Ileal biopsy: Clinical indications, endoscopic and histopathologic findings in 10,000 patients.

BACKGROUND: Ileal biopsies are often reported as having a low yield. Data from endoscopy practices in the private setting are lacking. AIMS: To correlate the frequency of histologic abnormalities in ileal biopsies with clinical indications and ileoscopic appearances. METHODS: Retrospective analysis of clinical, endoscopic, and histopathologic data from a large database. RESULTS: We studied 9785 unique adult patients (median age 46 years, 61.4% women) with ileal biopsies. The most common symptoms were diarrhoea (52.2%) and abdominal pain (37.1%). Ileoscopy was reported as being normal in 75.1% patients. Subjects screened for cancer had the highest prevalence of abnormal endoscopic findings (63.3%); patients with known or suspected Crohn's had the highest prevalence abnormal ileal histology (36.4%). Overall, 5.0% of ileal biopsies obtained from patients with normal endoscopy and 47.4% of biopsies from patients with an endoscopically abnormal ileum had significant histopathologic findings. CONCLUSIONS: In adults, biopsies from the endoscopically normal ileum rarely provide clinically relevant information and cannot be recommended. In contrast, half of the adult patients with an endoscopically abnormal ileum have significant histopathologic findings in ileal biopsies. Therefore, ileoscopy associated with a sensible use of the ileal biopsy is a valuable complement to the colonoscopy.

The current spectrum of gastric polyps: a 1-year national study of over 120,000 patients.

OBJECTIVES: To use a large pathology database (Caris Diagnostics) to analyze the frequency and associations of gastric polyps in a nationwide US population. METHODS: A total of 121,564 esophagogastroduodenoscopy (EGD) procedures from private practices in 36 states in the Caris Diagnostics database from 1 April 2007 to 31 March 2008 were searched for the endoscopic designations of polyp, nodule, and mass, and for the pathological diagnoses that commonly present as gastric polyps. Pertinent demographic data, clinical indications for EGD, and information regarding Helicobacter pylori infection, reactive gastropathy, chronic inactive gastritis, and intestinal metaplasia were also obtained. RESULTS: A total of 78,909 of the 121,564 patients who underwent EGD had gastric biopsies. The prevalence of gastric polyps in the EGD population was 6.35%; 77% were fundic gland polyps, 17% hyperplastic polyps/polypoid foveolar hyperplasia, 0.69% adenomas, and 0.1% inflammatory fibroid polyps. Malignant neoplasms were slightly >2%. None of the benign gastric polyps had a significant positive association with concurrent H. pylori infection; intestinal metaplasia was detected in the background of 52.2% of carcinoids, 29.6% of adenomas, 20.1% of xanthomas, and 13% of adenocarcinomas and hyperplastic polyps. Adenomas were rarely associated with synchronous adenocarcinomas. CONCLUSIONS: The relative prevalence of fundic gland polyps in this population was much higher than that reported earlier, most likely because of the widespread use of proton pump inhibitors. H. pylori- and atrophy-associated polyps, including adenomas, were less common than in earlier series.

Promoter hypermethylation profile of ovarian epithelial neoplasms.

