Is gallbladder disease hereditary: Are You At Risk For Gallbladder Disease?
Are You At Risk For Gallbladder Disease?
Are You At Risk for Gallbladder Disease?
Thursday, January 31st, 2019 | Written by Premier Surgical Staff
Many people don’t usually think too much of their gallbladder until they start experiencing problems. The gallbladder is the small organ located beneath the liver. Its main function is for storing and concentrating bile, the yellowish/brownish enzyme produced by the liver. Bile aids in the digestive process by breaking down fats.
Gallbladder problems (an umbrella term that includes gallstones, cholecystitis, and gallbladder cancer) can occur as a result of blockage to the tube that leads out of the gallbladder, overgrowth of cells in the gallbladder, or excessive cholesterol.
Are you at risk?
While anyone can develop gallbladder disease, there are certain factors that can increase your chances of having it. These factors include:
The tendency to develop a gallbladder disease usually runs in families. Gene mutation that affects the movement of cholesterol from the liver to the bile duct as well as defects in certain proteins may also increase your risk of developing a gallbladder disease.
Women are twice as likely as men to develop gallstones. This is especially true for pregnant women and those who are taking hormone replacement therapy. Too much estrogen can increase cholesterol in the bile and slow down the movement of the gallbladder.
Being overweight or obese increases your risk of having gallbladder disease. Excessive weight usually cause the liver to overproduce cholesterol. This can be a problem as it can overload the bile duct and eventually lead to gallstones.
A diet low in fiber, high in fat, and heme iron (iron found in meat and seafood) can significantly increase your risk of having a gallbladder disease.
Conditions like diabetes, metabolic syndrome, and Chron’s disease can put you at risk of developing a gallbladder disease. This has something to do with having high levels of fatty acids (in case of those with diabetes) and inability to absorb bile salts (in case of Chron’s disease).
Surgery is a common treatment option for gallbladder disease. Premier Surgical has years of experience in performing gallbladder surgery. With our experienced surgical staff, you are in good hands.
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Gallbladder Problems — Are You at Risk?
The gallbladder is a tiny organ located under your liver that most people don’t think too much about. That is, of course, until it develops problems, such as gallbladder disease.
More than 25 million men and women in the United States are affected by gallbladder disease, an umbrella term that includes:
Gallstones Hardened deposits of digestive fluid that can form in your gallbladder. They can range in size from as small as a grain of sand to as large as a golf ball. Gallstones can be painful and cause nausea and vomiting, but often they are asymptomatic and don’t require surgery.
Cholecystitis This inflammation of the gallbladder is often caused by gallstones blocking the tube that leads out of your gallbladder. Other causes include bile duct problems, tumors, serious illness, and certain infections. Cholecystitis can lead to life-threatening complications if left untreated.
Gallbladder cancer A form of cancer that starts in the gallbladder with a group of cells that grow out of control. About 9 out of 10 gallbladder cancers are adenocarcinomas — a cancer that starts in cells with gland-like properties that line many internal and external surfaces of the body.
Gallbladder disease can affect anyone, but some people are more vulnerable than others. You are most at risk of having gallbladder problems if you:
- Are a woman
- Are older than 60
- Have a family history of gallbladder problems
- Are overweight or obese
- Have diabetes
- Take certain medications
- Are Native American or Mexican American
Risk Factors for Gallbladder Problems Out of Your Control
Gender In all populations of the world, women are twice as likely as men to develop gallstones, according to research published in April 2012 in the journal Gut and Liver. Pregnant women and those taking hormone replacement therapy are more at risk for gallstones because of higher estrogen levels. Too much estrogen can increase cholesterol in the bile and lessen gallbladder movement, increasing the risk of gallstones. The sex difference narrows with increasing age, but is still prevalent.
Genes According to research published in 2013 in Advances in Clinical Chemistry, the tendency to develop gallstones and gallbladder disease often runs in families, indicating there may be a genetic link. Also, a mutation in a gene that controls the movement of cholesterol from the liver to the bile duct may increase a person’s risk of gallstones. Defects in certain proteins may increase the risk of gallbladder disease in some people.
Age Gallstones are 4 to 10 times more frequent in the older population, especially in people over 60. That’s because as you age your body tends to release more cholesterol into bile, which makes it more likely that stones will form in the gallbladder.
Ethnicity Studies have shown a clear association between race and risk of gallbladder problems that cannot be completely explained by environmental factors. Risk varies widely from extremely low (less than 5 percent) in Asian and African populations, to intermediate (10 to 30 percent) in European and Northern American populations, to extremely high (30 to 70 percent) in Native American populations. Native Americans and Mexican Americans are more likely to develop gallstones than other ethnic groups, probably as a result of dietary and genetic factors.
Risk Factors for Gallbladder Problems You Can Change
Although there are a number of things out of your control when it comes to your risk of developing gallbladder problems, you can reduce your risk by maintaining a healthy weight, watching your diet, and paying close attention to how your body reacts to certain medications.
People who are even moderately overweight or obese are at increased risk of gallbladder problems. When you’re overweight, the liver produces too much cholesterol, overloading the bile ducts and increasing the risk for gallstones. Women especially should watch their weight, because studies have found that a lithogenic risk of obesity is strongest in young women; this means they are more likely to develop calculi (buildup of mineral stones in an organ).
Rapid weight loss as a result of fasting or crash diets, and weight cycling — losing and then regaining weight — can increase cholesterol production in the liver, increasing a person’s risk of gallstones. In fasting associated with severely fat-restricted diets, gallbladder contraction is reduced, which can also lead to gallstone formation. But research shows that a shorter overnight fast is protective against gallstones in both men and women.
Diet plays a major role in gallbladder disease because diet influences your weight. People who are overweight and eat a high-fat, high-cholesterol, low-fiber diet are at increased risk of developing gallstones. Exposure to the Western diet (increased intake of fat, refined carbohydrates, and limited fiber content) is a high risk for developing gallstones. And too much heme iron — iron found in meat and seafood — may increase gallstone formation in men.
Coffee consumption seems to lower the risk of gallstone formation, by enhancing gallbladder motility, inhibiting gallbladder fluid absorption, and decreasing cholesterol crystallization in the bile, according to research published in the July–December 2013 issue of the Nigerian Journal of Surgery.
Certain cholesterol-lowering medications, such as Lopid (gemfibrozil) and Tricor (fenofibrate), can increase a person’s risk of gallstones. While these drugs successfully decrease blood cholesterol, they increase the amount of cholesterol in the bile, and thus the chance for gallstones to develop.
Other drugs that may increase the risk of gallstones include Sandostatin (octreotide) and a group of diuretics known as thiazides. Octreotide is used to treat certain hormonal disorders and severe diarrhea caused by cancer tumors. Prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.
If you are concerned that a medication you are taking may increase your risk of gallbladder disease, talk to your doctor. There may be another medication that will do the same thing without increasing your risk for gallbladder problems.
Other Risk Factors for Gallbladder Problems
In addition to genetic and lifestyle factors, certain medical conditions or surgical procedures can also increase your likelihood of developing gallbladder problems. These include:
Diabetes and metabolic syndrome People with diabetes generally have high levels of fatty acids, which may increase the risk of gallstones. Additionally, gallbladder function is impaired in the presence of diabetic neuropathy, and regulation of hyperglycemia with insulin seems to raise the lithogenic index (risk of developing mineral deposits in the gallbladder that can turn into gallstones). People with diabetes are at risk for developing a type of gallbladder disease called acalculous cholecystitis, meaning gallbladder disease without gallstones.
Crohn’s disease and other medical conditions People with Crohn’s disease, an inflammatory bowel disorder, are also at increased risk of gallbladder disease. There are a few reasons for this, but one of the main ones is that if bile salts are not reabsorbed in the ileum (the end of the small intestine), they pass out of the body. This loss of bile salts means that the liver has fewer bile salts to put into new bile. The new bile becomes overloaded with cholesterol, which can in turn result in gallstones.
In addition, cirrhosis of the liver and certain blood disorders, such as sickle cell anemia, also increase a person’s risk of pigment gallstones, which are gallstones made up of bilirubin instead of cholesterol. Low melatonin levels associated with diabetes could contribute to gallstones as well because melatonin inhibits cholesterol secretion from the gallbladder; melatonin is also an antioxidant that reduces oxidative stress to the gallbladder.
Surgery People who undergo bariatric surgery to lose weight are at increased risk for gallstones. Rapid weight loss in general is a risk factor. According to Bariatric Innovations of Atlanta, gallstone formation can be found in as many as 35 percent of weight loss surgery patients. Organ transplant surgery may also increase the risk of gallstones, and it is not uncommon for some doctors to recommend that their patients have their gallbladder removed before they undergo an organ transplant.
Ways to Prevent Gallbladder Problems
Many factors may increase your risk of developing gallbladder problems. While you can’t do much about your genes or ethnicity, you can watch your weight and eat healthfully: Focus on whole grains, fruits and vegetables, fish, and lean meats. Maintaining appropriate portion size and limiting processed foods and added sugars is also essential to a healthy diet. A study published in July 2016 in the journal Preventive Medicine found that vegetable protein is associated with lower gallbladder disease risk.
Additional reporting by Jamie Putman.
