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Liver Αbscess Secondary to Intrahepatic Gallbladder Perforation Report of three cases I. K. Skandalos, A. Th. Margioulas, E. A. Michailidou, D. A. Giannopoulou, E. A. Tsikrika, C. S. Karatziou, Ch. E. Stefanidou, Th. E. Drizis Received 13/12/2010 Accepted 20/02/2011

Abstract

Introduction

Background-Aim: Hepatic abscess secondary to intrahe-patic gallbladder perforation is very rare and only few cases are published in the literature. Methods: We present our experience of management of three cases of liver abscesses secondary to intrahepatic gallbladder perforation. All the patients manifested right upper quadrant abdominal pain and fever, accompanied by chills and vomiting in the first patient, by septic shock in the second and by general weakness in the third patient. In all three patients, liver abscess was diagnosed by sonography and computer tomography scanning, and attributed to intrahepatic perforation of the gallbladder. All patients underwent cholecystectomy and drainage of the liver abscess, preceded by percutaneous abscess drainage in one patient. Results: The postoperative period was not uneventful, resulting in two patients being discharged on the 28th and 33nd postoperative day, while the third patient died on the 27th postoperative day owing to sepsis. Conclusion: Liver abscesses secondary to intrahepatic gallbladder perforation is a serious illness that must be managed immediately by cholecystectomy and abscess drainage, while concomitant diseases should also be addressed. Furthermore, the mortality and morbidity rates are high primarily because of delayed diagnosis.

Hepatic abscesses are mainly amoebic or pyogenic in origin. The pyogenic liver abscess is usually caused by ascending cholangitis secondary to a benign or malignant biliary tract obstruction, while other rare causes include diverticulitis, appendicitis, pancreatic abscess, Crohn’s disease, trauma, endocarditis, and cryptogenic cirrhosis [1, 2, 3]. Cholecystohepatic fistula and liver abscess formation caused by intrahepatic perforation of the gallbladder is a very rare but life-threatening complication of acute cholecystitis. Very few cases of intrahepatic perforation and liver abscess formation secondary to acute cholecystitis have been reported in the literature [4, 5]. The presented cases in this study are true liver abscesses caused by contiguous spread of the inflammation of the perforated gallbladder intrahepatically.

Key words: Cholecystitis, Cholecystohepatic fistula, Gallbladder perforation, Liver abscess, Percutaneous transhepatic drainage. I. Skandalos (Corresponding author), A. Th. Margioulas, E. A. Michailidou, Th. E. Drizis - Department of Surgery D. A. Giannopoulou - Department of Anaesthesiology E. A. Tsikrika - Intensive Care Unit C. S. Karatziou - Department of Radiology Ch. E. Stefanidou - Laboratory of Microbiology General Hospital Agios Pavlos, Thessaloniki, Greece e-mail: [email protected]

Patients – methods Three cases of liver abscesses secondary to acute cholecystitis, caused by contiguous spread of the infection into the liver are presented. The first case involves a 76-year-old female who was admitted with symptoms of right upper quadrant pain, fever, chills and vomiting for the previous 24 hours. She had been hospitalized three weeks beforehand for acute pancreatitis and was under treatment with cefuroxime for a productive cough that had started 5 days earlier. Her concomitant diseases included diabetes mellitus, hypothyroidism, hypertension, atrial fibrillation. During physical examination, the patient complained of epigastric pain while Murphy’s sign was positive. Blood investigation revealed: Hct 33.1%, WBC 1900/μL, Neu 53.3%, Lym 40%, PLTs 150000/μL, glucose 138 mg/dl, urea 31mg/dl, alkaline phosphatase 342U/L, total bilirubin 1.2mg/dl with a direct fraction of 0.9mg/ dl, SGOT 35U/L, SGPT 31U/L, amylase 35U/L. Ultrasonography (US) scanning depicted a gallbladder under tension containing small gallstones and a communicating intrahepatic cystic mass. A computer tomography (CT) scan was subsequently performed which identified a cystic liver lesion

