Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy.

Despite combination chemotherapy demonstrating a positive effect on survival, the clinical outcomes of pancreatic adenocarcinoma (PDAC) remain poor. Radiotherapy was previously a component of the curative treatment of PDAC. Advances in imaging and computer sciences have enabled the prescription of higher dosage of radiation focused on tumours with minimal toxicity to normal tissue. However, the role of radiotherapy has not been established in the curative treatment of localized PDAC because of the conflicting results from large prospective trials. Most studies have demonstrated improved locoregional control but no survival benefit from additional chemoradiotherapy (CRT) in addition to chemotherapy for resectable, borderline or locally advanced PDAC. The improved locoregional control enabled by CRT does not cause extended survival because of rapid distant progression in a significant proportion of patients with PDAC. Several single-institute studies of prescribing intensive chemotherapy with modern ablative radiotherapy for locally advanced PDAC have demonstrated extended survival with an acceptable safety profile. In an analysis after long-term follow-up, the PREOPANC study demonstrated a survival benefit from neoadjuvant gemcitabine-based CRT in resected PDAC relative to upfront surgery followed by adjuvant gemcitabine only. These observations indicated that the role of radiotherapy in PDAC should be evaluated in a subgroup of patients without rapid distant progression because systemic therapy for PDAC remains underdeveloped. We reviewed critical imaging, tissue, liquid and clinical biomarkers to differentiate the heterogeneous biologic spectra of patients with PDAC to identify those who may benefit the most from local radiotherapy. Exclusion of patients with localised PDAC who develop distant progression in a short time and undergo extended upfront chemotherapy for over 4 months may enable the identification of a survival benefit of local radiotherapy. Though promising, the effectiveness of biomarkers must be validated in a multi-institutional prospective study of patients with PDAC receiving CRT or not receiving CRT.

Randomized trial of contrast-enhanced harmonic guidance versus fanning technique for EUS-guided fine-needle biopsy sampling of solid pancreatic lesions.

BACKGROUND AND AIMS: For EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions (SPLs), the role of sampling strategy between targeted biopsy sampling and wide sampling has not been reported. This study aimed to investigate the benefits of the 2 sampling techniques on EUS-FNB using rapid on-site evaluation. METHODS: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to undergo EUS-FNB using either contrast guidance or the fanning technique. The primary outcome was the total number of passes required to establish a diagnosis, and secondary outcomes were overall diagnostic accuracy and adverse event rates. RESULTS: One hundred eighteen patients were enrolled from February 2019 to January 2021, with 59 patients assigned to each group. There was no significant difference in the total number of passes required to establish a diagnosis between the contrast and fanning groups (median, 1 [interquartile range, 1-1] vs 1 [interquartile range, 1-2], respectively; P = .629). The sensitivity, specificity, and diagnostic accuracy in the contrast group was 100%, 66.7%, and 98.3% and in the fanning group 100%, 100%, and 100%, respectively (P = 1). An SPL <4 cm (odds ratio, 2.47; 95% confidence interval, 1.05-5.81; P = .037) and macroscopic visible core length >1 cm (odds ratio, 2.89; 95% confidence interval, 1.07-7.84; P = .037) were independently associated with increased cytologic and histologic accuracy. CONCLUSIONS: The diagnostic accuracy of EUS-FNB with the fanning technique for SPLs was comparable with the contrast guidance technique. Without additional cost, EUS-FNB with the fanning technique may be preferred for SPLs. (Clinical trial registration number: NCT04924725.).

Pilot imaging study of o-BMVC foci for discrimination of indeterminate cytology in diagnosing fine-needle aspiration of thyroid nodules.

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.

Factors predicting one or two sentinel lymph nodes to be accepted for sentinel lymph node biopsy alone after neoadjuvant therapy in initially node-positive breast cancer patients.

BACKGROUND: Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients. METHODS: Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model. RESULTS: The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age >52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count >530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991). CONCLUSION: When taxane was administered during NAT, the false-negative rate was predicted at <5% for patients aged <57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival.

INTRODUCTION: Metastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients. METHODS: We excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors. RESULTS: We identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014-2016 compared with 2011-2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors. CONCLUSIONS: MBC with LM is treatable-systemic BEEP are efficacious and may improve survival.

Rapid on-site cytologic evaluation by pulmonologist improved diagnostic accuracy of endobronchial ultrasound-guided transbronchial biopsy.

