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胆のう結石症

著者: 田妻進 広島大学病院 総合内科・総合診療科

監修: 田妻進 広島大学病院 総合内科・総合診療科

著者校正/監修レビュー済:2020/03/26
参考ガイドライン:
  1. 日本消化器病学会:胆石症診療ガイドライン2016(改訂第2版)
  1. 腹腔鏡下胆嚢摘出術における術中胆道造影の手技と意義について
  1. 腹腔鏡下胆嚢摘出術における開腹移行例の検討
患者向け説明資料

概要・推奨   

  1. 無症状胆石は原則として経過観察とする。ただし、結石多数例、胆のう造影陰性例、癌を否定できない壁肥厚例、超音波による胆のう内評価が十分できない例では患者と相談のうえ施設環境を考慮して手術適応を決定する(推奨度1)[1]
  1. 有症状の胆のう結石症に対する治療の基本は胆のう摘出術であり、腹腔鏡下胆のう摘出術が第1選択である。しかし、高度炎症例、胆のう癌の疑いのある症例、妊娠例では合併症を考慮して速やかに開腹術に移行すべきである(推奨度1)[1]
  1. 石灰化のないコレステロール胆石で胆のう内に浮遊する小結石は、胆のう機能が正常であれば胆汁酸製剤による経口溶解療法が有効であり、胆石が残存しても無症状化することが少なくない(推奨度2)[1]
  1. 石灰化のない孤立性純コレステロール石は体外衝撃波砕石術(ESWL)が有効であるが、胆のう機能が正常であることが必要である(推奨度2)[1]
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
田妻進 : 特に申告事項無し[2021年]
監修:田妻進 : 特に申告事項無し[2021年]

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文献 

著者: Kazuhiko Tsunoda, Yoshio Shirai, Katsuyoshi Hatakeyama
雑誌名: Hepatogastroenterology. 2004 Sep-Oct;51(59):1271-4.
Abstract/Text BACKGROUND/AIMS: Gallstone composition has changed over the past decades in East Asian countries with a prominent increase in the prevalence of cholesterol gallstones. This trend is possibly due to the westernization of dietary habits. This study was undertaken to delineate the changing trends in gallstone composition in Japan since the 1920s and to assess dietary influences on gallstone composition.
METHODOLOGY: Between 1971 and 1999, 1264 Japanese patients underwent cholecystectomy for gallstone disease in Niigata University Medical Hospital. Gallbladder stones retrieved from each patient were classified into four types by gross inspection of the cut surface and infrared spectroscopy: cholesterol stone, black pigment stone, brown pigment stone, and other stones. The literature was reviewed to find both changing trends in gallstone composition before 1971 and dietary changes since 1950 in Japan.
RESULTS: The prevalence of cholesterol gallstones among Japanese patients undergoing cholecystectomy increased steadily until the 1970s and declined thereafter (P<0.001). Among dietary factors, only per capita daily total calorie intake strongly correlated with cholesterol gallstone prevalence (r=0.93, P=0.02).
CONCLUSIONS: During the 20th century, the prevalence of cholesterol gallstones in the Japanese population increased steadily until the 1970s declining thereafter. Per capita daily total calorie intake appears to be the predominant dietary factor affecting cholesterol gallstone prevalence.

PMID 15362730  Hepatogastroenterology. 2004 Sep-Oct;51(59):1271-4.
著者: F Berr, M Mayer, M F Sackmann, T Sauerbruch, J Holl, G Paumgartner
雑誌名: Gastroenterology. 1994 Jan;106(1):215-24.
Abstract/Text BACKGROUND/AIMS: Supersaturation of bile with cholesterol, rapid nucleation of cholesterol crystals, and/or incomplete emptying of the gallbladder are believed to be required for gallstone formation. The importance of these factors for the recurrence of gallbladder stones was studied.
METHODS: Twenty patients, untreated after successful shock wave therapy, were studied in a matched case-control design for bile acid turnover, composition of duodenal bile, and gallbladder emptying. In 10 of them, gallstones had recurred within 12 +/- 2 months (X +/- SEM); the other 10 had been free of stones since 22 +/- 3 months.
RESULTS: In each group, duodenal bile was supersaturated with cholesterol in 8 of 10 patients and showed abnormal nucleation time of cholesterol crystals in half of the patients. Patients with recurrent stones had smaller pool sizes of cholic acid (-43%) and enhanced conversion of cholic acid to deoxycholic acid. The odds for stone recurrence were ninefold increased in the presence of excessive deoxycholic acid (exceeding cholic acid) in the bile acid pool or incomplete emptying of the gallbladder (residual volume > 5 mL) in response to cholecystokinin. The odds ratio was over 20-fold increased when incomplete emptying of the gallbladder coincided with supersaturated bile or with excessive deoxycholic acid.
CONCLUSIONS: Enhanced conversion of cholic acid to deoxycholic acid and incomplete emptying of the gallbladder could be important cofactors for the recurrence of gallstones.

