If you get gallstones, you have to cut the gallbladder? The medical community has quarreled over this

Current research suggests that the removal of the gallbladder containing the stones will lead to a considerable reduction in the rate of gallbladder cancer. Photo/Visual China

The "one-size-fits-all" battle for the gallbladder

Reporter/Yuan Suwen Intern/Yu Haoqing

In order to prevent gallbladder cancer, the king of cancer, can the gallbladder be abandoned directly? In the domestic medical community, doctors who support bile cutting and bile preservation have been arguing endlessly. Recently, a group of surgeons issued an expert consensus in the name of the Chinese Medical Association, which for the first time explicitly opposed the "gallstone preservation" operation, and listed "gallbladder stones, whether symptomatic or not" as the primary indication for "cholecystectomy".

The incidence of gallbladder stones is roughly estimated at 10%, which means that in China, which has a population of 1.4 billion, more than 100 million gallbladders need to be removed. This is difficult for doctors who are gentle on guts to accept, and it also hurts the feelings of many patients. Someone left a message online calling the consensus "one size fits all."

The treatment of diseases by medicine is often embodied in the attitude towards probability. In the case of gallbladder disease, although more than 100 million people in China have gallstones, the likelihood of actual gallbladder cancer is much lower. At present, there is no circulation data covering the whole country, but with reference to existing data and foreign situations, only no more than 10 people per 100,000 people may be recruited. But "the prognosis was poor. Hidden behind the obscure term doctors is a brutal odds — only 5 percent of gallbladder cancer patients live another five years.

How to reduce the number of patients who are "hit" by gallbladder cancer? Authoritative experts are ready to "sacrifice" all the galls that have grown stones. Existing studies have shown that gallstones are a high risk factor for gallbladder cancer, and if the gallbladder containing the stone is removed, the incidence of gallbladder cancer will be significantly reduced. In China, doctors are divided into two factions, one advocating bile cutting, and the other insisting on exploring "bile protection and stone".

The battle between the pros and cons of secondary surgery

On Yang Xue's belly, there was an exclamation point, a small cross, a lonely point, and a point hidden in the eyes of the navel. These are the five scars left by her two gallbladder surgeries, one gallstone-preserving surgery and one gallbladder removal surgery after a recurrence of stones. She was impressed by both visits, the first when she appeared in the newspaper as the youngest local bile-sparing patient, and the second, when the doctor rolled his eyes during a relapse consultation.

The white eye was not aimed at Yang Xue, but her previous bile-conserving surgery. Yang Xue remembers that it was in February 2016, when she saw a doctor at the West China Hospital of Sichuan University. When she recounted that she had performed a gallstone-preserving operation, the doctor acted dismissive. "It feels like he doesn't approve of it at all." Yang Xue recalled that the doctor told her that the bile protection surgery was not so magical, and the recurrence rate was high, and the doctor used a vulgar analogy, "There is no later matter after cutting early." ”

Yang Xue's gallstones first occurred in the fall of 2000. "Doctors have given two options, cut out the gallbladder, or try to preserve the gallbladder, but the gall can recur the stone." She recalls that at that time, when she was young and there was only one stone, her family decided to protect their guts.

The stone removal required open surgery, for which she stayed in front of and behind the hospital for three weeks. After the operation, she thought she was cured, "I don't want to eat meat, I want to eat meat, I want to eat hot pot and eat hot pot, I don't feel uncomfortable." "In 2016, when she was about to turn 30, the stone recurred.

After 16 years, medical concepts and technologies have been updated. The doctor performed a gallbladderectomy for Yang Xue using laparoscopic techniques, and she only stayed in the hospital for one day, and then went home with a "cross" and two "dots" attached with a large Band-Aid. The effect of removing the gallbladder made Yang Xue's digestion efficiency of fat meat become lower. "The doctor reminded me to eat less fatty and high-cholesterol foods." Yang Xue said that in addition to this, she did not have much discomfort, but from time to time she would have flatulence.

