gallbladder-evidence

The editorial announcing the 2017 staging changes for pancreas, liver and biliary cancers, including the split of muscle-invading gallbladder cancer into a free-side and a liver-side category.

Gallbladder cancer has been called scantily understood in 2004 and understudied in 2025 by its own researchers. Counting the money spent on it against the deaths it causes, country by country, would make the gap visible and give funders a target.

After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.

About six in every thousand gallbladders removed for stones contain cancer. A written pathway that sends every specimen to the pathologist, refers every T1b or deeper cancer to a liver surgeon within two weeks and books the second operation within eight would turn a lottery into a system.

The plan for an Indian trial comparing chemotherapy with chemotherapy plus radiotherapy before surgery for gallbladder cancer that has grown beyond the gallbladder wall.

Radiotherapy after gallbladder cancer surgery rests on one 79-patient trial with no comparison arm and a US insurance database. People whose surgery left cancer at the edge or in the nodes are the ones it might help, and they have never been randomised.

Muscle-invading gallbladder tumours on the free side of the organ recur in the liver far less often than those against it. Two meta-analyses found the liver resection helped only the liver-side group, so a randomised trial could test dropping it for the free side.

Across ten US centres, people whose second operation for a chance-found gallbladder cancer happened four to eight weeks after the first lived longest; rushing back in under four weeks, or waiting beyond eight, went with shorter survival.

The European oncology society's 2023 guideline for bile duct and gallbladder cancer, covering how the diseases are diagnosed, staged, operated on, treated with drugs and followed up.

The 2025 summary of the US NCCN guideline for gallbladder and bile duct cancers, focused on what to give after surgery.

The UK gastroenterology society's 2023 guideline for bile duct cancer, written with patient charities; there is no equivalent UK guideline written for gallbladder cancer.

The 1976 paper that first staged gallbladder cancer by how deeply it had grown through the wall, noting that almost every case had been found by chance during gallstone surgery.

In the first years of Chile's preventive gallbladder surgery guarantee, deaths from gallbladder cancer among 35 to 49 year olds fell twice as fast as before, but the national trend did not visibly change.

Gallbladder cancers found by chance often come back within six months of the second operation, usually far from the gallbladder, which suggests the disease was already in the bloodstream. Two randomised trials are testing chemotherapy first; one closed small, the other reports in 2028.

People who carry the typhoid bacterium in their gallbladder long term have about four times the usual risk of gallbladder cancer. Two meta-analyses suggest offering them gallbladder removal or regular scans; no programme has tried it.

Japan's surgical society guideline for bile duct, gallbladder and ampullary cancer, the only major guideline with a section on preventive treatment.

In 56 people after surgery for bile duct or gallbladder cancer, finding tumour DNA in the blood in the weeks after the operation meant the cancer came back within about seven months on average, while those without it had not relapsed by the end of follow-up.

Three and a half years on, adding durvalumab to chemotherapy for advanced bile duct and gallbladder cancer still showed a survival edge, and about one in seven patients were alive at three years compared with one in fourteen on chemotherapy alone.

India carries about a tenth of the world's gallbladder cancer, concentrated in the north and east, striking younger people than in the West, with gallstones present in four out of five patients and a list of environmental co-factors under suspicion.

The 2022 Nature Reviews primer on gallbladder cancer: the commonest biliary cancer, mostly found by chance at gallstone surgery, driven by long-standing inflammation, curable only by surgery and badly in need of screening biomarkers and separate study.

An epidemiological analysis, with US National Cancer Institute authors, of whether Chile's preventive gallbladder surgery programme has cut deaths from gallbladder cancer.

Chile has guaranteed gallbladder removal for people aged 35 to 49 with gallstones since 2006 to prevent gallbladder cancer; this review of official data finds deaths falling but already falling before the programme, and uptake not matching the regions where the cancer is commonest.

A 2004 review arguing that gallbladder cancer, rare and little studied, is worth understanding because its mix of inherited risk, geography, female predominance, chronic inflammation and congenital anomalies is unusual among cancers.

Sequencing 262 gallbladder tumours from Chile, China, India, Japan and South Korea showed that the mutations differ by country and ancestry, with Chinese tumours carrying the most mutations and Chilean the fewest.

In 140 resected bile duct and gallbladder cancers tested the way the zanidatamab trial did, about one in eleven was HER2-positive, and the HER2 signal was often patchy, present in under half the tumour cells.

Pooling 40 studies, about one in five bile duct and gallbladder cancers outside the liver over-express HER2, against fewer than one in twenty inside the liver, which is why HER2 drugs matter most for gallbladder cancer.

Of nearly 2,000 people with gallbladder cancer seen at Mumbai's Tata Memorial in four years, six in ten already had spread when they arrived and only one in six could be offered treatment aimed at cure.

When surgeons went back in after a gallbladder cancer had been found by chance, nearly half of patients had cancer left behind, and the deeper the original tumour the more likely it was.

Pooling 51 studies and more than 400,000 gallbladder operations, about six in every thousand gallbladders removed for benign disease contained an unsuspected cancer, and people whose cancer was found this way lived longer than those diagnosed with symptoms.

In a Korean trial, adding liposomal irinotecan to fluorouracil held second-line bile duct and gallbladder cancer still for about seven months rather than six weeks, at the cost of more low blood counts.

The 2022 European rules for gallbladder polyps found on ultrasound: operate at 10 mm or more, operate at 6 to 9 mm if there are risk factors, scan again for two years otherwise, and stop watching tiny polyps in people without risk factors.

