primary neoplasms of the biliary system are a heterogeneous group largely comprising of gallbladder carcinoma and cholangiocarcinoma with a few other much rarer tumours . traditionally these tumours have a high mortality rate , with surgical excision being the mainstay of long - term survival . advances in surgery have increased the likelihood of achieving local disease control and now limited distant spread may also be considered for resection . accurate staging is critical for this to occur , not only to aid surgical planning but also to prevent unnecessary surgical intervention in those with advanced disease . despite pre - operative assessment with traditional cross - sectional imaging techniques , up to a third of patients with primary biliary malignancy still undergo unnecessary laparotomy . the main contraindications to resectability found at surgery are occult peritoneal and liver metastases , and , less commonly , vascular and lymph node invasion [ 3 , 4 ] . these may not be detected due to inability of conventional imaging modalities ( computed tomography [ ct]/magnetic resonance imaging [ mri ] ) to accurately distinguish between benign and malignant processes based on size or anatomical criteria alone or when prior intervention distorts normal anatomy . gallbladder carcinoma in particular is associated with more frequent early dissemination , whereas cholangiocarcinoma is likely to be locally invasive and has a slightly longer survival . f - fluoro-2-deoxy - d - glucose ( fdg ) integrated positron emission tomography ( pet)-computed tomography ( ct ) is a non - invasive imaging technique that allows in vivo assessment of the metabolic processes underlying malignant disease . it has been shown to be more accurate than ct / mri in the assessment of several primary and recurrent tumours , including colorectal , lung and oesophageal cancer [ 57 ] . moreover , it is reported to have a consistent impact on intended management that is not restricted to cancer type . by providing additional functional information and in the correct setting , fdg pet - ct can allow earlier detection of tumours , identification of occult metastatic disease , characterisation of indeterminate lesions , assessment of therapeutic response and overall more accurate staging for potential resection . several previous studies have assessed the ability of fdg pet - ct to detect primary biliary tumours ; however , few report its overall efficacy in the management pathway of patients with primary biliary malignancy . the aim of this study was to assess the impact on clinical management of introducing fdg pet - ct in to the work - up of patients with potentially resectable primary biliary malignancy and in those undergoing fdg pet - ct for response assessment following chemotherapy or with suspected disease recurrence . consecutive patients with primary biliary tumours undergoing fdg pet - ct at a single large tertiary referral centre over a 35-month period were retrospectively analysed ( november 2007 to september 2010 ) . formal ethics committee approval was not required at our institution for a case review of this kind . data were accessed from the institutional radiology information system ( cris ; healthcare software systems , banbury , uk ) and patient pathway manager ( ppm , leeds , uk ; an electronic patient record system ) . referral for fdg pet - ct was made on a case - by - case basis after discussion at a specialist multidisciplinary team ( mdt ) meeting . the main indication for performing fdg pet - ct was for initial staging to determine suitability for surgical resection where there was some ambiguity on initial conventional imaging . patients with locally advanced disease or distant metastatic disease that was deemed unresectable on conventional imaging were referred for palliative chemotherapy where appropriate . both readers are dual trained in radiology and nuclear medicine and respectively have 13/11  years of experience in ct and mri and 9/7  years of experience in pet - ct . imaging , particularly that performed externally , was validated and accepted as consistent for diagnosis at time of mdt review . if imaging was deemed suboptimal for diagnosis , then it was repeated at our institution . imaging for each patient was retrieved from the institutional picture archiving and communications system ( pacs ) ( impax ; agfa healthcare , mortsel , belgium ) . contrast - enhanced ct ( cect ) thorax / abdomen / pelvis was performed in 76 cases . the mean time between the previous cect and the pet - ct was 38  days ( range 1125  days , lower quartile 22  days and upper quartile 46  days ) . most cases were scanned within a 90-day period with only four , all cholangiocarcinomas , scanned outside this time . cect was performed at our institution ( n  =  57 ) after referral from the regional oncology team on either a 16- or 64-slice scanner ( siemens healthcare , erlangen , germany ) using a contiguous 3-mm reconstruction and following a bolus of 100  ml iodinated contrast medium ( omnipaque 300  mg i / ml ; ge healthcare , oslo , norway ) . the remaining cts had been acquired at one of several referring hospitals on a range of different scanner types using similar acquisition parameters ( n  =  18 ) . the mean time between the previous mri and the pet - ct was 15  days ( range 188  days , lower quartile 3  days and upper quartile 21  days ) . mri was performed at our institution in 67 of the 72 cases on a 1.5-t system ( symphony / avanto ; siemens healthcare , erlangen , germany ) using a body phased array coil and a breath - holding technique . t1/t2/t2 * -weighted sequences were obtained with the use of intravenous gadolinium ( gadovist ; bayer healthcare pharmaceuticals , berlin , germany ) and , where appropriate , liver - specific contrast agents ( resovist prior to its withdrawal in 2009 and primovist thereafter ; bayer healthcare pharmaceuticals , berlin , germany ) . diffusion - weighted imaging was also performed for each case with b values of 50 , 200 , 500 and 750  s / mm . pet - ct scans were performed prior to 1st june 2010 on a 16-slice