Gallbladder tumors are recognized with increasing frequency, as a consequence of improvements in imaging techniques and increased utilization of these studies. Approximately 5% of patients evaluated with ultrasonography (US) for abdominal pain will have a gallbladder polyp. Cancer of the gallbladder is uncommon, though it is the fifth most common gastrointestinal (GI) malignancy.
It is possible to cure gallbladder cancer when tumors are treated surgically at an early stage. Given that gallbladder polyps are common, it is important to identify those that carry a high risk of malignancy. The size of a gallbladder polyp is generally the strongest predictor of malignant transformation.[1]
Benign lesions of the gallbladder are relatively common, but only adenomatous polyps are considered to have malignant potential. Although US can be useful in evaluating these lesions, considerable difficulty may be encountered in establishing the diagnosis preoperatively.
In 1924, Blalock suggested avoiding surgery on patients with gallbladder cancer if the diagnosis could be made preoperatively.[2] Therapeutic nihilism continued to define the approach to gallbladder cancer through most of the 20th century. Although most patients with gallbladder cancer continue to present with advanced disease, advances in imaging and hepatobiliary surgical techniques have made curative surgery possible in a greater number of cases.
The surgical approach to gallbladder cancer includes prevention, early detection, appropriate staging, and curative resection.
The gallbladder is a saccular structure located at the inferior surface of the liver, at the division of the right and left hemilivers, just below segments IV and V. It is composed of four different areas: the fundus, body, infundibulum, and neck. The gallbladder is approximately 7-10 cm long and about 2.5-3.5 cm wide. It normally contains approximately 30-50 mL of fluid, but it can distend and hold as much as 300 mL of fluid.
Gallbladder cancer generally spreads via the lymphatic channels and venous drainage, and peritoneal metastasis is common. Because the gallbladder is immediately adjacent to the liver, bile duct, portal vein, hepatic artery, duodenum, and transverse colon, involvement of these structures is common.
The cystic plate is the reflection of the visceral peritoneum between the liver and the gallbladder. The dissection between the gallbladder and the liver during cholecystectomy divides the plane between the cystic plate and the muscle layer of the gallbladder. This is the anatomic basis for the improved survival in patients undergoing liver resection for T1b gallbladder cancer.
The lymphatic drainage of the gallbladder proceeds from the cystic node to the pericholedochal nodes and then to the regional nodal basins, including the superior mesenteric, retropancreatic, retroportal, and celiac. Interestingly, direct drainage from the gallbladder to the aortocaval nodes has been demonstrated. For this reason, exposure of this region is a necessary step in the operative staging of gallbladder cancer.[3]
Cholesterol polyps account for approximately 50% of all polypoid lesions of the gallbladder. These lesions are thought to originate from a defect in cholesterol metabolism. They appear as yellow spots on the mucosal surface of the gallbladder and are identified histologically as epithelial-covered macrophages laden with triglycerides and esterified sterols in the lamina propria of the mucosal layer of the gallbladder. As a rule, cholesterol polyps exist as multiple lesions and are usually smaller than 10 mm. They are generally asymptomatic.
Inflammatory polyps
These lesions result from chronic inflammation. They extend into the gallbladder lumen by a narrow vascularized stalk.
Adenomyomatosis
Adenomyomatosis is characterized by extensions of Rokitansky-Aschoff sinuses through the muscular wall of the gallbladder. US reveals a thickened gallbladder wall with intramural diverticula. Although adenomyomatosis is generally considered a benign condition, serial US evaluation is indicated to rule out enlarging adenomatous polyps and gallbladder cancer. Some authors have reported gallbladder cancer occurring in localized adenomyomatosis and have suggested a more aggressive approach to these benign lesions.
Adenomatous polyps
Adenomatous polyps are benign epithelial neoplasms with malignant potential. Papillary adenomas grow as pedunculated, complex, branching tumors projecting into the gallbladder lumen. Tubular adenomas arise as flat, sessile neoplasms. Consequently, it can be difficult to distinguish some adenomas from other gallbladder polyps by means of US. As in many GI tumors, an adenoma-carcinoma sequence is generally thought to occur in these lesions.
Others
Other rare, benign lesions found in the gallbladder include fibromas, leiomyomas, lipomas, hemangiomata, granular cell tumors, and heterotopic tissue, including gastric, pancreatic, and intestinal epithelium.
