RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Management of difficult bile duct stones and indeterminate bile duct structures: Reduced ERCP radiation exposure with adjunct use of digital single-operator cholangioscopy.

INTRODUCTION: Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is an well-established endoscopic procedure for the management of biliary diseases. The use of fluoroscopy during ERCP has often raised concerns regarding potential risks from radiation exposure, particularly in complex cases. We investigated whether a new digital single-operator cholangioscopy (D-SOC) system, used adjunctively to ERCP, actually reduces patient radiation exposure. MATERIALS AND METHODS: We retrospectively analyzed a prospective database (April 2016 to October 2018) including consecutive patients who underwent successful management of difficult-to-treat biliary stones or indeterminate biliary strictures by using either conventional ERCP (ERCP cohort) or ERCP in conjunction with D-SOC (ERCP/D-SOC cohort). The overall patient radiation exposure outcomes were compared in terms of Kerma Area Product (KAP), Fluoroscopy time (T) and the total number of films (F). RESULTS: Overall, 47 patients (mean 71.8 years, 59.6% males) were included (ERCP cohort = 29, ERCP/D-SOC cohort = 18), referred either for difficult bile duct stones (n = 36) or indeterminate biliary strictures (n = 11). The median KAP, T and F in the ERCP/D-SOC cohort were 12.3 Gycm2, 3.7 min and 4 films respectively, compared with 52.1 Gycm2, 8.4 min, and 5 films respectively in the ERCP cohort. Statistically significant differences (P = 0.0001) were found for KAP and T. CONCLUSIONS: Adjunct use of a digital cholangioscopy platform appears to significantly reduce radiation exposure in patients undergoing ERCP for the management of difficult bile stones or indeterminate biliary strictures.

Split-bolus vs. multiphasic contrast bolus protocol in patients with pancreatic cancer or cholangiocarcinoma.

PURPOSE: To investigate the image quality, diagnostic accuracy, and dose reduction potential of a split-bolus protocol(SBP) compared with a multiphasic protocol(MPP) in the detection of recurrent or progressive pancreatic ductal adenocarcinoma(PDAC) or cholangiocarcinoma(CC) using contrast- enhanced computed tomography(CECT). MATERIALS AND METHODS: This prospective study included 56 patients who underwent CECT, 28 with our institutional standard MPP(100 ml contrast bolus) and 28 with a novel SBP(110 ml). Radiation exposure was determined in terms of total dose- length product(DLP) and computed tomography dose index(CTDI). Image quality was measured objectively by analysis of attenuation in Hounsfield units(HU) in regions of interest(ROIs) and subjectively by two blinded readers using a Likert scale. Diagnostic accuracy and interreader variability were tested. RESULTS: The total DLP of the SBP group(498.1 ± 43.7 mGy*cm) was significantly lower than in the MPP group(1,092.5 ± 106.9 mGy*cm; p < 0.001). The SBP showed higher contrast enhancement of all critical anatomical structures including portal vein, liver, and pancreas compared with the MPP, except for the aorta(SBP: 326.9 ± 15.7 HU vs. MPP: 246.7 ± 12.2 HU; p < 0.001). Subjective analysis revealed poorer image quality ratings for important landmarks with the MPP (resection surface: p = 0.624, portal vein: p = 0.395, liver p = 0.361). The two blinded readers correlated significantly. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and overall interreader variabilities correlated significantly. Furthermore, significantly fewer slices per exam were required for the SBP(1,823 vs. 3,235; p < 0.001). CONCLUSION: The SBP provides the same image quality and diagnostic accuracy as an MPP while significantly lowering radiation exposure in CT follow-up of PDAC or CC.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : A systematic analysis of 102 cases.

OBJECTIVE: Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. MATERIALS AND METHODS: We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. RESULTS: 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). CONCLUSION: iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Endoluminal Nd:YAG laser application in ex vivo biliary porcine tissue.

