Diagnostic efficacy of the cell block method in comparison with smear cytology of tissue samples obtained by endoscopic ultrasound-guided fine-needle aspiration

Background

The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology may vary greatly depending on the treatment of the samples obtained and the level of proficiency of the cytopathologist or cytoscreener.

Methods

We prospectively evaluated the diagnostic efficacy of the cell block (CB) method and that of smear cytology using tissue samples obtained in the same needle pass at EUS-FNA in 33 patients with pancreatic tumors, abdominal tumors or swollen lymph nodes. An average of 3.1 passes were applied during the procedure without affirmation by rapid cytology. About half of the material obtained by each single pass was subjected to smear cytology, while the other half was evaluated by the CB method. Four to 12 glass slides were prepared for both Papanicolaou stain and Giemsa stain. The CB sections were prepared using the sodium alginate method and subjected to HE, PAS-AB and immunohistochemical stains. Two pathologists independently made cytological and histological diagnoses. The final diagnosis was based on integration of cytohistological findings, diagnostic imaging, and clinical course.

Results

The diagnostic accuracy of the CB method and that of smear cytology were 93.9 and 60.6%, respectively (p = 0.003), and their respective sensitivities were 92.0 and 60.0% (p = 0.02). It was easier to make a definite diagnosis of not only malignancies but also benign conditions by the CB method than by the smear method.

Conclusion

The CB method with immunostaining showed a higher diagnostic yield than smear cytology in patients who had undergone EUS-FNA without rapid on-site cytology.     

Yield of endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography for solid pancreatic neoplasms

Objective: Both endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) cytology may provide tissue diagnoses in solid pancreatic neoplasms. However, there are scant data comparing these two methods. This study aims at retrospectively comparing EUS-FNA and ERCP tissue sampling and ability of cytopathological diagnosis in solid pancreatic neoplasms and to determine usefulness and adverse events of combining both procedures. Material and methods: Two hundred and thirty four patients suspected to have solid pancreatic mass on abdominal ultrasound and/or computed tomography (CT) were enrolled. EUS-FNA (group A), ERCP cytology (group B) and combined procedures (Group C) performed in 105, 91 and 38 cases, respectively. Results: Sensitivity, specificity and accuracy were 98.9%, 93.3% and 98.1% for group A, and 72.1%, 60% and 71.4% for group B. Those for group C were all 100%. Sensitivity for malignancy in the pancreas head was 100% for group A and 82.4% for group B, and in the pancreas body and tail, 97.6% for group A and 57.1% for group B. EUS-FNA was more sensitive than ERCP cytology in diagnosing malignant pancreatic neoplasms 21–30?mm in size (p?=?0.0068), 31–40?mm (p?=?0.028) and?≥41?mm (p?Conclusions: EUS-FNA is superior to ERCP cytology for diagnosis of solid pancreatic neoplasms. Although combination of both procedures provide efficient tissue diagnosis and with a minimal adverse events rate, a prospective study including larger number of patients is required.     

The safety and benefit of pancreatic juice cytology under ERCP in IPMN patients

BackgroundInternational consensus guidelines 2012 for intraductal papillary mucinous neoplasia (IPMN), defined two characteristics: high-risk stigmata (HRS) and worrisome features (WF). Patients with WF require detailed examination including cytology. However, routine endoscopic retrograde cholangiopancreatography (ERCP) for cytology is not recommended in the guidelines due to risk of post-ERCP pancreatitis (PEP). Our aim was to clarify what types of IPMN were susceptible for PEP and gain benefit of ERCP.Patients/methodsWe examined 138 consecutive IPMN patients who underwent ERCP in our hospital, retrospectively. Patients were classified into HRS, WF and the others (N) based on imaging findings before ERCP. We assessed pancreatic juice cytology, PEP frequency and rate of malignant IPMN at 12 months after ERCP.ResultsThe rates of cytological malignancy were 0% (N), 4.8% (WF) and 19.5% (HRS). The PEP frequency was 14.5%, and these risk factors were branch duct (BD)-IPMN, body/tail cysts and brush cytology by multivariate logistic analysis. The rates of malignant IPMN were 0% (N), 16.4% (WF) and 48.8% (HRS). Furthermore, we examined patients with WF in detail. The PEP frequency/rate of malignancy were 3.6%/23.1% in patients with main pancreatic duct (MPD) dilatation (5–9 mm), and the sensitivity of cytology was 33.3%. On the other hand, the PEP frequency/rate of malignancy were 17.2%/0% in patients with BD-IPMN fulfilling only cyst size over 30 mm.ConclusionsRoutine ERCP for IPMN, especially for BD-IPMN, is not recommended. ERCP may be beneficial for WF patients with MPD dilatation based on a balance between PEP risk and presence of malignancy.     

Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease.

Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients.     

Comparison of cytologic preparation methods in endoscopic ultrasound-guided fine needle aspiration for diagnosis of pancreatic adenocarcinoma

BackgroundThere are few studies about the diagnostic yield of cytologic preparation method of pancreatic samples obtained by Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to compare the accuracy of ThinPrep^® and smear method in diagnosis of pancreatic cancer.MethodsA total of 125 EUS-FNA procedures were performed between July 2010 and June 2015. Patients in group I (n = 36; July 2010 to June 2014) had cytology slides prepared by consecutive allocation of samples. Patients in group II (n = 12; July 2014 to June 2015) had cytology slides prepared by alternately allocation of samples.ResultsThere were 24 men and 24 women (median age: 67 years; range 39–84). The median size of lesions was 3.9 cm (range; 1.4–7.2 cm). The locations of the pancreatic cancer were 10 in head (20.8%), 21 in body (43.8%), and 17 in tail (35.4%). The ThinPrep^® method confirmed malignancy in 35 of 48 cases (72.9%). On the other hand, the smear method confirmed malignancy in 44 of 48 cases (91.7%). The diagnostic yield of smear method was statistically higher than liquid method (P = 0.012). Also, smear method is superior to liquid method in both consecutive and alternative allocation method. ThinPrep^® provided a correct diagnosis in one case where the smear method was incorrect.ConclusionsSmear method was a superior preparation method to liquid method in diagnosis of pancreatic cancer, even if splitting method was not used and variable allocation method was used.     

Relative contribution of Ki-ras gene analysis and brush cytology during ERCP for the diagnosis of biliary and pancreatic diseases

Background: Ki-ras mutation analysis from material collected during ERCP has been claimed to improve the diagnosis of pancreatic and bile duct carcinomas as compared with conventional cytology. Our aim was to study the relative contribution of both Ki-ras analysis and brush cytology in patients with a significant stricture at ERCP. Methods: Brushings were collected in duplicate for both analyses in 142 patients in whom a definitive diagnosis was obtained by histology or a minimal follow-up of 6 months. Results: For pancreatic strictures, sensitivity, specificity, and accuracy of Ki-ras analysis vs. cytology in detecting malignancy were 81% vs. 66%, 72% vs. 100%, and 70% vs. 74%, respectively. For biliary strictures, they were 25% vs. 42%, 100% vs. 100%, and 35% vs. 43%, respectively. The combination of the two methods only marginally increased their sensitivity and accuracy in both types of strictures. Conclusion: Ki-ras analysis is a sensitive method for diagnosing pancreatic but not biliary carcinoma. However, its specificity is lowered by a high frequency of Ki-ras mutations in patients with chronic pancreatitis (25%) who did not manifest cancer development within a 6-month follow-up period. In pancreatic duct strictures, brush cytology appears to be more specific in detecting malignancy; specificity for Ki-ras and cytology are equivalent for the diagnosis of malignant bile duct strictures. Therefore, making a clinical decision on the sole basis of Ki-ras analysis is probably not justified in the majority of the cases. (Gastrointest Endosc 1998;47:479-85.)     

Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration: clinical utility for diagnosis of pancreatic tumor

OBJECTIVES: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has become established in the diagnosis of pancreatic cancer. The combination of pathological diagnosis and analysis for mutant K-ras gene was investigated to improve the accuracy of diagnosis. METHODS: EUS-FNA was performed in 34 patients with pancreatic masses (26 adenocarcinomas and eight chronic pancreatitis). Mutant ras gene was analyzed semiquantitatively in the specimens obtained by EUS-FNA as well as in pancreatic juice obtained by ERCP. RESULTS: Mutant gene was detected at high amounts (more than 2% of total ras genes) in 20 of 26 (77%) specimens of EUS-FNA and in 12 of 19 (63%) of pancreatic juice in cases with pancreatic carcinoma. Cytological diagnosis of malignancy by EUS-FNA was found in 16 of 26 (62%) patients with pancreatic cancer. Accurate diagnosis of the carcinoma was 21 of 26 (81%) by combined cytology and molecular method of EUS-FNA, and increased to 23 of 26 (88%) by adding molecular analysis of pancreatic juice. In contrast, mutant gene was absent or low level despite suspicious cytology in patients with benign pancreatic lesion. CONCLUSION: Quantitative analysis of mutant ras gene supplemented conventional cytology of EUS-FNA and ERCP. Detection of mutation at high amounts may represent pancreatic cancer, whereas its absence increased the possibility of benign lesion.     

