The role of pancreatoscopy in the diagnostic work-up of intraductal papillary mucinous neoplasms: a systematic review and meta-analysis.

BACKGROUND: Confirming the diagnosis, invasiveness, and disease extent of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is challenging. The aim of this study was to summarize the literature on the efficacy and safety of peroral pancreatoscopy (POP) in the diagnosis of IPMN, including the impact of pre- and intraoperative POP on the management of IPMN. METHODS: The EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar databases were systematically searched for articles. Eligible articles investigated cohorts of patients who underwent POP for (suspected) IPMN. RESULTS: 25 articles were identified and included in this review; with 22 of these reporting on the diagnostic yield of POP in IPMN and 11 reporting on the effect of pre- or intraoperative POP on clinical decision-making. Cannulation and observation rates, and overall diagnostic accuracy were high across all studies. Frequently reported visual characteristics of IPMN were intraductal fish-egg-like lesions, hypervascularity, and granular mucosa. Overall, the adverse event rate was 12 %, primarily consisting of post-endoscopic retrograde cholangiopancreatography pancreatitis, with a pooled rate of 10 %, mostly of mild severity. Regarding the impact of POP on clinical decision-making, POP findings altered the surgical approach in 13 %-62 % of patients. CONCLUSION: POP is technically successful in the vast majority of patients with (suspected) IPMN, has a consistently high diagnostic accuracy, but an adverse event rate of 12 %. Data on intraoperative pancreatoscopy are scarce, but small studies suggest its use can alter surgical management. Future studies are needed to better define the role of POP in the diagnostic work-up of IPMN.

Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures.

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones.

BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis is associated with extrapancreatic organ failure, malignancy, and mortality in a prospective UK cohort.

OBJECTIVES: Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-related SC) are now recognized as components of a multisystem IgG4-related disease (IgG4-RD). We aimed to define the clinical course and long-term outcomes in patients with AIP/IgG4-SC recruited from two large UK tertiary referral centers. METHODS: Data were collected from 115 patients identified between 2004 and 2013, and all were followed up prospectively from diagnosis for a median of 33 months (range 1-107), and evaluated for response to therapy, the development of multiorgan involvement, and malignancy. Comparisons were made with national UK statistics. RESULTS: Although there was an initial response to steroids in 97%, relapse occurred in 50% of patients. IgG4-SC was an important predictor of relapse (P<0.01). Malignancy occurred in 11% shortly before or after the diagnosis of IgG4-RD, including three hepatopancreaticobiliary cancers. The risk of any cancer at diagnosis or during follow-up when compared with matched national statistics was increased (odds ratio=2.25, CI=1.12-3.94, P=0.02). Organ dysfunction occurred within the pancreas, liver, kidney, lung, and brain. Mortality occurred in 10% of patients during follow-up. The risk of death was increased compared with matched national statistics (odds ratio=2.07, CI=1.07-3.55, P=0.02). CONCLUSIONS: Our findings suggest that AIP and IgG4-SC are associated with significant morbidity and mortality owing to extrapancreatic organ failure and malignancy. Detailed clinical evaluation for evidence of organ dysfunction and associated malignancy is required both at first presentation and during long-term follow-up.

Impact of ERCP simulator training on early ERCP learning curves of novice trainees: a cohort study.

Background and study aim Simulator-based training has been extensively studied in training gastroduodenoscopy and colonoscopy and shown to significantly improve learning curves of novices. Data on simulator-based training in endoscopic retrograde cholangiopancreatography (ERCP) are scarce. We aimed to determine the impact of 2-day intensive hands-on simulator training on the course of the learning curve of novice trainees. Methods We conducted a prospective cohort study using a validated mechanical ERCP simulator (Boskoski-Costamagna ERCP Trainer). Six trainees were allocated to the simulation course program (SG). Each of these trainees were paired with an endoscopy trainee starting regular ERCP training at the same center who had no exposure to a simulation course program (control group; CG). The course included lectures, live ERCP demonstrations, and hands-on ERCP training to educate trainees in basic techniques related to cannulation, stent placement, stone extraction and stricture management. After the course, both the SG and CG started formal ERCP training in their respective centers. The Rotterdam Assessment Form for ERCP was used to register each performed ERCP. Simple moving average was applied to create learning curves based on successful common bile duct (CBD) cannulation. Outcomes were plotted against a historical cohort (HC). Results Thirteen trainees were included, six trainees in the SG and seven trainees in the CG, with a total of 717 ERCPs. Mean successful ERCP cannulation rate was higher for the simulator group at baseline compared to both CG and HC, 64% versus 43% and 42%, respectively. Differences became less explicit after 40 ERCPs, but persisted until a median of 75 ERCPs. Conclusions We demonstrate that 2-day hands-on simulator-based ERCP training course has a positive effect on the learning curves of ERCP trainees and should be considered an integral part of the training curricula for ERCP to develop skills prior to patient-based training.

