Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

GALLBLADDER AND BILE DUCTS

In general, an oral cholecystogram provides more information about adenomyomatosis and cholesterolosis than US but is a procedure seldom performed today. Adenomyomatosis tends to be more prominent after a fatty meal and is best seen on a post–fatty meal oral cholecystogram. A number of prior reports of gallbladder diverticula probably describe adenomyomatosis; their imaging differentiation is not clear, although some authors do attempt to differentiate between these two entities.

A typical appearance in a contrast-filled gallbladder consists of irregular diverticular-like outpouchings. When subtle, the fine granular outpouchings are difficult to identify with most current imaging techniques. At times imaging reveals a circumferential gallbladder fold resulting in an hourglass appearance (Fig. 8.19). Superficially the latter condition mimics a gallbladder septum. A rare adenomyoma appears polypoid.

Magnetic resonance RARE sequences and breath-hold are superior to other preand postcontrast techniques in detecting RokitanskyAschoff sinuses (54). Adenomyomatosis is identified as small intramural foci hypointense on T1and hyperintense on T2-weighted images. These outpouchings should not enhance postcontrast, but adjacent gallbladder mucosa does enhance, especially if concur-

Figure 8.19. T2–weighted image of adenomyomatosis. The gallbladder contains a transverse fold (arrow) and several gallstones (arrowhead). The pancreatic and bile ducts are dilated secondary to a pancreatic cancer. (Source: Burgener FA, Meyers SP, Tan RK, Zaunbauer W. Differential Diagnosis in Magnetic Resonance Imaging. Stuttgart: Thieme, 2002, with permission.)

rent inflammation is present, and thus the occasional description of adenomyomatosis as hypointense spots in a more hyperintense gallbladder wall. Small outpouchings blend into the gallbladder wall and result in a not uncommon postcontrast appearance of homogeneous, continuous wall enhancement.

Hyperplastic/Inflammatory Polyp

Macroscopic hyperplastic polyps are uncommon, although an occasional large one is detected. Larger ones tend to enhance with contrast and angiography may even reveal neovascularity and a tumor stain.

Ectopic Tissue (Pancreatic or Gastric)

Heterotopic gastric mucosa or pancreatic tissue is occasionally found in the gallbladder. Most are polypoid, often located in the fundus. Ultrasonography reveals an echogenic polyp in the gallbladder.

Benign Neoplasms

Adenoma

Gallbladder adenomas are uncommon. Small adenomas range from pedunculated to sessile in appearance. Some adenomas are located in a region of adenomyomatous hyperplasia. An occasional gallbladder villous adenoma is not detected by transabdominal US because the gallbladder is filled with mucinous material; CT should detect these. Gallbladder adenomyomas are rare.

Malignant Neoplasms

The overwhelming majority of gallbladder malignancies are primary carcinomas,with only an occasional sarcoma, lymphoma, carcinoid, or metastasis reported.

Adenocarcinoma

Clinical

Most early gallbladder carcinomas are detected by a pathologist after cholecystectomy for cholecystitis. In spite of an occasional early

stage, even when only a microscopic carcinoma is identified, metastases often are already present. Jaundice in a setting of cancer generally implies spread to lymph nodes adjacent to extrahepatic bile ducts. An occasional gallbladder carcinoma invades the liver, necroses, and becomes infected, and the patient presents with a liver abscess.

A rare gallbladder carcinoma results in a- fetoprotein secretion. Immunostaining detects overexpression of p53 protein in most gallbladder cancers and overexpression appears directly related to increasing carcinoma grade.

Ultrasonography screening of a high-risk population is occasionally proposed to detect early gallbladder carcinomas, but such a practice is not common. Even if detected early, prognosis is generally poor.

Compared to normal ducts, patients with a congenital anomalous pancreaticobiliary junction are at increased risk for developing gallbladder cancer (sphincter of Oddi anomalies are discussed in the earlier Congenital Abnormalities section).