PMID 8276184  Gastroenterology. 1994 Jan;106(1):215-24.
著者: K W Heaton, P M Emmett, C L Symes, F E Braddon
雑誌名: Lancet. 1993 Jan 2;341(8836):8-10.
Abstract/Text Many cases of gallstones can be explained in terms of the established risk factors, especially obesity. However, gallstones develop in some women who are not obese, and the causes are unknown. Biochemical studies have shown that slow intestinal transit is associated with lithogenic bile. We have tested the hypothesis that intestinal transit is abnormally slow in normal-weight women with gallstones. In a population survey, 1058 women aged 25-69 years, registered with general practitioners in Bristol, UK, underwent cholecystosonography. Gallstones were identified in 48 women, of whom 15 were of normal weight (body mass index < or = 25 kg/m2). These women and age-matched controls with healthy gallbladders then underwent measurement of whole-gut transit time (WGTT); the measurement was done directly when possible, or calculated from records of three defaecations. The mean WGTT was significantly longer in the women with gallstones than in the controls (82 vs 63 h; mean difference 19, 95% CI 2-37 h). Stool output was also lower in the women with gallstones (74 [SD 54] vs 141 [56] g per 24 h, p = 0.015). There was no significant difference between cases and controls in body mass index, waist-hip circumference ratio, parity, plasma triglyceride concentration, or alcohol intake. Normal-weight women with gallstones tend to have slow intestinal transit and this feature could explain why they have gallstones.

PMID 8093323  Lancet. 1993 Jan 2;341(8836):8-10.
著者: K Einarsson, K Hellström, M Kallner
雑誌名: Lancet. 1975 Mar 1;1(7905):484-7.
Abstract/Text The occurrence of gallbladder disease (G.B.D.) (cholelithiasis, cholecystitis, cholecystectomy) was examined in patients consecutively admitted beccause of hyperlipoproteinaemia types IIa and IV. Altogether 37 of the 52 patients with the type IIa pattern were women, whereas 56 of the 75 subjects with hyperlipoproteinaemia type IV were men. The overall incidence of G.B.D. in the group with the type IIa was 13 per cent in the males and 22 per cent in the females; the corresponding figures in type IV were 41 per cent and 68 per cent, respectively. The findings in the major age-group (40-59 years) were compared with those from three necropsy series covering subjects of the same age. The incidence of G.B.D. was then found to be normal in type IIa but abnormally high in type IV. Patients with and without G.B.D. did not differ with regard to body-weight or glucose tolerance.

PMID 46958  Lancet. 1975 Mar 1;1(7905):484-7.
著者: R L Gebhard, W F Prigge, H J Ansel, L Schlasner, S R Ketover, D Sande, K Holtmeier, F J Peterson
雑誌名: Hepatology. 1996 Sep;24(3):544-8. doi: 10.1002/hep.510240313.
Abstract/Text Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very-low-calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis. Obese subjects were randomized to one of two low-calorie liquid diets for rapid weight loss: a 520-kcal diet with less than 2 g fat/d, and a 900-kcal diet with 30 g fat/d (including one 10-g fat meal to stimulate maximal gallbladder emptying). Bile and blood lipids, saturation index, leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity, and ultrasonographic gallbladder emptying were measured repeatedly during dietary treatment. Both diets produced comparable weight loss of 22%. Bile cholesterol saturation index increased during both diets (26%), but fell to 15% below prediet level after weight loss. Compared with subjects' maximal gallbladder emptying fraction of 66%, the 520-kcal diet provided poor gallbladder emptying (35%), whereas the 10-g fat meal of the 900-kcal diet provided maximal emptying. Gallstones developed in four of six 520-kcal subjects and none of seven 900-kcal subjects (P = .021), an unanticipated difference that resulted in premature study termination for ethical reasons. Blood lipids and HMG CoA reductase activity in mononuclear leukocytes fell at week 8 during both diets, but recovered while weight was still being lost. The findings suggest that gallstone risk during rapid weight loss may be reduced by maintenance of gallbladder emptying with a small amount of dietary fat. Ultimately, weight loss reduced bile cholesterol saturation and improved highdensity lipoprotein (HDL) levels.

PMID 8781321  Hepatology. 1996 Sep;24(3):544-8. doi: 10.1002/hep.5102・・・
著者: M F Leitzmann, E B Rimm, W C Willett, D Spiegelman, F Grodstein, M J Stampfer, G A Colditz, E Giovannucci
雑誌名: N Engl J Med. 1999 Sep 9;341(11):777-84. doi: 10.1056/NEJM199909093411101.
Abstract/Text BACKGROUND: Physical activity may be an important determinant of the risk of gallstone disease in women, both independently and as a result of its role in maintaining body weight.
METHODS: We prospectively studied recreational physical activity (such as jogging, running, and bicycling) and sedentary behavior (such as spending hours watching television) in relation to the risk of cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 60,290 women who were 40 to 65 years of age in 1986 and had no history of gallstone disease. As part of the Nurses' Health Study, the women reported on questionnaires mailed to them every two years both their activity level and whether they had undergone cholecystectomy. During a 10-year follow-up period (1986 to 1996), 3257 cases of cholecystectomy were documented.
RESULTS: Recreational physical activity was inversely related to the risk of cholecystectomy. The multivariate relative risk for women in the highest as compared with the lowest quintile of physical activity was 0.69 (95 percent confidence interval, 0.61 to 0.78). In contrast, sedentary behavior was independently related to an increased risk of cholecystectomy. As compared with women who spent less than 6 hours per week sitting while at work or driving, women who spent 41 to 60 hours per week sitting had a multivariate relative risk of 1.42 (95 percent confidence interval, 1.06 to 1.89), and women who spent more than 60 hours per week sitting while at work or driving had a multivariate relative risk of 2.32 (95 percent confidence interval, 1.26 to 4.26). These associations persisted after we controlled for body weight and weight change.
CONCLUSIONS: In women, recreational physical activity is associated with a decreased risk of cholecystectomy. The association is independent of other risk factors for gallstone disease, such as obesity and recent weight loss.

