**2. Epidemiology**

Gallbladder cancer is the most common cancer of the bile ducts. It accounts for 3% of all malignant tumors and ranks fifth among digestive cancers after cancer of the colon, rectum, stomach and pancreas [2].

The incidence rates are high in Asia and Latin America, relatively high in some countries in eastern and central Europe, yet low in the United States and most Western and Mediterranean European countries [3]. Gallbladder cancer tends to afflict indigenous populations, according to a vast global cancer registry on five continents (representing 704.4 million people or 11% of the world population) [4]. Mapuche Indians from Valdivia, Chile and South America exhibit the highest rate of gallbladder cancer: 12.3/100,000 for males and 27.3/100,000 for females. American Indians in New Mexico, USA, follow with an average annual rate of 8.9/100,000. For these native people, GBC mortality rates exceed those for breast (8.7/100,000), cervical (8.0/100,000), pancreatic (7.4/100,000) and ovarian cancers (7.3/100,000) [5]. According to the literature, the sex ratio women-men ranges from 2:1 to 3:1. In India and South America, the sex ratio is particularly very high: 5/1 to 6/1. However, this difference between the two sexes is less pronounced in East Asia, where the sex ratio between men and women [6]. Gallbladder cancer rates tend to increase with advancing age. The median age was 67 years in a Memorial Sloan-Kettering report of 435 gallbladder cancer patients [7]. Gallbladder cancer is found in 1–2% of cholecystectomized patients. It is suggested that the presence of vesicular calculus may cause dysplasia of the vesicular mucosa after chronic irritation.

Usually, gallbladder cancer develops over 5–15 years, when metaplasia progresses to dysplasia, carcinoma in situ and, then, invasive cancer. Only 10% of patients are resectable at the time of surgery [6] with high recurrence rates [8].

### **3. Diagnosis**

#### **3.1 Symptoms and signs of gallbladder carcinoma**

The clinical presentation of GBC is often vague or delayed relative to pathologic progression, contributing to advanced staging and dismal prognosis at the time of diagnosis. The clinical presentation is nonspecific. Pain is the most constant symptom. It is present in 72–77% of patients [9]. Frequently, it is an intense paroxysmal pain with respiratory inhibition, sitting in the right hypochondrium, and with posterior irradiation to the tip of the right shoulder blade and anterior to the right shoulder, realizing the classic pain in sling. It could be atypical such as epigastralgia and diffuse abdominal pain [9].

Jaundice is observed in 58% of cases. It may be secondary to either tumor invasion or extrinsic compression of the bile ducts by lymphadenopathy or tumor or by the presence of liver metastases [10]. Nausea and vomiting are found in 20–49% of cases. Clinical examination may be strictly normal at the early stages. The most common signs are evidence of a very advanced disease. GBC is manifested in 15–50% of cases by a mass of the right hypochondrium [11]. Abdominal palpation shows a sensitivity of the right hypochondrium in 50–80% of cases [11]. A defense of the right hypochondrium or even a positive sign of Murphy can be found on the examination, but they remain an unspecific signs [11].

#### **3.2 Diagnosis**

Imaging modalities such as ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT), *magnetic resonance imaging* (MRI) and

**105**

**Figure 1.**

*gallbladder carcinoma.*

*Gall Bladder Carcinoma: Clinical Presentations and Different Modalities of Treatment*

MRI examinations are useful for local and metastatic staging [13].

magnetic resonance cholangiopancreatography (MRCP) are useful. EUS has good sensitivity in differentiating benign gallbladder diseases from GBC [12]. CT and

Ultrasonography is the first examination to be carried out in the diagnostic approach in front of a patient presenting a biliary symptomatology or for the preoperative study of a vesicular tumor (**Figure 1**, [14, 15]). It has a sensitivity of 85% and a specificity of 80% in the diagnosis of tumors of the gallbladder. Budding image is the most common image [15]. It is a vegetative lesion projecting into the vesicular lumen. It can be single or multiple and is manifested by a hypo or iso-echoic image without shadow cone, irregular edge and implantation base. EUS allows directly visualizing the tumor and evaluating its deep extension in the vesicular wall, in the hepatic parenchyma and the bile ducts [14]. It also makes it possible to differentiate an early tumor from an advanced tumor. It has a significant sensitivity for the

