Understanding Gallbladder Cancer- Problem Unique to India!
Gallbladder cancer (GBC), a notorious and aggressive cancer has the highest prevalence in Northern India, especially along the Gangetic belt and in the states of Utter Pradesh and Bihar. While a lot of factors contribute to the onset of cancer, its exact cause is unknown. Multiple studies have analyzed the reason for its high incidence in Northern India. Moreover, the poor survival associated with GBC emphasizes the urgency of knowing the causes. Late diagnosis remains to be an important cause for the dismal overall survival among these patients. The immediate solution to reducing the rate of late diagnosis is to create and spread awareness regarding cancer in general and especially regarding cancers that are common in our country and specific to our region. It is important for the general population and general physicians, who are usually the first point of contact, to understand this dreaded cancer. Awareness can go a long way in prevention when patients with otherwise neglected symptoms seek consultation at the right time. Timely referral by physicians to consult an expert contributes to the early detection of cancer. The first step towards creating awareness is educating the people about the possible symptoms.
What are the symptoms of gallbladder cancer or how does it present?
Gallbladder cancer can be asymptomatic for a variable period before the symptoms begin. The presentation of gallbladder cancer can also be varied and simulate other conditions. Thus, it is important to understand and be aware of the symptoms.
- Abdominal pain: usually experienced in the right upper or upper central part of the abdomen. The intensity and frequency of this pain can vary. Pain which changes its character and becomes continuous is typical of gallbladder cancer.
- Non-specific: dyspepsia, nausea, decreased appetite, unintentional weight loss (any of these or in combination).
- Asymptomatic: patient can present with an incidentally detected mass/abnormality of the gallbladder on imaging (ultrasound/CT scan) done for another reason or as a part of a health check-up.
- Jaundice, extreme weight loss, loss of muscle mass, confinement to bed, ascites (fluid in the tummy) is usually indicative of advanced gallbladder cancer.
- Incidental gallbladder cancer: one very important presentation is the diagnosis of gallbladder cancer on the biopsy report of the gallbladder removed for other reasons like gallbladder stones. It is important for the surgeons performing gallbladder removal to always check the biopsy report of the removed gallbladder. This can lead to timely detection of incidental gallbladder cancer, seen in ~ 1% of the removed gallbladders.
What are the risk factors for gallbladder cancer?
- Age and sex: the incidence of gallbladder cancer increase with age, peaking at around the 6th to 7th decade of life. Females are more prone to this cancer than males (2-3:1)
- Endemicity: North India has the highest incidence rate for gallbladder cancer, similar to Pakistan and South American countries like Chile. This might be attributed to poor socio-economic status and sanitation, higher incidence of infections like H. Pylori, Salmonella), nutritional deficiencies, pollutants in drinking water coupled with a high incidence of gallstones in this region. This is unlike the western countries, where the incidence of GBC is low despite a high burden of gallstones.
- Gallbladder stones: Gallstones are seen to be present in ¾ of the GBC cases. The larger and symptomatic stones are likely to be associated with a higher risk.
- Abnormal pancreaticobiliary duct junction (APBDJ): the abnormal communication of the bile duct and pancreatic duct leads to an increase in the incidence of GBC due to abnormal reflux of pancreatic juices into the biliary tree.
- Gallbladder polyps: Adenomatous polyps of the gallbladder have the potential to transform into GBC and thus it is important to recognize this premalignant entity.
- Porcelain gallbladder: the calcification of the gallbladder wall results in this rare premalignant entity.
Can gallbladder cancer be prevented?
Gallbladder cancer can be prevented if the gallbladder is removed promptly, whenever indicated. Examples of some of these situations are
- Gallbladder stones: especially those with symptoms
- Gallbladder polyp: size > 1 cm, that increases in size on follow up imaging
- Any abnormal and asymmetric gallbladder wall thickening on imaging
- Porcelain gallbladder
- Patients with APBDJ
It is important to re-emphasize that all removed gallbladders should undergo a pathological evaluation to avoid missing an incidental gallbladder cancer.
How is gallbladder cancer diagnosed?
As mentioned previously, one should be aware of the varied presentations of gallbladder cancer and have a low index of suspicion to diagnose gallbladder cancer promptly. Gallbladder cancer is usually suspected on imaging, most commonly, an ultrasound, and is seen as a mass in the gallbladder or abnormal thickening of the gallbladder wall. It can also be incidentally detected on the biopsy of gallbladder removed for other reasons e.g.: gallstones.
How is gallbladder cancer staged?
Once the diagnosis of gallbladder cancer is suspected (e.g., on ultrasound) or confirmed (incidental gallbladder cancer), the next step is to stage the disease. This is usually done with the help of a good quality cross-sectional imaging like a CT scan which nowadays is frequently combined with the PET scan. This helps in establishing the extent or the clinical stage of the disease- which is a prerequisite for deciding the correct treatment.
What is the treatment for gallbladder cancer?
Treatment for gallbladder cancer mainly depends on the clinical stage, presence of comorbidities, and symptoms. All cases should be discussed in a multidisciplinary tumor board consisting of surgical, medical, and radiation oncologists, radiologists, and pathologists to design the treatment plan. Patients with early-stage GBC are primarily treated with surgery. Patients with an advanced-stage GBC (non-resectable, metastasized) or those unfit for surgery are treated with non-surgical therapies like chemotherapy and sometimes radiotherapy. The treatment for those presenting at an intermediate stage (e.g.: large mass invading liver, adjacent organs/vessels, large nodes) is undefined, although a majority of these patients are operated on after chemotherapy.
What is the nature of surgery for gallbladder cancer?
The surgery for gallbladder cancer includes the removal of the tumor and the surrounding regional lymph nodes. This ensures proper pathological staging and can potentially cure these patients. The surgical extent depends on the local extent of the disease. Complete removal of the tumor requires removal of a surrounding part of the liver (wedge/segment) with or without bile duct. However, some of these patients might require removal of adjacent organs commonly the duodenum, colon, pancreas, or sometimes a major liver resection.
Surgery for gallbladder cancer is a major surgery including a lot of complexities and should be performed by a trained and experienced surgeon. The surgical procedure aims to remove the tumor resulting in negative margins and proper clearance. This can ensure a smooth postoperative recovery as well as a good chance of long-term control or cure of the disease.
What are the options for advanced gallbladder cancer?
The patients with advanced GBC at presentation are mainly treated with palliative treatment options like chemotherapy, immunotherapy, or chemoradiotherapy. These therapies are crucial in patients with advanced GBC associated with obstructive jaundice, gastric outlet obstruction, or colonic obstruction. Palliation of these symptoms should be done using interventional radiology or endoscopic interventions and surgery should be reserved for a selected few when these non-surgical palliative procedures are not feasible.
What is the prognosis for gallbladder cancer?
Gallbladder cancer has an overall dismal prognosis. Late presentation remains to be the main contributor to poor survival. However, treatment at early stages has shown improved survival results. A multidisciplinary approach including radical surgery (R0 resection) and chemotherapy has a maximum cure rate among the majority of resectable gallbladder cancers. The five-year overall survival rate ranges from 90% for stage I to between 20-30% for stage III GBC. Patients with advanced gallbladder cancers (Stage IV) rarely experience long-term survival. This reiterates the importance of early detection and proper stage-based treatment for these cancers.