PMID 10477775  N Engl J Med. 1999 Sep 9;341(11):777-84. doi: 10.1056/N・・・
著者: W Kratzer, R A Mason, V Kächele
雑誌名: J Clin Ultrasound. 1999 Jan;27(1):1-7.
Abstract/Text The use of diagnostic sonography allows determination of the prevalence of gallstones in a representative sample of the general population. The objective of this article is to review the reports of sonographically based studies of gallstone prevalence in the world literature. All available published epidemiologic studies on the prevalence of cholecystolithiasis as determined by diagnostic sonography are summarized. The sonographically based studies published to date confirm that there are significant regional differences in the prevalence of gallstones. Certain risk factors, notably age and heredity, are present worldwide.

PMID 9888092  J Clin Ultrasound. 1999 Jan;27(1):1-7.
著者: G D Friedman, W B Kannel, T R Dawber
雑誌名: J Chronic Dis. 1966 Mar;19(3):273-92.
Abstract/Text
PMID 5910970  J Chronic Dis. 1966 Mar;19(3):273-92.
著者: Lisa D Mills, Trevor Mills, Barbara Foster
雑誌名: South Med J. 2005 Feb;98(2):155-61. doi: 10.1097/01.SMJ.0000129927.88863.65.
Abstract/Text BACKGROUND: The purpose of this study was to determine how laboratory values and physical examination findings correlate with ultrasound findings in the setting of right upper quadrant pain.
METHODS: Patients undergoing emergent ultrasound for the evaluation of biliary disease between November 1999 and April 2000 were included. Physical examination findings, laboratory data, and ultrasound results were variables. Logistic regression was performed. Ultrasound diagnosis of acute cholecystitis, cholelithiasis, and normal biliary tract were end points. One hundred seventy-seven patients were enrolled.
RESULTS: Forty-two percent were diagnosed with acute cholecystitis, 30.5% with cholelithiasis, and 27.1% with normal biliary tract. Alkaline phosphatase, Murphy sign, white blood cell count, and total bilirubin were statistically significant predictors of acute cholecystitis. A Murphy sign was defined as arrest of inspiration with pressure over the right upper quadrant.
CONCLUSIONS: The findings from this study allow clinicians to apply objective significance to laboratory data and physical examination findings in patients with suspected gallstone disease. The data can be applied to create a predictive model.

PMID 15759944  South Med J. 2005 Feb;98(2):155-61. doi: 10.1097/01.SMJ・・・
著者: P A Aldea, J P Meehan, G Sternbach
雑誌名: J Emerg Med. 1986;4(1):57-63.
Abstract/Text The history of the acute abdomen describes a shift from emphasis on prognosis to treatment through correlation of clinical and pathological findings. John B. Murphy was an acclaimed leader of American surgery whose name is associated with several diagnostic maneuvers used in the evaluation of the acute abdomen. These include deep-grip palpation used in examination for suspected biliary disease.

PMID 3525662  J Emerg Med. 1986;4(1):57-63.
著者: J A Barakos, P W Ralls, S A Lapin, M B Johnson, D R Radin, P M Colletti, W D Boswell, J M Halls
雑誌名: Radiology. 1987 Feb;162(2):415-8. doi: 10.1148/radiology.162.2.3797654.
Abstract/Text Computed tomography (CT) is often the first imaging modality used in the diagnosis of patients with suspected abdominal disease. While it is known that early generation CT scanners often detect gallstones, the detection rate of newer equipment is not widely known. Abdominal CT scans of 226 patients who had undergone ultrasonographic (US) studies of the gallbladder were reviewed in a blinded study to determine the accuracy of state-of-the-art CT scanning equipment in the detection of cholelithiasis. Of 110 patients with US or surgical evidence of cholelithiasis, gallstones were demonstrated on CT images of 87 (79.1% sensitivity). Overall accuracy was 89.8%, while specificity was 100%. On CT images stones could appear densely (48.3%) or slightly (11.5%) calcified, as an area with a rim of increased density (21.8%), as an area of soft-tissue density (14.9%), or as an area of low density (3.4%). Stone size, stone density, section incrementation, and the pericholecystic anatomy affected the detection rate. Understanding the spectrum of findings and the other factors involved can optimize success of diagnosis of cholelithiasis on the basis of CT examinations.