BACKGROUND/PURPOSE: Rapid on-site cytologic evaluation (ROSE) has been shown to improve the diagnostic accuracy of endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB). However, ROSE by a cytopathologist or cytotechnologist is not always available during the procedure. The purposes of this study were to verify that a pulmonologist, after receiving training in cytology, could accurately assess an EBUS-TBB specimen on-site, and to evaluate the contribution of ROSE to EBUS-TBB. METHODS: A retrospective chart review of patients who underwent EBUS-TBB for diagnosis of peripheral pulmonary lesions (PPLs) from January 2014 to June 2017 was performed. PPLs without a malignant diagnosis were excluded. The ROSE result determined by a pulmonologist was compared to the formal imprint cytologic report and pathologic report. The diagnostic accuracy of EBUS-TBB was also compared between those with and without ROSE. RESULTS: Two hundred ninety-three patients who underwent 336 EBUS-TBB procedures for PPL diagnosis and were found to have proven malignancy were enrolled. Eighty-six procedures were performed with ROSE. With the formal imprint cytologic diagnosis as the standard, ROSE had 96.9% sensitivity, 68.2% specificity, 89.9% positive predictive value (PPV), 88.2% negative predictive value (NPV), and 89.5% diagnostic accuracy. With the formal pathologic result as the standard, ROSE had 88.2% sensitivity, 80% specificity, 97.1% PPV, 47.1% NPV, and 87.2% diagnostic accuracy, respectively. The diagnostic accuracy was significantly higher when ROSE was performed during EBUS-TBB (88.4% vs 68.0%, P < 0.001). CONCLUSION: A trained pulmonologist can interpret adequately cytologic smears on-site and effectively improve the accuracy of EBUS-TBB in the diagnosis of PPLs.

Validation of Indications for Surgery of European Evidence-Based Guidelines for Patients with Pancreatic Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: Which patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical intervention remains a controversial issue. The aim of this retrospective study was to validate the new European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) for the management of IPMNs. METHODS: One hundred fifty-eight patients with resected IPMNs at National Taiwan University Hospital between January 1994 and December 2016 were enrolled. Clinical information, including new-onset diabetes mellitus (DM) and preoperative CA 19-9 levels, were collected. All patients were stratified into three groups-absolute, relative indications, and conservative approach-according to EEBGPCN. The performance characteristics of EEBGPCN for high-grade dysplasia (HGD)/invasive carcinoma (IC) of IPMNs were calculated. RESULTS: One hundred seven (67.7%) patients with low-grade dysplasia and 51 patients with HGD/IC, including 10 HGD and 41 IC, were analyzed. The missed rate for HGD/IC by EEBGPCN was 1.9% (3/158). The sensitivity, specificity, positive and negative predictive values, and accuracy of the absolute or relative indications for resecting IPMN according to EEBGPCN were 94.1%, 28.0%, 38.4%, 90.9%, and 49.4%. Jaundice, enhancing mural nodule < 5 mm, cyst diameter > 40 mm, increased levels of serum CA 19-9, new-onset DM, and main pancreatic duct dilation were associated with HGD/IC. CONCLUSIONS: The missed rate for HGD/IC is low by EEBGPCN. Increased serum CA 19-9 and new-onset DM in EEBGPCN were verified as the indications for the surgical resection of IPMNs.

Computerized Cytological Features for Papillary Thyroid Cancer Diagnosis-Preliminary Report.

Fine needle aspiration cytology (FNAC) is the final diagnosis of thyroid nodules before surgery. It is important to further improve the indeterminate FNAC diagnosis results using computerized cytological features. This retrospective cross-sectional study included 240 cases, of whom 110 had histologic diagnosis of papillary thyroid cancers (PTC), 100 had nodular/adenomatous goiters/hyperplasia (benign goiters), 10 had follicular/Hurthle cell carcinomas, and 20 had follicular adenomas. Morphological and chromatic features of FNAC were quantified and analyzed. The result showed that six quantified cytological features were found significantly different between patients with a histologic diagnosis of PTC and patients with histologic diagnosis of benign goiters in multivariate analysis. These cytological features were used to estimate the malignancy risk in nodules with indeterminate FNAC results. The Area Under the Receiver Operating Characteristics (AUROC) of the diagnostic accuracy with a benign or malignant nature was 81.3% (p < 0.001), 78.7% (p = 0.014), and 56.8% (p = 0.52) for nodules with FNAC results of atypia, which is suspicious for malignancy and follicular neoplasm, respectively. In conclusion, quantification of cytological features could be used to develop a computer-aided tool for diagnosing PTC in thyroid nodules with indeterminate FNAC results.

