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1.  Preoperative biliary drainage for biliary tract and ampullary carcinomas 
We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ 1. Is preoperative biliary drainage necessary for patients with jaundice? The indications for preoperative drainage for jaundiced patients are changing greatly. Many reports state that, excluding conditions such as cholangitis and liver dysfunction, biliary drainage is not necessary before pancreatoduodenectomy or less invasive surgery. However, the morbidity and mortality of extended hepatectomy for biliary cancer is still high, and the most common cause of death is hepatic failure; therefore, preoperative biliary drainage is desirable in patients who are to undergo extended hepatectomy. CQ 2. What procedures are appropriate for preoperative biliary drainage? There are three methods of biliary drainage: percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) or endoscopic retrograde biliary drainage (ERBD), and surgical drainage. ERBD is an internal drainage method, and PTBD and ENBD are external methods. However, there are no reports of comparisons of preoperative biliary drainage methods using randomized controlled trials (RCTs). Thus, at this point, a method should be used that can be safely performed with the equipment and techniques available at each facility. CQ 3. Which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction? Unilateral biliary drainage of the future remnant hepatic lobe is usually enough even when intrahepatic bile ducts are separated into multiple units due to hilar malignancy. Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is difficult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. CQ 4. What is the best treatment for postdrainage fever? The most likely cause of high fever in patients with biliary drainage is cholangitis due to problems with the existing drainage catheter or segmental cholangitis if an undrained segment is left. In the latter case, urgent drainage is required. CQ 5. Is bile culture necessary in patients with biliary drainage who are to undergo surgery? Monitoring of bile cultures is necessary for patients with biliary drainage to determine the appropriate use of antibiotics during the perioperative period. CQ 6. Is bile replacement useful for patients with external biliary drainage? Maintenance of the enterohepatic bile circulation is vitally important. Thus, preoperative bile replacement in patients with external biliary drainage is very likely to be effective when highly invasive surgery (e.g., extended hepatectomy for hilar cholangiocarcinoma) is planned.
PMCID: PMC2794354  PMID: 18274841
Biliary; Drainage; Endoscopy; Percutaneous; Bile replacement; Guidelines
By a method of permanent intubation the entire output of bile from dogs has been obtained in a sterile state over long periods of time, and studied quantitatively. The secretion of the first few days after the initial operation is scanty, contains more pigment than that secreted later, and is sometimes so viscid as to cause temporary obstruction within the collecting tube. The small amount and thick consistency of the fluid are referable to direct injury of the liver and ducts, while the abundant bilirubin is derived, in part at least, from the hemoglobin of extravasated blood. In some animals in which there was accidental mercuric chloride poisoning at the time of operation a suppression of the bile followed which, in one instance, was complete during the 48 hours before death. In a dog developing mixed infection of the biliary tract, an almost colorless fluid, glairy as white of egg, gradually took the place of the bile. Not until a week or 10 days after operation does the bile acquire the character which it maintains later. The quantity of this later bile, as measured in successive 24 hour specimens, is greatly less than that recorded by previous investigators, a difference attributable to disturbing influences inevitable to the method of collection they employed. By our method, it averaged from 3.5 to 9.5 cc. per kilo of dog in 24 hours, though transient variations from 1 cc. up to 14 cc. were encountered. Some dogs give consistently far more bile than others. The frequently recorded effects of fasting to lessen the rate of secretion, and of a meat diet to increase it more than a carbohydrate one, were noted often. Contrary to expectation, vigorous exercise does not act to increase the quantity of the bile. During hot weather this may sink greatly, although the animal remains in good condition; and during intercurrent diseases unassociated with jaundice, the flow may almost cease. One of the best of cholagogues, bile by mouth, fails of effect under such circumstances. It acts best when the animal is healthy, the weather not oppressive, and the food intake abundant. The bilirubin output, after the immediate effects of the operation have worn off, remains nearly constant from day to day, though often exhibiting slow, wave-like variations, each extending over a week or more. These slow changes are synchronous with similar alterations in the hemoglobin percentage of the circulating blood. A recognition of them is important to studies of the bilirubin yield. A mild anemia, absent in controls maintained under like conditions, regularly develops in unexercised dogs completely deprived of bile, despite their apparent health, and as it does so the bilirubin output falls off. Prior to the development of the anemia the output averages about 7.5 mg. per kilo in 24 hours, a yield which closely corresponds with that recorded by previous workers. Vigorous exercise of animals previously sedentary causes an increased pigment output presumably as result of increased blood destruction. Since the daily pigment output is approximately constant, whereas the fluid quantity undergoes frequent and great changes, it follows that the pigment concentration must vary inversely as the fluid quantity, and vary greatly. It does both. No matter how large or small the 24 hour specimen of bile may be within "normal" limits, therein will be found the customary quota of pigment. When, under pathological conditions, the bile flow almost ceases, the pigment concentration becomes extremely great. A similar reciprocal relationship between concentration and fluid quantity would seem to hold for the mucinous element of the bile. Scanty biles are ropy as a rule, and copious ones are watery. Temporary obstruction was produced by clamping the outlet tube from the common duct, and the bile yield following upon its relief was studied. Secretion was for a time far more copious than usual, with a low pigment content per cubic centimeter, and tended to remain so until the accumulated pigment had been voided. As much extra bilirubin is put forth after 24 hours of obstruction as if the liver continued to manufacture the pigment without interruption during it. Obstruction for this length of time appears to cause no subjective disturbance in most instances, though bilirubinuria develops. Even this sign of bile retention may be lacking when obstruction endures but 12 hours. The physiological and clinical significance of these facts is briefly discussed.