Gallstones: genetics versus environment – PubMed
The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones.
Summary background data:
Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined.
A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease.
In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <. 02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease.
These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.
Gene Variant Causes Two- To Three-fold Increase In Risk — ScienceDaily
Scientists at the University of Bonn, together with colleagues from Romania, have discovered a gene variant that significantly increases the risk of developing gallstones . It is estimated that one in ten Europeans has this variant in their hereditary disposition.
For those affected, the likelihood of developing a gallstone in the course of their life is two to three times higher. The relevant gene contains the instructions for building a molecular pump which transports cholesterol from the liver into the bile ducts — cholesterol being the substance from which most gallstones are formed. The genetic modification appears to cause this pump to work permanently at high speed. Gallstones are a common disorder: in Germany alone more than 170,000 gallbladder operations a year are performed.
Gallstones occur very frequently, affecting 15 to 20 per cent of all Germans, usually without noticeable symptoms. But in around a quarter of cases the stones will announce their presence at some time in the form of a painful colic. In the end they often have to be operated. “Gallstones are among the gastrointestinal problems that incur the highest treatment costs,” says Professor Dr. Frank Lammert, the Bonn-based specialist for internal medicine.
Gallstones tend to be found at high levels within certain families. In particular, studies of twins provide evidence of a genetic component that boosts risk levels. “We reckon that environmental influences, like the wrong diet, are 70 to 80 per cent responsible for the disorder,” explains Lammert who works in the university hospital’s Department I headed by Professor Dr. Tilman Sauerbruch. “The rest is caused by genes.”
Professor Lammert — working together with his colleagues Dr. Frank Gruenhage, Maja Walier and Professor Dr. Thomas Wienker as well as scientists at the University Clinic of Cluj-Napoca in Romania — has been searching for the specific genes involved. And he has succeeded, thanks to a study covering 178 women and men from 84 families. They all suffer from gallstones. In 21.4 per cent of cases the subjects were found to be carrying a particular gene variant. In healthy individuals studied as a control group, this variant also occurred, but only at a frequency of 8.6 per cent.
Cholesterol pump at full speed
“The mutation concerns what is known as the ABCG8-gene,” Dr. Gruenhage explains. “It contains the instructions for building a pump responsible for transporting the blood lipid cholesterol from the liver into the bile ducts. ” Most of the gallstones consist to a high degree of crystallised cholesterol. The medical researcher concludes that, “The genetic alteration probably makes the pump run permanently at high speed.”
The researchers now hope that their finding will have positive consequences for prevention and therapy. Professor Lammert thinks that, “It may be possible for certain patients to be helped with drug treatments in future, thus avoiding the need for an operation.” However, the genetic contribution to the common problem of gallstones has not been fully explained by this study: “We believe there are at least three or four other gene variants that increase gallstone risk,” says the medical scientist.
Reference: Hepatology No. 46, 11 July 2007, DOI 10.1002/hep.21847
Materials provided by University of Bonn. Note: Content may be edited for style and length.
Risk Factors for Gallbladder Cancer
A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.
But having a risk factor, or even many risk factors, doesn’t mean that a person will get the disease. And many people who get the disease may have few or no known risk factors.
Scientists have found some risk factors that make a person more likely to develop
gallbladder cancer. Many of these are related in some way to chronic inflammation (long-lasting irritation and swelling) in the gallbladder.
Gallstones are the most common risk factor for gallbladder cancer. Gallstones are pebble-like collections of cholesterol and other substances that form in the gallbladder and can cause chronic inflammation. Up to 4 out of 5
people with gallbladder cancer have gallstones when they’re diagnosed. But gallstones are very common, and gallbladder cancer is quite rare, especially in the US. And most people with gallstones never develop gallbladder cancer.
Porcelain gallbladder is a condition in which the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after long-term inflammation of the gallbladder (cholecystitis), which can be caused by gallstones. People with this condition have a higher risk of developing gallbladder cancer, possibly because both conditions can be related to inflammation.
In the US, gallbladder cancer occurs 3 to 4 times
more often in women than in men. Gallstones and gallbladder inflammation are important risk factors for gallbladder cancer and are also much more common in women than men.
Patients with gallbladder cancer are more often overweight or obese than people without this disease. Obesity is also a risk factor for gallstones, which might help explain this link.
Gallbladder cancer is seen mainly in older people, but younger people can develop it as well. The average age of people when they are diagnosed is 72. Most people with gallbladder cancer are 65 or older when it’s found.
Ethnicity and geography
In the US, the risk of developing gallbladder cancer is highest among Mexican and Latin Americans and Native Americans.
They are also more likely to have gallstones than members of other ethnic and racial groups. The risk is lowest among African Americans. Worldwide, gallbladder cancer is much more common in India, Pakistan, and Central European and South American countries than it is in the US.
Choledochal cysts are bile-filled sacs along the common bile duct, the tube that carries bile from the liver and gallbladder to the small intestine. (Choledochal means having to do with the common bile duct.) The cysts can grow large over time and may contain as much as 1 to 2 quarts of bile. The cells lining the sac often have areas of pre-cancerous changes, which can progress to gallbladder cancer over time.
Abnormalities of the bile ducts
The pancreas is another organ that releases fluids through a duct into the small intestine to help digestion. This duct normally meets up with the common bile duct just as it enters the small intestine. Some people have a defect where these ducts meet that lets juice from the pancreas flow backward (reflux) into the bile ducts. This backward flow also keeps bile from flowing out of the bile ducts as quickly as it should. People with these abnormalities are at higher risk of gallbladder cancer. Scientists are not sure if the increased risk is due to damage caused by the pancreatic juice or is due to the bile that can’t quickly flow through the ducts causing them to be damaged by substances in the bile itself.
A gallbladder polyp is a growth that bulges from the surface of the inner gallbladder wall. Some polyps are formed by cholesterol deposits in the gallbladder wall. Others may be small tumors (either cancer or not cancer) or may be caused by inflammation. Polyps larger than 1 centimeter (almost a half inch) are more likely to be cancer, so doctors often recommend removing the gallbladder in patients with gallbladder polyps that size or larger.
Primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). People with PSC have an increased risk of gallbladder and bile duct
cancer. The cause of the inflammation is not usually known. Many people with PSC also have ulcerative colitis, a type of inflammatory bowel disease.
People chronically infected with salmonella (the bacterium that causes typhoid) and those who are carriers of typhoid are more likely to get gallbladder cancer than those not infected.
This is probably because the infection can cause gallbladder inflammation. Typhoid is very rare in the US.
Most gallbladder cancers are not found in people with a family history of the disease. A history of gallbladder cancer in the family seems to increase a person’s chances of developing this cancer, but the risk is still low because this is a rare disease.
Other possible risk factors
Studies have found other factors that might increase the risk of gallbladder cancer, but the links are not as clear. These include:
- Exposure to chemicals used in the rubber and textile industries
- Exposure to nitrosamines
Study Identifies Common Gene Variants Associated With Gallbladder Cancer
Findings lead to clues to causes for highly fatal disease
By comparing the genetic code of gallbladder cancer patients with those of healthy volunteers at nearly 700,000 different locations in the genome, researchers say they have found several gene variants which may predispose individuals to develop the disease.
The findings, published March 6 in The Lancet Oncology, could lead to a better understanding of the causes of this highly fatal condition, which could in turn lead to better treatments for the disease. The work is a collaboration between the Johns Hopkins Bloomberg School of Public Health, the National Cancer Institute and Tata Memorial Cancer Centre in Mumbai, India.
Although gallbladder cancer is rare in most parts of the world, it is far more common among some ethnic groups, such as Native Americans in North America, and in certain geographic regions, including Central and South America and East and Southeast Asia. The 178,000 new cases diagnosed worldwide each year are centered primarily in these high-risk regions.
“Using the latest technologies to look at the causes – notably the genetic underpinnings – of this understudied disease just makes a lot of sense,” says study co-leader Nilanjan Chatterjee, PhD, Bloomberg Distinguished Professor in the Department of Biostatistics at the Bloomberg School and a professor of oncology at the Johns Hopkins Kimmel Cancer Center
The gallbladder is a tiny organ in the abdomen which stores bile, the digestive fluid produced by the liver. When gallbladder cancer is discovered early, the chances for survival are good, but most gallbladder cancers are discovered late as it is difficult to diagnose since it often causes no specific symptoms.
To search for which genes might be important in gallbladder cancer, investigators at the Tata Memorial Centre gathered blood samples from 1,042 patients who were treated at the Centre’s Hospital in Mumbai between Sept. 2010 and June 2015. The researchers also collected blood samples during this time from 1,709 healthy volunteers with no known cancers who were visiting patients at the hospital.
To make the groups comparable, they were matched by their ages, sex and geographic regions in India from which the patients came from.
The scientists then ran these blood samples through a whole genome analysis of common single nucleotide polymorphisms (SNPs), places where the genome between different individuals vary by changes in single nucleotides, the smallest units that make up the genome.