Cholangiocarcinoma or IgG4-associated cholangitis: how feasible it is to avoid unnecessary surgical interventions?

OBJECTIVE: To evaluate the experience of a tertiary hepatopancreaticobiliary (HPB) center in the diagnostic approach and management of patients with suspicion of cholangiocarcinoma (CCa), focusing on excluding patients with IgG4-associated cholangitis (IAC) from unnecessary major surgical interventions. METHODS: Between January 2008 and September 2010, a total number of 152 patients with suspicion of CCa underwent evaluation through a HPB multidisciplinary team meeting. Patients without tissue diagnosis were managed surgically or medically on the basis of probable presence of IAC as underlying pathology. Serology, immunostaining, and imaging were reviewed and analyzed according to the HISORt (Histology, Imaging, Serology, Other organ involvement, Response to therapy) criteria for IAC. RESULTS: Tissue diagnosis during the diagnostic workup was achieved in 104 patients (68%), whereas the remaining 48 were classified as "highly suspicious for CCa" (n = 35) or as "probable IAC" (n = 13). Among 16 "highly suspicious for CCa" patients who underwent surgery, pathology revealed 2 patients harboring IAC (n = 1) and a benign chronic inflammatory biliary stricture (n = 1), respectively. Among the 13 patients with primarily medical management as "probable IAC," final diagnosis was CCa (n = 3) and IAC (n = 9), while 1 patient had no proven diagnosis. The accuracy of serum IgG4 for diagnosis of IAC reached 60%. Sensitivity and specificity of immunostaining for IAC in biopsy specimens were 56% and 89%, respectively. Imaging features suggesting IAC yielded sensitivity, specificity, and accuracy of 75%, 89%, and 83%, respectively. Initial imaging was revised at the referral institute in 75% of IAC patients (P = 0.009), while an isolated stricture (P = 0.038), a biliary mass (P = 0.006), and normal pancreas on computed tomography (P = 0.01) were statistically significant parameters for distinguishing between CCa and IAC. The mean time for establishing a diagnosis of IAC was 12.4 months (range: 2.5-32 months). CONCLUSIONS: Differential diagnosis between CCa and IAC mandates high index of suspicion and low threshold for referral in high volume institutes. The delayed establishment of diagnosis particularly for CCa needs to be balanced versus avoiding unnecessary surgery for IAC. Imaging features may be most helpful for optimal management.

Endoscopic retrograde cholangiography does not reliably distinguish IgG4-associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma.

BACKGROUND & AIMS: Distinction of immunoglobulin G4-associated cholangitis (IAC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma is challenging. We aimed to assess the performance characteristics of endoscopic retrograde cholangiography (ERC) for the diagnosis of IAC. METHODS: Seventeen physicians from centers in the United States, Japan, and the United Kingdom, unaware of clinical data, reviewed 40 preselected ERCs of patients with IAC (n = 20), PSC (n = 10), and cholangiocarcinoma (n = 10). The performance characteristics of ERC for IAC diagnosis as well as the κ statistic for intraobserver and interobserver agreement were calculated. RESULTS: The overall specificity, sensitivity, and interobserver agreement for the diagnosis of IAC were 88%, 45%, and 0.18, respectively. Reviewer origin, specialty, or years of experience had no statistically significant effect on reporting success. The overall intraobserver agreement was fair (0.74). The operating characteristics of different ERC features for the diagnosis of IAC were poor. CONCLUSIONS: Despite high specificity of ERC for diagnosing IAC, sensitivity is poor, suggesting that many patients with IAC may be misdiagnosed with PSC or cholangiocarcinoma. Additional diagnostic strategies are likely to be vital in distinguishing these diseases.

R0 but not R1/R2 resection is associated with better survival than palliative photodynamic therapy in biliary tract cancer.