An association of gallbladder cancer with chronic cholecystitis is well known. Likewise, because of the high risk for cancer, detection of a porcelain gallbladder is generally deemed an indication for elective cholecystectomy. Patients with chronic Salmonella typhi infection are at increased risk for several hepatobiliary cancers, including gallbladder carcinoma. A possible association between actinomycosis and gallbladder carcinoma is suggested.

An increased prevalence of gallbladder carcinoma is found in a setting of sclerosing cholangitis, although the much higher risk of primary bile duct carcinoma overshadows gallbladder involvement.

Synchronous primary gallbladder and extrahepatic bile duct carcinomas are uncommon. Often differentiation of separate primaries from metastases is difficult.

Pathology

Carcinoma-in-situ implies a tumor limited to the epithelium and is usually detected by the pathologist after cholecystectomy for cholelithiasis. Most in-situ carcinomas discovered after laparoscopic cholecystectomy do not manifest lymphatic, venous, or perineural invasion and thus are potentially curable.

ADVANCED IMAGING OF THE ABDOMEN

A diagnosis of early gallbladder carcinoma is rarely made outside of Japan. Japanese investigators divide these early tumors into superficial flat and superficial elevated types. The superficial flat carcinomas are not detected by imaging and are difficult to identify even by a pathologist. Sessile cancers are more common than pedunculated ones.

Histologic variants include papillary, mucinous, and an occasional clear cell carcinoma, although most are simply reported as adenocarcinomas. They range from well differentiated to anaplastic. A number of tumors contain more than one subtype, thus complicating the histologic subdivision. Papillary carcinomas tend to grow intraluminally, and some have a cauliflower-like appearance. Most gallbladder carcinomas, however, infiltrate early and extensively.

Detection

A number of studies confirm that a preoperative diagnosis of gallbladder cancer is achieved in only 30% to 40% of patients. In particular,stages 0 to II are diagnosed either at surgery or, more often, at histology. Imaging detection of a solitary gallstone, a gallstone elevated because of focal wall thickening, an intraluminal or invasive tumor, and discontinuity of the mucosal echo pattern suggests a carcinoma. Gallbladder wall thickening is found with both benign and malignant disease. An asymmetric or irregular wall thickening, however, is more common with a cancer. Also, a large polyp or an infiltrating tumor replacing most or all of the gallbladder lumen or invading adjacent structures suggests a cancer, regardless of whether or not gallstones are present. Nevertheless, a not uncommon scenario is a thickened gallbladder wall detected by CT or US, believed to represent chronic cholecystitis, containing a gallbladder cancer.

A necrotic, perforated gallbladder cancer mimics acute cholecystitis both clinically and by imaging. Some tumors contain hypodense regions, signifying necrosis. Viable tumor tends to enhance postcontrast. Currently the primary role of both CT and MR is in staging rather than diagnosis.

A rare mucus-secreting gallbladder carcinoma develops sufficient intratumoral calcifications to be visible by CT or even with conventional radiography.

GALLBLADDER AND BILE DUCTS

Ultrasonography reveals either focal gallbladder wall thickening or an inhomogeneous, hyperechoic, fungating, broad-based tumor within the lumen with little acoustic shadowing. With invasion of surrounding tissues quite often the gallbladder is not recognized and US simply identifies a poorly marginated, heterogeneous mass. Associated gallstones are common. Most authors agree that endoscopic US detects more and earlier gallbladder tumor than conventional US, yet concomitant cholecystitis or stones often prevent tumor identification. Color Doppler US of a carcinoma reveals color signals both in intraluminal tumors and gallbladder wall. The presence of a high-resistance index is uncommonly detected but is suggestive of a malignancy.

Gallbladder carcinomas most often are hypointense on T1and hyperintense on T2weighted images. Postcontrast MRI of carcinomas reveals early and irregular enhancement, in distinction to the delayed wall enhancement found in chronic cholecystitis. The usual threelayer gallbladder wall MR appearance is destroyed by a carcinoma but tends to be preserved with inflammatory disease.

