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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.
doi:10.1007/s00534-007-1277-7
PMCID: PMC2794354  PMID: 18274841
Biliary; Drainage; Endoscopy; Percutaneous; Bile replacement; Guidelines
2.  STUDIES ON THE TOTAL BILE  
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)
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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.
doi:10.5489/cuaj.1254
PMCID: PMC3926928  PMID: 24554976
5.  Stepwise approach to curative surgery using percutaneous transhepatic cholangiodrainage and portal vein embolization for severe bile duct injury during laparoscopic cholecystectomy: a case report 
Laparoscopic cholecystectomy (LC) has been recently adapted to acute cholecystitis. Major bile duct injury during LC, especially Strasberg-Bismuth classification type E, can be a critical problem sometimes requiring hepatectomy. Safety and definitive treatment without further morbidities, such as posthepatectomy liver failure, is required. Here, we report a case of severe bile duct injury treated with a stepwise approach using 99mTc-galactosyl human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging to accurately estimate liver function.
A 52-year-old woman diagnosed with acute cholecystitis underwent LC at another hospital and was transferred to our university hospital for persistent bile leakage on postoperative day 20. She had no jaundice or infection, although an intraperitoneal drainage tube discharged approximately 500 ml of bile per day. Recorded operation procedure showed removal of the gallbladder with a part of the common bile duct due to its misidentification, and each of the hepatic ducts and right hepatic artery was injured. Abdominal enhanced CT revealed obstructive jaundice of the left liver and arterial shunt through the hilar plate to the right liver. Magnetic resonance cholangiopancreatography revealed type E4 or more advanced bile duct injury according to the Bismuth-Strasberg classification. We planned a stepwise approach using percutaneous transhepatic cholangiodrainage (PTCD) and portal vein embolization (PVE) for secure right hemihepatectomy and biliary-jejunum reconstruction and employed 99mTc-GSA SPECT/CT fusion imaging to estimate future remnant liver function. The left liver function rate had changed from 26.2 % on admission to 26.3 % after PTCD and 54.5 % after PVE, while the left liver volume rate was 33.8, 33.3, and 49.6 %, respectively. The increase of liver function was higher than that of volume (28.3 vs. 15.8 %). On postoperative day 63, the curative operation, right hemihepatectomy and biliary-jejunum reconstruction, was performed, and posthepatectomy liver failure could be avoided.
Careful consideration of treatment strategy for each case is necessary for severe bile duct injury with arterial injury requiring hepatectomy. The stepwise approach using PTCD and PVE could enable hemihepatectomy, and 99mTc-GSA SPECT/CT fusion imaging was useful to estimate heterogeneous liver function.
doi:10.1186/s40792-016-0154-5
PMCID: PMC4798688  PMID: 26989053
Acute cholecystitis; Bile duct injury; Laparoscopic cholecystectomy; Portal vein embolization; Posthepatectomy liver failure; 99mTc-galactosyl human serum albumin single-photon emission CT/CT fusion imaging
6.  A Preliminary Study on Sinus Fungus Ball with MicroCT and X-Ray Fluorescence Technique 
PLoS ONE  2016;11(3):e0148515.
Background
Sinus fungus ball, an accumulation of fungal dense concretions, is a common disease in practice, and might cause fatal complications or lead to death once converted into invasive type. Early preoperative diagnosis of this disease can lead to appropriate treatment for patients and prevent multiple surgical procedures. Up to now, the diagnostic criteria of sinus fungus ball have been defined and computed tomography (CT) scan was considered as a valuable preoperative diagnostic tool. However, the sensitivity of clinical CT is only about 62%. Thus, investigating the factors which influence sensitivity is necessary for clinical CT to be a more valuable preoperative diagnosis tool. Furthermore, CT scan usually presents micro-calcifications or spots with metallic density in sinus fungus ball. Previous literatures show that there are some metallic elements such as calcium and zinc in fungus ball, and they concluded that endodontic treatment has a strong correlation with the development of maxillary sinus fungus ball and zinc ion was an exogenous risk factor. But the pathogenesis of sinus fungus ball still remains unclear because fungus ball can also develop in other non-maxillary sinuses or the maxillary sinus without root canal treatment. Is zinc ion the endogenous factor? Study on this point might be also helpful for investigating the pathogenesis of sinus fungus ball. In this paper, we tried to investigate the factors which influence the sensitivity of clinical CT by imaging sinus fungus ball with microCT. The origin of zinc ion was also studied through elements test for different fungal ball samples using x-ray fluorescence technique.