PMCID: PMC2128361  PMID: 19868735
3.  Operative choledochoscopy in common bile duct surgery. 
Surgical exploration of the common bile duct for gallstones is a common operation but carries a high residual stone rate. Conventional techniques for exploring the bile ducts are blind procedures. The surgeon cannot see what he is doing. Also there has been no reliable method for a postexploratory check of the bile ducts before closure, usually around a T-tube. Operative choledochoscopy allows the surgeon to see stones in the duct, may aid the removal of stones and provides visual postexploratory checks that the common bile duct and the hepatic ducts are clear, that papilla is patent and that no stone is left behind before closure. A personal series of 150 patients had operative choledochoscopy using a flexible fibreoptic choledochoscope. If there was a clear indication on preoperative investigations that the ducts should be explored, an operative cholangiogram was omitted and the choledochoscope used as the exploring instrument. In 127 patients with a diagnosis of gallstone disease, choledochoscopy was used at the primary operation. In 12 patients choledochoscopy was used at a secondary operation for recurrent gallstone disease, and 11 patients had malignant obstruction of the biliary tract. In 70 of the 127 patients, gallstones were found and extracted using the choledochoscope. In 53 patients the ducts were clear, and in 4, other lesions were found: 3 papillomas and one polycystic disease. One hundred and six of the patients had the common bile duct closed primarily with no T-tube drainage. There was no increase in complications and no deaths associated with choledochoscopy or primary closure of the common bile duct.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC2499558  PMID: 4051422
4.  Fungus ball in the urinary tract: A rare entity 
A fungal mass in the urinary tract (fungus ball), mainly occurring in compromised patients, is a rare and dangerous complication of candiduria. We report 2 cases of fungus ball associated with hydronephrosis and sepsis. As reported in the literature, we treated the first patient by prompt relief of obstruction by nephrostomy and local and systemic antifungal agent. The second patient failed to respond to this treatment due to a distal ureteral stenosis and required open surgery with fungus ball removal and ureteral reimplantation. Despite a large success in urinary tract drainage with antifungal treatments, some cases need a modified approach due to anatomical modification.
PMCID: PMC3926928  PMID: 24554976
5.  Intraluminal biliary obstruction. 
Archives of Disease in Childhood  1991;66(12):1395-1398.
Jaundice caused by intraluminal bile duct obstruction in infancy is rare but may occur in association with biliary sludge, inspissated bile plugs, or gall stones. Nine boys (aged 2 weeks-6 months) with obstruction caused by inspissated bile (n = 7) or gall stones (n = 2) are presented. Haemolysis was not a factor in the patients' histories but an abnormal entry of the common bile duct into the third part of the duodenum was demonstrated in two and one had an asymptomatic haemangioma. Ultrasonography was the most useful investigation. Surgical removal of the bile duct obstruction was necessary in eight cases and included biliary tract drainage in six and cholecystectomy for changes of cholecystitis in four. Obstruction resolved spontaneously in one infant after percutaneous cholangiography. There were no postoperative complications.
PMCID: PMC1793378  PMID: 1776884
6.  Cholangitis Due to Candidiasis of the Extra-Hepatic Biliary Tract 
HPB Surgery  1998;11(1):51-54.
A case of isolated candidal fungal balls in the common bile duct causing obstructive jaundice and cholangitis is described. There were no predisposing factors. The fungal balls were removed from the common bile duct and a transduodenal sphincteroplasty was performed. Microscopic analysis yielded colonies of candida. Postoperative period was uneventful. At follow-up no evidence of candida infection was evident. He is now 3 years post-surgery and is well.
