Optimising rapid on-site evaluation-assisted endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes: The real-time cytopathology intervention process.

INTRODUCTION: Lymph node sampling by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the state of art procedure for staging the mediastinum and hilar regions in lung cancer patients. Our experience of implementing the real-time cytopathology intervention (RTCI) process for intraoperative EBUS-TBNAs is presented. This study is aimed to describe in detail the RTCI process for EBUS-TBNAs, and assess its utility and diagnostic yield before and after its implementation in parallel to conventional rapid on-site evaluation (c-ROSE). METHODS: A retrospective review of all EBUS-TBNAs between July 2016 and July 2017 at the University of Rochester Medical Center was performed. Final diagnoses, patient clinical data, and number of non-diagnostic samples (NDS) were reviewed. The numbers of NDS obtained from EBUS-TBNAs with no cytology assistance (NCA), with RTCI and with c-ROSE were analysed. RESULTS: Non-diagnostic lymph node samples were found in 20 out of 116 (17%), three out of 114 (2.6%) and 33 out of 286 (11.5%) cases with NCA, RTCI and c-ROSE, respectively. Application of statistical analysis revealed significant difference in the NDS between the groups of cases in the operating room with NCA and RTCI (P = .005). The different settings and variables between the cases performed using RTCI in the operating room and those assisted with c-ROSE in the bronchoscopy suite preclude legitimate comparison. CONCLUSION: Our results indicate that the use of RTCI could yield a significantly low proportion of NDS when assisting EBUS-TBNA of mediastinal and hilar lymph node for lung cancer patients enhancing the diagnostic efficiency of the procedure.

Comparative Evaluation of the BD Phoenix Yeast ID Panel and Remel RapID Yeast Plus System for Yeast Identification.

Becton Dickinson Phoenix Yeast ID Panel was compared to the Remel RapID Yeast Plus System using 150 recent clinical yeast isolates and the API 20C AUX system to resolve discrepant results. The concordance rate between the Yeast ID Panel and the RapID Yeast Plus System (without arbitration) was 93.3% with 97.3% (146/150) and 95.3% (143/150) of the isolates correctly identified by the Becton Dickinson Phoenix and the Remel RapID, respectively, with arbitration.

Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models.

The efficacy of ionizing radiation (IR) for head and neck cancer squamous cell carcinoma (HNSCC) is limited by poorly understood mechanisms of adaptive radioresistance. Elevated glutaminase gene expression is linked to significantly reduced survival (p < 0.03). The glutaminase inhibitor, telaglenastat (CB-839), has been tested in Phase I/II cancer trials and is well tolerated by patients. This study investigated if telaglenastat enhances the cellular response to IR in HNSCC models. Using three human HNSCC cell lines and two xenograft mouse models, we examined telaglenastat's effects on radiation sensitivity. IR and telaglenastat combinatorial treatment reduced cell survival (p ≤ 0.05), spheroid size (p ≤ 0.0001) and tumor growth in CAL-27 xenograft bearing mice relative to vehicle (p ≤ 0.01), telaglenastat (p ≤ 0.05) or IR (p ≤ 0.01) monotherapy. Telaglenastat significantly reduced the Oxygen Consumption Rate/Extracellular Acidification Rate ratio in CAL-27 and HN5 cells in the presence of glucose and glutamine (p ≤ 0.0001). Telaglenastat increased oxidative stress and DNA damage in irradiated CAL-27 cells. These data suggest that combination treatment with IR and telaglenastat leads to an enhanced anti-tumor response. This pre-clinical data, combined with the established safety of telaglenastat justifies further investigation for the combination in HNSCC patients.

Biochemical Recurrence in Prostate Cancer and Temporal Association to Bone Metastasis.