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measuring 11 x 6 cm, in contact with the distended gallbladder (Fig. 1). The lesion was interpreted as a biloma caused by gallbladder perforation. The second case concerned a 78-year-old female that was admitted for septic shock with right upper quadrant pain of 5 days’ duration and fever reaching 39.2o C. Her concomitant diseases included diabetes mellitus, hypertension and atrial fibrillation. Blood investigations revealed Hct 34.1%, WBC 33000/μL, Neu 58.5%, Lym 40%, PLTs 186000/μL, glucose 212 mg/dl, urea 23 mg/dl, total bilirubin 1.0 mg/dl with a direct fraction of 0.60 mg/dl, γGT 234U/L, SGOT 48U/L, SGPT 58U/L. An ultrasonography scan was performed which was significant for a distended gallbladder with thickened walls and a cystic liver lesion. Subsequent CT imaging detected the pres-ence of complicated cholecystitis with luminal rup-ture, gallstones in the neck of the gallbladder and a low density (18 Hounsfield units) lobular lesion of the liver, in contact with the gallbladder.

neck, with thickening of the walls, in addition to multiple hepatic abscesses (densities ranging from 20 to 30 Hounsfield units). Moreover, an abscess located in the IV liver segment was in direct contact with the inflamed gallbladder. All patients were operated; the first and third patients as soon as diagnosis was established, while the second patient was first subjected to percutaneous transhepatic CT-guided drainage (Fig. 2) that did not successfully resolve the abscess. All patients underwent cholecystectomy, drainage of the communicating liver abscess and subsequent introduction of a No18 Foley tube in the remaining cavity, as well as drainage of the infrahepatic area using a Penrose drain. After the operation, all three patients were transferred to the Intensive Care Unit due to haemodynamic instability.

Fig. 2

Percutaneous transhepatic CT-guided drainage of the liver abscess

Fig. 1 CT imaging of gallbladder empyema and the adjacent liver abscess The third case was a 78-year-old male with right upper quadrant pain that had commenced 5 days before his admittance, fever up to 38.5o C, dizziness and general weakness. He mentioned a recent hospitalization for investigation of a fever of unknown origin that was attributed to a urine tract infection. His medical history was significant for coronary disease, CABG, the presence of a permanent pacemaker, and nephrolithiasis. His blood investigation showed Hct 33.7%, WBC 21490/μL, Neu 89.2%, Lym 6.1%, PLTs 515000/μL, glucose 116mg/dl, urea 160mg/dl, alkaline phosphatase 308U/L, total bilirubin 0.40mg/dl with a direct fraction of 0.30mg/dl, γGT 190U/L, SGOT 43U/L, SGPT 67U/L, amylase 67U/L, PCT (procalcitonin) 53,89 ng/ml and CRP 13,5 mg/dl. The US scan showed a contracted gallbladder as well as multiple liver cysts. CT imaging depicted a gallbladder containing gallstones in the

Results The culture of the aspirated pus was positive in the first patient for Klebsiella pneumoniae and Enterococcus faecium, in the second patient for Streptococcus anginosus and Lactobacillus gasseri, and in the third for Escherichia coli and Bacteroides fragilis. The antibiotic therapy was adjusted accord-ingly. The histopathology examination confirmed the diagnosis of acute cholecystitis without malig-nancy. The postoperative follow-up of the abscess cavity was done fluoroscopically in the first patient by contrast administration through the drainage tube (Fig. 3), and by CT imaging in the other two patients (Fig. 4). The drainage tubes were removed in the first patient on the 26th day, while in the second patient the Penrose drain was removed on the 31st postoperative day. The recovery of all patients was complicated by surgical site infections, treated with drainage of the accumulated pus, while the second

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patient also suffered from postoperative pneumonia. Two patients were discharged on the 28th and 33nd postoperative day, while the third patient died on the 27th postoperative day due to overwhelming sepsis.

