Unusual cases of acute cholecystitis and cholangitis: Tokyo Guidelines

Unusual cases of acute cholecystitis and cholangitis include (1) pediatric biliary tract infections, (2) geriatric biliary tract infections, (3) acalculous cholecystitis, (4) acute and intrahepatic cholangitis accompanying hepatolithiasis (5) acute biliary tract infection accompanying malignant pancreatic-biliary tumor, (6) postoperative biliary tract infection, (7) acute biliary tract infection accompanying congenital biliary dilatation and pancreaticobiliary maljunction, and (8) primary sclerosing cholangitis. Pediatric biliary tract infection is characterized by great differences in causes from those of adult acute biliary tract infection, and severe cases should be immediately referred to a specialist pediatric surgical unit. Because biliary tract infection in elderly patients, who often have serious systemic conditions and complications, is likely to progress to a serious form, early surgery or biliary drainage is necessary. Acalculous cholangitis, which often occurs in patients with serious concomitant conditions, such as those in intensive care units (ICUs) and those with disturbed cardiac, pulmonary, and nephric function, has a high mortality and poor prognosis. Cholangitis accompanying hepatolithiasis includes recurrent pyogenic cholangitis, an epidemic disease in Southeast Asia. Biliary tract infections, which often occur after a biliary tract operation and treatment of the biliary tract, may have a fatal outcome, and should be carefully observed. The causes of acute cholangitis associated with pancreaticobiliary maljunction differ before and after operation. Direct cholangiography is most useful in the diagnosis of primary sclerosing cholangitis. If cholangiography visualizes a typical bile duct, differentiation from acute pyogenic cholangitis is easy. This article discusses the individual characteristics, diagnostic criteria, treatment guidelines, and prognosis of these unusual types of biliary tract infection.     

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.     

TG13 miscellaneous etiology of cholangitis and cholecystitis

This paper describes typical diseases and morbidities classified in the category of miscellaneous etiology of cholangitis and cholecystitis. The paper also comments on the evidence presented in the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG 07) published in 2007 and the evidence reported subsequently, as well as miscellaneous etiology that has not so far been touched on. (1) Oriental cholangitis is the type of cholangitis that occurs following intrahepatic stones and is frequently referred to as an endemic disease in Southeast Asian regions. The characteristics and diagnosis of oriental cholangitis are also commented on. (2) TG 07 recommended percutaneous transhepatic biliary drainage in patients with cholestasis (many of the patients have obstructive jaundice or acute cholangitis and present clinical signs due to hilar biliary stenosis or obstruction). However, the usefulness of endoscopic naso-biliary drainage has increased along with the spread of endoscopic biliary drainage procedures. (3) As for biliary tract infections in patients who underwent biliary tract surgery, the incidence rate of cholangitis after reconstruction of the biliary tract and liver transplantation is presented. (4) As for primary sclerosing cholangitis, the frequency, age of predilection and the rate of combination of inflammatory enteropathy and biliary tract cancer are presented. (5) In the case of acalculous cholecystitis, the frequency of occurrence, causative factors and complications as well as the frequency of gangrenous cholecystitis, gallbladder perforation and diagnostic accuracy are included in the updated Tokyo Guidelines 2013 (TG13). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

TG13 flowchart for the management of acute cholangitis and cholecystitis

We propose a management strategy for acute cholangitis and cholecystitis according to the severity assessment. For Grade I (mild) acute cholangitis, initial medical treatment including the use of antimicrobial agents may be sufficient for most cases. For non-responders to initial medical treatment, biliary drainage should be considered. For Grade II (moderate) acute cholangitis, early biliary drainage should be performed along with the administration of antibiotics. For Grade III (severe) acute cholangitis, appropriate organ support is required. After hemodynamic stabilization has been achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. In patients with Grade II (moderate) and Grade III (severe) acute cholangitis, treatment for the underlying etiology including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has been improved. In patients with Grade I (mild) acute cholangitis, treatment for etiology such as endoscopic sphincterotomy for choledocholithiasis might be performed simultaneously, if possible, with biliary drainage. Early laparoscopic cholecystectomy is the first-line treatment in patients with Grade I (mild) acute cholecystitis while in patients with Grade II (moderate) acute cholecystitis, delayed/elective laparoscopic cholecystectomy after initial medical treatment with antimicrobial agent is the first-line treatment. In non-responders to initial medical treatment, gallbladder drainage should be considered. In patients with Grade III (severe) acute cholecystitis, appropriate organ support in addition to initial medical treatment is necessary. Urgent or early gallbladder drainage is recommended. Elective cholecystectomy can be performed after the improvement of the acute inflammatory process. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