BACKGROUND Prostate cancer is a common cancer in men. Radical prostatectomy, i.e., the surgical removal of the entire prostate, is a frequently used option. Biochemical recurrence (BCR), i.e., detectable prostate specific antigen (PSA), is common in some men following such treatment. The timing of BCR to metastatic spread of disease in bones is usually a few years. If the biochemical failure occurs after a longer duration from the time of curative intent, it is generally believed to lead to local recurrence. CASE REPORT We report on two cases. A 78-year-old male was diagnosed with Gleason 7, prostate cancer in 2001. He subsequently underwent an open radical prostatectomy. Serial post-operative PSA's were undetectable (<0.01 ng/mL) up to 2016. He was diagnosed with a detectable PSA for the first time with a value of 0.3 ng/mL, that year. The PSA continued to rise to a level of 1.1 ng/mL. This rise in the PSA was within a 12-month interval. Subsequent bone scan and bone biopsy detected prostate cancer metastasis in multiple bones. Our second case was a 65-year-old male who underwent a laparoscopic radical prostatectomy in the year 2006 for a biopsy proven prostate cancer with Gleason 3+4=7. Serial post-operative PSA's were undetectable up to 2017. Within a span of 8 months, the PSA rose from 0.3 ng/mL to 1.52 ng/mL. A positron emission tomography scan demonstrated pubic bone lesion indicative of prostate cancer metastasis. CONCLUSIONS BCR can occur a decade after curative intent treatment of prostate cancer. The duration from BCR to detectable metastasis can be shorter. We demonstrated here that the site of recurrence, in such scenarios, can be distant metastasis and not local recurrence alone. Better imaging modalities are needed to identify the spread of prostate cancer at low levels of PSA.

Hurthle cell predominance impacts results of Afirma gene expression classifier and ThyroSeq molecular panel performance in indeterminate thyroid nodules.

BACKGROUND: Molecular tests such as the Afirma gene expression classifier (GEC) and mutational panels (such as ThyroSeq) have been introduced to help risk stratify cytologically indeterminate thyroid nodules with the aim to reduce the number of unnecessary thyroidectomies. Some reports have suggested that samples with Hurthle cell predominance have higher false-positive rates on GEC testing, but data are limited. METHODS: We reviewed thyroid nodules with indeterminate (Bethesda III/IV) cytology at our institution. Patient demographics, cytologic and histologic diagnoses (where available), and molecular test results were collected. RESULTS: GEC was performed on 202 nodules, and ThyroSeq was performed on 81 nodules. In the GEC cohort, 66% of nodules with Hurthle cell predominance yielded "suspicious" result vs 46% of nodules without Hurthle cell predominance, with risk of malignancy (ROM) for surgically resected nodules of 16% and 33%, respectively. In ThyroSeq cohort, 8% of nodules with Hurthle cell predominance yielded a high-risk mutation vs 19% of nodules without Hurthle cell predominance, with ROM of 50% and 33%, respectively. CONCLUSIONS: For ThyroSeq molecular panel, while it did not appear that there was an increase in rate of high-risk mutations detected in the samples with Hurthle cell predominance, small numbers limit the generalizability of these results. For the GEC cohort, indeterminate thyroid nodules with predominance of Hurthle cells showed an increased rate of "suspicious" results compared to samples without Hurthle cell predominance. The ROM for GEC "suspicious" nodules with Hurthle cell predominance on surgical resection was lower in our study. Repeat FNA may be of use in patients with these types of nodules. In the context of a Hurthle cell predominant lesion, positive results on molecular testing may not carry a high rate of malignancy.

Negative Results on Thyroid Molecular Testing Decrease Rates of Surgery for Indeterminate Thyroid Nodules.

Molecular tests and mutational panels such as Afirma Gene Expression Classifier (GEC) and ThyroSeq, respectively, have been used to help risk stratify cytologically indeterminate thyroid nodules with the aim to reduce unnecessary surgeries. We studied the effect of molecular testing on the rate of surgical resection in these nodules. Thyroid nodules with indeterminate (Bethesda III/IV) cytology that underwent molecular testing (GEC or ThyroSeq) at our institution between June 2012 and August 2016 were retrospectively reviewed. We collected demographics, cytology diagnoses, molecular test results, and whether surgical resection was performed. Two hundred eighty-three nodules met inclusion criteria: 202 nodules tested with GEC and 81 tested with ThyroSeq. In the cohort of GEC-tested nodules, 99/202 (49%) yielded "suspicious" and 103/202 (51%) yielded "benign" results, with an overall resection rate of 70/99 (71%) in "suspicious" versus 13/103 (13%) in "benign" nodules. In the cohort of ThyroSeq-tested nodules, 13/81 (16%) of nodules yielded a "high-risk mutation" and 68/81 (84%) of nodules yielded "no high-risk mutation," with overall resection rates of 11/13 (85%) and 30/68 (44%), respectively. Rates of resection were higher for Bethesda IV than for III nodules, regardless of molecular results. For both GEC and ThyroSeq, molecular test results seemed to correlate with the rate of resection at our institution. Rates of resection for cytologically indeterminate nodules that were "benign" or "no high-risk mutation" appeared to differ from those that were "suspicious" or "high-risk mutation" on molecular panel testing by GEC and ThyroSeq, respectively. Our findings support that molecular test results are impacting management.