Adequate biliary drainage with endoscopic or percutaneous placement of self-expandable metal stents represents the goal of palliation in patients with inoperable malignant obstruction of the biliary tree. As an adjunct to stenting, various tissue ablation treatments have been proposed with conflicting results. The aim of this study was to test the effect on biliary tissue of a new ablation technique based on Nd:YAG laser light delivery. The study was conducted on ex vivo specimens of 18 healthy farm pigs, using cystic ducts that are the simplest biliary structures to isolate and cannulate ex vivo. A 22G cannula was positioned into the cystic duct and a quartz optical fibre, with a prototypal cooling system, was inserted into the cannula. Nd:YAG laser output powers of 10, 12, and 15 W were tested, with a total delivered energy of 1000 J in continuous mode in each case. After laser treatment, histological analysis was performed. At macroscopical examination, no lesions of the external wall of the cystic ducts were detected. At histopathological examination, a coagulative necrosis involving the entire mucosa up to the muscolaris propria without significant changes of periductal tissues was observed in all specimens. This study shows the possibility of using Nd:YAG laser on ex vivo porcine biliary ducts with the effect of obtaining a coagulative necrosis involving the whole mucosa.

No infectious hepatic complications following radioembolization with 90Y microspheres in patients with biliodigestive anastomosis.

AIM: To retrospectively evaluate infectious hepatic complications of transarterial radioembolization (RE) of the liver in patients with pre-existing biliodigestive anastomosis. PATIENTS AND METHODS: Patients who underwent RE were retrospectively analyzed. All patients had at least a contrast-enhanced magnetic resonance imaging or contrast-enhanced triple-phase computed tomographic scan before and 6-8 weeks after RE. RESULTS: Overall, 143 patients (67 women, 76 men; median age = 65 ± 11.2 years) were analyzed. Nine patients had a biliodigestive anastomosis. The complications were as follows: one case of cholecystitis, three of gastroduodenal ulcer with one ulcer perforation, and six of radioembolization-induced liver disease. There were no infectious complications. There were no major or minor complications in the group with previous biliodigestive anastomosis. CONCLUSION: Pre-existing bilioenteric anastomoses are not a negative predictive factor for the development of infectious hepatic complications after RE. RE with (90)Y microspheres can be safely performed following careful patient selection.

Percutaneous treatment of hepatocellular carcinoma in patients with cirrhosis: a comparison of the safety of cryoablation and radiofrequency ablation.

PURPOSE: To compare the safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis. MATERIALS AND METHODS: This retrospective HIPAA-compliant study received institutional review board approval. Forty-two adult patients with cirrhosis underwent image-guided percutaneous ablation of hepatocellular carcinoma from 2003 to 2011. Twenty-five patients underwent 33 cryoablation procedures to treat 39 tumors, and 22 underwent 30 radiofrequency ablation procedures to treat 39 tumors. Five patients underwent both cryoablation and radiofrequency ablation procedures. Complication rates and severity per procedure were compared between the ablation groups. Potential confounding patient, procedure, and tumor-related variables were also compared. Statistical analyses included Kruskal-Wallis, Wilcoxon rank sum, and Fisher's exact tests. Two-sided P-values <0.05 were considered significant. RESULTS: The overall complication rates, 13 (39.4%) of 33 cryoablation procedures versus eight (26.7%) of 30 radiofrequency ablation procedures and severe/fatal complication rates, two (6.1%) of 33 cryoablation procedures versus one (3.3%) of 30 radiofrequency ablation procedures, were not significantly different between the ablation groups (both P=0.26). Severe complications included pneumothoraces requiring chest tube insertion during two cryoablation procedures. One death occurred within 90 days of a radiofrequency ablation procedure; all other complications were managed successfully. CONCLUSION: No significant difference was seen in the overall safety of image-guided percutaneous cryoablation and radiofrequency ablation in the treatment of hepatocellular carcinoma in patients with cirrhosis.

Bilateral kidney preservation by volumetric-modulated arc therapy (RapidArc) compared to conventional radiation therapy (3D-CRT) in pancreatic and bile duct malignancies.