PMID 3797654  Radiology. 1987 Feb;162(2):415-8. doi: 10.1148/radiolog・・・
著者: L E Hammarström, T Holmin, H Stridbeck, I Ihse
雑誌名: J Am Coll Surg. 1996 May;182(5):408-16.
Abstract/Text BACKGROUND: There has been a resurgence of interest in recent years in preoperative infusion cholangiography (PIC). The role of routine PIC compared to routine intraoperative cholangiography (IOC) has not been clearly defined.
STUDY DESIGN: In our department between 1985 and 1991, 1,042 of 1,576 consecutive patients with biliary calculous disease had elective cholecystectomy: 694 patients were prospectively scheduled for PIC, and 348 patients were randomly allocated to IOC. The patients in the PIC and IOC groups were similar with regard to age, history of biliopancreatic complications, and laboratory findings. The cost of PIC in Sweden is nearly five times greater than the cost of IOC.
RESULTS: Satisfactory opacification of the biliary system was obtained in 90.1 and 96.8 percent of patients who underwent PIC and IOC, respectively. Preoperative infusion cholangiography required support by IOC in 19.5 percent of patients. There were no statistically significant differences between the PIC and IOC groups with regard to the incidence (7 percent in both groups) of or positive predictive value (68 and 80 percent, respectively) for bile duct stones, rate of retained stones (6 and 20 percent, respectively), intraoperative (5.6 and 6.3 percent, respectively) or postoperative (13.3 and 15.9 percent, respectively) morbidity, or incidence of bile duct anomalies (0.9 and 0.3 percent, respectively). Median operative time was longer in patients with (95 minutes) compared to those without (75 minutes) IOC (p < 0.001). More postoperative complications occurred after bile duct exploration (26 of 75 patients) compared to cholecystectomy alone (114 of 917 patients, p < 0.001). The 30-day mortality was zero. Minor bile duct injuries occurred in two patients (0.2 percent) at cholecystectomy, (one with and one without bile duct exploration). In no patient was the cholangiographic finding of a biliary anomaly crucial for the safe execution of cholecystectomy.
CONCLUSIONS: In our study, PIC and IOC were comparable, but routine use of either method did not promote the safety of cholecystectomy and thus their routine use is not warranted. The shorter operative time and preoperative identification of common bile duct (CBD) stones provided by PIC might favor this examination when applied selectively in patients with increased risk of having CBD stones. However, this potential advantage is offset by the need for PIC to be supported by IOC in approximately 20 percent of patients. Also, the cost of PIC is greater than the cost of IOC.

PMID 8620276  J Am Coll Surg. 1996 May;182(5):408-16.
著者: G D Friedman
雑誌名: Am J Surg. 1993 Apr;165(4):399-404.
Abstract/Text Review of the sparse literature on the prognosis of asymptomatic and mildly symptomatic gallstones reveals a diversity of methods, definitions, and groups of patients studied, which makes it difficult to draw conclusions. It appears that serious symptoms and complications develop in about 1% to 2% of patients with asymptomatic gallstones annually, with fewer complications developing in later years than in years soon after gallstones are discovered. In patients with stones with mild symptoms, rates of the development of complications are perhaps a little higher, about 1% to 3% per year. In patients who are initially mildly symptomatic, cholecystectomy for severe symptoms probably is undertaken in 6% to 8% per year in the early years, decreasing with longer follow-up. Other than symptoms, no factors related to prognosis have been established. Acute cholecystitis is the most common severe complication of gallstones. Based on follow-up studies, obstructive jaundice, cholangitis, pancreatitis, and cancer of the gallbladder are infrequent complications. Risk of subsequent colon cancer should not ordinarily be a factor when cholecystectomy is considered. Analyses of cost-effectiveness have not demonstrated substantial differences in life expectancy between patients with asymptomatic gallstones who undergo immediate open cholecystectomy compared with watchful waiting.

PMID 8480871  Am J Surg. 1993 Apr;165(4):399-404.
著者: E A Akriviadis, M Hatzigavriel, D Kapnias, J Kirimlidis, A Markantas, A Garyfallos
雑誌名: Gastroenterology. 1997 Jul;113(1):225-31.
Abstract/Text BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used to relieve biliary colic. Follow-up was limited in previous studies, and the role of NSAIDs in the natural history of biliary colic has not been clarified. The purpose of this study was to evaluate the efficacy of diclofenac, a potent NSAID, in the the immediate symptomatic relief of biliary colic and the prevention of cholelithiasis-related complications.
METHODS: Fifty-three patients with cholelithiasis and biliary colic were enrolled in this randomized, double-blind, placebo-controlled study. They received a single 75-mg (3 mL) intramuscular injection of diclofenac (n = 27) or similarly administered 3 mL of saline (n = 26). All patients were followed up for at least 3 days. The effect of either treatment was assessed by changes in the severity of pain and the development of cholelithiasis-related complications.
RESULTS: Complete relief of pain was obtained in 21 diclofenac and in 7 placebo patients; progression to acute cholecystitis was observed in 4 and 11 patients, respectively. Fewer overall complications were observed in the diclofenac group.
CONCLUSIONS: In patients with cholelithiasis who present with biliary colic, a single 75-mg intramuscular dose of diclofenac can provide satisfactory pain relief and decrease substantially the rate of progression to acute cholecystitis.

