human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients , in a subgroup of whom gallstone burden , type and number , gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide  were evaluated . Patients were divided into contractors ( n = 108 ) and hypocontractors ( n = 42 ) , according to their gallbladder motility pattern in vivo . Contractors showed slower gallbladder emptying and increased fasting and postpr and ial residual volumes , although the ejected amount of bile was greater than that of controls ( 20.2 + /- SEM 1.1 vs 16.0 + /- 0.7 ml ; p < 0.001 ) . In contrast , hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile . Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients , the thickness of the muscular layer was greater in hypocontractors than in contractors ( 1073 + /- 76 vs 745 + /- 75 microns , p < 0.01 ) and related inversely to postpr and ial ejected volume ( r = -0.42 ; p < 0.03 ; n = 32 ) but positively to gallstone volume ( r = 0.40 ; p < 0.03 ; n = 32 ) . Compared to contractors , gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide ( 0.1 nM-1 microM ) . Postpr and ial gallbladder evaculation was unaffected by stone number , and by the presence or absence of stone calcification . Gallstone volume was larger in hypocontractors ( 19.4 + /- 3.0 ml vs 9.6 + /- 0.9 ml , p < 0.001 ) than contractors . The comparison of in vitro contractility patterns between cholesterol , mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi . In conclusion , in gallstone patients : ( i ) gallbladder motor dysfunction manifests mainly with increased fasting and postpr and ial residual volumes in contractors and with markedly increased postpr and ial residual volumes and decreased gallbladder emptying in hypocontractors ; ( ii ) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number , calcification or mild chronic cholecystitis ; ( iii ) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function The National Cooperative Gallstone Study , a double-masked , placebo-controlled , therapeutic trial of chenodiol ( chenodeoxycholic acid ) , provided an opportunity to study the natural history of cholelithiasis in patients who choose nonsurgical management . The major component of the study comprised 916 patients , 305 of whom were r and omly assigned to receive a placebo for 24 months . Among these 305 patients , the probability of having biliary tract pain during the 24 months of prospect i ve evaluation was significantly increased if the patient had had a history of biliary tract pain in the 12 months before entry into the study ( 69 % versus 31 % ) . Thirty-eight percent of patients had stone growth ( greater than 0.5 cm3 ) , and 18 % had a spontaneous decrease in stone volume . Despite the high incidence of biliary tract pain , nonelective cholecystectomy was required in only 4 % of patients during the 24 months The results of cholecystectomy in terms of symptomatic improvement were prospect ively evaluated in 124 unselected gall stone patients interviewed before and two years after elective surgery . Indications for cholecystectomy were biliary pain ( n = 65 ) , previous complications of gall stone disease ( n = 52 ) , and flatulent dyspepsia ( n = 7 ) . At two years 93 patients could be re-evaluated , of whom only 49 ( 53 % ) were completely symptom free . Postcholecystectomy symptoms occurring in the remaining 44 patients were mainly flatulent dyspepsia ( which had relapsed in 22 of 46 patients who suffered it preoperatively ) , dull abdominal pain or diarrhoea . Incisional hernia was present in five patients and one had recurrence of pain because of retained common bile duct stones . Symptomatic cures after cholecystectomy decreased with the duration of the preoperative history . The results reconfirm that cholecystectomy  eradicates specific symptoms and complications of gall stone disease , but they also show that nearly one half of operated patients are dissatisfied with the procedure because of mild but distressing ' postcholecystectomy ' symptoms . These are probably caused by previously undiagnosed functional gut disease associated with , but unrelated to , gall stones . A systemic approach to multisymptomatic patients with gall stones is recommended Background After its introduction , laparoscopic cholecystectomy rapidly exp and ed around the world and was accepted the procedure of choice by consensus . However , analysis of evidence shows no difference regarding primary outcome measures between laparoscopic and small-incision cholecystectomy . In absence of clear clinical benefit it may be interesting to focus on the re source use associated with the available techniques , a secondary outcome measure . This study focuses on a difference in costs between laparoscopic and small-incision cholecystectomy from a societal perspective with emphasis on internal validity and generalisability Methods A blinded r and omized single-centre trial was conducted in a general teaching hospital in The Netherl and s. Patients with reasonable to good health diagnosed with symptomatic cholecystolithiasis scheduled for cholecystectomy were included . Patients were r and omized between laparoscopic and small-incision cholecystectomy .  