Malignant lesions
Chronic inflammation from a variety of stimuli has been implicated in the pathogenesis of gallbladder cancer. Numerous studies have investigated genetic abnormalities in gallbladder cancer and have shown that approximately 39-59% of these cancers are associated with the K-ras mutation, whereas more than 90% are associated with a p53 mutation. Other studies have identified higher levels of microsatellite instability and loss of heterozygosity when gallbladder cancers develop against a background of chronic cholecystitis.
A number of other genetic abnormalities have been associated with gallbladder cancer, including overexpression of the c-erb-2 gene, upregulation of cyclin D1, p16, p27, and MSH2.[4]
The most common risk factor for gallbladder cancer is gallstones, which are present in 75-90% of gallbladder cancer cases. The size of the gallstones plays a role in the risk of developing of gallbladder cancer. Gallbladders containing gallstones that are greater than 3 cm in diameter have a 10-fold greater risk for developing malignancy than do those containing gallstones that are 1 cm in diameter.
Causality is difficult to establish, but other chronic inflammatory conditions, such as cholecystoenteric fistula, primary sclerosing cholangitis, pancreaticobiliary maljunction, and chronic infection with Salmonella typhi, have also been associated with an increased risk of gallbladder cancer.
Modern series report about a 10% incidence of gallbladder cancer in porcelain gallbladders (in which the gallbladder wall is calcified), a much lower rate than that reported in older series. Stippled calcification of the mucosa is thought to carry a higher risk of gallbladder cancer than does generalized calcification of the gallbladder wall.[5, 6] On the basis of these associations, chronic inflammation is postulated to be involved in the pathogenesis of gallbladder cancer.
Gallbladder cancer is often discovered incidentally during a workup for gallstone disease, and about 50% of gallbladder cancer cases are diagnosed incidentally in cholecystectomy specimens. Unfortunately, about 35% of patients have distant metastases at the time of diagnosis. Gallbladder cancer spreads early via lymphatic, hematogenous, and transcoelomic dissemination. Local invasion into the liver and surrounding organs is common.
As noted, an adenoma-carcinoma sequence is thought to be involved in many cases of gallbladder cancer. Histologically, adenocarcinoma is found in 90% of gallbladder cancer cases, and squamous cell carcinoma is found in 2% of cases. A number of histologic subtypes of adenocarcinoma have been described, but papillary adenocarcinoma represents about 5% of gallbladder cancers; it tends to be well differentiated and carries a more favorable prognosis.
Rare types of gallbladder cancer include sarcoma, adenosquamous carcinoma, oat cell carcinoma, carcinoid, lymphoma, melanoma, and metastatic tumors.
Gallstones are present in 75-90% of gallbladder cancer cases, but an etiologic influence remains unproven. Risk factors for developing gallbladder cancer include the inflammatory conditions listed above, advanced age, and the presence of a gallstone larger than 3 cm. Anomalous pancreatobiliary junction also may be a risk factor for the development of gallbladder cancer.
Some authors have implicated bile acid composition, methyldopa, oral contraceptives, and occupational exposure to rubber, but these associations remain unproven. A 2008 study found evidence that excess body weight in women, specifically a 5 kg/m2 increase in the body-mass index (BMI), is strongly associated with an increased risk of gallbladder cancer.[7]
Approximately 5% of patients evaluated with US for abdominal pain will have a gallbladder polyp. Adenomatous polyps are found in about 1% of cholecystectomy specimens.
The American Cancer Society estimated that 12,360 new cases of gallbladder or other biliary cancer (~40% of which would be specifically gallbladder cancers) would be diagnosed in 2019, and that there would be 3960 deaths from the disease.[8] The incidence of gallbladder cancer has been reported to be 1.2 cases per 100,000 persons in the United States[9] ; the frequency is much higher in Mexican Americans and Native Americans, though the highest incidence has been found in the indigenous peoples of the Andes Mountains, in northeastern Europeans, and in Israelis.
The female-to-male ratio for gallbladder cancer is about 3:1; the incidence of the disease peaks in the seventh decade of life.[8, 4]
The overall survival rate for adenocarcinoma of the gallbladder 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.