Acute biliary conditions

Acute biliary complications may result from several medical conditions such as gallstone pancreatitis, acute cholangitis, acute cholecystitis, bile leak, liver abscess and hepatic trauma. Gallstones are the most common cause of acute pancreatitis. About 25% of theses patients will develop clinically severe acute pancreatitis, usually due to necrotizing pancreatitis. Choledocholithiasis, malignant and benign biliary strictures, and stent dysfunction may cause partial or complete obstruction and infection in the biliary tract with acute cholangitis. Bile leaks are most commonly associated with hepatobiliary surgeries or invasive procedures such as open or laparoscopic cholecystectomy, hepatic resection, hepatic transplantation, liver biopsy, and percutaneous transhepatic cholangiography. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) may have an essential role in the management of these complications.     

TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis

While referring to the evidence adopted in the Tokyo Guidelines 2007 (TG07) as well as subsequently obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular, new findings have accumulated on the occurrence of symptoms in patients with gallstones, frequency of severe cholecystitis and cholangitis, onset of cholecystitis and cholangitis after endoscopic retrograde cholangiopancreatography and medications, mortality rate, and recurrence rate. The primary etiology of acute cholangitis/cholecystitis is the presence of stones. Next to stones, the most significant etiology of acute cholangitis is benign/malignant stenosis of the biliary tract. On the other hand, there is another type of acute cholecystitis, acute acalculous cholecystitis, in which stones are not involved as causative factors. Risk factors for acute acalculous cholecystitis include surgery, trauma, burn, and parenteral nutrition. After 2000, the mortality rate of acute cholangitis has been about 10 %, while that of acute cholecystitis has generally been less than 1 %. After the publication of TG07, diagnostic criteria and severity assessment criteria were standardized, and the distribution of cases according to severity and comparison of clinical data among target populations have become more subjective. The concept of healthcare-associated infections is important in the current treatment of infection. The treatment of acute cholangitis and cholecystitis substantially differs from that of community-acquired infections. Cholangitis and cholecystitis as healthcare-associated infections are clearly described in the updated Tokyo Guidelines (TG13). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Clinical efficacy of i.v. doripenem,a new class of carbapenem,in patients with biliary tract infection: A multicenter trial

Aim: We conducted a multicenter trial to evaluate the efficacy and safety of i.v. doripenem (DRPM), a new class of carbapenem, in patients with moderate to severe biliary tract infection based on severity assessment using the Guidelines for the Management of Acute Cholangitis and Cholecystitis (1st Edition). Methods: One hundred and nineteen patients with moderate to severe acute cholangitis and/or cholecystitis were subjected to this study. After the initial collection of bile, patients were administrated DRPM 0.5 g three times daily by i.v. drip infusion. Results: The characteristics of the 119 patients were well balanced, including 60 with cholangitis, 44 with cholecystitis and 15 with cholangitis complicated by cholecystitis; there were 88.2% (105/119) moderate cases and 11.8% (14/119) severe. Based upon the assumption of the use of bile drainage, the rate of response to DRPM was 92.4% (110/119) in the group of all patients. The clinical response rates were 95.0% (57/60) for cholangitis, 93.2% (41/44) for cholecystitis and 80% (12/15) for cholangitis complicated by cholecystitis. Also, the clinical response rate was 80% (8/10) in 10 patients without drainage. In contrast, bacteriological efficacy was assessed in 50 patients, and the response rates were 87.0% (20/23) in patients with cholangitis, 100% (20/20) in patients with cholecystitis and 85.7% (6/7) in patients with cholangitis complicated by cholecystitis. Adverse events were found in six patients (5.0%), but were not serious and disappeared after treatment. Conclusion: These findings suggest that DPRM is useful as a new option for moderate to severe biliary tract infection.     

