The presence of a cytopathologist increases the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration cytology for pancreatic adenocarcinoma: a meta-analysis.

OBJECTIVE: A meta-analysis has not been previously performed to evaluate critically the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solely pancreatic ductal adenocarcinoma and address factors that have an impact on variability of accuracy. The aim of this study was to determine whether the presence of a cytopathologist, variability of the reference standard and other sources of heterogeneity significantly impacts diagnostic accuracy. METHODS: We conducted a comprehensive search to identify studies, in which the pooled sensitivity, specificity, likelihood ratios for a positive or negative test (LR+, LR-) and summary receiver-operating curves (SROC) could be determined for EUS-FNA of the pancreas for ductal adenocarcinoma using clinical follow-up, and/or surgical biopsy or excision as the reference standard. RESULTS: We included 34 distinct studies (3644 patients) in which EUS-FNA for a solid pancreatic mass was evaluated. The pooled sensitivity and specificity for EUS-FNA for pancreatic ductal adenocarcinoma was 88.6% [95% confidence interval (CI): 87.2-89.9] and 99.3% (95% CI: 98.7-99.7), respectively. The LR+ and LR- were 33.46 (95% CI: 20.76-53.91) and 0.11 (95% CI: 0.08-0.16), respectively. The meta-regression model showed rapid on-site evaluation (ROSE) (P = 0.001) remained a significant determinant of EUS-FNA accuracy after correcting for study population number and reference standard. CONCLUSION: EUS-FNA is an effective modality for diagnosing pancreatic ductal adencarcinoma in solid pancreatic lesions, with an increased diagnostic accuracy when using on-site cytopathology evaluation.

A mouse model of heterogeneous, c-MYC-initiated prostate cancer with loss of Pten and p53.

Human tumors are heterogeneous and evolve through a dynamic process of genetic mutation and selection. During this process, the effects of a specific mutation on the incipient cancer cell may dictate the nature of subsequent mutations that can be tolerated or selected for, affecting the rate at which subsequent mutations occur. Here we have used a new mouse model of prostate cancer that recapitulates several salient features of the human disease to examine the relative rates in which the remaining wild-type alleles of Pten and p53 tumor suppressor genes are lost. In this model, focal overexpression of c-MYC in a few prostate luminal epithelial cells provokes a mild proliferative response. In the context of compound Pten/p53 heterozygosity, c-MYC-initiated cells progress to prostatic intraepithelial neoplasia (mPIN) and adenocarcinoma lesions with marked heterogeneity within the same prostate glands. Using laser capture microdissection and gene copy number analyses, we found that the frequency of Pten loss was significantly higher than that of p53 loss in mPIN but not invasive carcinoma lesions. c-MYC overexpression, unlike Pten loss, did not activate the p53 pathway in transgenic mouse prostate cells, explaining the lack of selective pressure to lose p53 in the c-MYC-overexpressing cells. This model of heterogeneous prostate cancer based on alterations in genes relevant to the human disease may be useful for understanding pathogenesis of the disease and testing new therapeutic agents.

Diagnostic utility of mammaglobin and GCDFP-15 in the identification of metastatic breast carcinoma in fluid specimens.

Morphologic differentiation of breast carcinoma from nonmammary malignancies in fluid specimens can be a diagnostic challenge. Immunocytochemistry is often employed in the differential diagnosis. In this study, we evaluated the expression of mammoglobin (MGB1) in body-cavity fluid specimens and compared its efficacy as a marker for metastatic breast carcinomas with that of gross cystic disease fluid protein-15 (GCDFP-15). Cell blocks from 40 fluid specimens were immunostained with monoclonal antibodies against MGB1 and GCDFP-15. They included 15 breast carcinomas and 25 nonmammary carcinomas (10 lungs, 10 ovaries, 3 gastrointestinal tracts, 1 kidney, and 1 urinary bladder). Positivity was defined as the presence of cytoplasmic staining in 10% or more carcinoma cells. Thirteen (87%) and seven (47%) breast carcinomas showed positive staining with MGB1 and GCDFP-15, respectively. Three (12%) nonmammary carcinomas (2 ovarian and 1 colonic) showed positive MGB1 staining; one (3%) nonmammary carcinoma demonstrated positive GCDFP-15 staining. The differences of MGB1 and GCDFP-15 staining between breast and nonmammary carcinomas were statistically significant (P < 0.05). Both MGB1 and GCDFP-15 are specific markers for metastatic breast carcinomas in cell block fluid specimens (88 vs. 96%). However, MGB1 is more sensitive than GCDFP-15 as a marker for metastatic breast carcinoma (87 vs. 46%).

Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl-2, Ki-67 and p53.

OBJECTIVE: While the use of fine needle aspiration (FNA) in the diagnosis of gastrointestinal stromal tumours (GISTs) is well-established, it can be difficult to predict the prognosis of GIST based on morphology alone. The objective of the current study was to determine if expression of bcl-2, Ki-67 and p53 correlated with the outcome of GISTs based on cytological material. METHODS: Cell-blocks from 14 GISTs diagnosed by FNA were retrieved. Immunostaining was performed with antibodies against bcl-2, Ki-67 and p53. All cytological diagnoses were confirmed by positive immunostaining with c-kit and/or subsequent histological evaluation. Positivity for bcl-2, Ki-67 and p53 was defined as the presence of > or =10% cytoplasmic staining, > or =5% nuclear staining and > or =5% nuclear staining respectively. RESULTS: The 14 patients consisted of seven males and seven females with a mean age of 58 years. The average follow-up interval was 46 months. Six had a benign course and eight developed recurrences/metastases. Thirteen (93%) cases showed positive staining for bcl-2. Positive Ki-67 and p53 staining was noted in one (7%) and seven (50%) cases respectively. The difference in staining for p53 between aggressive and non-aggressive GISTs was statistically significant. No statistically significant difference was noted for bcl-2 staining or Ki-67 labelling index between the two groups. CONCLUSIONS: According to our observations, p53 immunostaining may be useful in predicting the outcome of GIST diagnosed by FNA; Ki-67 and bcl-2 are not useful as prognostic markers for GIST in FNA specimens.

Cumulative sum procedure in evaluation of EUS-guided FNA cytology: the learning curve and diagnostic performance beyond sensitivity and specificity.

BACKGROUND: Using cumulative sum (CUSUM) chart, we address two questions: (i) Over time, how will an EUS-FNA (endoscopic ultrasound guided fine needle aspiration) service maintain an acceptable non-diagnostic rate defined as technical failures, unsatisfactory specimens and atypical and suspicious diagnoses? (ii) Over time, how will EUS-FNA maintain acceptable diagnostic errors (false-positives plus false-negative diagnosis)? METHODS: The study included all consecutive patients who underwent EUS-FNA at our institution from July 2000 to October 2003 and were followed up until December 2004. Using a simple spread sheet, we designed CUSUM charts and used them to track trends and assess performance at a preset acceptable rate of 10% and a preset unacceptable rate of 15% for non-diagnostic rate and diagnostic errors. We assessed all cases collectively and then in groups defined by site, size and cytopathologist. RESULTS: Of 876 patients undergoing EUS-FNA, 83 (9.5%) had non-diagnostic results: 43 (51%) of these diagnoses were 'atypical', 27(33%) were 'suspicious for malignancy', eight (10%) were 'insufficient material for diagnosis' and five (6%) were 'technical failure'. In 585 cases with adequate follow up, there were 26 (6.3%) diagnostic errors: three (0.5%) were false positive and 23 (3.1) were false negative. The overall CUSUM charts for both non-diagnostic rate and for diagnostic error rate start with a small period of learning then cross to a significantly acceptable level at case numbers 121 and 97 respectively. Our diagnostic performance was better in lymph nodes than in the pancreas and other organs and was not significantly different for lesions 25 mm in diameter. Performance was better for pathologists with prior experience than for pathologists without experience. CONCLUSION: In the current climate of proficiency testing, error tracking and competence evaluation, there is a great potential for the use of CUSUM charts to assess procedure failure and error tracking in quality control programs, particularly when a new procedure such as EUS-FNA is introduced in the laboratory. Additionally, the method can be used to assess trainee competency and to track the proficiency of practicing cytologists.