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K‐ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19‐9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K‐ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K‐ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K‐ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P < 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K‐ras mutation and CEA level in pancreatic juice, as well as serum CA19‐9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K‐ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.     

Brush cytology evaluation of lesions encountered during ERCP

Malignant obstruction of the pancreaticobiliary system is a frequent indication for ERCP. Twenty-five patients with abnormalities suggestive of malignancy were encountered during ERCP at our institution and brush cytology was obtained. Positive cytology specimens were collected in 12 of 20 (60%) cases of malignancy causing biliary obstruction. Using a recently developed cytology brush for the biliary tree, detection of malignancy in strictures of the bile duct had a sensitivity of 50% and a specificity of 100%. Both cases of cholangiocarcinoma were diagnosed with cytology, as were 5 of 10 cases of pancreatic cancer. It is concluded that brush cytology is a diagnostically reliable, highly specific technique for malignant lesions encountered at ERCP. In experienced hands, a positive cytologic result may obviate the need for additional invasive diagnostic studies.     

细胞块结合免疫组化在内镜超声引导下穿刺诊断胰腺实性占位中的应用价值

目的探讨超声内镜引导下细针穿刺（EUS—FNA）物行不同细胞学检查方法对胰腺占位性病变的诊断价值。方法前瞻性研究广西医科大学第一附属医院2012年3月至2013年6月收治的胰腺实性占位性病变72例,均行超声内镜引导下细针穿刺活检取材,分别行常规涂片、液基涂片及细胞块结合免疫组化检查。结果72例患者中,最终确诊胰腺肿瘤61例,包括胰腺癌55例、胰腺假乳头状瘤2例、胰腺内分泌肿瘤4例;良性病变11例,包括慢性胰腺炎4例、胰腺结核2例、胰腺炎4例、黏液性囊腺瘤1例。常规涂片、液基涂片和细胞块结合免疫组化对胰腺肿瘤的诊断敏感度分别为68．9％（42／61）、75．4％（46／61）和90．2％（55／61）,特异度均为100．0％,准确率分别为73．6％（53／72）、79．2％（57／72）和91．7％（66／72）,细胞块结合免疫组化诊断准确率高于常规涂片细胞学及液基细胞学（P均〈0．05）。术后患者均无出血、感染、急性胰腺炎等并发症。结论EUS—FNA是一种安全有效的诊断胰腺占位病变的方法,具有高敏感度和特异度。EUS—FNA细胞块结合免疫组化有助于胰腺实性占位病变的定性诊断和组织学分型诊断,对治疗方案的选择有较大的临床应用价值。     

Myocardial ischemia during endoscopic retrograde cholangiopancreatography: An overlooked issue with significant clinical impact

Background and Aim: The occurrence of peri‐procedural myocardial ischemia with endoscopic retrograde cholangiopancreatography (ERCP) has been documented, but its significance remains controversial. This study aimed to investigate the incidence and risk factors of myocardial ischemia during ERCP procedures and to analyze the potential association between myocardial ischemia and post‐ERCP complications. Methods: Ambulatory 24‐h ST‐segment monitoring from 30 min prior to 24 h after ERCP was obtained on 71 patients from September 2006 to August 2007. Changes in vital signs during ERCP, post‐ERCP complications, and their outcomes were recorded and analyzed. Results: Cardiac ischemia occurred in 13 patients (18.3%) during ERCP and one patient developed myocardial infarction. More patients in the ischemic group (38.5%) than in the non‐ischemic group (5.2%) had ST‐T changes in pre‐ERCP resting electrocardiography (P < 0.01). Hypotension during ERCP was found only in the ischemic group (15.4% vs 0%; P = 0.03). Patients with cardiac ischemia during ERCP had a significantly higher rate of elevated serum amylase and lipase levels (53.8% vs 15.5%; P < 0.01) and post‐ERCP pancreatitis (30.8% vs 6.9%; P = 0.03). Multivariable logistic regression analysis revealed that cardiac ischemia during ERCP (OR: 5.21, P = 0.050) and pancreatic duct cannulation (OR: 5.7, P = 0.036) were independent predictors for post‐ERCP pancreatitis. Conclusions: ST‐T changes on resting electrocardiography and intra‐procedural hypotension are risk factors of myocardial ischemia during ERCP. Post‐ERCP hyperamylasemia, hyperlipasemia, and pancreatitis were associated with myocardial ischemia during ERCP.     

