The incidence of cholelithiasis (gallstones) increases with age. At the age of 60 years, approximately 25% of women and 12% of men in the United States have gallstones. In some countries (e.g., Sweden and Chile) and ethnic groups (e.g., Pima Indians), the incidence of gallstones may approach 50%.

Patients can be divided into three clinical stages: asymptomatic, symptomatic, and those with complications of cholelithiasis. There is generally a stepwise progression from stage to stage. Annually, only 1% to 2% of those with asymptomatic disease progress to the symptomatic stage. It is unusual (<0.5% per year) for an asymptomatic patient to develop complicated gallstone disease without first suffering symptoms.

Cholesterol gallstones (85% of stones, radiolucent) are associated with increasing age, obesity, female gender, and Western diet. The female-to-male ratio is 2:1, and the increased incidence among women is in part related to pregnancy and/or oral contraceptive use. Obesity is an independent risk factor, increasing the prevalence of cholesterol gallstones by a factor of 3. Western diet is closely related, and these stones are rare in vegetarians.

Pigment gallstones (15% of stones): some can be associated with blood conditions (sickle cell anaemia and others with bowel resection.

Asymptomatic gallstones

Diagnosis. Asymptomatic gallstones are usually discovered on routine imaging studies or incidentally at laparotomy for unrelated problems. Common abdominal symptoms such as dyspepsia, bloating, eructation, or flatulence without associated pain are probably not caused by gallstones. There is no role for prophylactic cholecystectomy in most patients with asymptomatic gallstones, with a few exceptions.

Patients with a porcelain gallbladder (in which the gallbladder wall is calcified) should undergo cholecystectomy due to a high risk of malignancy. Prophylactic cholecystectomy may be warranted in patients with asymptomatic gallstones who have other risk factors for gallbladder cancer or have some type of immunosuppression. In adult patients with diabetes mellitus, spinal cord trauma, and sickle cell anaemia, prophylactic cholecystectomy is generally not indicated for asymptomatic or uncomplicated gallstone disease. Even after cholecystectomy, sickle cell patients may still develop bile duct stones.

Symptomatic gallstones (biliary colic)

Biliary colic presents after the patient had a large meal, usually with large quantity of fat food, typically one to 2 hours after eating. Symptoms can vary from mild epigastric pain to important right upper quadrant colic type of pain. Differential diagnosis includes acute cholecystitis, peptic ulcer disease, renal colic, gastroesophageal reflux, myocardial ischemia/infarct or right-lower-lobe pneumonia (lung infection). Appropriate testing is dictated by clinical suspicion of these entities. So medical assistance should be sought.

The pain is initiated by impaction of a gallstone in the outlet of the gallbladder. It comes in distinct attacks lasting 30 minutes to several hours and is located in the epigastrium or right upper quadrant. It can be steady and intense and may cause the patient to restrict breathing. Gallbladder pain usually occurs within hours of eating a meal, often awakening the patient from sleep.

Other symptoms include back pain, left-upper-quadrant pain, nausea, and vomiting. These usually occur in addition to, rather than in place of, the pain as described.

Physical signs include mild right-upper-quadrant tenderness, although there may be few abdominal findings during an attack. Jaundice is not caused by impaction of a stone in the cystic duct without inflammation. If jaundice is present, another cause should be sought – maybe the stone has migrated to the main bile duct causing biliary obstruction (choledolithiasis).

Diagnostic imaging -> Ultrasound diagnosis is based on the presence of echogenic structures having posterior acoustic shadows. There is usually little or no associated gallbladder wall thickening or other evidence of cholecystitis. The bile ducts must be assessed for evidence of dilation or choledocholithiasis (gallstones in the common bile duct, CBD).

Laparoscopic cholecystectomy (LC) is the appropriate treatment of the vast majority of patients with symptomatic gallstones

Complications of cholelithiasis

Acute calculous cholecystitis is initiated by obstruction of the cystic duct by an impacted gallstone. Persistence of stone impaction leads to inflammation of the gallbladder. Although the onset and character of the resulting pain resemble those of biliary colic, the pain is unremitting. Severe complications include gangrene, contained or free gallbladder perforation with or without abscess formation.

Diagnosis depends on the constellation of symptoms and signs and the demonstration of characteristic findings with diagnostic imaging.

The symptoms of acute cholecystitis are similar to but more severe and persistent than those of biliary colic. As the inflammatory process spreads to the parietal peritoneum, tenderness develops in the right upper quadrant or even more diffusely, and movement becomes painful. Systemic complaints such as anorexia, nausea, and vomiting are common. Fever may or may not be present. Elderly patients tend to have mild symptoms and may present only with reduced food intake. Murphy's sign (inspiratory arrest during deep palpation of the right upper quadrant) is characteristic of acute cholecystitis and is most informative when the acute inflammation has subsided, and direct tenderness is absent. Mild jaundice may be present, but severe jaundice is rare and suggests the presence of CBD stones, cholangitis, or obstruction of the CBD caused by external compression from a stone impacted in an inflamed Hartmann's pouch (Mirizzi syndrome – a rare and difficult complication to be managed).

