic necrosis are often poor surgical candidates because of the underlying pancreatitis itself. At many institutions, surgery is often performed in acutely ill patients with infected pancreatic necrosis as soon as bacterial or fungal infection is confirmed by fine needle aspiration (2). Fine needle aspiration is almost always performed with CT or ultrasound guidance (13, 14). Debridement procedures performed early in the clinical course of these patients are often complex and difficult, requiring frequent intra-abdominal packing, subsequent operative procedures, and a long postoperative course with significant potential complications (most notably, fistula formation). Nonetheless, in most cases, surgery is performed in these patients in the hope that providing surgical drainage and debridement of infected tissue and fluid will arrest the patient’s clinical decline and allow for eventual improvement. Because the typical patient with infected pancreatic necrosis often has serious comorbid conditions, the surgical mortality associated with necrosectomy is high. At our own institution, in-hospital mortality associated with necrosectomy was 25% in a published series (15). Consequently, there has been interest in conservative management of patients with infected pancreatic necrosis (16). Runzi et al. (16) have reported on their experience in treating 13 patients with pancreatic necrosis nonsurgically, 11 of whom were infected. All patients received mezlocillin or ciprofloxacin in combination with metronidazole, or received antibiotic monotherapy with imipenem. Six patients received percutaneously placed drainage catheters (one of whom developed a colonic perforation from the catheter, which ultimately resulted in the patient’s demise). Of the remaining 12 patients, six were discharged without surgery a mean of 8 wk after admission. The other six patients ultimately underwent surgery in a semielective basis for well demarcated abscess formation or persistent pancreatic necrosis a mean of 36 ⫾ 16 days after admission. None of these patients died. Dubner et al. (17) reported three patients who were found to have infected pancreatic necrosis or infected peripancreatic fluid collections on fine needle aspiration. Two of these patients were found to be positive for E. coli infection, whereas the third was found to harbor an anaerobic, Gram negative rod that was not further identified. Dubner et al.
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treated these patients with a variety of antibiotics but predominately with agents known to penetrate the pancreas. All three patients had been evaluated by surgeons and advised to proceed to necrosectomy. In this series, the patients were either medically too unstable to undergo surgery or expressed a strong preference for medical therapy. In contrast, however, the patients in our series were surprisingly stable from a clinical point of view, despite having culture-proven infections of pancreatic necrosis or large peripancreatic fluid collections resulting from severe episodes of acute pancreatitis. The exact reasons for these relatively mild clinical courses in the face of apparent severe disease remain unclear. None of our patients developed multiorgan failure during their inpatient stays. In all three cases, surgeons with extensive experience in treating pancreatic diseases were consulted, who advocated ongoing conservative medical management with antibiotics. This was also partially prompted by the opinion that patients who were culture positive but clinically stable would best avoid the operative risks of debridement and the possible postoperative complications. In addition, in patients ultimately requiring debridement, a delay in operation might provide the surgeon a well demarcated, organized collection leading to a simplified (one stage) procedure, and reduced operative morbidity and mortality (e.g., case 3). Antibiotics with excellent pancreatic penetration, predominately imipenem and fluoroquinolones, were used in all three cases. It is interesting to note that all of our patients developed infection of pancreatic necrosis late in their clinical course, after their initial discharge from the hospital. This delayed presentation of infection may have been partially responsible for the clinical course and response to conservative therapy in our cohort. Runzi and Layer (16) and other authors (18) included cases in which patients with severe infections complicating acute pancreatitis have been successfully treated with antibiotics and percutaneous catheter drainage, both in patients with pancreatic necrosis and peripancreatic infections without necrosis. This was similar to the management used in case 1 in our series. Although one of our patients received a drainage catheter to decompress an infected fluid collection, two other patients without drainage catheters did well. One of these (patient 2) is an example of infection complicating peripancreatic fat necrosis without parenchymal involvement. This patient was successfully managed with antibiotics after diagnostic aspiration confirmed infection. The third patient in this series ultimately underwent an elective necrosectomy several weeks after completing a prolonged course of antibiotics. The authors recognize the unusual nature of the cases presented in this manuscript, and understand that the overwhelming majority of patients with infected pancreatic necrosis and clinical decompensation are best managed with early surgical drainage and debridement. This series demonstrates that some patients with infected pancreatic necro-
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sis are clinically stable and can be managed conservatively with prolonged, targeted antibiotics. After careful assessment by pancreatic surgeons and internists, some patients can delay or avoid surgery.