PMCID: PMC2423915  PMID: 9830582
As previous papers from our laboratory have shown, there exists a well defined tendency for calcium carbonate to come out of solution in the normal liver bile of the dog, and for it to be deposited on certain nuclei not infrequent in the secretion under pathological circumstances. Gall stones that had arisen in this fashion were a frequent occurrence in the intubated animals we studied. The present paper is concerned with the reasons for the absence of such stones from dogs with an intact biliary tract. The solubility of calcium carbonate is known to be markedly affected by the reaction of the fluid in which it is contained. The normal liver bile, out of which it tends to precipitate, is alkaline, with an average pH of 8.20 but in the gall bladder where conditions might otherwise seem especially favorable to precipitation, the secretion undergoes a change toward the acid side, becoming on long sojourn there, strongly acid to litmus (pH 5.18 to 6.00). From bile as thus altered, no carbonate precipitation takes place, even when it becomes greatly concentrated as in fasting animals or after obstruction of the common duct. Furthermore, carbonate which has precipitated out of liver bile on standing dissolves again in it when the fluid is rendered slightly acid in vitro, or, in some cases merely neutral to litmus. There are several obvious reasons for the absence of carbonate stones from the normal ducts under ordinary conditions,—notably the motility of these latter, the flushing that they undergo from an intermittently quickened bile stream, and the cleansing and possibly antagonistic action of the secretion elaborated by the duct mucosa. In the fasting animal, one at least of these influences is almost done away with, the rate of bile flow is so greatly cut down; while furthermore the calcium concentration of the secretion undergoes a considerable increase. But pari passu with these changes there occurs one in the bile reaction, a diminution in alkalinity so great that the pH often approximates that of the neutral point for litmus. That this change is not a direct consequence of the increase in calcium, may be inferred from the findings with stasis bile, the calcium content and reaction of which were observed to vary independently, if in general in the same direction. These adjustments within the organism, some of which may be thought to exhibit an element of the purposeful, when considered with the test-tube experiments, strongly suggest that the reaction of the bile plays a critical part in determining the occurrence of carbonate stones, as furthermore that their absence from the normal gall bladder is a consequence of the changes in the bile reaction there occurring. The changes come about through a functional activity of the bladder. This being the case, one might suppose that the failure to act would be followed by a formation of carbonate stones. There is sufficient evidence available in the literature to indicate that this happens, in rabbits at least. It is important to know whether changes in the bile reaction play any part in determining the cholelithiasis of man. To determine the matter will require a large material. But this much we have shown, that carbonate spheroliths not infrequently serve in human beings as centers in a formation of secondary stones of carbonate and cholesterol, as further that cholesterol precipitation out of human bladder bile can be induced or prevented by slightly altering the reaction of the fluid toward the alkaline and acid sides, respectively. The possibility that cholelithiasis may be a consequence of sins of omission on the part of the biliary channels and reservoir deserves to be considered.
PMCID: PMC2128469  PMID: 19868854
8.  Ureteric obstruction due to fungus-ball in a chronically immunosuppressed patient 
Candida albicans is a fungus that can cause opportunistic urinary tract infections in immunocompromised patients. Disseminated fungaemia secondary to Candida albicans is associated with considerable mortality and therefore merits aggressive treatment. Diagnostic investigations for urosepsis and disseminated fungaemaia secondary to Candida albicans include positive urine and blood cultures. Herein, we describe an extremely unusual case of disseminated fungaemia associated with an obstructive fungus-ball in the distal ureter of an immunosuppressed patient. We also describe a novel application of an established endourological technique for managing this clinical scenario and discuss appropriate perioperative management strategies.
PMCID: PMC3668396  PMID: 23766839
A variety of evidence is presented, all of which supports the view that in the uninfected animal the intestinal tract is the only place of origin of urobilin, not merely under normal circumstances, but when there is biliary obstruction. Animals rendered urobilin-free by collection of all of the bile from the intubated common duct remain urobilin-free even after severe hepatic injury. In our experiments urobilinuria was never found after liver damage except when bile pigment was present in the intestine. Thus, for example, it appeared during the first days after Ugation of the common duct, but disappeared as the stools became acholic. When this had happened a small amount of urobilin-free bile, given by mouth, precipitated a prompt urobilinuria. After obstruction of the duct from one-third of the liver, mild urobilinuria was found, but no bilirubinuria. In animals intubated for the collection of a part of the bile only, while the rest flowed to the duodenum through the ordinary channels, liver injury caused urobilinuria, unless indeed it was so severe as to lead to bile suppression, when almost at once the urobilinuria ceased, though the organism became jaundiced. The evidence here presented, when taken with that of our previous papers, clearly proves that urobilinuria is an expression of the inability of the liver cells to remove from circulation the urobilin brought by the portal stream, with result that the pigment passes on to kidney and urine. Urobilinuria occurs with a far less degree of liver injury than does bilirubinuria. Our work has, for the most part, been carried out with animals having uninfected livers and bile passages. But the influence of cholangitis with infection has been briefly discussed in the light of some preliminary observations. The influence of infection on the place of formation of urobilin and on the occurrence of urobilinuria will form the subject of another communication.
PMCID: PMC2130985  PMID: 19869039
10.  Total Laparoscopic Roux-en-Y Cholangiojejunostomy for the Treatment of Biliary Disease 
Total laparoscopic Roux-en-Y cholangiojejunostomy may be a first choice for patients with biliary disease that requires biliary-jejunal anastomosis.
Background and Objectives:
Roux-en-Y cholangiojejunostomy (RCJS) has been widely used in biliary bypass surgeries, but in most reported literature, an assisted mini-incision was needed, and studies reporting total laparoscopic Roux-en-Y cholangiojejunostomy (TLRCJS) are rare. The goal of this study was to investigate how to treat hepatic portal bile duct diseases and perform jejunojejunostomy and cholangiojejunostomy totally laparoscopically. We evaluated the feasibility of TLRCJS in treating biliary tract diseases.