Laboratory abnormalities may include elevated white cells (typically 12,000 to 15,000 cells/μL), although often the white blood cell count is normal. Complications, such as gangrene, perforation, or cholangitis, are suggested by an extremely high white blood cell count (>20,000 cells/μL). Liver function tests (LFTs), including serum bilirubin, alkaline phosphatase, alanine transaminase (ALT), aspartate transaminase (AST), and serum amylase, also may be abnormal.

Diagnostic imaging

Ultrasonography is the most commonly used test for diagnosing acute cholecystitis and any associated cholelithiasis. Findings indicative of acute cholecystitis include gallbladder wall thickening, pericholecystic fluid, and tenderness over the gallbladder when compressed by the ultrasound probe.

Radionuclide cholescintigraphy (rarely used nowadays) can be useful as an adjunct in the diagnosis of acute cholecystitis. Nonfilling of the gallbladder after 4 hours is deemed evidence of acute cholecystitis.

Computed tomographic (CT) scanning is now frequently performed to evaluate the patient with acute abdominal pain. CT can demonstrate gallstones, although it is less sensitive for these than ultrasonography. Other signs of acute cholecystitis on CT include gallbladder wall thickening, pericholecystic fluid, oedema, and emphysematous cholecystitis (air in the gallbladder wall).

Management

Initial management for patients with acute cholecystitis includes hospitalization, intravenous (IV) fluid resuscitation, and parenteral antibiotics.

For the treatment of acute cholecystitis, early LC is recommended. For moderate acute cholecystitis, either early or delayed cholecystectomy may be performed. Early LC should be performed only by an experienced surgeon with conversion to open cholecystostomy if operative conditions make identification of critical structures difficult.

Cholecystitis is a common disease nowadays that could have severe consequences if not managed properly. It is mostly caused by gallstones ( usually a stone blocks the duct that connects the gallbladder to the bile duct) and lead to inflammation and infection of the gallbladder. Some patients can be quite sick (mainly diabetics, immunosuppressed and old patients) .

The most common symptoms of gallbladder inflammation are:

Upper abdominal pain, usually in the right side but some times can be in the epigastrium: This pain often has a sudden onset, often occurring after a high-fat meal (30 min to 2h). It may start just above the bellybutton but will eventually settle under the edge of the ribcage on the right side of the abdomen, around the location of the gallbladder.

Nausea and vomiting.

Fever over 37.8 °Celsius occurs in about one-half of individuals with cholecystitis. Old, diabetic and immunosuppressed people can not present fever

Malaise: A person with an inflamed gallbladder may experience a general feeling of discomfort, illness, and uneasiness. Malaise is a common complaint with many illnesses and is often the first indication of inflammation or infection.

If you have all these symptoms you should seek medical advise.

The treatment for this condition is removal of the gallbladder along with antibiotics. Surgery should be done as early as possible to avoid complication (abscess, perforation and sepsis). Nowadays, laparoscopic cholecystectomy is the method of choice. If all goes well, patients are usually discharged home one day after operation. Patients with signs of major infection would be required to stay few days more to complete the intravenous antibiotic treatment.

Benign tumours of the bile ducts, usually adenomas, are rare and arise from the ductal glandular epithelium. They are characteristically polypoid and rarely are larger than 2 cm. Most are found adjacent to the ampulla, with the CBD being the next-most-common site. The malignant potential of these uncommon lesions is unclear and most of them will need a biopsy or excision. Most patients present with intermittent obstructive jaundice, often accompanied by right-upper-quadrant pain. This presentation may be confused with choledocholithiasis.

Treatment should involve complete resection of the tumour with a margin of duct wall.

Malignant bile duct tumours are called cholangiocarcinoma. They arise from the bile duct epithelium and can occur anywhere along the course of the biliary tree. Cholangiocarcinoma is an uncommon malignancy, with an incidence in the United States of approximately 0.85/100,000 population and representing about 2% of all cancers (approximately 5,000 new cases per year). Tumours tend to be locally invasive, and when they metastasize, they usually involve the liver and the peritoneum (a thin membrane that surrounds all intra abdominal organs). They characteristically spread along the bile ducts microscopically for long distances beyond the palpable end of the tumour. The median age of onset is approximately 65 years. Predisposing conditions include male gender, PSC (primary sclerosing cholangitis), choledochal cysts, intrahepatic stones and some parasitic infestations.

Classification.

Cholangiocarcinoma has been classified according to anatomic location and growth pattern. The anatomic location classification includes three main types:

1- intrahepatic (20%),

2- extrahepatic upper duct (also called hilar or Klatskin tumor, 40%),

3-extrahepatic lower duct (40%).

Tumour morphology is also divided in three primary types:

(1) a mass-forming type that grows in a nodular fashion and projects into both the bile duct lumen and the surrounding tissues.

(2) a periductal infiltrating type characterized by a cicatrizing growth pattern that infiltrates the walls of the bile ducts and grows both within them and along their exterior surfaces; and

(3) an intraductal growing type that displays a polypoid or sessile pattern that forms intraductal excrescences of tumor that may grow along the inside of, but do not penetrate, the wall of the duct (also commonly referred to as “papillary subtype”).