BACKGROUND: To compare volumetric-modulated arc therapy plans with conventional radiation therapy (3D-CRT) plans in pancreatic and bile duct cancers, especially for bilateral kidney preservation. METHODS: A dosimetric analysis was performed in 21 patients who had undergone radiotherapy for pancreatic or bile duct carcinoma at our institution. We compared 4-field 3D-CRT and 2 arcs RapidArc (RA) plans. The treatment plan was designed to deliver a dose of 50.4 Gy to the planning target volume (PTV) based on the gross disease in a 1.8 Gy daily fraction, 5 days a week. Planning objectives were 95% of the PTV receiving 95% of the prescribed dose and no more than 2% of the PTV receiving more than 107%. Dose-volume histograms (DVH) for the target volume and the organs at risk (right and left kidneys, bowel tract, liver and healthy tissue) were compared. Monitor units and delivery treatment time were also reported. RESULTS: All plans achieved objectives, with 95% of the PTV receiving ≥ 95% of the dose (D95% for 3D-CRT = 48.9 Gy and for RA = 48.6 Gy). RapidArc was shown to be superior to 3D-CRT in terms of organ at risk sparing except for contralateral kidney: for bowel tract, the mean dose was reduced by RA compared to 3D-CRT (16.7 vs 20.8 Gy, p = 0.0001). Similar result was observed for homolateral kidney (mean dose of 4.7 Gy for RA vs 12.6 Gy for 3D-CRT, p < 0.0001), but 3D-CRT significantly reduced controlateral kidney dose with a mean dose of 1.8 Gy vs 3.9 Gy, p < 0.0007. Compared to 3D-CRT, mean MUs for each fraction was significantly increased with RapidArc: 207 vs 589, (p < 0.0001) but the treatment time was not significantly different (2 and 2.66 minutes, p = ns). CONCLUSION: RapidArc allows significant dose reduction, in particular for homolateral kidney and bowel, while maintaining target coverage. This would have a promising impact on reducing toxicities.

Mathematical solutions of the TG-43 geometry function for curved line, ring, disk, sphere, dome and annulus sources, and applications for quality assurance.

Analytic solutions for the TG-43 geometry function for curved line, ring, disk, sphere, dome and annulus shapes containing uniform distributions of air-kerma are derived. These geometry functions describe how dose distributions vary strictly due to source geometry and not including attenuation or scatter effects. This work extends the use of geometry functions for individual sources to applicators containing multiple sources. Such geometry functions may be used to verify dose distributions computed using advanced techniques, including QA of model-based dose calculation algorithms. The impact of source curvature on linear and planar implants is considered along with the specific clinical case of brachytherapy eye plaques. For eye plaques, the geometry function for a domed distribution is used with published Monte Carlo dose distributions to determine a radial dose function and anisotropy function which includes all the scatter and attenuation effects due to the phantom, eye plaque and sources. This TG-43 model of brachytherapy eye plaques exactly reproduces azimuthally averaged Monte Carlo calculations, both inside and outside the eye.

Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy.

AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for non-parenchymal cell (NPC) transplantation. METHODS: Livers of dipeptidyl peptidase IV (DPPIV)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lobule. DPPIV-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation. RESULTS: Host liver staining demonstrated 3 different repopulation types. Well defined clusters of donor-derived hepatocytes with canalicular expression of DPPIV were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPPIV-positive duct-like structures which co-localized with biliary epithelial CD49f. CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells.

103Pd-induced apoptosis of proliferative smooth muscle cells in bile ducts of dogs: significance and effects on related genes.

BACKGROUND: With the objective of developing a locally-produced radioactive stent, the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation of the expression of genes caused by gamma-radiation in order to prevent bile duct restenosis. We therefore explored the effects and significance of gamma-radiation on the activity of caspase-3, Fas and Bcl-2 genes in apoptosis of proliferative smooth muscle cells in the bile duct walls of dogs. METHODS: Twelve dogs were randomly divided into 2 groups (6 in each group). A postinjury bile duct stenosis model was established and radioactive (103)Pd ((103)palladium) or ordinary bile duct stents were implanted into the bile ducts. HE staining, RT-PCR and immunohistochemistry were used to detect the proliferation and apoptosis of bile duct smooth muscle cells in proliferative endomembrane and the expression of related caspase-3, Bcl-2 and Fas genes. RESULTS: The expression of caspase-3 and Fas genes in the bile duct tissues of dogs with radioactive stents was higher than that of dogs with ordinary stents. There was significant apoptosis of proliferative smooth muscle cells in the bile ducts. The expression of the Bcl-2 gene in the bile duct tissues of dogs with radioactive stents was lower than that in those with ordinary stents. There was significant apoptosis of proliferative smooth muscle cells in the dogs with low Bcl-2 gene expression. CONCLUSIONS: Radiation increases the activity of caspase-3 and Fas genes and is associated with apoptosis. The radioactive (103)Pd stent may facilitate apoptosis of proliferative smooth muscle cells in the bile ducts of dogs by activating these genes. The Bcl-2 gene expression level is correlated with the occurrence of apoptosis and the radiosusceptibility of cells.