Age and cystic size are associated with clinical impact of endoscopic ultrasonography-guided fine-needle aspiration on the management of pancreatic cystic neoplasms.

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was to identify which patients with PCNs would benefit from EUS-FNA. Methods: A retrospective study was performed on patients with PCNs who underwent EUS-FNA between January 2009 and June 2018. A discordant or a consistent diagnosis after EUS-FNA was analyzed and was correlated with the clinical demographic data and cystic features. Predictors of the change in the diagnosis after EUS-FNA were analyzed. Results: One hundred eighty-eight cases of PCNs were analyzed. EUS-FNA changed the diagnosis in 45.7% of all patients with PCNs and 54.5% patients with presumed branch ductal type intraductal papillary mucinous neoplasm (BD-IPMN) and impacted the recommendation in 35.6% of patients with PCNs and 50.5% patients with BD-IPMN. Patients with a discordant diagnosis after EUS-FNA were younger in age (54.8 ± 12.6 vs. 61.2 ± 14.2; p=.037) and had a cyst size larger than 3 cm than patients with a consistent diagnosis after EUS-FNA. The only worrisome feature (WF) that differed between patients with a discordant and a consistent diagnosis after EUS-FNA was the main pancreatic duct (MPD) between 5 and 9 mm (p=.013). In multivariate analysis, a cyst size >3 cm and age were independent predictors of diagnostic changes after EUS-FNA (OR: 5.33, 95% CI: 1.79-15.88, p = .003; OR: 0.96, 95% CI: 0.93-0.99, p = .031). Conclusions: EUS-FNA made a significant change in the management of nearly half of the patients with PCNs, especially in younger patients and in patients with a cyst size larger than 3 cm.

The surgery and repeat aspiration outcomes of the atypia of undetermined significance/follicular lesion of undetermined significance category in The Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND/OBJECTIVE: The atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this study, we report the diagnostic distribution of thyroid fine needle aspiration (FNA) cytology and analyze the outcome of AUS/FLUS cases. METHODS: A total of 29,937 thyroid FNA results, reported between April 2012 and December 2016, were retrieved from the database of a medical center. We reviewed the electronic medical records and analyzed the management of these patients. RESULTS: Overall frequency of AUS/FLUS is 3.1% in our laboratory, which is at the lower limit of the recommended range. Of these, 891 reports of AUS/FLUS from 770 patients were identified. Out of the 770 patients, 367 had surgical intervention. In these 367 patients, final surgical pathology yielded 204 (55.6%) malignancies, 12 indeterminateness (3.3%), and 151 (41.1%) benignity. Among these surgical patients, 113 (30.8%) had received a repeat FNA of the thyroid before thyroid resection. The difference between the malignancy rates among patients who directly received surgery after the first AUS/FLUS diagnosis (132 of 254, 52.0%) and patients having a repeat FNA before surgery (72 of 113, 63.7%) was not statistically significant. CONCLUSION: Our results are in agreement with AUS/FLUS diagnoses in less than 7% of specimens, and confirm that it is appropriate to perform either a repeat thyroid FNA or thyroid lobectomy, with the clinical decision being subject to the standardized management protocols of the second edition of TBSRTC in the AUS/FLUS category.

Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature.

BACKGROUND/PURPOSE: The thyroid gland is an uncommon site for the presence of extramedullary hematopoiesis (EMH). We report the cases of four Taiwanese women with hematopoietic elements on the smears of thyroid fine needle aspiration (FNA) samples and compare the findings with those of previously reported cases. METHODS: We retrieved the data of cases in which thyroid FNA performed between January 2000 and December 2016. The clinical manifestations, laboratory data, and image findings of cases with thyroid EMH were reported. A review of English literature was performed, and the reported cases were compared with our series. RESULTS: During the study period, 63,361 specimens of thyroid FNAs were identified. Four specimens contained hematopoietic elements from four women. Ultrasound study revealed calcifications in three patients. A review of English literature yielded 18 reports of thyroid EMH involving 29 patients. Twenty-six patients were women, and three were men. Nodule calcifications were found in 13 patients. Four patients had primary myelofibrosis, and one had chronic anemia. None had a thyroid malignancy. CONCLUSION: Four patients were noted to have bone marrow elements on the smears among 63,361 thyroid FNA samples. These four Taiwanese women presented with nodular goiter and foci of hematopoietic elements by thyroid FNA without any chronic disease of hematopoietic tissue or any evidence of a thyroid malignancy.

