Chris S. Jensen

The role of fine-needle aspiration cytology in the evaluation of metastatic clear cell tumors

Clear cell tumors (CCTs) occur as primary neoplasms in a number of anatomic sites. Due to their overlapping morphologic features, these tumors can be challenging for the cytologist, particularly when they present as metastatic lesions.

Multiplatform comparison of molecular oncology tests performed on cytology specimens and formalin‐fixed, paraffin‐embedded tissue

Molecular oncology testing is important for patient management, and requests for the molecular analysis of cytology specimens are increasingly being made. Formalin‐fixed, paraffin‐embedded (FFPE) cell blocks of such specimens have been routinely used for molecular diagnosis. However, the inability to assess cellularity before cell block preparation is a pitfall of their use. In this study, various cytologic preparations were tested with several molecular test platforms, and the results were compared with paired FFPE tissue.

Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction

H. Gerke, M. K. Rizk, A. D. Vanderheyden and C. S. Jensen
Randomized study comparing endoscopic ultrasound‐guided Trucut biopsy and fine needle aspiration with high suction

Cytologic Diagnosis of Adenocarcinoma in Biliary and Pancreatic Duct Brushings

Biliary and pancreatic duct brush specimens are relatively uncommon specimens seen by pathologists. Not only can the findings of malignancy be subtle, the implications of a malignant diagnosis can be significant. This review focuses on cholangiocarcinoma and pancreatic ductal adenocarcinoma sampled by endoscopic brush cytology, with an emphasis on diagnostic criteria for adenocarcinoma. In addition, assessment of specimen adequacy, utilization of liquid-based preparations, molecular diagnosis, and timing of liver transplantation in patients with primary sclerosing cholangitis are also briefly discussed.

Lymphocytic esophagitis: A possible manifestation of pediatric upper gastrointestinal Crohn's disease

Background: Lymphocytic esophagitis (LE) is histologically defined by marked esophageal lymphocytosis with no or only rare intraepithelial granulocytes. This study was performed to investigate the association between LE and pediatric Crohns disease (CD). Methods: Blinded retrospective morphologic analysis was performed on gastrointestinal biopsies from pediatric patients with an established diagnosis of CD (n = 60) and ulcerative colitis (UC; n = 30), as well as a spectrum of non‐inflammatory bowel disease (IBD) patients (n = 38). The highest density of intraepithelial lymphocytes (IEL), neutrophils (IEN), and eosinophils (IEE) per high power field (hpf; 40×) were counted. LE was defined as >50 IEL/hpf and a ratio of >50:1 IEL to intraepithelial granulocytes (IEG). Results: LE was identified in 17/60 patients with CD, and only 2/30 patients with UC and 1/38 non‐IBD control patients; P = 0.0263 (CD versus UC) and P = 0.0002 (CD versus non‐CD). In all, 6/60 CD patients had esophagitis with granulomas and three of these met the diagnostic criteria for LE. There was no difference in the incidence of upper gastrointestinal (UGI) symptoms between the CD patients with LE (7/17, 41%) and CD patients with esophagitis with granulomas (3/6; P = 1.0). Conclusions: The histologic diagnosis of LE is associated with pediatric CD and was found in 28% of CD patients. If LE is identified in pediatric CD, it is likely a manifestation of UGI‐CD rather than esophagitis due to other etiologies or a variant of normal. (Inflamm Bowel Dis 2011;)

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma.

This retrospective study reviews our experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy–pancreaticoduodenectomy–orthotopic liver transplantation (OLT‐Whipple) to achieve complete eradication of early‐stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra‐beam radiotherapy, lesion‐focused brachytherapy, and OLT‐Whipple. Between 1988 and 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT‐Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT‐Whipple patients received combined external‐beam and brachytherapy radiotherapy. The median time from diagnosis to OLT‐Whipple was 144 days. One patient died 55 months post‐transplant of an unrelated cause, without tumor recurrence. The other 5 are well without recurrence at 5.7, 7.0, 8.7, 8.8, and 10.1 years. In conclusion, for patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion‐focused radiotherapy combined with OLT‐Whipple to remove the biliary epithelium en bloc offers promising long‐term, tumor‐free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT‐Whipple in patients with early‐stage hilar CC complicating PSC. Liver Transpl 14:279–286, 2008.

Efficacy and safety of EMR to completely remove Barrett's esophagus: experience in 41 patients.

BACKGROUND EMR is typically used to remove focal abnormalities of the esophageal mucosa. However, larger areas of Barretts esophagus (BE) can be resected through side-by-side resections. OBJECTIVE To assess the efficacy and safety of EMR to completely remove BE. DESIGN Retrospective, single-center study. SETTING University of Iowa Hospitals and Clinics. PATIENTS Between January 2006 and December 2010, 46 patients underwent EMR for complete removal of BE. Three were lost to follow-up, one died of unrelated causes before completion, and one was still undergoing EMR treatment at the conclusion of the study. The remaining 41 patients were included for analysis. The worst histologic grade was low-grade dysplasia in 4 patients, high-grade dysplasia without cancer in 26 patients, and high-grade dysplasia with superficial adenocarcinoma in 11 patients. BE was circumferential in 65.9% of cases, and the mean (± SD) length was 3.3 ± 2.3 cm. INTERVENTION EMR was performed by using a cap (n = 4), a multiband ligator device (n = 31), or both (n = 6), with a mean (± SD) of 2.4 ± 1.2 sessions per patient. MAIN OUTCOME MEASUREMENTS Remission rates and complications. RESULTS Remission of high-grade dysplasia and cancer, all dysplasia, and all BE was achieved in 94.6%, 85.4%, and 78.0%, respectively. Complications included minor bleeding (31.7%), perforations (4.9%), and strictures (43.9%). All complications were managed conservatively. LIMITATIONS Retrospective design. CONCLUSION Complete removal of BE with EMR is effective but associated with a high complication rate, which is mainly related to stricture formation. This needs to be considered when choosing between available treatment modalities.