Through a series of biostatistical and bioinformatics analyses, they found highly significant association for multiple DNA variants near two genes — ABCB4 and ABCB1 — known to be involved in moving lipids through the liver, gallbladder and bile ducts. A previous study had associated ABCB4 with the formation of gallstones, a known risk factor for gallbladder cancer. But the new results show for the first time that common inherited variants in this region may predispose individuals to gallbladder cancer itself, independent of gallstone status, Chatterjee says.
The researchers later replicated these results using blood samples gathered from 447 more patients with gallbladder cancer and 470 healthy volunteers from Tata Memorial Hospital and Sanjay Gandhi Postgraduate Institute of Medical Science in Uttar Pradesh, India.
They also ran another analysis to estimate how much variation in gallbladder cancer risk can be explained by the discovery of additional common variants. They say they hope to conduct similar studies of larger groups of people in the future.
“Gallbladder cancer, like many other cancers and complex diseases, is likely to be associated with many genetic markers, each of which may have small effects, but in combination they can explain substantial variation in risk,” Chatterjee says.
The researchers estimate as much as 25 percent of gallbladder cancer risk could be explained by common genetic variants. Although the specific genetic variants the current study has identified explain a small fraction of this risk, the fact that they are in close proximity to genes known to be important for transporting a certain class of lipids from liver to gallbladder could provide an important clue to the cause of the disease.
The team is currently planning to investigate the ABCB4/ABCB1 region in more depth by fully sequencing this region in some of the current study participants to understand whether there are additional risk variants there. They also plan to conduct larger studies to look for additional genes associated with gallbladder cancer. By better understanding the function of the genetic risk variants, as well as by investigating environmental and lifestyle causes, Chatterjee says, researchers might eventually be able to develop new treatments or interventions to prevent this disease from occurring in patients at high risk.
“Common Genetic Variation and Risk of Gallbladder Cancer: A Case-Control Genome Wide Association Study” was written by Sharayu Mhatre, Zhaoming Wang, Rajini Nagrani, Rajendra Badwe, Shubhada Chiplunkar, Balraj Mittal, S. Yadav, Haoyu Zhang, Charles C. Chung, Prachi Patil, Stephen Chanock, Rajesh Dikshit, Nilanjan Chatterjee and Preetha Rajaraman.
This study was supported by intramural funding from the Tata Memorial Centre, intramural funding by the National Institutes of Health’s National Cancer Institute, and by the Department of Biotechnology (DBT), India.
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Familial risks for gallstones in the population of Sweden
What is already known about this subject?
It is known that gallstone disease runs in families, but how the risk is modified by a detailed family history is not known.
Germline gene variants have been associated with the risk of gallstone disease.
What are the new findings?
Familial cases accounted for 36.0% of all patients with gallstone disease.
Of familial cases, 50.9% had a parental family history with a standardised incidence ratio (SIR) of 1.62 compared with those without the family history.
Of familial cases, 35.1% had a sibling history with an SIR of 1.75.
Of familial cases, 14.0% had a parental+sibling history with an SIR of 2.58.
Among the affected siblings, 15.6% were from families of two or more siblings diagnosed with an SIR >10.
The spousal risk was only 1.18.
How might it impact on clinical practice in the foreseeable future?
Family histories should be taken when patients are diagnosed with gallstones.
It would be important to identify the high-risk families and target counselling at patients and healthy individuals from such families.
Gallstones grow inside the gallbladder or biliary tract and if symptomatic they constitute gallstone disease or cholelithiasis.1 Gallstones may be classified by their composition into common cholesterol gallstones and bilirubin stones, by their colour into black pigment stones caused by haemolysis and brown pigment stones caused by obstructed or infected bile ducts, and by their localisation most commonly in the gallbladder or in the biliary tract.2 Over 10% of the US and European populations develop gallstones and the condition is becoming more widespread due to the increasing prevalence of risk factors such as obesity and physical inactivity. 1 3 Other risk factors are female sex, high age, pregnancy, certain ethnic background, family history and genetics.3 However, the female excess incidence could not be found in Taiwanese vegetarians.4 Gallstone disease has important medical consequences and costs; prevention should be of high priority.5 6
Based on familial clustering of gallstone disease, a 2.2-fold to 4.5-fold elevated risk has been reported in case–control studies among first-degree relatives and heritability estimates of 25% to 29% have been derived from family and twin studies.7–9 In one study, young women were at particular risk and the authors suggested that ‘female relatives of young gallstone patients should be routinely screened for gallstones’.7 A family study from the 1960s found no increased risk for gallstones among spouses, which suggests purely genetic origin for the familial clustering of gallstone disease.10 Several susceptibility genes have been identified, including apolipoproteins E (APOE) and B (APOB), cholesterol ester transporting protein (CETP), cholesterol 7 α-hydroxylase (CYP7A1), cholecystokinin receptor A (CCKAR) and LDL receptor (LDLR). 3 In some genome-wide association studies (GWASs), low-risk variants for the hepatic cholesterol secretion (ABCG8 19H and ABCB4) have been associated with gallstone disease. It has been estimated that the mutations in the hepatic cholesterol transporter ABCG8 confer the largest share of the genetic risk of developing gallstones.1 A meta-analysis of GWASs of individuals of European ancestry identified genetic risk variants for gallstone disease in ABCG8, TM4SF4, SULT2A1 and CYP7A1 genes.11
In view of the known inaccuracies in reporting family histories in case–control studies and the limited size of the published studies, we considered it timely to revisit familial risks of gallstone disease using the national cohort of Swedish families whose gallstones were medically diagnosed.12–15 In addition to the estimation of familial risks between genetically related relatives, we wanted to assess disease sharing between spouses in order to reconsider the contribution of the shared environment in adulthood. The study covered 15.8 million individuals and 660 732 patients with gallstones.
Patients and methods
Family relationships were obtained from the Multigeneration Register, which contains family data on the Swedish population and spans more than a century. ‘The offspring generation’ was born after 1931 and ‘the parental generation’ was born any time earlier. By the year 2015, the offspring generation had reached the age of 83 years; siblings can be defined only in the offspring generation. The offspring generation comprised 8.9 million index individuals in total. Patients with gallstones were identified using the nationwide Swedish Hospital Discharge Register (1964–2015) and the Outpatient Register (2001–2015). The first gallstone diagnosis in either register was considered and a patient was only entered once. Information from the registers was linked at the individual level via the national 10-digit civic registration number, which is issued to all permanent residents in Sweden on birth or immigration to the country. In the linked dataset, civic registration numbers were replaced with serial numbers to ensure anonymity. Revisions 7 (1964–1986), 9 (1987–1996) and 10 (1997–) of the International Classification of Diseases were used to identify gallstone diagnostic codes.
Standardised incidence ratios (SIRs) were calculated as the ratio of observed to expected number of cases. The expected numbers were calculated for all individuals without a history of gallstones (essentially the whole Swedish population), and the rates were standardised by 5-year-age, gender, period (5-year-group), socioeconomic status and residential area. The 95% CI of the SIR was calculated assuming a Poisson distribution. SIRs were calculated for offspring depending on the affected probands: parent, siblings or parents and siblings.
In order to assess possible roles of environmental risk factors for familial clustering of gallstones, we determined SIRs for gallstones in wives when husbands were diagnosed with gallstones and similarly for husbands when wives were diagnosed with gallstones. The period at risk for spouses was defined to start at the birth year of their first common child or at the first year that they were registered as living at the same address, whichever came first. The follow-up was terminated at gallstone diagnosis, death or when spouses no longer lived at the same address.16
The study was approved by the Regional Ethical Review Board of Lund University (no. 2012/795).
Patient numbers and mean diagnostic ages for gallstone disease are shown in table 1. The total population included 15.8 million individuals with men slightly outnumbering women. Patients with gallstone disease amounted to 660 732. Women (436 257, 66.0%) significantly outnumbered men (224 475). Mean and median diagnostic ages (ie, first hospital contact) were 55.7 and 57 years, respectively. The overall incidence was 131 per 100 000 person-years.
Population and number of cases of gallstone disease in Sweden, 1964–2015
Familial risks are shown in table 2 in age groups of the offspring generation 0 to 83 year old for whom familial risks were calculated. The overall familial risks were almost identical for men (SIR 1.79) and women (SIR 1.75), giving an overall SIR of 1.76. However, female SIRs were higher than male SIRs until age 19, but at higher age there was a male excess. The maximal SIR was 2.68 for men and 3.01 for women; this was reached at age 10 to 19 years, after which age the SIR uniformly decreased to age 60+ years. The total number of familial gallstone disease patients was 111 273 in the offspring generation. The total number of patients with gallstone in the offspring generation numbered 308 949, thus familial cases accounted for 36.0% of all patients with gallstone disease.
Familial SIR of gallstone disease by age groups
Age-specific incidence for all gallstone disease, with and without family history, is shown in figure 1. On top, female familial and non-familial incidence increased steeply up to ages 30 to 34, and after 34 years less steeply to age 75+ years. In bottom, male familial and non-familial incidence showed a continuous increase reaching the female rates at age 75+ years. At the reproductive age, from 20 to 34 years, female familial and non-familial rates exceeded the male rates up to 5-fold.
Incidence of gallstone disease in women (top) and men (bottom) per 100 000 person-years. Note that the difference between the curves is an estimate of crude incidence rates.