Radiation dose and risk from fluoroscopically guided percutaneous transhepatic biliary procedures.

PURPOSE: To estimate radiation dose and associated risks after fluoroscopically guided percutaneous transhepatic biliary (PTB) drainage and stent implantation procedures. MATERIALS AND METHODS: Organ and effective doses, normalized to dose-area product (DAP), were estimated for PTB procedures with use of a Monte Carlo transport code and an adult mathematical phantom. Exposure parameters from 51 consecutive patients were used to determine average examination parameters for biliary drainage and stent implantation procedures. Thermoluminescent dosimeters were used in an anthropomorphic phantom to verify Monte Carlo calculations. Radiation-induced cancer and genetic risks were estimated. RESULTS: The results consist of doses normalized to DAP so patient dose from any technique and x-ray unit can be easily calculated for left and right biliary access and for separate or combined biliary and metallic stent implantation sessions. A good agreement was found between Monte Carlo-calculated data and data derived from thermoluminescent dosimetry. The average effective dose varied from 1.8 to 5.4 mSv depending on procedure approach (left vs right access) and procedure scheme. A maximum effective dose of 13 mSv was estimated for 30 minutes of fluoroscopy. CONCLUSIONS: Doses delivered to patients undergoing PTB procedures are comparable to those that arise from computed tomography protocols. Radiation-induced cancer risk may be considerable for young patients undergoing PTB drainage and stent implantation procedures.

[Expression and significance of caspase-3 gene in apoptotic muscle cells 103Pd radioactive stent bile duct in dogs].

OBJECTIVE: To discuss the expression and significance of caspase-3 gene in the apoptotic muscle cells in gamma-radiation-induced muscle cell lines. METHODS: The caspase-3 mRNA in the control and gamma-radiation induced apoptotic muscle cells was analysed by RT-PCR. RESULTS: The expression of caspase-3 gene transcript was higher in 103Pd radioactive stent dog bile duct than in general stent dog bile duct, and apoptotic muscle cells were higher in 103Pd radioactive stent dog bile duct than in general stent dog bile duct. CONCLUSIONS: The high level expression of caspase-3 gene may help to understand the muscle cells sensitivity to gamma-radiation apoptosis. 103Pd radioactive stent may increase the expression of caspase-3 gene in dog bile duct and prevent the billiary narrow when dog bile duct was injured by balloon.

[Effect of 103palladium radioactive stent on expression of smooth muscle actin in bile duct during healing process and its significance].