Clinical impact of liquid‐based cytology test on diagnostic yields from transbronchial needle aspiration

Background and objective: Transbronchial needle aspiration (TBNA) is a well‐established diagnostic method that is underutilized due to the relatively high percentage of non‐diagnostic samples and low success rates. This study was designed to evaluate the impact of liquid‐based cytology test (LBC) on the diagnostic yield from TBNA. Methods: Ninety‐seven consecutive patients who underwent TBNA due to significant mediastinal adenopathy were enrolled in the study. Each target site was aspirated four times, with the first and third aspirates being prepared for LBC and the second and fourth aspirates being reserved for conventional pick‐and‐smear (CPS) cytology. Results: Paired aspirates were obtained from 114 target sites, giving a total of 228 test samples from 97 consecutive patients. The overall diagnostic sensitivity of TBNA was 63.6% (56/88). The yields from small cell lung cancers were better than those from non‐small cell lung cancers (P < 0.05), and TBNA of subcarinal nodes provided better diagnostic yields (P < 0.05). Nodal diameters > 20 mm on computed tomography were also associated with better yields than nodes with diameters of 10–20 mm (P = 0.001). The diagnostic sensitivity of TBNA was similar for each processing method—59.8% (61/102) for LBC and 64.7% (65/102) for CPS. Conclusions: LBC was not inferior to CPS with respect to diagnostic yields from TBNA, and enabled efficient pathological evaluation.     

Pancreatic juice cytology in IPMN of the pancreas.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.     

The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures.

BACKGROUND: Brush cytology, routinely performed at ERCP to assess malignant-appearing biliary strictures, is limited by relatively low sensitivity and negative predictive value. This study assessed whether the combination of stricture dilation, endoscopic needle aspiration, and biliary brushing improves diagnostic yield. METHODS: In a prospective nonrandomized study, 46 consecutive patients were evaluated with malignant-appearing biliary strictures at ERCP. Twenty-four patients (Group A) underwent standard brush cytology alone and 22 patients (Group B) underwent stricture dilatation to 10F, endoscopic needle aspiration, and subsequent biliary brushing by using the Howell biliary system. The diagnostic yields for both techniques were compared. RESULTS: Of the 46 patients, 34 had proven malignant strictures (14 Group A, 20 Group B). Compared with brushing alone, the combination of stricture dilatation, endoscopic needle aspiration, and subsequent biliary brushing significantly increased both the sensitivity (57% vs. 85%, p < 0.02) and specificity (80% vs. 100%, p < 0.02) of cytology with positive brushings in all patients with pancreatic or gallbladder carcinoma. CONCLUSIONS: The combination of stricture dilation, endoscopic needle aspiration, and biliary brushing significantly improves diagnostic yield for malignant bile duct strictures and may particularly be of benefit for extrinsic strictures caused by pancreatic or gallbladder carcinoma.     

Optimal indication of endoscopic retrograde pancreatography-based cytology in the preoperative pathological diagnosis of pancreatic ductal adenocarcinoma

BackgroundEndoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is extremely useful for pathological diagnosis of pancreatic ductal adenocarcinoma (PDAC); however, puncturing is difficult in some cases, and there is a risk of needle tract seeding. This study evaluated the indications for endoscopic retrograde pancreatography-based (ERP)-based cytology for the preoperative diagnosis of PDAC.MethodsThis study included 267 patients with PDAC who underwent preoperative ERP. The diagnostic performance of ERP-based cytology for PDAC was evaluated based on the sample collection method (pancreatic juice cytology [PJC] during ERP, brush cytology, PJC via endoscopic nasopancreatic drainage [ENPD] catheter), lesion site (pancreatic head, body/tail), and lesion size (≤10 mm, 10–20 mm, >20 mm), and compared with the diagnostic performance of EUS-FNA.ResultsThe overall sensitivity of ERP-based cytology was 54.9%; sensitivity by the sampling method was 34.7% for PJC during ERP, 65.8% for brush cytology, and 30.8% for PJC via an ENPD catheter. The sensitivity of EUS-FNA was 85.3%. Brush cytology and PJC via an ENPD catheter were performed more often in pancreatic body/tail lesions than in head lesions (P = 0.016 and P < 0.001, respectively), and the overall sensitivity of ERP-based cytology was better for body/tail lesions (63.2% vs. 49.0%, P = 0.025). The sensitivities of ERP-based cytology and EUS-FNA in diagnosing PDAC ≤10 mm were 92.3% and 33.3%, respectively. Post-ERP pancreatitis was observed in 22 patients (8.2%) and significantly less common with ENPD catheters (P = 0.002).ConclusionsERP-based cytology may be considered the first choice for pathological diagnosis of PDAC ≤10 mm and in the pancreatic body/tail.     