discovery ste pet - ct scanner ( ge healthcare , amersham , uk ) , and thereafter on a 64-slice philips gemini tf64 scanner ( philips healthcare , amsterdam , netherlands ) , 60  min following a 400-mbq dose of intravenous fdg . the ct component of the pet - ct was performed according to a standardised protocol with the following settings : 140  kv ; 80 mas ; tube rotation time 0.5  s per rotation ; pitch 6 ; section thickness 3.75  mm ( to match pet section thickness ) . imaging was reviewed on specialised pet - ct workstations ( xd3 ; mirada medical , oxford , uk ) . the clinical impact of fdg pet - ct on the management of patients was evaluated using the institutional oncological electronic patient record system ( patient pathway manager ) , which prospectively documents mdt decisions based on discussion between medical and radiation oncologists , surgeons , radiologists and pathologists . follow - up information was obtained for a minimum 12-month period subsequent to the date of the pet - ct scan . all pet - ct findings were correlated with the results of histological , radiological and clinical follow - up . a hypermetabolic fdg lesion was considered truly positive for involvement if malignancy was proven by histological analysis or if the lesion progressed on follow - up imaging or resolved after therapy . an fdg - negative lesion was considered truly negative if its size remained stable on imaging follow - up . the impact of fdg pet - ct in addition to ct / mri findings on the management of patients was assessed with respect to potential change of management by either the identification of distant unresectable disease or confirmation of its absence . three categories of impact were considered : major impact : evidence of unresectable metastatic disease on fdg pet - ct , which was either indeterminate or evaded detection on prior ct / mri.additional fdg pet - ct findings that would extend the surgical field.fdg pet - ct characterisation of indeterminate lesions on ct / mri as benign , allowing curative resection to be attempted . evidence of unresectable metastatic disease on fdg pet - ct , which was either indeterminate or evaded detection on prior ct / mri . fdg pet - ct characterisation of indeterminate lesions on ct / mri as benign , allowing curative resection to be attempted . minor impact : fdg pet - ct confirmation of suspicious unresectable findings on ct / mri . no impact : no additional findings on fdg pet - ct compared with ct / mri.indeterminate findings on fdg pet - ct which did not alter the status of the patient with regards to resectability . indeterminate findings on fdg pet - ct which did not alter the status of the patient with regards to resectability . if findings on fdg pet - ct fell into both a minor impact and a major impact category then overall the impact was considered as major . consecutive patients with primary biliary tumours undergoing fdg pet - ct at a single large tertiary referral centre over a 35-month period were retrospectively analysed ( november 2007 to september 2010 ) . formal ethics committee approval was not required at our institution for a case review of this kind . data were accessed from the institutional radiology information system ( cris ; healthcare software systems , banbury , uk ) and patient pathway manager ( ppm , leeds , uk ; an electronic patient record system ) . referral for fdg pet - ct was made on a case - by - case basis after discussion at a specialist multidisciplinary team ( mdt ) meeting . the main indication for performing fdg pet - ct was for initial staging to determine suitability for surgical resection where there was some ambiguity on initial conventional imaging . patients with locally advanced disease or distant metastatic disease that was deemed unresectable on conventional imaging were referred for palliative chemotherapy where appropriate . both readers are dual trained in radiology and nuclear medicine and respectively have 13/11  years of experience in ct and mri and 9/7  years of experience in pet - ct . imaging , particularly that performed externally , was validated and accepted as consistent for diagnosis at time of mdt review . if imaging was deemed suboptimal for diagnosis , then it was repeated at our institution . imaging for each patient was retrieved from the institutional picture archiving and communications system ( pacs ) ( impax ; agfa healthcare , mortsel , belgium ) . contrast - enhanced ct ( cect ) thorax / abdomen / pelvis was performed in 76 cases . the mean time between the previous cect and the pet - ct was 38  days ( range 1125  days , lower quartile 22  days and upper quartile 46  days ) . most cases were scanned within a 90-day period with only four , all cholangiocarcinomas , scanned outside this time . cect was performed at our institution ( n  =  57 ) after referral from the regional oncology team on either a 16- or 64-slice scanner ( siemens healthcare , erlangen , germany ) using a contiguous 3-mm reconstruction and following a bolus of 100  ml iodinated contrast medium ( omnipaque 300  mg i / ml ; ge healthcare , oslo , norway ) . the remaining cts had been acquired at one of several referring hospitals on a range of different scanner types using similar acquisition parameters ( n  =  18 ) . the mean time between the previous mri and the pet - ct was 15  days ( range 188  days , lower quartile 3  days and upper quartile 21  days ) . mri was performed at our institution in 67 of the 72 cases on a 1.5-t system ( symphony / avanto ; siemens healthcare , erlangen , germany ) using a body phased array coil and a breath - holding technique . t1/t2/t2 * -weighted sequences were obtained with the use of intravenous gadolinium ( gadovist ; bayer healthcare pharmaceuticals , berlin , germany ) and , where appropriate , liver - specific contrast agents ( resovist prior to its withdrawal in 2009 and primovist thereafter ; bayer healthcare pharmaceuticals , berlin , germany ) . diffusion - weighted imaging was also performed for each case with b values of 50 , 200 , 500 and 750  s / mm . pet - ct scans were performed prior to 1st june 2010 on