Undiagnosed fatal malignancy in adult autopsies: a 10-year retrospective study.

Autopsies reveal undiagnosed malignancies even in this era of modern diagnostic imaging and ancillary laboratory studies. The incidence of clinically undiagnosed malignancies related to primary cause of death in a university hospital setting has rarely been studied. Our objective was to determine the incidence of clinically undiagnosed fatal malignancies in an urban teaching hospital and to assess whether this incidence was influenced by the duration of hospital stay. We performed a retrospective analysis of consecutive adult hospital autopsies in which the primary cause of death was related to undiagnosed malignancy. The detailed autopsy report, clinical records, and relevant laboratory results from laboratory and hospital databases were reviewed. Eight hundred twenty-one adult autopsies were performed over 10 years. Sixty-nine clinically undiagnosed malignant neoplasms were found in 66 cases (8%). In 26 of these 66 cases, the undiagnosed malignant neoplasm was related to the primary cause of death (3.1%). The duration of hospital stay was less than 24 hours in 8 cases (30.7%), 2 to 7 days in 9 cases (34.6%), and greater than 7 days in 9 cases (34.6%). In 10 of these 26 cases (1.2%), there was suspicion of malignancy without definitive tissue diagnosis, and the average hospital stay was 4.9 days. In 16 (1.9%) of these 26 cases, malignancy was not clinically suspected, and the average hospital stay was 9.9 days. We conclude that despite the recent advances in diagnostic imaging and laboratory techniques, a subset of adult autopsies (3.1%) performed in an urban university hospital have clinically undiagnosed malignancy related to the primary cause of death. Malignancy was not clinically suspected in 1.9% of these cases. There is a need to conduct comprehensive "root cause" analysis in these cases for improvement of clinical care.

High prevalence of discordant human papillomavirus and p16 oropharyngeal squamous cell carcinomas in an African American cohort.

BACKGROUND: Most studies on human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) have been performed on white Americans. Our study examined the incidence of HPV in an African American oropharyngeal SCC cohort and its survival. METHODS: African American patients with oropharyngeal SCC in a combined tumor registry were identified. HPV16 testing was performed by polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16 staining was performed using standard immunohistochemistry. RESULTS: Forty-four patients were identified for analysis. Seventy-three percent of the tumors were HPV-positive. Only 39% of the patients who were HPV-positive were also p16-positive. Survival between all 3 tumor types, patients who tested HPV-positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was significantly different (p = .03). HPV/p16 status was significant on univariate and multivariate analysis. CONCLUSION: HPV oropharyngeal SCC is strongly present in this African American cohort. Two thirds of the patients who were HPV-positive were p16-negative. Greater study is needed to explain the high p16 negativity among this HPV-positive oropharyngeal SCC African American cohort. © 2015 Wiley Periodicals, Inc. Head Neck 38: E867-E872, 2016.

Peripheral primitive neuroectodermal tumor of the dura in a 51-year-old woman following intensive treatment for breast cancer.

PATIENT: Female, 51. FINAL DIAGNOSIS: Ewing sarcoma. SYMPTOMS: Visual disturbances. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Oncology. OBJECTIVE: Rare disease. BACKGROUND: Primitive neuroectodermal tumor/Ewing sarcoma (PNET/EWS) is a round blue cell sarcoma that shows varying degrees of neuroectodermal differentiation. PNET/EWS as a primary intracranial tumor is extremely uncommon. CASE REPORT: We report a unique case of peripheral PNET presenting as an intracranial mass in an adult following chemotherapy and radiotherapy for a solid tumor. A 51-year-old woman with previously treated left breast cancer was evaluated for a newly developed brain mass. She underwent craniotomy with resection. Surgical pathology was consistent with a peripheral PNET/EWS with Ewing sarcoma gene translocation. She was treated appropriately with vincristine, cyclophosphamide, and doxorubicin (later dactinomycin) alternating with ifosfamide and etoposide. CONCLUSIONS: Although development of PNET/EWS presenting along the CNS is exceedingly rare in adults, establishing the proper diagnosis of this "small blue cell tumor" is critical. The further distinction between central PNET and peripheral PNET can greatly impact both prognosis and treatment. Our case also highlights the importance of considering the impact of prior intensive therapies, including radiation and chemotherapy, on predisposing to future PNET/EWS.