The 5-year survival rates following extended cholecystectomy for T2 lesions have been reported to be in the range of 38-77%. Tumor location may affect survival for T2 lesions. In a study that included 252 patients who underwent curative resection for T2 disease, those with tumors on the hepatic side had higher rates of vascular invasion, neural invasion, and nodal metastasis and lower 3- and 5-year survival rates than patients with tumors on the peritoneal side.[10]
Extended resection is necessary for stage III and IV tumors and results in a 5-year survival rate 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%.[4, 11]
A study by Li et al indicated that the tumor-stroma ratio (TSR) may be an important prognostic indicator for gallbladder cancer.[12] In their study of 51 patients who underwent operations for gallbladder carcinoma, who were classified on the basis of the TSR as either stroma-poor or stroma-rich, the latter had a worse prognosis than the former. Univariate analysis found the TSR to have a statistically significant relation to overall survival.
Like most gallbladder lesions, early-stage adenocarcinoma tends to present with symptoms similar to those of cholelithiasis or biliary dyskinesia. Advanced gallbladder cancer presents with more significant symptoms, such as weight loss, jaundice, anorexia, ascites, and right-upper-quadrant mass.
Given this presentation, fewer than 50% of gallbladder cancers are diagnosed preoperatively. Many are diagnosed incidentally in gallbladders removed for biliary colic or cholecystitis. Unfortunately, most gallbladder cancers are not diagnosed until the later stages, and the overall 5-year survival rate is less than 5%.
General laboratory studies are not highly specific for gallbladder cancer.
In the later stages, liver function enzyme levels may be slightly elevated; these levels are generally not elevated in stages I and II. An elevated bilirubin or alkaline phosphatase (ALP) level generally indicates advanced or obstructive disease. Elevated carbohydrate (cancer) antigen 19-9 (CA19-9) is 79.4% sensitive and 79.5% specific for gallbladder cancer. Elevated carcinoembryonic antigen (CEA) is also associated with gallbladder cancer and is 93% specific and 50% sensitive.
Ultrasonography (US) is a very useful tool in the workup of gallbladder cancer. Polypoid lesions must be at least 5 mm in size to be detected by US. Cholesterol polyps generally appear as pedunculated lesions attached to the gallbladder wall.
US findings that indicate possible malignancy or the need for further workup include the following:
Thick gallbladder wall (see the image below)
Vascular polyp
Mass projecting into the lumen or invading the wall
Multiple masses or a fixed mass in the gallbladder
Porcelain gallbladder
Extracholecystic mass
View Image
Sagittal ultrasonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was pr....
Invasion of the liver can also be seen on US.
Displacement of a stone to one side of the gallbladder is suggestive of possible malignancy.
Endoscopic US (EUS) with fine-needle aspiration (FNA) can be used to evaluate for peripancreatic and periportal lymphadenopathy.
Computed tomography (CT) and magnetic resonance imaging (MRI) are useful in evaluating the extent of invasion and resectability of gallbladder tumors. CT results suggestive of gallbladder cancer include asymmetrical wall thickening or gallbladder mass, with or without invasion into the liver. CT of the chest, abdomen, and pelvis is a common staging modality that can determine the presence of distant metastases and give reliable information about involvement of other organs and vascular structures.
A porcelain gallbladder has been commonly associated with gallbladder cancer; however, studies have shown that the type of calcification is more important in determining the risk for malignancy. Selective mucosal calcifications carry an increased risk when compared to diffuse intramural wall calcification. (See the image below.)
View Image
A transaxial enhanced computed tomography (CT) scan of a 60-year-old man with right upper quadrant pain shows a partially calcified gallbladder (arrow....
View Image
Computed tomography (CT) scan in a 65-year-old man. This image depicts squamous cell carcinoma of the gallbladder and invasion of the liver.
Positron emission tomography (PET) has a sensitivity of 75% and a specificity of 88% in gallbladder cancer but is not used routinely in the preoperative staging or postoperative surveillance of the disease.[13, 14] Quantitative parameters of 18F-fluorodeoxyglucose (FDG) PET/CT, including metabolic tumor volume (MTV), have been found to be useful for the identification of patients with locally advanced and metastatic gallbladder cancer who have a poorer prognosis.[15]
Percutaneous CT-guided biopsy is avoided in patients whose tumors are considered resectable on the basis of preoperative imaging. Because of the substantial risk of peritoneal seeding, percutaneous biopsy and diagnostic cholecystectomy are not necessary in patients suspected of having gallbladder cancer. In these patients, exploration with curative intent is planned on the basis of preoperative imaging alone.
Percutaneous CT-guided biopsy is a useful diagnostic tool in patients who appear to have a nonresectable tumor. Tissue diagnosis is necessary for palliative treatment.
