Prognosis of gastric adenocarcinoma patients with various burdens of peritoneal metastases.

BACKGROUND: Peritoneal metastases (PM) in patients with gastric adenocarcinoma (GAC) may be identified by diagnostic laparoscopy (DL) or imaging (I). Although prognosis is poor, some patients have excellent outcome. We compared the overall survival (OS) of patients in 3 groups: those with positive cytology (CY+) by DL (DL-CY+), those with gross PM (GPM) by DL (DL-GPM+) and with GPM obvious on I (I-GPM+). METHODS: 146 GAC patients were identified. The Kaplan-Meier analysis, univariate, and multivariate Cox proportional hazards regression models were employed. RESULTS: Patients were primarily men (67%), with good ECOG scores (0-1; 89%), had DL (84%), had poorly differentiated GAC (92%), and had received chemotherapy (89%). The median OS for all patients was 15 months (5% CI, 12.9-18.2 months). The DL-CY+ group had median OS of 22.5 months (95% CI, 15-29.3 months). Patients with I-GPM+ had four times the risk of death than those with DL-CY+ (P < 0.001) and patients with DL-GPM+ had two times the risk of death than those with DL-CY+ (P = 0.001). At 36 months, all DL-GPM+ and I-GPM+ had died but 8 patients with DL-CY+ remained alive. CONCLUSIONS: Some GAC patients with DL-CY+ have long OS; therefore, novel strategies to further prolong their OS are needed.

Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics.

Increasing use of fine needle aspiration for oncological diagnosis, while minimally invasive, poses a challenge for molecular testing by traditional sequencing platforms due to high sample requirements. The advent of affordable benchtop next-generation sequencing platforms such as the semiconductor-based Ion Personal Genome Machine (PGM) Sequencer has facilitated multi-gene mutational profiling using only nanograms of DNA. We describe successful next-generation sequencing-based testing of fine needle aspiration cytological specimens in a clinical laboratory setting. We selected 61 tumor specimens, obtained by fine needle aspiration, with known mutational status for clinically relevant genes; of these, 31 specimens yielded sufficient DNA for next-generation sequencing testing. Ten nanograms of DNA from each sample was tested for mutations in the hotspot regions of 46 cancer-related genes using a 318-chip on Ion PGM Sequencer. All tested samples underwent successful targeted sequencing of 46 genes. We showed 100% concordance of results between next-generation sequencing and conventional test platforms for all previously known point mutations that included BRAF, EGFR, KRAS, MET, NRAS, PIK3CA, RET and TP53, deletions of EGFR and wild-type calls. Furthermore, next-generation sequencing detected variants in 19 of the 31 (61%) patient samples that were not detected by traditional platforms, thus increasing the utility of mutation analysis; these variants involved the APC, ATM, CDKN2A, CTNNB1, FGFR2, FLT3, KDR, KIT, KRAS, MLH1, NRAS, PIK3CA, SMAD4, STK11 and TP53 genes. The results of this study show that next-generation sequencing-based mutational profiling can be performed on fine needle aspiration cytological smears and cell blocks. Next-generation sequencing can be performed with only nanograms of DNA and has better sensitivity than traditional sequencing platforms. Use of next-generation sequencing also enhances the power of fine needle aspiration by providing gene mutation results that can direct personalized cancer therapy.

Ultrasound-guided fine-needle aspiration biopsy of internal mammary nodes: technique and preliminary results in breast cancer patients.

OBJECTIVE: The objective of our study was to describe our technique and preliminary results of ultrasound-guided fine-needle aspiration (FNA) of indeterminate internal mammary (IM) lymph nodes in patients with a history of breast cancer. CONCLUSION: Ultrasound-guided FNA of IM nodes is feasible and is particularly useful in the staging of breast cancer.

A first report of endoscopic ultrasound for the diagnosis of pancreatic amyloid deposition in immunoglobulin light chain (AL) amyloidosis (primary amyloidosis).

CONTEXT: Pancreatic involvement in systemic light chain (AL)-amyloidosis is exceedingly rare. Prior reports of endoscopic ultrasound (EUS) for the diagnosis of amyloidosis are also limited. CASE REPORT: We report the first description of EUS-guided fine needle aspiration (FNA) for the diagnosis of primary AL-amyloidosis involving the pancreas. CONCLUSION: EUS-FNA can be effectively utilized for the characterization and cytologic diagnosis of pancreatic amyloidosis and potentially other accessible extraluminal amyloid deposits.