If US suggest a resectable GBC, CT, MRI with magnetic resonance cholangiography (MRC) and/or traditional cholangiography often provide additional informa-

CT is to be done in second intension after the ultrasound. It allows the diagnosis of GBC in 60–74% of cases. However, its main interest lies in the establishment of the tumor extension report. The CT scan aspects are similar to those detected by ultrasound. A parietal thickening (**Figure 2**) or a budding tumor presenting as a hypodense, heterogeneous lesion containing hypodense zones and other hyperdense secondary to tumor necrosis may be found. The enhancement by the tumor may be diffuse or partial, preferentially, peripheral in case of avascular central necrosis [18, 19]. Although CT is inferior to ultrasound in depicting mucosal irregularity, mural thickening and cholelithiasis, it is superior for evaluating the thickness of portions of the gallbladder wall that are obscured by gallstones or mural calcification on ultrasound. In unclear cases, hybrid PET-CT systems may provide structural and functional information simultaneously and may offer early

The GBC appears hypo- or isosignal in T1 and hypersignal in T2 at MRI, the perilesional inflammation in hypersignal T2 and the calculations are hyposignal. Intravenous gadolinium injection increases sensitivity and provides additional data

*Ultrasonography shows hyperechoic shadowing portions of gallbladder wall (arrowheads) consistent with porcelain gallbladder and hypoechoic, polypoid mass (arrow) suggestive of malignant degeneration into* 

*DOI: http://dx.doi.org/10.5772/intechopen.81263*

etiological diagnosis of neoplastic icterus.

and accurate staging with high specificity [20].

tion [16]. These modalities allowed specific staging [17].

#### *Gall Bladder Carcinoma: Clinical Presentations and Different Modalities of Treatment DOI: http://dx.doi.org/10.5772/intechopen.81263*

magnetic resonance cholangiopancreatography (MRCP) are useful. EUS has good sensitivity in differentiating benign gallbladder diseases from GBC [12]. CT and MRI examinations are useful for local and metastatic staging [13].

Ultrasonography is the first examination to be carried out in the diagnostic approach in front of a patient presenting a biliary symptomatology or for the preoperative study of a vesicular tumor (**Figure 1**, [14, 15]). It has a sensitivity of 85% and a specificity of 80% in the diagnosis of tumors of the gallbladder. Budding image is the most common image [15]. It is a vegetative lesion projecting into the vesicular lumen. It can be single or multiple and is manifested by a hypo or iso-echoic image without shadow cone, irregular edge and implantation base. EUS allows directly visualizing the tumor and evaluating its deep extension in the vesicular wall, in the hepatic parenchyma and the bile ducts [14]. It also makes it possible to differentiate an early tumor from an advanced tumor. It has a significant sensitivity for the etiological diagnosis of neoplastic icterus.

If US suggest a resectable GBC, CT, MRI with magnetic resonance cholangiography (MRC) and/or traditional cholangiography often provide additional information [16]. These modalities allowed specific staging [17].

CT is to be done in second intension after the ultrasound. It allows the diagnosis of GBC in 60–74% of cases. However, its main interest lies in the establishment of the tumor extension report. The CT scan aspects are similar to those detected by ultrasound. A parietal thickening (**Figure 2**) or a budding tumor presenting as a hypodense, heterogeneous lesion containing hypodense zones and other hyperdense secondary to tumor necrosis may be found. The enhancement by the tumor may be diffuse or partial, preferentially, peripheral in case of avascular central necrosis [18, 19]. Although CT is inferior to ultrasound in depicting mucosal irregularity, mural thickening and cholelithiasis, it is superior for evaluating the thickness of portions of the gallbladder wall that are obscured by gallstones or mural calcification on ultrasound. In unclear cases, hybrid PET-CT systems may provide structural and functional information simultaneously and may offer early and accurate staging with high specificity [20].

The GBC appears hypo- or isosignal in T1 and hypersignal in T2 at MRI, the perilesional inflammation in hypersignal T2 and the calculations are hyposignal. Intravenous gadolinium injection increases sensitivity and provides additional data

#### **Figure 1.**

*Digestive System - Recent Advances*

the colon, rectum, stomach and pancreas [2].