Total costs were analyzed from a societal perspective . Results Operative costs were higher in the laparoscopic group using reusable laparoscopic instruments ( difference 203 euro ; 95 % confidence interval 147 to 259 euro ) . There were no significant differences in the other direct cost categories ( outpatient clinic and admittance related costs ) , indirect costs , and total costs . More than 60 % of costs in employed patients were caused by sick leave . Conclusion Based on differences in costs , small-incision cholecystectomy seems to be the preferred operative technique over the laparoscopic technique both from a hospital and societal cost perspective . Sick leave associated with convalescence after cholecystectomy in employed patients results in considerable costs to society . Trial registration IS RCT N Register , number IS RCT N67485658 BACKGROUND The uncertainty around true clinical manifestations of gallbladder stone disease is in contrast with the unanimous recommendation that only symptomatic gallstones should be treated . AIM To evaluate the relationship between biliary pain , other gastrointestinal symptoms and gallstones . DESIGN OF STUDY A pragmatic , prospect i ve cohort question naire study . SETTING Seventy-five general practice s in Rotterdam , The Netherl and s. METHOD All patients suspected by their general practitioner ( GP ) to have gallstone disease underwent ultrasound examination of the upper abdomen .  Using a self-administered question naire , the presence of 11 gastrointestinal symptoms was assessed at inclusion and after 1 year . Likelihood ratios ( LRs ) for the presence of gallstones and symptom relief rates after 1 year were calculated . The mean difference in health status at inclusion and after follow-up was calculated for patients without gallstones , for patients with gallstones who were operated on and for patients with gallstones who were not operated on . RESULTS In total , 61 % of the patients with gallstones diagnosed by ultrasound scan reported biliary pain , as did 45 % of the patients without gallstones ( LR = 1.34 , 95 % confidence interval [ CI ] = 1.05 to 1.71 ) . Patients operated on for gallstone disease did not show significant relief of biliary pain compared to patients not operated on for gallstones or patients without gallstones ( 87 % , 63 % and 83 % , respectively ) . Health status improved in all patients . The mean improvement in health status did not differ between the three patient groups . GPs were able to discriminate between patients with high and low probability of gallbladder stones by ultrasound examination ( 53 % versus 23 % ) . This selection , however , did not predict the outcome of cholecystectomy . CONCLUSION Neither biliary pain nor any other gastrointestinal symptom was consistently related to gallstone disease . Therefore , the indication for elective cholecystectomy can not be based on the presence of biliary pain alone . Relief of biliary pain in patients operated on for gallstones should not simply be attributed to a successful cholecystectomy Although laparoscopic cholecystectomy has rapidly developed in the treatment of gall bladder disease in the absence of controlled clinical trial data its outcome parameters compared with open cholecystectomy remain unclear . A prospect i ve audit of the introduction of laparoscopic cholecystectomy in the west of Scotl and over a two year period was carried out to attempt to assess this new procedure . A total of 45 surgeons in 19 hospitals performing laparoscopic cholecystectomy su bmi tted prospect i ve data from September 1990 - 1992 . A total of 2285 cholecystectomies were audited ( a completed data collection rate of 99 % ) . Laparoscopic cholecystectomy was attempted in 1683 ( 74 % ) patients and completed in 1448 patients ( median conversion rate to the open procedure 17 % ) . The median operation time in the completed laparoscopic cholecystectomy patients was 100 minutes ( range 30 - 330 ) and overall hospital stay three days ( 1 - 33 ) . There were nine deaths ( 0.5 % ) after laparoscopic cholecystectomy although only two were directly attributable to the laparoscopic procedure . In the laparoscopic cholecystectomy group there were 99 complications ( 5.9 % ) , 53 ( 3 % ) of these were major requiring further invasive intervention . Forty patients ( 2.4 % ) required early or delayed laparotomy for major complications such as bleeding or bile duct injuries . There were 11 ( 0.7 % ) bile duct injuries in the laparoscopic cholecystectomy series , five were noted during the initial procedure and six were recognised later result ing from jaundice or bile leaks . Ductal injuries occurred after a median of 20 laparoscopic cholecystectomies . In conclusion laparoscopic cholecystectomy has rapidly replaced open cholecystectomy in the treatment of gall bladder disease . Although the overall death and complication rate associated with laparoscopic cholecystectomy is similar to open cholecystectomy , the bile duct injury rate is higher This r and omized controlled trial compared the cost – utility of early laparoscopic cholecystectomy with that for conventional management of newly diagnosed acute