Fig. 3 Fluoroscopy: Imaging of the remaining cavity of the abscess by contrast administration through the drainage tube (30 days post-operatively)

Fig. 4 CT scan: Imaging of the remaining cavity of the abscess (25 days postoperatively)

Discussion The primary cause of acute cholecystitis is the per-

Liver Abscess Secondary to Intrahepatic Gallbladder Perforation

sistent occlusion of the cystic duct by an impacted stone that causes increased gallbladder wall tension, epithelial injury and release of phospholipases, degradation of adjacent cell membranes, and intense inflammatory reaction [6]. In the adult population, 10 to 20% of the individuals are affected by asymptomatic gallstones [7]. Among them, 1 to 2% will suffer from acute cholecystitis in their lifetime [8]. Perforation of the gallbladder is a rare complication that occurs in 2 to 11% of all cases of acute cholecystitis [9]. Perforation of the gallbladder may occur early in the course of acute cholecystitis or may develop as late as several weeks after the onset of the disease. Although acute cholecystitis is more common among females, gallbladder perforation is more frequent in males [10]. Spontaneous perforations of gallbladder are divided into three categories, according to Niemer’s classification. Type I (16%) is associated with bile peritonitis and causes the highest mortality rate, type II (68%) presents with the formation of a pericholecystic abscess and type III (16%) is associated with fistulous connections with adjacent organs or structures, usually the duodenum or the transverse colon [11,12]. Very few cases have been reported in the literature of intrahepatic perforation and liver abscess formation, secondary to acute cholecystitis [4]. A cholecystohepatic fistula is more common among elderly patients and is a more indolent process with unclear pathogenesis. Local factors, such as chronic inflammation and gallbladder wall ischaemia, are thought to be the most important components of the process, as well as the partially or totally intrahepatic positioning of the gallbladder [13]. However, systemic factors, such as immunosuppression, may also be of great importance. In our cases, all three patients were elderly with many systemic diseases, two of whom had recently been hospitalized due to acute inflammatory disease. Acute cholecystitis presents with a severe onset of abdominal pain, nausea, vomiting and fever. Leukocytosis and elevated liver enzymes, mainly of the alkaline phosphatase and bilirubin, are commonly seen. Our patients showed symptoms of acute cholecystitis and leucocytosis, with the exception of the first patient who had leucopenia. Occasionally, gallbladder perforation may not be clinically different from uncomplicated acute cholecystitis, since patients have no symptoms or signs of abscess formation and physical examination, laboratory tests and imaging methods may not establish a diagnosis. Two of our three patients had been admitted and treated in the recent past for febrile

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abdominal pain that was attributed to acute pancreatitis and urinary tract infection respectively. This may result in delayed diagnosis [10, 14] and a subsequently higher morbidity and mortality [15, 16]. A liver abscess can often be differentiated from a neoplasm by using sonography, CT scanning or magnetic resonance imaging [1, 2, 17, 18]. A pyogenic abscess, as typically appears on a CT scan, is a well-defined, round, hypodense mass with a central density of 0-45 Hounsfield units. The peripheral wall usually enhances with contrast administration and internal septa may be present. Small microabscesses may coalesce to form a larger abscess. At sonography, a pyogenic abscess generally appears round or ovoid, with variable internal echos while US findings of acute cholecystitis, such as gallbladder wall thickening, gallbladder distension, free pericholecystic fluid and positive sonographic Murphy’s sign may also be present in gallbladder perforation [10, 15, 18, 19]. The differential diagnosis for a liver abscess may include neoplasms, amoebic abscess, or haemorrhagic cyst [4] while there is high incidence of gallbladder cancer with acute cholecystitis [20, 21]. In our cases, the suspicion of intrahepatic perforation of the gallbladder that resulted from the ultrasonography scan was confirmed by CT imaging. Gallbladder perforation and its associated complications are considered surgical emergencies. The standard treatment of a pyogenic liver abscess secondary to gallbladder perforation includes cholecystectomy, drainage of the liver abscess, abdominal lavage and proper antibiotic coverage, while treating any concomitant diseases [10, 17, 22]. Treatment with antibiotics alone has been reported, especially early in the course of the disease and when there is no surgically correctable aetiological factor [23]. CT- or US- guided percutaneous drainage could also be successful in poor-risk patients with solitary abscesses [24, 25]. In addition, laparoscopy can facilitate diagnosis of the disease or even drainage of the abscess, when a percutaneous attempt has failed [26]. Early laparoscopic cholecystectomy during acute cholecystitis appears to be safe and shortens the total hospital stay [27] provided that it is performed by a laparoscopy-oriented surgeon [28]. Recent literature has also published a case of an intrahepatic abscess due to gallbladder perforation, successfully treated by endoscopic stent placement within the gallbladder, after poor response to percutaneous drainage [29]. All of our patients underwent cholecystectomy and drainage of the liver abscess, preceded by a percutaneous transhepatic CT-guided drainage in the second patient that failed to successfully resolve the process.

