Vascular Endothelial Growth Factor Levels in Bile Distinguishes Pancreatic Cancer from Other Etiologies of Biliary Stricture: A Pilot Study

Background

Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis.

Objective

The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture.

Methods

Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8).

Results

A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort.

Conclusions

This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.     

Cholangiocarcinoma and High-Grade Dysplasia in Young Patients with Primary Sclerosing Cholangitis

Introduction

Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare.

Aim

To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC.

Methods

Retrospective study

Results

Four patients with PSC (age range 15–18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn’s disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed.

Conclusions

Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.     

Pancreatic cancer causing acute pancreatitis: a comparative study with cancer patients without pancreatitis and pancreatitis patients without cancer

Background/purpose

Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III).

Methods

This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III.

Results

The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %, p < 0.05) and relapsed (39 vs. 16 %, p < 0.05) compared with Group III.

Conclusions

Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy.     

Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case-control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7-year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child-Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04-8.3). Serum carbohydrate antigen 19-9 (CA 19-9) was significantly higher in patients with CCA than those without (177 +/- 89 and 61 +/- 58 U/mL, respectively; P =.002). A serum CA 19-9 level > 100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19-9 appeared to have good ability to discriminate PSC patients with and without CCA.     

Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarcinoma

Background and Aims

Serum biomarkers for the early detection of pancreatic cancer are not currently available. We evaluated the usefulness of a novel serum marker, REG4, in the diagnosis of pancreatic cancer, as compared to carbohydrate antigen (CA) 19-9.

Methods

We collected pretherapeutic sera from 92 patients with pancreatic cancer, as well as sera from 28 patients with other pancreatic tumors, 11 patients with pancreatitis, and 69 healthy controls. Serum levels of REG4 were measured using a standard sandwich enzyme-linked immunosorbent assay (ELISA).

Results

Compared with healthy controls, serum levels of REG4 were higher in pancreatic cancer patients (P < 0.001), and in patients with pancreatitis (P < 0.001). Receiver operating characteristic (ROC) analysis indicated that serum REG4 performed better than serum CA19-9 for distinguishing patients with pancreatic cancer from healthy controls [areas under the curve (AUC) for REG4 and CA19-9 were 0.922 and 0.884, respectively]. When we validated the study, the sensitivity of REG4 for pancreatic cancer was 94.9%, specificity was 64.0%, and accuracy was 77.5% for the REG4 cutoff value of 3.49 ng/ml. No correlation was seen between serum REG4 and CA19-9 levels, with the sensitivity, specificity, and accuracy of the combined markers reaching 100.0, 60.0, and 77.5%, respectively. No significant differences were seen among any stages of pancreatic cancer. In surgical specimens, immunohistochemical analysis found a correlation between serum REG4 levels and REG4 expression in pancreatic cancers.

Conclusions

REG4 is expressed in pancreatic cancer, and serum levels of REG4 offer a useful indicator for distinguishing between patients with pancreatic cancer and healthy subjects. Serum REG4 has potential for use as a screening serum marker for pancreatic cancers, including early-stage cancers.     

ERCP with Probe-Based Confocal Laser Endomicroscopy for the Evaluation of Dominant Biliary Stenoses in Primary Sclerosing Cholangitis Patients

Background and Study Aim

The incidence of cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) ranges between 7 and 14 %. Despite using multiple tissue sampling modalities, detection of CCA remains a challenge. Probe-based confocal laser endomicroscopy (pCLE) has been utilized to visualize subepithelial biliary mucosa in patients with indeterminate strictures. We assessed the technical feasibility and operating characteristics of pCLE in a cohort of PSC patients with dominant biliary strictures (DS).

Patients and Methods

This was a chart review of a prospectively maintained database at a single tertiary referral center of 15 PSC patients with 21 dominant stenoses undergoing pCLE. A data collection sheet included demographics, ERCP, cholangioscopy, pCLE (Miami criteria), tissue sampling results, and follow-up to 12 months or liver transplantation. Operating characteristics for pCLE and ERCP tissue sampling were calculated.