OBJECTIVE: To observe the effect of radiation on the expression of smooth muscle actin (SMA) in the bile duct during the healing process and the inhibitory function of (103)palladium (Pd) radioactive stent on the stricture of bile duct after injury. METHODS: Twelve mongrel dogs were made models of bile duct injury: duodenotomy was performed, a balloon catheter was inserted into the general bile duct and saline with high pressure was perfused thereinto to cause laceration of the mucosa, and then the balloon catheter was withdrawn and ordinary alloy stent or (103)Pd radioactive stent was inserted into the general bile duct. Thirty days after the dogs were killed. Their bile ducts were taken out to undergo HE staining to observe the area of general bile duct, thickness of the tunica intima, area of residual bile duct cavity, stricture degree, and circumference of bile duct. The expression of SMA in the bile duct tissue was detected by immunoistochemistry. RESULTS: SMA was expressed in 5 of the 6 specimens of bile duct in the (103)Pd radioactive stent group and 2 of the 6 specimens of the ordinary stent group (P < 0.01). The maximum thickness of tunica intima of general bile duct was 0.78 mm +/- 0.12 mm in the (103)Pd radioactive stent group, significantly less than that of the ordinary stent group (1.86 mm +/- 0.14 mm, P < 0.01). The percentage of maximum stricture area of the (103)Pd radioactive stent group was 23% +/- 16%, significantly lower that that of the ordinary stent group (56% +/- 22%, P < 0.01). The circumference of bile duct cavity of the (103)Pd radioactive stent group was 9.7 mm +/- 1.6 mm, significantly longer that of the ordinary stent group (7.0 mm +/- 1.4 mm, P < 0.01). CONCLUSION: (103)Pd radioactive stent reduces the expression of SMA in the bile duct during the healing process, thus inhibiting the stricture of bile duct caused by scar contracture at the anastomotic stoma.

Intrabiliary radiation inhibits smooth muscle formation and biliary duct remodelling after balloon overstretching injury in dogs.

BACKGROUND: Internal metallic stents have been widely used in clinical practice, but a high postoperative restenosis rate limits its application. The purpose of this study was to determine the effect of intrabiliary radiation on muscle formation and biliary duct remodeling after biliary duct balloon injury in dogs. METHODS: Twenty male dogs (15 - 20 kg) were randomly divided into treatment group (n = 10) and control group (n = 10). Balloon overstretching injury was induced using a balloon catheter placed across the biliary duct. Subsequently, a 103Pd radioactive stent was positioned at the target site in each animal in the treatment group, providing the injured biliary duct with a radiation dose of 12.58 x 10(7) Bq. Dogs in the control group received Ni-Ti stents. All the dogs were killed one month after initial injury. The injured sections were dissected free from the dogs, and were processed for histological and morphological study. Cross-sections were stained with hematoxylin-eosin, Masson's trichrome, and Verhoef-van Giesen. Muscle formation area and lumen area were determined using a computer-assisted image analysis system. RESULTS: Compared with the control group, 103Pd radioactive stents significantly reduced muscle formation area (78.3%, P < 0.01), and percentage area of stenosis [control stents: (60.0 +/- 21.6)%, 103Pd radioactive stents: (31.6 +/- 9.5)%]. In addition, in the treatment group, the biliary duct lumen area was significantly larger than that in the control group (P < 0.01). CONCLUSIONS: 103Pd radioactive stents providing a radioactive dose of 12.58 x 10(7) Bq are effective in reducing muscle formation and biliary duct remodeling after balloon overstretching injury.

Dose dependence effects of ionizing radiation on bile acid metabolism in the rat.

PURPOSE: To study radiation dose-related changes of individual or total bile acids in various physiological fluids in order to identify potential bio-indicators of radiation-induced gastrointestinal injuries. MATERIALS AND METHODS: Wistar rats were sham- or whole-body gamma irradiated (1-12Gy). Total and individual bile acids were quantified, 3 days after exposure, in bile collected after catheterization of the bile duct. Total bile acid concentrations were also measured in plasma and colonic contents 1, 2 and 3 days after irradiation. These concentrations were determined by an enzymatic method whereas individual bile acids were quantified by HPLC. RESULTS: In bile, whereas total bile acid concentration remained unchanged after irradiation whatever the dose, the proportion of dihydroxy bile acids in the pool of total bile acids was gradually increased with the irradiation dose, especially from 8 Gy. In plasma samples, total bile acid concentrations fell for doses higher than 10 Gy. In colonic contents, bile acid concentrations increased progressively with time (from 1 to 3 days) and with irradiation dose (from 1 to 12Gy), reaching a plateau 3 days after exposure for doses higher than 10 Gy. CONCLUSIONS: These results show that changes in colonic bile acid concentrations which are reflected in faeces are perhaps a useful parameter to improve diagnosis and prognosis of radiation-induced gastrointestinal damage since it probably reflects directly intestinal bile acid malabsorption.

Magnetic resonance cholangiographic assessment of a delayed radiation-induced bile duct stricture.