TLRCJS were performed in 103 patients from January 2000 to August 2011. There were 28 cases of recurrent choledocholithiasis combined with stricture of the common bile duct (CBD) after several stone extractions, 3 patients with iatrogenic bile duct injury, 24 patients with choledochal cyst, 36 patients with hepatic portal cholangiocarcinoma, and 12 patients with cancer of the pancreatic head and periampullary cancer. All surgeries were performed through 5 trocars. First, laparoscopic surgery on the CBD was performed according to the original disease. The CBD was opened and stones were extracted in choledocholithiasis patients. In iatrogenic injury patients, strictured CBD was resected and repaired. Dilated CBD or choledochal cyst with tumor was transected. In patients with malignant jaundice, the CBD was opened longitudinally. At the same time, the bile duct was prepared for cholangiojejunostomy. Second, the positions of the laparoscope and surgeons were altered. The jejunal mesentery and jejunum were transected, and side-to-side jejunojejunostomy (JJS) was performed. The laparoscope and surgeon positions were exchanged again; the Roux-en-Y biliary limb was lifted close to the residual bile duct; and side-to-side or end-to-side choledochojejunostomy (CJS) was performed. Finally, an abdominal drainage tube was placed.
All the surgeries were performed successfully. The diameter of the residual bile duct ranged from 0.4 to 3.2 cm (average, 0.9 cm). Three patients had postoperative bile leakage and were treated from 1 week to approximately 1 month with abdominal drainage. Postoperative intraperitoneal hemorrhage and stress ulcer of the stomach occurred in 2 patients with biliary tract injury combined with obstructive jaundice. One with intraperitoneal hemorrhage was cured by another laparoscopic surgery. The other patient was cured after 2 days of abdominal drainage, antacids, and hemostatic drug therapy. The follow-up duration of 95 patients was 4 to 93 months (average, 48.3 months). The follow-up rate was 92.2% (95/103). Patients with cancer died of metastasis or cachexia during 14-month follow-up with no postoperative complication. Reflux cholangitis occurred in 3 patients 2, 3, and 5 years after the operation, respectively. No anastomotic stricture or other complication was found in other patients during the follow-up.
TLRCJS is the best and first choice for patients with biliary tract diseases that need biliary-jejunal anastomosis. But it is essential that the surgeon has proficiency in laparoscopic surgeries.
PMCID: PMC3771782  PMID: 23815976
Laparoscopy; Roux-en-Y cholangiojejunostomy; Common bile duct stone; Bile duct injury; Congenital choledochal cyst; Hepatic portal cholangiocarcinoma; Cancer of pancreatic head; Periampullary cancer
11.  Cholangiocarcinoma…Or Not? 
Cholangiocarcinoma includes all tumors originating in the epithelium of the bile duct and is the ninth most common gastrointestinal tract cancer. Metastatic disease may also rarely be present in the common bile duct. We present a case of metastatic malignant melanoma presenting as obstructive hepatitis and initially was thought to be and was almost treated as cholangiocarcinoma prior to adequate tissue sampling.
Case Report
A 76-year-old man presented with nausea, vomiting, and painless jaundice. He had a mixed hepatocellular pattern with transaminases and alkaline phosphatase greater than 1000 and total bilirubin of 12. A three-phase liver CT showed an enhancing mass within a dilated common bile duct and extension of the mass into the right and left intrahepatic bile ducts. He subsequently underwent ERCP with bile duct brushings and stent placement. Bile duct brushings showed benign reactive ductal epithelial cells. An endoscopic ultrasound with fine needle aspiration of the bile duct mass was performed. Pathology was negative for CK7, CK20, and positive for S100, Pan-melanoma, and negative for BRAF. No suspicious skin lesions were seen on close inspection by a dermatologist. However, two years prior the patient was diagnosed with cutaneous malignant melanoma in situ that was surgically resected. Thus, it was felt that this case represented metastatic melanoma to the bile duct. Due to significant comorbidities the patient was determined to be a poor surgical candidate. He has completed first line therapy for unresectable multiple melanoma with four rounds of ipilimumab.
Pathologic diagnosis of cholangiocarcinoma is often difficult to obtain from ERCP secondary to paucicellularity of these tumors and with no imaging modality that is specific for cholangiocarcinma. The hepatobiliary tract is a possible, though relatively rare, location for metastatic focus of malignant melanoma and should be considered in a patient with a history of melanoma and no tissue diagnosis after ERCP. There are multiple case reports of metastatic melanoma to the ampula of Vater causing obstructive hepatitis, but only 10 reports of disease found in the common bile duct. This case highlights the importance of obtaining tissue from suspected malignant lesions using various forms of endoscopy to ensure proper treatment and prolonged survival.
PMCID: PMC3764588
12.  Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol 
We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct. Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct. On d 46 after surgery, a retrograde transhepatic biliary drainage (RTBD) tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative management, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.
PMCID: PMC4087883  PMID: 16733869
Postoperative complication; Bile leakage; Ethanol ablation
13.  A case of branch duct type intraductal papillary neoplasm of the bile duct treated by open surgery after 11 years of follow-up 
Molecular and Clinical Oncology  2013;1(6):965-969.