Transgastric endoscopic ultrasound-guided fine-needle aspiration biopsy and flow cytometry of suspected lymphoma of the spleen.

BACKGROUND AND STUDY AIMS: Masses in the spleen can be sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) but the diagnosis of lymphoma using EUS-FNA and flow cytometry has not been reported. We report our experience with transgastric EUS-FNA and flow cytometry in the investigation of patients with suspected lymphoma of the spleen. PATIENTS AND METHODS: All patients with splenic lesions that had been detected by computed tomography and who were referred for transgastric EUS-FNA over a 3-year period were enrolled in this study. The tissue obtained by EUS-FNA was evaluated by flow cytometry in all patients. RESULTS: Six patients with splenic masses were enrolled (four men, two women; median age 58.5 years, range 41 - 82 years). The mean size of the short axis of the lesions was 37.8 mm (SD 23.76 mm) and the mean size of the long axis was 45.6 mm (SD 31.72 mm). EUS-FNA was performed successfully in all patients and the tissue obtained was evaluated by flow cytometry. Two patients were diagnosed with lymphoma; no pathology was identified in the other four patients. Lymphoma of the spleen appeared as sharply demarcated echo-poor lesions; benign lesions appeared echo-rich in comparison with the surrounding splenic tissue. The two patients who were diagnosed with lymphoma underwent chemotherapy. Of the four patients in whom no pathology was identified, one patient subsequently underwent splenectomy for evaluation of persistent abdominal pain and was diagnosed with lymphoma; the three other patients had true-negative disease on the evidence of long-term follow-up (mean 8 months; range 6 - 12 months). No complications related to the EUS-FNA procedure were encountered in any patient. CONCLUSIONS: EUS-FNA of spleen masses is a safe technique that aids in the diagnosis of lymphoma when used in conjunction with flow cytometry.

Endoscopic ultrasound-guided FNA biopsy of bile duct and gallbladder: analysis of 53 cases.

OBJECTIVE: Endoscopic retrograde cholangiopancreaticography (ERCP)-guided brushing has been the standard of practice for surveillance and detection of carcinoma in the biliary tree. Few studies have evaluated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in diagnosing clinically suspected cholangiocarcinoma. The role of this method in diagnosing clinically suspected gallbladder malignancies has not been extensively evaluated in the USA. This study investigates the role of EUS-FNA in the diagnosis of clinically suspected biliary tree and gallbladder malignancies in a large patient series. METHODS: EUS-FNAs were obtained from 46 bile duct and seven gallbladder lesions. On-site rapid interpretation was provided using air-dried Diff Quik stained smears. In addition, alcohol fixed Papanicoloau stained smears and Thin Prep preparations (Cytye Corp., Marlborough, MA, USA) were evaluated before providing a final cytological diagnosis. Tissue biopsies and/or clinical follow-up were used as the standards to determine operating characteristics for EUS-FNA. RESULTS: The mean ages for bile duct and gallbladder lesions were 66 years (range: 37-84 years), and 69 years (range 49-86 years), respectively. All cases diagnosed as suspicious/malignant on preliminary evaluation were confirmed on final cytological interpretation (27/27). The operating characteristics show that EUS-FNA is highly specific (100%) with sensitivity rates of 87% and 80% from clinically suspected malignancies of biliary tract and gallbladder, respectively. Sampling error in three cases and associated acute inflammation in two cases resulted in false-negative diagnoses. CONCLUSIONS: EUS-FNA of biliary tree and gallbladder carcinoma is highly specific and should be considered for evaluation of clinically suspicious lesions. Marked inflammation may result in false-negative diagnoses.