Results

Sufficient visualization of DS by pCLE was achieved in 20/21 (95 %). pCLE sensitivity, specificity, PPV, and NPV were 100 % (95 % CI 19.3–100 %), 61.1 % (95 % CI 35.8–82.6 %), 22.2 % (95 % CI 3.5–59.9 %), and 100 % (95 % CI 71.3–100 %), respectively, in detecting neoplasia. In comparison, concomitant tissue sampling yielded sensitivity, specificity, PPV, and NPV of 0 % (95 % CI 0–80.7 %), 94.4 % (95 % CI 72.6–99.1 %), 0 % (95 % CI 0–83.5 %), and 89.5 % (95 % CI 66.8–98.4 %), respectively.

Conclusions

pCLE achieves a high technical success rate in patients with PSC and DS. This single center, small series, suggests that pCLE may have a high sensitivity and negative predictive value to exclude neoplasia. If verified in larger prospective studies, the technology may be utilized to risk stratify dominant strictures in patients with PSC.     

Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy

Purpose

CA 19-9 is the only established tumor marker in pancreatic cancer (PC); the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined.

Methods

We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models.

Results

Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A CA 19-9 decline of ≥25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay.

Conclusion

Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.     

Circulating CD4+CD25+ Regulatory T Cells in the Pathobiology of Ulcerative Colitis and Concurrent Primary Sclerosing Cholangitis

Background

Immunopathogenetic features of primary sclerosing cholangitis (PSC) in ulcerative colitis (UC) still remains unclear. Peripheral blood CD4+CD25+ regulatory T cells have a key role in the induction and maintenance of peripheral self-tolerance and inhibit several organ-specific autoimmune diseases. Therefore, CD4+CD25+ T cells are believed to play an essential role in autoimmune diseases. The aim of the present study is to analyze the role of CD4+CD25+ T cells in the pathogenesis of UC-associated PSC.

Methods

This study evaluated the levels of CD4+CD25+ T cells in peripheral blood mononuclear cells (PBMC) of 27 UC patients with PSC and 20 UC patients as controls. CD4+CD25+ T cells were isolated from PBMC with a direct immunofluorescence technique, using mice monoclonal antibodies namely FITC-labeled anti-CD4 and PE-labeled anti-CD25. In each patient, CD4+CD25+ T cells percentage in PBMC were studied by flow cytometry, and then the number of CD4+CD25+ T cells were calculated.

Results

Twenty-seven UC patients with PSC and 20 UC patients without PSC as controls were enrolled in the present study. The percentage of CD4+CD25+ regulatory T cells among PBMC were significantly elevated in UC + PSC patients compared with UC patients without PSC (p = 0.04).

Conclusions

CD4+CD25+ T cells were found to be elevated in UC patients with PSC suggesting a partial role of activated T cell response in the disease pathophysiology. Our findings imply that CD4+CD25+ regulatory T cells may play a key role in the immunopathogenesis of UC-associated PSC and may affect the therapeutic management of these diseases.     

Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer

Background

Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration.

Methods

We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data.

Results

From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28–2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58–3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03–3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12–2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44–3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11–2.28) were negative prognostic factors for overall survival.

Conclusions

K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.     

Factors predicting stomal wound closure infection rates

Background

Stoma closure is associated with high wound infection rates. The aim of this study was to evaluate risk factors for infection rates in such wounds, with particular emphasis on assessing the importance of the stomal wound closure technique.

Methods

A retrospective analysis of 142 patients who had undergone ileostomy or colostomy closure between 2002 and 2011 was performed. Postoperative outcome as measured by wound infection rate was recorded. Three different closure techniques were identified: primary closure (PC), primary closure with Penrose drain (PCP) and purse-string circumferential wound approximation technique (PSC). Other factors such as age, sex, ASA score, type of prophylactic antibiotics used, diabetes, smoking and obesity were also analysed. All other techniques were excluded.

