Gallbladder Tumors Treatment & Management

Small gallbladder tumors are common and many can be safely followed with serial ultrasonographic examination. It is generally thought that polyps of less than 1 cm are safe to follow, although a study^[8] has recommended that polyps that are greater than or equal to 6 mm be considered for cholecystectomy. The factors listed above should be considered when deciding between surgery and observation for gallbladder polyps.

Chemotherapy is used in the adjuvant and palliative treatment of gallbladder cancer. Because of the rarity of the disease, the benefit of adjuvant treatment remains unproven. Phase II studies have shown that the use of single-agent chemotherapy (with gemcitabine, capecitabine, or 5-fluorouracil) in the palliative setting can be beneficial. Combination chemotherapy also has been shown to be beneficial and is usually based on gemcitabine, capecitabine, and 5-fluorouracil used in combination with cis-platinum or oxaliplatinum. Fluoropyrimidine-based chemoradiotherapy is commonly employed in the palliative and adjuvant setting as well. Since no regimen has shown superiority, participation in clinical trials is encouraged.

Operative resection offers the only chance for long-term survival. The details are described below.^[11]

Management of benign lesions

Cholecystectomy is recommended in patients with polyps larger than 1 cm or with polyps in the setting of primary sclerosing cholangitis, as well as in patients with a porcelain gallbladder. The decision about performing the operation laparoscopically or open depends on the risk of the lesion being malignant. Preoperative imaging should be reviewed to exclude the presence of invasion before planning a laparoscopic approach.

In these cases, the gall bladder is evaluated with frozen section. If a T1b or deeper cancer is identified, then more extensive surgery is performed as described below. The patient should be counseled about this possibility preoperatively.

Management of malignant lesions

Gall bladder cancer can be diagnosed incidentally in a surgical specimen excised for other reasons or based on imaging studies. When diagnosed incidentally, simple cholecystectomy alone is recommended for T1a lesions (limited to the mucosa) and further surgery is considered for deeper lesions. Patients may also present with jaundice. The benefit of preoperative drainage is debatable.

When patients are unresectable, tissue diagnosis and relief of jaundice (if present) are required prior to initiation of palliative treatment.

Percutaneous biopsy is avoided in resectable patients.

Treatment of benign lesions

The approach to treatment of benign lesions is described above.

Treatment of malignant lesions

Patients with localized gall bladder cancer are evaluated for surgical resection. Surgery is contraindicated in the presence of distant metastases. If the tumor was diagnosed incidentally in a surgical specimen, reresection is indicated for T1b or deeper lesions.

Malignant lesions are commonly staged laparoscopically in order to exclude the presence of undetected intra-abdominal metastases prior to curative laparotomy. Staging laparoscopy is also shown to be effective when the cancer was diagnosed following laparoscopic cholecystectomy.

T1a gall bladder cancer can be treated with simple cholecystectomy.

Patients with T1b or deeper gall bladder cancer are treated with hepatic resection and lymph node dissection that includes the portal, gastrohepatic ligament, and retroduodenal nodes. Resection of liver segments IVb and V are frequently adequate to achieve negative margins. In some cases, extended liver resection and/or bile duct resection may be necessary to achieve negative margins. (See images below.)

Adjuvant treatment with either fluoropyrimidine-based chemoradiotherapy or chemotherapy alone is recommended.

As outlined above, the preoperative evaluation of the patient with gall bladder cancer is similar whether the tumor is diagnosed incidentally following cholecystectomy or based on imaging studies. History and physical exam determine the suitability of the patient to undergo curative surgery. When the tumor is diagnosed incidentally following cholecystectomy, the pathology report and preoperative imaging are reviewed to note the margin status, location of the tumor, and depth of invasion. If the cystic duct margin is close or positive, bile duct resection may be considered, for example.