Table 3 shows familial risks for gallstone disease by different probands. The SIRs were highest (2.58 for men and women combined) when both a parent and a sibling were diagnosed with gallstone disease, compared with 1.62 when only a parent or 1.75 when only a sibling was diagnosed. The SIR was 2.44 when both parents were affected. Risks for sons were 1.71 when fathers were affected compared with daughters’ SIR of 1.62 when mothers were affected. The difference was not large, but because of large case numbers, it was significant (ie, 95% CIs did not overlap). Table 3 also shows spousal risks, 1.18 for husbands of affected wives and also 1.18 for wives of affected husbands.
Familial SIR of gallstone disease
In table 4, we show familial risk for gallstone disease by the number of affected siblings. For both sexes combined, the SIR was 1.55 when one sibling was affected, and it increased to 10.16 for persons with two affected siblings. SIRs remained at that level if up to four or more siblings were affected. However, considering persons diagnosed before age 30 years, there was a continuous increase in risk in these four proband categories, 2.06, 11.77, 14.18 and 17.02, respectively. Male risks were uniformly higher than female risks, and the difference between SIRs increased by the number of affected siblings and was always highest in the early onset group, for example, 39.80 in men diagnosed before age 30 and who had four or more affected siblings compared with 15.06 in women in this category. Data on siblings are shown figure 2, together with parental and spousal SIRs from table 3.
Familial risks (standardised incidence ratio (SIR) with 95% CI) for gallstone disease depending on the types of affected family members, collected from tables 3 and 4. The reference rate is at SIR=1. 00.
SIR of gallstone disease among siblings
The present study used nationwide hospital records on 660 732 inpatients and outpatients who were medically diagnosed with gallstone disease. The national cohort design is, in principle, unbiased and the results constitute by far the largest family study on gallstone disease yet published. The main novel finding was the complex population architecture of familial gallstone disease, with strong dependence of the risk on the age of onset and the number of affected family members, signalling genetic effects. Also, some unexpected results were found for the gender. Spousal correlation associated with gallstone disease, which signals environmental contributions, was modest. However, it was higher than reported in the literature but perhaps not unexpected because of the number of known environmental risk factors.10 The limitations of the study were unavailability of primary care data, which may include persons with transient abdominal pain.
Familial cases, that is, persons in the offspring generation with a parent or a sibling with gallstone disease, accounted for 36.0% of all patients. The overall incidence of gallstone disease (131 per 100 000 person-years) was doubled in women compared with men. The largest difference between female and male incidence rates was noted at reproductive ages. Relatively few incidence data are available from other countries. In the UK, age-standardised hospital admission rates for gallstone disease increased from 68.7 to 104.9 per 100 000 population between 1989/1990 and 1999/2000; female rates were more than doubled compared with men.17 The increasing trend appears to continue in developed countries.1 18 19 In Taiwan, hospitalisation rates were about 60 per 100 000 for both men and women around the year 2000.20 It is noteworthy if the female excess in gallstone disease is a feature of western populations.
The total number of familial gallstone disease patients was 111 273 in the offspring generation 0 to 83 years old. Of these, 50.9% had a parental family history (SIR 1.62), 35.1% had a sibling family history (SIR 1.75) and 14.0% had a parental+sibling family history (SIR 2.58). Among a total of 54 626 affected siblings, 84.4% were sibling pairs (SIR 1.55). However, the remaining 15.6% of the affected siblings constituted the high-risk group with an SIR >10; these 8527 persons accounted for 7.7% of all affected offspring. In this high-risk group, those diagnosed before the age of 30 years were at the highest risk, particularly if they were men. It is noteworthy that despite the doubled incidence in women, the overall familial risks were only marginally higher in men, but in the highest risk groups, they were much higher. Thus, the citation from the Introduction ‘female relatives of young gallstone patients should be routinely screened for gallstones’ should be modified from focusing on gender to a defined family history.7 The high-risk group constitutes families with at least two affected siblings.
In conclusion, the present results provide qualified evidence for the familial risk in gallstone disease, which covered 36.0% of all patients with gallstone disease in our study. The patterns of familial clustering suggest that the large majority of the population, with one affected family member, are at a 1.6-fold to 1.7-fold risk of being hospitalised for gallstone disease. A smaller group, which has both parents or a parent and a sibling diagnosed with gallstone disease, run a higher risk of about 2.5. The high-risk population constitutes those with at least two siblings, some 7.7% of all familial gallstone disease patients, and their risk is over 10-fold the background rate. One can assume that the majority of the familial risk is contributed by gene–environment interactions at a polygenic background of common low-risk variants while the high-risk population carries gene variants with high to moderate penetrance.1 3 11 It would be useful that clinical guidelines for gallstone disease would also consider prevention and counselling about avoidance of risk factors with a focus on patients and healthy individuals from high-risk families.21 The present results about familial risk should reassure about the importance of taking a detailed family history in the clinical setting and of targeting counselling accordingly.
We are thankful to Patrick Reilly for language editing.
90,000 About gallstone disease and cholecystectomy, removal of the gallbladder
Causes and risks of gallstone disease
The most common gallbladder disease is cholelithiasis (GSD). It is believed that this is one of the leaders among the diseases in the adult population. People over 50 are at particular risk.
The main causes of ZhKB are:
Genetic (hereditary) factor,
High blood cholesterol
Nutritional imbalance and obesity,
Obstructed outflow of bile from the bladder: congenital deformities of the bladder, impaired motility of the biliary tract (dyskinesia), long-term problems in the gastrointestinal tract (for example, increased pressure in the gastrointestinal tract),
Infectious lesions of the gallbladder,
Increase in the level of bilirubin in the liver and, as a result, in bile.
Stones or calculi lead to difficulty in the outflow of bile, destruction of the mucous membranes of the walls of the bladder and inflammation. External manifestations can be sharp pains on the right under the rib, nausea, jaundice, bitterness on the tongue.
The main threats to gallstone disease are fatal: bladder rupture and peritonitis, gastrointestinal and pancreatic lesions, and the development of gallbladder cancer.
Unfortunately, problems with the gallbladder do not appear immediately, and stones form for many years and do not make themselves felt.Therefore, it is very important to regularly monitor your overall health, in particular, maintain the proper level of low and high density cholesterol, blood sugar and bilirubin, eat right, and take into account heredity.
Minimally invasive removal of the gallbladder
Surgical treatment of gallstones is an effective method, but it is used only in the case of threatening conditions and is reduced to the removal of the affected gallbladder and stones in the ducts. In some cases, extraction of only calculi is practiced.
To reduce trauma and reduce the negative consequences of the operation, our clinic uses laparoscopic cholecystectomy – that is, intervention with endoscopic instruments through small punctures (minimally invasive method).
Briefly about the progress of the operation:
It is performed under general anesthesia.
- The surgeon makes 4 punctures in the abdomen and sets up narrow trocars.
To create space for manipulation and a comfortable view, carbon dioxide is injected into the peritoneum.
A laparoscope is inserted through two tubes – a camera for observing the place of manipulation and a light guide, through the other two – a clamp and a knife (mechanical scissors or coagulator).
The bladder is cut off (from the artery, liver) and the stones in the ducts are removed.The use of a coagulator allows you to simultaneously cut off tissues and solder them, which allows you to achieve maximum bloodlessness.
The main advantages of the minimally invasive method are less pain after surgery, the ability to move immediately after coming out of anesthesia, and the hospital stay is reduced to 4 days.
Cholecystectomy significantly reduces the risks to the patient’s life. Nevertheless, bringing the liver to normal and a special mode of life will become the main task of the patient in the future.
Successful treatment of gallbladder dyskinesia in the NEARMEDIC network
Dyskinesia of the gallbladder is a polyetiological condition, so doctors need to take into account all possible forms of predisposition to the disease. It is believed that the dysfunction of the gallbladder may be associated with the patient’s lifestyle, heredity and dietary habits.
Key risk factors
- Family history of functional diseases of the gallbladder and its ducts.Hereditary factors are often associated with anatomical abnormalities.
- Infectious processes in the liver and bile ducts. First of all, it is hepatitis A and B.
- Surgical treatment of abdominal organs, abdominal trauma.
- Asthenic constitution and neuropsychiatric disorders, accompanied by anxiety and apathy.
- Unhealthy diet: excess fatty foods in the diet, snacks before bedtime, insufficient fluid intake.
- Chronic stress and insomnia.
- Insufficient physical activity.
- Diabetes mellitus.
Many risk factors can be eliminated with a healthy diet and early treatment of primary gastrointestinal diseases.
Normally, the evacuation of bile is a coordinated process: the successive contraction of the smooth muscles of the body and the neck of the bladder leads to the reflux of fluid into the bile ducts. After cholecystokinin stimulates the relaxation of the sphincter of Oddi, the secret enters the small intestine and participates in digestion.The nervous system provides activation or inhibition of the functions of the gallbladder, depending on external factors. Specialists rarely manage to determine which link of regulation has changed when pathology occurs.
Dyskinesia of the gallbladder is primarily manifested by uneven contraction of different parts of the organ. So, a combination of a rapid contraction of the bladder neck with a weakened activity of the muscles of the body of the organ is possible. As a result, bile is not completely excreted, and the walls of the bladder are stretched, after which abdominal pain occurs.Additional symptoms are often due to other autonomic disorders that affect the pain threshold. A prolonged delay in the excretion of bile is complicated by the formation of calculi and complete blockage of the ducts.