Pancreatic cancer screening in different risk individuals with family history of pancreatic cancer-a prospective cohort study in Taiwan.

Pancreatic cancer (PC) is usually diagnosed at advanced stage. Our aim was to investigate the risk of malignant and premalignant pancreatic lesions in individuals with family history of PC. Individuals at risk of PC were enrolled prospectively in a screening program in Taiwan. All risk individuals received genetic testing of cationic trypsinogen (PRSS1) gene and the serine protease inhibitor Kazal type 1 (SPINK1) gene. They were stratified into three risk groups (high, moderate, and low) based on the family history and genetic testing. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatogram (MRCP) were performed in all screened individuals. A total of three hundred and three risk individuals in 165 families were enrolled with the mean age of 51.1 years, 38.3% of whom were male. A total of 24 of 303 (7.9%) screened individuals had the PRSS1 mutation, and 7/234 (0.3%) had the SPINK1 mutation. Nineteen (6.3%) risk individuals had pancreatic pathology including seven with pancreatic cancer, and four with pancreatic mucinous neoplasms. The earliest age of onset of PC in affected members was an independent factor associated with risk of developing PC in all risk groups. DM was associated with much-increased risk of developing PC in low and moderate risk groups (OR45.8. 95% CI. 13.82-151.64, P=0.001). Combined family history of non-PC malignancy in the family in the low-risk individual was associated with abnormal findings on MRI (OR8.4, 95% CI 3.29-21.88, P < 0.0001). There was no any complication of screening. In summary, pancreatic cancer screening may benefit in risk individuals with family history of pancreatic cancer in our population. The diagnostic yield is similar to prior studies. MRCP as initial screening modality is safe and effective. Future study will be needed to tailor PC screening strategy in different risk populations.

Bevacizumab might potentiate the chemotherapeutic effect in breast cancer patients with leptomeningeal carcinomatosis.

BACKGROUND/PURPOSE: Patients with leptomeningeal carcinomatosis (LC) from breast cancer is generally resistant to systemic chemotherapy. Bevacizumab may increase intratumor concentration of the chemotherapeutic agents through vascular normalization, although the overall clinical benefit of bevacizumab for metastatic breast cancer is under debate. METHODS: Successful treatment of two breast cancer patients who developed LC after whole brain irradiation treatment for the brain metastases is reported here. Both patients have refractory disease to taxane and anthracycline, and both of them have disease progression under intrathecal methotrexate treatment for LC. RESULTS: The two patients received systemic chemotherapy with bevacizumab (7.5 mg/kg infusion on Day 1), cisplatin (80 mg/m(2) infusion for 24 hours on Day 2), and etoposide (80 mg/m(2) infusion for 2 hours on Days 2-4) at 21-28 day intervals. Both patients achieved best response of negative cerebral spinal fluid cytology study and dramatic improvement of neurologic deficit after treatment. Their overall survival after development of LC was 8 months and 7.5 months respectively. CONCLUSION: Bevacizumab plus etoposide and cisplatin might be a new option for breast cancer patients with LC. Further prospective study is warranted.

Cytopathologic features of epithelioid inflammatory myofibroblastic sarcoma with correlation of histopathology, immunohistochemistry, and molecular cytogenetic analysis.