A Triple Approach for Diagnostic Assessment of Endoscopic Ultrasound-Guided Fine Needle Aspiration in Pancreatic Solid Masses and Lymph Nodes

Background and Aims

Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has been becoming the standard tool for acquiring pancreatic lesion tissue. However, a single cytologic or histologic evaluation is not satisfactory for diagnosis. In this study, we evaluated the diagnostic yield of EUS–FNA for pancreatic solid masses and intra-abdominal lymph nodes using a triple approach.

Methods

This study included patients undergoing evaluation for a solid pancreatic mass (n = 59) or intra-abdominal lymph nodes (n = 16) using EUS–FNA with a 22- or 25-gauge (G) needle, respectively. The specimens from each pass were analyzed by on-site cytology using Diff-Quick stain, cytology using Papanicolaou stain, and histology with immunohistochemical (IHC) staining.

Results

A total of 75 patients (49 males; mean age; 63.7 years) were included. The median number of needle pass for diagnosis of malignancy was 2.0, and there was no technical failure. The diagnostic accuracies with on-site cytology, cytology using Papanicolaou staining, and histology were 70.7, 80.0, and 80.0 %, respectively. The diagnostic accuracy using a triple approach was significantly greater than cytology using Papanicolaou staining alone (94.7 vs. 80.0 %; p = 0.007). In patients with malignant lesions, cytology identified 12 of 71 (16.9 %) malignant lesions that were not diagnosed by histology using IHC, and histology identified six (8.5 %) malignant lesions that were not diagnosed by cytology.

Conclusion

On-site cytopathologic evaluation combined with cytologic and histologic analysis with IHC stain for one-pass specimen is considered to be able to increase the overall accuracy of EUS–FNA in pancreatic solid masses and lymph nodes.     

Effect of Bile and Pancreatic Juice on Adenoviral-Mediated Gene Delivery

Current research in gene delivery to the liver is focused on the intravenous, intraarterial, intraportal, or intratumoral route. Another possible route for gene delivery is via the common bile duct through endoscopic retrograde cholangiopancreatography (ERCP). Whether bile and pancreatic juice have any effect on gene delivery is not established. To evaluate the effect of bile and pancreatic juice on adenoviral-mediated gene delivery, liver and pancreatic cell lines were infected with a recombinant adenovirus expressing an E. coli -galactosidase gene under the control of a cytomegalovirus promoter (rAdCMVpLacZ) in the absence or presence of various concentrations of bile and pancreatic juice. The proportion of cells infected was evaluated through X-gal staining. The toxicity of bile and pancreatic juice was also evaluated through cell morphology and detachment. Bile appeared to induce significant cytotoxicity in HepG2 and Huh7 cells (50% viability with 15 min of incubation). Neither bile nor pancreatic juice affected transgene expression. In the absence of bile/pancreatic juice, HepG2 (15–25%) and PANC-1 cells (10–18%) were less susceptible to rAdCMVpLacZ compared to Huh7 cells (75–84%, vs HepG2, P < 0.001) and BxPc-3 (82–95%, vs PANC-1, P < 0.001) at a multiplicity of infection (MOI) of 5. Bile reduced the transduction efficiency, but 5–10% HepG2 and 5–42% of Huh7 cells were still transduced in the presence of 80% bile for up to 10 min. Adenoviral-mediated gene delivery was reduced in the presence of pancreatic juice with a low multiplicity of infection (MOI of 5), but this effect was negated with an MOI of 50. These data provide encouragement to develop adenoviral-mediated gene delivery through ERCP.     

Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases.