Gastroenterologists classify gallbladder dyskinesia according to the clinical manifestations of the disease, etiology and the nature of the motor impairment. All these signs help to choose the optimal therapy for the disease.
Main types of dyskinesia
- Hypertensive motor disorder, manifested by rapid uncoordinated contractions of the walls of the gallbladder.In most cases, this form of dyskinesia is diagnosed in children and young patients. The main symptom is acute paroxysmal pain that lasts for several minutes.
- Hypotonic motor disorder, in which the muscles of the gallbladder contract too rarely or not strongly enough. Hypomotor dyskinesia is usually found in older patients. Pain sensations are less acute and prolonged.
Another classification includes secondary and primary forms of the disorder.Dyskinesia can occur on its own with a violation of innervation, anatomical defect or hormonal imbalance, but more often a secondary form of the disease is diagnosed, which is formed against the background of pathologies of other organs.
Symptoms and Signs
The clinical picture of the disease depends on the type of gallbladder motility disorder, the patient’s age and concomitant pathological conditions. The pain syndrome can last for several minutes or persist throughout the day.In general, the nature of pain is an important diagnostic marker.
- nausea and vomiting;
- deterioration in appetite;
- loose stools or constipation;
- bitterness in the mouth;
- yellowing of mucous membranes and skin;
- weakness and fatigue;
- emotional lability.
Almost all symptoms of gallbladder dyskinesia are nonspecific, therefore, accurate diagnosis is carried out only with the help of special examinations.
For the examination, the patient must consult a gastroenterologist. During the appointment, the doctor will ask the patient about the complaints, collect anamnestic data and conduct a physical examination. An external examination allows the specialist to detect jaundice, bloating and soreness in the right hypochondrium, but these pathological signs are not always presented. The final diagnosis is determined after instrumental and laboratory studies.
Required diagnostic manipulations
- Laboratory research. First of all, a blood test is performed to assess the number of leukocytes, determine hepatic functions and exclude infectious diseases. A Helicobacter test is also recommended.
- Ultrasound imaging of the gallbladder. This study does not always allow detecting dyskinesia, however, in some cases, doctors reveal an increase in organ volume and other abnormalities.It is also possible to perform imaging after meals and choleretic agents: in patients suffering from dyskinesia, the volume of the gallbladder is reduced by only 35-40%.
- Radionuclide diagnostics. The introduction of a special chemical marker into the patient’s body gives the specialist the opportunity to assess the functions of the liver and gallbladder.
- Retrograde cholangiopancreatography is a visual examination of the bile ducts and the mucous membrane of the gastrointestinal tract.
- Computed tomography or magnetic resonance imaging of the abdominal organs.Obtaining volumetric images of these anatomical structures allows the doctor to more accurately determine the cause of the disease.
The gastroenterologist may order a limited number of diagnostic tests after requesting medical history and examining symptoms.
If the violation of gallbladder motility is not complicated by severe structural pathologies, doctors prescribe only drug therapy. The main task is to normalize the work of the gallbladder and facilitate the evacuation of bile into the duodenum.Before prescribing specific medications, it is necessary to determine the type of disease.
- Myotropic antispasmodics that relax the smooth muscles of the gallbladder. These drugs are necessary for the hypertensive form of the disorder.
- Choleretic agents – substances that stimulate the functions of the liver and gallbladder. If the patient has too active muscle contractions, cholespasmolytics are needed, which slow down the motility of the organ and eliminate spastic phenomena.
- Cholekinetics and prokinetics with weakened gallbladder motility. These drugs both improve the contraction of the organ and facilitate the secretion of bile into the intestines.
- Additional medicines: anti-inflammatory drugs and antidepressants to eliminate complications of the disease.
In addition to drug therapy, patients must be prescribed a therapeutic diet. The recommended diet depends on the form of the motor disorder, but most often patients are prohibited from consuming too fatty foods and alcoholic beverages.
The indication for surgery may be complicated dyskinesia, which cannot be eliminated by drug therapy. Also, the operation is prescribed for severe pain and severe indigestion. Before surgical treatment, it is important to exclude other pathologies of the gallbladder, such as gallstone disease or the growth of a malignant tumor. According to modern research, radical treatment is more effective in relieving the symptoms of the disorder.
Depending on the indications and the patient’s condition, the doctor can perform open or laparoscopic cholecystectomy. The operation involves the removal of the gallbladder. After the intervention, the functions of the digestive system are normalized, however, some complications may develop, such as dyslipoproteinemia or dysfunction of the sphincter of Oddi.
Prognosis and complications
Predictive data depend on the form of pathology, concomitant diseases and the patient’s age. If gallbladder dyskinesia is not complicated by other disorders, the prognosis is good.In most cases, drug therapy can produce significant improvements.
- hepatic encephalopathy with prolonged bile retention;
- inflammation of the gallbladder and its ducts;
- occurrence of a secondary infection;
- insufficient intake of nutrients in the body.
To prevent the development of complications, it is necessary to follow a therapeutic diet.
Many diseases of the digestive system are remote consequences of an improper lifestyle, therefore, preventive measures help prevent dysfunction of the gallbladder and its ducts.First of all, doctors recommend paying attention to primary pathologies and dietary habits.
- Improving the diet: avoiding too fatty foods, fried foods, alcohol and excess spices. Sufficient fluid intake.
- Normalization of body weight and regular physical activity.
- Stress avoidance, anxiety treatment.
- Timely detection and treatment of inflammatory processes in the gallbladder and intestines.
- Regular examination by a gastroenterologist in the presence of chronic diseases of the digestive system.
- Refusal of hormonal contraceptives and somatostatin preparations.
Thus, gallbladder dyskinesia is a common disease manifested by impaired motility of the organ. Insufficient bile secretion can lead to serious complications, so such a disorder must be treated when the first symptoms appear.Medication and lifestyle changes are often enough.
Gallstone disease, operation to remove gallbladder stones price in joint venture
Chronic disease of the biliary tract, in which stones form in the gallbladder (more often) and bile ducts, is called gallstone (gallstone disease).
If stones are detected in the common bile duct, then this form of gallstone disease is called choledocholithiasis .
The disease has been known since ancient times. For the first time stones of the gallbladder were discovered during autopsy and described by Galen, a great surgeon, writer and philosopher who lived in the second half of the 2nd century AD in ancient Rome. During the Renaissance, in the writings of Gentile de Foligno in 1341, there is also a mention of ZhKB.
A detailed description of gallbladder stones appeared in the middle of the XYIII century (C.Galeati), and at the same time the study of their chemical composition was first undertaken. All information about ZhKB contained in the works of various authors was summarized by Albrecht Haller (1755). In his works, he showed that gallstones are found not only in humans, but also in horses, pigs, cows, marmots, monkeys and other animals.
He divided all stones of the gallbladder and ducts into 2 groups:
- Large ovoid, often solitary, composed of “a tasteless yellow substance that melts like sealing wax when heated and burns.”
- Smaller, darkly colored, multifaceted, which are often found not only in the gallbladder, but also in the bile ducts.
Since the mid-19th century, there have been various theories of the origin of gallstones. Of these, two main areas can be distinguished.
Supporters of one of them saw the cause of gallstones in the abnormal state of the liver. Such a liver produces bile of a modified composition, as a result of which its dense parts precipitate, forming stones.Other researchers considered stagnation of bile and inflammation of the biliary tract and gallbladder as the main cause of the disease.
More thorough work on housing and communal services appeared already in the twentieth century. In addition to a detailed study of the structure of gallstones, a theory of the occurrence of cholelithiasis was developed. It was based on the concept of “stagnant gallbladder” and metabolic disorders.
The incidence of cholelithiasis
The incidence of cholelithiasis has sharply increased in the last decade and continues to grow.According to the National Institutes of Health (1992), 10-15% of the world’s adult population suffers from gallstone disease. The number of people visiting doctors for stones of the bile ducts and gallbladder in the territory of the Russian Federation is about 1 million per year.
Women get sick 3-5 times more often than men, and they also had cholelithiasis more often (5-6 times) than men.
Modern understanding of the causes leading to gallbladder stones
- First, it is metabolic disorder , which affects the chemical composition of bile.Bile, which is a complex chemical solution, contains poorly soluble substances. In order for them not to precipitate, it is necessary to preserve them in strict proportions. If their percentage is violated in one direction or another, then a sediment is formed, which can then turn into stones.
- Secondly, it is a violation of the correct movement of bile along the biliary tract . The emergence of obstacles to the outflow of bile into the duodenum, long periods of fasting lead to stagnation of bile in the gallbladder, its thickening and precipitation.
In turn, the formation of stones contributes to the disruption of the normal process of digestion: there are failures in the formation, storage and secretion of bile, which is one of the most important components for the proper digestion of food. There are groups of people who have a high risk of gallstones and chronic calculous cholecystitis.
The following risk factors are distinguished:
- Inheritance . The likelihood of developing stones of the gallbladder and ducts increases in the presence of direct relatives suffering from this pathology.