Methods
Specimens including fungal ball material and sinus mucosa from patients confirmed by pathological findings were extracted after surgery. All fungal ball specimens came from sphenoid sinus, ethmoidal sinus and maxillary sinus with or without previous endodontic treatment respectively. All of them were imaged by microCT with spatial resolution up to 5μm to acquire three-dimensional structure, and then the heavy metal elements were detected with x-ray fluorescence spectrometer analysis.
Result
High concentration of zinc and calcium were detected in all fungal ball specimens compared to sinus mucosa membrane. Particles with different size varied from disperse to density, which have similar shape to the result of clinical CT but with different size, were found in three-dimensional reconstruction results of microCT.
Conclusions
Spatial resolution is an influent factor of clinical CT sensitivity for sinus fungus ball. Improving the resolution of clinical CT will help to improve its sensitivity. Besides iatrogenic endodontic materials, endogenous metal elements of zinc and calcium might associate with the growth of fungal ball and the micro-calcifications or spots with metallic density of CT imaging.
doi:10.1371/journal.pone.0148515
PMCID: PMC4792473  PMID: 26978273
7.  Fungus ball and emphysematous cystitis secondary to Candida tropicalis: A case report 
Canadian Urological Association Journal  2015;9(9-10):E683-E686.
Fungus ball and fungal emphysematous cystitis are two rare complications of fungal urinary tract infection. A 53-year-old male patient presented with these complications caused by Candida tropicalis simultaneously. The predisposing factors were diabetes mellitus and usage of broad-spectrum antibiotics. The fungus ball, measuring 3.5 × 2.0 cm on the left wall of the urinary bladder, shrank significantly to 1.6 × 0.8 cm after 5 days of intermittent irrigation with saline before surgery. With transurethral removal of the fungus ball and antifungal treatment with fluconazole, the patient fully recovered. We conclude that a bladder fungus ball and fungal emphysematous cystitis should always be suspected in patients with diabetes mellitus with uncontrolled funguria and abnormal imaging. Treatment should include a systemic antifungal therapy and thorough surgical removal of the fungus ball. A systemic antifungal therapy combined with a local irrigation with saline or antifungal drugs might help decrease the dissemination of fungemia during an invasive manipulation.
doi:10.5489/cuaj.3008
PMCID: PMC4581947  PMID: 26425243
8.  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.
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PMCID: PMC1793378  PMID: 1776884
9.  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.
doi:10.1155/1998/75730
PMCID: PMC2423915  PMID: 9830582
10.  OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION  
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
11.  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.
doi:10.5489/cuaj.1214
PMCID: PMC3668396  PMID: 23766839
12.  STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY  
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
13.  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.
Methods:
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.
Results:
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.
Conclusions:
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.
doi:10.4293/108680813X13654754535232
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
14.  Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis 
Obstructive jaundice as the main clinical feature is uncommon in patients with hepatocellular carcinoma (HCC). Only 1%-12% of HCC patients manifest obstructive jaundice as the initial complaint. Such cases are clinically classified as “icteric type hepatoma”, or “cholestatic type of HCC”. Identification of this group of patients is important, because surgical treatment may be beneficial. HCC may involve the biliary tract in several different ways: tumor thrombosis, hemobilia, tumor compression, and diffuse tumor infiltration. Bile duct thrombosis (BDT) is one of the main causes for obstructive jaundice, and the previously reported incidence is 1.2%-9%. BDT might be benign, malignant, or a combination of both. Benign thrombi could be blood clots, pus, or sludge. Malignant thrombi could be primary intrabiliary malignant tumors, HCC with invasion to bile ducts, or metastatic cancer with bile duct invasion. The common clinical features of this type of HCC include: high level of serum AFP; history of cholangitis with dilation of intrahepatic bile duct; aggravating jaundice and rapidly developing into liver dysfunction. It is usually difficult to make diagnosis before operation, because of the low incidence rate, ignorant of this disease, and the difficulty for the imaging diagnosis to find the BDT preoperatively. Despite recent remarkable improvements in the imaging tools for diagnosis of HCC, such cases are still incorrectly diagnosed as cholangiocarcinoma or choledocholithiases. Ultrasonography (US) and CT are helpful in showing hepatic tumors and dilated intrahepatic and /or extrahepatic ducts containing dense material corresponding to tumor debris. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP) remains the standard procedure to delineate the presence and level of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) is superior to ERCP in interpreting the cause and depicting the anatomical extent of the perihilar obstructive jaundice, and is particularly distinctive in cases associated with tight biliary stenosis and along segmental biliary stricture. Choledochoscopy and bile duct brushing cytology could be alternative useful techniques in the differentiating obstructions due to intraluminal mass, infiltrating ductal lesions or extrinsic mass compression applicable before and after duct exploration. Jaundice is not necessarily a contraindication for surgery. Most patients will have satisfactory palliation and occasional cure if appropriate procedures are selected and carried out safely, which can result in long-term resolution of symptoms and occasional long-term survival. However, the prognosis of icteric type HCC is generally dismal, but is better than those HCC patients who have jaundice caused by hepatic insufficiency.
doi:10.3748/wjg.v9.i3.385
PMCID: PMC4621546  PMID: 12632482
15.  Cholangiocarcinoma…Or Not? 
Introduction
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.