BACKGROUND: There is a need for better management strategies to improve the survival and quality of life in patients with biliary tract cancer (BTC). AIM: To assess prognostic factors for survival in a large, non-selective cohort of patients with BTC. METHOD: We compared outcomes in 321 patients with a final diagnosis of BTC (cholangiocarcinoma n = 237, gallbladder cancer n = 84) seen in a tertiary referral cancer centre between 1998 and 2007. Survival according to disease stage and treatment category was compared using log-rank testing. Cox's regression analysis was used to determine independent prognostic factors. RESULTS: Eighty-nine (28%) patients underwent a surgical intervention with curative intent, of whom 38% had R0 resections. Among the 321 patients, 34% were given chemo- and/or radiotherapy, 14% were palliated with photodynamic therapy (PDT) and 37% with biliary drainage procedures alone. The overall median survival was 9 months (3-year survival, 14%). R0-resective surgery conferred the most favourable outcome (3-year survival, 57%). Although patients palliated with PDT had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery but who had positive resection margins. On multivariable analysis, treatment modality, serum carbohydrate-associated antigen 19-9, distant metastases and vascular involvement were independent prognostic indicators of survival. CONCLUSION: In this large UK series of BTC, palliative PDT resulted in survival similar to those with curatively intended R1/R2 resections. Surgery conferred a survival advantage only in patients with R0 resection margins, emphasising the need for accurate pre-operative staging.

Clinical practice patterns in indirect peroral cholangiopancreatoscopy: outcome of a European survey.

Background and aims Indirect peroral cholangiopancreatoscopy (IPOC) is a relatively new diagnostic and therapeutic tool for biliopancreatic diseases. This international survey aimed to evaluate clinical practice patterns in IPOC among endoscopists in Europe. Methods An online survey was developed comprising 66 questions on the use of IPOC. Questions were grouped into four domains. The survey was sent to 369 endoscopists who perform IPOC. Results 86 respondents (23.3 %) from 21 different countries across Europe completed the survey. The main indications for cholangioscopy were determination of biliary strictures (85 [98.8 %]) and removal of common bile duct or intrahepatic duct stones (79 [91.9 %]), accounting for an estimated use of 40 % (interquartile range [IQR] 25-50) and 40 % (IQR 30-60), respectively, of all cases undergoing cholangioscopy. Pancreatoscopy was mainly used for removal of pancreatic duct stones (68/76 [89.5 %]), accounting for an estimated use of 76.5 % (IQR 50-95) of all cases undergoing pancreatoscopy. Only 13/85 respondents (15.3 %) had an institutional standardized protocol for targeted cholangioscopy-guided biopsy sampling. IPOC with lithotripsy was used as first-line treatment in selected patients with bile duct stones or pancreatic stones by 24/79 (30.4 %) and 53/68 (77.9 %) respondents, respectively. Conclusions This first European survey on the clinical practice of IPOC demonstrated wide variation in experience, indications, and techniques. These results emphasize the need for prospective studies and development of an international consensus guideline to standardize the practice and quality of IPOC.

Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection.

Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically "tolerant" since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.

Autoimmune pancreatitis/IgG4-associated cholangitis and primary sclerosing cholangitis--overlapping or separate diseases?

Autoimmune pancreatitis is a recently described fibroinflammatory disease which is characterised by raised serum levels of IgG4 (in >70% of cases), and an IgG4-positive lymphoplasmacytic tissue infiltrate. A favourable and rapid clinical response to oral steroid therapy is often seen. Biliary involvement is common, and the term IgG4-associated cholangitis has recently been coined. The cholangiographic appearances of IgG4-associated cholangitis and primary sclerosing cholangitis can be difficult to differentiate. Moreover, raised levels of serum IgG4 have been recently found in 9% of patients with primary sclerosing cholangitis (a much higher frequency than for other gastrointestinal diseases), and those with raised levels appear to progress more rapidly to liver failure. Here we review the similarities and differences between the biliary disease in autoimmune pancreatitis and primary sclerosing cholangitis, and address the issue of disease overlap. Improvements in understanding the relationship between these conditions might lead to an enhanced understanding of the aetiopathogenesis, and improved treatment of both conditions.

Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is a multisystem disorder that often has extrapancreatic manifestations such as immunoglobulin G4-associated cholangitis (IAC). Patients respond rapidly to steroids but can relapse after therapy. We assessed the clinical management of relapse in a group of patients with AIP/IAC. METHODS: We performed a prospective study of patients diagnosed with AIP from 2004-2007 who received steroids. Treatment outcome was defined clinically, radiologically, and biochemically as response to steroids, remission after steroids, failure to wean steroids, and relapse. Steroids +/- azathioprine (AZA) were used to treat patients who failed, relapsed, or could not be weaned from steroids. RESULTS: Twenty-eight patients with AIP were studied; 23 (82%) had IAC. All patients responded within 6 weeks to prednisolone therapy. Twenty-three patients achieved remission after a median of 5 months of treatment (range, 1.5-17 months), whereas 5 patients (18%) could not be weaned because of a disease flare. Of the patients who achieved remission, 8 of 23 (35%) subsequently relapsed. Overall, 13 of 23 patients (57%) with AIP/IAC relapsed, compared with 0 of the 5 with isolated AIP (P = .04, Fisher exact test). Steroids were increased/restarted in all patients who relapsed; 10 also received AZA. Remission was achieved and maintained in 7 patients; they remain on AZA monotherapy at a median of 14 months (range, 1-27 months). CONCLUSIONS: Relapse or failure to wean steroids occurred in 46% of patients with AIP. Patients with IAC are at particularly high risk of relapse. AZA appears to be effective in patients with post-treatment relapse or who cannot be weaned from steroids. To view this article's video abstract, go to the AGA's YouTube Channel.

Complications and diagnostic difficulties arising from biliary self-expanding metal stent insertion before definitive histological diagnosis.

BACKGROUND: Self-expanding metal bile duct stents provide good palliation for inoperable malignant disease. However, problems may arise if metal stents are inserted before definitive histological diagnosis. The aim of this study was to evaluate the outcome of such patients. METHODS: A retrospective case note review was conducted of patients referred to a tertiary pancreaticobiliary center between 1992 and 2004 in whom a metal bile duct stent was inserted for presumed unresectable malignant disease before definitive histological diagnosis. RESULTS: There were 21 patients identified. Final diagnoses were: group 1, benign disease (n = 3); group 2, resectable malignancy (n = 2); group 3, unresectable malignancy (n = 12); and group 4, diagnosis remains uncertain (n = 4). During a follow-up of 22, 38 and 111 months, the patients in group 1 had one, eight and five episodes of stent occlusion. In group 2, both patients underwent pancreaticoduodenectomy for ampullary carcinoma, 2 and 6 months after presentation. In group 3, the median time to a confirmed malignant diagnosis was 2 months (range 1-27 months). In group 4, a median of two biopsies (range 1-4) were negative for malignancy, during a median follow up of 13 months (range 3-46). Overall in eight patients, the metal stents caused artifacts on computed tomography and/or were associated with tissue in-growth making the differentiation between benign and malignant disease difficult. CONCLUSION: These cases indicate that metal bile duct stent insertion before definitive histological diagnosis can be problematic. A proportion of cases will have benign strictures and in others the confirmation of malignancy may be made more difficult.

The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is recognized increasingly as a multisystem disorder. We evaluated the use of immunoglobulin (Ig)G4 immunostaining of pancreatic and extrapancreatic biopsy specimens to make a definitive diagnosis of AIP. METHODS: Seventeen biopsy specimens and 3 gallbladder resections were assessed from 11 patients with clinical and radiologic features of AIP. Biopsy specimens from pancreas, liver, colon, stomach, duodenum, bone marrow, salivary gland, and kidney were analyzed morphologically, immunostained for IgG4-positive plasma cells, and compared with controls. RESULTS: Positive IgG4 immunostaining enabled a definitive diagnosis in 10 of 11 (91%) AIP patients. In both pancreatic and extrapancreatic tissues, high levels of IgG4 immunostaining (>10 IgG4-positive plasma cells/high-power field) were found in 17 of 20 (85%) specimens from AIP patients compared with 1 of 175 (0.6%) specimens from controls (P < .05). Positive extrapancreatic IgG4 immunostaining was found in 8 of 11 (73%) patients, including all those with diagnostic features in the pancreas. Increased tissue IgG4 was found irrespective of serum IgG4 level. CONCLUSIONS: The finding of IgG4 immunostaining within a range of clinically involved tissues supports the hypothesis that AIP is a multisystem disease. Positive IgG4 immunostaining in extrapancreatic tissues may allow a definitive diagnosis of AIP to be made in those with evidence of pancreatic disease, without the necessity of pancreatic biopsy or surgical exploration. Immunostaining of involved tissue for IgG4 may be particularly useful when AIP is suspected clinically but the serum IgG4 level is normal.

Inflammatory pseudotumour of the liver: the residuum of a biliary cystadenoma?