Nowadays, the high recurrence rate of gallstone preservation surgery has become the consensus of the industry, but in related studies at home and abroad, the recurrence rate is very different. Some surveys in the 1990s showed that the recurrence rate of biliary lithotripsy could reach 50%, while in some domestic statistics in recent years, the recurrence rate was less than 10%, behind which there were differences in statistical methods and the contribution of technological progress to the reduction of recurrence rates.

Hu Hai is the director of the Cholelithiasis Specialty of Shanghai Oriental Hospital and has been studying bile preservation for more than 30 years. He told China News Weekly that despite being a surgeon, he believes it is more beneficial for patients to preserve organs than to cut them off at will. "Even if the gallbladder stones recur after the gallbladder, is it meaningless that we can extend the life of the gallbladder and make it work for you longer?"

The deputy chief physician of the Department of Hepatobiliary Surgery of a top three hospital in Qingdao basically agrees with the concept of bile cutting. However, he believes that for teenagers, if there is only one stone, the thickness of the gallbladder wall does not change and the hairiness is rough, and after a detailed evaluation, it may be possible to try to preserve the gallbladder.

But Zhang Yongjie, chief physician of the Oriental Hepatobiliary Surgery Hospital of the Naval Military Medical University, has a more distinct attitude towards this: the younger the person, the less he can protect his guts. In this regard, he explained to China News Weekly, "If a person grows gallstones after the age of 60, it may be related to many factors, but if a person grows gallstones before the age of 20, I have to ask why?" He believes that the younger the gallbladder problem, the more it proves that patients are susceptible to gallbladder disease, and because the pathogenesis of cancer is related to genes, susceptible people should be extra careful.

Zhang Yongjie also admitted that although gallbladder resection is not a perfect method for the rational treatment of benign gallbladder diseases, "cholecystectomy is an effective and deterministic method to reduce the incidence of gallbladder cancer after more than 100 years of testing." This is a fact and is supported by evidence-based medicine."

"Chinese characteristics" of gallstone surgery

Although pioneered by foreign scholars, stone preservation has now become a "Chinese-style" operation. Zhang Yongjie remembers that before the outbreak of the epidemic, foreign gallbladder surgery experts often came to China to communicate, and whenever these foreigners heard that China was still carrying out gallstone protection surgery, they were always full of doubts and asked a few "why?" ”

Zhang Yongjie introduced that around 1985, a british urologist used percutaneous nephrochotoscopy to remove kidney stones, and the wound was only as large as the key hole, which set off a boom in minimally invasive surgery. In 1988, doctors used the same method to remove gallstones and developed percutaneous nephrolithotomy to protect stones, but in the early 1990s, follow-up studies found that the recurrence rate of stones after gallstones was more than 40%, and with the emergence of laparoscopic cholecystectomy (LC), gallstones were abandoned internationally.

In 1991, the Chinese Journal of Surgery also published the first report of laparoscopic cholecystectomy in China. But Chinese doctors are still exploring the possibility of preserving the gallbladder. In 1987, drawing on the experience of extracorporeal shock wave lithotripsy in urology, Shanghai Zhongshan Hospital introduced a lithotripsy machine from France and took the lead in trying to use extracorporeal shock waves (ESWL) to treat gallbladder stones in China.

Also in this year, Hu Hai entered Ruijin Hospital to pursue graduate studies, where he was taught by Professor Fu Peibin, the founder of the department of surgery, and his disciple Zhang Shengdao. Hu Hai recalled that as a surgical hero, Fu Peibin also agreed that tissues and organs could not be cut off casually, so Hu Hai joined the research team of using shock wave lithotripsy and other means to dissolve stones in the gallbladder. Shockwave gravel was once all the rage. In January 1991, the Biliary Surgery Group of the Surgical Society of the Chinese Medical Association held the first national biliary extracorporeal shock wave lithotripsy seminar, and received 64 papers on shock wave lithotripsy, with a total of 6357 cases of lithotripsy treatment. But later, due to complications and other reasons, this therapy is less used in clinical practice.