PMID 9207282  Gastroenterology. 1997 Jul;113(1):225-31.
著者: Iván Serra, Masaharu Yamamoto, Alfonso Calvo, Gabriel Cavada, Sergio Báez, Kazuo Endoh, Hidenobu Watanabe, Kazuo Tajima
雑誌名: Int J Cancer. 2002 Dec 1;102(4):407-11. doi: 10.1002/ijc.10716.
Abstract/Text We explored the risk factors for gallbladder cancer and explanations for its sharp and constant incidence increase in Chile since the 1970s. We compared 114 consecutive patients with verified gallbladder cancer, diagnosed 1992-1995, to 114 matched hospital patients with gallstones, using conditional logistic regression analysis. Low education showed a nonsignificant positive relationship with gallbladder cancer [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.8-6.2], and low socioeconomic level showed a significant relationship (OR = 5.0, 95% CI 1.5-17.3). A very long history of gallstone disease was significantly more prevalent among cases (OR = 11.0, 95% CI 1.4-85.2). Significant red chili pepper consumption was observed in gallbladder cancer patients (OR = 2.9, 95% CI 1.6-5.2). Low intake of both fresh fruit and sugar as soft drinks was associated with gallbladder cancer, with ORs of 6.4 (95% CI 1.4-30.3) and 3.6 (95% CI 1.3-10.1), respectively. Multivariate analysis kept only a very low socioeconomic status and red chili pepper consumption as significant independent risk factors for gallbladder cancer, ORs of 6.3 (95% CI 1.7-23.0) and 3.2 (95% CI 1.7-5.9). Longstanding gallstone cases were removed from the multivariate model because all were in the low and very low socioeconomic groups, reinforcing the association. Patients with gallbladder cancer differed from matched controls by exhibiting lower socioeconomic levels, having a much longer history of gallstone disease and presenting a dietary pattern characterized by high red chili pepper consumption and low fresh fruit intake.

Copyright 2002 Wiley-Liss, Inc.
PMID 12402311  Int J Cancer. 2002 Dec 1;102(4):407-11. doi: 10.1002/ij・・・
著者: A B Lowenfels, A M Walker, D P Althaus, G Townsend, L Domellöf
雑誌名: Int J Epidemiol. 1989 Mar;18(1):50-4.
Abstract/Text To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7-2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (greater than or equal to 3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones greater than or equal to 3 cm was 9.2 compared with subjects with stones less than 1 cm. (95% confidence interval: 2.3-37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (greater than or equal to 3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.

PMID 2722383  Int J Epidemiol. 1989 Mar;18(1):50-4.
著者: A K Diehl
雑誌名: JAMA. 1983 Nov 4;250(17):2323-6.
Abstract/Text Gallstones are a major risk factor for gallbladder cancer, but few persons with stones experience development of tumors. To examine this relationship, a case-control study was performed. Each of 81 cancer cases was matched for age, sex, hospital, and admission date with two controls, one with benign gallbladder disease and one with a nongallbladder diagnosis. Persons with large gallstones were found to be at increased risk for cancer. For those with stone diameters of 2.0 to 2.9 cm, the odds ratio (v stone size less than 1 cm) was 2.4; for stones 3 cm or larger, the ratio was 10.1. This association of large gallstones with cancer was not hypothesized before data analysis and should be replicated in other settings before being accepted. If confirmed, however, this finding might have implications for the management of silent gallstones.

PMID 6632129  JAMA. 1983 Nov 4;250(17):2323-6.
著者: A Csendes, M Becerra, J Rojas, E Medina
雑誌名: J Gastrointest Surg. 2000 Sep-Oct;4(5):481-5.
Abstract/Text The development of gallbladder carcinoma has been correlated with the presence of a single large gallstone in two retrospective studies. The objective of the present study was to determine the number and size of gallstones in patients with gallbladder carcinoma compared to asymptomatic and symptomatic female patients with gallstones. The following three groups of patients were included in this prospective trial: (A) 78 asymptomatic patients with gallstones; (B) 365 symptomatic patients with gallstones; and (C) 149 patients with gallbladder carcinoma. At the end of the operation, the resected gallbladder was opened and the number of stones counted. The maximum size of the stones was determined using calipers. Patients with gallbladder carcinoma were significantly older than patients in the other two groups (P <0.001). In the group with asymptomatic gallstones, there were significantly more patients with one single stone, whereas in the group with gallbladder carcinoma there were significantly more patients with multiple stones (more than 11; P <0.01). Patients with gallbladder carcinoma had significantly larger stones, regardless of the number of stones present (P <0.001). We postulate that the increase in the number and size of the stones among patients with gallbladder carcinoma could simply be an effect of aging or it could be a reflection of the long-term presence of stones in the gallbladder rather than some particular chemical or physical influence.

PMID 11077323  J Gastrointest Surg. 2000 Sep-Oct;4(5):481-5.
著者: Iván Roa, Gilda Ibacache, Juan Roa, Juan Araya, Xabier de Aretxabala, Sergio Muñoz
雑誌名: J Surg Oncol. 2006 Jun 15;93(8):624-8. doi: 10.1002/jso.20528.
Abstract/Text BACKGROUND: Gallstones are considered the most important risk factor for gallbladder cancer.
AIM: To identify differences in the number, weight, volume, and density of gallstones associated with chronic cholecystitis (CC), gallbladder dysplasia (GD), and gallbladder cancer (GBC).
METHODS: A total of 125 cases were selected, of which 93 had gallstones associated with GBC and 31 had gallstones associated with GD. The controls were those with CC, matched by sex and age. The number, weight, volume, and density of these gallstones were examined in order to determine differences and relative cancer risk.
RESULTS: Number: Multiple gallstones were present in over 76% of cases (GBC and GD) and controls (P = ns). The average number of multiple stones was 21 in GBC versus 14 in controls (P < 0.01). Weight: The average weight of the gallstones was 9.6 g in GBC versus 6.0 g in controls (P = 0.0004). The average weight in multiple stones over 10 g had strong association with GBC (P = 0.0006). Volume: The average volume was 11.7 and 6.48 ml in GBC and controls (P = 0.0002). Average volumes of 6, 8, and 10 ml had a relative cancer risk of 5, 7, and 11 times, respectively. Size: No differences were shown between GBC, GD, and controls.
CONCLUSIONS: The volume of gallstones associated with other risk factors of GBC may be helpful in prioritizing cholecystectomies in symptomatic patients.

