What is the signs and symptoms of biliary obstruction with important considerations?

Low Common Bile Duct Obstruction

The majority of patients with low CBD obstruction have pancreatic carcinoma. These patients are most often palliated endoscopically, but occasionally endoscopic stent insertion fails and the patient is referred for biliary drainage and stent placement. It is important not to place a metal stent if the patient is an operative candidate, so this information should be obtained by consultation with the referring clinician or surgeon before the biliary drainage (Fig. 20-17). If the patient is not a candidate for surgery, then a stent can be placed at the time of initial biliary drainage. For patients with low CBD obstruction, it is not as important to gain peripheral access into the biliary tree, but it is again important to overstent and to ensure that there is no duodenal encasement by the pancreatic tumor. This can be done by injecting contrast material into the duodenal loop using the hockey-stick catheter when the tumor has been crossed. It is very important to do this before stenting. Obviously, if there is duodenal encasement, the stent will not provide effective palliation and the patient may need a gastro-jejunostomy or other form of surgical decompression. Occasionally, if the patient is not fit for surgery, a duodenal stent can be placed or a long-term internal/external drainage catheter can be placed with its tip placed in the proximal jejunum (Fig. 20-18).

The stent is placed in a similar fashion as for hilar stenting. Approximately 3-4 cm of the stent is placed above the proximal edge of the tumor and the distal end of the stent is left in the duodenum. Again, a safety catheter is not left in place if the procedure has been uneventful, but the stent is balloon dilated if a safety catheter is not left in situ (Box 20-5).

29 How is distal CBD obstruction diagnosed and treated?

Distal CBD obstruction should be suspected in the setting of CP with elevated alkaline phosphatase, as an early finding. Subsequently, jaundice and/or ascending cholangitis may occur. They are caused by inflammation, fibrosis, or pseudocyst formation at the head of the pancreas. Imaging studies such as ERCP or MRCP may demonstrate narrowing of the distal CBD in form of gradual tapering, bird beak stenosis or hourglass stricture.

Treatment options: In the case of no complications (cholangitis, secondary biliary cirrhosis), observe the patients for less than 2 months with serial liver function tests (LFTs). If any complication or persistent elevated LFTs are seen, surgical decompression is warranted. Endoscopic biliary stent may provide temporary relief but needs to be frequently exchanged due to stent blockage or migration. For younger patients, surgical biliary bypass with cholecystojejunostomy or choledochojejunostomy is preferred. If pseudocyst is the cause of the biliary obstruction, surgical biliary decompression may be combined with cystojejunostomy.

Additional Tests

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Complete blood count: Reveals leukocytosis; hematocrit (Hct) may be initially increased as a result of hemoconcentration; decreased Hct may indicate hemorrhage or hemolysis.

Blood urea nitrogen (BUN) is increased because of dehydration. Serial BUN measurements are the most valuable lab test for predicting mortality during the initial 48 hr.

Elevation of serum glucose in a previously normal patient correlates with the degree of pancreatic malfunction and may be related to increased release of glycogen, catecholamines, and glucocorticoid release and decreased insulin release.

Liver profile: Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) are increased as a result of tissue necrosis; bilirubin and alkaline phosphatase may be increased from common bile duct obstruction. A threefold or greater rise in serum alanine aminotransferase concentrations is an excellent indicator (95% probability) of biliary pancreatitis.

Serum calcium is decreased because of saponification, precipitation, and decreased parathyroid hormone response.

Arterial blood gases: Pao2 may be decreased as a result of ARDS, pleural effusion(s); pH may be decreased as a result of lactic acidosis, respiratory acidosis, and renal insufficiency.

Serum electrolytes: Potassium may be increased from acidosis or renal insufficiency; sodium may be increased from dehydration.