The intraductal papillary neoplasm of the bile duct (IPNB) is a novel disease concept that was recently classified as a biliary cystic tumor by the revised World Health Organization classification. This is the case report of a 70-year-old female patient who experienced repeated episodes of obstructive jaundice and cholangitis since 2000, attributed to a mucus-producing hepatic tumor. Surgery was advised due to the repeated episodes; however, the patient refused. In May, 2011, the patient developed jaundice and fever and was treated with antibiotics. Since there was no improvement, the patient was admitted to the Tokyo Rosai Hospital. Abdominal computed tomography (CT) revealed a 50-mm cystic mass with an internal septum in the left hepatic lobe. Although the tumor size had remained almost unchanged compared to the initial CT scan performed in 2000, intra- and extra-hepatic bile duct dilation was more prominent on the second CT scan. Following admission, endoscopic retrograde cholangiopancreatography was performed and revealed an expanded papilla of Vater due to a mucous plug. A balloon catheter was inserted into the bile duct to remove the mucous plug, resulting in the drainage of copious amounts of mucus and infected bile. The patient finally consented to surgery and left hepatic lobectomy was performed. Consequently, the diagnosis of low-grade IPNB was made. Branch duct type IPNB, which is characterized by imaging appearance of a cystic mass and slow progression, is attracting increasing attention. In the present case, a cystic mass was identified in the left hepatic lobe, with no significant change in size after 11 years of follow-up, leading to the diagnosis of branch duct type IPNB. Considering the fact that IPNB is usually treated surgically at the time of diagnosis, the present case, due to the long-term follow-up, provides valuable insight into the natural history of the tumor.
PMCID: PMC3916194  PMID: 24649278
intraductal papillary neoplasm of bile duct; branch type; intestinal type; low-grade intraepithelial neoplasia
14.  Role of Endoscopic Retrograde Cholangiography and Nasobiliary Drainage in the Management of Postoperative Biliary Leak 
In order to assess the role of endoscopic retrograde cholangiography in evaluating the patients with post-operative biliary leak and of endoscopic nasobiliary drainage in its management, 36 patients with biliary leak seen over a period of 9 years were studied. Thirty-two had biliary leak following cholecystectomy, 3 following repair of liver trauma and 1 following choledochoduodenostomy. Patients presented at an interval of 4 days to 210 days (mean ± SEM, 32.4 ± 6.7 days) following laparotomy. Hyperbilirubinemia was noticed in only 13 patients (36.1%), while abdominal ultrasonogram showed ascites or biloma in 24 (66.7%). Endoscopic retrograde cholangiography showed the leak to involve the common bile duct in 55.6%, cystic duct in 33.3% and intrahepatic biliary radicles in 8.3%. Associated lesions included bile duct obstruction due to stricture or accidental ligature in 20%, bile duct stone in 20% and liver abscess in 2.8%.
Endoscopic nasobiliary drainage using a 7 Fr pig-tail catheter was attempted in 14 patients and could be established in 12 of them. Bile duct leak sealed in all but one of these 12 patients after an interval of 3 days to 40 days (mean ± SEM, 12.2 ± 3.2 days). A single patient with large defect and a proximal bile duct stricture did not respond and required surgery. Common bile duct stones were removed by endoscopic sphincterotomy in 3 out of 4 patients. One patient with large stone required surgical choledocholithotomy. In conclusion, endoscopic retrograde cholangiography was safe and useful in confirming the presence of leak as well as its site, size and associated abnormalities. Endoscopic nasobiliary drainage proved an effective therapy in post-operative biliary leak and could avoid re-exploration in 71.4% patients.
PMCID: PMC2362575  PMID: 18493440
15.  Toll-Like Receptors in Secondary Obstructive Cholangiopathy 
Secondary obstructive cholangiopathy is characterized by intra- or extrahepatic bile tract obstruction. Liver inflammation and structural alterations develop due to progressive bile stagnation. Most frequent etiologies are biliary atresia in children, and hepatolithiasis, postcholecystectomy bile duct injury, and biliary primary cirrhosis in adults, which causes chronic biliary cholangitis. Bile ectasia predisposes to multiple pathogens: viral infections in biliary atresia; Gram-positive and/or Gram-negative bacteria cholangitis found in hepatolithiasis and postcholecystectomy bile duct injury. Transmembrane toll-like receptors (TLRs) are activated by virus, bacteria, fungi, and parasite stimuli. Even though TLR-2 and TLR-4 are the most studied receptors related to liver infectious diseases, other TLRs play an important role in response to microorganism damage. Acquired immune response is not vertically transmitted and reflects the infectious diseases history of individuals; in contrast, innate immunity is based on antigen recognition by specific receptors designated as pattern recognition receptors and is transmitted vertically through the germ cells. Understanding the mechanisms for bile duct inflammation is essential for the future development of therapeutic alternatives in order to avoid immune-mediated destruction on secondary obstructive cholangiopathy. The role of TLRs in biliary atresia, hepatolithiasis, bile duct injury, and primary biliary cirrhosis is described in this paper.