PURPOSE: Ovarian carcinomas are believed to arise de novo from surface epithelium, but the actual molecular pathogenesis is unknown. The aim of this study was to compare the promoter hypermethylation profiles of ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. EXPERIMENTAL DESIGN: We analyzed the DNA promoter methylation status of eight tumor suppressor and cancer-related genes (p16, RARbeta, E-cadherin,H-cadherin, APC, GSTP1, MGMT, RASSF1A) in 23 benign cystadenomas, 23 low malignant potential (LMP) tumors, and 23 invasive carcinomas by methylation-specific PCR. RESULTS: Benign cystadenomas exhibited promoter hypermethylation in only two genes, p16 (13%) and E-cadherin (13%). LMP tumors also showed p16 (22%) and E-cadherin (17%) methylation, in addition to RARbeta (9%) and H-cadherin (4%). All eight genes were hypermethylated in invasive cancers at a frequency of 9% to 30%. The mean methylation index was highest in invasive tumors [0.20 versus 0.065 (LMP) and 0.033 (cystadenomas); P = 0.001]. Promoter methylation of at least one gene was most commonly observed among invasive cancers [78% versus 44% (LMP; P = 0.03) and 26% (cystadenomas; P = 0.0009)]. Three genes exhibited higher methylation frequencies in invasive tumors: RASSF1A (30% versus 0%; P = 0.0002), H-cadherin (22% versus 2%; P = 0.013), and APC (22% versus 0%; P = 0.003). CONCLUSIONS: Promoter hypermethylation is a frequent epigenetic event that occurs most commonly in invasive epithelial ovarian carcinomas. The profile of aberrant methylation suggests that an accumulation of events at specific genes may trigger malignant transformation of some benign cystadenomas and LMP tumors.

Evaluation of flashlamp-pumped pulsed-dye laser (585 nm) in nonsurgical delay of dorsal rat cutaneous flaps.

BACKGROUND: This study evaluated the efficiency of a flashlamp-pumped pulsed-dye laser operating at 585 nm in the delay of a caudally based, 10 x 3-cm dorsal rat skin flap. Two different laser treatment patterns (only longitudinal borders and the entire surface of the proposed flap) for two different fluences (6 J/cm and 8 J/cm) were compared with an acute untreated control flap as well as two surgical delay methods (incision of longitudinal borders and incision of longitudinal borders plus flap undermining). METHODS: Twelve male Sprague-Dawley rats were used in each of seven groups. Two additional rats were used for histologic evaluation and two rats were used for in vivo real-time video monitoring studies. Two weeks after delay procedures, the flaps were raised and sutured on the primarily closed flap donor area. After 5 days, the length of flap survival was measured. The effects of the laser on the cutaneous vasculature and perfusion were assessed by intravenous fluorescein injection, histologic analysis, microangiography, and in vivo real-time video monitoring. RESULTS: No statistically significant improvement in flap survival was observed in any of the laser treatment groups. CONCLUSIONS: The overall findings indicate that the flashlamp-pumped pulsed-dye laser operating at 585 nm did not penetrate deep into skin and coagulate the subdermal plexus with tested laser settings and did not induce the delay phenomenon.

Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography-guided pancreatic fine-needle aspirations.

Fine-needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic FNAs. Material obtained, prospectively, from ERCP-guided pancreatic FNAs was split to prepare CSs (2-5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty-one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow-up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail.

Reprocessing unsatisfactory ThinPrep Papanicolaou test specimens increases sample adequacy and detection of significant cervicovaginal lesions.

BACKGROUND: The objective of the current study was to determine the effect of reprocessing bloody ThinPrep (TP) samples using a glacial acetic acid technique on the unsatisfactory rate. METHODS: During a 12-month study period, all TP gynecologic samples received by the Cytology Laboratory from inpatient, outpatient, and community-based clinics at the University of Texas Southwestern Medical Center and the Parkland Health and Hospital System in Dallas, Texas, were enrolled prospectively into the study. The initial TP slides were evaluated for specimen adequacy based on the 2001 Bethesda System. Any TP sample that contained abnormal cells, by definition, was not considered unsatisfactory. The criteria for reprocessing included scant cellularity in a background of abundant blood. Biopsy correlations for all abnormal cytologic diagnoses were established between TP smears and follow-up biopsies. RESULTS: During the course of the 1-year study period, a total volume of 57,296 TP samples were evaluated by the study laboratory. Prior to reprocessing, the laboratory unsatisfactory rate was 8.32% (4767 of 57,296 TP samples). After reprocessing those samples that were compromised by blood (2593 of 4767 TP samples), the unsatisfactory rate was reduced to 5.47% (3134 of 57,296 TP samples), with an overall reduction by 34.25% (2.85 of 8.32 TP samples). Of 2593 samples that were reprocessed, 62.98% (1633 of 2593 TP samples) changed from inadequate to adequate for the purposes of evaluation. Of those 1633 adequate samples, 1509 samples (92.41%) were negative for intraepithelial lesion or malignancy, 72 samples (4.40%) were atypical squamous cells of unknown significance, 5 samples (0.31%) were atypical glandular cells of undetermined significance, 36 samples (2.20%) were low-grade squamous intraepithelial lesions, 10 samples (0.61%) were high-grade squamous intraepithelial lesions, and 1 sample (0.06%) was adenocarcinoma. CONCLUSIONS: The authors conclude that the reprocessing of unsatisfactory ThinPrep cervicovaginal cytology samples decrease the unsatisfactory rate considerably, with an increase in the detection of significant abnormal cervicovaginal lesions.

