The combined survival effect of codon 72 polymorphisms and p53 somatic mutations in breast cancer depends on race and molecular subtype.

BACKGROUND: The codon 72 polymorphism in the p53 gene relates to the risk of breast cancer (BC), but this relationship in racially diverse populations is not known. The present study examined the prognostic value of this polymorphism for African American (AA) and Caucasian (CA) BC patients separately and considered the confounding variables of molecular subtypes and somatic mutations in p53. METHODS: Tissue sections of BCs from 116 AAs and 160 CAs were evaluated for p53 mutations and genotyped for the codon 72 polymorphism. The relationships of phenotypes to clinicopathologic features were determined by χ2 analyses; patient survival was estimated by Kaplan-Meier univariate and Cox regression multivariate models in a retrospective cohort study design. RESULTS: The proportion of single nucleotide polymorphism (SNP) 72 alleles differed for races. Many cancers of AAs were Pro/Pro, but most for CAs were Arg/Arg. A higher frequency of missense p53 mutations was evident for AAs. There was an interaction between the SNP allele and p53 mutations for AA women only. The proportion of women with both the Pro/Pro allele and a p53 somatic mutation was higher for AA than CA women. The interaction between missense p53 mutations and Pro/Pro had a negative effect on survival, particularly for AAs with luminal cancers. CONCLUSIONS: For BCs, the survival effect of SNP72 combined with a p53 missense mutation is dependent on race and molecular subtype. Although such a mutation is a marker of poor prognosis, it is relevant to identify the variant Pro/Pro in the case of AAs, especially those with luminal subtypes of BC.

Not Your Usual Suspect: Clear Cell Renal Cell Carcinoma Presenting as Ulcerative Esophagitis.

Renal cell carcinoma (RCC) has the propensity to hematogenously metastasize to the lung, bone, or liver, however, metastasis to the esophagus is exceedingly rare. We report a case of ulcerative esophagitis secondary to recurrent metastatic renal cell cancer status post remote nephrectomy. An 82-year-old Caucasian male presented with dark tarry stools for two days, progressive dysphagia to solid food for several weeks and unintentional weight loss. His past medical history was significant for hypertension, diverticulosis and right-sided renal cell cancer for which he underwent nephrectomy 13 years ago. Physical examination was unremarkable. Laboratory data showed hemoglobin of 12.5 g/dL, with normal platelet count and an international normalized ratio (INR). His stools were positive for occult blood. Esophagogastroduodenoscopy (EGD) revealed a fragile mid esophageal mass and antral erosive gastritis which were both biopsied. Colonoscopy showed diverticulosis without stigmata of active gastrointestinal (GI) bleed. CT scan (computed tomography) of the chest showed a solid esophageal mass in the lower esophagus as well as a right upper lobe lung mass for which CT-guided needle biopsy was obtained. The histopathology revealed metastatic renal cell cancer of clear cell subtype. The patient was started on palliative radiotherapy. On completion of radiotherapy two months later, his dysphagia had resolved. The patient is currently on chemotherapy with Sunitinib. Metastatic involvement of esophagus is relatively uncommon and is reported in 6% of patients with metastatic lung, breast and prostate cancer. Esophageal metastasis of clear cell RCC is very rare and so far only seven cases have been reported. Diagnosis is confirmed by endoscopy, imaging and histopathology. Treatment options include surgical or endoscopic resection for a solitary metastatic lesion. If the tumor is unresectable, multidisciplinary treatment including radiation and chemotherapy is indicated.

Randomized trial comparing the Franseen and Fork-tip needles for EUS-guided fine-needle biopsy sampling of solid pancreatic mass lesions.