Malignant pleural effusions due to small-cell lung carcinoma: a cytologic and immunocytochemical study.

Patients with small-cell lung carcinoma (SCLC) rarely present with pleural effusions. Based on morphology alone, recognition of SCLC in effusion cytology may be challenging because of the resemblance of neoplastic cells to lymphocytes. Immunocytochemistry may be helpful in its diagnosis. The objective of this study was to review the morphology and evaluate the use of immunocytochemistry in diagnosing SCLC in pleural fluids. Patients with SCLC who presented with pleural effusions were identified during a 6-yr period. The cytology and medical records were reviewed. Formalin-fixed, paraffin-embedded cell blocks of fluid specimens were immunostained with neuroendocrine markers (chromogranin A and synatophysin), cytokeratin 20 (CK20), and thyroid transcription factor-1 (TTF-1). The latter is a nuclear transcription protein that is expressed in normal respiratory epithelium and also in more than 90% of SCLCs. Of the 256 patients diagnosed with SCLC during the study period, 8 (2.7%) patients (3 females and 4 males, age range from 56-85 yr) also developed pleural effusions. One patient had 2 fluid specimens during the course of their disease, giving a total of 9 specimens. Four specimens had a positive cytologic diagnosis of SCLC, and 2 were initially diagnosed as suspicious for SCLC. The remaining 3 specimens were negative for SCLS. The specimens with a positive or suspicious diagnosis showed single and aggregates of small to medium-sized single cells with a high nuclear:cytoplasmic (N:C) ratio, round to angulated nuclei, and salt-and-pepper chromatin. Nuclear molding was also noted. Five out of 6 (83%) specimens with a positive or suspicious diagnosis of SCLC were positive for both chromogranin A and TTF-1. Synaptophysin was positive in 3 of 6 (50%) positive or suspicious cases. None of the cases were positive for CK20. All cases with a negative cytologic diagnosis were negative for chromogranin A, synatophysin, CK20, and TTF-1. In conclusion, patients with SCLC rarely present with pleural effusions. The cytology of SCLC is characteristic. The use of immunocytochemistry, particularly with antibodies to chromogranin A, TTF-1, and CK 20, aids in the differential diagnosis.

Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP).

Latent prostate tumors are commonly found with similar frequency in many countries and ethnic groups. In contrast, aggressive prostate cancer (PC) is significantly less prevalent among Asian men, where the intake of soy products is very high. High consumption of foods containing soy results in high plasma, urine, and prostatic fluid concentrations of phytoestrogens, including genistein. The objective of the present study was to test the hypothesis that dietary genistein might prevent PC progression in a transgenic mouse model of PC (TRAMP). By 28-30 weeks of age, all TRAMP mice in the study had developed prostate tumors, with about half of them displaying well-differentiated prostatic adenocarcinoma (WD, score 4), and the other half divided between moderately differentiated (MD, score 5) and poorly differentiated adenocarcinoma (PD, score 6). Two lines of evidence supported the possibility that prostates with PD may represent a more advanced stage of PC in TRAMP mice: (a) the weight of prostates with PD was two orders of magnitude higher than that of prostates with WD or MD; and (b) expression of androgen receptor transcripts was altered in PD as compared with WD and MD. To test the potential of genistein to prevent the incidence of mice with PD, starting at 5-6 weeks of age, transgenic males were fed a phytoestrogen-free diet (AIN-76A) containing 0, 100, 250, or 500 mg of genistein per kg AIN-76A (25, 10, 17, and 7 mice/group, respectively). Mice were on the diet until they were 28-30 weeks of age. Each mouse was weighed once a week throughout the study. At necropsy, selected organs were weighed and prepared for histopathological evaluation. Serum levels of genistein in mice on diet containing 0, 250, or 500 mg of genistein per kg AIN-76A were 52.4 +/- 32.7, 138.9 +/- 69.6, and 397.3 +/- 104.9 nM, respectively, comparable with those found in Asian men on regular soy diet (276 nM). Using body and organ weights as indicators, dietary genistein had no toxic effect on TRAMP mice. The percentage of transgenic males that developed PD was reduced in a dose-dependent manner by dietary genistein.