Discussion
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
16.  Endoscopic Management of Portal Cavernoma Cholangiopathy: Practice, Principles and Strategy 
Portal cavernoma cholangiopathy (PCC) is the presence of typical cholangiographic changes in patients with a portal cavernoma due to chronic portal vein thrombosis, in the absence of other biliary tract diseases. Probably due to biliary stasis related to the cavernoma, there is a high incidence of biliary sludge and calculi in PCC, which trigger symptoms that resolve with appropriate interventions. Persistent and troublesome symptoms are usually due to biliary stenoses or strictures, which may occur with or without biliary calculi and may be short or long, solitary or multifocal, extrahepatic or intrahepatic. Experience with endoscopic interventions in PCC over the last twenty years has shown that it is the procedure of choice for bile duct calculi. Plastic stenting with repeated, timely, stent exchanges is the first line intervention for jaundice or cholangitis due to biliary strictures. If biliary obstruction does not resolve, portosystemic shunt surgery (PSS) or transjugular intrahepatic portosystemic stent shunt (TIPS) is performed to decompress the portal cavernoma. However, for patients with non-shuntable veins or blocked shunts, repeated plastic stent exchanges are the only option though there are reports of the use of biliary self-expandable metal stents in this situation. If symptomatic biliary obstruction persists after successful PSS or TIPS, second stage biliary surgery may be necessary. Recent experience suggests that treating biliary strictures in PCC on the lines of postoperative benign biliary strictures with balloon dilatation and repeated exchanges of plastic stent bundles may be effective therapy. Endoscopic management appears to be associated with an increased frequency of hemobilia, which usually responds to standard management. Recurrent cholangitis with formation of sludge and concretions may be a problem with repeated stent exchanges, especially if patient compliance is poor. In conclusion, the current understanding is that symptomatic PCC is best managed jointly by the endoscopist and surgeon with sequential interventions designed initially to establish and maintain biliary drainage, then to decompress the portal cavernoma and, finally, if required, second stage biliary surgery or endotherapy for biliary strictures. Endoscopic therapy occupies a central role in management before, during and after surgical therapy. Paradigms of endoscopic therapy continue to evolve as knowledge of pathogenesis and natural history improves and newer approaches and techniques are applied.
doi:10.1016/j.jceh.2013.08.011
PMCID: PMC4244828  PMID: 25755598
portal hypertensive biliopathy; portal biliopathy; pseudosclerosing cholangitis; portal hypertension; extrahepatic portal venous obstruction; PCC, portal cavernoma cholangiopathy; PSS, portosystemic shunt surgery; TIPS, transjugular intrahepatic portosystemic shunt; EHVPO, extrahepatic portal venous obstruction; ERCP, endoscopic retrograde cholangiopancreatography
17.  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.
doi:10.3748/wjg.v12.i21.3450
PMCID: PMC4087883  PMID: 16733869
Postoperative complication; Bile leakage; Ethanol ablation
18.  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.
doi:10.3892/mco.2013.160
PMCID: PMC3916194  PMID: 24649278
intraductal papillary neoplasm of bile duct; branch type; intestinal type; low-grade intraepithelial neoplasia
19.  Outcome of gallbladder preservation in surgical management of primary bile duct stones 
AIM: To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones.
METHODS: Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months.
RESULTS: In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders.
CONCLUSION: The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation.
doi:10.3748/wjg.v9.i8.1871
PMCID: PMC4611565  PMID: 12918142
20.  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.
doi:10.1155/DTE.3.221
PMCID: PMC2362575  PMID: 18493440
21.  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.
Images
PMCID: PMC2502382  PMID: 7979073
22.  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.
doi:10.1155/2011/265093
PMCID: PMC3205723  PMID: 22114589
23.  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.
doi:10.3748/wjg.v19.i34.5750
PMCID: PMC3769915  PMID: 24039371
Paracoccidioidomycosis; Pancreas; Fungus infection; Pancreatic tumors; Differential diagnosis
24.  Outcomes and risk factors for cancer patients undergoing endoscopic intervention of malignant biliary obstruction 
BMC Gastroenterology  2015;15:171.