- Diseases associated with metabolic disorders: diabetes mellitus, gout, obesity, atherosclerosis, decreased thyroid function.
- Liver diseases : cirrhosis, fatty hepatosis, chronic hepatitis.
- Diseases of the digestive system , for example, pancreatitis, duodenitis, colitis, dysbiosis and others. Sometimes there is the so-called “Saint’s triad” – a combination of cholelithiasis with diaphragmatic hernia and colon diverticulosis.
- Improper nutrition: abuse of fatty high-calorie foods, sweets.
- Prolonged fasting, diet . A break in food for more than 8 hours, as well as a long diet that does not contain animal fats, leads to stagnation in the gallbladder.
- Taking certain medications, such as steroid hormones and oral contraceptives.
- Changes in hormonal balance during pregnancy.
- Smoking and alcohol abuse.
Symptoms of gallstone disease
The manifestations of the disease are extremely diverse. Most often, the following forms of ZhKB are distinguished:
- chronic dyspeptic,
- chronic pain,
- chronic relapsing,
- other forms.
In a sense, these forms can be considered as stages of development of gallstone disease.After a period of latency, the same patient may develop dyspeptic disorders, after a while – moderate pain syndrome and, finally, typical attacks of hepatic colic. However, such a development of the disease is far from necessary. Often, its first manifestation may be an attack of acute cholecystitis and hepatic colic.
Dyspeptic form ZhKB
It is characterized by complaints related to digestive disorders.There is a feeling of heaviness in the stomach, heartburn, flatulence, unstable stools. Usually these sensations arise periodically, but they can also be permanent. They are most often observed after eating. Moreover, patients often associate their appearance with the use of certain foods: fatty, fried, spicy foods. The appearance of complaints can also be associated with the intake of too large portions of food.
Painful chronic form of JCB
It proceeds without bouts of acute pain.The pains are aching in nature, localized under the spoon and in the right hypochondrium, worse after eating, especially fatty foods. Their irradiation to the area of the right scapula is characteristic. Long-term existence of stones in the gallbladder can continue indefinitely, but ultimately leads to the occurrence of an inflammatory process in it.
Chronic calculous cholecystitis
One of the frequent manifestations of chronic calculous cholecystitis is constant severity and pain in the right hypochondrium, nausea, aggravated by the intake of fatty and spicy foods.Small stones can manifest as hepatic colic: an attack of acute pain in the right side of the abdomen, sometimes in the epigastric region. An attack can be triggered by the ingestion of fatty spicy foods or alcohol, as well as shaking when driving or stress. Vomiting and nausea are common companions to pain. Irradiation of pain to the right scapula, right shoulder or right arm is characteristic. The cause of a painful attack may be the wedging of a stone into the neck of the gallbladder. This leads to severe cramping. The gallbladder itself at this time is significantly reduced, trying to push out the bile, but it prevents it from getting out of the stuck stone.The duration of a painful attack is different – from several minutes to many hours and even days. If the obstacle is removed and the stone ceases to block the exit from the gallbladder, the symptoms quickly subside. Vomiting stops, the temperature returns to normal; general well-being improves. For some time, weakness and a feeling of weakness persist, and dyspeptic symptoms are occasionally noted. The patient’s condition may remain quite satisfactory until the next attack, which may develop in a few days, weeks, months or years.
Consequences of chronic cholecystitis
People with long-term chronic cholecystitis end up risking their health and even their lives. The inflammatory process from the gallbladder spreads to neighboring organs, primarily to the pancreas and liver. Almost all of these patients have a chronic form of pancreatitis and changes in the liver. In this case, irreversible changes occur in the gallbladder, which leads to three variants of the development of the disease.
- 1. The process of formation of stones in the gallbladder does not stop. The addition of infection and inflammation create favorable conditions for the growth and formation of new stones. The bladder fills with stones and ceases to be a reservoir for the accumulation of bile. It cannot fulfill its basic functions in the digestive process. Food is poorly absorbed.
- 2. Frequent inflammation of the gallbladder due to attacks of hepatic colic leads to a change in the wall of the gallbladder: it becomes overgrown with adhesions, and the muscles are replaced by dense scar tissue.The cavity of the bladder is sharply reduced in size, a “scar-wrinkled bladder” is formed, which also does not participate in the process of digestion.
- 3. When the cystic duct is blocked by a stone, the bubble becomes large and overstretched. Overflowing with bile, which does not find a way out, the bladder loses its ability to contract, and even after the stone leaves the duct it remains stretched, while it is no longer able to push out bile. Gradually the contents become colorless – “white bile”. Dropsy of the gallbladder develops.Sometimes it is asymptomatic (apparently, the patient simply forgets about the attack). However, if dropsy appeared after an attack of hepatic colic, the enlarged gallbladder remains painful for a long time. Such a gallbladder also turns out to be excluded from the digestion process. In addition, bile, which remains in the gallbladder and is not renewed, easily suppurates when an infection is attached, and empyema of the gallbladder develops.
It is necessary to carry out a differential diagnosis of biliary (hepatic) colic from an attack of acute calculous cholecystitis.This is an inflammation of the gallbladder, provoked by the presence of stones in it, which is manifested not only by severe pain syndrome, but also by the presence of fever, signs of intoxication, sometimes positive peritoneal symptoms and requires emergency hospital treatment. The appearance of fever, jaundice, and a decrease in blood pressure in a patient with gallstone disease requires the exclusion of such possible complications as acute cholecystitis, pancreatitis, cholangitis, etc.
The main methods for diagnosing gallbladder stones
- With exacerbation of gallstones, changes are observed in the clinical analysis of blood: the number of leukocytes increases with the appearance of their young forms, the ESR rises, which indicates the presence of an inflammatory process.Changes in blood biochemical parameters may occur: an increase in the level of hepatic transaminases, amylase, lipase, total bilirubin. In most cases of asymptomatic stone carrying, the blood test may not be changed. Also, without changes in laboratory parameters, short attacks of biliary colic can occur.
- 1. The most accessible and effective method of screening diagnostics of all stages of gallstone disease is ultrasound examination of the abdominal cavity organs (US). Ultrasound of the liver and gallbladder allows you to see stones in the cavity of the bladder, determine their size, mobility, assess the size of the residual cavity of the gallbladder, identify signs of inflammation or deformation of its wall. Also, with ultrasound, the intra- and extrahepatic bile ducts are clearly visible, it is possible to assess their deformation, expansion and the presence of additional inclusions (calculi) in them.
- 2. A more accurate diagnosis of the state of the biliary tract is shown by magnetic resonance imaging – MR cholangiography.
When performing MR – cholangiography, an image of the gallbladder, cystic duct, segmental, lobar ducts, common hepatic duct, common bile duct and the main pancreatic duct is obtained. It is possible to assess their deformation, to reveal the expansion or narrowing of their lumen in certain areas. It becomes possible to accurately visualize stones not only in the gallbladder, but also in the lumen of the bile ducts. Additional methods of examination for gallstones include computed tomography (CT) and video duodenoscopy.
- 3. Computed tomography (CT) of the abdominal cavity is performed if there is a suspicion of pathology of neighboring organs (liver, pancreas), or if there is a suspicion of oncological pathology in the biliary system.
- 4. Videogastroduodenoscopy – an endoscopic examination, which resembles videogastroscopy, but is performed using a special endoscope with lateral optics, which allows you to see well the area of the large duodenal papilla or “Vater papilla” (the place where the bile ducts enter the duodenum).
Treatment of gallstones and chronic calculous cholecystitis
Conservative treatment of gallstones
In the arsenal of doctors there are preparations of ursodeoxycholic acid, which changes the chemical composition of bile. These are drugs henofalk and ursofalk, they are prescribed for the purpose of medication litosis (dissolution of stones). Treatment should be carried out against the background of strict adherence to diet and diet, as well as anti-inflammatory therapy. The duration of treatment is up to 2.5-3 years and does not always achieve the desired result.It should be remembered that true “stones”, consisting mainly of calcium, do not dissolve. Therefore, drug treatment can be used only in the initial stages of the disease, when the sediment in the bile is mainly represented by cholesterol stones.
Operation to remove the gallbladder with stones
Cholecystectomy – removal of the gallbladder – the main method of surgical treatment. The operation is performed either openly through an abdominal wall incision, or laparoscopically – endovideosurgical cholecystectomy.Purpose of the operation: removal of the gallbladder with stones. The only difference is in what tools the surgeon works and in what way the gallbladder with stones is removed.
In open surgery, the incision through which the bladder is removed can be made from the xiphoid process to the navel, or a second approach – in the right hypochondrium. The laparoscopic method is less traumatic – special instruments and optics are inserted through 4 small incisions in the skin. With the help of these instruments, the gallbladder is removed.After such an operation, the scars are hardly noticeable. The length of stay in a hospital bed is 2-3 days. A week later, the patient is healthy.
Essential for the patient
In the modern world, gallstone disease is a well-studied pathology, and laparoscopic surgery is the “gold standard of treatment”. Unfortunately, many people do not pay attention to the initial manifestations of the disease, do not undergo medical examination or preventive examination to detect stones in the gallbladder.As a result, the disease is detected at later stages, when drug treatment is not only ineffective, but also contraindicated, and the success of minimally invasive surgery also becomes questionable.