ACKNOWLEDGMENT We thank Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, for his assistance in the preparation of this manuscript. Reprint requests and correspondence: Douglas G. Adler, M.D., Mayo Clinic, Department of Internal Medicine, Division of Gastroenterology and Hepatology, 200 1st Street, SW, Rochester, MN 55901. Received Apr. 18, 2002; accepted Aug. 26, 2002.
REFERENCES 1. Isenmann R, Buchler MW. Infection and acute pancreatitis. Br J Surg 1994;81:1707–8. 2. Beger HG, Isenmann R. Surgical management of necrotizing pancreatitis. Surg Clin North Am 1999;79:783–80. 3. Beger HG, Bittner R, Block S, et al. Bacterial contamination of pancreatic necrosis: A prospective clinical study. Gastroenterology 1986;91:433–8. 4. Buchler M, Malfertheiner P, Frieb H, et al. Human pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 1992;103:1902–8. 5. Pederzoli R, Bassi C, Vesentini S, Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 1992;176:480 –3. 6. Sainio V, Kemppainen E, Puolakkainen P, et al. Early antibiotic treatment in acute necrotizing pancreatitis. Lancet 1995; 346:663–7. 7. Grewe M, Tsiotos GG, Luque de-leon EL, Sarr MG. Fungal infections in acute necrotizing pancreatitis. J Am Coll Surg 1999;188:408 –14. 8. Lumsden A, Bradley EL. Secondary pancreatic infections. Surg Gynecol Obstet 1990;170:459 –67. 9. Imrie CW. Surgical management of necrotizing pancratitis: Indications for surgical management. In: Beger GH, Warshaw AL, Buchel MW, et al., eds. The pancreas. Oxford: Blackwell Scientific, 1998:557–61. 10. Howard JM. Delayed debridement and external drainage of massive pancreatic and peripancreatic necrosis. Surg Gynecol Obstet 1989;168:25–9. 11. Sarr MG, Nagorney DM, Much P, et al. Acute necrotizing pancreatitis: Management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. Br J Surg 1991;78:576 –81. 12. Bradley EL, Allen K. A prospective longitudinal study of observation versus intervention in the management of necrotizing pancreatitis. Am J Surg 1991;161:19 –25. 13. Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997;92:377–86. 14. Rau B, Pralle U, Mayer JM, et al. Role of ultrasonographically guided fine-needle aspiration cytology in the diagnosis of infected pancreatic necrosis. Br J Surg 1998;85:179 –84. 15. Tsiotos GG, Luque de Leon E, Soreide JA, et al. Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique. Am J Surg 1998;175:91–8.
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16. Runzi M, Layer P. Nonsurgical management of acute pancreatitis: Use of antibiotics. Surg Clin North Am 1999;79:759 – 65. 17. Dubner H, Steinberg W, Hill M, et al. Infected pancreatic necrosis and peripancreatic fluid collections: Serendipitous
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response to antibiotics and medical therapy in three patients. Pancreas 1996;12:298 –302. 18. Ashley S, Perez A, Pierce EA. Necrotizing pancreatitis: Contemporary analysis of 99 consecutive cases. Ann Surg 2001; 234:572–9.
