Multifactorial analysis of recurrence of cholecystolithiasis in Shanghai area

Abstract

AIM: To explore the risk factors of gallbladder stone recurrence.

METHODS: A multifactorial analysis was made for 1058 patients in Shanghai area whose gall-bladder stones disappeared after different kinds of nonsurgical therapy, including oral litholytic therapy, extracorporeal shock wave lithotripsy and percutaneous choledocholithotripsy. Serum level of in sulin and total bile acid were deter-mined in 122 patients.

RESULTS: After 1-8.8 years of follow-up, the re-currence rate of gallbladder stone was 11.6%, 22.4%, 29.5%, 36.4%, 39.3% and 39.7% re-spectively within 1, 2, 3, 4, 5 and over 5 years. The risk factors for the recurrence are: primary multiple gallstones (P < 0.05); family history of cholecysto lithiasis (P < 0.05); greasy food in-take (P < 0.01); low mean value of serum insulin (P < 0.01); and high mean value of total bile acid (P < 0.01).

CONCLUSION: The recurrence of cholecys-tolithiasis is related to overintake of high fat and high cholesterol food, and might also be related to low level of serum insulin.

Key Words: cholecystolithiasis/ therapy; recurrence; follow-up studies

INTRODUCTION

With the clinical application of different kinds of nonsurgical therapy, such as oral dissolution of gall-stone (ODG), extracorporeal shock wave lithotripsy (ESWL), percutaneous transhepatic gallbladder catheterization (PTGC) and contact dissolution, and percutaneous choledocholithotripsy (PCCL), the recurrence and anti-recurrence of cholecys-tolithiasis come as a problem now. The clinical value of these methods mostly depends on the recur-rence rate of this desease. Discover y of the risk factors of the recurrence of cholecystolithiasis, and in-terference procedures make it possible to lower the recurrence rate of gallstone. A multifactorial analysis of the recurrence of cholecystolithiasis in Shang-hai area was carried out by the Shanghai Gallstone Research Coordination Group.

MATERIALS AND METHODS

Research subjects

A total of 1058 patients whose gallbladder stones had disappeared after different kinds of non-surgical therapy in Shanghai area entered this study, includ-ing 454 cases after ESWL, 594 cases after PCCL and 10 cases after ODG.

Collection of follow-up materials

Formulation of follow-up table Let patients mark the items in the table and put the database into com-puter. The table includes sex, age of gallstone incip-ient occurrence, height, weight, diet hobby, symp-tom and medical treatment, related diseases (such as diabetes mellitus, coronary heart disease, liver dis-ease), family history of gallstone, size and number of gallstone, recurrence and recurrence time of cholecystolithiasis.

Examination of patients One hundred and twenty-two patients were randomly selected from gallstone patients. Stone recurrence was found in 48 patients and non recurrence in 74. Venous blood of 5ml was drawn before breakfast in the morning. After standing still for half an hour, serum was sealed af-ter centrifugation. Serum insulin level was deter-mined with Coat-Acount insulin kit, and serum total bile acid (TBA) level by Ausbile Auto kit at the same time. Ultrasound examination was performed to evaluate the condition of gallbladder (length, width, height, stones), the degree of the liver lipid infiltration and the condition of the common bile duct (CBD), about 1 h after greasy food. Ultra- som ography was repeated to reveal the width, length and height of the constricted gallbladder. With the formula V = (3.1416 × L × H × W)/ 6, the volume of gallbladder when starve or after diet, and the contraction ratio of the gallbladder volume were calculated.

Statistical method

(1) There were 792 pieces of subjective materials and 122 objective materials when database was set up. (2) The follow-up rate, recurrence rate and loss to follow-up rate of patients after ESWL, PCCL and ODG were calculated. (3) To find out the statistical difference between the recurrence and non-recurrence groups (Table 1, Table 2). (4) To find out the statisti-cal difference between the multiple and solitary stones groups(Table 3, Table 4). (5) With the help from Epidemiology Teaching and Research group of Shanghai Medical University, the Epi-info Version 5.01a software was used to process the data.

Table 1 Difference between recurrence and non-recurrence groups.