Copyright 2006 Wiley-Liss, Inc.
PMID 16724353  J Surg Oncol. 2006 Jun 15;93(8):624-8. doi: 10.1002/jso・・・
著者: D F Ransohoff, W A Gracie
雑誌名: Ann Intern Med. 1993 Oct 1;119(7 Pt 1):606-19.
Abstract/Text PURPOSE: To critically review the risks and benefits of therapy for asymptomatic and symptomatic persons with gallstones who are considering therapy to prevent future episodes of biliary pain or complications including acute cholecystitis, pancreatitis, or gallbladder cancer.
DATA SOURCES: Review of English-language literature regarding the natural history of persons with gallstones and the operative mortality rates for open cholecystectomy and laparoscopic cholecystectomy. Mathematical simulation modeling was used to derive estimates of lifetime risks for gallstone-related mortality and for life expectancy, for prophylactic cholecystectomy and expectant management, for men and women of different ages.
RESULTS: For persons with asymptomatic gallstones, natural history is so benign that treatment is generally not recommended. For persons with symptomatic gallstones, (that is, that have caused an episode of biliary pain), the rate for subsequent pain is high so that many persons probably choose cholecystectomy to avoid pain; however, about 30% of persons who have had pain do not have further episodes of pain. The expected loss of life for persons with symptomatic stones managed expectantly is roughly several months, on average, and may not be considered high enough in itself to warrant therapy. Although laparoscopic cholecystectomy has become popular with patients and physicians, its safety is yet unknown compared with open cholecystectomy.
CONCLUSION: Prophylactic cholecystectomy should be recommended for most persons with symptomatic gallstones unless the person wants to try a period of watchful waiting to see if pain recurs. Nonsurgical therapy may be suitable for persons with high operative risk. For persons with asymptomatic gallstones, watchful waiting is the best course.

PMID 8363172  Ann Intern Med. 1993 Oct 1;119(7 Pt 1):606-19.
著者: I Halldestam, E-L Enell, E Kullman, K Borch
雑誌名: Br J Surg. 2004 Jun;91(6):734-8. doi: 10.1002/bjs.4547.
Abstract/Text BACKGROUND: Gallbladder stones are common in the developed world. Complications of gallstones contribute substantially to healthcare costs and may be life threatening. The identification of individuals likely to develop complications would be of benefit in clinical practice as elective cholecystectomy could then be performed.
METHODS: Seven hundred and thirty-nine subjects aged 35-85 years from the general population were screened for gallbladder problems by ultrasonography and questionnaire assessment of putative risk factors and digestive symptoms. Gallstones, cholesterolosis or sludge in the gallbladder were diagnosed in 123 (16.3 per cent) of 739 subjects, 120 of whom were followed for a median of 87 (range 3-146) months to May 2003 or until treatment was required.
RESULTS: Fourteen patients were admitted to hospital and treated for gallstone-related complications or symptoms. The cumulative risk of being treated during the first 5 years after detection of asymptomatic gallstones was 7.6 per cent and there was no indication of this risk levelling off. There were no significant differences between treated and untreated subjects with regard to digestive symptoms or any of the risk factors monitored at the initial screening, although treated subjects were significantly younger than those who were not treated.
CONCLUSION: Nearly one in ten individuals with asymptomatic gallbladder stones in the general population may be expected to develop symptoms or complications that require treatment within 5 years. Age may be inversely related to the incidence of complications.

Copyright 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
PMID 15164444  Br J Surg. 2004 Jun;91(6):734-8. doi: 10.1002/bjs.4547.・・・
著者: J S Barkun, A N Barkun, J S Sampalis, G Fried, B Taylor, M J Wexler, C A Goresky, J L Meakins
雑誌名: Lancet. 1992 Nov 7;340(8828):1116-9.
Abstract/Text Laparoscopic cholecystectomy (LC) has gained wide acceptance for treatment of cholelithiasis in preference to open cholecystectomy, though it has not been formally compared with mini cholecystectomy (MC). We have compared these two techniques in a randomised trial. 70 patients with ultrasound-proven cholelithiasis were randomly allocated LC (38) or MC (32); 37 and 25, respectively, underwent the assigned procedure. The mean hospital stay (including 1 preoperative day) was significantly shorter in the LC than the MC group (median 3 [interquartile range 2-3] vs 4 [3-5], p = 0.001) as was duration of convalescence (mean 11.9 [SD 9.1] vs 20.2 [16.5] days, p = 0.04). The rate of return to normal activities was 1.77 times greater in the LC group than in the MC group (95% confidence interval 1.01-3.11, p = 0.03). In regression analysis, the type of cholecystectomy done was the only variable significantly associated with the duration of convalescence. Although there was significant postoperative improvement in all of three quality of life scores in both groups, LC patients improved more quickly than did MC patients. This randomised trial shows the superior effectiveness of LC over MC in treating cholelithiasis.