Ethnic differences in the prevalence of cryptogenic cirrhosis.

OBJECTIVES: Nonalcoholic steatohepatitis (NASH) associated with obesity and type 2 diabetes mellitus (DM) is postulated to be the cause of most cases of cryptogenic cirrhosis (CC). While ethnic differences in the prevalence of obesity and DM in the United States are well documented, there is little information regarding prevalence of CC or NASH among different U.S. ethnic groups. This study was performed to assess the demographic characteristics of patients with CC at a U.S. county hospital with a racially and ethnically diverse patient population. METHODS: Medical records and pathology databases were reviewed to identify patients at Parkland Memorial Hospital, Dallas County, Texas from 1990 to 2001 with CC or cirrhosis attributed to NASH. RESULTS: Forty-one patients (12 men, 29 women) were found to meet these criteria. Of these, 68% were obese (BMI > or = 30) and/or had type 2 DM and 74% of liver biopsies revealed one or more features of NASH. Of patients with CC 68% were Hispanic while only 7% were African American, despite the fact that Hispanics comprised < 26% and African Americans > 40% of adult medicine patients. Prevalence of CC among Hispanic and African American patients was 3.1-fold higher and 3.9-fold lower, respectively, than among European American patients despite similar prevalence of DM among Hispanics and African Americans. CONCLUSION: These findings support the hypothesis that NASH associated with obesity and DM is responsible for the majority of cases of CC among Hispanics and European Americans. However, the current findings also indicate that this form of cirrhosis is unexpectedly rare among African Americans.

Comparison of ThinPrep and conventional smears in detecting carcinoma in bile duct brushings.

BACKGROUND: Bile duct brushing cytology is a common procedure for the exclusion of adenocarcinoma in the bile duct. The authors evaluated the use of ThinPrep (TP) to determine whether the information obtained is equivalent to that found with conventional smear cytology (CS). METHODS: Thirty-eight prospectively collected endoscope retrograde cholangiopancreatography-guided bile duct brushing samples were split in the following manner. First, two to four CS were prepared and immediately spray-fixed or wet-fixed. Second, the remaining sample was rinsed in PreservCyt (Cytyc Corp., Boxborough, MA). In the laboratory, one TP slide was prepared from each sample. TP and CS were stained by routine Papanicolaou stain. For the current study, TP and CS were reviewed independently by two cytopathologists. The diagnoses made by the two methods were compared with the final histology. RESULTS: The cytologic diagnoses for both TP and CS were categorized into five main groups: 1) unsatisfactory, 2) negative, 3) reactive, 4) suspicious for malignancy, and 5) malignant. The diagnoses on the 38 TP bile duct brushings and CS were categorized as follows: 1) unsatisfactory-2, 4; 2) negative-7, 4; 3) reactive-10, 14; 4) suspicious for malignancy-9, 9; and 5) malignant-10, 7, respectively. Histologic follow-up was available in 14 cases (reactive-4, suspicious for malignancy-1, and malignant-9). The sensitivity was 77% for TP and 66% for CS. The specificity was 100% for both methods. CONCLUSIONS: The two methods described in the current study detected equivalent disease on bile duct brushings. TP was found to provide better preservation and cytologic detail. However, the diagnostic criteria may require modification.