a 16-slice discovery ste pet - ct scanner ( ge healthcare , amersham , uk ) , and thereafter on a 64-slice philips gemini tf64 scanner ( philips healthcare , amsterdam , netherlands ) , 60  min following a 400-mbq dose of intravenous fdg . the ct component of the pet - ct was performed according to a standardised protocol with the following settings : 140  kv ; 80 mas ; tube rotation time 0.5  s per rotation ; pitch 6 ; section thickness 3.75  mm ( to match pet section thickness ) . imaging was reviewed on specialised pet - ct workstations ( xd3 ; mirada medical , oxford , uk ) . the clinical impact of fdg pet - ct on the management of patients was evaluated using the institutional oncological electronic patient record system ( patient pathway manager ) , which prospectively documents mdt decisions based on discussion between medical and radiation oncologists , surgeons , radiologists and pathologists . follow - up information was obtained for a minimum 12-month period subsequent to the date of the pet - ct scan . all pet - ct findings were correlated with the results of histological , radiological and clinical follow - up . a hypermetabolic fdg lesion was considered truly positive for involvement if malignancy was proven by histological analysis or if the lesion progressed on follow - up imaging or resolved after therapy . an fdg - negative lesion was considered truly negative if its size remained stable on imaging follow - up . the impact of fdg pet - ct in addition to ct / mri findings on the management of patients was assessed with respect to potential change of management by either the identification of distant unresectable disease or confirmation of its absence . three categories of impact were considered : major impact : evidence of unresectable metastatic disease on fdg pet - ct , which was either indeterminate or evaded detection on prior ct / mri.additional fdg pet - ct findings that would extend the surgical field.fdg pet - ct characterisation of indeterminate lesions on ct / mri as benign , allowing curative resection to be attempted . evidence of unresectable metastatic disease on fdg pet - ct , which was either indeterminate or evaded detection on prior ct / mri . fdg pet - ct characterisation of indeterminate lesions on ct / mri as benign , allowing curative resection to be attempted . minor impact : fdg pet - ct confirmation of suspicious unresectable findings on ct / mri . no impact : no additional findings on fdg pet - ct compared with ct / mri.indeterminate findings on fdg pet - ct which did not alter the status of the patient with regards to resectability . indeterminate findings on fdg pet - ct which did not alter the status of the patient with regards to resectability . if findings on fdg pet - ct fell into both a minor impact and a major impact category then overall the impact was considered as major . in total , 111 patients underwent 118 fdg pet - ct scans ( 45 men , 66 women ) . mean patient age was 65  years ( range 2487 , lower quartile 58 and upper quartile 73 ) . there were 30 patients with suspected gallbladder carcinoma and 81 with cholangiocarcinoma ( 47 intra - hepatic , 34 extra - hepatic ) . eighty - nine scans were performed for initial staging ( table  1 ) , five scans for restaging following chemotherapy prior to consideration of radical surgery and 24 scans for assessment of suspected disease recurrence ( table  2).table 1pet - ct findings in comparison to ct / mri for scans performed for initial staging and re - staging following chemotherapy . the findings on pet - ct compared with findings on ct / mri are presented as a fraction of the total number of cases in each categoryct / mr imaging for disease resectability at initial stagingpet - ct negativepet - ct indeterminatepet - ct positivepet - ct false - negativepet - ct false - positiveresectable  gbc5/270/278/273/270/27  cc37/672/6710/673/671/67  total42/942/9418/946/941/94indeterminate  gbc0/271/271/270/271/27  cc2/670/671/670/670/67  total2/941/942/940/941/94suspected unresectable  gbc0/270/278/270/270/27  cc0/670/6710/671/670/67  total0/940/9418/941/940/94gbc gallbladder carcinoma , cc cholangiocarcinomatable 2pet - ct findings in comparison to ct / mri for scans performed for possible recurrence . the findings on pet - ct compared with findings on ct / mri are presented as a fraction of the total number of cases in each categoryct / mr imaging for suspected recurrencepet - ct negativepet - ct indeterminatepet - ct positivepet - ct false - negativepet - ct false - positiveclear  gbc1/40/42/40/40/4  cc1/200/203/200/200/20  total2/240/245/240/240/24indeterminate  gbc1/40/40/40/40/4  cc2/200/202/201/200/20  total3/240/242/241/240/24suspected  gbc0/40/40/40/40/4  cc0/200/2011/200/200/20  total0/240/2411/240/240/24gbc gallbladder carcinoma , cc cholangiocarcinoma pet - ct findings in comparison to ct / mri for scans performed for initial staging and re - staging following chemotherapy . the findings on pet - ct compared with findings on ct / mri are presented as a fraction of the total number of cases in each category gbc gallbladder carcinoma , cc cholangiocarcinoma pet - ct findings in comparison to ct / mri for scans performed for possible recurrence . the findings on pet - ct compared with findings on ct / mri are presented as a fraction of the total number of cases in each category gbc gallbladder carcinoma , cc cholangiocarcinoma the majority of patients underwent initial staging with cect thorax / abdomen / pelvis with or without mri . a minority only underwent mri of the upper abdomen prior to pet - ct ; however , in none of these patients did pet - ct have an impact by finding disease outside of the imaging field performed for mri . overall , fdg pet - ct had a major impact on subsequent patient management in 33 cases ( 28  % ) . this consisted of 39  % ( n  =  12 ) of gallbladder carcinomas , 26  % ( n  =  14 ) of intra - hepatic cholangiocarcinomas and 21  % ( n  =  7 ) of extra - hepatic cholangiocarcinomas . eleven of these patients had occult metastatic disease : sites included liver ( n  =  4 ) , peritoneum ( n  =  6 ) and bone ( n  =  