Imaging Studies

Right upper quadrant US noninvasively diagnoses gallstones in 95% of patients with cholecystitis (Fig. 158-5). US can also exclude common bile duct obstruction and may occasionally show bile duct stones. In cholecystitis, the gallbladder wall may be thickened, and free pericholecystic fluid may be present. Murphy's sign is also useful and can be elicited by the ultrasonographer or on physical examination. Gentle pressure is placed by the probe or hand at the border of the rectus sheath in the right upper quadrant, and the patient is asked to inspire. The gallbladder moves down with inspiration onto the examiner's hand or ultrasound probe, and the patient complains of pain when the inflamed gallbladder comes into contact with the examining hand. US can also exclude gangrenous cholecystitis with free air in the gallbladder wall, perforation, and abscess. The most specific test for acute cholecystitis is a technetium-labeled hepatobiliary iminodiacetic acid (HIDA) scan. Intravenously, HIDA is normally taken up by the liver, excreted into the biliary tract, and concentrated in the gallbladder. When a stone obstructs the cystic duct, the gallbladder fails to fill with HIDA; the sensitivity of HIDA scanning is 95%, but the specificity varies markedly and can be as poor as 50% in critically ill or jaundiced patients.

Treatment

Relevant Anatomy/Pathogenesis

Acute cholangitis results from obstruction of the common bile duct. Bile is inherently sterile due to the continuous flow of bile, immunoglobulin A secreted in the biliary tree, and bile salts, which contain a bacteriostatic mechanism. Biliary stasis results in development of infection when bacteria enter the biliary tree through the sphincter of Oddi (ascending cholangitis) and proliferate often with the presence of a stone or stent to act as the nidus for infection. Systemic spread causing bacteremia and sepsis occurs via translocation into the portal vein into the systemic blood supply. Direct inoculation of the biliary tree via intervention and placement of biliary stents can also lead to acute cholangitis. Finally, an increasing occurrence occurs when existing stents or drains become mispositioned or develop partial or complete obstruction resulting from sludge or tumor ingrowth, leading to biliary stasis and subsequent cholangitis.

Although the bacterial profile in acute cholangitis is polymicrobial, gram-negative rods are the most prominent bacteria present in acute cholangitis (Table 1).Escherichia coli is present in 25% to 50% of cases. Initial empiric antibiotic treatment should cover gram-positive and gram-negative bacteria as well as anaerobes. After culture sensitivities are determined, the antibiotic regimen can be narrowed to appropriate coverage. Patients should be treated 7 to 14 days with at least 2 weeks of treatment for patients with bacteremia and sepsis.

The obstruction can be intrinsic (stone, stricture, polyp, tumor, blood clot, infectious parasite, food impaction) or result from external compression on the duct. Similarly, causes can be benign or malignant. Benign strictures can be inflammatory (from chronic pancreatitis or Mirrizi syndrome with compression by a stone-filled gallbladder) or iatrogenic resulting from ischemia or injury. Benign iatrogenic strictures can develop following prior surgery without biliary reconstruction (most commonly cholecystectomy) or with biliary reconstruction following pancreaticoduodenectomy, liver transplant, or Roux-en-Y or other forms of biliary bypass. Malignant obstruction can be intrinsic to the common bile duct such as cholangiocarcinoma, or extrinsic from any malignancy causing compression of the common bile duct such as pancreatic, ampullary, gallbladder, or duodenal adenocarcinoma; however, malignant obstruction alone does not often result in cholangitis, and most patients with malignancy develop acute cholangitis only following prior intervention and manipulation of the biliary tree.

Biliary obstruction of the common bile duct can be at all levels but most commonly occurs distally resulting from a stone lodged at the sphincter. Obstruction from stricture or cancer leading to cholangitis can occur at any location from proximally at the right and/or left hepatic ducts duct to distally at the ampulla. The location of the obstruction along the CBD traditionally has affected treatment strategy, although currently nonoperative techniques are successful for managing obstructions at any location. Patients with biliary obstruction and previously placed stents will have infection proximal to the level of the stent and require exchange of the stent to reestablish free biliary drainage.

Eosinophilic Pancreatitis

Eosinophilic pancreatitis is a rare condition characterized by the presence of a prominent eosinophilic infiltrate that may, in some circumstances, result in the development of a mass lesion or common bile duct obstruction.142–145 True (primary) eosinophilic pancreatitis, in which the inflammatory infiltrate is predominantly, if not exclusively, composed of eosinophils, is an extraordinarily rare condition.146 In contrast to primary eosinophilic pancreatitis, other dis-ease processes that may manifest with increased pan-creatic eosinophils146 include parasitic infection, pancreatic allograft rejection,147 hypersensitivity reaction to medication,148 milk allergy,149 inflammatory myofibroblastic tumor,150, 151 pseudocyst formation in chronic pancreatitis,152, 153 lymphoplasmacytic sclerosing pancreatitis,154 and carcinoma, among others.