Gallbladder cancer is the most common cancer of the bile ducts. It accounts for 3% of all malignant tumors and ranks fifth among digestive cancers after cancer of

The incidence rates are high in Asia and Latin America, relatively high in some countries in eastern and central Europe, yet low in the United States and most Western and Mediterranean European countries [3]. Gallbladder cancer tends to afflict indigenous populations, according to a vast global cancer registry on five continents (representing 704.4 million people or 11% of the world population) [4]. Mapuche Indians from Valdivia, Chile and South America exhibit the highest rate of gallbladder cancer: 12.3/100,000 for males and 27.3/100,000 for females. American Indians in New Mexico, USA, follow with an average annual rate of 8.9/100,000. For these native people, GBC mortality rates exceed those for breast (8.7/100,000), cervical (8.0/100,000), pancreatic (7.4/100,000) and ovarian cancers (7.3/100,000) [5]. According to the literature, the sex ratio women-men ranges from 2:1 to 3:1. In India and South America, the sex ratio is particularly very high: 5/1 to 6/1. However, this difference between the two sexes is less pronounced in East Asia, where the sex ratio between men and women [6]. Gallbladder cancer rates tend to increase with advancing age. The median age was 67 years in a Memorial Sloan-Kettering report of 435 gallbladder cancer patients [7]. Gallbladder cancer is found in 1–2% of cholecystectomized patients. It is suggested that the presence of vesicular calculus

may cause dysplasia of the vesicular mucosa after chronic irritation.

resectable at the time of surgery [6] with high recurrence rates [8].

**3.1 Symptoms and signs of gallbladder carcinoma**

examination, but they remain an unspecific signs [11].

Usually, gallbladder cancer develops over 5–15 years, when metaplasia progresses to dysplasia, carcinoma in situ and, then, invasive cancer. Only 10% of patients are

The clinical presentation of GBC is often vague or delayed relative to pathologic progression, contributing to advanced staging and dismal prognosis at the time of diagnosis. The clinical presentation is nonspecific. Pain is the most constant symptom. It is present in 72–77% of patients [9]. Frequently, it is an intense paroxysmal pain with respiratory inhibition, sitting in the right hypochondrium, and with posterior irradiation to the tip of the right shoulder blade and anterior to the right shoulder, realizing the classic pain in

Jaundice is observed in 58% of cases. It may be secondary to either tumor invasion or extrinsic compression of the bile ducts by lymphadenopathy or tumor or by the presence of liver metastases [10]. Nausea and vomiting are found in 20–49% of cases. Clinical examination may be strictly normal at the early stages. The most common signs are evidence of a very advanced disease. GBC is manifested in 15–50% of cases by a mass of the right hypochondrium [11]. Abdominal palpation shows a sensitivity of the right hypochondrium in 50–80% of cases [11]. A defense of the right hypochondrium or even a positive sign of Murphy can be found on the

Imaging modalities such as ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT), *magnetic resonance imaging* (MRI) and

sling. It could be atypical such as epigastralgia and diffuse abdominal pain [9].

**2. Epidemiology**

**3. Diagnosis**

**104**

**3.2 Diagnosis**

*Ultrasonography shows hyperechoic shadowing portions of gallbladder wall (arrowheads) consistent with porcelain gallbladder and hypoechoic, polypoid mass (arrow) suggestive of malignant degeneration into gallbladder carcinoma.*

#### **Figure 2.**

*Contrast-enhanced CT scan during portal venous phase shows focal nodular thickening (arrow) and diffuse gallbladder wall thickening.*

#### **Figure 3.**

*Axial fat-saturated T2 fast spin image shows a mildly hyperintense, polypoidal and intraluminal gallbladder mass (arrow).*


**107**

*Gall Bladder Carcinoma: Clinical Presentations and Different Modalities of Treatment*

on vascular involvement (**Figure 3**). The section thickness should be 5 mm or less,

Cholangio-MRI is a very useful test for jaundice. It allows to specify the tumor extension. It may be the only examination to be performed after ultrasound in patients with jaundice. Dynamic MRI with MRCP is an accurate and a reliable method of showing GBC and in assessing its local and regional extent as part of preoperative assessment [13]. However, only the pathological study could confirm

