Gallbladder carcinoma requiring hospitalization-Health Ministry Guidelines

The gallbladder is a distensible pear-shaped structure located in a fossa on the undersurface of the right lobe of the liver. It is a storage reservoir that allows bile acids to be delivered in a high concentration and a controlled manner to the duodenum for the solubilization of dietary lipid. Gallbladder has a storage capacity of approximately 30 to 50 mL in a normal adult. The portions of the gallbladder are the fundus, body, infundibulum, and neck.

Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Gallbladder carcinoma (GBC) requiring hospitalization. Following are the major recommendations :

Case definition (for situation 1 and 2)

• The term Gallbladder carcinoma (GBC) refers to malignant tumor arising from epithelial lining of gallbladder. It is an aggressive tumor which can spread to adjacent organs, lymph nodes and metastasize to distant sites resulting in death if left untreated.


• Incidental GBC - GBC that is not suspected before or at operation and even on gross examination of the opened gallbladder specimen by the surgeon, but is detected for the first time on histopathological examination (HPE) of a gallbladder removed for presumed (clinical, ultrasound, operative) diagnosis of gallstone disease (GSD).

Incidence in our country

• GBC is more common in Northern and Eastern India compared to other regions.


• Age standardized incidence rate in males ranged from 0.3 /1,00,000 men in low incidence areas to 5.3/1,00,000 men in high incidence areas.


• Age standardized incidence rate in females ranged from 0.4/1,00,000 in low incidence areas to 14.3/1,00,000 in high incidence areas.


• GBC is becoming one of the most common cancers among women in north and northeast India.

Diagnosis

Situation 1

Clinical : Clinical diagnosis is based on evaluation of symptoms and examination.

Symptoms due to tumor in gallbladder

• Right upper abdominal pain – colicky or continuous with or without radiation to shoulder or back


• Abdominal lump

Symptoms due to adjacent organ involvement

• Jaundice (bile duct involvement)


• Vomiting (gastroduodenal involvement)


• Intestinal obstruction (colonic involvement)

Constitutional symptoms

• Anorexia


• Weight loss

Symptoms due to metastasis

• Bone pain (bone metastasis)


• Abdominal distension (peritoneal dissemination with ascites)


• Dyspnoea (lung metastasis)

Situation 2

Clinical : Same as in situation 1

Differential diagnosis

Presentation with upper abdominal pain

• Cholelithiasis and cholecystitis


• Pancreatitis


• Peptic ulcer disease

Presentation with jaundice

• Choledocholithiasis (CBD stones)


• Periampullary carcinoma


• Carcinoma head of pancreas

Presentation with vomiting

• Benign gastric outlet obstruction (peptic ulcer disease related)


• Carcinoma stomach


• Duodenal tuberculosis

Presentation with abdominal lump

• Hepatocellular carcinoma


• Periampullary/carcinoma head of pancreas with palpable gallbladder


• Hydatid cyst


• Carcinoma hepatic flexure

Management (situation 1)

Investigations :

Ultrasound abdomen:Features suggestive of GBC are

• Irregular /focal GB wall thickening


• Large intraluminal polypoidal mass


• GB mass with liver infiltration.

Treatment

Situation 1

Out patient

Patients with clinical findings suggestive of GBC should be evaluated with Ultrasound abdomen.

If ultrasound findings are suggestive of GBC patient should be referred to tertiary centre with expertise in management of GBC.

In patient

• Patients with clinical findings suggestive of GBC should be evaluated with Ultrasound abdomen.