In the presence of the complaints described above, as well as the listed risk factors, it is necessary to contact a surgeon or gastroenterologist for recommendations on examination and selection of optimal treatment or preventive measures.
Our Clinic provides a full range of diagnostics, surgical and endoscopic treatment of gallstone disease and its complications. Surgical operations in most cases are performed minimally invasive using laparoscopic and endoscopic technologies.
Cancer of the gallbladder and biliary tract
Risk factors for gallbladder cancer
The presence of cholelithiasis increases the risk of gallbladder cancer, therefore, its removal is thus a preventive measure.In most cases, gallbladder cancer is found during surgery to remove gallstones. Risk factors for the disease include overweight and female sex. The risk of cholangiocarcinoma increases significantly with chronic inflammation of the biliary tract, caused by either an autoimmune disease or an infection (the latter is extremely rare in Finland).
Symptoms of gallbladder cancer
Yellow skin, pain, fever, nausea and vomiting can be symptoms of cancer.Most often, they indicate that the disease is at an advanced stage. Some symptoms may be caused by obstruction of the bile ducts due to a tumor (yellow skin, itching) or general symptoms (weight loss, appetite, fatigue). Autoimmune bile duct disease may be diagnosed during a general physical examination (such as blood tests) based on elevated liver readings or when tested for another autoimmune disorder (such as ulcerative colitis).
Diagnosis of gallbladder cancer
The diagnosis of gallbladder cancer cannot be made only on the basis of laboratory tests. Routine x-rays are also not helpful in diagnosing gallbladder cancer. Frequent and difficult to treat inflammation of the gallbladder can be a sign of a tumor in the gallbladder. An ultrasound or computed tomography (CT) scan may show a thickened gallbladder wall and / or enlarged lymph nodes. It can be very difficult to distinguish between changes caused by inflammation.
When screening for the prevalence of cancer, ultrasound and CT are used as complementary procedures. Cancer is often diagnosed by examining the bile ducts with a contrast agent. Today, this manipulation is most often performed using endoscopy (internal examination) of the duodenum (ERC study). Such a study as magnetic resonance cholangiography (MR cholangiography) on an MRI machine well determines the obstruction of the bile ducts and shows its localization.
Treatment of gallbladder cancer
Cancer of the gallbladder is treated with surgery. During the operation, the gallbladder itself is removed and often also the adjacent lymph nodes and the surrounding liver tissue. Whenever possible, for cancer of the bile ducts that are inside the liver, surgery is always performed. However, very often, at the time of diagnosis of cancer, the tumor already has time to spread to places where it is impossible to remove it surgically. Surgery to remove a tumor of the external biliary tract resembles surgery to remove a tumor of the pancreas, in which you have to remove the bile ducts, gallbladder, part of the pancreas, duodenum and adjacent lymph nodes.The operation gives a chance for recovery only if it is possible to remove the cancerous tumor along with the surrounding healthy tissue, which is a very difficult task, especially when it comes to the liver.
Cancers of the gallbladder and bile ducts respond differently to chemotherapy. The same can be said about the growth rate of such tumors – it varies greatly. In certain cases, chemotherapy gives good results for a long time, which significantly prolongs the patient’s life.
Cholelithiasis – Official site of the Federal State Budgetary Healthcare Institution KB No. 85 FMBA of Russia
Cholelithiasis is a chronic pathology, which is characterized by the formation of calculi in the gallbladder and biliary tract against the background of burdened heredity. In addition to the genetic factor, dietary habits play a role in the development of gallstone disease, in particular, the use of large amounts of simple carbohydrates (sweets, candies, flour products, etc.).
In Russia, as in Europe, the incidence rate is quite high – 10-15%.For comparison, in Asian countries it is not higher than 5%.
The disease is asymptomatic for a long time. For the first time, an attack of biliary colic may appear, which is characterized by severe pain in the right hypochondrium, nausea, vomiting and other “food” complaints. Sometimes acute inflammation of the gallbladder develops.
The earlier the pathology is detected, the lower the need for urgent operations, for which the frequency of complications is higher than with planned.
Gallstone disease may not manifest itself clinically for a long time.Symptoms appear when the biliary tract is blocked by calculus (biliary colic) or when inflammation develops (acute cholecystitis).
Biliary colic is one of the most common manifestations of gallstone disease. It develops when the stone moves, when it clogs the exit from the gallbladder or ducts. Against this background, the intraluminal pressure increases and pain syndrome appears. Its distinctive features are:
- Appearance 1-1.5 hours after eating fatty foods or an episode of excessive overeating
- Rapid increase in pain in a short period of time;
- the nature of the pain is constant and bursting;
- duration from several minutes to several hours;
- localization of pain – in the epigastrium and in the hypochondrium on the right, and irradiation may be noted in the right hand, between the shoulder blades and the neck on the right;
- accompanying symptoms – nausea and vomiting without relief, fever, bloating;
Acute cholecystitis is another clinical manifestation of cholelithiasis.As a rule, they begin to think about this condition if an attack of biliary colic lasts more than 6 hours, and the pain does not go away, but, on the contrary, increases. Pain in this case captures the entire right hypochondrium, intensifies with deep breathing and concussion of the peritoneum.
Body temperature rises to 38-39 ° C, jaundice may join).
Speaking about gallstone disease, it is worth noting that pathology develops mainly in genetically predisposed people.
Aggravated heredity plays a primary role in the development of the disease. In addition, the following factors increase the likelihood of gallstone disease:
- Age. The highest incidence peak is recorded at 40-69 years.
- Obesity and high levels of triglycerides in the blood.
- Diabetes mellitus and metabolic syndrome.
It is worth noting that lately gallstone disease has “rejuvenated”.Often, calculi are detected even in children and adolescents, which scientists associate with an epidemic of obesity and malnutrition.
Diagnosis of gallstone disease
Diagnosis of the disease begins with a thorough analysis of complaints and the results of an objective examination. Therefore, in order to establish an accurate diagnosis, the doctor draws up an individual examination program, which may include:
- general clinical analysis of urine and blood;
- biochemical study of blood composition;
- ultrasound scanning of abdominal organs;
- electrocardiography and determination of cardiospecific enzymes in the blood;
- X-ray of the abdominal cavity and chest;
- X-ray contrasting of the bile ducts;
- endoscopic retrograde cholangiography (the research probe is inserted through the mouth and brought to the duodenal papilla).
Computed tomography and magnetic resonance cholangiopancreatography can be used in difficult diagnostic cases.
The choice of treatment tactics depends on the severity of clinical symptoms. If symptoms are present, conservative or surgical treatment may be chosen.
Surgical treatment of gallstone disease
In most cases of gallstone disease, proceeding with vivid clinical symptoms, cholecystectomy is recommended – this is the removal of the gallbladder.The operation can be performed both laparotomically (through an abdominal incision) and laparoscopically (through 3 miniature punctures on the anterior abdominal wall).
Laparoscopic cholecystectomy has a number of advantages:
- good cosmetic result;
- fast recovery;
- minimum complication rate;
- minimal tissue trauma;
- mild pain syndrome in the postoperative period.
Rehabilitation after laparoscopic cholecystectomy is rather fast. The patient is in the hospital from 1 to 3 days. At this time, mild analgesics are prescribed, as well as antibiotic prophylaxis or antibiotic treatment (depending on the infectious risk). Early activation is recommended – you can and should get out of bed soon after being transferred to the common ward.
Effective treatment of gallstone disease | Clinic of Chinese medicine TAO
Cholelithiasis is a disease in which metabolic processes are disturbed, as a result of which stones begin to form in the gallbladder and bile ducts.Most often this is due to a violation of cholesterol metabolism. The disease most often affects middle-aged females.
The main symptom of the disease is recurrent pain localized in the upper abdominal cavity. Moreover, the most severe pain occurs at the site of localization of stones. An attack of biliary colic can occur as a result of blockage of stones in the bile ducts or the neck of the gallbladder. Most often, gallstone disease is asymptomatic and is characterized by only minor aching pains in the right hypochondrium.This is what we know from Western medicine.
Chinese medicine specialists make the diagnosis using the topography of the tongue. So, in case of gallstone disease, the tongue is dry, covered with cracks, sometimes there is a so-called geographical language resembling an atlas. However, this state of the tongue is often the norm, so doctors at the TAO clinic most often observe the “state of the tongue in dynamics.” In addition, with gallstone disease, a thick layer of plaque may form on the tongue. Sometimes this indicates the neglect of the disease.Usually it is a white dry bloom with black blotches in the form of small “thorns”.
During the period of remission, the pain subsides somewhat and is localized in the upper abdominal cavity with a slight shift to the right. Most often, a specialist is consulted only in an acute case. Diagnosis by means of Chinese medicine is possible at any stage of the development of the disease. This is one of its main advantages.
During exacerbation of gallstone disease, pain can radiate to the right shoulder.The disease during this period is accompanied by intolerance to fatty foods, nausea, vomiting, a feeling of bitterness in the mouth, fever, poor appetite.
Causes and mechanism of gallstone disease
According to doctors of traditional Chinese medicine, the cause of the disease lies in the improper functioning of the “liver meridians”, in the imbalance of the “Qi” energy.