BACKGROUND: Epithelioid inflammatory myofibroblastic sarcoma (E-IMS) is a recently established rare variant of inflammatory myofibroblastic tumor. It is characterized by a distinctive constellation of clinical, pathological, and molecular features, including a nearly exclusive intraabdominal location, strong male predilection, aggressive clinical course, predominance of epithelioid tumor cells, and Ran-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) fusion in the majority of cases. To the authors' knowledge, the cytologic features of E-IMS have not been described to date. METHODS: Cases of E-IMS that had corresponding cytology were searched. Six cytology samples (1 fine-needle aspiration sample, 2 imprint samples, and 3 effusion fluids) containing tumor cells were identified in 5 patients with E-IMS. RESULTS: The cytomorphology included large monotonous epithelioid cells arranged in loose aggregates or singly, with admixed myxoid stroma, and an inflammatory background rich in neutrophils. The tumor cells had a large, round, eccentric nucleus with vesicular chromatin, prominent nucleoli, and moderate amounts of pale cytoplasm. Delicate thin-walled branching vessels traversing tumor aggregates was a prominent feature in a fine-needle aspiration sample. Immunohistochemically, ALK was positive in all 5 tumors, with a nuclear membranous staining pattern noted in 3 cases and a cytoplasmic pattern observed in the other 2 cases. ALK rearrangement was confirmed in all 5 tumors by molecular genetic studies. CONCLUSIONS: The cytologic features of E-IMS recapitulate its histologic characteristics. E-IMS merits inclusion in the differential diagnosis of any intraabdominal, large epithelioid cell neoplasm. Confirmation of ALK rearrangement is advisable because patients may benefit from targeted therapies.

Cystic fibrosis transmembrane conductance regulator gene variants are associated with autoimmune pancreatitis and slow response to steroid treatment.

BACKGROUND: Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis. To date, the association of CFTR gene variants with AIP has not been studied. METHODS: The entire coding and intronic regions of the CFTR gene were examined using next-generation sequencing in 89 AIP patients. Clinical features, including imaging, histology, serology, steroid treatment response and extra-pancreatic involvement, were compared between AIP patients with and without CFTR gene variants. RESULTS: A total of 28.1% (25/89) of the AIP patients carried 26 CFTR variants, including nine with I556V, seven with 5T, four with S42F, two with I125T, and one each with R31C, R553X, S895N, and G1069R. The presence of CFTR variants and age was independent predictors of the response to steroid treatment, as shown by multivariate analysis. CONCLUSIONS: CFTR variants are associated with AIP. Because AIP patients with CFTR variants show slower and reduced steroid treatment responses, different treatments should be considered in AIP patients with CFTR variants.

Comparison and validation of International Consensus Diagnostic Criteria for diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese cohort.

OBJECTIVES: The International Consensus Diagnostic Criteria (ICDC) designed to diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The diagnostic performance of ICDC has not been previously evaluated in diffuse-type and focal-type AIP, respectively, in comparison with the revised HISORt and Asian criteria in Taiwan. DESIGN: Prospective, consecutive patient cohort. SETTING: Largest tertiary referred centre hospital managing pancreatic disease in Taiwan. PARTICIPANTS: 188 patients with AIP and 130 with tissue proofed pancreatic adenocarcinoma were consecutively recruited. INTERVENTIONS: The ICDC, as well as revised HISORt and Asian criteria, was applied for each participant. Each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2 in diffuse-type and focal-type AIP. OUTCOMES: Sensitivity, specificity and accuracy. Each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2 in AIP and focal-type AIP. RESULTS: The sensitivity, specificity and accuracy of ICDC for all AIP were the best: 89.4%, 100% and 93.7%, respectively, in these three criteria. The sensitivity, specificity and accuracy of ICDC for focal-type AIP (84.9%, 100% and 93.8%) were also the best among these three criteria. The area under the curve of receiver-operator characteristic of ICDC was 0.95 (95% CI 0.92 to 0.97) in all AIP and 0.93 (95% CI 0.88 to 0.97) in focal-type AIP. CONCLUSIONS: The sensitivity, specificity and accuracy of ICDC are higher than the revised HISORt and Asian criteria. The sensitivity, specificity and accuracy of each criterion are higher in diffuse-type AIP compared with focal-type AIP. Under the same specificity, the sensitivity and accuracy of ICDC are higher than other diagnostic criteria in focal-type AIP. ICDC has better diagnostic performance compared with previously proposed diagnostic criteria in diffuse-type and focal-type AIP.

Human cationic trypsinogen but not serine peptidase inhibitor, Kazal type 1 variants increase the risk of type 1 autoimmune pancreatitis.