Vol. 98, No. 1, 2003 ISSN 0002-9270/03/$30.00 PII S0002-9270(02)05830-6
Conservative Management of Infected Necrosis Complicating Severe Acute Pancreatitis Douglas G. Adler, M.D., Suresh T. Chari, M.D., Tamela J. Dahl, R.N., Michael B. Farnell, M.D., and Randall K. Pearson, M.D., F.A.C.G. Department of Internal Medicine, Division of Gastroenterology and Hepatology, and Department of Surgery, Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, Minnesota
OBJECTIVES: Patients with severe necrotizing pancreatitis are at risk for infection, a major cause of morbidity and mortality. Most patients with infected pancreatic tissue require surgical intervention (necrosectomy), which is associated with high morbidity and mortality. A subset of these patients can be managed successfully with conservative management combined with prolonged courses of antibiotics. METHODS: Three cases of severe acute pancreatitis seen at our institution are described, in which the patients developed aspirate-proven pancreatic infections. The patients were nonetheless stable from a clinical standpoint and were treated with long courses of antibiotics known to penetrate the pancreas; emergent surgery was deferred. RESULTS: In two patients, surgery was completely avoided, with good clinical outcome. In the third patient, elective surgery was undertaken 12 wk after the episode of acute pancreatitis, to perform necrosectomy on organized pancreatic necrosis and to evaluate the patient’s biliary tree. There were no postoperative complications. CONCLUSIONS: A subset of patients with severe acute pancreatitis complicated by infection can be successfully managed with long term antibiotics and other supportive measures. High risk necrosectomy can, in some instances, be delayed or avoided entirely. (Am J Gastroenterol 2003;98: 98 –103. © 2003 by Am. Coll. of Gastroenterology)
INTRODUCTION Patients with severe necrotizing pancreatitis are at high risk for developing concomitant infections, usually of necrotic tissue or in peripancreatic fluid collections. Standard management dictates urgent surgical debridement and drainage of infected pancreatic necrosis. The morbidity and mortality associated with surgical necrosectomy are high because of the complexity of the surgery and the compromised nature of these patients, many of whom are also experiencing multiorgan failure. In some patients, a protracted course of antibiotics and supportive measures can delay or obviate surgery. We present a series of three patients with proven infected pancreatic necrosis or severe infected peripancre-
atic collections in whom surgical debridement was delayed (n ⫽ 1) or entirely avoided (n ⫽ 2). Case 1 A 74-yr-old woman without a history of alcohol use presented to our institution with 48 h of epigastric abdominal pain without significant nausea or vomiting. Physical examination was remarkable for normal vital signs. Admission temperature was 36.7°C. Physical examination showed an ill-appearing elderly woman with a normal cardiopulmonary examination. She had mild to moderate pain on palpation of her epigastrium, with active bowel sounds and no peritoneal signs. Initial laboratory evaluation revealed: amylase 2156 and lipase 2506 U/L with normal AST, ALT, ALP, bilirubin, creatinine, Hb, and glucose. A CT scan with oral contrast was obtained and revealed edema of the head, uncinate, and proximal body of the pancreas consistent with acute pancreatitis (Fig. 1A). There was no evidence of gallbladder disease or gallstones. The patient was taking a thiazide diuretic for chronic hypertension, and this agent was discontinued as a potential confounding etiology. The patient was managed in the hospital for 6 days without antibiotics and with aggressive hydration, pain management, and gradual reintroduction of oral intake. She was dismissed on a regular diet, which she was tolerating well. She was readmitted 10 days later with recurrent abdominal pain and fever to 38.5°C. Repeat CT scan (with i.v. contrast) showed extensive pancreatic necrosis with gas formation (Fig. 1B). Although febrile, she was otherwise clinically stable. A nasojejunal tube was placed. Treatment with i.v. imipenem, fluids, and nasojejunal feedings led to prompt resolution of fever, and the patient felt well. Based on the CT findings, ultrasound-guided aspiration of an accessible subhepatic collection was performed, which produced copious purulent material and debris that grew Escherichia coli as well as anaerobic Gram negative bacilli species (Fusobacterium and Campylobacter showae). A catheter was placed into a larger collection and an initial drainage of 700 ml of purulent and necrotic material was achieved. General surgical consultation was obtained, and continued conservative therapy was recommended because
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On discharge, the patient was prescribed levofloxacin 500 mg p.o. once daily, and metronidazole 500 mg p.o. q.i.d. for 30 days. After 4 wk, a sinogram demonstrated complete collapse of the collection and the drain was pulled. A repeat CT scan demonstrated marked improvement in the peripancreatic and pancreatic fluid collections (Fig. 1C). The patient has remained pain free and without recurrence of pancreatitis 7 months after presentation. No surgical interventions were performed.