PMCID: PMC3205723  PMID: 22114589
16.  Outcome of surgery for failed endoscopic extraction of common bile duct stones in elderly patients. 
Endoscopic sphincterotomy (ES) is the treatment of choice for common bile duct stones in elderly patients. For those in whom endoscopic clearance of the common bile duct fails the treatment options include stenting, dissolution therapy and lithotripsy. Surgery is often avoided because of the reported high morbidity and mortality in elderly patients. We have reviewed the outcome of patients referred for surgery after failed endoscopic clearance of common bile duct stones. Over a 3-year period, 100 patients with common bile duct stones were referred specifically for endoscopic clearance of the common bile duct (median age 69 years, range 19-97 years). In seven patients duct clearance was possible without ES and in five patients ES was considered inappropriate. ES was attempted in 88 patients and was successful in 75 (85%). Of the 13 patients failing ES or stone removal, surgery was performed in nine and four were stented. Of patients having successful ES (n = 75), ten were referred for surgery because of incomplete duct clearance. Surgery was performed to obtain duct clearance in 19 patients (eight male, 11 female, median age 77 years, range 47-90 years). Of the 19, eight had previously undergone a cholecystectomy (42%) and 17 of the 19 had biliary tract drainage preoperatively (90%). The procedures performed consisted of choledocholithotomy in all plus cholecystectomy (11), choledochoduodenostomy (7) and choledochojejunostomy (7). There were no deaths and only one major complication. The median total inpatient stay was 26 days (range 14-75 days) and the median postoperative stay was 12 days (range 7-50 days). We would conclude that open surgery can be performed safely and effectively in elderly patients with retained bile duct stones.
PMCID: PMC2502382  PMID: 7979073
17.  Pancreatic paracoccidioidomycosis simulating malignant neoplasia: Case report 
Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and must be considered in the differential diagnosis of intra-abdominal tumors in endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A 45-year-old man was referred to our institution with a 2-mo history of epigastric abdominal pain that was not diet-related, with night sweating, inappetence, weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of approximately 7 cm × 5.5 cm on the pancreas head. Abdominal computerized tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5 in the head region), with dilation of the major pancreatic duct. The patient underwent exploratory laparotomy, and the surgical description consisted of a tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior planes and mesenteric vessels, showing an enlarged bile duct. External drainage of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and biopsies were performed, but malignant neoplasia was not found. Microscopic analysis showed chronic pancreatitis and a granulomatous chronic inflammatory process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus screening were negative. Fine-needle aspiration of the pancreas was performed under US guidance. The smear was compatible with infection by Paracoccidioides brasiliensis. We report a rare case of paracoccidioidomycosis simulating a malignant neoplasia in the pancreas head.
PMCID: PMC3769915  PMID: 24039371
Paracoccidioidomycosis; Pancreas; Fungus infection; Pancreatic tumors; Differential diagnosis
18.  Endoscopic Ultrasound-guided Bilio-pancreatic Drainage 
Endoscopic Ultrasound  2012;1(3):119-129.
The echoendoscopic biliary drainage is an option to treat obstructive jaundices when endoscopic retrograde cholangiopancreatography (ERCP) drainage fails. These procedures compose alternative methods to the side of surgery and percutaneous transhepatic biliary drainage, and it was only possible by the continuous development and improvement of echoendoscopes and accessories. The development of linear sectorial array echoendoscopes in early 1990 brought a new approach to diagnostic and therapeutic dimension on echoendoscopy capabilities, opening the possibility to perform punction over direct ultrasonografic view. Despite of the high success rate and low morbidity of biliary drainage obtained by ERCP, difficulty could be found at the presence of stent tumor ingrown, tumor gut compression, periampullary diverticula and anatomic variation. The echoendoscopic technique starts performing punction and contrast of the left biliary tree. When performed from gastric wall, the access is made through hepatic segment III. From duodenum, direct common bile duct punction. Diathermic dilatation of the puncturing tract is required using a 6-Fr cystostome and a plastic or metal stent is introducted. The techincal success of hepaticogastrostomy is near 98%, and complications are present in 20%: pneumoperitoneum, choleperitoneum, infection and stent disfunction. To prevent bile leakage, we have used the 2-stent techniques. The first stent introduced was a long uncovered metal stent (8 or 10 cm) and inside this first stent a second fully covered stent of 6 cm was delivered to bridge the bile duct and the stomach. Choledochoduodenostomy overall success rate is 92%, and described complications include, in frequency order, pneumoperitoneum and focal bile peritonitis, present in 14%. By the last 10 years, the technique was especially performed in reference centers, by ERCP experienced groups, and this seems to be a general guideline to safer procedure execution. The ideal approach for pancreatic pseudocyst (PPC) puncture combines endos-copy with real time endosonography using an interventional echoendoscope. Several authors have described the use of endoscopic ultrasound (EUS) longitudinal scanners for guidance of transmural puncture and drainage procedures. The same technique could be used to access a dilated pancreatic duct in cases in which the duct cannot be drained by conventional ERCP because of complete obstruction.