	Odds ratio	M-H Chi square	P value
Incipient stone	1.52	6.43	< 0.05
Sex proportion	0.91	0.31	0.58
Diet hobby	0.66	6.02	< 0.05
Related disease	0.85	0.87	0.35
Clinical symptom	12.51	190.97	< 0.01
Medical treatment	1.70	9.03	< 0.01
Family history	1.55	4.54	< 0.05
Mean thickness of gallbladder wall	1.95	2.75	0.10
Adipose infiltration of liver	1.01	0.00	0.98

Table 2 Difference between recurrence and non-recurrence groups.

	Recurrence	Non-recurrence	F test	P value
Mean age	43.85 ± 11.3	43.15 ± 11.9	0.534	0.528
Mean weight/height	0.387 ± 0.05	0.380 ± 0.05	2.701	0.097
Mean contraction ratio of gallbladder	0.500 ± 0.264	0.522 ± 0.277	0.196	0.663
Mean value of serum insulin	0.611 ± 0.320	0.753 ± 0.261	7.289	< 0.01
Mean value of serum TBA	5.963 ± 1.883	5.00 ± 1.955	7.545	< 0.01

Table 3 Difference between multiple stones and solitary stone groups.

	Odds ratio	M-H Chi square	P value
Recurrence	1.52	6.43	< 0.05
Sex proportion	1.08	0.21	0.65
Diet hobby	1.26	2.10	0.15
Related disease	0.95	0.09	0.76
Medical treatment	1.42	4.35	< 0.05
Clinical symptom	1.21	1.38	0.24
Family history	1.08	0.13	0.72
Mean thickness of \gallbladder wall	0.55	2.15	0.14
Adipose infiltration of liver	0.91	0.05	0.83

*Because of abnormal distribution of the value of ser um insulin, all data were changed into log value.

Table 4 Difference between multiple stones and solitary stone groups.

	Multiple stones	Solitary stone	F test	P value
Mean age	45.52 ± 12.02	43.98 ± 11.47	2.438	0.115
Mean weight/height	0.382 ± 0.048	0.383 ± 0.052	0.108	0.742
Mean contraction ratio of gallbladder	0.538 ± 0.251	0.50 ± 0.28	0.528	0.524
Mean value of serum insulin*	0.586 ± 0.331	0.739 ± 0.266	7.526	< 0.01
Mean value of serum TBA	5.590 ± 1.788	5.349 ± 2.063	0.391	0.540

*Because of abnormal distribution of the value of ser um insulin, all data were changed into log value.

RESULTS

Total follow-up rate and stone recurrence rate

From January 1988 to October 1995,there were 1058 patients whose gallbladder stones had disappeared after different kinds of non-surgical therapy. Seven hundred and ninety-two patients were followed up for 1-8.8 years with a rate of 74.8%. The stone recurrence rate was 11.6%, 22.4%, 29.5%, 36.4%, 39.3% and 39.7% respectively within 1, 2, 3, 4, 5 and over 5 years. The total recurrence rate was 30.8%.

Follow-up rate and recurrence rate after EWSL

Among 454 patients treated with ESWL, 413 pa-tients are followed up, with a rate of 91.0%. There were 285 cases with non- recurrence and 128 with re-currence (17 were treated surgically, the others re-ceived conserrative treatment). Fourty-one patients were lost to follow-up. The recurrence rate of gall-stone was 11.9%, 20.2%, 34.8%, 35.7%, 37.2% respectively within 1, 2, 4, 5 and over 5 years. The total recurrence rate was 31.0%.

Follow-up and stone recurrence rate after PCCL

Among 594 patients treated with PCCL, 370 were followed up, the follow-up rate being 62.3%. There were 262 cases with non-recurrence and 108 with recurrence. Seven of them were treated surgi-cally, the others received consecutive treatment, and 224 patients were lost to follow-up. The recur-rence rate of gallstone was 8.8%, 22.4%, 29.5%, 36.7%, 47.4% respectively within 1, 2, 3, 4 and 5 years. The total recurrence rate was 29.9%.

Follow-up and stone recurrence rate after ODG

Nine of 10 patients treated with ODG were followed up. The stone recurrence occurred in 8 patients. One case was lost to follow-up. Average follow-up length was 5 years and 4 months. The stone recur-rence rate was 88.9%.