Figure 1. (A) Noncontrast CT showing peripancreatic inflammation around the head, uncinate process, and proximal body. (B) Contrast-enhanced CT showing lack of perfusion in the region of the pancreatic head (arrows) and gas-filled fluid collections (star). (C) CT scan demonstrating near total resolution of fluid collections.
of the patient’s lack of fever and improving clinical status. Imipenem was given i.v. for 3 wk on an inpatient basis, with continued clinical improvement. Nasojejunal feedings were discontinued and the patient was gradually advanced to a regular diet.
Case 2 A 52-yr-old woman with a 24-yr history of alcohol abuse presented with abdominal pain and biochemical evidence of acute pancreatitis (amylase 599, lipase 1261 U/L) after drinking approximately 1 L of vodka. Physical examination found the patient to be afebrile but in moderate distress. Her abdomen was tender to palpation over her epigastrium. The remainder of the examination was unremarkable. Transabdominal ultrasound was performed, which was negative for gallstones and revealed a gallbladder that was normal in appearance. Initial CT (Fig. 2A) demonstrated a well perfused pancreas with inflammation and peripancreatic fat necrosis. Conservative treatment, including antibiotic prophylaxis with i.v. imipenem, was instituted. Surgical consultation recommended continued medical therapy in light of clinical improvement. The patient remained in hospital for 4 wk because of intense abdominal pain, which gradually abated. During her admission, she was placed on clear liquids and was eventually able to tolerate a full diet. She was weaned from pain medications before discharge, and was discharged from the hospital to an alcohol rehabilitation program. Six weeks after discharge, the patient again presented to our institution. She complained of fever, nausea, vomiting, and weight loss. Repeat abdominal CT demonstrated persistent pancreatic inflammation with complex, poorly organized peripancreatic fluid collections (Fig. 2B). Despite these findings, the patient seemed to be clinically stable. Ultrasound-guided aspiration of a pancreatic collection demonstrated purulent material that was culture positive for Staphylococcus aureus. Zosyn was administered i.v. for 9 days during hospitalization, which resulted in prompt resolution of fever. The patient was discharged with instructions to take ciprofloxacin (500 mg p.o. b.i.d.) and to receive daily cefazolin (1 g i.v. every 8 h) for 4 wk through our outpatient infusion center. She was compliant with this regimen. After cessation of antibiotics, this patient did well and subsequently gained 15 pounds. One year later, she continues to do well and has not had any recurrences of pancreatitis. Follow-up CT showed resolution of all fluid collections and pancreatitis (Fig. 2C). The patient remains abstinent from alcohol. Case 3 A 70-yr-old woman without significant past medical history presented to an outside hospital after the onset of acute
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Figure 3. (A) Extensive peripancreatic fluid collections containing gas. (B) Organizing pancreatic necrosis containing persistent gas. (C) Fully organized fluid collection. Figure 2. (A) Contrast-enhanced CT scan showing findings of acute pancreatitis with peripancreatic fat stranding and a homogenously, well perfused pancreatic body and tail (arrow). (B) Diffuse, poorly defined peripancreatic fluid collections. (C) Resolution of peripancreatic fluid collections.