So-called sclerosing hemangioma of lung: current concept.

Sclerosing hemangioma of the lung is a rare neoplasm with polymorphic histologic features. Despite various patterns, there are 2 unifying cellular components: "surface cells" and "round cells." Although histogenesis has been debated for decades, most ultrastructural, immunocytochemical, and molecular studies strongly indicate a neoplastic epithelial derivation for both cellular components. Herein, we present a review of sclerosing hemangioma and summarize the essential data regarding histologic, cytologic, and ancillary findings of this distinctive pulmonary neoplasm.

Cervical cytology reproducibility and associated clinical and demographic factors.

BACKGROUND: Although the Pap test has been the standard screening method for cervical precancer/cancer detection, it has been criticized for having a relatively low sensitivity and a low reproducibility between pathologists. There is limited knowledge about inter-rater agreement and what clinical and demographic factors are associated with disagreements between pathologists reading the same Pap smear. METHODS: This study aimed to assess inter- and intra- rater agreement of the Pap smear in 1619 cytologic slides with biopsy confirmation, using kappa statistics. Clinical and demographic factors associated with higher odds of inter-rater agreement were also examined and stratified by histologic diagnosis grade. RESULTS: Using a five grade classification system, the overall kappa statistics for total, inter-rater, and intra-rater samples were 0.62, 0.57, and 0.88 (unweighted) and 0.83, 0.81, and 0.95 (weighted), respectively. In stratified analyses by histologic grade, total kappas ranged from 0.40 (atypia) to 0.64 (human papilloma virus/CIN 1). Factors such as referral for abnormal Pap test (diagnostic vs screening population), recruiting site, and parity were found to be associated with higher agreement between the two cytologic readings. CONCLUSIONS: We observed relatively higher levels of agreement compared with other studies. However, variability was considerable and agreement was generally moderate, suggesting that cervical screening test accuracy and reproducibility needs to be improved.

Clinical significance of distinguishing between follicular lesion and follicular neoplasm in thyroid fine-needle aspiration biopsy.

BACKGROUND: Subclassifying indeterminate thyroid fine-needle aspiration (FNA) biopsy findings as follicular lesion or follicular neoplasm has been suggested as useful in triaging patients to observation or surgery, respectively. However, terminology and therefore the probability of malignancy vary between pathologists and institutions. The purpose of this study was to evaluate a single institution's experience with indeterminate thyroid FNA results to determine if subclassification (neoplasm versus lesion) aids in identifying patients at higher risk for malignancy. METHODS: From 1990 to 2006, all patients with indeterminate thyroid FNA results (follicular lesion or neoplasm) at The University of Texas M.D. Anderson Cancer Center were evaluated for FNA correlation with the surgical specimen diagnosis. Patients with FNAs suspicious for papillary thyroid carcinoma or with definitive malignant disease (i.e., metastases) were excluded. RESULTS: Indeterminate FNA results were present in 540 patients, including 410 as follicular lesion and 130 as follicular neoplasm. Two hundred ninety-seven (55.0%) patients underwent surgical resection: 199 (48.5%) follicular lesions and 98 (75.4%) follicular neoplasms. Incidence of malignancy was higher in thyroid nodules classified as neoplasm compared with lesion (21.4% versus 7.0%, respectively; P=0.0005) and increased in follicular neoplasms with nodule size (37.5% malignant if nodule was [4 cm, P=0.03). CONCLUSIONS: Subclassification of indeterminate thyroid FNA biopsy results into neoplasm and lesion successfully defines high- and low-risk nodules, respectively. These findings support surgical resection for follicular neoplasms, selective use of surgical intervention for follicular lesions at our institution, and continued efforts to define unified terminology between institutions.

Accuracy of diagnosing mantle cell lymphoma and identifying its variants on fine-needle aspiration biopsy.