BACKGROUND AND AIMS: Recently, a 3-plane symmetric needle with Franseen geometry and a Fork-tip biopsy needle have been developed for histologic tissue procurement. We compared 22-gauge Franseen and 22-gauge Fork-tip needles in patients undergoing EUS-guided sampling of pancreatic masses. METHODS: Fifty patients underwent sampling using both 22-gauge Franseen and 22-gauge Fork-tip needles, with randomization of needle order. Two dedicated passes were performed using both needles for cell block. Subsequent passes were performed for rapid onsite evaluation (ROSE) using both needles alternately until diagnosis was established. The main outcome was to evaluate for histologic core tissue by comparing area of total tissue, tumor, desmoplastic fibrosis, and rate of retained tissue architecture between cohorts. Other outcomes were rates of diagnostic cell block and diagnostic adequacy at ROSE. RESULTS: Final diagnosis was pancreatic cancer in 44 patients, neuroendocrine tumor in 2, lymphoma in 1, and chronic pancreatitis in 3. There was no significant difference in area of total tissue (median 6.1 [interquartie range {IQR}, 3.5-10.5] vs 8.2 mm2 [IQR, 4.0-13.0], P = .50), tumor (median .9 [IQR .3-2.8] vs 1.0 mm2 [IQR .4-2.7], P = .33), desmoplastic fibrosis (median 4.3 [IQR, 2.0-6.7] vs 5.2 mm2 [IQR, 1.7-6.1], P = .71), retained architecture (100% vs 83%, P = .25), diagnostic cell block (96.0% vs 92.0%, P = .32), and diagnostic adequacy at ROSE (94.0% vs 98.0%, P = .32) between Franseen and Fork-tip needles, respectively. CONCLUSIONS: There was no significant difference between Franseen and Fork-tip needles in yielding histologic tissue. Given their ability to yield diagnostic cell block in greater than 90% of patients, the new-generation fine-needle biopsy needles may obviate the need for ROSE. (Clinical trial registration number: NCT02910960.).

Endosonographer-driven dynamic telecytopathology of pancreatic lesions-a pilot study.

INTRODUCTION: Telecytopathology for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been shown to be an alternative to rapid on-site evaluation (ROSE). Gastroenterologists (endosonographers) performing EUS-FNA can be trained to evaluate a specimen for adequacy. This study examined the ability of an endosonographer with focused cytopathologic training to assess the adequacy of pancreatic FNA specimens and transmit diagnostic images to a remotely located cytopathologist as compared to an experienced cytotechnologist. MATERIALS AND METHODS: This was a retrospective study of consecutive pancreatic lesions sampled by EUS-FNA reviewed by an endosonographer and a cytotechnologist. The participants were assessed based on their ability to (1) determine adequacy, (2) locate and transmit representative cell groups, (3) provide a preliminary diagnosis, and (4) provide concordance with actual diagnosis. RESULTS: 105 consecutive cases of EUS-FNA of the pancreas were analyzed, including: adenocarcinoma (n = 39), cyst (n = 17), neuroendocrine neoplasia (n = 7), pancreatitis (n = 14), benign pancreas (n = 9), other neoplasms (n = 6), suspicious/atypical (n = 3), and nondiagnostic (n = 10). The cytotechnologist demonstrated superiority in accuracy 92.7% versus 70% (P = 0.003) and subcategorization 95.0% versus 76% (P = 0.007). There was no difference in "broad" categorization (benign/malignant) between the endosonographer and cytotechnologist, 98% and 98.2% (P = 0.946), respectively. Also, there was no difference with regard to adequacy assessment (P = 0.29). A steady learning curve for the endosonographer was demonstrated in their cytologic assessment (P = 0.041). The endosonographer was shown to be able to remotely transmit diagnostic images to a pathologist. CONCLUSION: An endosonographer with limited training can examine for specimen adequacy, transmit images, and demonstrate representative cell groups. Larger studies are required though preliminary results are encouraging.

Falling under the umbrella cells: A single institutional experience and literature review of urothelial carcinoma presenting as a primary pancreatic mass on endoscopic ultrasound-guided fine-needle aspiration.

Metastases to the pancreas are much less common than primary pancreatic lesions, and there are few reports in the literature of metastatic urothelial carcinoma (UC) found in the pancreas. We report two cases of metastatic UC mimicking a primary pancreatic lesion. Two female patients, aged 48 and 83 years, presented with isolated pancreatic lesions causing obstructive jaundice suspicious for pancreatic adenocarcinoma and underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with rapid on-site evaluation (ROSE). On cytopathology, the lesions were found to be UC, confirmed with immunohistochemical (IHC) staining. UC rarely metastasizes to the pancreas, and diagnosis through EUS-FNA can be challenging. However, the utilization of ROSE, dedicated cell block passes, and IHC have proved to be effective in obtaining this unusual pancreatic diagnosis by EUS-FNA.

