Evaluation of surgical margin status in patients with early glottic cancer (Tis-T2) treated with transoral CO2 laser microsurgery, on local control.

PURPOSE: To assess the impact of surgical margins status on local control in patients with primary early glottic (Tis-T2) squamous cell carcinoma after treatment with transoral CO2 laser microsurgery (TLM) and to assess the significance of additional wound bed biopsies. METHODS: Patients with Tis-T2 tumours treated with TLM type I-III resections according to the European Laryngological Society classification between 2009 and 2013 were included in retrospective analysis. Recurrence rate was determined in patients with free versus non-free specimen margins and wound biopsies. Five-year survival rates were determined using the Kaplan-Meier method. Prognostic impact of pT-category, resection margin status, tumour differentiation, wound bed biopsy status, and number of biopsies on local control (LC) were tested with the log-rank test. RESULTS: Eighty-four patients were included in the analysis. Positive margins were seen in 68 patients (81.0%). Margin status after TLM did not significantly influence LC (p = 0.489), however, additional wound bed biopsies were significantly associated with lower LC (p = 0.009). Five-year LC, disease-specific survival, overall survival and laryngeal preservation were 78.6, 78.0, 98.6 and 100%, respectively. CONCLUSIONS: Additional wound bed biopsies can help predict local recurrence in patients treated with TLM for early glottic carcinoma. We propose that there is enough evidence to support a wait-and-see policy in patients with positive specimen margins and negative wound bed biopsies. For patients with positive wound bed biopsies, further treatment is warranted.

Cytomorphological analysis of uterine cervical pap smears in relation to human papillomavirus infection in Indonesian women.

OBJECTIVE: Cervical cancer is the number one cause of cancer-associated death in Indonesian women (30/100,000 annually), where no screening program is present. The Papanicolaou test is widely accepted as an effective screening method for cervical neoplasia detection and often shows certain cytological features associated with human papillomavirus (HPV) infection. Especially in developing countries, cytological investigation is still the method of choice as compared to the frequent use of HPV DNA testing in western countries. STUDY DESIGN: In the present study, we investigated the validity of the use of cytomorphological changes as a marker for HPV infection. A total of 140 smears collected in three different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV DNA testing was performed using INNO-LiPA assays. RESULTS AND CONCLUSIONS: We found a highly significant association of classical koilocytosis, multinucleated cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei, moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using classical and nonclassical cytomorphological parameters we found an overall sensitivity of 42% and a specificity of 90%. The combination of classical and nonclassical parameters led to a higher sensitivity of HPV positivity prediction. These results are of importance for cytologists in developing countries as molecular HPV testing still poses a major financial, logistic and expertise problem.

Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial.

CONTEXT: Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging. OBJECTIVE: To compare the 2 recommended lung cancer staging strategies. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography. INTERVENTION: Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread. MAIN OUTCOME MEASURES: The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications. RESULTS: Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P = .11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P = .02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P = .47) and 94% (62/66; 95% CI, 85%-98%) (P = .02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P = .02). The complication rate was similar in both groups. CONCLUSIONS: Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00432640.

Toward optical guidance during endoscopic ultrasound-guided fine needle aspirations of pancreatic masses using single fiber reflectance spectroscopy: a feasibility study.

Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ? 5 ?? min . An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p = 0.038 ; 166 ?? ? mol / L versus 17 ?? ? mol / L , p = 0.039 , respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling.

Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of lung cancer and its impact on surgical staging.

PURPOSE: The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions. PATIENTS AND METHODS: Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point. RESULTS: EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non-small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded. CONCLUSION: EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.

EUS-guided FNA of centrally located lung tumours following a non-diagnostic bronchoscopy.

OBJECTIVE: To assess the feasibility and yield of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) in diagnosing centrally located lung tumours after a previously non-diagnostic bronchoscopy. BACKGROUND AND HYPOTHESIS: Bronchoscopy fails to establish a diagnosis in up to 30% of patients with suspected lung cancer. Intrapulmonary tumours located near or adjacent to the esophagus might be visualized and biopsied under real-time ultrasound guidance by EUS-FNA. DESIGN: Patients with suspected lung cancer and an intrapulmonary tumour located near or adjacent to the esophagus who had undergone a non-diagnostic bronchoscopy, underwent EUS-FNA for diagnostic purposes. Surgical-pathological verification occurred when EUS-FNA was non-diagnostic and in those patients diagnosed with non-small-cell lung cancer by EUS-FNA who were surgical candidates. RESULTS: EUS-FNA diagnosed lung cancer in 31 of 32 patients (97%). No complications occurred. The diagnosis obtained by EUS-FNA was confirmed in all 11 patients who were operated. In one case, in which EUS-FNA was non-diagnostic, a lymphoma was diagnosed after pneumonectomy. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA qualifies as the next diagnostic step in patients with suspected lung cancer and a non-diagnostic bronchoscopy if the intrapulmonary mass is located adjacent or near the esophagus. In these cases, EUS-FNA may replace computed tomography of the chest (CT)-guided biopsies and reduce the number of exploratory thoracotomies.

Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer.

CONTEXT: Up to 40% of thoracotomies performed for non-small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion (T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus. OBJECTIVE: To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer. DESIGN, SETTING, AND PATIENTS: Prospective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed. INTERVENTION: The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients. MAIN OUTCOME MEASURE: Detection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone. RESULTS: The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval [CI], 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive. CONCLUSION: These preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.

Mediastinal restaging: EUS-FNA offers a new perspective.

STUDY OBJECTIVE: We hypothesized that transoesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has the potential to be a valuable and accurate new diagnostic technique for mediastinal restaging in non-small cell lung cancer (NSCLC) after induction chemotherapy. The current restaging modalities either have a low diagnostic accuracy (computed tomography (CT) scan of the thorax) or they are invasive, can be technically difficult and are therefore not commonly performed (remediastinoscopy). METHODS AND PATIENTS: Nineteen consecutive patients with NSCLC and proven ipsilateral or subcarinal lymph node metastases (N2 disease) who had been treated with induction chemotherapy underwent mediastinal restaging by EUS-FNA. Patients had either a partial response (n=14) or stable disease (n=5) based on sequential CT scans of the thorax. INTERVENTIONS: EUS-FNA was performed in an ambulatory setting with biopsy of mediastinal lymph nodes (LN). No complications occurred. When EUS-FNA restaged the mediastinum as no regional lymph node metastasis (N0), surgical resection of the tumour with lymph node sampling or dissection was performed. RESULTS: The positive predictive value, negative predictive value, sensitivity, specificity and diagnostic accuracy of EUS-FNA in restaging mediastinal LN were 100, 67, 75, 100 and 83%, respectively. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA qualifies as an accurate, safe and minimally invasive diagnostic technique for the restaging of mediastinal lymph nodes after induction therapy in NSCLC. In the future EUS-FNA might play an important role in the mediastinal restaging in NSCLC, particularly to identify the subgroup of down staged patients who benefit most from further surgical treatment.

Rapid KRAS, EGFR, BRAF and PIK3CA mutation analysis of fine needle aspirates from non-small-cell lung cancer using allele-specific qPCR.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) and Trans-esophageal Ultrasound Scanning with Fine Needle Aspiration (EUS-FNA) are important, novel techniques for the diagnosis and staging of non-small cell lung cancer (NSCLC) that have been incorporated into lung cancer staging guidelines. To guide and optimize treatment decisions, especially for NSCLC patients in stage III and IV, EGFR and KRAS mutation status is often required. The concordance rate of the mutation analysis between these cytological aspirates and histological samples obtained by surgical staging is unknown. Therefore, we studied the extent to which allele-specific quantitative real-time PCR with hydrolysis probes could be reliably performed on EBUS and EUS fine needle aspirates by comparing the results with histological material from the same patient. We analyzed a series of 43 NSCLC patients for whom cytological and histological material was available. We demonstrated that these standard molecular techniques can be accurately applied on fine needle cytological aspirates from NSCLC patients. Importantly, we show that all mutations detected in the histological material of primary tumor were also identified in the cytological samples. We conclude that molecular profiling can be reliably performed on fine needle cytology aspirates from NSCLC patients.

Analysis of subcarinal lymph nodes in (suspected) non-small-cell lung cancer after a negative transbronchial needle aspiration -- what's next? A preliminary report.

BACKGROUND: Transbronchial needle aspiration (TBNA) of subcarinal lymph nodes (LN) has a variable yield. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has demonstrated a high accuracy in the analysis of enlarged subcarinal LN. OBJECTIVE: To assess the diagnostic accuracy of EUS-FNA in the analysis of enlarged subcarinal LN previously staged tumor negative by TBNA. METHODS AND PATIENTS: In this retrospective study, we included all patients with (suspected) lung cancer and enlarged (>1 cm on CT) subcarinal LNs staged tumor negative by TBNA, who were subsequently staged by EUS-FNA. In addition, surgical-pathological information had to be available in those cases in which EUS-FNA was tumor negative. RESULTS: Subcarinal LN metastases were assessed by EUS-FNA in 10 of 14 patients (71%). In 1 patient granulomas without necrosis were found. The remaining 3 patients staged tumor negative by both TBNA and EUS-FNA had reactive LN tissue, which was confirmed by surgical-pathological staging. Sensitivity, specificity and diagnostic accuracy of EUS in analyzing TBNA-negative LNs was 100% in all. CONCLUSIONS: In patients with (suspected) lung cancer and enlarged subcarinal LNs staged tumor negative by TBNA, additional staging by EUS-FNA confirmed subcarinal LN metastasis in 71% of the patients. These data suggest that for the analysis of the subcarinal LNs the real-time controlled technique of EUS-FNA is superior to the 'blind' technique of TBNA.