BACKGROUND: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma portending an aggressive clinical course; the blastoid and pleomorphic morphological variants have an even worse prognosis. In addition, patients with classic morphology and a high proliferation index (HPI), also have reduced survival. Although variants have been defined, to the authors' knowledge the ability to detect these subtypes by fine-needle aspiration biopsy (FNAB) has not been described. METHODS: MCL cases diagnosed by lymph node FNAB with concurrent core needle biopsy were reviewed from 146 patients, accounting for 172 specimen pairs. FNAB and core needle biopsy diagnoses were compared to determine concordance rates. Flow cytometric immunophenotype and Ki-67 rates were evaluated. RESULTS: The classic subtype was diagnosed in 58% of cases (99 of 172 pairs) and variant morphology was diagnosed in 42% of cases (73 of 172 pairs) by histology. Twenty-nine patients presented with variant morphology whereas 28 underwent transformation. A nontraditional immunophenotype including loss of CD5 or FMC-7 and expression of CD23 and CD10 was found in 44% of variants (29 of 66 variants) and 19% of classic subtypes (18 of 94 classic subtypes) (P = .0008). Ki-67 rates averaged from 56% to 76% for blastoid and pleomorphic cases, 53% to 55% for MCL-HPI cases, and 17% to 19% for classic cases. The sensitivity and specificity to detect MCL variants by FNAB were 74% and 93%, respectively. CONCLUSIONS: The accuracy of diagnosing MCL is high when adequate samples for cytomorphology and flow cytometry are obtained. Subtyping variants by cytomorphology alone has challenges, but overall demonstrates high sensitivity and specificity. The performance of Ki-67 on cytology specimens is useful for detecting MCL with HPI.

Does neoadjuvant treatment for gastric cancer patients with positive peritoneal cytology at staging laparoscopy improve survival?

BACKGROUND: The purpose of this study was to identify clinicopathologic factors associated with positive peritoneal cytology (PPC) in patients with gastric cancer and to compare the overall survival (OS) of patients with PPC treated with and without neoadjuvant therapy. METHODS: The medical records of 3,747 patients with gastric or gastroesophageal adenocarcinoma presenting to our institution (January 1995 to December 2005) were reviewed to identify those patients who underwent diagnostic laparoscopy as a staging procedure prior to consideration for neoadjuvant therapy. Associations between various clinicopathologic factors and OS were examined with Cox proportional hazards models. Kaplan-Meier curves were created to compare OS between groups. RESULTS: Of 381 patients who underwent diagnostic laparoscopy for staging, 39 were found to have PPC without gross metastatic disease. Linitis plastica and tumors located at the gastroesophageal junction were identified as predictors of PPC (P < 0.01). Median follow-up for living patients was 51 months. Median OS for patients with PPC and no gross metastatic disease at laparoscopy (13 months) was no different from that for patients with gross metastatic disease at laparoscopy (10 months, P = 0.06). For the 39 patients with PPC and no gross metastatic disease, use of neoadjuvant therapy resulted in a 3-year OS rate of 12% versus 0% for patients who did not receive neoadjuvant therapy. CONCLUSION: Outcomes for patients with PPC without gross metastatic disease are not significantly different from those patients with gross metastatic disease at laparoscopy. However, some patients can achieve long-term survival and should be considered for neoadjuvant treatment prior to attempts at surgical resection.

Combined EUS with FNA and ERCP for the evaluation of patients with obstructive jaundice from presumed pancreatic malignancy.

BACKGROUND: An EUS-guided FNA (EUS-FNA) and a therapeutic ERCP are frequently required for the evaluation of patients who were seen for an obstructing periampullary lesion. OBJECTIVE: To determine the feasibility and outcomes of combining an EUS-FNA and a therapeutic ERCP into a single session. DESIGN: Retrospective single-center study. SETTING: Tertiary-referral cancer center. PATIENTS: A total of 114 patients with a suspected malignant obstructing lesion in the pancreatic head. INTERVENTIONS: An EUS with or without FNA plus an ERCP. MAIN OUTCOME MEASUREMENTS: Duration, diagnostic yield, and complication rate of the combined procedures. RESULTS: The mean (SD) total procedure time (EUS, with or without FNA plus ERCP) was 73.6 +/- 30 minutes, with a median of 66 minutes (range 25-148 minutes). In many cases, cytologic diagnosis from FNA became available during an ERCP, which obviated the need for further sampling. EUS-FNA had a sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 84.6%, 100%, 100%, 62.9%, and 87.8%, respectively. During an ERCP, endoscopic sphincterotomies were performed in 51 patients, and biliary stents were placed in 96 patients. Twelve patients (10.5%) had a complication, with 6 having postprocedural pancreatitis. LIMITATIONS: Retrospective single-center experience. CONCLUSIONS: Combined EUS-FNA and therapeutic ERCP is technically feasible, with a complication rate no higher than the component procedures, while efficiently providing tissue diagnosis and biliary drainage.