• If ultrasound findings are suggestive of GBC patient should be referred to tertiary centre with expertise in management of GBC

Intra-op

Patient taken up for cholecystectomy for suspected gall stone disease ^→ Intraoperative findings suggestive of mass in gallbladder ^→ If no expertise in management ^→ it is preferable to refer the patient to tertiary centre with expertise in management of GBC instead of performing simple cholecystectomy

Post-op

• All cholecystectomy specimens performed for gallstone disease should be sent for histopathological examination (HPE)


• If HPE suggestive of GBC patient should be referred to tertiary centre with expertise in management of GBC

Management (situation 2)

Investigations

For diagnosis and staging

Ultrasound with Doppler abdomen : Doppler to assess vascular involvement

Contrast enhanced computed tomography (CECT) abdomen or Magnetic resonance imaging (MRI) abdomen with Magnetic Resonance Cholangio Pancreatography (MRCP)

• Both CECT and MRI abdomen are more sensitive for diagnosis and staging compared to ultrasound abdomen


• MRI preferred in patients with jaundice

Whole body Positron emission tomography (PET)

• Not required in all patients


• In selected cases (locally advanced disease) with no evidence of metastasis on CECT/MRI abdomen to detect metastatic disease

Upper GI endoscopy : In patients with suspected gastroduodenal involvement Tumor markers (CEA,CA 19-9, CA 125, CA 242)

• Not required for diagnosis


• Prognostic value


• Useful in follow up

Pathological diagnosis (image guided FNAC or biopsy)

Not required in all patients

Required in selected cases

• Planned for neoadjuvant therapy in view of locally advanced disease


• Planned for palliative therapy in view of metastatic disease

To assess fitness for surgery

• Hemogram


• Serum electrolytes


• Kidney function test


• Liver function test


• ECG


• Chest x-ray

Treatment

Outpatient

• Patients with clinical findings suggestive of GBC and fit for surgery should be evaluated with Ultrasound abdomen.


• If ultrasound findings are suggestive of GBC further evaluation with CECT/MRI abdomen for diagnosis and staging.


• Early admission and surgical intervention should be advised

In patient

Staging laparoscopy should be preferably done in all patients prior to laparotomy

T1b –T2 GBC

• Radical cholecystectomy is the standard treatment.


• Radcical cholecystectomy includes – liver resection with lymphadenectomy


• Liver resection - cholecystectomy with 2cm wedge or anatomical segment IVb-V resection


• Lymphadenectomy – Extent of lymphadenectomy varies from clearance of only nodes along the hepatoduodenal ligament skeletonizing the vascular structures and the bile ducts to additional clearance of nodes anterior and posterior to the head of the pancreas and the hepatic artery till its origin from the celiac axis.

T3 GBC

• Radical cholecystectomy is the standard treatment.


• Extended right hepatectomy in patients with extensive liver infiltration

T4 GBC

• Radical cholecystectomy with resection of adjacent involved organs if deemed resectable

IGBC

Completion radical cholecystectomy for all cases with stage T1b and above.

Contraindications for curative surgery (absolute and relative)

• Distant metastasis - liver metastasis and peritoneal deposits


• Vascular involvement (main portal vein, common hepatic artery)


• Extensive nodal disease or multiple adjacent organ involvement


• Extensive biliary involvement.

Adjuvant chemoradiotherapy

It can be considered in patients with

• Advanced stage disease (stage III and IV)


• Nodal positive disease


• Non curative resection (R1 and R2 resection)

Post-operative care

• Analgesics


• Antibiotics – duration depends upon postoperative course


• Intravenous fluid supplementation till oral feeds are started


• Wound care


• DVT prophylaxis in high risk patients

Complications

• Wound infection


• Chest infection


• Bleeding


• Bile leak


• Anastomotic leak in patients with resection of adjacent organs


• Liver failure following major hepatectomy

Prevention



Risk factors for GBC

• Female gender


• Increasing age


• Dietary factors (higher consumption of mustard oil contaminated with argemone oil, high cholesterol intake, intake of red meat, drinking water contaminated with pesticides)


• Exposure to potential carcinogens (methylcholanthrene, aflatoxin B)


• Cholelithiasis and chronic cholecystitis


• Gallbladder polyps


• Choledochal cysts


• Anomalous pancreaticobiliary duct junction


• Genetic factors (p53 and K-ras mutations)

Guidelines by The Ministry of Health and Family Welfare :

Anil K Aggarwal
Department of Surgical Gastroenterology and Liver Transplantation
GB Pant Hospital
New Delhi