Results

Our series consisted of 142 stomal closures (90 ileostomy and 52 colostomy closures). The patients had a median age of 63.5 years with an interquartile range of 50.1–73.2 years. The overall wound infection rate was 10.7 %. PC, PCP and PSC were associated with wound infection rates of 17.9, 10.5 and 3.6 %, respectively. Compared to PSC, PC and PCP were associated with significantly higher wound infection rates (p = 0.027 and p = 0.068, respectively). Obesity was a significant risk factor for wound infection (p = 0.024). Use of triple-agent antibiotics prophylactically had a protective effect on the infection rate (p = 0.012).

Conclusions

To reduce stomal wound closure infection rates, we recommend institution of closure techniques other than PC with or without a drain. Risk factors such as obesity should be addressed, and prophylactic triple antibiotics should be administered.     

Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma

Aims

The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection.

Serum Level of Ca 19-9 Increases Ability of IgG4 Test to Distinguish Patients with Autoimmune Pancreatitis from Those with Pancreatic Carcinoma

Background

Autoimmune pancreatitis (AIP) is often difficult to distinguish from pancreatic carcinoma or other pancreatobiliary diseases. High serum levels of carbohydrate antigen 19-9 (Ca 19-9) are indicative of malignancies, whereas high levels of immunoglobulin (Ig)G4 (>1.4 g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases.

Methods

We measured levels of Ca 19-9 and IgG4 in serum samples from 33 patients with AIP, 53 with pancreatic carcinoma, and 145 with other pancreatobiliary disorders. We determined cut-off levels for each assay. Logistic regression analysis was used to evaluate combined data on Ca 19-9, IgG4, and bilirubin levels.

Results

Low levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95 % confidence interval (CI) 0.13–0.59; p = 0.0001]. Using an upper level of 74 U/ml, the assay for Ca 19-9 identified patients with AIP with 73 % sensitivity and 74 % specificity. Using a lower level of 2.6 g/l, the assay for IgG4 identified these patients with 70 % sensitivity and 100 % specificity. Combining data, levels of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l identified patients with AIP with 94 % sensitivity and 100 % specificity.

Conclusions

Patients with AIP have lower levels of Ca 19-9 than those patients with pancreatic carcinoma. Measurement of either the Ca 19-9 or the IgG4 level alone are not accurate enough for diagnosis. However, the combination of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94 % sensitivity and 100 % specificity.     

Analysis of U2 Small Nuclear RNA Fragments in the Bile Differentiates Cholangiocarcinoma from Primary Sclerosing Cholangitis and Other Benign Biliary Disorders

Background and Objectives

Up to now the diagnosis of early stage cholangiocarcinoma (CC) has remained difficult, with low sensitivities reported for current diagnostic methods. Based on recent promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic and colorectal adenocarcinoma, we studied the utility of RNU2-1f as a diagnostic marker of CC in bile fluid.

Methods

Bile fluid was collected from patients with CC (n = 12), controls (patients with choledocholithiasis) (n = 11) and with primary sclerosing cholangitis (PSC; n = 11). RNU2-1f levels were measured by real-time polymerase chain reaction normalized to cel-54.

Results

Measurement of RNU2-1f levels in bile fluids enabled the differentiation of patients with CC from controls in all cases. Furthermore, RNU2-1f levels in bile fluids of patients with CC were significantly higher than in patients with PSC, resulting in a receiver-operating characteristic curve area of 0.856, with sensitivity of 67 % and specificity of 91 %.

Conclusions

Our data suggest that the measurement of RNU2-1 fragments detected in the bile fluid can be used as a diagnostic marker for CC and should be included in future prospective diagnostic studies for this disease entity.     