Inflammatory pseudotumour is a rare form of a liver mass. We report the case of a 28-year-old man presenting with obstructive jaundice, in whom an inflammatory pseudotumour arose with the resolution of a mucus secreting cystic liver lesion. The initial features suggested an intrahepatic cystadenoma or cystadenocarcinoma, which on its involution left a solid mass. Histopathology showed an inflammatory pseudotumour with no evidence of malignancy. A similar case has been reported recently, with the development of an inflammatory pseudotumour following collapse of a liver cyst seen on imaging. These two cases may shed some light on the origins of these rare liver lesions.

Pancreatoscopy-Directed Electrohydraulic Lithotripsy for Pancreatic Ductal Stones in Painful Chronic Pancreatitis Using SpyGlass.

OBJECTIVE: Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy, or endoscopic approaches. Here, we report our experience of pancreatoscopy + electrohydraulic lithotripsy (EHL) for pancreatic duct (PD) stones using SpyGlass. METHODS: We retrospectively audited the use of SpyGlass (Legacy and DS) + EHL. Indication, procedural details, and clinical outcomes were assessed. RESULTS: A total of 118 SpyGlass + EHL procedures for stones were performed, of which 8 (7%) for pancreatic stones, in 6 patients (3 female; mean [standard deviation] age, 45 [7] years). All patients had painful chronic pancreatitis, with radiological evidence of a dilated PD, and main duct stone disease. Surgical options had been considered in all cases. Stone fragmentation and PD decompression were achieved in 83% (n = 5) without complications. Two patients required 2 EHL procedures to achieve clearance. In 1 patient with failed clearance, pancreatoscopy revealed a stone in the adjacent parenchyma and not in PD. All patients with successful EHL had pain relief/marked improvement at clinical review (mean [standard deviation] follow-up, 2.7 [1.1] years). CONCLUSIONS: Pancreatoscopy + EHL may have a valuable role in treating obstructing PD stones, possibly avoiding the need for surgery in some patients.

The role of multidisciplinary meetings for benign pancreatobiliary diseases: a tertiary centre experience.

Multidisciplinary meetings are central to the management of chronic and complex diseases and they have become widely established across the modern healthcare. Patients with pancreatobiliary diseases can often present with complex clinical dilemmas, which fall out with the scope of current guidelines. Therefore, these patients require a personalised management approach discussed in a multidisciplinary meeting.

Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C.

BACKGROUND: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy. OBJECTIVES: our aim was to evaluate the prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C. STUDY DESIGN: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were further studied histologically, with morphometric analyses and immunostaining techniques. Twenty-five were treated with alpha Interferon and ribavirin and followed for at least 18 months. RESULTS: HBV DNA was detected in 29.4% of liver tissue specimens and in only one (1.9%) serum sample. Three liver specimens were positive for surface gene, nine for core gene, three for both and none for the X gene. No significant difference in mean transaminase values, HCV viral titre, HCV genotype, or grading and staging and morphometric analysis was observed in patients with or without HBV DNA. Moreover, all 51 liver specimens were negative for both HBsAg and HBcAg. Sustained response to combination therapy was achieved in 40% of patients with and in 53% of patients without HBV DNA in the liver specimens (P=NS). CONCLUSIONS: HBV DNA is frequently found in the liver of patients with chronic hepatitis C. However, the lack of any significant impact on HCV viral titre, liver enzymes, histological parameters and response to therapy, suggests that in most cases HBV DNA detected in the liver by PCR may be either an integrated or low level replicative form.

Hepatic ischemia associated with coarctation of the aorta in pregnancy: key issues in differential diagnosis.

BACKGROUND: Hepatic ischemia associated with coarctation of the aorta has not previously been reported in an adult; pregnancy increases the pressure gradient across a coarctation. CASE: A young woman with known coarctation of the aorta developed severe hepatic ischemia in pregnancy. A pregnancy-induced increase in the mean pressure gradient across the coarctation, from 18 mm Hg before pregnancy to 40 mm Hg in the third trimester, predisposed to critical hepatic hypoperfusion in the setting of dehydration. CONCLUSION: This case documents an association between coarctation of the aorta and hepatic ischemia, precipitated by pregnancy and dehydration in combination. It emphasizes the need in the assessment of patients with liver disease in pregnancy to consider not only "traditional" pregnancy-related conditions such as acute fatty liver and the hemolysis, elevated liver enzymes, low platelets syndrome, in which delivery may be necessary as a clinical emergency, but also those in which the circulatory and metabolic demands of pregnancy may precipitate liver injury.