Anatomic pathology databases and patient safety

CONTEXT The utility of anatomic pathology discrepancies has not been rigorously studied. OBJECTIVE To outline how databases may be used to study anatomic pathology patient safety. DESIGN The Agency for Healthcare Research and Quality funded the creation of a national anatomic pathology errors database to establish benchmarks for error frequency. The database is used to track more frequent errors and errors that result in more serious harm, in order to design quality improvement interventions intended to reduce these types of errors. In the first year of funding, 4 institutions (University of Pittsburgh, Henry Ford Hospital, University of Iowa, and Western Pennsylvania Hospital) reported cytologic-histologic correlation error data after standardizing correlation methods. Root cause analysis was performed to determine sources of error, and error reduction plans were implemented. PARTICIPANTS Four institutions self-reported anatomic pathology error data. MAIN OUTCOME MEASURES Frequency of cytologic-histologic correlation error, case type, cause of error (sampling or interpretation), and effect of error on patient outcome (ie, no harm, near miss, and harm). RESULTS The institutional gynecologic cytologic-histologic correlation error frequency ranged from 0.17% to 0.63%, using the denominator of all Papanicolaou tests. Based on the nongynecologic cytologic-histologic correlation data, the specimen sites with the highest discrepancy frequency (by project site) were lung (ranging from 16.5% to 62.3% of all errors) and urinary bladder (ranging from 4.4% to 25.0%). Most errors detected by the gynecologic cytologic-histologic correlation process were no-harm events (ranging from 10.7% to 43.2% by project site). Root cause analysis identified sources of error on both the clinical and pathology sides of the process, and error intervention programs are currently being implemented to improve patient safety. CONCLUSIONS A multi-institutional anatomic pathology error database may be used to benchmark practices and target specific high-frequency errors or errors with high clinical impact. These error reduction programs have national import.

Frequency and outcome of cervical cancer prevention failures in the United States.

We measured the frequency and outcome of cervical cancer prevention failures that occurred in the Papanicolaou (Pap) and colposcopy testing phases involving 1,646,580 Pap tests in 4 American hospital systems between January 1, 1998, and December 31, 2004. We defined a screening failure as a 2-step or greater discordant Pap test result and follow-up biopsy diagnosis. A total of 5,278 failures were detected (0.321% of all Pap tests); 48% and 52% of failures occurred in the Pap test and colposcopy phases, respectively. Missed squamous cancers (1 in 187,786 Pap tests), glandular cancers (1 in 19,426 Pap tests), and high-grade lesions (1 in 6,870 Pap tests) constituted 4.1% of all failures. Unnecessary repeated tests or diagnostic delays occurred in 70.8% and 63.9% of failures involving high- and low-grade lesions, respectively. We conclude that cervical cancer prevention practices are remarkably successful in preventing squamous cancers, although a high frequency of failures results in low-impact negative outcomes.

TRPM8 ion channel is aberrantly expressed and required for preventing replicative senescence in pancreatic adenocarcinoma: Potential role of TRPM8 as a biomarker and target

Pancreatic adenocarcinoma is mostly fatal and generally resistant to conventional treatments, such that effective therapies with tolerable side effects are desperately needed. Ion channels including the transient receptor potential (TRP) channels have been implicated in human malignancies, but their roles in pancreatic cancer were mostly unknown. Recent identification of the melastatin-subfamily members of the TRP family of ion channels, and their functions in pancreatic epithelia and adenocarcinoma, is expected to provide a new perspective to understanding the mechanism underlying pancreatic tumorigenesis. In this report, we present the clinical and pathological features of a mini-series of patients with pancreatic adenocarcinoma, which aberrantly exhibits immunoreactivity against the TRPM8 channel. We have recently demonstrated the proliferative role of TRPM8 channel in pancreatic cancer cells. Here, we present evidence that RNA interference-mediated silencing of TRPM8 induces replicative senescence in pancreatic adenocarcinoma cells. This suggests that the aberrantly expressed TRPM8 channel may contribute to pancreatic tumorigenesis by preventing oncogene-induced senescence, and targeted inhibition of TRPM8 may enhance tumor sensitivity to therapeutics. Based on these observations, we hypothesize that the TRPM8 ion channel plays a crucial role in the growth and progression of pancreatic neoplasia during tumorigenesis. We propose that TRPM8 can be exploited as a clinical biomarker and as a therapeutic target for developing personalized therapy in pancreatic adenocarcinoma.