Endoscopic ultrasonography-guided biopsy using a Franseen needle design: Initial assessment.

BACKGROUND AND AIM: Recently, a 22-gauge (G) needle with a Franseen tip design was developed for endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB). The present study evaluated the performance of the Franseen biopsy needle in EUS-guided tissue acquisition. METHODS: This is a retrospective study of patients who underwent EUS-FNB using the Franseen needle. Lesions were sampled using either the Franseen needle only or after failed diagnostic fine-needle aspiration (FNA). After rapid onsite evaluation (ROSE), two dedicated passes were carried out for histological assessment using the cell block technique. Main outcomes were: (i) rates of diagnostic adequacy for ROSE and histological diagnosis; and (ii) quality of histology as determined by total tissue area and tumor percentage in tissue. RESULTS: Thirty patients underwent EUS-FNB of pancreatic or other masses over a 3-month period. Twenty-four lesions were sampled using the Franseen needle only and six after failed diagnostic FNA. Final diagnosis was pancreatic cancer in 12, gastrointestinal stromal cell tumor in five, other tumors in four and benign disease in nine. Diagnostic adequacy for ROSE was 96.6% and histological diagnosis was established in 96.7% of patients. Median tissue area was 2.9 mm2 (IQR = 0.68-8.71 mm2 ) and median tumor percentage in tissue was 73.9% (IQR = 44-97.6). Rates of technical success and adverse events were 96.7 and 3.3%, respectively. CONCLUSION: Preliminary data suggest that the Franseen needle yields diagnostic material for ROSE and histology in >95% of patients.

Improving the diagnostic yield of single-operator cholangioscopy-guided biopsy of indeterminate biliary strictures: ROSE to the rescue? (with video).

BACKGROUND AND AIMS: Tissue diagnosis, regardless of technique or endoscope used, can be challenging in patients with indeterminate biliary strictures (IDBSs). This exploratory study evaluated the utility and role of rapid onsite evaluation of touch imprint cytology (ROSE-TIC) when single-operator cholangioscopy (SOC)-guided biopsies of IDBSs are performed. METHODS: Patients with IDBSs were evaluated by intraprocedural ROSE-TIC during SOC-guided biopsy procedures. Final diagnosis was established by long-term patient follow-up in conjunction with off-site findings or surgical histology. The main outcome measure was to evaluate the utility of ROSE-TIC by determination of its operating characteristics and comparison with off-site histologic assessment. RESULTS: Of 31 patients with IDBSs, tissue diagnosis was indeterminate at prior ERCP-guided brush and/or biopsy in 14, prior EUS-guided FNA (EUS-FNA) in 6, and a mass could not be identified at EUS in 11. The mean number of biopsies performed was 3.3 (range 1-8), and diagnostic interpretation by ROSE-TIC was diagnostic and/or suspicious for carcinoma in 15, benign in 13, atypical-reactive in 2, and bile duct intraductal papillary mucinous neoplasm in 1. Final diagnosis by surgical histology (n = 4), death by disease (n = 10), and patient follow-up (n = 17) showed that the overall sensitivity of ROSE-TIC for diagnosing malignancy was 100%, specificity 88.9%, positive predictive value 86.7%, negative predictive value 100%, and diagnostic accuracy 93.5%. CONCLUSIONS: Preliminary data suggest that the diagnostic outcomes of SOC-guided biopsies in IDBSs can be significantly improved by using ROSE-TIC. This technique also may benefit centers that rely mainly on fluoroscopy-guided intraductal biopsies.

Digital, single-operator cholangiopancreatoscopy in the diagnosis and management of pancreatobiliary disorders: a multicenter clinical experience (with video).