Mortality rates for pyogenic liver abscess range between 5 and 40%, the highest appearing in patients with underlying advanced malignancy, immunosuppression, multiple liver abscesses (as in our third case), and are primarily associated with delayed diagnosis, old age and sepsis [12]; improvement in mortality rates is mainly attributed to the advancements in anaesthesiology and intensive care. Morbidity and mortality rates for this condition have improved significantly over the last few decades [2, 6]. In conclusion, formation of a liver abscess secondary to gallbladder perforation is a rare but potentially lethal illness. Early diagnosis, immediate surgical intervention, correction of the underlying process while addressing the concomitant diseases, timely use of the appropriate systemic antibiotics and transfer of the patient to the Intensive Care Unit, are all essential to the provision of optimal care for the patient.

Conflict of interest The authors declare that they have no conflict of interest.

References

1. Rustgi AK, Richter JM. Pyogenic and amebic liver abscess. Med Clin North Am 1989; 73: 847-858 2. Frey CF, Zhu Y, Suzuki M, Isaji S. Liver abscesses. Surg Clin North Am 1989; 69: 259-271 3. Mehta RB, Parija SC, Chetty DV, Smile RR. Management of 240 cases of liver abscess. Int Surg 1986; 71: 91-94 4. Izadi K, Moser FG, Haker K, Satey S. Gallstone liver abscess secondary to gallbladder perforation. Radiol Cases Rep 2009; 4: 280 5. Bakalakos EA, Melvin WS, Kirkpatrick R. Liver abscess secondary to intrahepatic perforation of the gallbladder, presenting as a liver mass. Am J Gastroenterol 1996; 91: 1644-1646 6. Aljiffry M, Walsh M, Peltekian K, Molinari M. Type II gall bladder perforation with abdominal wall abscess in a cirrhotic patient: case report and review of the literature. J Surg Educ 2008; 65: 367-371 7. Gibney EJ. Asymptomatic gallstones. Br J Surg 1990; 77: 368372 8. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg 1993; 165: 399-404 9. Abu-Dalu J, Urca I. Acute cholecystitis with perforation into the peritoneal cavity. Arch Surg 1971; 102: 108-110 10. Derici H, Kara C, Bozdag AD, Nazli O, Tansug T, Akca E. Diagnosis and treatment of gallbladder perforation. World J Gastroenterol 2006; 12: 7832-7836 11. Swayne LC, Fillipone A. Gallbladder perforation: Correlation of cholescintigraphic and sonographic findings with the Niemeir classification. J Nucl Med 1990; 31: 1915-1920 12. Chong VH, Lim KS, Mathew VV. Spontaneous gallbladder perforation, perocholecystic abscess and cholecystoduodenal fistula as the first manifestations of gallstone disease. Hepatobiliary Pancreat Dis Int 2009; 8: 212-214 13. Peer A, Witz E, Manor H, Strauss S. Intrahepatic abscess due to gallbladder perforation. Abdominal Imag 1995; 20: 452-455 14. Zerman G, Bonfiglio M, Borzellino G et al. Liver abscess