Pryce's type I pulmonary intralobar sequestration presenting with massive hemoptysis.

Pryce's type I intralobar sequestration, in which a region of lung exhibits tracheobronchial continuity and aberrant systemic arterial supply, is most frequently asymptomatic and discovered incidentally. While hemoptysis may be a common presenting symptom, massive hemoptysis is rarely seen. We document a case of a 58-year-old man, previously asymptomatic, whose initial presentation was that of massive hemoptysis. The radiographic, intraoperative and pathologic findings in our patient confirm that his sequestration was of Pryce's type I. Ann Diagn Pathol 5:91-95, 2001.

Sex steroid receptor regulation by genistein in the prepubertal rat uterus.

We evaluated the mechanism of action by the phytoestrogen genistein in the prepubertal rat uterus, when administered pharmacologically or physiologically. Female rats were injected with genistein (500 microg/g body weight), estradiol benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased circulating estradiol and decreased progesterone concentrations. Uterine estrogen receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and progesterone receptors (PR) were increased, as measured by western blot analyses. Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but not in ER-beta, PR and AR mRNA levels following genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not altered significantly. We conclude that pharmacologic, but not physiologic concentrations of genistein can modulate sex steroid receptor expression in the rat uterus.

Laser capture microdissection.

Laser capture microdissection (LCM) offers a rapid and precise method of isolating and removing specified cells from complex tissues for subsequent analysis of their RNA, DNA, or protein content, thereby allowing assessment of the role of the cell type in the normal physiologic or disease process being studied. In this unit, protocols for the preparation of mammalian frozen tissues, fixed tissues, and cytologic specimens for LCM, including hematoxylin and eosin staining, are presented, as well as a protocol for the performance of LCM utilizing the PixCell I or II Laser Capture Microdissection System manufactured by Arcturus Engineering. Also provided is a protocol for tissue processing and paraffin embedding, and recipes for lysis buffers for the recovery of nucleic acids and proteins. The Commentary section addresses the types of specimens that can be utilized for LCM and approaches to staining of specimens for cell visualization. Emphasis is placed on the preparation of tissue or cytologic specimens as this is critical to effective LCM.

Primary gastrointestinal sarcomas.

Gastrointestinal (GI) sarcomas are uncommon tumors with the majority of previous studies performed over long time intervals. The purpose of this review is to analyze our single-institution experience with primary GI sarcomas. Between January 1990 and June 1998, 27 adult patients with primary GI sarcomas were identified in the tumor registry at the University Hospital, School of Medicine of University of Alabama at Birmingham and retrospectively reviewed. Patient, tumor, and treatment factors as well as expression of p53 and Ki-67 were analyzed with overall survival as the main outcome variable. Statistical analysis was performed by log rank test and Cox regression. Significance was defined as P < 0.05. Median age was 55 years (range 36-80 years). The stomach was the most common site of presentation (59%) followed by small bowel (29%). The average tumor size was 15 cm (range 2-46 cm). A complete resection was performed in 22 patients (81.5%). Fifteen tumors were classified as low grade (55.5%). Actuarial 3-year survival was 43 per cent with a median follow-up of 16 months. Overexpression of p53 and Ki-67 correlated with a trend to decreased survival but it did not reach statistical significance. Multivariate analysis found incomplete resection (P = 0.00001) and high grade (P = 0.003) to be significant negative prognostic factors. We conclude that GI sarcomas tend to be large tumors with most arising in the stomach and proximal GI tract. Complete surgical resection is associated with prolonged survival and despite the large size of these tumors should be attempted whenever possible.

Epithelioid variant of malignant peripheral nerve sheath tumor (malignant schwannoma) of the urinary bladder.