PMID 1359210  Lancet. 1992 Nov 7;340(8828):1116-9.
著者: G R May, L R Sutherland, E A Shaffer
雑誌名: Aliment Pharmacol Ther. 1993 Apr;7(2):139-48.
Abstract/Text To define better the efficacy of bile acid therapy for dissolution of radiolucent gallstones, we performed a meta-analysis of published trials from January 1966 to September 1992. Studies were identified using a MEDLINE computer search followed by an extensive manual search. The inclusion criteria used were: randomized trial, radiolucent gallstones in a visualizing gallbladder on oral cholecystography, and complete stone dissolution confirmed by oral cholecystography or ultrasound. Study results were pooled into 6 groups: placebo: high- and low-dose chenodeoxycholic acid (CDCA) (> or = 10 mg.kg/day and < 10 mg.kg/day); high- and low-dose ursodeoxycholic acid (UDCA) (> or = 7 mg.kg/day and < 7 mg.kg/day) and combined CDCA plus UDCA. Homogeneity calculations were performed and the percentage of complete stone dissolution calculated for each group with 95% confidence intervals. Of 66 trials identified, 23 comprising 1949 patients met the inclusion criteria. A total of 1062 patients were treated with CDCA, 819 with UDCA and 78 combination therapy. In studies > 6 months' duration, high-dose UDCA completely dissolved stones in 37.3% of patients (95% C.I. 33-42%), low-dose UDCA in 20.6%) and high-dose CDCA 18.2% (95% C.I. 15-21%). Based on only two studies, combination therapy achieved dissolution in 62.8% (95% C.I. 51-74%) of patients. Stones less than 10 mm dissolved significantly more frequently than stones larger than 10 mm. This analysis shows that UDCA in doses greater than 7 mg.kg/day taken for greater than 6 months will dissolve radiolucent gallstones in 38% of patients. The combination of UDCA and CDCA may be more efficacious but this observation is based upon only 78 patients and requires confirmation in further randomized trials.

PMID 8485266  Aliment Pharmacol Ther. 1993 Apr;7(2):139-48.
著者: J P Nicholl, J E Brazier, P C Milner, L Westlake, B Kohler, B T Williams, B Ross, E Frost, A G Johnson
雑誌名: Lancet. 1992 Oct 3;340(8823):801-7.
Abstract/Text Inpatient extracorporeal shockwave lithotripsy for treatment of gallbladder stones has not previously been compared with open cholecystectomy in terms of cost-effectiveness. In a randomised controlled trial, 163 patients, stratified by gallstone bulk (over 4 cm3 or not), were randomised to lithotripsy or cholecystectomy (38 large-bulk and 27 small-bulk cholecystectomy; 37 large-bulk and 61 small-bulk lithotripsy) and followed up for 1 year. Both treatments gave significant health gains in terms of a reduction in episodes of biliary pain, improved perceived health status, and symptom relief, but few differences between treatments were found. There was some evidence that biliary-pain episodes were less severe after cholecystectomy. Cholecystectomy patients also had greater improvements in mean health gain for three related symptoms: vomiting, feeling sick, and fatty-food upset. However, there were no differences between groups in perceived health status. Among lithotripsy patients, health gain was not related to stone clearance. Lithotripsy was more expensive than cholecystectomy, principally because of the costs of the inpatient stay and adjuvant bile-salt therapy. Conventional lithotripsy appears at least as cost-effective as cholecystectomy for patients with small-bulk stones but less cost-effective for those with large-bulk stones. To some extent treatment choice can be guided by patient preference.

PMID 1357242  Lancet. 1992 Oct 3;340(8823):801-7.
著者: Eric C Lai, Wan Yee Lau
雑誌名: ANZ J Surg. 2006 Apr;76(4):251-7. doi: 10.1111/j.1445-2197.2006.03690.x.
Abstract/Text BACKGROUND: Mirizzi syndrome was reported in 0.3-3% of patients undergoing cholecystectomy. The distortion of anatomy and the presence of cholecystocholedochal fistula increase the risk of bile duct injury during cholecystectomy.
METHODS: A Medline search was undertaken to identify articles that were published from 1974 to 2004. Additional papers were identified by a manual search of the references from the key articles.
RESULTS: A preoperative diagnosis was made in 8-62.5% of cases. Open surgical treatment gave good short-term and long-term results. There was a lack of good data in laparoscopic treatment. Conversion to open surgery rates was high, and bile duct injury rate varied from 0 to 22.2%.
CONCLUSION: A high index of clinical suspicion is required to make a preoperative or intraoperative diagnosis, which leads to good surgical planning to treat the condition. Open surgery is the gold standard. Mirizzi syndrome should still be considered as a contraindication for laparoscopic surgery.

PMID 16681544  ANZ J Surg. 2006 Apr;76(4):251-7. doi: 10.1111/j.1445-2・・・
著者: M Vetrhus, O Søreide, G E Eide, J H Solhaug, I Nesvik, K Søndenaa
雑誌名: Scand J Gastroenterol. 2004 Mar;39(3):270-6.
Abstract/Text BACKGROUND: Cholecystectomy is intended to relieve symptoms of gallstones, but unfortunately some patients will experience postcholecystectomy symptoms, including pain. There is limited information in the literature on gallstone-related pain and its influence on quality of life. The aim of this study was to examine how pain and quality of life in patients with symptomatic, uncomplicated gallbladder stones were affected by observation of their condition compared with removal of the gallbladder.
METHODS: One-hundred and thirty-seven patients were randomized to observation (watchful waiting; n = 69) or cholecystectomy (n = 68) and answered questionnaires on pain, quality of life (PGWB index and NHP Part II) at randomization and fixed intervals (6, 12 and 60 months). All gallstone-related events (hospital admission for pain, complications of gallstone disease and cholecystectomy) and crossover between treatment groups were recorded.
RESULTS: Of patients randomized to observation, 35 of 69 patients (51%) eventually underwent a cholecystectomy. Significant improvements in quality of life and pain scores were detected regardless of surgical treatment. Patients that subsequently experienced gallstone-related events had significantly higher pain scores at randomization than patients that did not experience any subsequent events, and this difference was maintained throughout follow-up.
CONCLUSIONS: Unexpectedly, in the majority of patients symptoms did abate without any significant differences between groups in pain and quality of life. Patients that had high intensity and frequency of pain at randomization had a higher risk of experiencing subsequent events.