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due to acute cholecystitis. Report of five cases. Chir Ital 2003; 55: 195-198 15. Menakuru SR, Kaman L, Behera A, Singh R, Katariya RN. Current management of gall bladder perforations. ANZ J Surg 2004; 74: 843-846 16. Doherty GM, Way LW. Billiary tract. In: Way LW, Doherty GM. Current Diagnosis and Treatment Surgery. 13th ed. New York: McGray-Hill, 2010: 544-571 17. Klatchko BA, Schwartz SI. Diagnosis and therapeutic approaches to pyogenic abscess of the liver. Surg Gynecol Obstet 1989; 168: 332-336 18. Sood B, Jain M, Khandelwal N, Singh P, Suri S. MRI of perforated gallbladder. Australas Radiol 2002; 46: 438-440 19. Chen JJ, Lin HH, Chiu CT, Lin DY. Gallbladder perforation with intrahepatic abscess formation. J Clin Ultrasound 1990; 18: 43-45 20. Lam CM, Yuen AW, Wai AC et al. Gallbladder cancer presenting with acute cholecystitis: a population-based study. Surg Endosc 2005; 19: 697-701 21. Kim JH, Kim WH, Kim JH, Yoo BM, Kim MW. Unsuspected gallbladder cancer diagnosed after laparoscopic cholecystectomy: focus on acute cholecystitis. World J Surg 2010; 34: 114-120 22. Miedema BW, Dineen P. The diagnosis and treatment of pyogenic liver abscesses. Ann Surg 1984; 200: 328-335 23. Stain SC, Yellin AE, Donovan AJ, Brien HW. Pyogenic liver abscess. Modern treatment. Arch Surg 1991; 126: 991-996 24. Robert JH, Mirescu D, Ambrosetti P, Khoury G, Greenstein AJ, Rohner A. Critical review of the treatment of pyogenic hepatic abscess. Surg Gynecol Obstet 1992; 174: 97-102 25. Mischinger HJ, Hauser H, Rabl H et al. Pyogenic liver abscess: studies of therapy and analysis of risk factors. World J Surg 1994; 18: 852-857 26. Yanaga K, Kitano S, Hashizume M, Ohta M, Matsumata T, Sugimachi K. Laparoscopic drainage of pyogenic liver abscess. Br J Surg 1994; 81: 1022 27. Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR. Meta-analysis of randomized controlled trials on the safety and effectiveness of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 2010; 97: 141-150 28. Kortram K, Reinders JS, van Ramshorst B, Wiezer MJ, Go PM, Boerma D. Laparoscopic cholecystectomy for acute cholecystitis should be performed by a laparoscopic surgeon. Surg Endosc 2010; 24: 2206-2209 29. Kang MS, Park do H, Kwon KD et al. Endoscopic transcystic stent placement for an intrahepatic abscess due to gallbladder perforation. World J Gastroenterol 2007; 7: 1458-1459

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Ηπατικό Aπόστηµα Λόγω Ενδοηπατικής Διάτρησης της Χοληδόχου Κύστης Αναφορά Tριών Περιπτώσεων Ι. Κ. Σκάνδαλος, Α. Θ. Μαργιούλας, Ε. Α. Μιχαηλίδου, Δ. Α. Γιαννοπούλου, Ε. Α. Τσικρίκα, Χ. Σ. Καράτζιου, Χ. Ε. Στεφανίδου, Θ. Ε. Δρίζης