Nephrectomy after radiofrequency ablation-induced ureteropelvic junction obstruction: potential complication and long-term assessment of ablation adequacy.

Little information is available concerning the morbidity of radiofrequency ablation (RFA) or the evolution of an RFA lesion over time. We report our findings in a kidney removed 1 year after RFA of a 2.3-cm renal tumor. After RFA, the patient experienced flank pain, followed by hydronephrosis, ureteropelvic junction obstruction, and eventual loss of function in the treated kidney. Nephrectomy revealed no residual renal cell carcinoma. RFA can completely destroy renal cell carcinoma in situ without histologic evidence of persistence or recurrence for up to 1 year after treatment. Care must be taken to avoid concurrent damage to the collecting system.

Reflex human papillomavirus DNA testing on residual liquid-based (TPPT) cervical samples: focus on age-stratified clinical performance.

BACKGROUND: Liquid-based ThinPrep technology has made reflex human papillomavirus (HPV) DNA testing possible. In the current study, the clinical performance of reflex HPV testing as an adjunct to routine ThinPrep testing (TPPT) and the impact of age on various test parameters in a predominantly high-risk, minority population were evaluated retrospectively. METHODS: Reflex HPV testing was performed in 2114 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology, using probes for low-risk (LR) and high-risk (HR) HPV types. Six hundred thirty women underwent subsequent biopsies with which HPV testing results were correlated. RESULTS: Approximately 86% of the patients were Hispanic and African-American and 12% were white. Of the younger women (ages 14-29 years), 81% were positive for HR types versus 50% in the older women (ages 30-77 years) (P < 0.0001). In women with ASCUS, 47% were found to be positive for HR types versus 78% of women with LSIL. The percentage of histologic high-grade lesions was 24% in younger patients versus 17% in older patients. Overall, 91% of high-grade lesions were positive for HPV DNA (HR-positive = 89% and LR-positive = 2%), and 9% were negative for both types. The sensitivities and specificities in "younger" versus "older" women were 92% (95% confidence interval [95% CI], 89-95%) and 22%% (95% CI, 17-26%), respectively, versus 84% (95% CI, 77-90%) and 59% (95% CI, 53-65%), respectively. CONCLUSIONS: The results of the current study demonstrate that reflex HPV testing performed in a routine clinical practice helps to identify the majority of women with high-grade disease. However, testing may be more beneficial in older women (age > or = 30 years) with ASCUS. Strategy using out-of-vial reflex testing is more cost-effective and sensitive than referring all women for colposcopies.

Detrimental effects of a high fat diet in early renal injury are ameliorated by fish oil in Han:SPRD-cy rats.

Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory injury. We previously demonstrated that a high fat (HF) diet worsens early renal disease progression in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet) diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF compared with those fed LF diets had larger kidneys, more renal fibrosis and lower creatinine clearance (main effects of fat level). Rats fed MO rather than CO and SO diets had significantly lower kidney weights, kidney water content, cyst volumes and serum cholesterol and triglyceride concentrations (main effects of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO diets, but the least fibrosis was in rats fed SO diets. Analysis of simple effects (due to interactions between fat level and type) revealed that HF diets increased renal inflammation in rats fed CO diets, but reduced inflammation was present in those fed SO and MO diets; HF diets also increased compared with LF diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not the SO diet. These results confirm that high dietary fat worsens early disease progression in this model of renal disease, and further demonstrate that diets with oils containing (n-3) fatty acids ameliorate some of the detrimental effects of a high fat diet.

Cell block findings from residual PreservCyt samples in unsatisfactory ThinPrep Paps: no additional benefit.