gallbladder disease BACKGROUND Cholecystectomy has been recognized as the treatment of choice for symptomatic gallbladder stone disease . Not all patients are cured by an operation and the reason for having the gallbladder removed may rest on common practice rather than evidence -based medicine . The aim was to compare cholecystectomy with observation ( watchful waiting ) in patients with uncomplicated symptomatic GBS disease . Three-hundred- and -thirty-eight patients were considered for participation in the study ; 45 patients were excluded according to predefined criteria and 156 did not join for other reasons . The remaining 137 were r and omized to cholecystectomy ( n = 68 ) or non-operative , expectant treatment ( n = 69 ) . METHODS R and omized patients were contacted regularly and followed for a median of 67 months . All gallstone-related hospital contacts were registered in both r and omized and excluded patients . RESULTS Eight of the patients r and omized to cholecystectomy did not undergo operation , while 35 of the patients r and omized to observation later had their gallbladders removed . The cumulative risk of having a cholecystectomy seemed to level off after 4 years . Gallstone-related complications occurred in 3 patients in the observation group , 1 in the operation group and 5 of 201 excluded patients . After cholecystectomy , 16 of 222 patients had a major complication and 10 a minor . CONCLUSIONS We found that non-operative expectant treatment carries a low risk of complications . Patients should be informed that watchful waiting is a safe option To estimate patient preferences for gallstone-related treatments and outcomes , and assess how preferences vary by patient characteristics and scaling technique , the authors r and omly assigned 40 patients without gallstones to interviews based on a rating scale ( n = 22 ) and a st and ard gamble ( n = 18 ) . The patients assigned preference values ( possible values 0 to 1 ) to open cholecystectomy ( mean 0.45 by rating scale , 0.78 by st and ard gamble ) , laparoscopic cholecystectomy ( 0.71 , 0.91 ) , extracorporeal shock-wave lithotripsy ( 0.77 , 0.89 ) , acute cholecystitis ( 0.36 , 0.77 ) , lifetime biliary colic ( 0. 
    Output:
    
agent
The results of the economic evaluation suggest that , on average , the surgery strategy costs £ 1236 more per patient than the conservative management strategy but was , on average , more effective .
An increase in the number of people requiring surgery while treated conservatively corresponded to a reduction in the cost-effectiveness of the conservative strategy .
The results of this assessment indicate that cholecystectomy is still the treatment of choice for many symptomatic people .
However , approximately half of the people in the observation group did not require surgery or suffer complications in the long term indicating that a conservative therapeutic approach may represent a valid alternative to surgery in this group of people .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients , in a subgroup of whom gallstone burden , type and number , gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide  were evaluated . Patients were divided into contractors ( n = 108 ) and hypocontractors ( n = 42 ) , according to their gallbladder motility pattern in vivo . Contractors showed slower gallbladder emptying and increased fasting and postpr and ial residual volumes , although the ejected amount of bile was greater than that of controls ( 20.2 + /- SEM 1.1 vs 16.0 + /- 0.7 ml ; p < 0.001 ) . In contrast , hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile . Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients , the thickness of the muscular layer was greater in hypocontractors than in contractors ( 1073 + /- 76 vs 745 + /- 75 microns , p < 0.01 ) and related inversely to postpr and ial ejected volume ( r = -0.42 ; p < 0.03 ; n = 32 ) but positively to gallstone volume ( r = 0.40 ; p < 0.03 ; n = 32 ) . Compared to contractors , gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide ( 0.1 nM-1 microM ) . Postpr and ial gallbladder evaculation was unaffected by stone number , and by the presence or absence of stone calcification . Gallstone volume was larger in hypocontractors ( 19.4 + /- 3.0 ml vs 9.6 + /- 0.9 ml , p < 0.001 ) than contractors . The comparison of in vitro contractility patterns between cholesterol , mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi . In conclusion , in gallstone patients : ( i ) gallbladder motor dysfunction manifests mainly with increased fasting and postpr and ial residual volumes in contractors and with markedly increased postpr and ial residual volumes and decreased gallbladder emptying in hypocontractors ; ( ii ) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number , calcification or mild chronic cholecystitis ; ( iii ) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function The National Cooperative Gallstone Study , a double-masked , placebo-controlled , therapeutic trial of chenodiol ( chenodeoxycholic acid ) , provided an opportunity to study the natural history of cholelithiasis in patients who choose nonsurgical management . The major component of