PMCID: PMC4062224  PMID: 24949349
endoscopic ultrasound; biliary drainage
19.  Clinical Study on Causative Factors and Recurrence of Choledocholithiasis 
To identify factors involved in choledocholithiasis, clinical characteristics were studied using univariate and multivariate analyses. Factors involved in recurrence were also investigated. The subjects consisted of 51 patients with calcium bilirubinate stones (B group) and 52 patients with cholesterol stones (C group). All patients had choledocholithiasis and underwent lithotripsy by endoscopic sphincterotomy (EST) during the past 9 years. Twenty variables, including clinical symptoms and endoscopic retrograde cholangiopancreatography (ERCP) findings, were analyzed using a Statistical Analysis System (SAS) software package. Univariate analysis were done using Student's t-test and the chi-square test. Multivariate analyses were done by stepwise logistic regression analysis. In univariate analyses, there were significant differences between the B group and C group in nine variables: age, common bile duct diameter, common hepatic duct diameter, common bile duct stone diameter, cystic duct diameter, and the presence of gallbladder stones, atypical arrangement of the hepatic duct, parapapillary diverticulum, and large parapapillary diverticulum. In multivariate analysis, the four variables of no gallbladder stone, large parapapillary diverticulum, cystic duct less than 8 mm, and atypical arrangement of the hepatic duct were significant independent factors for the development of stones in the B group, with relative risks of 37.75, 16.73, 5.56, and 5.49, respectively. The results indicated that calcium bilirubinate stones were frequently associated with parapapillary diverticulum and abnormal arrangement of the bile duct. The formation of these stones was attributed to chronic biliary stasis caused by dysfunction of the biliary tract, including the papilla. In contrast, most cholesterol stones found in the common bile duct had apparently descended from the gallbladder. Common bile duct stones recurred after EST in 9 patients, all of whom had calcium bilirubinate stones. On ERCP, recurrence was found to be frequently associated with gallbladder stones, large parapapillary diverticula, and atypical arrangement of the hepatic duct. Patients with these characteristics on initial ERCP should therefore receive appropriate treatment and undergo strict follow-up observations owing to the increased risk of recurrence caused by dysfunction of the biliary tract.
PMCID: PMC2362557  PMID: 18493421
20.  Development of bile duct bezoars following cholecystectomy caused by choledochoduodenal fistula formation: a case report 
The formation of bile duct bezoars is a rare event. Its occurrence when there is no history of choledochoenteric anastomosis or duodenal diverticulum constitutes an extremely scarce finding.
Case presentation
We present a case of obstructive jaundice, caused by the concretion of enteric material (bezoars) in the common bile duct following choledochoduodenal fistula development. Six years after cholecystectomy, a 60-year-old female presented with abdominal pain and jaundice. Endoscopic retrograde cholangiopancreatography demonstrated multiple filling defects in her biliary tract. The size of the obstructing objects necessitated surgical retrieval of the stones. A histological assessment of the objects revealed fibrinoid materials with some cellular debris. Post-operative T-tube cholangiography (9 days after the operation) illustrated an open bile duct without any filling defects. Surprisingly, a relatively long choledochoduodenal fistula was detected. The fistula formation was assumed to have led to the development of the bile duct bezoar.
Bezoar formation within the bile duct should be taken into consideration as a differential diagnosis, which can alter treatment modalities from surgery to less invasive methods such as more intra-ERCP efforts. Suspicions of the presence of bezoars are strengthened by the detection of a biliary enteric fistula through endoscopic retrograde cholangiopancreatography. Furthermore, patients at a higher risk of fistula formation should undergo a thorough ERCP in case there is a biliodigestive fistula having developed spontaneously.
PMCID: PMC1351192  PMID: 16396681
21.  Experimental Candida albicans, Staphylococcus aureus, and Streptococcus faecalis pyelonephritis in diabetic rats. 
Infection and Immunity  1981;34(3):773-779.
Pyelonephritis was studied after an intravenous injection of Candida albicans, Staphylococcus aureus, or enterococcus in alloxan-diabetic rats and in water-diuresing or non-diuresing nondiabetic rats. The renal microbial populations of C. albicans or S. aureus were found to be greater than 10(5) colony-forming units per g for up to 42 days in diabetic rats, whereas the kidneys tended to become sterile in nondiabetic rats. No significant difference was found in the course of enterococcal pyelonephritis in diabetic versus control rats. The difference in the 50% infective dose for each microorganism between diabetic and control rats was less than or equal to log10. Neither duration of diabetes nor weight loss contributed to the greater and more sustained renal populations of C. albicans and S. aureus in diabetic rats. The inflammatory reaction in kidneys infected with S. aureus or C. albicans was greater in diabetic rats. Fungus balls associated with ureteral obstruction and gross multiple renal abscesses occurred in diabetic, but not in nondiabetic, rats infected with Candida. Growth of C. albicans and S. aureus in vitro in urine from diabetic rats was significantly greater than it was in urine from control rats. Addition of water or glucose to the urine of non-diuresing, nondiabetic rats significantly increased in vitro growth of S. aureus and C. albicans. These studies demonstrate greater severity of infection in the diabetic kidney due to S. aureus and C. albicans, which can be partially explained by decreased inhibitory activity of urine for these organisms in diabetic rats.
PMCID: PMC350938  PMID: 6800956
22.  Strategies for Management of Bile Duct Injury During Laparoscopic Cholecystectomy 
We encountered 10 patients with bile duct injuries during laparoscopic cholecystectomy. Their causes were electrocautery in 2 patients, misjudgment in 2, mechanical injury in 3, aberrant bile duct in 2, and weakness of the bile duct wall in one. The sites of injury were cystic duct in 4 patients, common bile duct in 2, aberrant bile duct in 2, common hepatic duct in one, and common bile duct plus right hepatic duct in one. Treatments for the injuries discovered intraoperatively consisted of T-tube drainage above in 2 patients, re-ligation of the cystic duct in one, ligation of an aberrant bile duct in one, simple suture and T-tube in one, and choledochojejunostomy in one. In the remaining 4 patients discovered postoperatively, 2 were conservatively treated by endoscopic retrograde biliary drainage. The duration of hospitalization was 9–12 days in the 4 patients with simple suture or ligation, 10–21 days in 2 cases of bile drainage, and 34–43 days in 3 with T-tube drainage. The patient with choledochojejunostomy suffered repeated cholangitis, resulting in hepatic abscess with hospitalization for 6 months. Since laparoscopic surgery should be minimally invasive, meticulous attention is necessary before and during surgery to avoid bile duct injury.