1 ) . there were seven cases of unsuspected lymph node involvement ; four unsuspected lymph node involvement and peritoneal disease ; two unsuspected liver metastases and lymph node involvement ; two were found to have unsuspected synchronous primary cancers . in a further seven patients , fdg pet - ct clarified indeterminate lesions seen on cross - sectional imaging as either malignant ( n  =  2 ) or benign ( n  =  5 ) . fdg pet - ct had a minor impact in 17  % of cases ( 20/118 ) and no impact in 55  % of cases ( 65/118 ) . these results are summarised in table  3 , with a breakdown of the impact of fdg pet - ct performed for initial staging versus suspected disease recurrence.table 3clinical impact of pet - ctmajorminorno impactgbinitial staging33  % ( 9/27)7  % ( 2/27)60  % ( 16/27)suspected recurrence75  % ( 3/4)0  % ( 0/4)25  % ( 1/4)total39  % ( 12/31)6  % ( 2/31)55  % ( 17/31)cc intrahepaticinitial staging20  % ( 9/45)11  % ( 5/45)69  % ( 31/45)suspected recurrence56  % ( 5/9)44  % ( 4/9)0  % ( 0/9)total26  % ( 14/54)17  % ( 9/54)57  % ( 31/54)cc extrahepaticinitial staging23  % ( 5/22)9  % ( 2/22)68  % ( 15/22)suspected recurrence18  % ( 2/11)64  % ( 7/11)18  % ( 2/11)total21  % ( 7/33)27  % ( 9/33)52  % ( 17/33)cc allinitial staging21  % ( 14/67)10  % ( 7/67)69  % ( 46/67)suspected recurrence35  % ( 7/20)55  % ( 11/20)10  % ( 2/20)total24  % ( 21/87)21  % ( 18/87)55  % ( 48/87)total28  % ( 33/118)17  % ( 20/118)55  % ( 65/118)gbc gallbladder carcinoma , cc cholangiocarcinoma clinical impact of pet - ct gbc gallbladder carcinoma , cc cholangiocarcinoma thirty patients with suspected gallbladder carcinoma underwent a total of 31 fdg pet - ct scans . fdg pet - ct had a major impact on patient management in 39  % of cases ( 12/31 ) , including finding disease recurrence in two , characterising indeterminate peritoneal nodules as benign in one , and finding new disease sites in seven ( retroperitoneal lymph node involvement n  =  1 ; lymph node and liver / peritoneal metastases overall , fdg pet - ct upstaged 26  % ( 7/27 ) of the scans performed for initial staging and downstaged a further 4  % ( 1/27).fig . 1axial image panels of contrast - enhanced ct , fused pet - ct and pet in a patient with incidental gallbladder carcinoma in a cholecystectomy specimen . pet - ct showed uptake in a 10-mm segment iii liver metastasis ( arrow ) unsuspected on the initial contrast enhanced ct and subsequently confirmed with mri axial image panels of contrast - enhanced ct , fused pet - ct and pet in a patient with incidental gallbladder carcinoma in a cholecystectomy specimen . pet - ct showed uptake in a 10-mm segment iii liver metastasis ( arrow ) unsuspected on the initial contrast enhanced ct and subsequently confirmed with mri fdg pet - ct had a minor impact on patient management in 6  % of cases ( 2/31 ) by confirming the presence of suspicious unresectable peritoneal disease in one case and liver metastases in the other , as suspected on ct / mri . fdg pet - ct had no impact on patient management in the remaining 55  % of cases ( 17/31 ) . fdg pet - ct was falsely negative in three cases for peritoneal involvement that was later found at surgery . fdg pet - ct was falsely positive in one patient with a suspected malignant gallbladder mass , where the final histology showed xanthogranulomatous cholecystitis only . of the 26 confirmed gallbladder carcinomas , only 15 remained in situ at time of pet - ct . all showed uptake of fdg ( suv mean 15.2 , range 4.038.4 ; sensitivity 100  % ) . eighty - one patients with suspected cholangiocarcinoma ( 47 intra - hepatic , 34 extra - hepatic ) underwent a total of 87 fdg pet - ct scans . sixty - two scans were performed for initial staging ( 39 intra - hepatic , 23 extra - hepatic ) , 20 for suspected disease recurrence ( 9 intra - hepatic , 11 extra - hepatic ) and 5 for restaging following chemotherapy prior to consideration of radical surgery ( 4 intra - hepatic , 1 extra - hepatic ) . fdg pet - ct had a major impact on patient management in 24  % of cases ( 21/87 ) . of these , 26  % were intra - hepatic ( 14/54 ) and 21  % extra - hepatic ( 7/33 ) . fdg pet - ct found disease recurrence at sites not suspected on ct / mri ( n  =  5 ) and characterised four indeterminate lesions as malignant ( pulmonary nodule n  =  1 ) or benign ( pulmonary nodule n  =  1 ; peritoneal nodule n  =  1 ; peritoneal haziness / lymph node enlargement in a case of suspected recurrence n  =  1 ) . fdg pet - ct confirmed response to chemotherapy in a patient with a large intra - hepatic cholangiocarcinoma and a bone metastasis that was unsuspected on ct / mri ( fig .  2 ) . fdg pet - ct found new disease sites in 11 ( lymph node involvement n  =  6 ; liver and lymph node involvement n  =  1 ; peritoneal disease n  =  2 ; lymph node involvement and peritoneal disease n  =  1 [ fig  3 ] ; bone metastasis n  =  1 ) . overall , fdg pet - ct upstaged 19  % ( 12/62 ) and downstaged 3  % ( 2/62 ) of the scans performed for initial staging ( downstaged one peritoneal deposit and one pulmonary nodule , both in intra - hepatic cholangiocarcinomas).fig . 2pet maximum intensity projection ( mip ) and axial image panels of ct and fused pet - ct in a patient with a large intra - hepatic cholangiocarcinoma . initial pet - ct ( upper row panel and left hand mip ) showed fdg - avid primary tumour ( a ) with unsuspected uptake in t2 vertebral body . pet - ct performed 6-months following chemotherapy ( lower row panel and right hand mip ) showed mild residual uptake at t2 with sclerotic changes in the underlying bone in keeping with a healed / treated bone metastasisfig . 