Diagnosis

Jaundice (yellow skin, eyes and dark urine), followed by weight loss and pain, is the most frequently encountered clinical feature at presentation. Tumour markers can help in diagnose and follow up patients with cholangiocarcinomas however has some limitations.

Carbohydrate antigen 19-9 (CA19-9) is a carbohydrate antigen that is traditionally associated with pancreatic cancer but is also the most commonly used marker in the diagnosis of cholangiocarcinoma. Sensitivity and specificity vary depending on the threshold used and on coexisting conditions such as inflammation and cholestasis. It is not used as a screening tool because of many reasons.

Carcinoembryonic antigen (CEA). Although most commonly used for the diagnosis of colorectal cancer, CEA has also demonstrated some elevation in patients with malignancies of biliary origin

Imaging

MRCP – a specific biliary and liver MRI – demonstrates the tumour and its relationship to key structures

CT scan – delineates the anatomy and tumour relationship with surrounding structures.

PET scan – can be helpful in identifying metastatic disease elsewhere. Its use is as standard test is controversial at the moment, being only used in specific circumstances.

ERCP (endoscopic retrograde cholangiopancreatography) is the most valuable diagnostic tool for cholangiography of lower duct tumours. Distal lesions may be indistinguishable from small pancreatic tumours on preoperative evaluation, and the distinction is often not made until final pathologic analysis. It is also valuable for upper duct tumours, but if the tumour has obstructed the biliary system completely, the upper extension of the lesions cannot be evaluated. Since the advent of MR cholangiography, ERCP is increasingly being used for preoperative therapeutic decompression of the biliary tree with the placement of a trans tumoral stent. Preoperative decompression of the biliary tree has the advantage of improving liver function prior to resection but has the risk of cholangitis (infection in the biliary system) and increased postoperative infection. ERCP carries the potential added benefit of obtaining cellular material for cytologic analysis, either via ductal brushing, fine needle aspiration (FNA), or forceps biopsy. In an attempt to increase diagnostic yields, new molecular techniques have been applied to biopsy samples, including digital image analysis (DIA) and fluorescence in situ hybridization (FISH). These tests can detect genetic aneuploidy and chromosomal rearrangements as indicators of malignancy, mainly in patients at risk of bile duct cancer (PSC).

PTC - percutaneous transhepatic cholangiography (a technique in which the biliary system is approached by a direct puncture guided usually by ultrasound) has been used when ERCP and MRI cannot precisely delineate the upper limit of a tumour. Under PTC guidance, FNA cytology can also provide a tissue diagnosis in many of patients. If a tumour is resectable, extensive efforts to obtain a tissue diagnosis before resection are inappropriate.

Endoscopic ultrasound (EUS) with FNA represents an important development in the investigation of lower bile duct strictures and masses. It is useful as an alternative to ERCP for obtaining tissue to establish a cytologic diagnosis, especially if a primary pancreatic mass is suspected. The potential value of such a biopsy needs to be weighed against risks such as bleeding and potentially seeding the traversed peritoneal cavity with malignant.

Treatment

Resection remains the primary treatment of cholangiocarcinoma, although only 15% to 20% are resectable at presentation.

The type of the operation will depend on tumour location and patient’s clinical conditions.

For hilar cholangiocarcinomas, large liver resections should be done to achieve a clear margin. Resection of liver, bile ducts and lymph nodes around the liver is a challenging procedure and should only be done with experts. Dr Perini has published extensively in the management of this type of tumour, including new surgical techniques that can be used to avoid complications.

For cholangiocarcinomas located in the distal bile duct, a Whipple’s operation is the procedure to be done. This is the same operation performed for head of pancreas cancer and carries a considerable risk of complication. Dr Perini had extensive training and have accumulated a lot of expertise in this type of procedure. He also has published methods to decrease the risk of leaks and new methods to replace the vessels around this area when it needs to be done (when the tumour is invading the portal vein - a major vein that carries blood from the gut to the liver).

Adjuvant radiation and chemotherapy have been attempted, but clinical trials are limited by the paucity of eligible patients. Multidisciplinary approach, including techniques that will allow the relief of jaundice and the growth of the future liver remnant) is essential to achieve the best outcome.

The interplay with oncologists, radiologists, dietitian and gastroenterologists is crucial. At Darebin Specialists we can offer you a high quality team of doctors with expertise in the treatment of this condition.

Palliation for patients with unresectable disease involves surgical, radiologic, or endoscopic biliary decompression. When unresectability is demonstrated preoperatively or at staging laparoscopy, the first choice for biliary decompression is via endoscopic or percutaneous internal stenting.

Prognosis is highly dependent on resectability of the tumour at presentation. Patients with resectable cholangiocarcinoma with microscopically negative margins and negative lymph nodes have a 5-year survival of approximately 35%, whereas median survival for patients with unresectable cholangiocarcinoma is only 3 to 6 months. A complete resection is necessary for any chance of a cure because recurrence is almost universal within 5 years in patients with incomplete resection (residual tumour). Other factors associated with increased survival include lower tumour grade, unaffected local lymph nodes, and a lack of vascular involvement.