Radiation-induced bile duct strictures are rare since bile ducts are considered to be resistant in radiation injury. We report a case of bile duct stenosis where evidence is presented that bile duct stricture was the result of radiation injury and which illustrates the major contribution of magnetic res-onance cholangiography in biliary tract disease evaluation.

Intraoperative radiotherapy for resectable extrahepatic bile duct cancer.

PURPOSE: Through a retrospective study of intraoperative radiation therapy (IORT) in bile duct cancer, we hope to help clarify its clinical usefulness. METHODS AND MATERIALS: Between 1976 and 1996, IORT was carried out in 35 patients with bile duct cancer at the Tokyo Metropolitan Komagome Hospital. Of the 35 patients, resection proved to be curative in 15. Intraoperative irradiation of 15-30 Gy (average 20.1 Gy) was delivered by electron beam in the 5- to 19-MeV energy ranges. Postoperative external-beam radiation therapy (EBRT) was also delivered in 16 patients. The EBRT was fractionated to 2 Gy/day, in principle, and was delivered at 8.8-54 Gy (average 40.4 Gy) by 10-MV X-rays. RESULTS: The median survival in our patients was 19 months. The 1-year, 2-year, and 5-year survival rates were 57%, 43%, and 19%, respectively. Statistical analysis identified the following prognostic factors: performance status, curative surgical resection, lymph node metastasis, IORT dosage, and treatment period. Only 1 patient (3%) died within 30 days after surgery, and the incidence of late-onset complications was 21%. CONCLUSION: The combination of IORT and EBRT is useful for patients with bile duct cancer who undergo noncurative resection or who have lymph node metastasis.

The role of radiotherapy in the management of extrahepatic bile duct cancer: an analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy.

PURPOSE: To determine the feasibility of high dose radiotherapy and to evaluate its role in the management of extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS: Between 1983 and 1991, 145 consecutive patients with EHBD cancer were treated by low dose rate intraluminal 192Ir irradiation (ILRT) either alone or in combination with external beam radiotherapy (EBRT). Among the primarily irradiated, 77 patients unsuitable for surgical resection, 54 were enrolled in radical radiotherapy, and 23 received palliative radiotherapy. Fifty-nine received postoperative radiotherapy, and the remaining 9 preoperative radiotherapy. The mean radiation dose was 67.8 Gy, ranging from 10 to 135 Gy. Intraluminal 192Ir irradiation was indicated in 103 patients, and 85 of them were combined with EBRT. Expandable metallic biliary endoprosthesis (EMBE) was used in 32 primarily irradiated patients (31 radical and 1 palliative radiotherapy) after the completion of radiotherapy. RESULTS: The 1-, 3-, and 5-year actuarial survival rates for all 145 patients were 55%, 18%, and 10%, for the 54 patients treated by radical radiotherapy (mean 83.1 Gy), 56%, 13%, and 6% [median survival time (MST) 12.4 months], and for the 59 patients receiving postoperative radiotherapy (mean 61.6 Gy), 73%, 31%, and 18% (MST 21.5 months), respectively. Expandable metallic biliary endoprosthesis was useful for the early establishment of an internal bile passage in radically irradiated patients and MST of 14.9 months in these 31 patients was significantly longer than that of 9.3 months in the remaining 23 patients without EMBE placement (p < 0.05). Eighteen patients whose surgical margins were positive in the hepatic side bile duct(s) showed significantly better survival compared with 15 patients whose surgical margins were positive in the adjacent structure(s) (44% vs. 0% survival at 3 years, p < 0.001). No survival benefit was obtained in patients given palliative or preoperative radiotherapy. Gastroduodenal complications increased in those receiving doses of 90 Gy or more, and serious biliary bleeding was experienced in three preoperatively irradiated patients. Complications in other patients was tolerable. CONCLUSIONS: High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of EHBD cancer, and it offers a survival advantage for patients not suited for surgical resection and patients with positive margins in the resected end of the hepatic side bile duct. Expandable metallic biliary endoprosthesis assists the internal bile flow and may lengthen survival after high dose radiotherapy.