Sarcoma represents less than 2% of all neoplasms diagnosed or recognized in effusions. Epithelioid peripheral nerve sheath tumor is a rare tumor that is difficult to differentiate from other epithelioid tumors without the use of ancillary studies. A 39-year-old paraplegic man presented with hematuria and a bladder mass that extended to involve the pelvic peritoneum. Light microscopy using hematoxylin-eosin, Papanicolaou, and immunohistochemical stains as well as transmission electron microscopy showed features of epithelioid malignant peripheral nerve sheath tumor with rhabdoid features and an accompanying eosinophilic infiltrate. Cytologic smears confirmed the similarities between the primary tumor in the bladder and the cells in the pelvic fluid and excluded the possibility of reactive changes related to postsurgical radiation. Ancillary studies were critical in narrowing the differential diagnoses and reaching the final conclusion.

Mortality due to schistosomiasis mansoni: a field study in Sudan.

Although schistosomiasis affects 200 million persons, 20 million of whom have advanced disease, little is known about the mortality pattern in areas of endemic schistosomiasis mansoni. In an attempt to assess the mortality rates in an endemic area in Sudan, we conducted two demographic surveys in a village in the Gezira area. Clinical, sonographic, and parasitologic examinations were performed in a randomly selected sample of 25% of the population in 1987 and 1994. One of us asked each head of household about the names, sex, and age of family members. Particularly, we asked about death in the family if any, history of schistosomiasis, abdominal swelling, and hematemesis. Possible causes of death were ascertained by reviewing medical records in the village dispensary and the district hospital. There were 42 deaths in the village. Four males died of hematemesis secondary to portal fibrosis. The crude mortality rate of schistosomiasis was is 51/100,000/year. The overall schistosomiasis fatality rate per year was 1/1,000 infected persons, but was as high as 11/100/infected patients with bleeding varices. These findings showed the impact of schistosomiasis on public health in this economically important region of Sudan.

Usefulness of molecular detection of human herpesvirus-8 in the diagnosis of Kaposi sarcoma by fine-needle aspiration.

Kaposi sarcoma (KS), a multifocal angioproliferative disorder, occurs most commonly in patients with AIDS, in whom it remains an important cause of morbidity and mortality. KS is often in the differential diagnosis in HIV-infected patients undergoing fine-needle aspiration (FNA). FNA diagnosis of KS is usually made by morphologic observation of scant tissue fragments composed of bland spindle cells and crush artifact. Human herpesvirus-8 (HHV-8) has been identified by polymerase chain reaction (PCR) amplification of DNA samples isolated from various epidemiologic forms of KS. In an attempt to improve the accuracy of KS diagnosis by FNA, we analyzed for the presence of HHV-8 DNA in 13 spindle-cell lesions evaluated by FNA: KS, 8 cases; granulomatous inflammation due to Mycobacterium avium-intracellulare, 1; nodular fasciitis, 1; dermatofibrosarcoma protuberans, 1; dermatofibroma, 1; benign spindle-cell lesion of nerve sheath origin, 1; and 2 lesions with lymphoid hyperplasia. DNA isolated from archival Wright-Giemsa-stained glass slides was used for the PCR amplification of the HHV-8 DNA sequences. All of the cases diagnosed as KS and 1 of the lymphoid hyperplasia cases were PCR-positive for HHV-8 DNA, while all other cases of spindle-cell lesions were negative. The molecular demonstration of HHV-8 DNA may be a useful adjunct in the diagnosis of KS by FNA.

Intraoperative cytologic diagnosis of granulomas: a retrospective study of 156 cases.