Background
Malignant bile duct obstruction is a common problem among cancer patients with hepatic or lymphatic metastases. Endoscopic retrograde cholangiography (ERC) with the placement of a stent is the method of choice to improve biliary flow. Only little data exist concerning the outcome of patients with malignant biliary obstruction in relationship to microbial isolates from bile.
Methods
Bile samples were taken during the ERC procedure in tumor patients with biliary obstruction. Clinical data including laboratory values, tumor-specific treatment and outcome data were prospectively collected.
Results
206 ERC interventions in 163 patients were recorded. In 43 % of the patients, systemic treatment was (re-) initiated after successful biliary drainage. A variety of bacteria and fungi was detected in the bile samples. One-year survival was significantly worse in patients from whom multiresistant pathogens were isolated than in patients, in whom other species were detected. Increased levels of inflammatory markers were associated with a poor one-year survival. The negative impact of these two factors was confirmed in multivariate analysis.
In patients with pancreatic cancer, univariate analysis showed a negative impact on one-year survival in case of detection of Candida species in the bile. Multivariate analysis confirmed the negative prognostic impact of Candida in the bile in pancreatic cancer patients.
Conclusion
Outcome in tumor patients with malignant bile obstruction is associated with the type of microbial biliary colonization. The proof of multiresistant pathogens or Candida, as well as the level of inflammation markers, have an impact on the prognosis of the underlying tumor disease.
doi:10.1186/s12876-015-0399-7
PMCID: PMC4670509  PMID: 26637394
Cancer; Pancreatic cancer; Biliary obstruction; Cholangitis; Chemotherapy; Systemic therapy
25.  Biliary Tract Anatomy and its Relationship with Venous Drainage 
Portal cavernoma develops as a bunch of hepatopetal collaterals in response to portomesenteric venous obstruction and induces morphological changes in the biliary ducts, referred to as portal cavernoma cholangiopathy. This article briefly reviews the available literature on the vascular supply of the biliary tract in the light of biliary changes induced by portal cavernoma. Literature pertaining to venous drainage of the biliary tract is scanty whereas more attention was focused on the arterial supply probably because of its significant surgical implications in liver transplantation and development of ischemic changes and strictures in the bile duct due to vasculobiliary injuries. Since the general pattern of arterial supply and venous drainage of the bile ducts is quite similar, the arterial supply of the biliary tract is also reviewed. Fine branches from the posterior superior pancreaticoduodenal, retroportal, gastroduodenal, hepatic and cystic arteries form two plexuses to supply the bile ducts. The paracholedochal plexus, as right and left marginal arteries, run along the margins of the bile duct and the reticular epicholedochal plexus lie on the surface. The retropancreatic, hilar and intrahepatic parts of biliary tract has copious supply, but the supraduodenal bile duct has the poorest vascularization and hence susceptible to ischemic changes. Two venous plexuses drain the biliary tract. A fine reticular epicholedochal venous plexus on the wall of the bile duct drains into the paracholedochal venous plexus (also called as marginal veins or parabiliary venous system) which in turn is connected to the posterior superior pancreaticoduodenal vein, gastrocolic trunk, right gastric vein, superior mesenteric vein inferiorly and intrahepatic portal vein branches superiorly. These pericholedochal venous plexuses constitute the porto-portal collaterals and dilate in portomesenteric venous obstruction forming the portal cavernoma.
doi:10.1016/j.jceh.2013.05.002
PMCID: PMC4244820  PMID: 25755590
epicholedochal plexus; paracholedochal plexus; parabiliary venous system; porto-portal collaterals; LHD, left hepatic duct; RASD, right anterior sectoral duct; RPSD, right posterior sectoral duct; RHD, right hepatic duct; CHD, common hepatic duct; CBD, common bile duct; GDA, gastroduodenal artery; PSPDA, posterior superior pancreaticoduodenal artery; PSPDV, posterior superior pancreaticoduodenal vein; CHA, common hepatic artery; RHA, right hepatic artery; LHA, left hepatic artery; CD, cystic duct; CBD, common bile duct; PD, pancreatic duct; SMV, superior mesenteric vein; SV, splenic vein; SRCV, superior right colic vein; RGV, right gastric vein; IHBD, intrahepatic bile ductules; PBP, peribiliary plexus; HABr, hepatic arteriolar branches; PVBr, portal vein branches; CA, communicating arcade; FJV, first jejunal vein; GCT, gastrocolic trunk; AIPDV, anterior inferior pancreaticoduodenal vein; ASPDV, anterior superior pancreaticoduodenal vein

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