In most instances cholangiography is not helpful in detecting a gallbladder cancer because of concurrent cystic duct obstruction. Not uncommon is hepatic duct invasion due to metastasis (Fig. 8.20).

Occasionally US-guided percutaneous transhepatic fine-needle aspiration cytology from a tumor provides a diagnosis, although a malignant focus in an adenoma is readily missed.

Staging

The tumor, node, metastasis (TNM) gallbladder cancer staging system is outlined in Table 8.3. A majority of cancers are already at an advanced stage when first discovered. A gallbladder carcinoma spreads outside the gallbladder to adjacent liver and along the cystic duct to pericholedochal and superior pancreaticoduodenal lymph nodes. Patients with T1 tumors tend not to have lymph node involvement, but a majority of those with T2–T4 tumors have lymph node metastases, with pericholedochal and cystic lymph nodes being most often involved. Involvement of multiple nodes is common.

Figure 8.20. Hepatic duct obstruction (arrow) secondary to metastatic gallbladder carcinoma. Other metastases can have a similar appearance.

Computer tomography is commonly used to stage gallbladder cancers, although the reported CT detection of cancer spread outside the gallbladder varied considerably (Table 8.4). Similar to a number of other tumors, CT has poor sensitivity with T1 tumors. Some studies have achieved helical CT accuracies in assessing resectability of over 90% (48), keeping in mind that resectability differs from cure. In particular, accuracy of gauging lymph node involvement is poor even with multidetector CT. Still, CT appears helpful in treatment planning. Ultrasonography is considered inadequate in staging gallbladder cancer.

Tumor spread to right and left bile duct confluence or Portal vein invasion renders a gallbladder carcinoma inoperable. In some patients percutaneous transhepatic portography and intraportal US are necessary to distinguish between vein compression and invasion.

Therapy

With the exception of carcinoma-in-situ, most gallbladder cancers discovered at surgery imply a poor prognosis. Even with an early lesion a simple cholecystectomy is not necessarily cura-

Table 8.3. Tumor, node, metastasis (TNM) staging of gallbladder tumors

Primary tumor:

Lymph nodes:

Nx Regional nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Regional lymph node metastasis

Distant metastasis:

Mx Distant metastases cannot be assessed M0 No distant metastasis

M1 Distant metastasis

Source: From the AJCC Cancer Staging Manual, 6th edition (2002), published by Springer-Verlag, New York, NY, used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL.

tive; an extended cholecystectomy with lymph node dissection, at times combined with extrahepatic bile duct or hepatic resection, offers a possible cure. A 5-year survival of 10% to 15% is typical, with long-term survivors being stage

Table 8.4. Helical CT detection of gallbladder carcinoma

Source: Adapted from Yoshimitsu et al. (55).

ADVANCED IMAGING OF THE ABDOMEN

I or II. Aggressive surgery appears to improve survival. A University of Bonn (Germany) study of patients undergoing curative resection, consisting of an extended cholecystectomy (cholecystectomy with lymphadenectomy and wedge hepatic resection), anatomic segmentectomy of segments IVa and V, or extended hepatectomy, achieved an actuarial 5-year survival rate of 55% (56).

An endoprosthesis, placed either endoscopically or percutaneously, is useful for palliation in some patients with an unresectable carcinoma.

Chemotherapy has had little impact on survival.

Metastases/Recurrence

Gallbladder carcinomas metastasize widely, even to bone. Spread to extrahepatic bile ducts, gastrointestinal tract, and adjacent structures is common. Occasionally a distant metastasis is the first clue to an underlying gallbladder carcinoma. An exceptional patient with extensive metastases, treated aggressively has prolonged survival.

More than most cancers, gallbladder carcinoma spreads readily along laparoscopic trocar sites. A number of patients have an unsuspected carcinoma first detected by a pathologist, with trocar site recurrence identified several months later. Even several recurrences have developed at laparoscopic ports (57). Peritoneal seeding also occurs, including localized seeding in the right subphrenic space.