abdominal pain accompanied by nausea and vomiting. Initial laboratory tests were remarkable for an amylase of 3,800, lipase of 14,000 U/L, and white blood cell count of 25,000. A CT scan was performed and confirmed the diagnosis of acute pancreatitis, revealing significant pancreatic and peripancreatic inflammation. The patient was admitted
to the hospital and was managed conservatively for 5 days, with marked clinical improvement. She was discharged home feeling well with only trace abdominal discomfort. One month later, the patient presented to our institution with gradually escalating abdominal pain, nausea, vomiting, and fevers. A CT scan showed a large necrotic sequestrum containing air, extrinsically compressing the patient’s stomach and duodenum (Fig. 3A). She was febrile but clinically stable. Imipenem (1 g i.v. every 8 h) was begun because of a strong suspicion of infection with prompt resolution of fever. Her abdominal symptoms improved with conserva-
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tive management. The patient was slowly advanced to a regular diet, which was well tolerated. Imipenem was administered i.v. for 1 wk on an inpatient basis. Subsequently, CT-guided aspiration of the fluid collection yielded 310 ml of purulent fluid that was culture positive for E. coli. (Fig. 3B). A drainage catheter was not placed, as the radiologist believed that the collection was not suitable for CT-guided drainage. Of note, air was seen in the biliary tree. Based on her otherwise stable clinical appearance, our surgical colleagues advised against immediate surgical intervention. A 6-wk outpatient course of oral levofloxacin (500 mg p.o. once daily) was initiated on discharge from the hospital. Subsequent CT-guided aspiration fluid collection after completion of antibiotic therapy produced necrotic debris that was culture negative. Three months after this patient’s initial presentation to our institution, an abdominal CT scan (Fig. 3C) showed consolidation of the sequestrum into a thickwalled structure. An elective necrosectomy and cholecystectomy was then performed, and the patient had an uneventful postoperative course. The surgery was prompted, in part, by a wish to perform a concomitant surgical evaluation of the biliary system, as the patient was seen to have air in the biliary tree on a CT scan. The referring surgeon was concerned about a possible fistula between the infected pancreatic collection and the biliary tree, which, if present, could lead to chronic biliary infection or biliary lithiasis. At surgery, a cholecystoduodenal fistula was found and repaired. Gram stain of the necrotic pancreatic tissue revealed that there were no organisms present at the time of surgery.
DISCUSSION Infection is the most dreaded late complication of acute pancreatitis. Early mortality (within 2 wk) is primarily due to the systemic inflammatory response syndrome leading to multisystem organ failure. Late mortality in the setting of acute pancreatitis is usually a consequence of bacterial infection of necrotic pancreatic parenchyma (1). Although the majority of patients with acute pancreatitis will not have any infectious complications, up to 12% of patients with acute pancreatitis will develop some pancreatic or peripancreatic infection during the course of disease, the majority of whom will also have developed some degree of pancreatic necrosis (2). Tissue samples from patients with infected pancreatic necrosis typically yield Gram negative organisms of intestinal origin such as E. coli, Klebsiella, and Enterococcus species. Less commonly seen organisms include Enterobacter species, staphylococci, anaerobic organisms, and fungi (3). Oral bowel decontamination is sometimes used as a prophylactic agent in patients with severe acute pancreatitis to prevent bacterial translocation from the gut. Antibiotic therapy with agents that penetrate the pancreas (cefuroxime, imipenem, and quinolone agents) are thought to decrease the rate of infection and to increase survival in patients with severe acute pancreatitis with pancreatic ne-
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crosis (4 – 6). Although encouraging, these studies were not double-blinded in design, and definitive proof of efficacy is lacking. Furthermore, there is concern about the emergence of fungal superinfections with the use of broad-spectrum antibiotics (e.g., imipenem) (7). Despite these limitations, prophylactic broad-spectrum antibiotics are widely used in the setting of acute necrotizing pancreatitis. The standard approach to the management of infected necrosis complicating acute pancreatitis is early surgical drainage and debridement (8 –11). Surgical management has been shown to significantly decrease overall mortality (12), despite the fact that many patients with infected pancreatic necrosis are often poor surgical candidates because of the underlying pancreatitis itself. At many institutions, surgery is often performed in acutely ill patients with infected pancreatic necrosis as soon as bacterial or fungal infection is confirmed by fine needle aspiration (2). Fine needle aspiration is almost always performed with CT or ultrasound guidance (13, 14). Debridement procedures performed early in the clinical course of these patients are often complex and difficult, requiring frequent intra-abdominal packing, subsequent operative procedures, and a long postoperative course with significant potential complications (most notably, fistula formation). Nonetheless, in most cases, surgery is performed in these patients in the hope that providing surgical drainage and debridement of infected tissue and fluid will arrest the patient’s clinical decline and allow for eventual improvement. Because the typical patient with infected pancreatic necrosis often has serious comorbid conditions, the surgical mortality associated with necrosectomy is high. At our own institution, in-hospital mortality associated with necrosectomy was 25% in a published series (15). Consequently, there has been interest in conservative management of patients with infected pancreatic necrosis (16). Runzi et al. (16) have reported on their experience in treating 13 patients with pancreatic necrosis nonsurgically, 11 of whom were infected. All patients received mezlocillin or ciprofloxacin in combination with metronidazole, or received antibiotic monotherapy with imipenem. Six patients received percutaneously placed drainage catheters (one of whom developed a colonic perforation from the catheter, which ultimately resulted in the patient’s demise). Of the remaining 12 patients, six were discharged without surgery a mean of 8 wk after admission. The other six patients ultimately underwent surgery in a semielective basis for well demarcated abscess formation or persistent pancreatic necrosis a mean of 36 ⫾ 16 days after admission. None of these patients died. Dubner et al. (17) reported three patients who were found to have infected pancreatic necrosis or infected peripancreatic fluid collections on fine needle aspiration. Two of these patients were found to be positive for E. coli infection, whereas the third was found to harbor an anaerobic, Gram negative rod that was not further identified. Dubner et al.