PMID 15074398  Scand J Gastroenterol. 2004 Mar;39(3):270-6.
著者: Morten Vetrhus, Tewelde Berhane, Odd Søreide, Karl Søndenaa
雑誌名: J Gastrointest Surg. 2005 Jul-Aug;9(6):826-31. doi: 10.1016/j.gassur.2005.01.291.
Abstract/Text After removal of the gallbladder, pain may persist in some patients. To study this condition, 124 patients from two randomized trials, including those with symptomatic noncomplicated gallbladder stones (n = 90) and acute cholecystitis (n = 34), were interviewed, while 139 patients (90%) excluded from both trials responded to a questionnaire 5 years after the operation. Thirty-four patients (27%) of those randomized had pain; 23 (18%) had diffuse, steady pain; and 11 (9%) had pain attacks resembling their preoperative symptoms. A significant dominance of diffuse pain occurred in women (P = 0.024), especially those younger than 60 years (P = 0.004). A tendency for the diffuse type to be dominant was also present in the group of female patients with symptomatic noncomplicated gallbladder stones (P = 0.052). Of the excluded patients, 18% (25/139) had pain, but 88% of them (96% of the men and 87% of the women) were satisfied with the result of the operation. The overall number of patients with postoperative pain was 22% (59/263). We conclude that persisting abdominal pain 5 years after the operation was mainly of a nonspecific type, found mostly in younger women who had had noncomplicated gallstone disease. Eighty-eight percent of the excluded patients declared themselves satisfied with the result of cholecystectomy.

PMID 15985239  J Gastrointest Surg. 2005 Jul-Aug;9(6):826-31. doi: 10.・・・
著者: Gerd H Sauter, Ahmed C Moussavian, Guenther Meyer, Heinrich O Steitz, Klaus G Parhofer, Dieter Jüngst
雑誌名: Am J Gastroenterol. 2002 Jul;97(7):1732-5. doi: 10.1111/j.1572-0241.2002.05779.x.
Abstract/Text OBJECTIVE: Bile acid malabsorption has been supposed to play a major pathogenetic role in postcholecystectomy diarrhea. Therefore, the aim of this study was to define the effect of cholecystectomy (CHE) on bowel habits and bile acid absorption.
METHODS: Fifty-one patients were prospectively studied before, at 4 wk, and 12 wk after elective CHE for changes of bowel habits, occurrence of diarrhea, and signs of bile acid malabsorption. Bowel habits were assessed by interview. Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one were used as a marker of bile acid malabsorption. Statistics were performed with the McNemar chi2 test for discrete values and Student's paired t test for continuous values.
RESULTS: After CHE, there was an increase of patients reporting more than one bowel movement per day (from 22% before CHE to 51% [p < 0.001] and 45% [p < 0.005] at 1 month and 3 months after CHE, respectively) and of patients reporting loose stools (from 2% to 47% [p < 0.001] and 33% [p < 0.001], respectively). Three months after CHE, three patients (6%) reported intermittent diarrhea. Serum levels of 7alpha-hydroxy-4-cholesten-3-one increased from 25.4+/-14.5 ng/ml to 46.5+/-29.5 ng/ml (p < 0.001) and 52.5+/-33.0 ng/ml (p < 0.001), respectively. Unexpectedly, changes of 7alpha-hydroxy-4-cholesten-3-one in serum were unrelated to changes of bowel habits.
CONCLUSIONS: CHE results in considerable changes of bowel habits and an increased loss of bile acids from the intestine in some patients. Bile acid malabsorption, however, may not explain changes of bowel habits after CHE.

PMID 12135027  Am J Gastroenterol. 2002 Jul;97(7):1732-5. doi: 10.1111・・・
著者: G Jonson, D M Nilsson, T Nilsson
雑誌名: Eur J Surg. 1991 Oct;157(10):583-6.
Abstract/Text To assess the importance of cystic duct remnants in causing biliary symptoms after cholecystectomy 80 patients undergoing routine cholecystectomy were randomised to have conventional cholecystectomy (n = 40) or cholecystectomy with removal of the whole cystic duct (n = 40). Fifteen were withdrawn, leaving 65 (32 who had standard cholecystectomy and 33 who had cholecystectomy by the new technique) for analysis. Thirty of the 32, and 27 of the 33, were available for follow up one, two, three, and eight years after operation; 11 of the 30 (37%) compared with 23 of the 27 (85%) were free of biliary symptoms during the eight year period (p less than 0.001). We conclude that removal of the stump of the cystic duct improves the success rate of cholecystectomy in the treatment of gallstones.

PMID 1687248  Eur J Surg. 1991 Oct;157(10):583-6.

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