A suspected gallbladder carcinoma probably is a contraindication to laparoscopic cholecystectomy. When a laparoscopic cholecystectomy is performed for an unsuspected carcinoma, surgical and adjuvant radiotherapy to the trocar sites appears reasonable.

Computed tomography identifies port track recurrence as a homogeneous abdominal wall tumor, often directly involving adjacent omental fat (57). Recurrences tend to enhance markedly on postcontrast CT.

Other Primary Carcinomas/Sarcomas

Both squamous and adenosquamous gallbladder carcinomas are uncommon. Often a large tumor with invasion of adjacent structures is

GALLBLADDER AND BILE DUCTS

found at initial presentation. These tumors tend to spread widely, including hematogenously.

A gallbladder carcinosarcoma is rare. These tumors tend to be large when first detected.

Small cell carcinomas are rare tumors spreading diffusely and having a poor prognosis. Immunochemistry reveals some of these tumors to have a neuroendocrine cell origin, and presumably they are derived from intestinal metaplasia.

Lymphoma

Primary gallbladder lymphoma is sufficiently rare that only case reports exist. Computed tomography and US detects a complex tumor confined to the gallbladder. Systemic lymphoma also uncommonly involves the gallbladder.

MALT lymphomas have a propensity to involve numerous mucosal sites. Thus a 53-year- old woman with low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma underwent a total gastrectomy, developed small bowel recurrence 18 years later, underwent chemotherapy, was in clinical remission, and then was found to have gallbladder recurrence 3 years later (58).

Melanoma

Both primary and metastatic malignant gallbladder melanomas are reported. The presence of another obvious primary site argues for a metastasis; otherwise, a distinction between primary and metastatic melanoma is difficult. Indeed, the question can be raised: Does primary gallbladder melanoma occur?

Autopsies of patients with malignant melanoma show gallbladder metastases in 15% to 20%; US reveals soft tissue tumors projecting into the lumen; an occasional one is polypoid.

Metastases to Gallbladder

Aside from melanomas, metastases to the gallbladder are not common. Renal cell carcinoma and gastric carcinoma are found occasionally. A rare metastasis appears as a polyp. An occasional metastasis presents as cholecystitis. Confusing the issue, histologic differentiation of a primary clear cell gallbladder carcinoma from a metastatic renal cell carcinoma is difficult.

Bile Duct Obstruction/Tumors

Clinical

In considering bile duct disease, the initial task is to establish whether jaundice is secondary to nonobstructive or obstructive causes. Clinical evaluation, including blood tests, makes this distinction in a majority of patients. The causes of nonobstructive jaundice range from diffuse liver disease, such as cancer, cirrhosis, and inflammation, to a congenital or metabolic condition. An occasional cause is partial distal duodenal obstruction. Once biliary obstruction is suspected, the etiology is best approached by subdividing patients by age and site of obstruction (Table 8.5). Thus a differential diagnosis can be narrowed down considerably by combining the clinical and imaging findings.

Liver function changes vary after the relief of a biliary obstruction. Aminotransferase enzymes respond differently to complete and partial decompression; after complete decompression these enzymes decline for a week or so and then remain slightly higher than normal. After partial decompression the enzyme levels continue being elevated. Serum alkaline phosphatase, g-glutamyl transpeptidase (GGT), serum total and direct bilirubins, and serum albumin tend to decrease after both complete and partial decompression in an inconstant manner.

Detection

The borderline between a normal duct caliber and a dilated duct is one of gradation; different criteria have been established for different imaging modalities. In general, if during ERC study the extrahepatic bile duct diameter is greater than the endoscope, the ducts are probably dilated. With US, if a bile duct diameter is <40% of an adjacent portal vein branch, it probably is not dilated. When markedly dilated, bile ducts tend to assume a somewhat beaded outline.

Numerous studies have compared CT and US in their ability to identify the etiology of an obstruction, with inconclusive results. Ultrasonography appears to be more sensitive than CT in identifying carcinomas, while CT sensitivity is greater in detecting stones. Many