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treated these patients with a variety of antibiotics but predominately with agents known to penetrate the pancreas. All three patients had been evaluated by surgeons and advised to proceed to necrosectomy. In this series, the patients were either medically too unstable to undergo surgery or expressed a strong preference for medical therapy. In contrast, however, the patients in our series were surprisingly stable from a clinical point of view, despite having culture-proven infections of pancreatic necrosis or large peripancreatic fluid collections resulting from severe episodes of acute pancreatitis. The exact reasons for these relatively mild clinical courses in the face of apparent severe disease remain unclear. None of our patients developed multiorgan failure during their inpatient stays. In all three cases, surgeons with extensive experience in treating pancreatic diseases were consulted, who advocated ongoing conservative medical management with antibiotics. This was also partially prompted by the opinion that patients who were culture positive but clinically stable would best avoid the operative risks of debridement and the possible postoperative complications. In addition, in patients ultimately requiring debridement, a delay in operation might provide the surgeon a well demarcated, organized collection leading to a simplified (one stage) procedure, and reduced operative morbidity and mortality (e.g., case 3). Antibiotics with excellent pancreatic penetration, predominately imipenem and fluoroquinolones, were used in all three cases. It is interesting to note that all of our patients developed infection of pancreatic necrosis late in their clinical course, after their initial discharge from the hospital. This delayed presentation of infection may have been partially responsible for the clinical course and response to conservative therapy in our cohort. Runzi and Layer (16) and other authors (18) included cases in which patients with severe infections complicating acute pancreatitis have been successfully treated with antibiotics and percutaneous catheter drainage, both in patients with pancreatic necrosis and peripancreatic infections without necrosis. This was similar to the management used in case 1 in our series. Although one of our patients received a drainage catheter to decompress an infected fluid collection, two other patients without drainage catheters did well. One of these (patient 2) is an example of infection complicating peripancreatic fat necrosis without parenchymal involvement. This patient was successfully managed with antibiotics after diagnostic aspiration confirmed infection. The third patient in this series ultimately underwent an elective necrosectomy several weeks after completing a prolonged course of antibiotics. The authors recognize the unusual nature of the cases presented in this manuscript, and understand that the overwhelming majority of patients with infected pancreatic necrosis and clinical decompensation are best managed with early surgical drainage and debridement. This series demonstrates that some patients with infected pancreatic necro-
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sis are clinically stable and can be managed conservatively with prolonged, targeted antibiotics. After careful assessment by pancreatic surgeons and internists, some patients can delay or avoid surgery.
ACKNOWLEDGMENT We thank Thomas Smyrk, M.D., Department of Pathology, Mayo Clinic, for his assistance in the preparation of this manuscript. Reprint requests and correspondence: Douglas G. Adler, M.D., Mayo Clinic, Department of Internal Medicine, Division of Gastroenterology and Hepatology, 200 1st Street, SW, Rochester, MN 55901. Received Apr. 18, 2002; accepted Aug. 26, 2002.
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