In unclear cases, fluorodeoxyglucose-positron emission tomography (FDG-PET) can be considered to establish the benign or the malignant nature of the lesion and

**Table 1** showed TNM classification (7th edition)—UICC—AJCC (2010) cancers

*4.1.1.1 Tis, T1a, T1b and T2 cancers discovered incidentally on the cholecystectomy*

The reference is IVb-V bisegmentectomy with lymph node dissection and possibly resection of the bile duct. Bisegmentectomy can be discussed in favor of resection of the vesicular bed for these "small cancers," especially if the cancer is located on the free side of the gallbladder. Similarly, resection of the bile duct is recommended only in cases of cystic involvement or patent nodal invasion

Systematic secondary resection of trocar orifices is currently controversial.

*DOI: http://dx.doi.org/10.5772/intechopen.81263*

with a 1–2 mm gap between sections.

*PET/CT image: gallbladder carcinoma (arrow) with lymph nodes (asterisk).*

the diagnosis of gallbladder carcinoma.

of gall bladder.

**Figure 4.**

**4. Treatment**

*4.1.1 Surgery*

(**Figure 5**) [21].

**4.1 Localized GCC**

to obtain a primary staging study (**Figure 4**).

*\*\*Peri-aortic, peri-cellar, celiac trunk and superior mesenteric artery.*

#### **Table 1.** *TNM classification (7th edition).*

*Gall Bladder Carcinoma: Clinical Presentations and Different Modalities of Treatment DOI: http://dx.doi.org/10.5772/intechopen.81263*

#### **Figure 4.** *PET/CT image: gallbladder carcinoma (arrow) with lymph nodes (asterisk).*

on vascular involvement (**Figure 3**). The section thickness should be 5 mm or less, with a 1–2 mm gap between sections.

Cholangio-MRI is a very useful test for jaundice. It allows to specify the tumor extension. It may be the only examination to be performed after ultrasound in patients with jaundice. Dynamic MRI with MRCP is an accurate and a reliable method of showing GBC and in assessing its local and regional extent as part of preoperative assessment [13]. However, only the pathological study could confirm the diagnosis of gallbladder carcinoma.

In unclear cases, fluorodeoxyglucose-positron emission tomography (FDG-PET) can be considered to establish the benign or the malignant nature of the lesion and to obtain a primary staging study (**Figure 4**).

**Table 1** showed TNM classification (7th edition)—UICC—AJCC (2010) cancers of gall bladder.

#### **4. Treatment**

*Digestive System - Recent Advances*

**Extension M0 M1**

*Axial fat-saturated T2 fast spin image shows a mildly hyperintense, polypoidal and intraluminal gallbladder* 

*Contrast-enhanced CT scan during portal venous phase shows focal nodular thickening (arrow) and diffuse* 

Tis Carcinoma in situ 0 — — — T1a Tumor invades the lamina propria I IIIB IVB

T1b Tumor invades the muscular layer

T2 Tumor invades the perimuscular connective tissue; no

T3 Tumor perforates the serosa and/or invades the liver and/

T4 Tumor invades the main portal vein or the hepatic artery

*\*\*Peri-aortic, peri-cellar, celiac trunk and superior mesenteric artery.*

extension beyond the serosa or into the liver

or other adjacent organ or extrahepatic bile ducts

or two or more extrahepatic organs

*\*Along the cystic duct, the common hepatic duct, the common hepatic artery and the portal vein.*

**N0 N1\* N2\*\***

II

IIIA

IVA

**106**

**Table 1.**

**Figure 2.**

**Figure 3.**

*mass (arrow).*

*gallbladder wall thickening.*

*TNM classification (7th edition).*

#### **4.1 Localized GCC**

#### *4.1.1 Surgery*

#### *4.1.1.1 Tis, T1a, T1b and T2 cancers discovered incidentally on the cholecystectomy*

The reference is IVb-V bisegmentectomy with lymph node dissection and possibly resection of the bile duct. Bisegmentectomy can be discussed in favor of resection of the vesicular bed for these "small cancers," especially if the cancer is located on the free side of the gallbladder. Similarly, resection of the bile duct is recommended only in cases of cystic involvement or patent nodal invasion (**Figure 5**) [21].

Systematic secondary resection of trocar orifices is currently controversial.