3axial image panels of contrast enhanced ct ( first column ) , fused pet - ct ( second column ) and pet ( third column ) in a patient with hilar cholangiocarcinoma . fdg - avid primary tumour ( a ) with unsuspected nodal ( b ) and peritoneal ( c ) metastases . the peritoneal metastasis was not apparent on the contrast enhanced ct performed approximately 4 weeks prior to pet - ct pet maximum intensity projection ( mip ) and axial image panels of ct and fused pet - ct in a patient with a large intra - hepatic cholangiocarcinoma . initial pet - ct ( upper row panel and left hand mip ) showed fdg - avid primary tumour ( a ) with unsuspected uptake in t2 vertebral body . pet - ct performed 6-months following chemotherapy ( lower row panel and right hand mip ) showed mild residual uptake at t2 with sclerotic changes in the underlying bone in keeping with a healed / treated bone metastasis axial image panels of contrast enhanced ct ( first column ) , fused pet - ct ( second column ) and pet ( third column ) in a patient with hilar cholangiocarcinoma . fdg - avid primary tumour ( a ) with unsuspected nodal ( b ) and peritoneal ( c ) metastases . the peritoneal metastasis was not apparent on the contrast enhanced ct performed approximately 4 weeks prior to pet - ct fdg pet - ct had a minor impact on patient management in 21  % of cases ( 18/87 ) by confirming suspicious unresectable findings seen on ct / mri ( 9/54 of intra - hepatic and 9/33 of extra - hepatic cholangiocarcinomas ) . fdg pet - ct had no impact on patient management in the remaining 55  % of cases ( 48/87 ) . the first was a patient with primary sclerosing cholangitis ( psc ) and a suspicious right liver mass on surveillance mri , later confirmed to be a well - differentiated cholangiocarcinoma ( no mucinous differentiation on histology ) . fdg pet - ct was also falsely negative in another psc patient where cect showed a filling defect in the distal cbd associated with biliary dilatation ; surgery was undertaken based on the cect findings and post - operative histology confirmed two small foci of cholangiocarcinoma measuring 8  mm and 13  mm . fdg pet - ct was falsely negative for peritoneal disease in a patient with an fdg - avid intra - hepatic cholangiocarcinoma and in two patients with extra - hepatic cholangiocarcinomas ( both primary tumours were also fdg negative ) . fdg pet - ct was falsely positive in one patient found to have a hilar mass on mri . fdg pet - ct showed uptake in the liver , mesenteric nodes and peritoneal deposits thought to represent disseminated malignancy . however , the patient had cholangitis with bile leak at the time of fdg pet - ct , as confirmed on subsequent staging laparoscopy . fdg pet - ct was indeterminate in two cases , one with several enlarged lymph nodes showing low grade uptake and the other with mild fdg activity in a trace of pelvic free fluid . fourteen of the 62 confirmed primary cholangiocarcinomas were fdg negative on pet - ct , with an overall sensitivity of 77  % . three of 39 intra - hepatic cholangiocarcinomas ( suv mean 14.4 , range 3.745.8 ) and 11 of 23 extra - hepatic cholangiocarcinoma ( suv mean 6.9 , range 4.418.5 ) were fdg negative , giving sensitivities of 92  % and 52  % respectively . with regards to tumour morphology , 15 of the 62 confirmed primary cholangiocarcinomas were of the infiltrative type ( 6 of which were fdg negative giving a sensitivity of 60  % ) , whilst 47 were mass forming ( 8 of which were fdg negative giving a sensitivity of 83  % ) . thirty patients with suspected gallbladder carcinoma underwent a total of 31 fdg pet - ct scans . fdg pet - ct had a major impact on patient management in 39  % of cases ( 12/31 ) , including finding disease recurrence in two , characterising indeterminate peritoneal nodules as benign in one , and finding new disease sites in seven ( retroperitoneal lymph node involvement n  =  1 ; lymph node and liver / peritoneal metastases n  =  2 ( fig . overall , fdg pet - ct upstaged 26  % ( 7/27 ) of the scans performed for initial staging and downstaged a further 4  % ( 1/27).fig . 1axial image panels of contrast - enhanced ct , fused pet - ct and pet in a patient with incidental gallbladder carcinoma in a cholecystectomy specimen . pet - ct showed uptake in a 10-mm segment iii liver metastasis ( arrow ) unsuspected on the initial contrast enhanced ct and subsequently confirmed with mri axial image panels of contrast - enhanced ct , fused pet - ct and pet in a patient with incidental gallbladder carcinoma in a cholecystectomy specimen . pet - ct showed uptake in a 10-mm segment iii liver metastasis ( arrow ) unsuspected on the initial contrast enhanced ct and subsequently confirmed with mri fdg pet - ct had a minor impact on patient management in 6  % of cases ( 2/31 ) by confirming the presence of suspicious unresectable peritoneal disease in one case and liver metastases in the other , as suspected on ct / mri . fdg pet - ct had no impact on patient management in the remaining 55  % of cases ( 17/31 ) . fdg pet - ct was falsely negative in three cases for peritoneal involvement that was later found at surgery . fdg pet - ct was falsely positive in one patient with a suspected malignant gallbladder mass , where the final histology showed xanthogranulomatous cholecystitis only . of the 26 confirmed gallbladder carcinomas , only 15 remained in situ at time of pet - ct . all showed uptake of fdg ( suv mean 15.2 , range 4.038.4 ; sensitivity 100  % ) . eighty - one patients with suspected cholangiocarcinoma ( 47 intra - hepatic , 34 extra - hepatic ) underwent a total of 87 fdg pet - ct scans . sixty - two scans were performed for initial staging ( 39 intra - hepatic , 23 extra - hepatic ) , 20 for suspected disease recurrence ( 9 intra - hepatic , 11 extra - hepatic ) and 5 for restaging following chemotherapy prior to consideration of radical surgery ( 4 intra - hepatic , 1 extra - hepatic ) . fdg pet - ct had a major impact on patient management in 24  % of cases ( 21/87 ) . of these , 26  % were intra - hepatic ( 14/54 ) and 21  % extra - hepatic ( 7/33 ) . fdg pet - ct found disease recurrence at sites not suspected on ct / mri ( n  =  5 ) and characterised four indeterminate lesions as malignant ( pulmonary nodule n  =  1 ) or benign ( pulmonary nodule n  =  1 ; peritoneal nodule n  =  1 ; peritoneal haziness / lymph node enlargement in a case of suspected recurrence n  =  1 ) . fdg pet - ct confirmed response to chemotherapy in a patient with a large intra - hepatic cholangiocarcinoma and a bone metastasis that was unsuspected on ct / mri ( fig .  