However, the use of endoscopy to "protect the gall and take stones" has continued. After searching the CNKI, the reporter found that the relevant papers have been published since 1991. The earliest article was published in the Journal of Practical Surgery on May 1, 1991, which wrote, "Since 1990, Nanjing First Hospital has applied the West German Storz percutaneous gallbladder mirror to take the stone after the shock wave of lithotripsy, and the effect is satisfactory", "It is a valuable means of diagnosis and treatment". The earliest fiber path mirror minimally invasive biliary stone extraction study on CNKI was published in 1996 and carried out by the Department of General Surgery of Nanyang City Hospital of Traditional Chinese Medicine in Henan Province.

In the 21st century, relevant practices and research have further increased. In 2009, the Endoscopic Minimally Invasive Bile Preservation Professional Committee of the Endoscopic Physician Branch of the Chinese Medical Doctor Association was established, and since then, the "Expert Consensus on endoscopic Minimally Invasive Biliary Surgery for the Treatment of Benign Diseases of the Gallbladder" has been updated in real time every two years. The industry related to the bile protection stone is also developing, and the reporter used "bile protection" as a keyword search and found that there are 158 patents related to bile protection devices that have been registered.

Biliary stone removal surgery was once all the rage, but this operation is mainly carried out in primary hospitals. In 2010, scholars analyzed 53 Chinese articles published as of 2009, of which 12 were from 7 provincial and ministerial hospitals, reporting 1620 patients; 33 from 14 prefectural and municipal hospitals, including 1968 patients; and 8 from county and district hospitals, involving 866 patients. Nearly two-thirds of cases were reported in prefectural and county hospitals.

Increased surgery also failed to address high recurrence rates and gallbladder hazards. In 2010, Zhang Yongjie published "Some Questions on the Advocacy of Defending courage and taking stones at this stage", which wrote that when putting forward academic views, there must be objective basis as a support, otherwise it will be unscientific and make common sense mistakes. In this article, he argues that sparing stones focus on the starting point for the protection of the structure and function of the gallbladder, in line with the basic principles of medical activities. But the procedure was still "devoid of evidence-based medical evidence."

In 2011, the Biliary Surgery Group of the Surgery Branch of the Chinese Medical Association issued the "Expert Consensus on the Treatment decision of benign diseases of the gallbladder (2011 Edition)", which suggested that cholecystectomy is the standard treatment method for benign diseases of the gallbladder and should be used as the first choice, "and the practical value of gallbladder lithotripsy needs to be further studied".

The current situation of biliary stone extraction surgery concentrated in China's primary hospitals has not changed. Zhang Yongjie searched the literature of CNKI from 2010 to 2021 with the keyword of "protecting the gall and taking stones" in the title of the paper, and the number of articles reached 1430, and the publishing units were still mainly grass-roots hospitals. In contrast, he searched for "gallbladder incision stone extraction" and "bile preservation" in the title of the paper in the foreign database Pubmed, and there were only 31 articles from 2010 to 2021, of which 23 were from China.

In 2021, Zhang Yongjie published "Re-cognition of the history and current situation of biliary stone extraction", pointing out that "unfortunately, the normativity of the vast majority of domestic research on gallstone preservation is not yet accurate, and there is a lack of long-term follow-up data to explore the risk of secondary cancer." ”

Cholecystectomy is written into the consensus of authoritative experts. On September 26, 2021, the Chinese Journal of Surgery released the "Expert Consensus on the Surgical Treatment of Benign Diseases of the Gallbladder (2021 Edition)", which for the first time listed "gallbladder stones, whether symptomatic or not" as the surgical indication for "cholecystectomy", and ranked first.