The main reasons for the appearance of gallstone disease, both in the opinion of Western doctors and doctors of Eastern (Chinese) medicine, include an improper diet, for example, refusing a full breakfast or replacing it with a cup of coffee, abuse of fatty foods, alcohol, chronic cholecystitis (inflammation of the gall bladder), as well as obesity, hereditary predisposition, diabetes mellitus, inflammation of the biliary tract.
First of all, Chinese medicine specialists try to restore the correct diet, cleanse the liver and bile ducts.
The approximate mechanism of the appearance of gallstone disease is as follows. The gallbladder serves as a kind of reservoir in which bile accumulates, which takes part in the process of digesting food. With stagnation of bile or with a high content of cholesterol in it, the process of crystallization of cholesterol, the main substance contained directly in bile, begins. In addition, salts of other substances contained in bile, as well as a change in its composition, take part in the loss of stones.
The stones found in the gallbladder can be divided into several main groups. The most commonly used classification is according to the composition of the salts found in them.
So, the types of stones in the gallbladder:
- Homogeneous. There are lime stones, bilirubin and cholesterol.
- Mixed. These stones are the most common. Their composition is characterized by the presence of calcium salts, bilirubin and cholesterol.
- Complex.These stones are multi-layered, contain all the previously listed components.
The main diagnostic methods of Chinese medicine for this disease are language diagnostics and pulse diagnostics.
Diagnostics by language includes several main stages:
- Determine the size of the language.
- Assessment of the condition of its surface.
- Mobility Features.
- Tongue colors.
- Presence or absence of plaque.
- Possible rash or ulcers on the surface of the tongue.
Pulse diagnosis is palpation of the radial artery in the wrist with the index, middle and ring fingers. Diagnostics are performed on both hands. With the help of this type of diagnosis, it is possible to identify violations, both in dense and in hollow organs, where the gallbladder belongs.
It is important that pulse diagnostics allows you to identify pathologies of all organs, therefore, along the way, you can deal with the treatment of other existing diseases.
The methods of diagnosing this disease by means of Western medicine include an ultrasound examination, which allows to clarify the location of stones, a complete blood count, as well as a blood test for reticulocytes, a coprogram, hepatic sampling and a study of blood plasma glucose.A general urine test is also required.
To confirm the diagnosis of cholelithiasis, computed tomography, magnetic resonance cholangiopancreatography, and general radiography of the gallbladder are performed. Possible instrumental studies such as cholecystography and CT of the abdominal organs.
Treatment of gallstones
A good alternative to Western medicine in the treatment of gallstone disease is the application of the methods of Chinese medicine.The latter came to us from time immemorial and embodied the knowledge of many generations of doctors. The priority of TCM (traditional Chinese medicine) is that it identifies and treats not only the disease itself, but also eliminates its cause, affects the entire body as a whole, heals and strengthens it.
For the treatment of gallstone disease by methods of Chinese medicine, numerous herbal complexes, herbal preparations are used. The latter are aimed at significant stabilization of the patient’s condition.It is extremely important to establish the emotional background of a person, to contribute to his maximum relaxation, to teach how to counteract stress, and, in particular, to suppress anger. Chinese medicine specialists believe that it is due to anger and anger that the correct, physiological production of bile is disrupted.
The intake of herbal teas is usually accompanied by acupuncture, which stimulates numerous metabolic processes, triggers the self-medication mechanism, and helps to stop the pain syndrome, which is extremely painful during exacerbation of gallstone disease.
One of the methods used to treat gallbladder disease is relaxing baths and foot massage. The latter have nerve endings and various kinds of acupuncture points, upon pressing on which the self-healing mechanism is activated.
The methods of Chinese medicine are designed to cure gallstone disease without surgery. These methods also help to avoid possible complications of this disease, significantly improve the quality of life.
To understand what phytocomplex is necessary for your stage of cholelithiasis, specialists of the clinic of traditional Chinese medicine “TAO” in Moscow will help. Self-medication, as well as delay in this disease, can sometimes be fatal for the patient. Therefore, it is extremely important to consult a specialist on time.
The methods of treatment of this disease by doctors of Western medicine can be divided into medication and radical, carried out by means of surgery.Conservative treatment is not always possible. Acceptance of “stone dissolving” drugs is permissible in the presence of so-called X-ray negative stones, that is, those that are not visible on X-ray. In addition, it is necessary to take the drugs for a long time (at least six months), while, unfortunately, no doctor will give a 100% guarantee for the complete dissolution of the stones.
The second treatment is to remove the inflamed gallbladder. In at least half of the cases, they resort to this radical way of getting rid of gallstone disease.Nowadays, laparoscopic technique is most often used due to the rather quick healing and low trauma of the operation. In any case, this is a surgical intervention that can be avoided by timely contacting a specialist for advice.
Treatment of gallstone disease (cholelithiasis) in Moscow | TN Clinic-examination by a gastroenterologist
Gallstone disease (cholelithiasis, cholelithiasis) is an metabolic disease that is associated with impaired metabolism of bilirubin and cholesterol, which causes the formation of stones in the gallbladder or bile ducts.In terms of prevalence, cholelithiasis ranks third after diseases of the heart and blood vessels, diabetes mellitus. Most often found in countries with highly developed economies, in people whose work is associated with stress and a sedentary lifestyle.
Causes of gallstones
The gallbladder is a reservoir for the accumulation of bile. When its physical and chemical properties are violated, conditions are created for stagnation of bile, its thickening and disruption of its entry into the intestine.As a result, a stone begins to form, which gradually grows.
The main causes of gallstone disease:
- endocrine disorders: diabetes mellitus, thyroid hormone deficiency (hypothyroidism), impaired exchange of female sex hormones, contraception, pregnancy (in this case, the ducts are poorly contracted and stagnation and thickening of bile occurs),
- stones are formed in violation of cholesterol metabolism in atherosclerosis, obesity or gout, with an increase in the level of bilirubin in hemolytic anemias, with a hereditary predisposition to cholelithiasis, as well as fasting and malnutrition, excessive consumption of fatty foods with cholesterol.
- inflammation of the bile ducts and gallbladder (cholangitis and cholecystitis),
- gallbladder infections: microbes convert bilirubin into an insoluble form that precipitates
Symptoms of gallstone disease
The manifestations of gallstone disease can be varied. For a long period of time, the disease can be latent and can be accidentally detected during an ultrasound examination of the abdominal cavity. If the stones move, inflammation and infection in the ducts join, symptoms appear that mimic an attack of cholecystitis.Manifestations will largely depend on the location of the stones, the size of each, the severity of inflammation and damage to the adjacent digestive organs.
The exit of stones from the cavity of the bladder and their movement inside the bile ducts leads to the formation of an attack of biliary colic. It is provoked by the abuse of fatty foods, physical activity, working conditions (for example, vibration when working with various mechanized tools in production), stress.
Main manifestations of biliary colic :
- sudden sharp pain in the upper abdomen, pain in the right hypochondrium, radiating to the right shoulder and right shoulder blade,
- pains accompanied by nausea and vomiting, which do not bring relief,
- dry mouth,
- itching of the skin,
- yellowing of the white membranes of the eyes and skin,
- darkening of urine, while feces become completely light or discolored.
Colic attacks can last from several minutes to several days, pains can subside on their own or after the use of pain medications.
Sometimes, with gallstone disease, the only symptom of the lesion is the so-called cholecystocardial syndrome , when pain in the gallbladder mimics heart pain, and there are simply no other manifestations.
Outside the period of exacerbation, gallstone disease may not manifest itself in any way, or the following symptoms may occur :
- recurrent dull pains after heavy food in the right side,
- alternation of diarrhea and constipation,
- discomfort after eating fatty foods,
90,015 indigestion with nausea, intestinal discomfort and flatulence.
With an attack of biliary colic, emergency care is needed with pain relief and removal of the obstacle to the outflow of bile. This is usually carried out in a hospital or at home under the strict supervision of a doctor, after an attack or without an exacerbation, the main task of treatment is to carry out measures to dissolve stones and normalize the main properties of bile, its outflow from the gallbladder.
Diagnosis and treatment of gallstone disease in TN-Clinic
Gallstone disease, due to its well-studied and widespread prevalence, is successfully treated using various methods.During an exacerbation, it is important to quickly eliminate pain and improve the patient’s condition. This is the goal that TN-Clinic doctors pursue when patients with symptoms of cholelithiasis refer to them. If necessary, various studies are carried out to clarify the diagnosis and localization of stones (blood and urine tests, ultrasound of the liver and gallbladder, abdominal x-rays, MRI, etc.). If necessary, additional consultations with a surgeon and hepatologist are carried out.
Various methods of treatment are used to treat gallstones.In the presence of small cholesterol stones, gastroenterologists use methods of dissolving them with special drugs, which are taken for 6-12 months or more. In parallel with this, it is necessary to follow a special diet that will help the outflow of bile and normalize its properties. The dietary regimen, individually selected by a specialist-nutritionist, in combination with medicinal preparations, gives a good effect.
Surgical treatment is not necessary in all cases of cholelithiasis.In addition, today minimally invasive methods are used that allow you to eliminate the problem most quickly and comfortably.
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