To avoid contamination of equipment and reduce risks of infection, intraoperative cytology (IOC) is a useful substitute to conventional frozen section in the diagnosis of infectious diseases. One of the various histomorphologic patterns of infections is the granuloma, which sometimes may be difficult to diagnose cytologically. In an attempt to assess accuracy and pitfalls of IOC in the diagnosis of granuloma, cases diagnosed as granuloma on IOC or on permanent sections (PS) at George Washington University Medical Center were collected for the period of September 1990 to March 1996. Cyto-histologic correlation was performed. During that time, a diagnosis of granuloma in either the IOC or PS was rendered in 156 of 5,901 IOC cases. IOC showed definite granuloma (87), suspicious for granuloma (23), and neither definite nor suspicious for granuloma in 46 cases. The latter group corresponded to neoplasms (5) and benign conditions (41). Eighty-five cases were accurately diagnosed as definite granuloma by both IOC and PS. Fifty-seven cases diagnosed as granuloma by PS corresponded on IOC to suspicious for granuloma (11), benign smear (41), and neoplasms (5). Only two cases were incorrectly diagnosed as granuloma on IOC: a neoplasm and a case of fibrosis. Overall, four cases of neoplasms were interpreted as suspicious for granuloma (3) or definite granuloma (1) on IOC, and five cases of granulomas were misdiagnosed as neoplasms on IOC. Four of these nine case were deferred for a PS diagnosis. IOC is a useful tool in the diagnosis of granulomas with a sensitivity of 60% and specificity of 99% and positive and negative predictive values of 98% and 99%, respectively. Rarely, neoplasms may be misdiagnosed as granulomas and vice versa.

The effectiveness of annual versus biennial mass chemotherapy in reducing morbidity due to schistosomiasis: a prospective study in Gezira-Managil, Sudan.

The most serious complication of schistosomiasis is periportal fibrosis, which affects a large number of subjects in endemic areas. Population-based chemotherapy remains the most effective way of controlling this disease. In an attempt to find the best way to deliver chemotherapy to the endemic population, we compared the impact of repeated annual versus biennial mass chemotherapy on morbidity due to schistosomiasis in two villages in Gezira, Sudan. One village was given five rounds of mass chemotherapy annually in the years 1990-1994 while the other village was given three rounds of mass chemotherapy biennially from 1988 to 1994. Before treatment, these villages had similar intensity of infection and prevalence. One round of either annual or biennial treatment reduced the intensity of infection, but not prevalence or morbidity. After two rounds of annual chemotherapy, infection rates, bloody diarrhea, and fibrosis in those 20 years of age and less were significantly reduced. Two rounds of biennial chemotherapy had a similar effect on rates and bloody diarrhea; however, fibrosis was reduced only after the third round of biennial chemotherapy. Prevalence of hepatosplenomegaly increased after both treatment regimens. Reinfection was most prominent in those 5-14 years of age. These findings support the general notion that repeated chemotherapy may be needed in areas of high transmission of schistosomiasis. We recommend two rounds of annual mass chemotherapy to significantly reduce infection and morbidity.

Suppressive effect of interleukin-4 neutralization differs for granulomas around Schistosoma mansoni eggs injected into mice compared with those around eggs laid in infected mice.

The principal pathological manifestation of murine Schistosoma mansoni infection is the egg-induced granuloma. Synchronous pulmonary granulomas forming around intravenously injected schistosome eggs are widely used to study the immunopathology of schistosomiasis. A number of anticytokine antibody treatments have a remarkable effect in modulating granulomas in this model but little effect on the size of hepatic granulomas around laid eggs during experimental infection. To examine this discrepancy, we examined the effects of anticytokine antibodies on liver and lung granulomas around injected eggs and around eggs laid during infection in both locations. Anti-interleukin-4 (IL-4) treatment greatly reduced the volume of granulomas around eggs injected into the liver via the portal vein and around eggs injected into the lung via the tail vein. On the contrary, granulomas around eggs laid by worms in either the liver or the lung during the course of infection were not significantly decreased in size by anti-IL-4 treatment. Thus, site is not important for the disparate effects of anti-IL-4 in granuloma formation around injected versus laid eggs. This effect is seen in naive and sensitized animals and is most probably due to differences in the quality of injected eggs versus those laid in situ by the worms.