BACKGROUND AND AIM: Autoimmune pancreatitis (AIP) is a distinct disease entity. Whether the genes involved in pancreatic acinar cell injury, cationic trypsinogen gene (protease, serine, 1 [trypsin 1] [PRSS1]) and the pancreatic secretory trypsin inhibitor gene (serine peptidase inhibitor, Kazal type 1 [SPINK1]), are associated with AIP remains to be explored. METHODS: Genetic analyses of PRSS1 variants (exon 2 and 3) and SPINK1 variants (exon 1, 2, and 3) including the intronic areas in 118 patients with AIP and 200 control subjects were performed by direct DNA sequencing. Clinical features including imaging, histology, serology, response to steroid, and extra-pancreatic organ involvement in AIP patients with and without variants were compared. RESULTS: A total of 19 PRSS1 variants and one SPINK1 variant were identified in 20 (16.9%) out of 118 AIP patients. They included one K92N, nine R116C, seven T137M, one C139S, and one C139F of PRSS1 and one 2(IVS3 + 2) of SPINK1. No PRSS1 or SPINK1 variant was identified in the control group. Patients with PRSS1 variants had an increased risk of AIP with odds ratio 22.37 (95% confidence interval: 2.96-168.8, P = 0.003) and higher frequency of serum IgG4 above 280 mg/dL. Using immunosuppressive agent and PRSS1 variant were predictors of less disease relapse in univariate analysis. Presence of PRSS1 variants was the only negative predictor for disease relapse in multivariate analysis. CONCLUSIONS: We found a significantly higher frequency of PRSS1 variants in AIP patients than in geographically and ethnically matched control subjects. PRSS1 variants are associated with less disease relapse in AIP.

BMVC test, an improved fluorescence assay for detection of malignant pleural effusions.

The diagnosis of malignant pleural effusions is an important issue in the management of malignancy patients. Generally, cytologic examination is a routine diagnostic technique. However, morphological interpretation of cytology is sometimes inconclusive. Here an ancillary method named BMVC test is developed for rapid detection of malignant pleural effusion to improve the diagnostic accuracy at low cost. A simple assay kit is designed to collect living cells from clinical pleural effusion and a fluorescence probe, 3,6-Bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), is used to illuminate malignant cells. The fluorescence intensity is quantitatively analyzed by ImageJ program. This method yields digital numbers for the test results without any grey zone or ambiguities in the current cytology tests due to intra-observer and inter-observer variability. Comparing with results from double-blind cytologic examination, this simple test gives a good discrimination between malignant and benign specimens with sensitivity of 89.4% (42/47) and specificity of 93.3% (56/60) for diagnosis of malignant pleural effusion. BMVC test provides accurate results in a short time period, and the digital output could assist cytologic examination to become more objective and clear-cut. This is a convenient ancillary tool for detection of malignant pleural effusions.

Multi-gene analyses from waste brushing specimens for patients with peripheral lung cancer receiving EBUS-assisted bronchoscopy.

OBJECTIVES: Although flexible bronchoscopy with the assistance of miniature radial-probe endobronchial ultrasound (EBUS) is increasingly employed to diagnose peripheral lung cancer, transbronchial biopsies typically offer an insufficient amount of tissue to conduct additional molecular analysis. We evaluated the feasibility of multi-gene analyses from waste brushing samples obtained by EBUS-assisted bronchoscopy. MATERIALS AND METHODS: For lung cancer patients with positive brushing cytology, analysis of EGFR, K-ras and EML4-ALK fusions were carried out, utilizing reverse transcription-polymerase chain reaction and Sanger sequencing on the cell-derived RNA retrieved from waste brushing samples. RESULTS: EBUS-guided brushings were judged positive for tumor cells in 84 (68.9%) of the 122 patients with peripheral lung cancer receiving flexible bronchoscopy. Genotyping of EGFR and K-ras was successfully implemented in 80 (95.2%) of the 84 cytology-proven brushing samples, along with satisfactory yields to detect EGFR (55.0%) and K-ras (2.5%) mutations. The results of EGFR genotyping from the brushing specimens were highly concordant with those provided from other corresponding samples (concordance rate: 94%, kappa: 0.92). Of the 19 patients with adenocarcinoma or non-small cell lung cancer not otherwise specified harboring wild-type EGFR and K-ras, two cases (10.5%) were identified to harbor EML4-ALK fusions. CONCLUSION: Our results suggest that multi-gene analyses from waste brushing specimens using RNA-based Sanger sequencing is highly feasible. This approach offers an opportunity to overcome the dilemma of flexible bronchoscopy in molecular diagnostics for lung cancer, and could potentially recruit more patients for targeted therapy according to the molecular characteristics of the tumor cells.