Our objective was to determine whether cell blocks (CB) performed on unsatisfactory ThinPrep Pap Test residual samples rendered additional clinically significant pathologic findings not detected in the original ThinPrep Pap smears. One hundred consecutive ThinPrep Paps categorized as unsatisfactory were selected for this study. The cytologic diagnosis of unsatisfactory was based on lack of cellularity (squamous) or complete obscuring blood or inflammation. Residual PreservCyt samples from these consecutive unsatisfactory ThinPrepPaps were used to prepare a cell block, using the inverted filter technique. One hematoxylin-eosin (H&E)-stained slide was prepared and evaluated. The amount and the cellular changes were noted for all smear constituents and compared with the original slides. The average patient age was 32 +/- 11 yr. The ThinPrepPap was performed as a follow-up on a previous abnormal smear (12%), pregnancy (25%), abnormal bleeding (22%), or previous unsatisfactory ThinPrepPap (5%), or as routine screening (36%). Variable amounts of endocervical cells, endometrial cells, and metaplastic cells, as well as a variable number of squamous epithelial cells, were present in 89%, 9%, 50%, and 35% in the CB method vs. ThinPrep, respectively. Abnormal cellular changes were noted in 15% of patients (9% with LSIL, and 6% with atypia of undetermined significance); 9 patients with squamous dysplasia had a previous abnormal ThinPrep Pap. A follow-up Pap smear and/or cervical biopsy were performed in 10 of the 15 patients with abnormal cytology detected on CB method revealing: LSIL (1 patient), HSIL (1 patient), ASCUS (1 patient), and within normal limits (7 patients). The findings indicate that the preparation of a CB does not contribute significantly. Importantly, no carcinomas or HSILs were identified on CB preparations. Since a large majority of lesions identified were LSILs, a repeat Pap smear in these cases represented a more cost-effective strategy than cell block preparation, although a cell block preparation may be useful in selected cases.

Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration samples.

BACKGROUND: The cytopathologic distinction between hepatocellular carcinoma (HCC) and metastatic carcinoma (MC) in the liver can be problematic, especially in patients with poorly differentiated HCC, in whom a trabecular pattern, bile production, and Mallory bodies may not be apparent on small fine-needle aspiration (FNA) samples. HepPar1 (OCH1E5) is a monoclonal antibody specifically developed to react with hepatocytes. It rarely reacts with bile duct and nonparenchymal liver cells. METHODS: FNA samples (cell blocks) from 75 liver tumors were selected. These included 50 moderate to poorly differentiated HCC cases, 5 cholangiocarcinoma (CC) cases, and 20 MC cases (4 from the breast, 4 from the stomach, 4 from the pancreas, and 8 from the colon). Immunohistochemical staining for HepPar1 was performed to differentiate HCC from MC. RESULTS: The HepPar1 antibody was positive in 50 of 50 HCC cases (100%). The positivity was cytoplasmic, diffuse, and granular. All 5 cases of CC were found to be negative (0%). Although focal positivity within tumor cells was noted in one case, cytologically these were entrapped normal hepatocytes between the tumor cells. In addition, 3 of 20 MC cases (15%) also were positive for HepPar1. All three cases originated from gastric primary tumors and exhibited diffuse, granular cytoplasmic staining. CONCLUSIONS: The results of the current study demonstrate that HepPar1 is an effective marker with which to differentiate between HCC and CC and/or MC. HepPar1 was found to demonstrate 100% positivity in HCC cases, compared with 0% and 15% positivity, respectively, in CC and MC cases. In addition, HepPar1 is extremely helpful in limited tissue samples from FNA. Although 15% of the MC cases in the current study were found to be positive, with the help of clinical correlation and other immunohistochemical stains a definite diagnosis could be rendered. Potential pitfalls include residual benign hepatocyte staining within a non-HCC malignancy, as was observed in one of the CC cases in the current study.