The vast majority of gallbladder cancers are adenocarcinomas. Papillary adenocarcinomas have a better prognosis, because they tend to be well-differentiated and less invasive. A number of other histologic subtypes have been described, but the prognostic implications are unknown. Some authors have described metaplastic and nonmetaplastic subtypes and have suggested that metaplastic tumors have a more favorable prognosis.
Unfortunately, most gallbladder cancers are poorly differentiated and present at an advanced stage; accordingly, the prognostic importance of histologic subtypes is limited.
Gallbladder tumors are commonly staged according to the tumor-node-metastasis (TNM) system of the American Joint Committee on Cancer (AJCC; see Tables 1 and 2 below).[16]
Table 1. AJCC TNM Classification of Gallbladder Tumors
View Table
See Table
Table 2. AJCC Staging of Gallbladder Tumors According to TNM Classification
Cholecystectomy is recommended for suspicious gallbladder polyps in order to facilitate early detection and treatment. Risk factors for malignancy include the following:
Polyp larger than 1 cm
Primary sclerosing cholangitis
Presence of a single polyp
Patient older than 50 years
Vascularity and invasion of the gallbladder wall seen on ultrasonography (US) are suspicious findings. One study demonstrated that 7.4% of gallbladder polyps that were 1 cm in size or smaller were neoplastic.[17] The report's authors recommended cholecystectomy for lesions that are 6 mm in size or larger.
Gallbladder cancer is diagnosed incidentally following cholecystectomy or based on preoperative imaging. The surgical indications are based on stage and margin status (see Staging).
Incidentally discovered T1a gallbladder cancers (limited to the mucosa) can generally be treated with cholecystectomy alone. T1b tumors (invading the muscle layer) are typically treated with resection of liver segments IVb and V and portal lymph node dissection. Bile duct resection is sometimes required to achieve a negative margin, especially if the cystic duct margin was positive on the cholecystectomy specimen. T2 and T3 lesions are also treated with liver resection and portal lymph node dissection, but extended right hepatectomy may be necessary to achieve negative margins.[4]
Contraindications for surgery with curative intent include the following:
Presence of distant metastatic disease (including biopsy-proven metastatic aortocaval lymphadenopathy)
T4 lesion (local invasion of the hepatic artery, main portal vein, and multiple adjacent structures)
Inability to obtain a negative margin
Most North American surgeons have considered the presence of celiac and retroperitoneal lymph node metastases a contraindication for resection because of the poor oncologic outcome of these patients with available treatments. For the same reason, there has been some controversy about the benefit of resecting patients with T3 lesions. Some patients may have lesions that are technically resectable but may be unable to tolerate the necessary procedure.
Small gallbladder tumors are common, and many can be safely followed with serial US examination. It is generally thought that polyps smaller than 1 cm are safe to follow, though one study[17] recommended that polyps that are 6 mm in size or larger 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 this cancer, the benefit of adjuvant treatment remains unproven, and no standard adjuvant treatment protocol has been defined.
Phase II studies have shown that the use of single-agent chemotherapy (with gemcitabine, capecitabine, or 5-fluorouracil [5-FU]) in the palliative setting can be beneficial. Combination chemotherapy also has been shown to be beneficial and is usually based on gemcitabine,[18] capecitabine, or 5-FU used in combination with cisplatinum or oxaliplatinum. Fluoropyrimidine-based chemoradiotherapy is commonly employed in the palliative and adjuvant setting as well. No regimen has been conclusively established as superior.
A 2008 study found that only 20% of patients with gallbladder cancer received adjuvant treatment.[19] 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.[20] Because of the high cure rate with surgery alone for T1N0 lesions, adjuvant therapy is not commonly offered to these patients.
A 2017 review by Mitin et al found that the use of adjuvant chemotherapy for resected gallbladder cancer did not increase appreciably between 2005 and 2013, even though statistically significant improvements in 3-year overall survival were reported in several studies (except in cases of T1N0 disease).[21]
A 2019 guideline from the American Society for Clinical Oncology (ASCO) recommended that patients with resected biliary tract cancer be offered adjuvant capecitabine chemotherapy for 6 months.[22] Patients with extrahepatic cholangiocarcinoma or gallbladder cancer and a microscopically positive surgical resection margin (R1 resection) may be offered chemoradiation therapy.
Operative resection offers the only chance for long-term survival. The details are described below.[23]
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 between a laparoscopic and an open operation depends on the risk of the lesion being malignant. Preoperative imaging should be reviewed to exclude the presence of invasion before a laparoscopic approach is planned.