Efficacy of telecytopathology for preliminary assessment of fine-needle aspirations performed at a remote facility.

INTRODUCTION: The need for real time anatomic pathology services has grown as healthcare systems, traditionally found at large medical centers, expand into smaller communities. The placement of a pathologist is not cost-, time-, or resource-efficient. Telecytopathology can provide rapid offsite evaluation of cytology tissues. This study evaluated the accuracy rate of rendered preliminary assessments for telecytopathology of ultrasound (US)-guided fine-needle aspirations (FNAs) for an offsite facility by comparing preliminary assessment results with the final diagnosis. MATERIALS AND METHODS: The pathology database was searched for telecytopathology US-guided FNAs with rapid offsite evaluation performed at a regional care center from August 2014 to June 2016. A total of 674 consecutive US-guided FNAs from 444 patients were obtained. FNA sites included lymph node (345 cases), breast (178 cases), thyroid gland (71 cases), and others (80 cases). RESULTS: Preliminary assessments of the 674 FNAs were adequate/benign in 275 (41%) cases, adequate/malignant in 182 (27%) cases, adequate/further review needed in 162 (24%) cases, indeterminate/borderline cellularity in 37 (5%) cases, and nondiagnostic in 18 (3%) cases. Final FNA diagnoses rendered included 391 (58%) negative for malignancy, 205 (30%) malignant, 34 (5%) atypical/suspicious for malignancy, 26 (4%) indeterminate cellularity-favor benign, and 18 (3%) nondiagnostic specimens. Concurrent core biopsy was performed in 42 cases and 83 cases were triaged for ancillary studies. The majority (99%) of US-guided FNAs demonstrated concordant preliminary assessments with the final diagnoses. A major discrepancy occurred in 1 case; 5 cases had minor discrepancies. CONCLUSIONS: Remote facility telecytopathology can be utilized as an accurate modality in guiding appropriate tissue acquisition and final diagnosis.

Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients.

BACKGROUND: Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes. CASE PRESENTATION: We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57 years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6 months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5 months since initiation of treatment. CONCLUSIONS: The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.

Immunocytochemical study of the expression of mesothelin in fine-needle aspiration biopsy specimens of pancreatic adenocarcinoma.

Mesothelin is a potential marker of pancreatic adenocarcinoma that was recently identified by serial analysis of gene expression. We evaluated the sensitivity and specificity of mesothelin as a marker of pancreatic adenocarcinoma on destained Papanicolaou (Pap) smears and unstained cellblocks from 28 patients using a monoclonal antibody to mesothelin. Intensity and proportion of staining was semiquantitatively graded on a scale of 1-3, and as 0%, 1 to <10%, 10-50%, or >50%. Positive staining for mesothelin was seen in 64% of the direct smears and in 36% of cell block sections. Focal positivity for mesothelin was noted in benign pancreatic tissue in one of 10 cases. Staining was most often focal (<50% of cells) in both direct smears and cell block sections. The overall sensitivity and specificity of mesothelin as a marker for pancreatic adenocarcinoma were 68% and 90%, respectively. Sensitivity was higher in Pap smears than in cell block sections (64% versus 36%). The presence of occasional mesothelin expression in benign tissue, its very focal expression in malignant tissue may limit the utility of mesothelin as a marker of pancreatic adenocarcinomas in fine-needle aspiration (FNA) specimens.

Utility of endoscopic ultrasound-guided fine-needle aspiration of regional lymph nodes that are proximal to and far from the primary distal esophageal carcinoma.

Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert's I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of the pancreas allows the diagnosis of pancreatic cancer to be established without exploratory surgery. We reviewed our recent experience with EUS-FNA in patients with presumed pancreatic cancer and report the diagnostic accuracy and complications of this procedure. Data were reviewed from all patients who presented with CT evidence of a pancreatic mass or a malignant biliary stricture and underwent EUS-FNA at our institution between November 1, 1999, and October 1, 2001. Based on the findings of contrast-enhanced, multislice CT scanning, patients were categorized as having resectable, locally advanced, or metastatic disease. EUS-FNA was performed in 233 patients. A final diagnosis of cancer was established in 216 patients (93%), 15 patients (6%) were found to have benign disease, and the final diagnosis remains unknown in two patients (1%). The sensitivity, specificity, and accuracy of EUS-FNA for diagnosis of a pancreatic malignancy were 91%, 100%, and 92%, respectively. For the 216 patients subsequently proven to have cancer, the results of EUS-FNA were diagnostic in 197 (91%); 96 (90%) of 107 patients with resectable disease, 62 (97%) of 64 with locally advanced disease, and 39 (87%) of 45 with metastatic disease. Four patients (2%) developed a clinically apparent complication that required hospital admission, including two patients who required surgery for duodenal perforation. There were no EUS-related deaths. We conclude that EUS-FNA can safely and accurately establish a cytologic diagnosis in patients with both early-stage and advanced pancreatic cancer. This enables consideration of all treatment options including protocol-based therapy.

Fine-needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients.

BACKGROUND: False-positive, false-negative, and indeterminate fine-needle aspiration (FNA) biopsy results complicate the management of patients with thyroid nodules. METHODS: Thyroid FNA results from 240 consecutive patients (seen 1991 to 2002) were categorized into four groups: positive for malignancy, negative for malignancy, indeterminate for malignancy, and nondiagnostic. Indeterminate results included follicular neoplasm, Hürthle cell neoplasm, and suspicious for papillary carcinoma. The FNA results were compared with histopathologic analysis after thyroidectomy. RESULTS: The FNA results were 76 (32%) positive for malignancy, 53 (22%) negative for malignancy, 100 (42%) indeterminate for malignancy, and 11 (5%) nondiagnostic. There were 3 (4%) false-positive and 2 (4%) false-negative FNA results. Among the 100 indeterminate FNA results, carcinoma was found in 11 (15%) of 73 follicular neoplasms, 2 (20%) of 10 Hürthle cell neoplasms, and 14 (82%) of 17 suspicious for papillary carcinoma. For the 73 patients with follicular neoplasms, nodule diameter >2 cm was associated with an increased risk of malignancy (P <0.03). CONCLUSIONS: False-negative FNA results are uncommon, supporting the practice of observation in most of these patients. Among those with indeterminate biopsy results, high-risk subgroups include patients with FNA results suspicious for papillary carcinoma and follicular neoplasms >2 cm.

Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma.

BACKGROUND: The objectives of this study were to evaluate the validity of Cervista human papillomavirus (HPV) assays in head and neck fine-needle aspiration (FNA) specimens from patients with head and neck squamous carcinomas and to verify that the Cervista assay in FNA specimens is a valid option for determining HPV status in patients with oropharyngeal carcinomas. METHODS: The authors retrospectively retrieved 64 head and neck FNA specimens from patients who had head and neck squamous carcinoma. The specimens were tested for HPV types 16 and 18 (HPV16/18) and for high-risk (HR) HPV DNA using the Cervista HPV16/18 and HPV HR assays, respectively. The results from those assays were compared with the results from polymerase chain reaction (PCR)-based HPV assays in the same tissues and with the results from HPV in situ hybridization assays/p16 immunostaining in the corresponding primary tumors. RESULTS: In total, 64 FNA specimens were analyzed. The Cervista HPV16/18 and/or HPV HR assays were positive in 48 of 64 specimens (75%), and there was a predominance of HPV16 (42 of 48 specimens; 88%). In the 49 specimens that had PCR-based test results, overall agreement with Cervista assay results was 96% (47 of 49 specimens; κ = 0.883). In the 49 specimens that had PCR-based HPV16/18 genotyping results, overall agreement with the Cervista HPV16/18 results was 94% (46 of 49 specimens; κ = 0.847). In the 36 primary carcinoma specimens that had valid HPV in situ hybridization/p16 immunostaining results, overall agreement with the Cervista assay results was 92% (33 of 36 specimens; κ = 0.679). CONCLUSIONS: Cervista HPV16/18 and Cervista HPV HR testing of head and neck FNA specimens is a valid option for determining HPV16/18 status in patients with oropharyngeal carcinoma.