2 ) . fdg pet - ct found new disease sites in 11 ( lymph node involvement n  =  6 ; liver and lymph node involvement n  =  1 ; peritoneal disease n  =  2 ; lymph node involvement and peritoneal disease n  =  1 [ fig  3 ] ; bone metastasis n  =  1 ) . overall , fdg pet - ct upstaged 19  % ( 12/62 ) and downstaged 3  % ( 2/62 ) of the scans performed for initial staging ( downstaged one peritoneal deposit and one pulmonary nodule , both in intra - hepatic cholangiocarcinomas).fig . 2pet maximum intensity projection ( mip ) and axial image panels of ct and fused pet - ct in a patient with a large intra - hepatic cholangiocarcinoma . initial pet - ct ( upper row panel and left hand mip ) showed fdg - avid primary tumour ( a ) with unsuspected uptake in t2 vertebral body . pet - ct performed 6-months following chemotherapy ( lower row panel and right hand mip ) showed mild residual uptake at t2 with sclerotic changes in the underlying bone in keeping with a healed / treated bone metastasisfig . 3axial image panels of contrast enhanced ct ( first column ) , fused pet - ct ( second column ) and pet ( third column ) in a patient with hilar cholangiocarcinoma . fdg - avid primary tumour ( a ) with unsuspected nodal ( b ) and peritoneal ( c ) metastases . the peritoneal metastasis was not apparent on the contrast enhanced ct performed approximately 4 weeks prior to pet - ct pet maximum intensity projection ( mip ) and axial image panels of ct and fused pet - ct in a patient with a large intra - hepatic cholangiocarcinoma . initial pet - ct ( upper row panel and left hand mip ) showed fdg - avid primary tumour ( a ) with unsuspected uptake in t2 vertebral body . pet - ct performed 6-months following chemotherapy ( lower row panel and right hand mip ) showed mild residual uptake at t2 with sclerotic changes in the underlying bone in keeping with a healed / treated bone metastasis axial image panels of contrast enhanced ct ( first column ) , fused pet - ct ( second column ) and pet ( third column ) in a patient with hilar cholangiocarcinoma . fdg - avid primary tumour ( a ) with unsuspected nodal ( b ) and peritoneal ( c ) metastases . the peritoneal metastasis was not apparent on the contrast enhanced ct performed approximately 4 weeks prior to pet - ct fdg pet - ct had a minor impact on patient management in 21  % of cases ( 18/87 ) by confirming suspicious unresectable findings seen on ct / mri ( 9/54 of intra - hepatic and 9/33 of extra - hepatic cholangiocarcinomas ) . fdg pet - ct had no impact on patient management in the remaining 55  % of cases ( 48/87 ) . the first was a patient with primary sclerosing cholangitis ( psc ) and a suspicious right liver mass on surveillance mri , later confirmed to be a well - differentiated cholangiocarcinoma ( no mucinous differentiation on histology ) . fdg pet - ct was also falsely negative in another psc patient where cect showed a filling defect in the distal cbd associated with biliary dilatation ; surgery was undertaken based on the cect findings and post - operative histology confirmed two small foci of cholangiocarcinoma measuring 8  mm and 13  mm . fdg pet - ct was falsely negative for peritoneal disease in a patient with an fdg - avid intra - hepatic cholangiocarcinoma and in two patients with extra - hepatic cholangiocarcinomas ( both primary tumours were also fdg negative ) . fdg pet - ct was falsely positive in one patient found to have a hilar mass on mri . fdg pet - ct showed uptake in the liver , mesenteric nodes and peritoneal deposits thought to represent disseminated malignancy . however , the patient had cholangitis with bile leak at the time of fdg pet - ct , as confirmed on subsequent staging laparoscopy . fdg pet - ct was indeterminate in two cases , one with several enlarged lymph nodes showing low grade uptake and the other with mild fdg activity in a trace of pelvic free fluid . fourteen of the 62 confirmed primary cholangiocarcinomas were fdg negative on pet - ct , with an overall sensitivity of 77  % . three of 39 intra - hepatic cholangiocarcinomas ( suv mean 14.4 , range 3.745.8 ) and 11 of 23 extra - hepatic cholangiocarcinoma ( suv mean 6.9 , range 4.418.5 ) were fdg negative , giving sensitivities of 92  % and 52  % respectively . with regards to tumour morphology , 15 of the 62 confirmed primary cholangiocarcinomas were of the infiltrative type ( 6 of which were fdg negative giving a sensitivity of 60  % ) , whilst 47 were mass forming ( 8 of which were fdg negative giving a sensitivity of 83  % ) . most previous studies examining the role of fdg pet - ct in biliary malignancy have focused on the effectiveness of fdg pet - ct in assessing the primary tumour and extent of any spread , with few considering its overall impact on patient management . this study aimed to evaluate the impact of fdg pet - ct on the management pathway of patients with primary biliary malignancy and to help define its role in the work - up of these tumours . fdg pet - ct was concordant with findings on ct / mri in 74 cases ( 63  % ) 44 with no distant disease on fdg pet - ct or ct / mri , 1 with indeterminate findings on both fdg pet - ct and ct / mri and 29 with suspected distant disease on both fdg pet - ct and ct / mri . overall , fdg pet - ct had a major impact in 28  % of cases ( 33/118 ) . it detected occult sites of disease in 24 patients , helped to characterise 7 indeterminate lesions on cross - sectional imaging and detected 2 incidental synchronous primary cancers . fdg pet - ct had the biggest influence in the gallbladder carcinoma group , having a major impact in 39  % of cases ( 12/31 ) , including upstaging 27  % of the scans performed for initial staging ( 7/26 ) . fdg pet - ct changed management mainly by identifying occult sites of disease not detected by ct / mri ( in nine patients ) and finding unsuspected sites of disease recurrence ( in two patients ) . few published studies describe rates of impact of fdg pet - ct in gallbladder cancer ; however , our rate is somewhat higher than that reported previously . in a recent study by corvera et al . , fdg - pet ( without ct ) altered management in 20  % ( 25/126 ) of patients with biliary cancer , including 23  % ( 7/31 ) of patients with gallbladder carcinoma . similarly , petrwosky et al .   