In these cases, the gallbladder 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.
Guidelines on the management and follow-up of gallbladder polyps have been jointly developed by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the European Association for Endoscopic Surgery and Other Interventional Techniques (EAES), the International Society of Digestive Surgery–European Federation (EFISDS), and the European Society of Gastrointestinal Endoscopy (ESGE).[24] (See Guidelines.)
Malignant lesions
Gallbladder cancer can be diagnosed either incidentally in a surgical specimen excised for other reasons or on the basis of imaging studies. When it is 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.
Patients with localized gallbladder 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 gallbladder cancer can be treated with simple cholecystectomy. Patients with T1b or deeper gallbladder cancer are typically treated with hepatic resection and lymph node dissection that includes the portal, gastrohepatic ligament, and retroduodenal nodes. Resection of liver segments IVb and V is frequently adequate to achieve negative margins. (See the images below.) Some have suggested that simple cholecystectomy may be sufficient for T1b lesions smaller than 1 cm.[25]
View Image
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
View Image
Gallbladder tumors. A schematic drawing of the extent of resection of liver segments IV-b and V for gallbladder cancer.
In some cases, extended liver resection or bile duct resection or both may be necessary to achieve negative margins. A study by He et al found that simple cholecystectomy was the optimal surgical procedure for stages 0 and I, whereas radical cholecystectomy was preferable for stages II and III.[26]
Adjuvant treatment with either fluoropyrimidine-based chemoradiotherapy or chemotherapy alone is recommended.
When patients have unresectable tumors, tissue diagnosis and relief of jaundice (if present) are required prior to initiation of palliative treatment.
Percutaneous biopsy is avoided in cases where the tumor is resectable.
Preparation for surgery
As outlined above, the preoperative evaluation of the patient with gallbladder cancer is similar whether the tumor is diagnosed incidentally after cholecystectomy or on the basis of imaging studies.
The history and physical examination determine the suitability of the patient for 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. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) values may be helpful as baseline studies that inform treatment decisions in the future. Computed tomography (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.
Operative details
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 US (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 in 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 (eg, stomach, duodenum, or 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 on the basis of 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 necessitate 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 study by Ito et al indicated that accurate staging requires examination of at least six lymph nodes.[27] A study by Tsilimigras et al suggested that examination of four to seven nodes may be optimal in terms of staging and survival.[28]
The overall rate of complications and morbidity 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 after extended hepatectomy, especially if jaundice is present preoperatively.
There are no data to support aggressive surveillance after resection of gallbladder cancer, because treatment of recurrences generally is not effective. However, many clinicians and patients prefer follow-up imaging every 6 months.
ESGAR/EAES/EFISDS/ESGE Guidelines for Gallbladder Polyps
In 2017, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the European Association for Endoscopic Surgery and other Interventional Techniques (EAES), the International Society of Digestive Surgery–European Federation (EFISDS), and the European Society of Gastrointestinal Endoscopy (ESGE) issued joint guidelines regarding the management and follow-up of gallbladder polyps,[24] which included the following:
For a polypoid gallbladder lesion ≥10 mm, cholecystectomy is recommended if the patient is fit for and accepts surgery (moderate-quality evidence; 89% agreement)
For a polypoid gallbladder lesion with symptoms attributable to the gallbladder, cholecystectomy is suggested if there is no other cause for the symptoms and the patient is fit for and accepts surgery (low-quality evidence; 89% agreement)
If cholecystectomy is not indicated, risk factors for gallbladder malignancy (age >50 years; history of primary sclerosing cholangitis; Indian ethnicity; sessile polyp, including focal gallbladder wall thickening >4 mm) should be established and a more intensive management plan followed (low- to moderate-quality evidence; 78% agreement).