For the doctor community, the effectiveness of the "expert consensus" is not as good as the "clinical diagnosis and treatment guidelines", but it is also an authoritative view. This article is signed "Chinese Medical Association Surgery Branch Biliary Surgery Group" and "Chinese Medical Doctor Association Surgeon Branch Biliary Surgery Committee", in its editorial review committee, there are 27 surgeons signed, the leader Quan Zhiwei is a national member of the Chinese Medical Association Surgical Branch, and many other members are surgical experts who have been operating for decades.

Among them, it is also proposed for the first time that "the implementation of gallstone preservation surgery for benign diseases of the gallbladder" is also proposed, and the use of treatment methods such as drug lithification, stone removal and extracorporeal shock wave lithotripsy is not recommended; cholecystectomy is the only cure for benign diseases of the gallbladder.

The "one-size-fits-all" rhetoric sparked a backlash from doctors who were still performing bile-conserving surgery. Half a year after the debate, on March 3, 2022, the Chinese Journal of Surgery published the Interpretation, proposing that biliary preservation surgery can neither change the cause of gallbladder stones, nor can it avoid the risk of gallbladder cancer, and the gallbladder is a risk factor for gallbladder cancer after bile preservation surgery.

It is possible to prevent cancer

If you want to choose the king of cancer, gallbladder cancer is the top "seed player". Located on the right in the middle of the human body, this sac hidden in the lower edge of the liver, 8 cm long and 3 cm wide, plays the role of a warehouse - the bile secreted by the liver flows into it through the common bile duct, stores and concentrates inside, and then "out of the reservoir" as needed, flows into the small intestine to digest fat. The gallbladder is a low-key "warehouse" next to other organs, so that once cancer cells grow in between, they can circulate rapidly and quickly invade everywhere. When people perceive it, it is often in the middle and late stages.

Yongjie Zhang is a member of the Consensus Editorial Committee. He recalled that during the consensus writing process, when it came to the recommendation that asymptomatic gallbladder stones should also be included in the gallbladder removal indications, some controversy arose within the editorial board. "Finally put this sentence in it, the only reason is that there are too many chaos in the treatment of gallbladder stones in China, and the removal of gallstones may delay the timely prevention of gallbladder cancer in many patients."

As a gallbladder surgeon who has been operating for more than 30 years, Zhang Yongjie encounters new cases of gallbladder cancer every week, "and more than one", the youngest of whom is only 18 years old.

In textbooks, the incidence of gallbladder cancer is 2/100,000, but this is not the actual incidence in China. Studies have shown that the incidence of gallbladder cancer (GBC) varies greatly geographically, with Chile having the highest incidence globally, reaching 9.7/100,000 in 2014, compared with relative rarity in Europe. This phenomenon may differ from the prevention of risk factors and, at the genetic level, the expression level of C-reactive protein (CRP) as an indicator of chronic inflammation.

According to statistics from 339 tumor registries across the country in 2014, the prevalence of gallbladder cancer in China was estimated to be 2.37 per 100,000 and the mortality rate was 1.71 per 100,000. However, Zhang Yongjie believes that there is still a lack of comprehensive and effective investigation of domestic medical institutions at all levels, so the actual occurrence of gallbladder cancer is unknown, and the actual survival status of gallbladder cancer treatment and non-treatment is also lacking reliable research.

At present, some retrospective studies of patients with gallbladder cancer are being carried out in China, but no full report has been released. According to Zhang Yongjie, a retrospective study involving more than 3,000 Chinese gallbladder cancer patients showed that more than 50% of the patients who were first diagnosed were in the fourth stage, and if the third stage patients were included, the proportion reached about 80%. This fully illustrates the secretive and rapid development of gallbladder cancer in the early stages, and by the time it is discovered, most people have reached the middle and advanced stages.

Of the 3,000 patients in the study, more than 1,500 were surgically treated, and only 40 percent of them achieved radical resection, i.e., removal of all tumor cysts. But resection does not mean radical cure. After resection, patients often have to undergo comprehensive treatment, chemotherapy, radiotherapy, and even immunotherapy and targeted therapy, stepping into a long anti-cancer road.