The clinical presentation varies depending on the setting in which pancreatic eosinophilia occurs. Patients may present with abdominal pain and obstructive jaundice mimicking pancreatic cancer.155, 156 Patients with primary eosinophilic pancreatitis often have systemic manifestations, including peripheral eosinophilia, elevated serum IgE levels, and eosinophilic infiltrates in other organs, including the GI tract.146 Some of these patients may develop the hypereosinophilic syndrome,157 characterized by an elevated eosinophil count (more than 1500 cells/mm3) of at least 6 months' duration, allergies (e.g., asthma, rhinitis), and multiorgan involvement, including the skin, heart, and GI tract, in the absence of any other identifiable causes of serum or tissue eosinophilia.

Pathologically, the pancreas may be enlarged and fibrotic. The extent and intensity of the eosinophilic infiltrate varies on the setting in which the disease occurs. Eosinophils may diffusely infiltrate the pancreas or may be localized.146 In cases with diffuse involvement, the eosinophils surround ducts and acini, often within septa, and may involve blood vessels (phlebitis, arteritis) as well.146 When localized, an intense eosinophilic infiltrate may be associated with pseudocyst formation, either with or without eosinophilic phlebitis.146 The adjacent pancreatic parenchyma may show atrophic changes; however, the parenchyma located outside the area of involvement is usually histologically unremarkable.146 In three cases reported by Abraham and colleagues,146 none of the patients had a known systemic vasculitic disease (e.g., Churg-Strauss syndrome) or a systemic autoimmune disease (e.g., primary sclerosing cholangitis, inflammatory bowel disease).

IgG4-related sclerosing cholecystitis

Gallbladders accompanying pancreatoduodenectomy specimens with autoimmune pancreatitis type 1 (IgG4-related lymphoplasmacytic sclerosing pancreatitis) are frequently also inflamed.127–132 Since the sclerosing pancreatitis is often associated with distal CBD obstruction,133–135 the inflammation in the gallbladder is usually of the mucosal-predominant lymphoplasmacytic type121 just discussed. Sometimes, more distinctive features characteristic of those seen in IgG4-related autoimmune pancreatitis (e.g. plasma cells lying in lacunae between bands of wavy basophilic sclerosis that surround glands) are observed.127,136 A diagnosis of IgG4-related sclerosing cholecystitis may be entertained in the rare case when all these features are observed in a gallbladder of a patient without pancreatic involvement or obstruction. Careful clinical correlation is required in such cases to exclude other processes. IgG4-positive plasma cells are entirely nonspecific and are present in many inflammatory conditions,137 including the usual cholelithiasis-associated cholecystitis.127 Therefore before the diagnosis of IgG4-related sclerosing cholecystitis is made, both the morphological criteria and the presence of >50 IgG4-positive plasma cells per high-power field (hpf) in multiple fields should be met.