BACKGROUND: A preoperative tissue diagnosis of pancreatic cancer is desirable but difficult to obtain. METHODS: Pancreatic brush cytology, salvage cytology, and collection of pancreatic juice were attempted prospectively during ERCP in 34 patients with pancreatic cancer and 11 with chronic pancreatitis. K-ras-2 codon 12 was analyzed for presence and type of point mutations. RESULTS: Brush cytology coupled with salvage cytology had a sensitivity of 74%. The addition of cytologic analysis of pancreatic juice did not substantially improve sensitivity (76%). K-ras-2 was mutated in both cancer (87%) and pancreatitis (40%). The specificity for cytology was 100% and for K-ras-2 mutations 60%. Combining cytology with mutation analysis increased sensitivity to 93% but reduced the positive predictive value. The negative predictive value never exceeded 75%. None of the patients with chronic pancreatitis had cancer develop (median follow-up 60 months). CONCLUSIONS: Pancreatic ductal brushing with salvage cytology is useful in the diagnosis of cancer, whereas cytologic analysis of pancreatic juice can be abandoned. At present, K-ras-2 mutation is not useful for differentiating pancreatic cancer from chronic pancreatitis or the identification of patients with chronic pancreatitis at risk for malignant transformation.     

MORE ACCURATE PREDICTION OF POST‐ERCP PANCREATITIS BY 4‐H SERUM LIPASE LEVELS THAN AMYLASE LEVELS

Background: The aim of the present study was to evaluate and compare 4‐h post‐endoscopic retrograde cholangiopancreatography (ERCP) hyperamylasemia and hyperlipasemia as predictors of post‐ERCP pancreatitis. Methods: We reviewed 1631 consecutive cases consisting of 910 cases of diagnostic ERCP and 721 cases of therapeutic ERCP. Pancreatitis was diagnosed when abdominal pain persisted for 24 h after ERCP and the pain was associated with high serum amylase level and/or lipase level. Results: Pancreatitis developed in 69 (4.2%) of the 1631 cases. The receiver‐operator characteristic (ROC) curve of both the 4‐h amylase level and the 4‐h lipase level after diagnostic ERCP showed good test performance, with area under the curve of 0.88 (95% CI: 0.85–0.91) and 0.94 (95% CI: 0.92–0.96), respectively. The ROC of both the 4‐h amylase level and the 4‐h lipase level after therapeutic ERCP also showed good test performance, with an area under the curve of 0.92 (95% CI: 0.90–0.93) and 0.96 (95% CI: 0.94–0.97), respectively. The optimal cut‐off value for lipase after both diagnostic and therapeutic ERCP was 10‐fold the upper limit of the normal range. The serum lipase value after both diagnostic ERCP (P = 0.025) and therapeutic ERCP (P = 0.035) was a more effective predictor of post‐ERCP pancreatitis based on the areas under the ROC curve than was the serum amylase value. Conclusions: The 4‐h post‐ERCP lipase value is more useful for predicting pancreatitis after both diagnostic and therapeutic ERCP.     

A new grading system to evaluate the risk of endoscopic retrograde cholangiopancreatography

Background  The aim of our study was to develop a system to grade the risk of the procedures summarized under the term endoscopic retrograde cholangiopancreatography (ERCP). Methods  In a controlled prospective study, we evaluated the early complications of ERCP in 526 consecutive patients at a single endoscopy center in a defined period. The relation between endoscopic procedures and related complications was analyzed for significance. A grading system based on significant risk factors and clinical implications was developed. Results  Of the ERCP procedures, 29% were diagnostic and 71% therapeutic. A total of 45 complications occurred in 42 patients: pancreatitis (2%), perforation (1%), cardiorespiratory problems (0.6%), stent-related complications (0.5%), leakages (1.5%), and bleeding (3%). A native papilla was a significant risk factor for the development of complications (P = 0.046). On the basis of these findings, we defined five groups of ERCP-related complications: nonnative papillae with either diagnostic (A) or therapeutic interventions (B); native papillae with diagnostic (C) or therapeutic (D) interventions; and special therapeutic interventions (E). Complication rates differed significantly between individual groups, A versus D (P = 0.013), A versus E (P = 0.010), B versus D (P = 0.005), and B versus E (P = 0.003), as well as between A/B and C/D (P = 0.003). Conclusions  A grading system based on differentiating between native and nonnative papillae and diagnostic versus therapeutic procedures demonstrated significantly different complication rates. This grading system has the potential to predict the risk of ERCP-related complications.