Zhang Yongjie told reporters that a search of the National Cancer Institute's "surveillance, epidemiology and results" database could not find five-year survival rate data for gallbladder cancer. According to his understanding, there are relatively few patients with malignant tumors of the biliary system in the United States because the treatment of gallbladder stones in the United States has a "four-matter" principle, that is, regardless of age, sex, race and whether there are symptoms, it is recommended to remove them. Therefore, the incidence of gallbladder cancer in the United States is about 2/100,000. Prophylactic resection has a significant effect on reducing the incidence of gallbladder cancer. The latest evidence is in Chile, which was once the country with the highest incidence of gallbladder cancer, and Chile included a gallbladder stone treatment program in the cancer prevention system, and the incidence of cancer was reduced by 30% after the removal of the stone gallbladder.

Severe removal recommendations stem from the dangers of gallbladder cancer. "In the field of cancer, we all like to call the king of cancer, some people say that liver cancer is called the king of cancer, and some people say that pancreatic cancer is the king of cancer, but I often tell students in class, no matter what other cancers are, gallbladder cancer must be the king of kings." Zhang Yongjie said.

He explained that like cholangiocarcinoma and liver cancer, a 5-year survival rate after radical resection can exceed 50%. Even for the more dangerous pancreatic cancer, as research progresses, survival after treatment improves dramatically. For gallbladder cancer, the current domestic research is backward, and the international community due to the concept of preventive resection, the incidence is not high, and there is no investment in a lot of research resources, "The current treatment of gallbladder cancer is still imitating pancreatic cancer." ”

Among the high-risk factors for gallbladder cancer, the first to bear the brunt of it is stones. Zhang Yongjie said that he found clinically that gallbladder cancer accounted for about 90% of gallbladder stones. The correlation between gallstones, cholecystitis and gallbladder cancer was 90%, exceeding the correlation of hepatitis, cirrhosis and liver cancer, which was about 80%.

The gallbladder is located deep in the internal organs and may invade the bile ducts, liver, hepatic duodenal ligament, stomach, and even down to the colon and inferior vena cava after cancer. "How big can a so-called radical resection of gallbladder cancer be?" Zhang Yongjie said that he had had an operation, in addition to removing the gallbladder, he also added part of the liver, half of the stomach, half of the pancreas, duodenum, the entire extrahepatic bile duct, plus the right half of the colon.

And such a serious result can be prevented in advance. "A small gallbladder removal could have solved it, so why wait until then?" He and his colleagues have almost all encountered patients who do not listen to advice, and when the symptoms first appeared, they did not follow the advice of gallbladder removal, and when they went to the clinic, they were already advanced gallbladder cancer, "already jaundice, has metastasized, it is a pity."

Behind the differences among the doctors

Zhang Yongjie believes that not only patients, but also medical workers should be more vigilant about gallbladder cancer. In his consultation, many gallbladder cancer patients will tell the history of gallbladder stones, and whenever this happens, he will ask "Why didn't you remove the gallbladder earlier?" Patients usually have two kinds of answers, one is "there has been no discomfort", but when it is "uncomfortable", the gallbladder cancer is detected. That's why he recommends cholecystectomy for patients with asymptomatic gallstones — the "symptoms" have a subjective factor and vary in tolerance from patient to patient. Another answer is, "I have consulted an internal medicine or traditional Chinese medicine or ultrasound doctor, and the other party said that gallstones are very common, and no symptoms can be ignored." ”

"A lot of doctors haven't seen gallbladder cancer and don't know the risk of cancer." Zhang Yongjie said that he has repeatedly called for multidisciplinary discussion of gallbladder cancer at national academic conferences, "As long as you have seen what gallbladder cancer looks like once, how dangerous its aggression is, how bad it is after healing, and how painful the patient is, I believe they will no longer despise their opponents." ”

Zhang Yongjie's vigilance could not convince Hu Hai. Hu Hai feels that experts sometimes have excessive vigilance, "thinking that seeing gallbladder stones will be gallbladder cancer", he insists that the incidence of gallbladder cancer is only a minority in the population, for a small probability, most of the "good" gallbladder is removed, "lack of dialectical materialist views".