Randomized clinical trial of endobronchial ultrasound needle biopsy with and without aspiration.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) is performed with a dedicated 22- or 21-gauge needle while suction is applied. Fine-needle sampling without suction (capillary sampling) has been studied for endoscopic ultrasound and for biopsies at various body sites and has resulted in similar diagnostic yield and fewer traumatic samples. However, the role of EBUS-guided transbronchial needle capillary sampling (EBUS-TBNCS) is still to be determined. METHODS: Adults with suspicious hilar or mediastinal lymph nodes (LNs) were included in a single-blinded, prospective, randomized trial comparing EBUS-TBNA and EBUS-TBNCS. The primary end point was the concordance rate between the two techniques in terms of adequacy and diagnosis of cytologic samples. The secondary end point was the concordance rate between the two techniques in terms of quality of samples. RESULTS: A total of 115 patients and 192 LNs were studied. Concordance between EBUS-TBNA and EBUS-TBNCS was high, with no significant difference in adequacy (88% vs 88%, respectively [P ± .858]; concordance rate, 83.9% [95% CI, 77.9-88.8]); diagnosis (36% vs 34%, respectively [P ± .289]; concordance rate, 95.8% [95% CI, 92-92.8]); diagnosis of malignancy (28% vs 26%, respectively [P ± .125]; concordance rate, 97.9% [95% CI, 94.8-99.4]); or sample quality (concordance rate, 83.3% [95% CI, 73.3-88.3]). Concordance between EBUS-TBNA and EBUS-TBNCS was high irrespective of LN size (≤ 1 cm vs > 1 cm). CONCLUSIONS: Regardless of LN size, no differences in adequacy, diagnosis, or quality were found between samples obtained using EBUS-TBNA and those obtained using EBUS-TBNCS. There is no evidence of any benefit derived from the practice of applying suction to EBUS-guided biopsies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00886847; URL: www.clinicaltrials.gov

Cystic lymph nodes in the lateral neck as indicators of metastatic papillary thyroid cancer.

OBJECTIVE: To determine whether radiographic findings portend to metastatic disease in patients with papillary thyroid carcinoma (PTC) and whether cystic lymph node metastasis can be recognized by preoperative, ultrasound-guided fine-needle aspiration (FNA). METHODS: We performed a retrospective review of patients with cystic lymph nodes in the lateral neck identified on preoperative ultrasonography between March 1996 and December 2009. Factors examined included demographic information; stage; cytologic and final pathologic findings; and imaging characteristics including location, size, and presence of vascularity and calcifications. Time of cystic node identification in relationship to initial diagnosis was also recorded. RESULTS: Thirty patients had cystic lymph nodes in the lateral neck on cervical ultrasonography during the study period. Among this group, 28 (93%) had PTC, 1 (3%) had papillary serous carcinoma of the ovary, and 1 (3%) had poorly differentiated thyroid cancer. Median age at initial cancer diagnosis was 41 years (range, 16-64 years). Twenty-one patients (70%) were women, and median lymph node size was 1.8 cm (range, 0.6-4.8 cm). Twenty-three patients (77%) had a solitary cystic lymph node, and the remainder had more than 1 cystic lymph node. Cystic lymph nodes were identified at initial presentation in 11 patients (37%), while cystic lymph nodes were discovered in 19 patients (63%) after the initial operation. FNA was performed on the cystic lymph nodes of 23 patients (77%). Cytologic findings were positive for metastatic disease in 18 of 23 patients (78%). Among the 5 of 23 patients with negative cytologic findings, thyroglobulin aspirate was obtained in 1 patient, confirming metastatic PTC. Final pathologic review after surgical resection of cystic lymph nodes with negative cytologic findings from FNA was consistent with metastatic disease in 4 of 5 patients (80%). CONCLUSIONS: In patients with PTC, the presence of a cystic lymph node by ultrasonographic examination is highly suggestive of locally metastatic disease. Confirmation of metastatic PTC may sometimes be achieved with thyroglobulin aspirate from cystic lymph nodes when cytologic findings are negative. Clinicians should strongly consider surgical lymph node resection of cystic lymph nodes regardless of the preoperative cytologic findings by FNA.

Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.

PURPOSE: This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. RESULTS: Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). CONCLUSION: This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.