PMCID: PMC2362830  PMID: 18493547
23.  Atypical presentation of an advanced obstructive biliary cancer without jaundice 
Patient: Female, 60
Final Diagnosis: Cholangiocarcinoma
Symptoms: Abdominal pain • abdominal discomfort
Medication: —
Clinical Procedure: —
Specialty: Oncology
Unusual natural history/clinical course
Cholangiocarcinoma remains to be a challenging case to diagnose and manage as it usually presents in advanced stage and survival rate remains dismal despite the medical breakthroughs. It is usually classified as intrahepatic, perihilar or distal tumor which can lead to bile duct obstruction causing sluggish flow of bile through the biliary tract and promoting increased absorption of bilirubin, bile acids and bile salts into systemic circulation accounting for the occurrence of jaundice, dark-colored urine and generalized pruritus. It usually becomes symptomatic when the tumor has significantly obstructed the biliary drainage causing painless jaundice and deranged liver function with cholestatic pattern. Jaundice occurs in 90% of the cases when the tumor has obstructed the biliary drainage system. A markedly dilated gallbladder as initial presenting feature in the absence of other typical obstructive clinical manifestations of an advanced stage of the cholangiocarcinoma is rare.
Case Report:
This case report presents an atypical case of an elderly woman who presented with advanced metastatic ductal cholangiocarcinoma with markedly dilated gallbladder and liver mass without other clinical manifestations and laboratory evidence of cholestatic jaundice.
The mere presence of Courvoisier’s sign, even in the absence of other signs of biliary obstruction, could be suggestive of advanced neoplastic process along the biliary tract. Laboratory evidence of cholestasis might lag behind the clinical severity of the biliary obstruction in cholangiocarcinoma.
PMCID: PMC3823417  PMID: 24223234
cholangiocarcinoma; Courvoisier’s sign; adenocarcinoma; obstructive jaundice
24.  Six Rare Biliary Tract Anatomic Variations: Implications for Liver Surgery 
The variations in the anatomy of the biliary tract need to be recognized in modern liver surgery. The purpose of this clinical and anatomical study is to describe several novel biliary tract variations and to outline their practical importance for liver resections and transplantations.
Materials and Methods:
Over the previous 10 years, the anatomic variations of the bile ducts were examined during 600 intraoperative cholangiographies, 104 segmentectomies and 54 hemihepatectomies in patients with liver diseases. The intraoperative anatomies of the right and left hepatic ducts and the common hepatic duct confluence were analyzed.
Twenty-two variations occurred in 59.5% of the patients. Six variations were described for the first time: an accessory right hepatic duct in which a cystic duct drained; a tetrafurcation from the right anterior hepatic duct, right posterior hepatic duct and bile ducts for Segments 2 and 3 with aberrant bile drainage from Segment 4 into the bile duct for Segment 8; an aberrant bile drainage from Segments 6 and 7 into the common hepatic duct; an accessory bile duct for Segment 6 that drained into the bile duct for Segment 3; a tetrafurcation from the right anterior hepatic duct and the bile ducts for Segments 6, 3 and 2 with bile from Segment 7 draining into the bile duct for Segment 2; and an accessory bile duct for the left hemiliver that drained bile from the Type 4 small accessory hepatic lobe (according to Caygill & Gatenby) into the common hepatic duct.
These newly described biliary tract variations should be recognized by liver surgeons to avoid unwanted postoperative complications.
PMCID: PMC4261355  PMID: 25610166
Bile ducts; Biliary tract variations; Cholangiography; Hepatectomy; Liver segments
25.  Maxillary sinusitis caused by Pleurophomopsis lignicola. 
Journal of Clinical Microbiology  1997;35(8):2136-2141.
An immunocompetent 59-year-old man developed sinusitis over a 6- to 8-month period after cutting down a rotted maple tree (Acer sp.). A polypoid obstruction with a bloody drainage was evident in his right nasal cavity. A computed tomographic scan showed an opacification of the maxillary sinus. Surgery was performed to remove a fungus ball that had extended into the patient's medial sinus cavity. Sections of the sinonasal mucosa revealed marked acute and chronic sinusitis with inflammation, congestion, and hemorrhage. Sections from the pasty brown to black debrided material revealed a fungus ball consisting of an extensive network of brown-pigmented, septate, profusely branched hyphae. When grown on oat agar, the phaeoid fungus produced pycnidia and was identified as Pleurophomopsis lignicola. The genus Pleurophomopsis includes seven species, which are all known from plant material. This report documents for the first time a coelomycetous fungus, P. lignicola, causing sinusitis in an immunocompetent patient.
PMCID: PMC229919  PMID: 9230398

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