42.3.3.6 Cholestasis

Hepatocyte bile acid uptake transporters are downregulated in cholestasis.101,104,198 For example, following common bile duct ligation in the rat, NTCP protein and mRNA expression are profoundly reduced.95,199–201 However, a number of studies suggest that bile acid uptake following common bile duct ligation is relatively well maintained. In one study, rats were subjected to 5 days of common bile duct obstruction following which obstruction was removed.202 Serum bile acids, which had been highly elevated, returned to normal within 60–90 minutes of relief of obstruction. This was accompanied by prompt excretion of bile acids into bile. Plasma clearance of a tracer dose of taurocholate injected at the time of relief of biliary obstruction was near normal. This normalization of transport function would be expected to occur faster than the return of NTCP levels to normal. In another study,199 hepatocytes were isolated from rats in which the common bile duct had been ligated for 7 days. The NTCP protein levels were reduced by 90% while the Vmax for Na+-dependent taurocholate uptake was reduced by only 70%. When basolateral plasma membrane vesicles were prepared from livers of rats in which the common bile duct was ligated for 50 hours, Na+-dependent taurocholate uptake remained normal.203 Transport studies were also performed in isolated perfused livers from rats 24 and 72 hours following common bile duct ligation.204 Quantitation of bile acid uptake following addition of 3H-taurodeoxycholate to the perfusate (16 nmol/min/g) showed little if any difference in uptake between control and bile duct ligated livers. Perfusion with a larger dose of this bile acid (4000 nmol/min/g) resulted in an approximately 35% reduction in maximal uptake by livers that had undergone common bile duct obstruction for either 24 or 72 hours. In the aggregate, these studies show at most a modest reduction of hepatocyte bile acid uptake following mechanical cholestasis in the face of a profound reduction in NTCP protein and mRNA. These data suggest the possibility of other Na+-dependent bile acid transporters in addition to NTCP. They also point out the potential importance of upregulation of bile acid efflux pumps on the sinusoidal plasma membrane (e.g., MRP3 and MRP4) as a mechanism to protect the hepatocyte from toxic concentrations of bile salts during cholestasis.205,206

Treatment for Pain

No single therapy is effective in all patients and the choice of a treatment depends on a variety of factors. The most important include pancreatic ductal anatomy, presence of complications, and local expertise. The first step is to make sure the diagnosis is correct. It is inappropriate to consider therapies with potential side effects or complications unless the diagnosis is secure. Second, it is worthwhile to look for specific complications that have specific therapy, such as pancreatic pseudocyst, duodenal obstruction, common bile duct obstruction, peptic ulcer disease, or pancreatic carcinoma (these are discussed below). Medical therapy is appropriate in all patients. This should include encouragement of abstinence from alcohol (if applicable), a low-fat diet, and analgesics. The choice of subsequent therapy depends in large part whether the patient has small-duct or big-duct disease. In those with small-duct disease, a trial of high-dose non-enteric-coated enzymes coupled with acid suppression is appropriate. Treatment options for those with big-duct disease are largely mechanical, with either endoscopic or surgical attempts to decompress the enlarged pancreatic duct. Patients who fail the above therapies may be considered for more experimental therapies such as celiac plexus block, splanchnicectomy, or octreotide. Significant pancreatic resections are considered an option of last resort in both groups of patients.

Exocrine pancreas

Cystic fibrosis is discussed in Chapter 3.

Extrahepatic obstruction caused by an annular pancreas is rare and a diagnosis of exclusion.286 Acute pancreatitis is complicated by jaundice, often transient, in 15–75% of patients; this may result from inflammatory bile duct obstruction or a common cause such as alcohol excess or gallstones.287 Chronic pancreatitis is complicated by intrapancreatic common bile duct obstruction in 3–10% cases, which may be transient, recurrent or persistent and with or without jaundice.288 Transient jaundice usually manifests during acute inflammatory excacerbations; pressure from a pancreatic pseudocyst can be a contributing factor,288,289 and there is an increased risk of secondary biliary cirrhosis.290 Steatosis, portal tract inflammation, ductular reaction with fibrosis and cirrhosis may be seen in patients with chronic pancreatitis but probably reflect the common underlying causes of alcohol liver injury or cholelithiasis. Type I autoimmune pancreatitis (the pancreatic manifestation of IgG4-related disease) often presents with obstructive jaundice caused by concurrent IgG4-related sclerosing cholangitis, which itself can infrequently be associated with lymphoplasmacytic hilar inflammatory pseudotumours (see Chapter 9). Segmental or localized portal hypertension occurs in some patients with chronic hepatitis on a background of pancreatitis, most probably as a consequence of splenic vein occlusion or stenosis.291 Vascular complications such as hepatic artery injury and portal vein thrombosis after pancreatic surgery are relatively uncommon. Anastomotic biliodigestive stenosis and biloma can be observed as late complications after pancreatic surgery.292 Pancreatic pseudocysts have been described within the liver.293 Pancreatic malignancy presents with obstructive jaundice in about 30% of patients.294

Acute pancreatitis has been found in a third of patients with panacinar liver cell necrosis.295 It may also occur in acute fatty liver of pregnancy296 and with acute hepatitis A297 and C.298