If the patient has risk factors for gallbladder malignancyand a polyp 6-9 mm, cholecystectomy is recommended if the patient is fit for and accepts surgery (low- to moderate-quality evidence; 78% agreement)
If the patient has either (a) no risk factors for gallbladder malignancy and a polyp of 6-9 mm or (b) risk factors for malignancy and a gallbladder polyp ≤5 mm, follow-up ultrasonography (US) of the gallbladder is recommended at 6 months and 1 year and then yearly up to 5 years; If the patient has no risk factors for malignancy and a polyp of ≤5 mm or less, follow-up is advised at 1, 3, and 5 years (low-quality evidence, 78% agreement)
If polyp size increases by ≥2 mm during follow-up, cholecystectomy is advised (moderate-quality evidence; 78% agreement)
If polyp size reaches 10 mm during follow-up, cholecystectomy is advised (moderate-quality evidence; 100% agreement)
If the polyp disappears during follow-up, then follow-up should be discontinued (moderate-quality evidence; 100%agreement)
Primary investigation should be with abdominal US, and routine use of other imaging modalities is not recommended; if appropriate expertise and resources are available, other modalities (eg, endoscopic US [EUS]) may be considered as aids to decision-making in difficult cases (low-quality evidence; 100% agreement)
Thomas J VanderMeer, MD, Assistant Professor of Surgery, State University of New York Upstate Medical University; Chief, Section of General Surgery, Program Director of General Surgery Residency Program, Guthrie Health System
Disclosure: Nothing to disclose.
Coauthor(s)
Michael Kent McLeod, MD, MBA, FACE, FACS, Associate Chair, Professor of Surgery and Program Director, Integrated General Surgery Program, Department of Surgery, Michigan State University College of Human Medicine
Disclosure: Nothing to disclose.
Michel M Murr, MD, Professor, Department of Surgery, Director of Bariatric Surgery, University of South Florida
Disclosure: Received consulting fee from Covidien for consulting.
Tara Mancl, MD, Staff Physician, Department of Surgery, Michigan State University, Kalamazoo Center for Medical Studies
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
John Geibel, MD, MSc, DSc, AGAF, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital
Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons
Davis JL, Kingham TP. Tumors of the gallbladder. Jarnagin WR, Allen PJ, Chapman WC, et al, eds. Blumgart's Surgery of the Liver, Biliary Tract, and Pancreas. 6th ed. Philadelphia: Elsevier; 2017. 786-804.
Cancer Facts and Figures 2019. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. 2019; Accessed: June 28, 2019.
Howlader N, Noone AM, Krapcho M, et al, eds. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. Available at https://seer.cancer.gov/csr/1975_2014/. April 14, 2017; Accessed: May 30, 2017.
Gallbladder cancer treatment (PDQ®)–health professional version. National Cancer Institute. Available at https://www.cancer.gov/types/gallbladder/hp/gallbladder-treatment-pdq#section/_6. March 23, 2019; Accessed: July 2, 2019.
Hepatobiliary cancers. Version 2.2019. NCCN Clinical Practice Guidelines in Oncology™. Available at https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. March 6, 2019; Accessed: July 2, 2019.
Sagittal ultrasonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was primary papillary adenocarcinoma of the gallbladder.
A transaxial enhanced computed tomography (CT) scan of a 60-year-old man with right upper quadrant pain shows a partially calcified gallbladder (arrow). At laparotomy and histology, an infiltrating adenocarcinoma of the gallbladder was confirmed.
Computed tomography (CT) scan in a 65-year-old man. This image depicts squamous cell carcinoma of the gallbladder and invasion of the liver.
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
Gallbladder tumors. A schematic drawing of the extent of resection of liver segments IV-b and V for gallbladder cancer.
A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
Gallbladder tumors. A schematic drawing of the extent of resection of liver segments IV-b and V for gallbladder cancer.
Sagittal ultrasonogram in a 71-year-old woman. This image demonstrates heterogeneous thickening of the gallbladder wall (arrows). The diagnosis was primary papillary adenocarcinoma of the gallbladder.
A transaxial enhanced computed tomography (CT) scan of a 60-year-old man with right upper quadrant pain shows a partially calcified gallbladder (arrow). At laparotomy and histology, an infiltrating adenocarcinoma of the gallbladder was confirmed.
Computed tomography (CT) scan in a 65-year-old man. This image depicts squamous cell carcinoma of the gallbladder and invasion of the liver.
Tumor (T), Node (N), Metastasis (M)
Description
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor invades lamina propria (T1a) or muscle layer (T1b)
T2
Tumor invades perimuscular connective tissue on peritoneal side, without involvement of serosa (visceral peritoneum) (T2a); or tumor invades perimuscular connective tissue on hepatic side, with no extension into liver (T2b)
T3
Tumor perforates serosa (visceral peritoneum) and/or directly invades liver and/or 1 other adjacent organ or structure, such as stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts
T4
Tumor invades main portal vein or hepatic artery or invades multiple extrahepatic organs or structures
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