Gallbladder tumor is the fifth most common gastrointestinal cancer. It is 2-3 times more common in women than in men (due to the higher prevalence of gallstones in women) and affects more than 75% of patients older than 65 years. With the exception of incidentally recognized early-stage cases in gallbladders removed for stone disease, the prognosis is generally poor. At the time of diagnosis, many of these patients are not amenable to radical oncological surgical treatment, so most patients receive non-surgical treatment. An aggressive surgical approach in early-stage cases has shown encouraging results with acceptable morbidity.
Etiology
Gallstones (i.e., the presence of stones in the gallbladder) are the main risk factor studied due to their high prevalence in the population. Cholelithiasis and/or chronic cholecystitis are present in 75–90% of cases of gallbladder cancer and pose a risk about seven times greater than in the general healthy population. Among patients who undergo cholecystectomy for lithiasis, about 1% turn out to be carriers of occult gallbladder cancer.
Other predisposing factors include abnormalities of the pancreatobiliary junction (i.e., the anatomical region connecting the pancreatic duct to the duodenum, where the pancreas discharges its juices), the porcelain gallbladder, and other benign biliary diseases, such as choledochal cysts and primary sclerosing cholangitis.
Clinic
In most cases, gallbladder cancer presents with the initial symptoms of acute cholecystitis (with the onset of short-term right upper quadrant pain associated with vomiting, fever with chills, and abdominal guarding) or chronic (with more nuanced symptoms). Often, the clinical picture is characterized by a recent change in the quality and frequency of pain episodes. Another common presentation mimics acute cholangitis.
Less common presenting symptoms are weight loss, jaundice, and palpation of a mass. belly.. Gastrointestinal bleeding or obstruction occur less frequently. Due to nonspecific initial symptoms, gallbladder cancer is often unrecognized and confused with chronic cholecystitis, pancreatic cancer, acute cholecystitis, choledocholithiasis, and gallbladder hydrops.
Diagnosis
As with patients with simple cholelithiasis, ultrasound is usually the first diagnostic test, with a sensitivity of 70–100%. It is usually followed by a CT scan and/or an MRI in order to precisely define the entity and extent of the disease, which often replaces the gallbladder, causes biliary obstructions, or affects adjacent vessels or organs.
Cholangiography may be helpful for patients with jaundice. A definitive diagnosis, in cases where the mass cannot be clearly characterized by radiological investigations, requires a biopsy.
Treatment
The most appropriate therapeutic method is determined based on the stage of the disease. Patients with tumors confined to the gallbladder wall are often occult carriers of gallbladder cancer who receive cholecystectomy for gallstone disease and in whom the finding of malignancy is a postoperative acquisition. These lucky cases only require cholecystectomy and have a survival rate close to 100% 5 years after surgery. Involvement beyond the gallbladder wall by the tumor is associated with a progressive increase in risk due to the increasing possibility of locoregional lymphatic metastases (i.e., extension of disease to lymph nodes proximal to the gallbladder and, through them, to other distant organs). These conditions require an "extended cholecystectomy" that includes, in addition to the tumor, also a margin of the liver parenchyma, with lymphadenectomy, that is, adequate removal of the surrounding lymph nodes. In the case of large tumors, a regulated hepatectomy may be necessary because it is oncologically radical.
If diagnostic studies show that radical surgery is not feasible (i.e., capable of completely removing all tumor tissue safely), nonsurgical palliation is considered. Many of these patients have obstructive jaundice that may improve with the placement of a stent or biliary drainage, both percutaneously and endoscopically. In addition, pain is a relevant clinical problem that requires aggressive drug treatment to improve quality of life.
The results of chemotherapy in the treatment of patients with gallbladder cancer are poor, even when new drugs are being studied.
The use of radiotherapy, both intraoperative and external, has not been shown to be valid in terms of survival benefit.
Follow-up
At diagnosis, 25% of patients have a location within the gallbladder wall, 35% have regional lymph node metastases or spread to adjacent organs, and 40% have distant metastases.
The stage of the disease is the main factor affecting survival. Patients with cancer limited to the mucosa and submucosa generally have an excellent prognosis. Tumor invasion of the muscular layer of the gallbladder increases the risk of neoplastic recurrence after radical resective surgery; survival 5 years after surgery in these patients is 72%. Invasion of the outer wall of the gallbladder by the tumor increases the risk that it has spread to the lymph nodes.
There are frequent cases in which, at the time of diagnosis, the neoplastic diffusion is such that it precludes the possibility of a radical resection.