Gallstones in elderly patients: impact of laparoscopic cholecystectomy.

The use of laparoscopic cholecystectomy (LC) in elderly patients may pose problems because of their poor general condition, especially of cardiopulmonary function. Moreover, these patients present with acute cholecystitis and associated common bile duct stones more often than their younger counterparts. From 1990 to 1999, the authors performed 943 LCs; 31 (3.2%) were attempted on elderly patients, 11 (35%) of which were on an emergency basis because of acute cholecystitis, cholangitis or acute biliary pancreatitis. Ten per cent of LCs needed to be converted to an open cholecystectomy, most often because of an increase in the partial pressure of carbon dioxide in the blood produced by excessive operative time. A gasless procedure was used in the last three years of the study on eight cases; the overall rate of conversion from LC to open cholecystectomy in this group was 0%. Associated gallbladder and common bile duct stones were found in five (16%) patients (four preoperative LC endoscopic sphincterotomy and one transcystic approach). The success rate in both of these cases was 100%, overall morbidity was 29% and there was no mortality. These results show that LC is a feasible and safe procedure for use in elderly patients. Gasless LC should be preferred in patients classified as American Society of Anesthesiologists' class III because an excessive duration of operation is the most common reason for converting to an open cholecystectomy.     

Biliary sludge: When should it not be ignored

Opinion statement Biliary sludge is usually seen on transabdominal sonography as low-level echoes that layer in the dependent portion of the gallbladder without acoustic shadowing. Synonyms for biliary sludge include microlithiasis, biliary sand or sediment, pseudolithiasis, and microcrystalline disease. In most patients, biliary sludge is composed of calcium bilirubinate and cholesterol monohydrate crystals. A variety of predisposing factors are associated with biliary sludge formation. In most of these patients, removal of the risk factor can lead to resolution of sludge. In asymptomatic patients, biliary sludge can be managed expectantly. In patients who develop biliary-type pain, cholecystitis, cholangitis, or pancreatitis, the treatment of choice is cholecystectomy for those who can tolerate surgery. In patients who are not operative candidates, endoscopic sphincterotomy can prevent further episodes of cholangitis and pancreatitis, whereas medical therapy with ursodeoxycholic acid can prevent sludge formation and recurrent acute pancreatitis.     

Hepatobiliary and pancreatic infections in AIDS: Part one

Infections of the liver and biliary tract are common during the course of AIDS. A variety of viral, bacterial, fungal, and other opportunistic infections can present with hepatobiliary involvement as either the primary site of infection or secondary to a disseminated process. Coinfection with hepatitis B and C are particularly common due to the shared means of transmission of these viruses with HIV. The typical presenting features of hepatobiliary infections are right upper quadrant (RUQ) pain and abnormal liver function tests. Initial evaluation should include an RUQ ultrasonogram, which will usually identify abnormalities in the biliary tract and may demonstrate some parenchymal abnormalities as well. A liver biopsy is necessary to determine the etiology of focal hepatic lesions or opportunistic infections within hepatic parenchyma when other less invasive tests are negative or inconclusive. Special stains and culture techniques are required to identify specific organisms in the biopsy specimen. HIV-related biliary disorders include acalculous cholecystitis, which is a potentially serious condition requiring prompt recognition and gallbladder decompression. AIDS-cholangiopathy is a form of cholangitis involving the intra- and/or extrahepatic biliary tree. Endoscopic retrograde cholangio-pancreatography (ERCP) is the test of choice, demonstrating the stricturing, dilatation, and beading of bile ducts seen in this condition. Endoscopic sphincterotomy of the papilla of Vater may provide symptomatic relief for patients with papillary stenosis. Opportunistic infections of the pancreas have been reported. Evaluation should include a computerized tomogram of the abdomen and possible pancreatic tissue aspiration or biopsy. Management of pancreatitis is supportive.     