in a study that included 14 patients with gallbladder carcinoma report a change of management in 17  % , whilst lee et al .   in a study of 16 patients report a change of management in 9.8  % of patients who were deemed resectable after standard staging ; however both these studies also included patients with cholangiocarcinoma with no subgroup data . a possible explanation for the discrepancy in the rates of impact may be due to the process of patient selection . all patients in our study were individually selected for fdg pet - ct following discussion at a specialised mdt , where specific indications for performing the test were considered on a case - by - case basis . fdg pet - ct was not deemed necessary in some patients if conventional imaging with ct / mri was thought to be clear - cut . other published studies were less selective and included all patients with a suspected diagnosis of gallbladder carcinoma . the time lag to fdg pet - ct following conventional imaging may also have contributed to some patients with very aggressive tumours developing new sites of disease , which were then detected on fdg pet - ct . however , the vast majority of cases were scanned within a 90-day period with a mean time to pet - ct of 38  days . the other studies described did not report a time - frame for performing pet - ct and hence a comparison can not be made . gallbladder carcinoma is associated with a rate of peritoneal metastasis as high as 3075  % , and the risk of metastasis strongly correlates with the presenting t stage . while fdg pet - ct can detect occult sites of disease not seen on conventional imaging , it may still fail to identify carcinomatosis due to reduced sensitivity in detection of sub - centimetre lesions ( a recognised limitation of pet ) and , in particular , small volume peritoneal disease . three of the gallbladder cancers in our group thought resectable after fdg pet - ct were found to have unresectable peritoneal disease at laparotomy , with similar findings reported by others . in the study by corvera et al . , five of the gallbladder cancers deemed resectable on pet were found to be unresectable at surgical exploration , three having locally advanced disease and two small volume peritoneal disease . anderson et al .   in a study of 14 patients with gallbladder carcinoma detected peritoneal carcinomatosis in only three of six affected patients , attributing the results to the small size of the lesions . 4 ) , a finding also reported by wakabayashi et al .   and koh et al . anderson et al .   described a false - positive in a patient studied 1 month after cholecystectomy with fdg uptake in residual post - surgical inflammatory change , thought to represent metastatic disease . although this was not our experience , it does highlight the importance of considering the time interval between surgery and performing fdg pet - ct in order to minimise uptake in inflammatory tissue , especially when the gallbladder carcinoma is incidental and post - surgical staging is performed . in our experience , it is advisable to wait a minimum of 4  weeks and preferably at least 6  weeks following surgery to avoid false - positive uptake in post - surgical inflammation.fig . 4pet maximum intensity projection ( mip ) image , axial image panels of fused pet - ct , pet and contrast enhanced mri demonstrating false - positive fdg uptake and abnormal gallbladder enhancement in a patient with suspected gallbladder carcinoma ( arrows ) . post - operative histology showed xanthogranulomatous cholecystitis with no evidence of malignancy pet maximum intensity projection ( mip ) image , axial image panels of fused pet - ct , pet and contrast enhanced mri demonstrating false - positive fdg uptake and abnormal gallbladder enhancement in a patient with suspected gallbladder carcinoma ( arrows ) . post - operative histology showed xanthogranulomatous cholecystitis with no evidence of malignancy fdg pet - ct identified 100  % of the 15 primary gallbladder carcinomas left in situ . this is consistent with previous published studies , which report sensitivity rates of 87.5 - 100  % for fdg pet - ct [ 10 , 11 ] and 75 - 86  % for pet alone [ 9 , 13 , 15 , 16 ] . the overall sensitivity of fdg pet - ct for the detection of primary cholangiocarcinoma was generally lower at 77  % ( 48/62 ) , with a much higher sensitivity for intra - hepatic than for extra - hepatic cholangiocarcinoma ( 92  % , 36/39 versus 52  % , 12/23 ) . similar findings have been reported by petrowsky et al .   with fdg pet - ct sensitivity of 93  % for intra - hepatic ( n  =  19 ) versus 55  % for extra - hepatic cholangiocarcinoma ( n  =  36 ) . kim et al .   in a study of 123 patients with suspected cholangiocarcinoma also reported higher sensitivity of fdg pet - ct for intra - hepatic cholangiocarcinoma with pet - ct being falsely negative for the primary tumour in 15 patients ( 14 of which were extra - hepatic cholangiocarcinomas ) . as well as its location similar to our results , anderson et al .   in a study of 36 patients with suspected extra - hepatic cholangiocarcinoma reported a sensitivity of fdg - pet of 85  % for nodular morphology ( mass > 1  cm ) versus only 18  % for infiltrating morphology . the difference has been attributed to infiltrating tumours having lower cellular density and causing little structural abnormality . fdg pet - ct is known to have low sensitivity for mucinous tumours and hence may miss mucinous types of cholangiocarcinoma . whilst pet - ct may have little diagnostic advantage over traditional imaging modalities in detecting the primary cholangiocarcinoma , it has been shown to be substantially sensitive and specific for the detection and characterisation of metastases . in this series , fdg pet - ct had a major impact on patient management in 24  % ( 21/87 ) of cholangiocarcinomas , 26  % ( 14/54 ) of intra - hepatic and 21  % ( 7/33 ) of extra - hepatic tumours , finding occult sites of disease in 16 ( including 5 cases of recurrence ) and characterizing indeterminate lesions in another 5 . overall , fdg pet - ct upstaged 19  % ( 12/62 ) and downstaged 3  % ( 2/62 ) of the scans performed for initial staging . this rate of impact is similar to that reported previously . in the study by anderson et al . , fdg - pet led to a change in surgical management in 30  % ( 11/36 ) of patients with suspected extra - hepatic cholangiocarcinoma due to detection of unsuspected metastases . kim et al .   