the study comprised 916 patients , 305 of whom were r and omly assigned to receive a placebo for 24 months . Among these 305 patients , the probability of having biliary tract pain during the 24 months of prospect i ve evaluation was significantly increased if the patient had had a history of biliary tract pain in the 12 months before entry into the study ( 69 % versus 31 % ) . Thirty-eight percent of patients had stone growth ( greater than 0.5 cm3 ) , and 18 % had a spontaneous decrease in stone volume . Despite the high incidence of biliary tract pain , nonelective cholecystectomy was required in only 4 % of patients during the 24 months The results of cholecystectomy in terms of symptomatic improvement were prospect ively evaluated in 124 unselected gall stone patients interviewed before and two years after elective surgery . Indications for cholecystectomy were biliary pain ( n = 65 ) , previous complications of gall stone disease ( n = 52 ) , and flatulent dyspepsia ( n = 7 ) . At two years 93 patients could be re-evaluated , of whom only 49 ( 53 % ) were completely symptom free . Postcholecystectomy symptoms occurring in the remaining 44 patients were mainly flatulent dyspepsia ( which had relapsed in 22 of 46 patients who suffered it preoperatively ) , dull abdominal pain or diarrhoea . Incisional hernia was present in five patients and one had recurrence of pain because of retained common bile duct stones . Symptomatic cures after cholecystectomy decreased with the duration of the preoperative history . The results reconfirm that cholecystectomy  eradicates specific symptoms and complications of gall stone disease , but they also show that nearly one half of operated patients are dissatisfied with the procedure because of mild but distressing ' postcholecystectomy ' symptoms . These are probably caused by previously undiagnosed functional gut disease associated with , but unrelated to , gall stones . A systemic approach to multisymptomatic patients with gall stones is recommended Background After its introduction , laparoscopic cholecystectomy rapidly exp and ed around the world and was accepted the procedure of choice by consensus . However , analysis of evidence shows no difference regarding primary outcome measures between laparoscopic and small-incision cholecystectomy . In absence of clear clinical benefit it may be interesting to focus on the re source use associated with the available techniques , a secondary outcome measure . This study focuses on a difference in costs between laparoscopic and small-incision cholecystectomy from a societal perspective with emphasis on internal validity and generalisability Methods A blinded r and omized single-centre trial was conducted in a general teaching hospital in The Netherl and s. Patients with reasonable to good health diagnosed with symptomatic cholecystolithiasis scheduled for cholecystectomy were included . Patients were r and omized between laparoscopic and small-incision cholecystectomy .  Total costs were analyzed from a societal perspective . Results Operative costs were higher in the laparoscopic group using reusable laparoscopic instruments ( difference 203 euro ; 95 % confidence interval 147 to 259 euro ) . There were no significant differences in the other direct cost categories ( outpatient clinic and admittance related costs ) , indirect costs , and total costs . More than 60 % of costs in employed patients were caused by sick leave . Conclusion Based on differences in costs , small-incision cholecystectomy seems to be the preferred operative technique over the laparoscopic technique both from a hospital and societal cost perspective . Sick leave associated with convalescence after cholecystectomy in employed patients results in considerable costs to society . Trial registration IS RCT N Register , number IS RCT N67485658 BACKGROUND The uncertainty around true clinical manifestations of gallbladder stone disease is in contrast with the unanimous recommendation that only symptomatic gallstones should be treated . AIM To evaluate the relationship between biliary pain , other gastrointestinal symptoms and gallstones . DESIGN OF STUDY A pragmatic , prospect i ve cohort question naire study . SETTING Seventy-five general practice s in Rotterdam , The Netherl and s. METHOD All patients suspected by their general practitioner ( GP ) to have gallstone disease underwent ultrasound examination of the upper abdomen .  