BACKGROUND AND AIMS: Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with fiberoptic instruments. The role of a new, digital, single-operator cholangiopancreatoscopy (SOC) system for diagnosis and treatment of pancreatobiliary disorders in clinical practice is not known. METHODS: We performed a multicenter, observational study of 105 consecutive patients with suspected pancreatobiliary disorders. The main outcome measures were (1) sensitivity and specificity of SOC visual appearance and biopsies in the diagnosis of indeterminate biliary strictures and (2) achieving complete duct clearance in patients with biliary or pancreatic duct stones. RESULTS: A total of 98 cholangioscopy and 7 pancreatoscopy procedures were performed in 105 patients. Superior views of the ductal lumen and mucosa were obtained in all 44 patients with indeterminate biliary strictures. Among the 44 patients who underwent SOC-guided biopsies, the specimen was adequate for histologic evaluation in 43 patients (97.7%). The sensitivity and specificity of SOC visual impression for diagnosis of malignancy was 90% (95% confidence interval [CI], 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively. The sensitivity and specificity of SOC-guided biopsies for diagnosis of malignancy was 85% (95% CI, 64.0%-94.8%) and 100% (95% CI, 86.2%-100%). In patients with biliary or pancreatic duct stones (N = 36), complete duct clearance with stone removal in 1 session was accomplished in 86.1% of patients (31/36). Three patients (2.9%) experienced SOC-related adverse events that included cholangitis in 2 patients and postprocedure pancreatitis in 1 patient. CONCLUSIONS: SOC has become an integral part of the ERCP armamentarium and has high accuracy in the evaluation of indeterminate biliary strictures. Complete stone clearance was achieved in all but 1 patient with challenging biliary or pancreatic duct stones. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01815619.).

Randomized Trial Comparing the Flexible 19G and 25G Needles for Endoscopic Ultrasound-Guided Fine Needle Aspiration of Solid Pancreatic Mass Lesions.

OBJECTIVES: Although a large gauge needle can procure more tissue at endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its advantage over smaller needles is unclear. This study compared flexible 19G and 25G needles for EUS-FNA of solid pancreatic masses. METHODS: This was a randomized trial of patients undergoing EUS-FNA of pancreatic masses using flexible 19G or 25G needle. Main outcome measure was to compare median number of passes for on-site diagnosis. Secondary measures were to compare specimen bloodiness, complications, technical failures, and histological core tissue procurement. RESULTS: One hundred patients were randomized to EUS-FNA using flexible 19G or 25G needle. Median of 1 pass was required to achieve on-site diagnosis of 96% and 92% (P = 0.68) in 19G and 25G cohorts. There was no significant difference in technical failure (0% vs 2%, P = 0.99) or adverse events (2% vs 0%, P = 0.99) between 19G and 25G cohorts. Although histological core tissue procurement was significantly better with flexible 19G needle (88% vs 44%, P < 0.001), specimens were bloodier (severe bloodiness, 36% vs 4%; P < 0.001). CONCLUSIONS: As there is no significant difference in the performance of flexible 19G and 25G needles, needle choice for sampling pancreatic masses should be based on endoscopist preference and need for histology.

Training endosonographers in cytopathology: improving the results of EUS-guided FNA.

BACKGROUND: Although on-site cytopathology services have a significant impact on efficiency and accuracy of EUS-guided FNA (EUS-FNA), the availability of this service is variable. OBJECTIVE: To evaluate the impact of an intensive 2-day training program to educate endosonographers in EUS-related cytopathology. DESIGN: Pilot study. SETTING: Tertiary care medical center. SUBJECTS: Six endosonographers (5 male, median age, 35 years) with minimal previous cytopathology exposure comprised the study cohort. METHODS: Pre- and posttraining testing was administered. Training commenced with a cytopathology tutorial focusing on 4 performance measures: specimen adequacy, sample interpretation, specimen processing, and preliminary diagnosis. Eight live EUS-FNA cases were then performed, and study participants independently completed 4 questions based on performance measures for each case. The ability to independently smear and stain slides and operate a microscope was additionally assessed after a hands-on tutorial. MAIN OUTCOME MEASUREMENTS: Comparison of pretraining and posttraining scores, improvement in performance measures for live cases, and ability to independently handle specimens and operate a microscope. RESULTS: Compared with pretraining, mean posttraining test scores improved by 63% from 48 to 78 out of 100. Mean live case performance score was 95%. Performances improved from 89% on day 1 to 100% on day 2. After training, all endosonographers could independently smear/stain slides and operate a microscope. LIMITATIONS: Long-term impact is unclear. CONCLUSIONS: An intensive 2-day program was effective in training endosonographers in the basics of EUS-related cytopathology. Incorporating basic cytopathology in EUS fellowship curriculum will likely improve diagnostic performance of tissue acquisition procedures.