Περίληψη Εισαγωγή: Το ηπατικό απόστημα που οφείλεται σε ενδοηπατική διάτρηση της χοληδόχου κύστης αποτελεί μία εξαιρετικά σπάνια αλλά βαρεία κλινική κατάσταση, με αναφορά λίγων περιπτώσεων στη βιβλιογραφία. Υλικό - μέθοδοι: Την τελευταία πενταετία αντιμετωπίσαμε τρεις περιπτώσεις ηπατικού αποστήματος οφειλόμενου σε ενδοηπατική διάτρηση της χοληδόχου κύστης, 2 γυναίκες και ένα άνδρα ηλικίας 76, 78 και 78 ετών. Όλοι οι ασθενείς εκδήλωσαν ως κύριο σύμπτωμα άλγος δεξιού υποχονδρίου και πυρετό που συνοδεύονταν σε ένα ασθενή από ρίγος και εμέτους, σε άλλο από γενικευμένη καταβολή και στον τρίτο από σηπτική καταπληξία. Δύο ασθενείς παρουσίαζαν λευκοκυττάρωση ενώ ένας λευκοπενία. Η διάγνωση τεκμηριώθηκε σε όλες τις περιπτώσεις με υπερηχοτομογραφικό έλεγχο και αξονική τομογραφία. Όλοι οι ασθενείς υποβλήθηκαν σε χειρουργική επέμβαση χολοκυστεκτομής και παροχέτευσης του ηπατικού αποστήματος, ενώ σε ένα ασθενή προηγήθηκε της χειρουργικής επέμβασης διαδερμική παροχέτευση του ηπατικού αποστήματος χωρίς όμως πλήρη εξάλειψη του. Μετεγχειρητικά οι ασθενείς αντιμετωπίσθηκαν στη Μονάδα Εντατικής Θεραπείας. Ο έλεγχος της υπολειμματικής κοιλότητας του αποστήματος σε ένα ασθενή έγινε ακτινολογικά με έγχυση ιωδιούχου σκιαστικού μέσω του σωλήνα παροχέτευσης ενώ σε δύο με αξονική τομογραφία. Αποτελέσματα: Η καλλιέργεια πύου του ηπατικού αποστήματος ήταν θετική και στις τρεις περιπτώσεις με απομόνωση συνδυασμού μικροβίων. Η ιστολογική εξέταση της χοληδόχου κύστης επιβεβαίωσε την κλινική διάγνωση οξείας χολοκυστίτιδας χωρίς ευρήματα κακοήθειας. Η νοσηλεία των ασθενών

ήταν μακρά. Οι δύο εξήλθαν του νοσοκομείου την 28η και την 33η ενώ ο τρίτος ασθενής απεβίωσε την 27η μετεγχειρητική ημέρα σε σηπτική κατάσταση. Συζήτηση: Η ενδοηπατική διάτρηση της χοληδόχου κύστης σε έδαφος οξείας χολοκυστίτιδας αποτελεί εξαιρετικά σπάνια κλινική κατάσταση. Προδιαθεσικοί παράγοντες είναι η χρόνια φλεγμονή και η ισχαιμία του τοιχώματος της χοληδόχου κύστης καθώς και η μερική ή ολική ενδοηπατική εντόπιση της. Κλινικά εκδηλώνεται με εντοπισμένο άλγος δεξιού υποχονδρίου, ναυτία, εμετό και πυρετό, ενώ στον εργαστηριακό έλεγχο, συνήθως, βρίσκεται λευκοκυττάρωση και αύξηση των ηπατικών ενζύμων. Η τεκμηρίωση της διάγνωσης γίνεται με υπερηχοτομογραφικό έλεγχο και αξονική τομογραφία.Η θεραπεία είναι σύνθετη με χορήγηση αντιβιοτικών, αντιμετώπιση συνοδών παθήσεων, χολοκυστεκτομή και παροχέτευση του ηπατικού αποστήματος. Η νοσηρότητα και θνητότητα είναι υψηλές, ενώ έχουν βελτιωθεί τα τελευταία χρόνια με την έγκαιρη διάγνωση και αντιμετώπιση των ασθενών.

Λέξεις κλειδιά Χολοκυστίτιδα, Χολοκυστοηπατικό συρίγγιο, Διάτρηση χοληδόχου κύστης, Ηπατικό απόστημα, Διαδερμική διηπατική παροχέτευση

Χειρουργικό Τμήμα, Τμήμα αναισθησιολογίας, Μονάδα Εντατικής Θεραπείας, Ακτινολογικό Τμήμα, Μικροβιολογικό Εργαστήριο, Γενικό Νοσοκομείο “Άγιος Παύλος”, Θεσσαλονίκης