also reported about 94/123 patients who went on to have a final histological diagnosis of cholangiocarcinoma , for whom fdg pet - ct findings changed management in 15 ( 15.9  % ) , upgrading from resectable to unresectable in 7 patients ( 7.4  % ) and downgrading a further 8 ( 8.5  % ) . moon et al . , in a series of 54 patients , reported that fdg - pet ( without ct ) detected nine metastatic lesions not found by other imaging studies , stopping two patients from undergoing unnecessary laparotomy . fdg pet - ct was falsely negative in two out of three patients with psc , failing to detect the primary cholangiocarcinoma in both . one was a very small extra - hepatic tumour , which may have been below the size threshold for detection by pet . the lack of fdg uptake in the second tumour , a large well - differentiated intra - hepatic cholangiocarcinoma , is less clear . there are limited published data regarding the efficacy of fdg pet - ct in patients with psc . performed fdg - pet on 24 patients with psc awaiting liver transplantation with no evidence of malignancy on ct , mri or ultrasound . three patients had cholangiocarcinoma that was correctly identified by pet and the authors concluded that fdg - pet may be useful in screening for cholangiocarcinoma in patients with psc . however , this did not prove to be the case in our experience or of others . similar to the gallbladder carcinoma group , fdg pet - ct was also falsely negative in three cholangiocarcinomas with unsuspected peritoneal disease found at laparotomy . in the study by kim et al . , fdg pet - ct also failed to detect distant metastases in five patients , including four with peritoneal disease . we found a single false - positive in a patient with suspected peritoneal disease due to disseminated fdg uptake , however staging laparotomy was negative and appearances had been secondary to cholangitis and bile leak at the time of pet - ct . false - positive fdg uptake due to benign inflammatory causes is well recognised and a degree of caution has to be observed to avoid misinterpretation . the referral mechanism for fdg pet - ct was determined on a case - by - case basis via a specialist mdt meeting , with each patient specifically chosen for the test to help answer a clinical or radiological ambiguity and therefore creating a selection bias . the time lag between studies also causes a potential bias for pet - ct superiority in patients with rapidly progressive disease . another limitation is that data were collected retrospectively at a large tertiary referral centre , receiving patients from a wide geographical area . consequently , a proportion of imaging studies were performed at referring regional hospitals using different equipment and acquisition protocols , possibly biasing image interpretation . the injection rate and volume of contrast medium were not patient tailored , which may also affect diagnostic accuracy . assessment of impact was determined following a comprehensive review of all clinical and imaging data ; however , such an assessment may be imperfect in a retrospective study . despite these issues , we found fdg pet - ct to be reliable in characterising indeterminate lesions and discriminating between benign and malignant disease with few false - positive results . the majority of false - negative findings were due to small volume peritoneal disease , which is a limitation for all imaging studies at present . fdg pet - ct was particularly effective at detecting metastatic disease that was unsuspected or equivocal on cross - sectional imaging studies , changing the stage of disease and influencing management in a significant number of patients . by detecting occult metastatic disease and characterizing indeterminate lesions , fdg pet - ct can have a major influence on clinical decision making in primary biliary malignancy both as part of initial work - up and for identifying recurrent disease , overall helping triage patients to the most appropriate treatment .
objectivesto assess the impact on clinical management of introducing 18f - fluoro-2-deoxy - d - glucose ( fdg ) positron emission tomography ( pet)-computed tomography ( ct ) in to the work - up of patients with primary and recurrent biliary malignancy.methodsconsecutive patients with primary biliary tumours undergoing fdg pet - ct at a single large tertiary referral centre between november 2007 and september 2010 were retrospectively analysed . 
 findings on fdg pet - ct compared with ct / magnetic resonance imaging ( mri ) and impact on subsequent patient management were evaluated . 
 impact was divided into : ( 1 ) major  detection of occult disease or characterisation of indeterminate lesion(s ) on ct / mri ; ( 2 ) minor  confirmation of suspected metastases seen on ct / mri ; ( 3 ) no impact.resultsone hundred and eleven patients underwent 118 fdg pet - ct scans , including 30 with suspected gallbladder carcinoma and 81 with cholangiocarcinoma . 
 eighty - nine scans were performed for initial staging , five for restaging following neoadjuvant chemotherapy and 24 for suspected disease recurrence . in 33 cases ( 28  % ) , 
 fdg pet - ct had a major impact on subsequent patient management ( 39  % gallbladder carcinoma , 26  % intrahepatic cholangiocarcinoma and 21  % extrahepatic cholangiocarcinoma ) . 
 fdg pet - ct had a minor impact in 20 cases ( 17  % ) and no impact in 65 cases ( 55  % ) .conclusionsby detecting occult metastatic disease and characterising indeterminate lesions , fdg pet - ct can have a major influence on clinical decision - making in primary and recurrent biliary malignancy .