Using a self-administered question naire , the presence of 11 gastrointestinal symptoms was assessed at inclusion and after 1 year . Likelihood ratios ( LRs ) for the presence of gallstones and symptom relief rates after 1 year were calculated . The mean difference in health status at inclusion and after follow-up was calculated for patients without gallstones , for patients with gallstones who were operated on and for patients with gallstones who were not operated on . RESULTS In total , 61 % of the patients with gallstones diagnosed by ultrasound scan reported biliary pain , as did 45 % of the patients without gallstones ( LR = 1.34 , 95 % confidence interval [ CI ] = 1.05 to 1.71 ) . Patients operated on for gallstone disease did not show significant relief of biliary pain compared to patients not operated on for gallstones or patients without gallstones ( 87 % , 63 % and 83 % , respectively ) . Health status improved in all patients . The mean improvement in health status did not differ between the three patient groups . GPs were able to discriminate between patients with high and low probability of gallbladder stones by ultrasound examination ( 53 % versus 23 % ) . This selection , however , did not predict the outcome of cholecystectomy . CONCLUSION Neither biliary pain nor any other gastrointestinal symptom was consistently related to gallstone disease . Therefore , the indication for elective cholecystectomy can not be based on the presence of biliary pain alone . Relief of biliary pain in patients operated on for gallstones should not simply be attributed to a successful cholecystectomy Although laparoscopic cholecystectomy has rapidly developed in the treatment of gall bladder disease in the absence of controlled clinical trial data its outcome parameters compared with open cholecystectomy remain unclear . A prospect i ve audit of the introduction of laparoscopic cholecystectomy in the west of Scotl and over a two year period was carried out to attempt to assess this new procedure . A total of 45 surgeons in 19 hospitals performing laparoscopic cholecystectomy su bmi tted prospect i ve data from September 1990 - 1992 . A total of 2285 cholecystectomies were audited ( a completed data collection rate of 99 % ) . Laparoscopic cholecystectomy was attempted in 1683 ( 74 % ) patients and completed in 1448 patients ( median conversion rate to the open procedure 17 % ) . The median operation time in the completed laparoscopic cholecystectomy patients was 100 minutes ( range 30 - 330 ) and overall hospital stay three days ( 1 - 33 ) . There were nine deaths ( 0.5 % ) after laparoscopic cholecystectomy although only two were directly attributable to the laparoscopic procedure . In the laparoscopic cholecystectomy group there were 99 complications ( 5.9 % ) , 53 ( 3 % ) of these were major requiring further invasive intervention . Forty patients ( 2.4 % ) required early or delayed laparotomy for major complications such as bleeding or bile duct injuries . There were 11 ( 0.7 % ) bile duct injuries in the laparoscopic cholecystectomy series , five were noted during the initial procedure and six were recognised later result ing from jaundice or bile leaks . Ductal injuries occurred after a median of 20 laparoscopic cholecystectomies . In conclusion laparoscopic cholecystectomy has rapidly replaced open cholecystectomy in the treatment of gall bladder disease . Although the overall death and complication rate associated with laparoscopic cholecystectomy is similar to open cholecystectomy , the bile duct injury rate is higher This r and omized controlled trial compared the cost – utility of early laparoscopic cholecystectomy with that for conventional management of newly diagnosed acute gallbladder disease BACKGROUND Cholecystectomy has been recognized as the treatment of choice for symptomatic gallbladder stone disease . Not all patients are cured by an operation and the reason for having the gallbladder removed may rest on common practice rather than evidence -based medicine . The aim was to compare cholecystectomy with observation ( watchful waiting ) in patients with uncomplicated symptomatic GBS disease . Three-hundred- and -thirty-eight patients were considered for participation in the study ; 45 patients were excluded according to predefined criteria and 156 did not join for other reasons . The remaining 137 were r and omized to cholecystectomy ( n = 68 ) or non-operative , expectant treatment ( n = 69 ) . METHODS R and omized patients were contacted regularly and followed for a median of 67 months . All gallstone-related hospital contacts were registered in both r and omized and excluded patients . RESULTS Eight of the patients r and omized to cholecystectomy did not undergo operation , while 35 of the patients r and omized to observation later had their gallbladders removed . The cumulative risk of having a cholecystectomy seemed to level off after 4 years . Gallstone-related complications occurred in 3 patients in the observation group , 1 in the operation group and 5 of 201 excluded patients . After cholecystectomy , 16 of 222 patients had a major complication and 10 a minor . CONCLUSIONS We found that non-operative expectant treatment carries a low risk of complications . Patients should be informed that watchful waiting is a safe option To estimate patient preferences for gallstone-related treatments and outcomes , and assess how preferences vary by patient characteristics and scaling technique , the authors r and omly assigned 40 patients without gallstones to interviews based on a rating scale ( n = 22 ) and a st and ard gamble ( n = 18 ) . The patients assigned preference values ( possible values 0 to 1 ) to open cholecystectomy ( mean 0.45 by rating scale , 0.78 by st and ard gamble ) , laparoscopic cholecystectomy ( 0.71 , 0.91 ) , extracorporeal shock-wave lithotripsy ( 0.77 , 0.89 ) , acute cholecystitis ( 0.36 , 0.77 ) , lifetime biliary colic ( 0. 
    Output:
    