Jaundice caused by hydatid disease of the liver

Between 1980 and 1985, 40 patients were treated surgically for hydatid disease of the liver. In 4 cases (10%) jaundice was the first and most conspicuous sign of this disease. The patients originated from Spain, Morocco, Turkey and Lebanon. In 2 of these cases the initial diagnosis was hepatitis; one patient was operated on for suspected acute cholecystitis. All 4 patients had an eosinophilia and positive hydatid serology. Hydatid material was found in the biliary tract in two cases, while bile-stained hydatid fluid proved that there was a communication between cystic cavity and biliary tract in the other two patients. Obstruction of the common bile duct by hydatid elements causes jaundice and probably also cholangitis. Calcifications in the cyst are no guarantee against future complications. Surgery is the treatment of choice. When patients from an endemic area present with jaundice, hydatid disease of the liver should be suspected, particularly if eosinophilia also exists.     

Surgical treatment of choledochal cysts in children

Choledochal cyst is often associated with pancreatobiliary malunion, and pancreatic juice usually refluxes into the bile duct via the malunion. Various pathological conditions develop in the biliary tract, pancreas, and liver: cholangitis, biliary dilatation, biliary perforation, biliary cancer, acute pancreatitis, and/or biliary cirrhosis. The performance of cystenterostomy has recently been abandoned because of high morbidity after surgery. Accurate delineation of the biliary tree and the pancreatobiliary junction obtained by endoscopic retrograde cholangiopancreatography or operative cholangiography is necessary. Cyst excision should be performed to prevent ascending cholangitis and biliary cancer. Many types of procedures are employed in biliary reconstruction, but free drainage of bile is imperative for preventing cholangitis and stone formation. This can be achieved only by a wide anastomosis performed at the hilum after ductoplasty.     

The use of antibiotics for acute pancreatitis: Is there a role?

Infections due to pancreatic necrosis and abscesses are observed in one third of patients with severe acute pancreatitis (SAP). Based on results of double-blind, randomized, placebo-controlled trials, antibiotic prophylaxis in SAP is ineffective for reducing the frequency of infected necrosis and to decrease hospital mortality. Antibiotic treatment using carbapenems and quinolones is indicated on demand in patients with SAP and multiorgan failure at admission and in those with hemodynamic shock. Patients with biliary acute pancreatitis (AP) and clinically acute cholecystitis and/or cholangitis benefit from antibiotic treatment. Patients with AP associated with bacteremia, positive bronchoalveolar lavage, and urinary tract infection should receive antibiotics. In necrotizing pancreatitis, evidence-based data do not support late use of antibiotic prophylaxis after onset. Further high-quality, randomized, controlled trials are needed to evaluate antibiotic prophylaxis in the first 24 to 48 hours after SAP onset.     

Microflora of the biliary tree and liver--clinical correlates

Microbiologic aspects of hepatobiliary tracts are reviewed. The gallbladder, the common duct and the liver are discussed separately. Special attention is paid to bacteriologic sampling technique. Factors associated with bactibilia are surveyed. The relation between biliary bacteria and stone formation is evaluated. The etiology of acute calculous and acalculous cholecystitis, cholangitis and pyogenic liver abscess is discussed from a microbiological point of view. The importance of new imaging techniques, such as ultrasound, radionuclide scanning and computerized tomography, in the diagnosis and treatment of biliary obstruction or hepatic abscess is recognized. The type of bacteria and their incidence in bile was strongly associated with the underlying condition and various host factors. The flora in acute cholecystitis closely resembled that of the small intestine, while cholangitis and hepatic abscess specimens grew species often found in the colon. In addition, 'microaerophilic streptococci' were especially abundant in hepatic abscess. Nonetheless, coliforms predominated at all loci. Depending on selection criteria of the study population, bacteria of biliary origin played varying roles in the development of postoperative sepsis. Principles of perioperative antibiotic prophylaxis and treatment of manifest infection are outlined.     

Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis

Eosinophilic cholangiopathy is a rare condition characterized by eosinophilic infiltration of the biliary tract and causes sclerosing cholangitis. We report a patient with secondary sclerosing cholangitis with eosinophilic cholecystitis. A 46-year-old Japanese man was admitted to our hospital with jaundice. Computed tomography revealed dilatation of both the intrahepatic and extrahepatic bile ducts, diffuse thickening of the wall of the extrahepatic bile duct, and thickening of the gallbladder wall. Under the diagnosis of lower bile duct carcinoma, he underwent pyloruspreserving pancreatoduodenectomy and liver biopsy. On histopathological examination, conspicuous fibrosis was seen in the lower bile duct wall. In the gallbladder wall, marked eosinophilic infiltration was seen. Liver biopsy revealed mild portal fibrosis. He was diagnosed as definite eosinophilic cholecystitis with sclerosing cholangitis with unknown etiology. The possible etiology of sderosing cholangitis was consequent fibrosis from previous eosinophilic infiltration in the bile duct. The clinicopathological findings of our case and a literature review indicated that eosinophilic cholangiopathy could cause a condition mimicking primary sclerosing cholangitis （PSC）. Bile duct wall thickening in patients with eosinophilic cholangitis might be due to fibrosis of the bile duct wall. Eosinophilic cholangiopathy might be confused as PSC with eosinophilia.     

Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.     

经皮肝穿刺皮维碘灌洗在急性胆道感染治疗中的作用

目的 探讨超声引导下经皮经肝穿刺皮维碘灌洗对急性胆道感染的治疗作用。方法 对19例急性胆囊炎和11例急性化脓性梗阻性胆管炎在我院行超声引导下经皮经肝胆囊穿刺和经皮经肝胆管穿刺置管(PTCD)抽脓、皮维碘灌洗治疗及15例对照组患进行回顾性分析。结果 治疗组30例患于术后24h内症状迅速缓解，其中12例临床治愈无需进一步外科处理，18例于灌洗术后3～6周行择期手术，手术率占60％，术后无并发症；对照组15例中有12例行择期手术，手术率80％，3例不能手术也未治愈，而仅缓解症状。结论 超声引导下经皮经肝穿刺皮维碘灌洗是治疗急性胆道感染简便、安全、有效的方法。     

Histological analysis of liver parenchyma and choledochal wall, and external diameter and intraluminal pressure of the common bile duct in controls and patients with common bile duct stones with and without acute suppurative cholangitis

The purpose of this prospective controlled study was to determine the changes in intraluminal pressure and diameter of the common bile duct in a total of 121 bile patients with choledocholithiasis, and the consequences of these alterations for choledochal mucosa and liver histology. In fact, the reflux of bacteria from the obstructed biliary tract into the bloodstream is responsible for producing the clinical syndrome of acute suppurative cholangitis. Group I (26 patients) served as controls, Group II (50) had choledocholithiasis with clear green bile, and Group III (45) were patients with acute suppurative cholangitis with pus in the biliary tract. Ultrasonography revealed gallstones in all the patients. The external diameter of the common bile duct in patients with choledocholithiasis and acute suppurative cholangitis was significantly greater than in those of the other groups. Patients with acute suppurative cholangitis also had a higher intraluminal pressure than those of Groups I or II.     

Clonorchiasis-associated perforated eosinophilic cholecystitis

Clonorchiasis, a disease caused by infection with Clonorchis sinensis, is endemic in the Far East. Cholelithiasis, pyogenic cholangitis, cholecystitis, and biliary tract obstruction are common complications of chronic infection. Although cholecystitis caused by clonorchiasis is common, it is rarely reported as resulting from eosinophilic infiltration. We report a rare case of clonorchiasis-associated perforated eosinophilic cholecystitis and review the relevant literature.