Carbohydrate antigen 19-9 is a valuable prognostic factor in colorectal cancer patients with normal levels of carcinoembryonic antigen and may help predict lung metastasis

Purpose

We retrospectively analyzed preoperative levels of carbohydrate antigen (CA) 19-9 in colorectal cancer (CRC) patients to determine the prognostic value of CA19-9 in CRC patients with normal carcinoembryonic antigen (CEA) levels.

Methods

A total of 639 patients who underwent curative surgery at Taipei Veterans General Hospital between 2002 and 2006 were enrolled. We excluded 254 patients (39.7?%) with high preoperative CEA levels and analyzed 385 patients with normal CEA levels. The measured endpoint was the postoperative disease-free survival (DFS). The prognostic value of CA19-9 was determined using log-rank test and Cox regression analysis.

Results

High CA19-9 levels were significantly associated with advanced disease and were detected in 5.8?% of patients with stage I disease, 11.7?% of those with stage II disease, and 22.5?% of those with stage III disease (P?P?Conclusions CA19-9 may be a prognostic factor for CRC patients with normal CEA levels. An aggressive follow-up protocol for lung metastasis should be used for these patients.     

The role of peroral video cholangioscopy in patients with IgG4-related sclerosing cholangitis

Background

The cholangioscopic features of IgG4-related sclerosing cholangitis (IgG4-SC) remain undefined. The aim of this study was to clarify these endoscopic features using peroral video cholangioscopy (PVCS) in IgG4-SC patients.

Methods

PVCS was performed in 33 patients: IgG4-SC (n = 13); primary sclerosing cholangitis (PSC; n = 5); and cholangiocarcinoma (n = 15), which included hilar cholangiocarcinoma (HCCA; n = 5) and distal cholangiocarcinoma (DCCA; n = 10).

Results

The most frequent findings on PVCS in the IgG4-SC patients were dilated (62 %) and tortuous (69 %) vessels, and absence of partially enlarged vessels. The incidence of dilated and tortuous vessels was significantly higher in IgG4-SC patients than in PSC patients (p = 0.015). Scarring and pseudodiverticula were found significantly more often in PSC patients than in IgG4-SC patients (p = 0.001 and p = 0.0007, respectively). The incidence of partially enlarged vessels was significantly higher in DCCA patients than in IgG4-SC patients (p = 0.004). In contrast, the incidence of dilated vessels was significantly higher in IgG4-SC patients than in HCCA patients (p = 0.015). PVCS performed after corticosteroid therapy showed resolution of bile duct stenosis and dilated, tortuous, or partially enlarged vessels, as well as resolution of friability in all patients with IgG4-SC.

Conclusion

Cholangioscopy was useful in differentiating IgG4-SC from PSC. In addition, monitoring the patterns of proliferative vessels on PVCS may be useful to differentiate IgG4-SC from cholangiocarcinoma.     

For Biliary Dilatation, a Negative Endosonography Needs Additional Image Studies in Weight Loss Suggesting Malignancy

Background and Aim

Biliary dilatation frequently raises concerns about the possibility of pancreatobiliary diseases. This study assessed the etiologic yield of endosonography (EUS) in this situation.

Methods

A retrospective review was completed with 163 consecutive patients who had undergone EUS for a dilated common bile duct (CBD) without definite pathology on ultrasonography.

Results

Binary logistic regression analysis disclosed that malignancy was positively related to weight loss and was inversely related to abdominal pain; nevertheless, choledocholithiasis was positively related to fever and elevated carbohydrate antigen 19-9 (p < 0.05). The accuracy of EUS was 95.1 % (155/163) for overall cause of biliary dilatation, 100 % (73/73) for no pathological finding, 96.3 % (26/27) for ampullary cancer, 84.6 % (11/13) for pancreatic cancer, 40.0 % (2/5) for CBD cancer, and 92.6 % (25/27) for choledocholithiasis, respectively. The accuracy of EUS decreased in the presence of malignancy (86.7 %, 39/45 vs. 98.3 %, 116/118, p = 0.006). EUS missed three CBD cancers, two pancreatic cancers, and one ampullary cancer; however, the diagnosis was rescued by computed tomography in two pancreatic cancers and one CBD cancer.