DISCUSSION

Recurrence rate of gallbladder stone

According to the literature, the recurrence rate of cholecystolithiasis is about 7%-11.8% after ODG, ESWL, PTGC and PCCL treatment[1-3]. In this study, the 1-year stone recurrence rate was 8.8%-11.9%, similar to the literature. It has been report-ed that the stone recurrence rate increases by about 10% each year, and by the fifth year it reaches 50%. After 5 years, a plateau with no further re-currence is usually seen[4]. The recurrence rates after ESWL, PCCL and ODG in the fifth year were 35.7%, 47.7% and 88.9% in this study. The lower gallstone recurrence rate after ESWL was probably related to strict selection of cases and higher ratio of solitary stone. More research should be done about the relatively high recurrence rate of gallstone, otherwise the non-surgical therapy of gallbladder stone will lose their clinical application value.

Risk factors for recurrence of gallstone

The occurrence and the recurrence of the gallblad-der stone probably have similar physiopathologic mechanism. It is related to many factors such as sex, age, weight index, diet hobby, labor strength, endocrine and metabolism, the size, number and character of the gallstone. In our study, no differ-ence exists between recurrence and non-recurrence groups on such items as sex, average age, average weight/height, thickness of gallbladder wall, aver-age ratio of gallbladder const riction, average degree of liver lipid infiltration and related diseases (dia-betes, coronary heart disease, etc). Some items have significant difference between the two groups. The following in the recurrence group were signifi-cantly different from the non-recurrence groups: more clinical symptoms, more patients receiving medical treatment, low mean value of serum insulin and high mean value of serum TBA. The group with multiple gallstones, family history of gallstone and intake of greasy food has a higher recurrence rate. All of these differences are sta tistically significant (P < 0.05).

Multiple gallstones seem to recur more often than solitary stone probably because (1) most of soli-tary stones are cholesterol caculus, and lithotripsy and litholysis are effective treatment. The propor-tion of combined caculus is quiet higher in multiple stones. The insoluble bile sludge after lithotripsy and dissolution might become the nuclear of the re-currence stone. (2) Solitary stone is easier to be hit during the lithotripsy. The treatment takes less time and the broken stones are easier to be removed. There were less fine stones left and less injury to the gallbladder, while results were different for multiple stones.

Patients with family histories of gallstone had higher recurrence rates probaly because of similar component and hobby of the diet, and hereditary factors.

Most literature reports that the serum insulin level in patients with gallstone is high[5]. The mech-anism might be that insulin activates the cholesterol synthesis reductase of liver, causing the increase of cholesterol synthesis and accelerating gallstone for-mation. Some authors have found no statistical dif-ference in serum insulin level between diabetes pa-tients with or without gallstone. In our cases, the mean serum insulin level in stone recurrence and multiple stone groups is significantly lower than in non-recurrence and solitary stone gro ups. When in-sulin is deficient, most glucose produced by glyco-neogenesis was consumed, and the amount of pyru-vate used to synthesize acetyl coenzyme A decreased. Most of acetyl coenzyme A is derived from lipose. A great quantit y of acetyl coenzyme A provides the material for cholesterol synthesis. At the mean time, the deficiency of insulin reduces the capability of cholesterol utilization of liver, resulting in the hypercholesterolemia. This abnormal metabolism of lipid is often related to the formation of gallstone.

It has been proven that food is closely related to gallbladder stone. Epidemiological investigation al-so indicated that the high morbidity of cholecys-tolithiasis is correlated with the intake of low fiber and refined food in some developed countries. With the changing of the food components and reduction of the labor intensity, the morbidity of cholecys-tolithiasis is rising progressively.

Content and hobby of diet, over intake and low consumption of high fat and cholesterol food, rela-tive deficiency of serum insulin, abnormal metabolism of glucose and lipose, liver disease and dysfunction of gallbladder might be all related to the formation of gallstone. Effective propaganda and e-ducation, reasonable diet structure, constant phy-sical exercise and a certain amount of labor might help control the occurrence and recurrence of chole-cystothiasis.