Laboratory evaluation determines the extent of hepatic reserve and the presence of biliary obstruction. CEA and CA19-9 may be helpful as baseline studies that inform treatment decisions in the future. CT scans of the chest, abdomen, and pelvis are carefully reviewed to determine the presence of distant metastatic disease, the extent of local invasion, and the presence of vascular or biliary involvement. The operative plan can usually be determined preoperatively. The need for biliary drainage in patients with preoperative jaundice is individualized, but some surgeons believe that the increased risk of infection with preoperative biliary drainage outweighs the risk of hepatectomy in the setting of biliary obstruction.

Staging laparoscopy discovers undetected metastatic disease in a high percentage of patients and can be used to avoid a nontherapeutic laparotomy. The yield is reasonably high in patients that had a prior noncurative cholecystectomy as well. Many surgeons will plan staging laparoscopy for all patients prior to laparotomy with curative intent.

The initial exploration focuses on the presence of metastatic disease that was not detected by preoperative imaging and staging laparoscopy. As many as 15% of patients may be found to have metastatic disease that was not detected by these methods. In the view of most North American surgeons, biopsy-proven metastases in the celiac nodes preclude resection. Aortocaval nodal metastases are considered distant metastatic disease. Biopsy-proven metastases in the portal nodes may affect the risk-benefit analysis for individual patients as well.

Intraoperative ultrasonography (IOUS) is used to evaluate the extent of involvement of the liver, as well as the portal and intrahepatic vasculature. The intrahepatic vascular anatomy is evaluated as a guide to liver resection techniques. This information is especially useful when ligating the pedicle to segment V and avoiding injury to the right anterior portal pedicle or segment VIII pedicle. Extended right hepatectomy may be necessary to achieve tumor clearance if the tumor involves the right portal pedicle.

Surgical exploration will determine the need to resect other organs that may be involved, such as the stomach, duodenum, and colon. It may be difficult to distinguish scar from malignancy. In these cases, suspicious tissue should be treated as malignancy in order to improve the chances of a margin-negative resection. If tumor is suspected on the bile duct based on a previous pathology report or operative exploration, the presence of tumor on the right hepatic duct must be evaluated. Suspicion of tumorous involvement of the right hepatic duct will require an extended right hepatectomy, excision of the extrahepatic biliary tree, and Roux-en-Y hepaticojejunostomy to the left hepatic duct.

A lymph node dissection to include the portal lymph nodes, peripancreatic lymph nodes, and retroduodenal lymph nodes is performed. A recent study indicates that accurate staging requires examination of at least 6 lymph nodes.^[12]

No standard adjuvant treatment protocol has been defined for gall bladder cancer. A 2008 study found that only 20% of patients with gall bladder cancer received adjuvant treatment.^[13] In the report, no benefit from adjuvant therapy could be demonstrated, but only a small number of patients received this treatment. Generally, fluoropyrimidine-based chemoradiotherapy or single-agent chemotherapy with fluoropyrimidines or gemcitabine is used.^[14] Because of the high cure rate with surgery alone for T1N0 lesions, adjuvant therapy is not commonly offered to these patients.

There are no data to support aggressive surveillance following resection of gall bladder cancer, because treatment of recurrences is not generally effective. However, many clinicians and patients prefer follow-up imaging every 6 months.

The overall complication and morbidity rate is approximately 25%. Complications are similar to those experienced with cholecystectomy and include infection, hematoma, and bile leaks. Complication rates are higher in patients undergoing more extensive resections. Liver failure can occur following extended hepatectomy, especially if jaundice is present preoperatively.

The overall survival rate for adenocarcinoma of the gall bladder depends on the stage at presentation. For T1 lesions, many studies report 5-year survival rates of 100%, especially when hepatectomy is used routinely for T1b or deeper lesions. Five-year survival following extended cholecystectomy for T2 lesions varies in the literature from 38% to 77%. Extended resection is necessary for stage III and IV tumors and results in 5-year survival of about 25%. Patients with unresectable disease have a median survival of 2-4 months and a 1-year survival rate of less than 5%.^{[6, 15]}

Improvements in the treatment of gallbladder cancer will rely on more effective chemotherapy to more effectively treat patients with systemic disease.