Conclusions

EUS is accurate in patients with fever suggestive of choledocholithiasis. However, a negative EUS finding should call for additional image studies in patients with weight loss suggestive of malignancy.     

Backwash Ileitis and the Risk of Colon Neoplasia in Ulcerative Colitis Patients Undergoing Restorative Proctocolectomy

Background

The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial.

Aim

We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen.

Methods

From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation.

Results

Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01–12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92–17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06–9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54–80.9, p = 0.01) was the only factor independently associated with an increased risk.

Conclusions

The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.     

Improved Post-Transplant Survival in the United States for Patients with Cholangiocarcinoma After 2000

Background

The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally.

Aims

The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA.

Methods

A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan–Meier method and compared using log-rank test.

Results

Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28–98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14–27.8).

Conclusions

Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results.     

Identification and verification of transthyretin as a potential biomarker for pancreatic ductal adenocarcinoma

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide and is difficult to detect at its early stages when treatment is most effective. Therefore, we performed a comparative proteomic study to identify new biomarkers for the detection of PDAC.

Methods

Serum samples from patients with PDAC, chronic pancreatitis and normal controls were compared using two-dimensional difference gel electrophoresis (2D-DIGE). Differentially expressed separated proteins were subsequently identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF–MS). Then, transthyretin (TTR), one of the differentially expressed proteins, was validated through real-time PCR, western blot and immunohistochemistry. Finally, enzyme-linked immunosorbent assays (ELISA) were employed to confirm the levels of transthyretin in the sera.

Results

A total of 21 protein spots showed greater than 1.5-fold changes in expression level in the sera from PDAC patients compared with the normal controls. Among the identified proteins, validation experiments verified the differential expression of transthyretin in PDAC tissue, confirming the proteomic data showing that transthyretin was significantly elevated in patients with PDAC. The ELISA results revealed that the sensitivity and specificity for TTR and CA19-9 in distinguishing PDAC patients from normal individuals were 90.5, 47.6, 66.7 and 85.7 %, respectively, and 81.0 and 85.7 % for their combination.

Conclusions

These results suggest that the level of transthyretin is elevated in patients with PDAC. In combination with CA19-9, transthyretin may provide additional information for the detection of PDAC and should be further investigated.     

The Phenotypic Expression of Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholangitis Differs in the Distribution of Colitis

Background

Inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) is reported to be mild and prone to right-side predominance with rectal sparing. However, no dedicated studies evaluating patterns of presentation of liver disease with respect to IBD are available.

Methods

We performed a detailed histological examination of the colonic biopsies in the context of PSC, identifying 97 patients [89 with ulcerative colitis and ten with Crohn’s disease (CD)] stratified into two groups, based on their initial disease presentation: hepatic/biliary (group 1—PSC-IBD; n = 56) versus colonic (group 2—IBD-PSC; n = 41).

Results

Inflammatory bowel disease that preceded PSC had a tendency to have a “pan-colitis” distribution; this group included all patients with CD. Inflammatory bowel disease diagnosis that followed PSC presentation was more likely to be right-sided, sparing the descending, sigmoid and rectal regions (p = 0.002). In both groups, colitis was mild with focal deep plasmacytosis and occasional mild cryptitis. Active cryptitis with crypt abscesses, surface erosion and ulceration were not identified in any of the patients.

Conclusion

Colitis associated with PSC shows mild disease activity and the colitis pattern is associated with disease presentation, i.e. colitis preceding PSC (IBD-PSC cohort) typically have a pancolitic distribution, while colitis following PSC (PSC-IBD cohort) demonstrates right-sided predominance. Awareness by pathologists and clinicians of these patterns of inflammatory bowel disease is important and of use in directing appropriate investigations for patients.