The first UK-wide picture of gallbladder cancers found by chance: across 24 centres over nine years, two thirds went on to liver surgery and those who did stayed free of disease far longer.

The design of the German GAIN trial: chemotherapy before and after the second operation for gallbladder cancer found by chance, against surgery first.

A review of whether chemotherapy should come before the second operation for gallbladder cancer found by chance: recurrences after that operation are early and distant, so treating the whole body first makes sense, and the limited evidence favours three to four cycles of gemcitabine-based chemotherapy in higher-risk cases.

Using US Medicare records from 1,137 older patients, a calculator was built to estimate who might gain from radiotherapy with chemotherapy after gallbladder cancer surgery; it points to those whose tumour had reached the muscle layer or the nodes.

Across 14 specialist centres in Korea, Japan, Chile and the United States, people with a gallbladder cancer that had just reached the muscle layer did equally well whether or not they had a second, bigger operation: about 95 in 100 were alive and free of the disease at five years either way.

Following more than 600,000 people for two decades, those with gallbladder polyps on ultrasound were no more likely to get gallbladder cancer than those without, though the risk did climb for polyps of a centimetre or more; the authors question whether watching polyps finds cancer at all.

In the Dutch national pathology archive fewer than one in a hundred removed gallbladders contained a polyp, more than four in ten of those polyps were harmless, and the one-centimetre rule for operating sorted them only moderately well.

Gallbladder tumours from the United States and Chile carried the same set of mutated genes but very different immune cell make-up, which may bear on why immunotherapy helps only modestly and on how trials should be designed across regions.

Pooling seven studies, muscle-invading gallbladder cancers on the liver side were about twice as likely to be fatal as those on the free side, yet the bigger operation did not clearly improve survival in either group.

In the Dutch national registry only one in four people with a chance-found gallbladder cancer had the recommended second operation; those who did lived about four times longer, and a third of them had cancer left behind that the operation removed.

In 167 people whose bile duct or gallbladder cancer had been removed, a blood test for tumour DNA in the weeks after surgery picked out those whose cancer would return far better than the standard blood markers.

Chile has paid for preventive gallbladder removal in 35 to 49 year olds with stones since 2006 without a design that can show whether it prevents cancer deaths. Targeting the operation by region, ancestry and risk score, with an evaluation built in, would answer the question the world's only such programme has left open for twenty years.

Between one in eleven and one in five gallbladder cancers is HER2-positive and two HER2 drugs are now approved, but testing still happens only when someone asks. Making it automatic on every advanced biliary diagnosis, on resection tissue where it exists, would find the patients the trials were built for.

Every drug gallbladder cancer patients receive was tested in mixed bile duct trials where they were a subgroup. Requiring trials to pre-specify and publish gallbladder results, with a minimum number enrolled, would give the disease its own evidence at almost no cost.

In parts of Chile and northern India gallbladder cancer is common enough that a cheap ultrasound programme aimed at the highest-risk people might catch it while surgery can still cure it. Nobody has run the trial.

Pooling more than a thousand cases, people with signs of past or chronic typhoid infection were four to five times more likely to have gallbladder cancer, though the bacterium itself was not recovered from the Chilean patients studied.

The UK trial that showed a second chemotherapy, FOLFOX, helps people with advanced bile duct or gallbladder cancer live about a month longer on average once gemcitabine and cisplatin stop working, with one in four alive at a year instead of one in nine.

Among 516 people operated on for gallbladder cancer at 24 UK centres, how far the tumour had grown and whether nodes were involved decided survival, and chemotherapy after surgery showed no measurable benefit once like was compared with like.

A Korean series suggesting that muscle-invading gallbladder tumours on the free side may not always need part of the liver removed, while those against the liver bed do.

In the only prospective trial of chemotherapy then radiotherapy after surgery for gallbladder or bile duct cancer, two in three patients were alive at two years, including those whose cancer had reached the cut edge, but there was no comparison group.

A British Journal of Surgery review of what to do when a gallbladder removed for stones turns out to hold cancer: about one in 200 do, tumours confined to the lining are cured by the first operation, deeper ones need a second, and cutting out the keyhole port sites does not help.

Across 17 studies, mostly from India and China, people who carried the typhoid bacterium long term were about four times as likely to have gallbladder cancer, and the authors suggest offering them gallbladder removal or ultrasound checks.

Guidelines send everyone whose chance-found gallbladder cancer has just reached the muscle layer back for liver and lymph node surgery, yet the largest international series found 95 in 100 alive without the disease at five years whether or not they had it. A prospective study could spare thousands of operations, or confirm they are needed.

A Liverpool review of twelve studies found that about one in 175 gallbladder polyps seen on ultrasound turned out to be cancer, and argued for risk-based surveillance decided in a multidisciplinary team.

Pooling individual records from more than 2,000 patients, the timing of the second operation for chance-found gallbladder cancer made no measurable difference to survival, and studies did not even agree on what early or late meant.

A second pooled analysis of muscle-invading gallbladder cancer found tumours on the liver side about three times as deadly, found removing part of the liver helped only that group, and found chemotherapy after surgery did not change the risk of death.

Where a muscle-invading gallbladder tumour sits matters: those on the side against the liver spread more and killed more, with five-year survival of 43 in 100 against 65 in 100 for tumours on the free side.

Tested on 7,743 US patients, the 2017 gallbladder cancer staging system predicted survival no better than the 2010 one it replaced.