Hu Hai believes that gallbladder cancer can be prevented. "The probability of gallstone patients getting gallbladder cancer is less than one in a thousand." He said that after the gallstone is taken, dynamic observation and follow-up can avoid risks. In fact, Hu Hai's views are contrary to some studies. Foreign scientists have found that due to the mysterious occurrence of gallbladder cancer, follow-up is difficult to effectively reduce the occurrence of cancer.

Zhang Yongjie pointed out that for the diagnosis of early gallbladder cancer, there is still a lack of reliable and sensitive means, and now it can only be vigilant. In addition, those with a family history of cluster tumor disease, the gallbladder has a long time of disease, or the pain characteristics of the gallbladder have changed, which is also a high-risk group. When a red flag is found, further examination should be actively carried out, in addition to ultrasound, you can also screen for hidden dangers by CT, MRI, blood draw to check tumor markers, etc.

However, even with the above means, cunning gallbladder cancer may still escape. Zhang Yongjie proposed that more accurate ways to screen for gallbladder cancer are still being explored, such as his team is studying the use of puncture to obtain bile and analyze tumor markers in bile. However, this innovative type of examination is difficult to implement on a large scale and is still in the research stage.

Chinese pay attention to the integrity of the body, which is one of the factors that the gallstone has a market in China. But Zhang Yongjie reminded that the gallbladder that is retained by surgical removal of stones is already a deteriorated gallbladder. According to existing research, gallbladder lithotripsy is linked to the environment, body, genetics, metabolism, inflammation, functional structure, and immunity. Removing the stone does not change the hotbed of the lesion.

Biliary preservation surgery is facing a situation of total denial. This is difficult for Hu Hai to accept, he believes that no matter what era, the protection of organs is a valuable direction of effort. Nowadays, in Hu Hai's department, bile protection also tends to be rational, "Two-thirds of the patients who come to us want to cut off the bile, and only about one-third will try to protect the bile." Our patients followed up, the overall recurrence rate is 5.6%, if the patient is more carefully selected, the recurrence rate will be lower, right? ”

Hu Hai believes that rational bile preservation should have two conditions, first of all, to protect useful bile, the use of "poached egg experiment", to detect the response of the gallbladder after ingestion of high cholesterol, the contraction function of the gallbladder needs to reach more than 50%; secondly, after preserving the gallbladder, it is necessary to continue to use drugs to improve the bile composition and prevent the recurrence of stones.

Without scientific research as a basis, any argument would be like building a castle on a pile of sand. Zhang Yongjie admits that for gallbladder cancer, there is still a lack of the most basic scientific research, which is also the root cause of the endless debate. "When I was young, as a surgeon, I only operated on surgery and rarely studied the causes of disease." Now in his sixties, he is leading a team of researchers into genes or markers that may be linked to gallbladder cancer, "which can help screen who is more susceptible, and it's a small contribution."

In the interview, he mentioned american actress Angelina Jolie several times, who had both breasts removed while still in good health because of her breast cancer susceptibility gene. "It's a very extreme case, but it's probably the easiest and most effective way to solve her individual problems."

Zhang Yongjie acknowledged the "arbitrariness" of the expert consensus wording. He also stressed that this is just an expert consensus, not a treatment guideline, "the guidelines need very strict high-level evidence, but we don't have these studies now." He said that the use of "expert consensus" to disseminate the views that everyone agrees on is not contrary to scientific principles, because this is the personal experience and experience of experts, and it is also one of the evidence, but the level of evidence is slightly lower." ”